Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data

PubMed Central

Griesdale, Donald E.G.; de Souza, Russell J.; van Dam, Rob M.; Heyland, Daren K.; Cook, Deborah J.; Malhotra, Atul; Dhaliwal, Rupinder; Henderson, William R.; Chittock, Dean R.; Finfer, Simon; Talmor, Daniel

2009-01-01

Background Hyperglycemia is associated with increased mortality in critically ill patients. Randomized trials of intensive insulin therapy have reported inconsistent effects on mortality and increased rates of severe hypoglycemia. We conducted a meta-analysis to update the totality of evidence regarding the influence of intensive insulin therapy compared with conventional insulin therapy on mortality and severe hypoglycemia in the intensive care unit (ICU). Methods We conducted searches of electronic databases, abstracts from scientific conferences and bibliographies of relevant articles. We included published randomized controlled trials conducted in the ICU that directly compared intensive insulin therapy with conventional glucose management and that documented mortality. We included in our meta-analysis the data from the recent NICE-SUGAR (Normoglycemia in Intensive Care Evaluation — Survival Using Glucose Algorithm Regulation) study. Results We included 26 trials involving a total of 13 567 patients in our meta-analysis. Among the 26 trials that reported mortality, the pooled relative risk (RR) of death with intensive insulin therapy compared with conventional therapy was 0.93 (95% confidence interval [CI] 0.83–1.04). Among the 14 trials that reported hypoglycemia, the pooled RR with intensive insulin therapy was 6.0 (95% CI 4.5–8.0). The ICU setting was a contributing factor, with patients in surgical ICUs appearing to benefit from intensive insulin therapy (RR 0.63, 95% CI 0.44–0.91); patients in the other ICU settings did not (medical ICU: RR 1.0, 95% CI 0.78–1.28; mixed ICU: RR 0.99, 95% CI 0.86–1.12). The different targets of intensive insulin therapy (glucose level ≤ 6.1 mmol/L v. ≤ 8.3 mmol/L) did not influence either mortality or risk of hypoglycemia. Interpretation Intensive insulin therapy significantly increased the risk of hypoglycemia and conferred no overall mortality benefit among critically ill patients. However, this therapy may be beneficial to patients admitted to a surgical ICU. PMID:19318387

Using computerized text analysis to assess communication within an Italian type 1 diabetes Facebook group.

PubMed

Troncone, Alda; Cascella, Crescenzo; Chianese, Antonietta; Iafusco, Dario

2015-07-01

The purpose of this study was to assess messages posted by mothers of children with type 1 diabetes in the Italian Facebook group "Mamme e diabete" using computerized text analysis. The data suggest that these mothers use online discussion boards as a place to seek and provide information to better manage the disease's daily demands-especially those tasks linked to insulin correction and administration, control of food intake, and bureaucratic duties, as well as to seek and give encouragement and to share experiences regarding diabetes and related impact on their life. The implications of these findings for the management of diabetes are discussed.

Strict glycaemic control in patients hospitalised in a mixed medical and surgical intensive care unit: a randomised clinical trial

PubMed Central

De La Rosa, Gisela Del Carmen; Donado, Jorge Hernando; Restrepo, Alvaro Humberto; Quintero, Alvaro Mauricio; González, Luis Gabriel; Saldarriaga, Nora Elena; Bedoya, Marisol; Toro, Juan Manuel; Velásquez, Jorge Byron; Valencia, Juan Carlos; Arango, Clara Maria; Aleman, Pablo Henrique; Vasquez, Esdras Martin; Chavarriaga, Juan Carlos; Yepes, Andrés; Pulido, William; Cadavid, Carlos Alberto

2008-01-01

Introduction Critically ill patients can develop hyperglycaemia even if they do not have diabetes. Intensive insulin therapy decreases morbidity and mortality rates in patients in a surgical intensive care unit (ICU) and decreases morbidity in patients in a medical ICU. The effect of this therapy on patients in a mixed medical/surgical ICU is unknown. Our goal was to assess whether the effect of intensive insulin therapy, compared with standard therapy, decreases morbidity and mortality in patients hospitalised in a mixed ICU. Methods This is a prospective, randomised, non-blinded, single-centre clinical trial in a medical/surgical ICU. Patients were randomly assigned to receive either intensive insulin therapy to maintain glucose levels between 80 and 110 mg/dl (4.4 to 6.1 mmol/l) or standard insulin therapy to maintain glucose levels between 180 and 200 mg/dl (10 and 11.1 mmol/l). The primary end point was mortality at 28 days. Results Over a period of 30 months, 504 patients were enrolled. The 28-day mortality rate was 32.4% (81 of 250) in the standard insulin therapy group and 36.6% (93 of 254) in the intensive insulin therapy group (Relative Risk [RR]: 1.1; 95% confidence interval [CI]: 0.85 to 1.42). The ICU mortality in the standard insulin therapy group was 31.2% (78 of 250) and 33.1% (84 of 254) in the intensive insulin therapy group (RR: 1.06; 95%CI: 0.82 to 1.36). There was no statistically significant reduction in the rate of ICU-acquired infections: 33.2% in the standard insulin therapy group compared with 27.17% in the intensive insulin therapy group (RR: 0.82; 95%CI: 0.63 to 1.07). The rate of hypoglycaemia (≤ 40 mg/dl) was 1.7% in the standard insulin therapy group and 8.5% in the intensive insulin therapy group (RR: 5.04; 95% CI: 1.20 to 21.12). Conclusions IIT used to maintain glucose levels within normal limits did not reduce morbidity or mortality of patients admitted to a mixed medical/surgical ICU. Furthermore, this therapy increased the risk of hypoglycaemia. Trial Registration clinicaltrials.gov Identifiers: 4374-04-13031; 094-2 in 000966421 PMID:18799004

Is reducing variability of blood glucose the real but hidden target of intensive insulin therapy?

PubMed

Egi, Moritoki; Bellomo, Rinaldo; Reade, Michael C

2009-01-01

Since the first report that intensive insulin therapy reduced mortality in selected surgical critically ill patients, lowering of blood glucose levels has been recommended as a means of improving patient outcomes. In this initial Leuven trial, blood glucose control by protocol using insulin was applied to 98.7% of patients in the intensive group but to only 39.2% (P < 0.0001) of patients in the control group. If appropriately applied, such protocols should decrease both the mean blood glucose concentration and its variability (variation of blood glucose concentration). Thus, it is logically possible that the benefit of intensive insulin therapy in the first Leuven trial was due to a decrease in mean glucose levels, a decrease in their variability, or both. Several recent studies have confirmed significant associations between variability of blood glucose levels and patient outcomes. Decreasing the variability of blood glucose levels might be an important dimension of glucose management, a possible mechanism by which an intensive insulin protocol exerts its putative beneficial effects, and an important goal of glucose management in the intensive care unit. Clinicians need to be aware of this controversy when considering the application of intensive insulin therapy and interpreting future trials.

[Use of computer programs in the education and self-management of patients with insulin-dependent diabetes mellitus].

PubMed

Picco, P; Di Rocco, M; Buoncompagni, A; Gandullia, P; Lattere, M; Borrone, C

1991-01-01

A computerized program for children and adolescents with insulin dependent diabetes mellitus (IDDM) and their parents has been developed. Our program consists of computed assisted education, of aid to routine insulin dosage self adjustment and of records of home and hospital controls. Technically it has been implemented in DBIII plus: it runs on IBM PC computers (and compatible computers) and MS DOS (version 3.0 and later). Computed assisted education consists of 80 multiples choice questions divided in 2 parts: the first concerns basic informations about diabetes while the second one behavioral attitudes of patient in particular situations. Explanations are displayed after every question, apart from correct of incorrect choice. Help for self-adjustment of routine insulin dosage is offered in the third part. Finally daily home urine and/or blood controls and results of hospital admissions are stored in a database.

Preoperative Computerized Tomography and Magnetic Resonance Imaging of the Pancreas Predicts Pancreatic Mass and Functional Outcomes After Total Pancreatectomy and Islet Autotransplant

PubMed Central

Young, Michael C.; Theis, Jake R.; Hodges, James S.; Dunn, Ty B.; Pruett, Timothy L.; Chinnakotla, Srinath; Walker, Sidney P.; Freeman, Martin L.; Trikudanathan, Guru; Arain, Mustafa; Robertson, R. Paul; Wilhelm, Joshua J.; Schwarzenberg, Sarah J.; Bland, Barbara; Beilman, Gregory J.; Bellin, Melena D.

2015-01-01

Objectives About two-thirds of patients will remain on insulin therapy after total pancreatectomy with islet autotransplant (TPIAT) for chronic pancreatitis. We investigated the relationship between measured pancreas volume on computerized tomography (CT) or magnetic resonance imaging (MRI), and features of chronic pancreatiits on imaging, with subsequent islet isolation and diabetes outcomes. Methods CT or MRI was reviewed for pancreas volume (Vitrea software), and presence or absence of calcifications, atrophy, and dilated pancreatic duct in 97 patients undergoing TPIAT. Relationship between these features and: (1) islet mass isolated and (2) diabetes status at 1 year post-TPAIT were evaluated. Results Pancreas volume correlated with islet mass measured as total islet equivalents (r=0.50, p<0.0001). Mean islet equivalents was reduced by more than half if any one of calcifications, atrophy, or ductal dilatation were observed. Pancreatic calcifications increased the odds of insulin dependence 4.0 fold (1.1, 15). Collectively, the pancreas volume and 3 imaging features strongly associated with 1 year insulin use (p=0.07), islet graft failure (p=0.003), Hemoglobin A1c (p=0.0004), fasting glucose (p=0.027), and fasting C-peptide level (p=0.008). Conclusions Measures of pancreatic parenchymal destruction on imaging, including smaller pancreas volume and calcifications associate strongly with impaired islet mass and 1 year diabetes outcomes. PMID:26745861

Safety and efficacy of an intensive insulin protocol in a burn-trauma intensive care unit.

PubMed

Cochran, Amalia; Davis, Lynn; Morris, Stephen E; Saffle, Jeffrey R

2008-01-01

Aggressive glycemic management in critically ill patients with acute burn injury or life-threatening soft-tissue infections has not been thoroughly evaluated. An intensive insulin protocol with target glucose values of less than 120 mg/dl was implemented in October 2005 in our regional Burn-Trauma intensive care unit. We reviewed our initial experience with this protocol to evaluate the safety and efficacy of aggressive glycemic control in these patient groups. Patients were placed on the intensive insulin protocol based upon the need for glycemic management during their hospitalization for burn or soft-tissue disease. Patient information prospectively collected while on protocol included all measured blood glucose values, total daily insulin use, and incidence of hypoglycemic episodes, defined as serum glucose <60 mg/dl. Thirty patients (17 burns, 13 soft-tissue infections) were placed on the intensive insulin protocol during the first 16 months of use. The mean daily blood glucose level for burn patients was 115.9 mg/dl and for soft-tissue disease patients was 119.5 mg/dl. There was a 5% incidence of hypoglycemic episodes per protocol day. All hypoglycemic episodes were treated by holding the insulin infusion, and no episode had known adverse effects. Hyperglycemia in critically ill patients with burns and extensive soft-tissue disease can be effectively managed with an insulin protocol that targets blood glucose values of less than 120 mg/dl with minimal incidence of hypoglycemia. A multicenter prospective randomized trial would provide the ideal forum for evaluating clinical outcome benefits of using an intensive insulin protocol.

An intensive insulinotherapy mobile phone application built on artificial intelligence techniques.

PubMed

Curran, Kevin; Nichols, Eric; Xie, Ermai; Harper, Roy

2010-01-01

Software to help control diabetes is currently an embryonic market with the main activity to date focused mainly on the development of noncomputerized solutions, such as cardboard calculators or computerized solutions that use "flat" computer models, which are applied to each person without taking into account their individual lifestyles. The development of true, mobile device-driven health applications has been hindered by the lack of tools available in the past and the sheer lack of mobile devices on the market. This has now changed, however, with the availability of pocket personal computer handsets. This article describes a solution in the form of an intelligent neural network running on mobile devices, allowing people with diabetes access to it regardless of their location. Utilizing an easy to learn and use multipanel user interface, people with diabetes can run the software in real time via an easy to use graphical user interface. The neural network consists of four neurons. The first is glucose. If the user's current glucose level is within the target range, the glucose weight is then multiplied by zero. If the glucose level is high, then there will be a positive value multiplied to the weight, resulting in a positive amount of insulin to be injected. If the user's glucose level is low, then the weights will be multiplied by a negative value, resulting in a decrease in the overall insulin dose. A minifeasibility trial was carried out at a local hospital under a consultant endocrinologist in Belfast. The short study ran for 2 weeks with six patients. The main objectives were to investigate the user interface, test the remote sending of data over a 3G network to a centralized server at the university, and record patient data for further proofing of the neural network. We also received useful feedback regarding the user interface and the feasibility of handing real-world patients a new mobile phone. Results of this short trial confirmed to a large degree that our approach (which also can be known as intensive insulinotherapy) has value and perhaps that our neural network approach has implications for future intelligent insulin pumps. Currently, there is no software available to tell people with diabetes how much insulin to inject in accordance with their lifestyle and individual inputs, which leads to adjustments in software predictions on the amount of insulin to inject. We have taken initial steps to supplement the knowledge and skills of health care professionals in controlling insulin levels on a daily basis using a mobile device for people who are less able to manage their disease, especially children and young adults. 2010 Diabetes Technology Society.

An Intensive Insulinotherapy Mobile Phone Application Built on Artificial Intelligence Techniques

PubMed Central

Curran, Kevin; Nichols, Eric; Xie, Ermai; Harper, Roy

2010-01-01

Background Software to help control diabetes is currently an embryonic market with the main activity to date focused mainly on the development of noncomputerized solutions, such as cardboard calculators or computerized solutions that use “flat” computer models, which are applied to each person without taking into account their individual lifestyles. The development of true, mobile device-driven health applications has been hindered by the lack of tools available in the past and the sheer lack of mobile devices on the market. This has now changed, however, with the availability of pocket personal computer handsets. Method This article describes a solution in the form of an intelligent neural network running on mobile devices, allowing people with diabetes access to it regardless of their location. Utilizing an easy to learn and use multipanel user interface, people with diabetes can run the software in real time via an easy to use graphical user interface. The neural network consists of four neurons. The first is glucose. If the user's current glucose level is within the target range, the glucose weight is then multiplied by zero. If the glucose level is high, then there will be a positive value multiplied to the weight, resulting in a positive amount of insulin to be injected. If the user's glucose level is low, then the weights will be multiplied by a negative value, resulting in a decrease in the overall insulin dose. Results A minifeasibility trial was carried out at a local hospital under a consultant endocrinologist in Belfast. The short study ran for 2 weeks with six patients. The main objectives were to investigate the user interface, test the remote sending of data over a 3G network to a centralized server at the university, and record patient data for further proofing of the neural network. We also received useful feedback regarding the user interface and the feasibility of handing real-world patients a new mobile phone. Results of this short trial confirmed to a large degree that our approach (which also can be known as intensive insulinotherapy) has value and perhaps that our neural network approach has implications for future intelligent insulin pumps. Conclusions Currently, there is no software available to tell people with diabetes how much insulin to inject in accordance with their lifestyle and individual inputs, which leads to adjustments in software predictions on the amount of insulin to inject. We have taken initial steps to supplement the knowledge and skills of health care professionals in controlling insulin levels on a daily basis using a mobile device for people who are less able to manage their disease, especially children and young adults. PMID:20167186

A comparison between simplified and intensive dose-titration algorithms using AIR inhaled insulin for insulin-naive patients with type 2 diabetes in a randomized noninferiority trial.

PubMed

Mathieu, C; Cuddihy, R; Arakaki, R F; Belin, R M; Planquois, J-M; Lyons, J N; Heilmann, C R

2009-09-01

Insulin initiation and optimization is a challenge for patients with type 2 diabetes. Our objective was to determine whether safety and efficacy of AIR inhaled insulin (Eli Lilly and Co., Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc., Cambridge, MA) using a simplified regimen was noninferior to an intensive regimen. This was an open-label, randomized study in insulin-naive adults not optimally controlled by oral antihyperglycemic medications. Simplified titration included a 6 U per meal AIR insulin starting dose. Individual doses were adjusted at mealtime in 2-U increments from the previous day's four-point self-monitored blood glucose (SMBG) (total < or =6 U). Starting Air insulin doses for intensive titration were based on fasting blood glucose, gender, height, and weight. Patients conducted four-point SMBG daily for the study duration. Insulin doses were titrated based on the previous 3 days' mean SMBG (total < or =8 U). End point hemoglobin A1C (A1C) was 7.07 +/- 0.09% and 6.87 +/- 0.09% for simplified (n = 178) and intensive (n = 180) algorithms, respectively. Noninferiority between algorithms was not established. The fasting blood glucose (least squares mean +/- standard error) values for the simplified (137.27 +/- 3.42 mg/dL) and intensive (133.13 +/- 3.42 mg/dL) algorithms were comparable. Safety profiles were comparable. The hypoglycemic rate at 4, 8, 12, and 24 weeks was higher in patients receiving intensive titration (all P < .0001). The nocturnal hypoglycemic rate for patients receiving intensive titration was higher than for those receiving simplified titration at 8 (P < 0.015) and 12 weeks (P < 0.001). Noninferiority between the algorithms, as measured by A1C, was not demonstrated. This finding re-emphasizes the difficulty of identifying optimal, simplified insulin regimens for patients.

Light-intensity physical activity is associated with insulin resistance in elderly Japanese women independent of moderate-to vigorous-intensity physical activity.

PubMed

Gando, Yuko; Murakami, Haruka; Kawakami, Ryoko; Tanaka, Noriko; Sanada, Kiyoshi; Tabata, Izumi; Higuchi, Mitsuru; Miyachi, Motohiko

2014-02-01

It is unclear whether light physical activity is beneficially associated with insulin resistance, similar to moderate and/or vigorous physical activity. This cross-sectional study was performed to determine the relationship between the amount of light physical activity, as determined with a triaxial accelerometer, and insulin resistance. A total of 807 healthy men and women participated in this study. Physical activity was measured using a triaxial accelerometer worn for 28 days and summarized as light intensity (1.1-2.9 METs) or moderate to vigorous intensity (≥ 3.0 METs). Insulin resistance was evaluated by HOMA_R (FPG [mg/dL] × IRI [μU/mL]/405). The daily time spent in light physical activity was inversely associated with HOMA_R (r = -0.173, P < 0.05). After adjustment for confounders, the association between light physical activity and HOMA_R remained statistically significant (β = -0.119, P < .05). Light physical activity remained significantly associated with HOMA_R following further adjustment for moderate to vigorous intensity activity (β = -0.125, P < .05). Similar results were observed when light physical activity was modeled as quartiles, especially in elderly women. These cross-sectional data suggest that light-intensity physical activity is beneficially associated with insulin resistance in elderly Japanese women.

Determinants of intensive insulin therapeutic regimens in patients with type 1 diabetes: data from a nationwide multicenter survey in Brazil

PubMed Central

2014-01-01

Background To evaluate the determinants of intensive insulin regimens (ITs) in patients with type 1 diabetes (T1D). Methods This multicenter study was conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. Data were obtained from 3,591 patients (56.0% female, 57.1% Caucasian). Insulin regimens were classified as follows: group 1, conventional therapy (CT) (intermediate human insulin, one to two injections daily); group 2 (three or more insulin injections of intermediate plus regular human insulin); group 3 (three or more insulin injections of intermediate human insulin plus short-acting insulin analogues); group 4, basal-bolus (one or two insulin injections of long-acting plus short-acting insulin analogues or regular insulin); and group 5, basal-bolus with continuous subcutaneous insulin infusion (CSII). Groups 2 to 5 were considered IT groups. Results We obtained complete data from 2,961 patients. Combined intermediate plus regular human insulin was the most used therapeutic regimen. CSII was used by 37 (1.2%) patients and IT by 2,669 (90.2%) patients. More patients on IT performed self-monitoring of blood glucose and were treated at the tertiary care level compared to CT patients (p < 0.001). The majority of patients from all groups had HbA1c levels above the target. Overweight or obesity was not associated with insulin regimen. Logistic regression analysis showed that economic status, age, ethnicity, and level of care were associated with IT (p < 0.001). Conclusions Given the prevalence of intensive treatment for T1D in Brazil, more effective therapeutic strategies are needed for long term-health benefits. PMID:24920963

Sodium-Glucose Cotransporter 2 Inhibitors Reduce Prandial Insulin Doses in Type 2 Diabetic Patients Treated With the Intensive Insulin Therapy.

PubMed

Hakoshima, Mariko; Yanai, Hidekatsu; Kakuta, Kouki; Adachi, Hiroki

2018-06-01

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are anti-diabetic drugs which improve blood glucose control by blocking reabsorption of glucose from the proximal tubule of kidney. Anti-atherosclerotic properties and cardiovascular protective effects of SGLT2i have been demonstrated by recent studies; however, the efficacy and safety of addition of SGLT2i to the intensive insulin therapy remain largely unknown. We retrospectively picked up patients hospitalized for treatment of type 2 diabetes, who had been treated by the intensive insulin therapy and whose treatment using by SGLT2i started during their hospitalization. Such patients were picked up between June 2014 and May 2017 based on medical charts. We found 12 eligible patients. Observation period was 10.2 ± 4.7 days, and SGLT2i was started at 12.2 ± 12.9 days after the admission. During observation period, nobody developed hypoglycemia. In spite of showing decrease of blood glucose (non-significant) before each meal, the addition of SGLT2i significantly reduced daily prandial insulin doses by approximately 4.6 units/day (-66%). The SGLT2i addition also decreased body weight by approximately 1.3 kg. Present study demonstrated that the addition of SGLT2i to intensive insulin therapy reduced prandial insulin doses and body weight, without the development of hypoglycemia. This result may be due to SGLT2i-mediated improvement of postprandial hyperglycemia by increasing urinary glucose excretion not via insulin secretion.

A Mobile Computerized Decision Support System to Prevent Hypoglycemia in Hospitalized Patients With Type 2 Diabetes Mellitus

PubMed Central

Spat, Stephan; Donsa, Klaus; Beck, Peter; Höll, Bernhard; Mader, Julia K.; Schaupp, Lukas; Augustin, Thomas; Chiarugi, Franco; Lichtenegger, Katharina M.; Plank, Johannes; Pieber, Thomas R.

2016-01-01

Background: Diabetes management requires complex and interdisciplinary cooperation of health care professionals (HCPs). To support this complex process, IT-support is recommended by clinical guidelines. The aim of this article is to report on results from a clinical feasibility study testing the prototype of a mobile, tablet-based client-server system for computerized decision and workflow support (GlucoTab®) and to discuss its impact on hypoglycemia prevention. Methods: The system was tested in a monocentric, open, noncontrolled intervention study in 30 patients with type 2 diabetes mellitus (T2DM). The system supports HCPs in performing a basal-bolus insulin therapy. Diabetes therapy, adverse events, software errors and user feedback were documented. Safety, efficacy and user acceptance of the system were investigated. Results: Only 1.3% of blood glucose (BG) measurements were <70 mg/dl and only 2.6% were >300 mg/dl. The availability of the system (97.3%) and the rate of treatment activities documented with the system (>93.5%) were high. Only few suggestions from the system were overruled by the users (>95.7% adherence). Evaluation of the 3 anonymous questionnaires showed that confidence in the system increased over time. The majority of users believed that treatment errors could be prevented by using this system. Conclusions: Data from our feasibility study show a significant reduction of hypoglycemia by implementing a computerized system for workflow and decision support for diabetes management, compared to a paper-based process. The system was well accepted by HCPs, which is shown in the user acceptance analysis and that users adhered to the insulin dose suggestions made by the system. PMID:27810995

Physical Training Improves Insulin Resistance Syndrome Markers in Obese Adolescents.

ERIC Educational Resources Information Center

Kang, Hyun-Sik; Gutin, Bernard; Barbeau, Paule; Owens, Scott; Lemmon, Christian R.; Allison, Jerry; Litaker, Mark S.; Le, Ngoc-Anh

2002-01-01

Tested the hypothesis that physical training (PT), especially high-intensity PT, would favorably affect components of the insulin resistance syndrome (IRS) in obese adolescents. Data on teens randomized into lifestyle education (LSE) alone, LSE plus moderate -intensity PT, and LSE plus high-intensity PT indicated that PT, especially high-intensity…

[Influence and mechanism of a tight control of blood glucose by intensive insulin therapy on human sepsis].

PubMed

Yu, Wen-kui; Li, Wei-qin; Wang, Xiao-dong; Yan, Xiao-wen; Qi, Xiao-ping; Li, Ning; Li, Jie-shou

2005-01-01

To investigate the effect of a tight control of blood glucose by intensive insulin therapy on human sepsis, and to explore the potential mechanism of the intensive insulin therapy. Eligible patients were randomized by a blinded pharmacist to receive tight control of blood glucose by intensive insulin therapy (maintenance of blood glucose at a level between 4.4 and 6.1 mmol/L) or to receive conventional treatment (maintenance of glucose at a level between 10.0 and 11.1 mmol/L). The expression of HLA-DR on peripheral monocytes was measured in 54 patients by flow cytometry on 24 h, 3 d, 5 d, 7 d, 10 d and 14 d of intensive care in parallel with serum c-reactive protein (CRP), severity of the disease (APACHE II score, SOFA score) and clinical data collection. Patients receiving intensive insulin therapy were less likely to require prolonged mechanical ventilation. Tight control of blood glucose significantly reduced the number of days during which leukopenia or leukocytosis and the days with hypo- or hyperthermia (P < 0.05). Hypoglycemia occurred in 3 patients (10.7%) in the tight control of blood glucose group. There were no instance of hemodynamic deterioration or convulsions. Compared with the conventional treatment, tight control of blood glucose also increased the HLA-DR expression of peripheral monocytes, and there were significantly difference on 3 d, 5 d and 7 d (P < 0.05). Whereas it suppressed the elevated serum CRP concentrations, there was significantly difference on 7 d (P < 0.05). Tight control of blood glucose by intensive insulin therapy expedited healing of human sepsis, and increased the HLA-DR expression of peripheral and suppressed the elevated serum CRP. So, it is necessary to use insulin to strict control the glucose levels in human sepsis.

[Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy].

PubMed

Pesić, Milica; Zivić, Sasa; Radenković, Sasa; Velojić, Milena; Dimić, Dragan; Antić, Slobodan

2007-04-01

Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin) for basal insulin supply in patients with type 1 diabetes. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IT) were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15); 2. NPH insulin twice daily (n = 15); 3. insulin glargine once daily (n = 18). Meal time insulin aspart was continued in all groups. Fasting blood glucose (FBG) was lower in the glargine group (7.30+/-0.98 mmol/1) than in the twice daily NPH group (7.47+/-1.06 mmol/1), but without significant difference. FBG was significantly higher in the once daily NPH group (8.44+/-0.85 mmol/l; p < 0.05). HbAlc after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72+/-0.86% to 6.87+/-0.50%), as well as in the twice daily NPH group (from 7.80+/-0.83% to 7.01+/-0.63%). Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56+/-2.09) than in both NPH groups (9.0+/-1.65 in twice daily NPH group and 8.13+/-1.30 in other NPH group) (episodes/patients-month, p < 0.05). Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbAlc and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

Anesthesia with propofol induces insulin resistance systemically in skeletal and cardiac muscles and liver of rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yasuda, Yoshikazu; Fukushima, Yuji; Kaneki, Masao

Highlights: ► Propofol, as a model anesthetic drug, induced whole body insulin resistance. ► Propofol anesthesia decreased glucose infusion rate to maintain euglycemia. ► Propofol decreased insulin-mediated glucose uptake in skeletal and cardiac muscles. ► Propofol increased hepatic glucose output confirming hepatic insulin resistance. -- Abstract: Hyperglycemia together with hepatic and muscle insulin resistance are common features in critically ill patients, and these changes are associated with enhanced inflammatory response, increased susceptibility to infection, muscle wasting, and worsened prognosis. Tight blood glucose control by intensive insulin treatment may reduce the morbidity and mortality in intensive care units. Although some anestheticsmore » have been shown to cause insulin resistance, it remains unknown how and in which tissues insulin resistance is induced by anesthetics. Moreover, the effects of propofol, a clinically relevant intravenous anesthetic, also used in the intensive care unit for sedation, on insulin sensitivity have not yet been investigated. Euglycemic hyperinsulinemic clamp study was performed in rats anesthetized with propofol and conscious unrestrained rats. To evaluate glucose uptake in tissues and hepatic glucose output [{sup 3}H]glucose and 2-deoxy[{sup 14}C]glucose were infused during the clamp study. Anesthesia with propofol induced a marked whole-body insulin resistance compared with conscious rats, as reflected by significantly decreased glucose infusion rate to maintain euglycemia. Insulin-stimulated tissue glucose uptake was decreased in skeletal muscle and heart, and hepatic glucose output was increased in propofol anesthetized rats. Anesthesia with propofol induces systemic insulin resistance along with decreases in insulin-stimulated glucose uptake in skeletal and heart muscle and attenuation of the insulin-mediated suppression of hepatic glucose output in rats.« less

A decade of temporal trends in overweight/obesity in youth with type 1 diabetes after the Diabetes Control and Complications Trial.

PubMed

Baskaran, Charumathi; Volkening, Lisa K; Diaz, Monica; Laffel, Lori M

2015-06-01

Youth with type 1 diabetes (T1D) are at risk for weight gain due to the epidemic of childhood overweight/obesity and common use of intensive insulin therapy; the latter resulted in weight gain in the Diabetes Control and Complications Trial. To assess overweight/obesity prevalence and intensive insulin therapy use in youth with T1D over a decade and identify factors associated with weight status and glycemic control. We obtained cross-sectional data from four unique cohorts (1999, 2002, 2006, and 2009). Youth (N = 507, 49% male) were 8-16 yr old with T1D duration ≥6 months, A1c 6.0-12.0% (42-108 mmol/mol), and daily insulin dose ≥0.5 U/kg. Across cohorts, age, body mass index (BMI) percentile, and A1c ranged from 12.0 ± 2.2 to 12.8 ± 2.3 yr, 70 ± 22 to 72 ± 21, and 8.3 ± 1.0 (67 ± 11) to 8.5 ± 1.1% (69 ± 12 mmol/mol), respectively. Intensive insulin therapy use increased from 52 to 97% (p < 0.001) between 1999 and 2009. However, prevalence of overweight/obesity remained similar, 27% (1999), 36% (2002), 33% (2006), and 31% (2009) (p = 0.54), as did z-BMI. In multivariate analysis, higher A1c was related to higher insulin dose (p < 0.01), less frequent blood glucose monitoring (p < 0.001), and non-white race (p < 0.001); A1c was not related to z-BMI, intensive insulin therapy, or cohort. z-BMI was related to insulin dose (p < 0.005) but not intensive insulin therapy or cohort. Despite near-universal implementation of intensive insulin therapy, overweight/obesity prevalence in youth with T1D remained stable over a decade, similar to the general pediatric population. However, A1c remained suboptimal, underscoring the need to optimize T1D treatment to reduce future complication risk. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

An Evaluation of Computerized Behavioral Skills Training to Teach Safety Skills to Young Children

ERIC Educational Resources Information Center

Vanselow, Nicholas R.; Hanley, Gregory P.

2014-01-01

Previous research has demonstrated the efficacy of behavioral skills training (BST) and in situ training (IST) for teaching children to protect themselves. However, BST may be resource intensive and difficult to implement on a large scale. We evaluated a computerized version of BST (CBST) to teach safety skills and determined the extent to which…

Objectively measured sedentary time and associations with insulin sensitivity: Importance of reallocating sedentary time to physical activity.

PubMed

Yates, Thomas; Henson, Joseph; Edwardson, Charlotte; Dunstan, David; Bodicoat, Danielle H; Khunti, Kamlesh; Davies, Melanie J

2015-07-01

The aim of this study is to quantify associations between objectively measured sedentary time and markers of insulin sensitivity by considering allocation into light-intensity physical activity or moderate- to vigorous-intensity physical activity (MVPA). Participants with an increased risk of impaired glucose regulation (IGR) were recruited (Leicestershire, United Kingdom, 2010-2011). Sedentary, light-intensity physical activity and MVPA time were measured using accelerometers. Fasting and 2-hour post-challenge insulin and glucose were assessed; insulin sensitivity was calculated by HOMA-IS and Matsuda-ISI. Isotemporal substitution regression models were used. Data were analysed in 2014. 508 participants were included (average age=65years, female=34%). Reallocating 30min of sedentary time into light-intensity physical activity was associated a 5% (95% CI 1, 9%; p=0.024) difference in Matsuda-ISI after adjustment for measured confounding variables. Reallocation into MVPA was associated with a 15% (7, 25%; p<0.001) difference in HOMA-IS and 18% (8, 28%; p<0.001) difference in Matsuda-ISI. Results for light-intensity physical activity were modified by IGR status with stronger associations seen in those with IGR. Reallocating sedentary time into light-intensity physical activity or MVPA was associated with differences in insulin sensitivity, with stronger and more consistent associations seen for MVPA. Copyright © 2015. Published by Elsevier Inc.

Effects of active recovery during interval training on plasma catecholamines and insulin.

PubMed

Nalbandian, Harutiun M; Radak, Zsolt; Takeda, Masaki

2018-06-01

BACKGROUNDː Active recovery has been used as a method to accelerate the recovery during intense exercise. It also has been shown to improve performance in subsequent exercises, but little is known about its acute effects on the hormonal and metabolic profile. The aim of this research was to study the effects of active recovery on plasma catecholamines and plasma insulin during a high-intensity interval exercise. METHODSː Seven subjects performed two high-intensity interval training protocols which consisted of three 30-second high-intensity bouts (constant intensity), separated by a recovery of 4 minutes. The recovery was either active recovery or passive recovery. During the main test blood samples were collected and plasma insulin, plasma catecholamines and blood lactate were determined. Furthermore, respiratory gasses were also measured. RESULTSː Plasma insulin and blood lactate were significantly higher in the passive recovery trial, while plasma adrenaline was higher in the active recovery. Additionally, VO2 and VCO2 were significantly more increased during the active recovery trials. CONCLUSIONSː These results suggest that active recovery affects the hormonal and metabolic responses to high-intensity interval exercise. Active recovery produces a hormonal environment which may favor lipolysis and oxidative metabolism, while passive recovery may be favoring glycolysis.

Endocrinology and Adolescence: aerobic exercise reduces insulin resistance markers in obese youth: a meta-analysis of randomized controlled trials.

PubMed

García-Hermoso, Antonio; Saavedra, Jose M; Escalante, Yolanda; Sánchez-López, Mairena; Martínez-Vizcaíno, Vicente

2014-10-01

The purpose of this meta-analysis was to examine the evidence for the effectiveness of aerobic exercise interventions on reducing insulin resistance markers in obese children and/or adolescents. A secondary outcome was change in percentage of body fat. A computerized search was made from seven databases: CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, ERIC, MEDLINE, PsycINFO, and Science Citation Index. The analysis was restricted to randomized controlled trials that examined the effect of aerobic exercise on insulin resistance markers in obese youth. Two independent reviewers screened studies and extracted data. Effect sizes (ES) and 95% confidence interval (CI) were calculated, and the heterogeneity of the studies was estimated using Cochran's Q-statistic. Nine studies were selected for meta-analysis as they fulfilled the inclusion criteria (n=367). Aerobic exercise interventions resulted in decreases in fasting glucose (ES=-0.39; low heterogeneity) and insulin (ES=-0.40; low heterogeneity) and in percentage of body fat (ES=-0.35; low heterogeneity). These improvements were specifically accentuated in adolescents (only in fasting insulin), or through programs lasting more than 12 weeks, three sessions per week, and over 60 min of aerobic exercise per session. This meta-analysis provides insights into the effectiveness of aerobic exercise interventions on insulin resistance markers in the obese youth population. © 2014 European Society of Endocrinology.

The effects of electromagnetic pulses (EMP) on the bioactivity of insulin and a preliminary study of mechanism.

PubMed

Chen, Yong Bin; Li, Jing; Qi, Yuhong; Miao, Xia; Zhou, Yongchun; Ren, Dongqing; Guo, G Z

2010-01-01

To investigate the effects of electromagnetic pulse (EMP) exposure on the bioactivity of insulin and a preliminary mechanism for these effects. A tapered parallel plate Gigahertz Transverse Electromagnetic (GTEM) cell with a flared rectangular coaxial transmission line was used to expose the insulin solution to EMP. Concurrent sham-exposed insulin solutions were used as a control. The effect of EMP-exposed insulin on fasting blood glucose levels of type I diabetes model mice, the effect of EMP on binding affinity between insulin and its receptor and the effect of EMP on insulin's fluorescence intensity were detected, respectively. (i) After EMP exposure, compared with sham-exposed insulin, the bioactivity of insulin in decreasing fasting blood glucose levels in type I diabetes model mice was reduced significantly (p = 0.023). (ii) Compared with sham-exposed insulin group, the percentage fluorescein isothiocyannate (FITC) labelling of HL-7702 cells was significantly reduced in the EMP-exposed insulin group (22.7-13.8%, respectively). (iii) Compared with sham-exposed insulin, the fluorescence intensity was significantly reduced in EMP-exposed insulin (p < 0.001). EMP exposure significantly decreased the bioactivity of insulin to reduce the blood glucose levels in type I diabetic mice. This could be due to a decreased binding affinity between insulin and its receptor. This mechanism could involve an alteration of insulin's' conformation caused by EMP exposure.

Computer versus paper system for recognition and management of sepsis in surgical intensive care.

PubMed

Croft, Chasen A; Moore, Frederick A; Efron, Philip A; Marker, Peggy S; Gabrielli, Andrea; Westhoff, Lynn S; Lottenberg, Lawrence; Jordan, Janeen; Klink, Victoria; Sailors, R Matthew; McKinley, Bruce A

2014-02-01

A system to provide surveillance, diagnosis, and protocolized management of surgical intensive care unit (SICU) sepsis was undertaken as a performance improvement project. A system for sepsis management was implemented for SICU patients using paper followed by a computerized system. The hypothesis was that the computerized system would be associated with improved process and outcomes. A system was designed to provide early recognition and guide patient-specific management of sepsis including (1) modified early warning signs-sepsis recognition score (MEWS-SRS; summative point score of ranges of vital signs, mental status, white blood cell count; after every 4 hours) by bedside nurse; (2) suspected site assessment (vascular access, lung, abdomen, urinary tract, soft tissue, other) at bedside by physician or extender; (3) sepsis management protocol (replicable, point-of-care decisions) at bedside by nurse, physician, and extender. The system was implemented first using paper and then a computerized system. Sepsis severity was defined using standard criteria. In January to May 2012, a paper system was used to manage 77 consecutive sepsis encounters (3.9 ± 0.5 cases per week) in 65 patients (77% male; age, 53 ± 2 years). In June to December 2012, a computerized system was used to manage 132 consecutive sepsis encounters (4.4 ± 0.4 cases per week) in 119 patients (63% male; age, 58 ± 2 years). MEWS-SRS elicited 683 site assessments, and 201 had sepsis diagnosis and protocol management. The predominant site of infection was abdomen (paper, 58%; computer, 53%). Recognition of early sepsis tended to occur more using the computerized system (paper, 23%; computer, 35%). Hospital mortality rate for surgical ICU sepsis (paper, 20%; computer, 14%) was less with the computerized system. A computerized sepsis management system improves care process and outcome. Early sepsis is recognized and managed with greater frequency compared with severe sepsis or septic shock. The system has a beneficial effect as a clinical standard of care for SICU patients. Therapeutic study, level III.

Short-term intensive insulin therapy in type 2 diabetes mellitus: a systematic review and meta-analysis.

PubMed

Kramer, Caroline Kaercher; Zinman, Bernard; Retnakaran, Ravi

2013-09-01

Studies have shown that, when implemented early in the course of type 2 diabetes mellitus, treatment with intensive insulin therapy for 2-3 weeks can induce a glycaemic remission, wherein patients are able to maintain normoglycaemia without any anti-diabetic medication. We thus did a systematic review and meta-analysis of interventional studies to assess the effect of short-term intensive insulin therapy on the pathophysiological defects underlying type 2 diabetes mellitus (pancreatic β-cell dysfunction and insulin resistance) and identify clinical predictors of remission. We identified studies published between 1950 and Nov 19, 2012, which assessed the effect of intensive insulin therapy on β-cell function or insulin resistance, or both, or assessed long-term drug-free glycaemic remission in adults aged 18 years or older with newly diagnosed type 2 diabetes mellitus. We calculated pooled estimates by random-effects model. This study is registered with International Prospective Register of Systematic Reviews, number CRD42012002829. We identified 1645 studies of which seven fulfilled inclusion criteria (n=839 participants). Five studies were non-randomised. A pooled analysis of the seven studies showed a post-intensive insulin therapy increase in Homeostasis Model Assessment of β-cell function as compared with baseline (1·13, 95% CI 1·02 to 1·25) and a decrease in Homeostasis Model Assessment of Insulin Resistance (-0·57, -0·84 to -0·29). In the four studies that assessed glycaemic remission (n=559 participants), the proportion of participants in drug-free remission was about 66·2% (292 of 441 patients) after 3 months of follow-up, about 58·9% (222 of 377 patients) after 6 months, about 46·3% (229 of 495 patients) after 12 months, and about 42·1% (53 of 126 patients) after 24 months. Patients who achieved remission had higher body-mass index than those who did not achieve remission (1·06 kg/m(2), 95% CI 0·55 to 1·58) and lower fasting plasma glucose (-0·59 mmol/L, 95% CI -1·11 to -0·07) at baseline. Short-term intensive insulin therapy can improve the underlying pathophysiology in early type 2 diabetes mellitus, and thus might provide a treatment strategy for modifying the natural history of diabetes. None. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of Exercise Intensity on Postprandial Improvement in Glucose Disposal and Insulin Sensitivity in Prediabetic Adults

PubMed Central

Rynders, Corey A.; Weltman, Judy Y.; Jiang, Boyi; Breton, Marc; Patrie, James; Barrett, Eugene J.

2014-01-01

Background: A single bout of exercise improves postprandial glycemia and insulin sensitivity in prediabetic patients; however, the impact of exercise intensity is not well understood. The present study compared the effects of acute isocaloric moderate (MIE) and high-intensity (HIE) exercise on glucose disposal and insulin sensitivity in prediabetic adults. Methods: Subjects (n = 18; age 49 ± 14 y; fasting glucose 105 ± 11 mg/dL; 2 h glucose 170 ± 32 mg/dL) completed a peak O2 consumption/lactate threshold (LT) protocol plus three randomly assigned conditions: 1) control, 1 hour of seated rest, 2) MIE (at LT), and 3) HIE (75% of difference between LT and peak O2 consumption). One hour after exercise, subjects received an oral glucose tolerance test (OGTT). Plasma glucose, insulin, and C-peptide concentrations were sampled at 5- to 10-minute intervals at baseline, during exercise, after exercise, and for 3 hours after glucose ingestion. Total, early-phase, and late-phase area under the glucose and insulin response curves were compared between conditions. Indices of insulin sensitivity (SI) were derived from OGTT data using the oral minimal model. Results: Compared with control, SI improved by 51% (P = .02) and 85% (P < .001) on the MIE and HIE days, respectively. No differences in SI were observed between the exercise conditions (P = .62). Improvements in SI corresponded to significant reductions in the glucose, insulin, and C-peptide area under the curve values during the late phase of the OGTT after HIE (P < .05), with only a trend for reductions after MIE. Conclusion: These results suggest that in prediabetic adults, acute exercise has an immediate and intensity-dependent effect on improving postprandial glycemia and insulin sensitivity. PMID:24243632

Glucose control and use of continuous glucose monitoring in the intensive care unit: a critical review.

PubMed

De Block, Christophe; Manuel-y-Keenoy, Begoña; Rogiers, Peter; Jorens, Philippe; Van Gaal, Luc

2008-08-01

Stress hyperglycemia recently became a major therapeutic target in the Intensive Care Unit (ICU) since it occurs in most critically ill patients and is associated with adverse outcome, including increased mortality. Intensive insulin therapy to achieve normoglycemia may reduce mortality, morbidity and the length of ICU and in-hospital stay. However, obtaining normoglycemia requires extensive efforts from the medical staff, including frequent glucose monitoring and adjustment of insulin dose. Current insulin titration is based upon discrete glucose measurements, which may miss fast changes in glycemia and which does not give a full picture of overall glycemic control. Recent evidence suggests that continuous monitoring of glucose levels may help to signal glycemic excursions and eventually to optimize insulin titration in the ICU. In this review we will summarise monitoring and treatment strategies to achieve normoglycemia in the ICU, with special emphasis on the possible advantages of continuous glucose monitoring.

What Are the Safety Considerations for Insulin Control for Athletes?

ERIC Educational Resources Information Center

McDaniel, Larry W.; Olson, Sara; Gaudet, Laura; Jackson, Allen

2010-01-01

Athletes diagnosed with diabetes may have difficulty with their blood sugar levels fluctuating during intense exercise. Considerations for athletes with insulin concerns may range anywhere from exercise rehabilitation to the use of an automatic insulin pump. The automatic insulin pump is a small battery-operated device about the size of a pager.…

Low intensity exercise prevents disturbances in rat cardiac insulin signaling and endothelial nitric oxide synthase induced by high fructose diet.

PubMed

Stanišić, Jelena; Korićanac, Goran; Ćulafić, Tijana; Romić, Snježana; Stojiljković, Mojca; Kostić, Milan; Pantelić, Marija; Tepavčević, Snežana

2016-01-15

Increase in fructose consumption together with decrease in physical activity contributes to the development of metabolic syndrome and consequently cardiovascular diseases. The current study examined the preventive role of exercise on defects in cardiac insulin signaling and function of endothelial nitric oxide synthase (eNOS) in fructose fed rats. Male Wistar rats were divided into control, sedentary fructose (received 10% fructose for 9 weeks) and exercise fructose (additionally exposed to low intensity exercise) groups. Concentration of triglycerides, glucose, insulin and visceral adipose tissue weight were determined to estimate metabolic syndrome development. Expression and/or phosphorylation of cardiac insulin receptor (IR), insulin receptor substrate 1 (IRS1), tyrosine-specific protein phosphatase 1B (PTP1B), Akt, extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and eNOS were evaluated. Fructose overload increased visceral adipose tissue, insulin concentration and homeostasis model assessment index. Exercise managed to decrease visceral adiposity and insulin level and to increase insulin sensitivity. Fructose diet increased level of cardiac PTP1B and pIRS1 (Ser307), while levels of IR and ERK1/2, as well as pIRS1 (Tyr 632), pAkt (Ser473, Thr308) and pERK1/2 were decreased. These disturbances were accompanied by reduced phosphorylation of eNOS at Ser1177. Exercise managed to prevent most of the disturbances in insulin signaling caused by fructose diet (except phosphorylation of IRS1 at Tyr 632 and phosphorylation and protein expression of ERK1/2) and consequently restored function of eNOS. Low intensity exercise could be considered as efficient treatment of cardiac insulin resistance induced by fructose diet. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Performance of an Electronic Diary System for Intensive Insulin Management in Global Diabetes Clinical Trials

PubMed Central

Zhang, Shuyu; Mou, Jiani; Hackett, Andy P.; Raymond, Stephen A.; Chang, Annette M.

2015-01-01

Abstract Background: This report describes the performance of a wireless electronic diary (e-diary) system for data collection and enhanced patient–investigator interactions during intensive insulin management in diabetes clinical trials. Materials and Methods: We implemented a customized electronic communication system featuring an e-diary and a Web portal in three global, randomized, controlled Phase 3 clinical trials testing basal insulin peglispro compared with insulin glargine, both combined with prandial insulin lispro, in patients with type 1 or type 2 diabetes mellitus (T1DM and T2DM, respectively). We collected data during 28 weeks of study e-diary use for the report. Results: Patients (n=2,938) in 31 countries used e-diaries to transmit 2,439,087 blood glucose (BG) values, 96% of which were associated by the patient with a protocol time point during the 72-h response window. Of 208,192 hypoglycemia events captured, 96% had a BG value, and 95% had treatments and outcomes entered by patients within the 72-h window. Patients recorded administration of 1,964,477 insulin doses; 93% of basal insulin doses were adherent with the investigator prescription. Investigators adjusted 13 basal and 92 bolus insulin prescriptions per patient-year using the e-diary system. After 26 weeks of treatment and e-diary use in the combined study arms, hemoglobin A1c values decreased by 0.6% or 1.6% and fasting BG decreased by 7.8 or 28 mg/dL in patients with T1DM or T2DM, respectively. Conclusions: The e-diary system enabled comprehensive data collection and facilitated communication between investigators and patients for intensive insulin management in three global clinical trials testing basal insulins. PMID:25826466

A single bout of high-intensity interval exercise and work-matched moderate-intensity exercise has minimal effect on glucose tolerance and insulin sensitivity in 7- to 10-year-old boys.

PubMed

Cockcroft, Emma J; Williams, Craig A; Jackman, Sarah R; Bassi, Shikhar; Armstrong, Neil; Barker, Alan R

2018-01-01

The purpose of this study was to assess the acute effect of high-intensity interval exercise (HIIE) and moderate-intensity exercise (MIE) on glucose tolerance, insulin sensitivity and fat oxidation in young boys. Eleven boys (8.8 ± 0.8 y) completed three conditions: 1) HIIE; 2) work-matched MIE; and 3) rest (CON) followed by an oral glucose tolerance test (OGTT) to determine glucose tolerance and insulin sensitivity (Cederholm index). Fat oxidation was measured following the OGTT using indirect calorimetry. There was no effect for condition on plasma [glucose] and [insulin] area under the curve (AUC) responses following the OGTT (P > 0.09). However, there was a "trend" for a condition effect for insulin sensitivity with a small increase after HIIE (P = 0.04, ES = 0.28, 9.7%) and MIE (P = 0.07, ES = 0.21, 6.5%) compared to CON. There was an increase in fat oxidation AUC following HIIE (P = 0.008, ES = 0.79, 38.9%) compared to CON, but with no differences between MIE and CON and HIIE and MIE (P > 0.13). In conclusion, 7- to 10-year-old boys may have limited scope to improve insulin sensitivity and glucose tolerance after a single bout of HIIE and MIE. However, fat oxidation is augmented after HIIE but not MIE.

Effects of Multi-Electrode Renal Denervation on Insulin Sensitivity and Glucose Metabolism in a Canine Model of Type 2 Diabetes Mellitus.

PubMed

Pan, Tao; Guo, Jin-He; Ling, Long; Qian, Yue; Dong, Yong-Hua; Yin, Hua-Qing; Zhu, Hai-Dong; Teng, Gao-Jun

2018-05-01

To evaluate the effects of multi-electrode catheter-based renal denervation (RDN) on insulin sensitivity and glucose metabolism in a type 2 diabetes mellitus (T2DM) canine model. Thirty-three dogs were divided equally into 3 groups: bilateral renal denervation (BRDN) group, left renal denervation (LRDN) group, and sham operation (SHAM) group. Body weight and blood biochemistry were measured at baseline, 20 weeks, and 32 weeks, and renal angiography and computerized tomographic (CT) angiography were determined before the procedure and 1 month, 2 months, and 3 months after the procedure. Western blot was used to identify the activities of gluconeogenic enzymes and insulin-signaling proteins. Fasting plasma glucose (9.64 ± 1.57 mmol/L vs 5.12 ± 1.08 mmol/L; P < .0001), fasting insulin (16.19 ± 1.43 mIU/mL vs 5.07 ± 1.13 mIU/mL; P < .0001), and homeostasis-model assessment of insulin resistance (HOMA-IR; 6.95 ± 1.33 vs 1.15 ± 0.33; P < .0001) in the BRDN group had significantly decreased at the 3-month follow-up compared with the SHAM group. Western blot analyses showed that RDN suppressed the gluconeogenetic genes, modulated insulin action, and activated insulin receptors-AKT signaling cascade in the liver. CT angiography and histopathologic analyses did not show any dissection, aneurysm, thrombus, or rupture in any of the renal arteries. These findings identified that multi-electrode catheter-based RDN could effectively decrease gluconeogenesis and glycogenolysis, resulting in improvements in insulin sensitivity and glucose metabolism in a T2DM canine model. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

Short-term intensive insulin therapy at diagnosis in type 2 diabetes: plan for filling the gaps.

PubMed

Weng, Jianping; Retnakaran, Ravi; Ariachery C, Ammini; Ji, Linong; Meneghini, Luigi; Yang, Wenying; Woo, Jeong-Taek

2015-09-01

Short-term intensive insulin therapy is unique amongst therapies for type 2 diabetes because it offers the potential to preserve and improve beta-cell function without additional pharmacological treatment. On the basis of clinical experience and the promising results of a series of studies in newly diagnosed patients, mostly in Asian populations, an expert workshop was convened to assess the available evidence and the potential application of short-term intensive insulin therapy should it be advocated for inclusion in clinical practice. Participants included primary care physicians and endocrinologists. We endorse the concept of short-term intensive insulin therapy as an option for some patients with type 2 diabetes at the time of diagnosis and have identified the following six areas where additional knowledge could help clarify optimal use in clinical practice: (1) generalizability to primary care, (2) target population and biomarkers, (3) follow-up treatment, (4) education of patients and providers, (5) relevance of ethnicity, and (6) health economics. © 2014 The Authors. Diabetes Metabolism Research and Reviews published by John Wiley & Sons, Ltd.

Intensive insulin treatment improves forearm blood flow in critically ill patients: a randomized parallel design clinical trial.

PubMed

Žuran, Ivan; Poredos, Pavel; Skale, Rafael; Voga, Gorazd; Gabrscek, Lucija; Pareznik, Roman

2009-01-01

Intensive insulin treatment of critically ill patients was seen as a promising method of treatment, though recent studies showed that reducing the blood glucose level below 6 mmol/l had a detrimental outcome. The mechanisms of the effects of insulin in the critically ill are not completely understood. The purpose of the study was to test the hypothesis that intensive insulin treatment may influence forearm blood flow independently of global hemodynamic indicators. The study encompassed 29 patients of both sexes who were admitted to the intensive care unit due to sepsis and required artificial ventilation as the result of acute respiratory failure. 14 patients were randomly selected for intensive insulin treatment (Group 1; blood glucose concentration 4.4-6.1 mmol/l), and 15 were selected for conventional insulin treatment (Group 2; blood glucose level 7.0 mmol/l-11.0 mmol/l). At the start of the study (t0, beginning up to 48 hours after admittance and the commencement of artificial ventilation), at 2 hours (t1), 24 hours (t2), and 72 hours (t3) flow in the forearm was measured for 60 minutes using the strain-gauge plethysmography method. Student's t-test of independent samples was used for comparisons between the two groups, and Mann-Whitney's U-test where appropriate. Linear regression analysis and the Pearson correlation coefficient were used to determine the levels of correlation. The difference in 60-minute forearm flow at the start of the study (t0) was not statistically significant between groups, while at t2 and t3 significantly higher values were recorded in Group 1 (t2; Group 1: 420.6 +/- 188.8 ml/100 ml tissue; Group 2: 266.1 +/- 122.2 ml/100 ml tissue (95% CI 30.9-278.0, P = 0.02); t3; Group 1: 369.9 +/- 150.3 ml/100 ml tissue; Group 2: 272.6 +/- 85.7 ml/100 ml tissue (95% CI 5.4-190.0, P = 0.04). At t1 a trend towards significantly higher values in Group 1 was noted (P = 0.05). The level of forearm flow was related to the amount of insulin infusion (r = 0.40). Compared to standard treatment, intensive insulin treatment of critically ill patients increases forearm flow. Flow increase was weakly related to the insulin dose, though not to blood glucose concentration. ISRCTN39026810.

Intensive insulin treatment improves forearm blood flow in critically ill patients: a randomized parallel design clinical trial

PubMed Central

2009-01-01

Introduction Intensive insulin treatment of critically ill patients was seen as a promising method of treatment, though recent studies showed that reducing the blood glucose level below 6 mmol/l had a detrimental outcome. The mechanisms of the effects of insulin in the critically ill are not completely understood. The purpose of the study was to test the hypothesis that intensive insulin treatment may influence forearm blood flow independently of global hemodynamic indicators. Methods The study encompassed 29 patients of both sexes who were admitted to the intensive care unit due to sepsis and required artificial ventilation as the result of acute respiratory failure. 14 patients were randomly selected for intensive insulin treatment (Group 1; blood glucose concentration 4.4-6.1 mmol/l), and 15 were selected for conventional insulin treatment (Group 2; blood glucose level 7.0 mmol/l-11.0 mmol/l). At the start of the study (t0, beginning up to 48 hours after admittance and the commencement of artificial ventilation), at 2 hours (t1), 24 hours (t2), and 72 hours (t3) flow in the forearm was measured for 60 minutes using the strain-gauge plethysmography method. Student's t-test of independent samples was used for comparisons between the two groups, and Mann-Whitney's U-test where appropriate. Linear regression analysis and the Pearson correlation coefficient were used to determine the levels of correlation. Results The difference in 60-minute forearm flow at the start of the study (t0) was not statistically significant between groups, while at t2 and t3 significantly higher values were recorded in Group 1 (t2; Group 1: 420.6 ± 188.8 ml/100 ml tissue; Group 2: 266.1 ± 122.2 ml/100 ml tissue (95% CI 30.9-278.0, P = 0.02); t3; Group 1: 369.9 ± 150.3 ml/100 ml tissue; Group 2: 272.6 ± 85.7 ml/100 ml tissue (95% CI 5.4-190.0, P = 0.04). At t1 a trend towards significantly higher values in Group 1 was noted (P = 0.05). The level of forearm flow was related to the amount of insulin infusion (r = 0.40). Conclusions Compared to standard treatment, intensive insulin treatment of critically ill patients increases forearm flow. Flow increase was weakly related to the insulin dose, though not to blood glucose concentration. Trial Registration Trial number: ISRCTN39026810. PMID:20003200

High intensity interval training is associated with greater impact on physical fitness, insulin sensitivity and muscle mitochondrial content in males with overweight/obesity, as opposed to continuous endurance training: a randomized controlled trial.

PubMed

De Strijcker, Dorien; Lapauw, Bruno; Ouwens, D Margriet; Van de Velde, Dominique; Hansen, Dominique; Petrovic, Mirko; Cuvelier, Claude; Tonoli, Cajsa; Calders, Patrick

2018-06-01

To evaluate the effect of high intensity training (HIT) on physical fitness, basal respiratory exchange ratio (bRER), insulin sensitivity and muscle histology in overweight/obese men compared to continuous aerobic training (CAT). 16 male participants with overweight/obesity (age: 42-57 years, body mass index: 28-36 kg/m2) were randomized to HIT (n=8) or CAT (n=8) for 10 weeks, twice a week. HIT was composed of 10 minutes high intensity, 10 minutes continuous aerobic, 10 minutes high intensity exercises. CAT was composed of three times 10 minutes continuous exercising. Changes in anthropometry, physical and metabolic fitness were evaluated. Muscle histology (mitochondria and lipid content) was evaluated by transmission electron microscopy (TEM). HIT showed a significant increase for peak VO2 (P=0.01), for insulin sensitivity (AUC glucose (P<0,001), AUC insulin (P<0,001), OGTT composite score (P=0.007)) and a significant decrease of bRER (P<0.001) compared to CAT. Muscle mitochondrial content was significantly increased after HIT at the subsarcolemmal (P=0.004 number and P=0.001 surface) as well as the intermyofibrillar site (P<0.001 number and P=0.001 surface). High intensity training elicits stronger beneficial effects on physical fitness, basal RER, insulin sensitivity, and muscle mitochondrial content, as compared to continuous aerobic training.

Intensive lifestyle intervention including high-intensity interval training program improves insulin resistance and fasting plasma glucose in obese patients.

PubMed

Marquis-Gravel, Guillaume; Hayami, Douglas; Juneau, Martin; Nigam, Anil; Guilbeault, Valérie; Latour, Élise; Gayda, Mathieu

2015-01-01

To analyze the effects of a long-term intensive lifestyle intervention including high-intensity interval training (HIIT) and Mediterranean diet (MedD) counseling on glycemic control parameters, insulin resistance and β-cell function in obese subjects. The glycemic control parameters (fasting plasma glucose, glycated hemoglobin), insulin resistance, and β-cell function of 72 obese subjects (54 women; mean age = 53 ± 9 years) were assessed at baseline and upon completion of a 9-month intensive lifestyle intervention program conducted at the cardiovascular prevention and rehabilitation center of the Montreal Heart Institute, from 2009 to 2012. The program included 2-3 weekly supervised exercise training sessions (HIIT and resistance exercise), combined to MedD counseling. Fasting plasma glucose (FPG) (mmol/L) (before: 5.5 ± 0.9; after: 5.2 ± 0.6; P < 0.0001), fasting insulin (pmol/L) (before: 98 ± 57; after: 82 ± 43; P = 0.003), and insulin resistance, as assessed by the HOMA-IR score (before: 3.6 ± 2.5; after: 2.8 ± 1.6; P = 0.0008) significantly improved, but not HbA1c (%) (before: 5.72 ± 0.55; after: 5.69 ± 0.39; P = 0.448), nor β-cell function (HOMA-β, %) (before: 149 ± 78; after: 144 ± 75; P = 0.58). Following a 9-month intensive lifestyle intervention combining HIIT and MedD counseling, obese subjects experienced significant improvements of FPG and insulin resistance. This is the first study to expose the effects of a long-term program combining HIIT and MedD on glycemic control parameters among obese subjects.

Age, sex, and symptom intensity influence test taking parameters on functional patient-reported outcomes.

PubMed

Cheville, Andrea L; Wang, Chun; Ni, Pengsheng; Jette, Alan M; Basford, Jeffrey R

2014-11-01

Item response theory-based patient-reported outcomes such as the Activity Measure for Post Acute Care Computerized Adaptive Test are gaining use because of their flexibility and ease of administration. Their psychometric properties are being explored, but little is known about how respondent characteristics may impact precision. The goal of this study was, therefore, to assess the effects of age, sex, and symptom intensity on respondents' test taking behaviors and scores. Three hundred eleven adults with late-stage lung cancer were consecutively enrolled between April 2008 and April 2009. Demographics and comorbidities were abstracted from their electronic medical records. The participants were followed on a 3- to 4-wk basis by telephonic interviews that involved administration of the Activity Measure for Post Acute Care Computerized Adaptive Test, followed by numerical rating scales scoring of their pain, fatigue, and dyspnea. In more than 2538 computerized adaptive test (CAT) sessions, three findings were prominent. First, the women and the older patients took longer to complete CAT sessions, were more likely to skip items, and produced scores with larger standard errors. Second, the respondents with higher levels of dyspnea and fatigue, but not pain, completed their CAT sessions more rapidly and were less likely to skip items. Third, fatigue and dyspnea interact with age but not sex to influence CAT duration and skip count. The findings of this study suggest that certain common clinical populations, for example, women, geriatric patients, and patients with intense symptoms, differ systematically in the time they are willing to devote to testing and the precision of their responses. The latter finding, unstable precision, is unlikely to be CAT specific and has implications for the interpretation of the scores of the Activity Measure for Post Acute Care Computerized Adaptive Test and other patient-reported outcomes.

The Effectiveness of Intensive Interaction, A Systematic Literature Review

ERIC Educational Resources Information Center

Hutchinson, Nick; Bodicoat, Anna

2015-01-01

Background: Intensive Interaction is an approach used for communicating with people with profound and multiple intellectual disabilities [PMID] or autism. It has gained increased recognition as a helpful technique, but the evidence has not been systematically reviewed. Method: Computerized and hand searches of the literature were conducted using…

How to implement information technology in the operating room and the intensive care unit.

PubMed

Meyfroidt, Geert

2009-03-01

The number of operating rooms and intensive care units looking for a data management system to perform their increasingly complex tasks is rising. Although at this time only a minority is computerized, within the next few years many centres will start implementing information technology. The transition towards a computerized system is a major venture, which will have a major impact on workflow. This chapter reviews the present literature. Published papers on this subject are predominantly single- or multi-centre implementation reports. The general principles that should guide such a process are described. For healthcare institutions or individual practitioners that plan to undertake this venture, the implementation process is described in a practical, nine-step overview.

Insulin Infusion Sets: A Critical Reappraisal.

PubMed

Heinemann, Lutz

2016-05-01

An insulin infusion set (IIS) is a key component of insulin pumps. In daily practice issues with the IIS appear to be as relevant for a successful insulin therapy as the pumps themselves. The insulin is applied to the subcutaneous tissue via a Teflon(®) (Dupont, Wilmington, DE) or steel cannula. There are intensive discussions about the impact the choice of material for insulin application has on insulin pharmacokinetics. In this review, this factor and others that are known to have an impact on the successful usage of IIS are discussed.

The Impact of Intensive Insulin Protocols and Restrictive Blood Transfusion Strategies on Glucose Measurement in American Burn Association (ABA) Verified Burn Centers

DTIC Science & Technology

2008-10-01

of these therapies is to concomi- tantly increase the prevalence of anemia and hypoglycemia in intensive care unit patients. Such a development is...ence of hypoglycemia . We hypothesized that most American Burn Association (ABA) veri- fied burn centers have adopted intensive insulin therapy while...simultaneously restricting blood transfusions potentially increasing risk of hypoglycemia . All ABA verified burn cen- ters (N 44) were contacted

Impact of high-intensity concurrent training on cardiovascular risk factors in persons with multiple sclerosis - pilot study.

PubMed

Keytsman, Charly; Hansen, Dominique; Wens, Inez; O Eijnde, Bert

2017-10-27

High-intensity concurrent training positively affects cardiovascular risk factors. Because this was never investigated in multiple sclerosis, the present pilot study explored the impact of this training on cardiovascular risk factors in this population. Before and after 12 weeks of high-intense concurrent training (interval and strength training, 5 sessions per 2 weeks, n = 16) body composition, resting blood pressure and heart rate, 2-h oral glucose tolerance (insulin sensitivity, glycosylated hemoglobin, blood glucose and insulin concentrations), blood lipids (high- and low-density lipoprotein, total cholesterol, triglyceride levels) and C-reactive protein were analyzed. Twelve weeks of high-intense concurrent training significantly improved resting heart rate (-6%), 2-h blood glucose concentrations (-13%) and insulin sensitivity (-24%). Blood pressure, body composition, blood lipids and C-reactive protein did not seem to be affected. Under the conditions of this pilot study, 12 weeks of concurrent high-intense interval and strength training improved resting heart rate, 2-h glucose and insulin sensitivity in multiple sclerosis but did not affect blood C-reactive protein levels, blood pressure, body composition and blood lipid profiles. Further, larger and controlled research investigating the effects of high-intense concurrent training on cardiovascular risk factors in multiple sclerosis is warranted. Implications for rehabilitation High-intensity concurrent training improves cardiovascular fitness. This pilot study explores the impact of this training on cardiovascular risk factors in multiple sclerosis. Despite the lack of a control group, high-intense concurrent training does not seem to improve cardiovascular risk factors in multiple sclerosis.

Exercise, adipokines and pediatric obesity: a meta-analysis of randomized controlled trials.

PubMed

García-Hermoso, A; Ceballos-Ceballos, R J M; Poblete-Aro, C E; Hackney, A C; Mota, J; Ramírez-Vélez, R

2017-04-01

Adipokines are involved in the etiology of diabetes, insulin resistance, and the development of atherosclerosis and other latent-onset complications. The objective of this meta-analysis was to determine the effectiveness of exercise interventions on adipokines in pediatric obesity. A computerized search was made using three databases. The analysis was restricted to studies that examined the effect of exercise interventions on adipokines (adiponectin, leptin, resistin and visfatin) in pediatric obesity (6-18 years old). Fourteen randomized controlled trials (347 youths) were included. Weighted mean difference (WMD) and 95% confidence intervals were calculated. Exercise was associated with a significant increase in adiponectin (WMD=0.882 μg ml -1 , 95% CI, 0.271-1.493) but did not alter leptin and resistin level. Likewise, exercise intensity and change in body fat; as well as total exercise program duration, duration of the sessions, and change in body fat all significantly influenced the effect of exercise on adiponectin and leptin, respectively. Exercise seems to increase adiponectin levels in childhood obesity. Our results also suggested that exercise on its own, without the concomitant presence of changes in body composition levels, does not affect leptin levels.

Prediction of the association state of insulin using spectral parameters.

PubMed

Uversky, Vladimir N; Garriques, Liza Nielsen; Millett, Ian S; Frokjaer, Sven; Brange, Jens; Doniach, Sebastian; Fink, Anthony L

2003-04-01

Human insulin exists in different association states, from monomer to hexamer, depending on the conditions. In the presence of zinc the "normal" state is a hexamer. The structural properties of 20 variants of human insulin were studied by near-UV circular dichroism, fluorescence spectroscopy, and small-angle X-ray scattering (SAXS). The mutants showed different degrees of association (monomer, dimers, tetramers, and hexamers) at neutral pH. A correlation was shown between the accessibility of tyrosines to acrylamide quenching and the degree of association of the insulin mutants. The near-UV CD spectra of the insulins were affected by protein association and by mutation-induced structural perturbations. However, the shape and intensity of difference CD spectra, obtained by subtraction of the spectra measured in 20% acetic acid (where all insulin species were monomeric) from the corresponding spectra measured at neutral pH, correlate well with the degree of insulin association. In fact, the near-UV CD difference spectra for monomeric, dimeric, tetrameric, and hexameric insulin are very distinctive, both in terms of intensity and shape. The results show that the spectral properties of the insulins reflect their state of association, and can be used to predict their oligomeric state. Copyright 2003 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:847-858, 2003

Low-volume high-intensity swim training is superior to high-volume low-intensity training in relation to insulin sensitivity and glucose control in inactive middle-aged women.

PubMed

Connolly, Luke J; Nordsborg, Nikolai B; Nyberg, Michael; Weihe, Pál; Krustrup, Peter; Mohr, Magni

2016-10-01

We tested the hypothesis that low-volume high-intensity swimming has a larger impact on insulin sensitivity and glucose control than high-volume low-intensity swimming in inactive premenopausal women with mild hypertension. Sixty-two untrained premenopausal women were randomised to an inactive control (n = 20; CON), a high-intensity low-volume (n = 21; HIT) or a low-intensity high-volume (n = 21; LIT) training group. During the 15-week intervention period, HIT performed 3 weekly 6-10 × 30-s all-out swimming intervals (average heart rate (HR) = 86 ± 3 % HRmax) interspersed by 2-min recovery periods and LIT swam continuously for 1 h at low intensity (average HR = 73 ± 3 % HRmax). Fasting blood samples were taken and an oral glucose tolerance test (OGTT) was conducted pre- and post-intervention. After HIT, resting plasma [insulin] was lowered (17 ± 34 %; P < 0.05) but remained similar after LIT and CON. Following HIT, 60-min OGTT plasma [insulin] and [glucose] was lowered (24 ± 30 % and 10 ± 16 %; P < 0.05) but remained similar after LIT and CON. Total area under the curve for plasma [glucose] was lower (P < 0.05) after HIT than LIT (660 ± 141 vs. 860 ± 325 mmol min L(-1)). Insulin sensitivity (HOMA-IR) had increased (P < 0.05) by 22 ± 34 % after HIT, with no significant change after LIT or CON, respectively. Plasma soluble intracellular cell adhesion molecule 1 was lowered (P < 0.05) by 4 ± 8 and 3 ± 9 % after HIT and CON, respectively, while plasma soluble vascular cell adhesion molecule 1 had decreased (P < 0.05) by 8 ± 23 % after HIT only. These findings suggest that low-volume high-intensity intermittent swimming is an effective and time-efficient training strategy for improving insulin sensitivity, glucose control and biomarkers of vascular function in inactive, middle-aged mildly hypertensive women.

Utilization patterns of insulin therapy and healthcare services among Japanese insulin initiators during their first year: a descriptive analysis of administrative hospital data.

PubMed

Ikeda, Shunya; Crawford, Bruce; Sato, Masayo

2016-01-12

Type 2 diabetes poses an increasing healthcare burden in Japan. Although insulin treatment has diversified in recent years, the literature on the utilization of healthcare services among patients with type 2 diabetes undergoing different insulin therapy regimens is scarce. The current study aimed to characterize the real-world insulin treatment patterns and associated utilization of healthcare services among patients with type 2 diabetes who initiated insulin therapy during the study period. We examined data from a hospital-based database consisting of administrative and laboratory data from 121 acute-phase hospitals throughout Japan from April 2008 to August 2012. Patients diagnosed with type 2 diabetes and receiving continuous insulin therapy, defined by three insulin claims or more, were included in the analysis. Of the 2,145 insulin initiators, at initiation 46.5% received rapid-acting insulin alone, 36.6% received an intensive regimen, 11.4% received long-acting insulin alone, and 5.5% received pre-mixed insulin alone. Patients treated with rapid-acting insulin alone were older, experienced more comorbid conditions, had lower HbA1c, and more often had initiated their insulin treatment at inpatient admission, compared to patients treated with other types of insulin. Inpatient admission was more common and longer for patients taking rapid-acting insulin and an intensive regimen than those taking long-acting or pre-mixed insulin, and most were readmitted within 1 year. Utilization of outpatient clinics was approximately once per month, and emergency department visits were observed to be rare. This retrospective observational descriptive study found varied treatment and healthcare service utilization patterns, as well as disparities in patient characteristics across insulin regimens. Future research should assess the basis for these various utilization patterns associated with insulin to conduct robust analyses of clinical and economic outcomes.

When Intensive Insulin Therapy (MDI) Fails in Patients With Type 2 Diabetes: Switching to GLP-1 Receptor Agonist Versus Insulin Pump.

PubMed

Cohen, Ohad; Filetti, Sebastiano; Castañeda, Javier; Maranghi, Marianna; Glandt, Mariela

2016-08-01

Treatment with insulin, alone or with oral or injectable hypoglycemic agents, is becoming increasingly common in patients with type 2 diabetes. However, approximately 40% of patients fail to reach their glycemic targets with the initially prescribed regimen and require intensification of insulin therapy, which increases the risks of weight gain and hypoglycemia. Many of these patients eventually reach a state in which further increases in the insulin dosage fail to improve glycemic control while increasing the risks of weight gain and hypoglycemia. The recently completed OpT2mise clinical trial showed that continuous subcutaneous insulin infusion (CSII) is more effective in reducing glycated hemoglobin (HbA1c) than intensification of multiple daily injection (MDI) insulin therapy in patients with type 2 diabetes who do not respond to intensive insulin therapy. CSII therapy may also be useful in patients who do not reach glycemic targets despite multidrug therapy with basal-bolus insulin and other agents, including glucagon-like peptide (GLP)-1 receptor agonists; current guidelines offer no recommendations for the treatment of such patients. Importantly, insulin and GLP-1 receptor agonists have complementary effects on glycemia and, hence, can be used either sequentially or in combination in the initial management of diabetes. Patients who have not previously failed GLP-1 receptor agonist therapy may show reduction in weight and insulin dose, in addition to moderate improvement in HbA1c, when GLP-1 receptor agonist therapy is added to MDI regimens. In subjects with long-standing type 2 diabetes who do not respond to intensive insulin therapies, switching from MDI to CSII and/or the addition of GLP-1 receptor agonists to MDI have the potential to improve glycemic control without increasing the risk of adverse events. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Elevated Glucose Oxidation, Reduced Insulin Secretion, and a Fatty Heart May Be Protective Adaptions in Ischemic CAD.

PubMed

Hannukainen, J C; Lautamäki, R; Mari, A; Pärkkä, J P; Bucci, M; Guzzardi, M A; Kajander, S; Tuokkola, T; Knuuti, J; Iozzo, P

2016-07-01

Insulin resistance, β-cell dysfunction, and ectopic fat deposition have been implicated in the pathogenesis of coronary artery disease (CAD) and type 2 diabetes, which is common in CAD patients. We investigated whether CAD is an independent predictor of these metabolic abnormalities and whether this interaction is influenced by superimposed myocardial ischemia. We studied CAD patients with (n = 8) and without (n = 14) myocardial ischemia and eight non-CAD controls. Insulin sensitivity and secretion and substrate oxidation were measured during fasting and oral glucose tolerance testing. We used magnetic resonance imaging/spectroscopy, positron emission and computerized tomography to characterize CAD, cardiac function, pericardial and abdominal adipose tissue, and myocardial, liver, and pancreatic triglyceride contents. Ischemic CAD was characterized by elevated oxidative glucose metabolism and a proportional decline in β-cell insulin secretion and reduction in lipid oxidation. Cardiac function was preserved in CAD groups, whereas cardiac fat depots were elevated in ischemic CAD compared to non-CAD subjects. Liver and pancreatic fat contents were similar in all groups and related with surrounding adipose masses or systemic insulin sensitivity. In ischemic CAD patients, glucose oxidation is enhanced and correlates inversely with insulin secretion. This can be seen as a mechanism to prevent glucose lowering because glucose is required in oxygen-deprived tissues. On the other hand, the accumulation of cardiac triglycerides may be a physiological adaptation to the limited fatty acid oxidative capacity. Our results underscore the urgent need of clinical trials that define the optimal/safest glycemic range in situations of myocardial ischemia.

Elevated Glucose Oxidation, Reduced Insulin Secretion, and a Fatty Heart May Be Protective Adaptions in Ischemic CAD

PubMed Central

Hannukainen, J. C.; Lautamäki, R.; Mari, A.; Pärkkä, J. P.; Bucci, M.; Guzzardi, M. A.; Kajander, S.; Tuokkola, T.; Knuuti, J.

2016-01-01

Background: Insulin resistance, β-cell dysfunction, and ectopic fat deposition have been implicated in the pathogenesis of coronary artery disease (CAD) and type 2 diabetes, which is common in CAD patients. We investigated whether CAD is an independent predictor of these metabolic abnormalities and whether this interaction is influenced by superimposed myocardial ischemia. Methods and Results: We studied CAD patients with (n = 8) and without (n = 14) myocardial ischemia and eight non-CAD controls. Insulin sensitivity and secretion and substrate oxidation were measured during fasting and oral glucose tolerance testing. We used magnetic resonance imaging/spectroscopy, positron emission and computerized tomography to characterize CAD, cardiac function, pericardial and abdominal adipose tissue, and myocardial, liver, and pancreatic triglyceride contents. Ischemic CAD was characterized by elevated oxidative glucose metabolism and a proportional decline in β-cell insulin secretion and reduction in lipid oxidation. Cardiac function was preserved in CAD groups, whereas cardiac fat depots were elevated in ischemic CAD compared to non-CAD subjects. Liver and pancreatic fat contents were similar in all groups and related with surrounding adipose masses or systemic insulin sensitivity. Conclusions: In ischemic CAD patients, glucose oxidation is enhanced and correlates inversely with insulin secretion. This can be seen as a mechanism to prevent glucose lowering because glucose is required in oxygen-deprived tissues. On the other hand, the accumulation of cardiac triglycerides may be a physiological adaptation to the limited fatty acid oxidative capacity. Our results underscore the urgent need of clinical trials that define the optimal/safest glycemic range in situations of myocardial ischemia. PMID:27045985

High intensity interval training improves liver and adipose tissue insulin sensitivity.

PubMed

Marcinko, Katarina; Sikkema, Sarah R; Samaan, M Constantine; Kemp, Bruce E; Fullerton, Morgan D; Steinberg, Gregory R

2015-12-01

Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine-alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC.

Two weeks of moderate-intensity continuous training, but not high-intensity interval training, increases insulin-stimulated intestinal glucose uptake

PubMed Central

Savolainen, Anna M.; Eskelinen, Jari-Joonas; Toivanen, Jussi; Ishizu, Tamiko; Yli-Karjanmaa, Minna; Virtanen, Kirsi A.; Parkkola, Riitta; Kapanen, Jukka; Grönroos, Tove J.; Haaparanta-Solin, Merja; Solin, Olof; Savisto, Nina; Ahotupa, Markku; Löyttyniemi, Eliisa; Knuuti, Juhani; Nuutila, Pirjo; Kalliokoski, Kari K.

2017-01-01

Similar to muscles, the intestine is also insulin resistant in obese subjects and subjects with impaired glucose tolerance. Exercise training improves muscle insulin sensitivity, but its effects on intestinal metabolism are not known. We studied the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on intestinal glucose and free fatty acid uptake from circulation in humans. Twenty-eight healthy, middle-aged, sedentary men were randomized for 2 wk of HIIT or MICT. Intestinal insulin-stimulated glucose uptake and fasting free fatty acid uptake from circulation were measured using positron emission tomography and [18F]FDG and [18F]FTHA. In addition, effects of HIIT and MICT on intestinal GLUT2 and CD36 protein expression were studied in rats. Training improved aerobic capacity (P = 0.001) and whole body insulin sensitivity (P = 0.04), but not differently between HIIT and MICT. Insulin-stimulated glucose uptake increased only after the MICT in the colon (HIIT = 0%; MICT = 37%) (P = 0.02 for time × training) and tended to increase in the jejunum (HIIT = −4%; MICT = 13%) (P = 0.08 for time × training). Fasting free fatty acid uptake decreased in the duodenum in both groups (HIIT = −6%; MICT = −48%) (P = 0.001 time) and tended to decrease in the colon in the MICT group (HIIT = 0%; MICT = −38%) (P = 0.08 for time × training). In rats, both training groups had higher GLUT2 and CD36 expression compared with control animals. This study shows that already 2 wk of MICT enhances insulin-stimulated glucose uptake, while both training modes reduce fasting free fatty acid uptake in the intestine in healthy, middle-aged men, providing an additional mechanism by which exercise training can improve whole body metabolism. NEW & NOTEWORTHY This is the first study where the effects of exercise training on the intestinal substrate uptake have been investigated using the most advanced techniques available. We also show the importance of exercise intensity in inducing these changes. PMID:28183816

High-intensity interval training without weight loss improves exercise but not basal or insulin-induced metabolism in overweight/obese African American women.

PubMed

Arad, Avigdor D; DiMenna, Fred J; Thomas, Naketa; Tamis-Holland, Jacqueline; Weil, Richard; Geliebter, Allan; Albu, Jeanine B

2015-08-15

The purpose of this randomized controlled clinical trial was to determine the effect of a 14-week high-intensity interval training (HIIT) intervention with weight stability on metabolic flexibility, insulin sensitivity, and cardiorespiratory fitness in sedentary, premenopausal, nondiabetic, overweight/obese African American women. Twenty-eight subjects were allocated to one of two groups: HIIT, which performed three sessions per week of four high-intensity cycling intervals, or a control group (CON), which maintained their normal level of physical activity. Diet was controlled for all subjects to ensure weight stability. Pre- and postintervention (pre/post), subjects completed an incremental cycling test to limit of tolerance and, following a 10-day high-fat controlled feeding period, a euglycemic-hyperinsulinemic clamp to determine insulin sensitivity and substrate oxidation. Nine members of HIIT (age, 29 ± 4 yr; body mass, 90.1 ± 13.8 kg) and eleven members of CON (age, 30 ± 7 yr; body mass, 85.5 ± 10.7 kg) completed the study. HIIT experienced an increased limit of tolerance (post, 1,124 ± 202 s; pre, 987 ± 146 s; P < 0.05), gas exchange threshold (post, 1.29 ± 0.34 liters/min; pre, 0.97 ± 0.23 liters/min; P < 0.05), and fat oxidation at the same absolute submaximal work rate compared with CON (P < 0.05 for group-by-time interaction in all cases). However, changes in peak oxygen consumption (V̇o2peak), insulin sensitivity, free fatty acid suppression during insulin stimulation, and metabolic flexibility were not different in HIIT compared with CON. High-intensity interval training with weight stability increased exercise fat oxidation and tolerance in subjects at risk for diabetic progression, but did not improve insulin sensitivity or fat oxidation in the postabsorptive or insulin-stimulated state. Copyright © 2015 the American Physiological Society.

Body fat distribution, serum glucose, lipid and insulin response to meals in Alström syndrome.

PubMed

Paisey, R B; Hodge, D; Williams, K

2008-06-01

Alström syndrome is an autosomal recessive condition characterized by obesity, insulin resistance and hypertriglyceridaemia. Responses to fat and carbohydrate ingestion are important in planning dietetic advice and may help to explain the mechanism of metabolic disorder in the syndrome. After a 12-h fast, five Alström subjects received a 3.1 MJ (742 kcal), 75.8% fat breakfast on day 1, and a 3.3 MJ (794 kcal), 77.5% carbohydrate breakfast on day 2. Serum glucose, triglyceride and insulin levels were measured at baseline, and 2 and 3.5 h post-meal. Abdominal computerized tomography in three subjects and magnetic resonance imaging in one demonstrated distribution of abdominal fat. Body fat was distributed subcutaneously, as well as viscerally. There were no changes in serum glucose, insulin or triglycerides after the high fat meal. Triglycerides remained stable after the high carbohydrate meal but glucose and log insulin levels increased [8.4 +/- 4.1 to 13.4 +/- 6.9 mmol L(-1) (P < 0.05) and 2.6 +/- 0.27 to 3.15 +/- 0.42 pmol L(-1) (P < 0.05), respectively]. Dietetic advice in Alström syndrome must include calorie restriction to reduce obesity, which is predominantly subcutaneous. This study has shown that low carbohydrate advice may prove more effective than fat restriction in control of hyperglycaemia and hyperinsulinism. A single high energy meal does not exacerbate hypertriglyceridaemia.

The Development of Dynamic Facial Expression Recognition at Different Intensities in 4- to 18-Year-Olds

ERIC Educational Resources Information Center

Montirosso, Rosario; Peverelli, Milena; Frigerio, Elisa; Crespi, Monica; Borgatti, Renato

2010-01-01

The primary purpose of this study was to examine the effect of the intensity of emotion expression on children's developing ability to label emotion during a dynamic presentation of five facial expressions (anger, disgust, fear, happiness, and sadness). A computerized task (AFFECT--animated full facial expression comprehension test) was used to…

Glucose supply and insulin demand dynamics of antidiabetic agents.

PubMed

Monte, Scott V; Schentag, Jerome J; Adelman, Martin H; Paladino, Joseph A

2010-03-01

For microvascular outcomes, there is compelling historical and contemporary evidence for intensive blood glucose reduction in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). There is also strong evidence to support macrovascular benefit with intensive blood glucose reduction in T1DM. Similar evidence remains elusive for T2DM. Because cardiovascular outcome trials utilizing conventional algorithms to attain intensive blood glucose reduction have not demonstrated superiority to less aggressive blood glucose reduction (Action to Control Cardiovascular Risk in Diabetes; Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; and Veterans Affairs Diabetes Trial), it should be considered that the means by which the blood glucose is reduced may be as important as the actual blood glucose. By identifying quantitative differences between antidiabetic agents on carbohydrate exposure (CE), hepatic glucose uptake (HGU), hepatic gluconeogenesis (GNG), insulin resistance (IR), peripheral glucose uptake (PGU), and peripheral insulin exposure (PIE), we created a pharmacokinetic/pharmacodynamic model to characterize the effect of the agents on the glucose supply and insulin demand dynamic. Glucose supply was defined as the cumulative percentage decrease in CE, increase in HGU, decrease in GNG, and decrease in IR, while insulin demand was defined as the cumulative percentage increase in PIE and PGU. With the glucose supply and insulin demand effects of each antidiabetic agent summated, the glucose supply (numerator) was divided by the insulin demand (denominator) to create a value representative of the glucose supply and insulin demand dynamic (SD ratio). Alpha-glucosidase inhibitors (1.25), metformin (2.20), and thiazolidinediones (TZDs; 1.25-1.32) demonstrate a greater effect on glucose supply (SD ratio >1), while secretagogues (0.69-0.81), basal insulins (0.77-0.79), and bolus insulins (0.62-0.67) demonstrate a greater effect on insulin demand (SD ratio <1). Alpha-glucosidase inhibitors, metformin, and TZDs demonstrate a greater effect on glucose supply, while secretagogues, basal insulin, and bolus insulin demonstrate a greater effect on insulin demand. Because T2DM cardiovascular outcome trials have not demonstrated macrovascular benefit with more aggressive blood glucose reduction when using conventional algorithms that predominantly focus on insulin demand, it would appear logical to consider a model that incorporates both the extent of blood glucose lowering (hemoglobin A1c) and the means by which the blood glucose was reduced (SD ratio) when considering macrovascular outcomes. (c) 2010 Diabetes Technology Society.

Effect of intensive insulin treatment on plasma levels of lipoprotein-associated phospholipase A2 and secretory phospholipase A2 in patients with newly diagnosed type 2 diabetes.

PubMed

Lin, Xiu-Hong; Xu, Ming-Tong; Tang, Jv-Ying; Mai, Li-Fang; Wang, Xiao-Yi; Ren, Meng; Yan, Li

2016-11-23

China has the highest absolute disease burden of diabetes worldwide. For diabetic patients, diabetes-related vascular complications are major causes of morbidity and mortality. The roles of lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) and secretory phospholipase A 2 (sPLA 2 ) as inflammatory markers have been recently evaluated in the pathogenesis of both diabetes and atherosclerosis. We aimed to determine the mechanism through which patients with newly diagnosed type 2 diabetes gain long-term vascular benefit from intensive insulin therapy by evaluating the change in Lp-PLA 2 and sPLA 2 levels after early intensive insulin treatment and its relevance with insulin resistance and pancreatic β-cell function. In total, 90 patients with newly diagnosed type 2 diabetes mellitus were enrolled. All patients received continuous subcutaneous insulin infusion (CSII) for approximately 2 weeks. Intravenous glucose-tolerance test (IVGTT) and oral glucose-tolerance test (OGTT) were performed, and plasma concentrations of Lp-PLA 2 and sPLA 2 were measured before and after CSII. Levels of Lp-PLA 2 and sPLA 2 were significantly higher in diabetic patients with macroangiopathy than in those without (P < 0.05). After CSII, the sPLA 2 level decreased significantly in all diabetic patients (P < 0.05), while the Lp-PLA2 level changed only in those with macroangiopathy (P < 0.05). The area under the curve of insulin in IVGTT and OGTT, the acute insulin response (AIR 3-5 ), early phase of insulin secretion (ΔIns30/ΔG30), modified β-cell function index, and homeostatic model assessment for β-cell function (HOMA-β) increased after treatment even when adjusted for the influence of insulin resistance (IR; P < 0.001). The HOMA-IR was lower after treatment, and the three other indicators adopted to estimate insulin sensitivity (ISI ced , IAI, and QUICKI) were higher after treatment (P < 0.05). Correlation analysis showed that the decrease in the Lp-PLA 2 and sPLA 2 levels was positively correlated with a reduction in HOMA-IR after CSII (P < 0.05). Additionally, multiple linear regression analysis showed that Lp-PLA 2 and sPLA 2 independently correlated with HOMA-IR (P < 0.05). Lp-PLA 2 and sPLA 2 are closely related to insulin resistance and macroangiopathy in diabetic patients. Intensive insulin therapy might help improve IR and protect against diabetic macroangiopathy by influencing the Lp-PLA 2 and sPLA 2 levels. ChiCTR-TRC-10001618 2010 September 16.

High intensity interval training improves liver and adipose tissue insulin sensitivity

PubMed Central

Marcinko, Katarina; Sikkema, Sarah R.; Samaan, M. Constantine; Kemp, Bruce E.; Fullerton, Morgan D.; Steinberg, Gregory R.

2015-01-01

Objective Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine–alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. Conclusions These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC. PMID:26909307

Insulin-like molecules in the beetle Tenebrio molitor.

PubMed

Sevala, V M; Sevala, V L; Loughton, B G

1993-07-01

Immunocytochemical staining of the nervous system of larva, pupa, and adult stage of Tenebrio molitor with anti-insulin serum demonstrated insulin-like peptides in the protocerebrum, corpora allata, and suboesophageal ganglion. During pupal development, marked changes in staining intensity of the protocerebral cells were detected. The staining pattern suggests release of insulin-like peptides early on day 0 and again on day 3 of the stadium. Injections of anti-insulin at these times caused significant delays in the timing of pupal/adult ecdysis. An immunoblot of haemolymph from day-3 pupae revealed a 6.5-kDa insulin-like molecule. These results suggest that the prothoracicotropic hormone of T. molitor is an insulin-like molecule.

User's manual for a computer program for simulating intensively managed allowable cut.

Treesearch

Robert W. Sassaman; Ed Holt; Karl Bergsvik

1972-01-01

Detailed operating instructions are described for SIMAC, a computerized forest simulation model which calculates the allowable cut assuming volume regulation for forests with intensively managed stands. A sample problem illustrates the required inputs and expected output. SIMAC is written in FORTRAN IV and runs on a CDC 6400 computer with a SCOPE 3.3 operating system....

An observational study comparing continuous subcutaneous insulin infusion (CSII) and insulin glargine in children with type 1 diabetes.

PubMed

Schiaffini, Riccardo; Ciampalini, Paolo; Spera, Sabrina; Cappa, Marco; Crinó, Antonino

2005-01-01

The advantages of continuous subcutaneous insulin infusion (CSII) or insulin glargine have been demonstrated both in adult and paediatric diabetic patients; however, as no data comparing these two approaches during childhood are available, we have examined the efficacy of these two intensive approaches. We retrospectively evaluated data from 36 diabetic children, who had changed their previous insulin regimen [with isophane insulin (NPH) at bedtime] because of HbA1c levels >8.0%. Twenty patients underwent CSII, while the other 16 (significantly younger for age) started insulin glargine at bedtime. At 6 and 12 months, CSII-treated patients showed a significant reduction in HbA1c values from 8.5 +/- 1.8 to 7.4 +/- 1.1% and to 7.6 +/- 1.2%, respectively. The insulin requirement significantly decreased from 0.93 +/- 0.2 IU/kg to 0.73 +/- 0.2 IU/kg of body weight and to 0.74 +/- 0.15 IU/kg of body weight, respectively, while no significant differences were observed for BMI SDS, fructosamine and severe hypoglycaemic events. The patients treated with glargine showed a small decline in HbA1c values from 8.9 +/- 1.7 to 8.3 +/- 0.9% (not significant) in the first 6 months of treatment and to 8.2 +/- 0.9% after 12 months. The basal insulin supplementation can be supplied effectively in children with type 1 diabetes by either CSII or insulin glargine. As previously reported for adults, it is confirmed that CSII is the best current intensive approach aimed to the improvement of glycaemic control.

Brief Report: Parent's Health Literacy among High-Risk Adolescents with Insulin Dependent Diabetes

PubMed Central

Naar-King, Sylvie; Ellis, Deborah

2010-01-01

Objective To describe the health literacy of parents of high-risk adolescents with insulin dependent diabetes and to examine the relation of parent's health literacy with treatment adherence. Methods Participants were 93 adolescents in poor metabolic control diagnosed with insulin dependent diabetes and their primary caregivers. Results All parents had adequate health literacy as defined by the S-TOFHLA. Better parent reading comprehension scores were significantly related to family structure, race, and treatment regimen. Reading comprehension in turn significantly predicted adherence for adolescents on an intensive insulin regimen but not for those on conventional regimens. Conclusions Parents with low health literacy may struggle to help their children adhere to the increasingly complex diabetes regimens being used at present. Such families may benefit from more intensive diabetes education or different approaches to teaching diabetes management skills. PMID:19755494

Insulin Oedema in Newly Diagnosed Type 1 Diabetes Mellitus

PubMed Central

Çetinkaya, Semra; Yılmaz Ağladıoğlu, Sebahat; Peltek Kendirici, Havva Nur; Bilgili, Hatice; Yıldırım, Nurdan; Aycan, Zehra

2010-01-01

Despite the essential role of insulin in the management of patients with insulin deficiency, insulin use can lead to adverse effects such as hypoglycaemia and weight gain. Rarely, crucial fluid retention can occur with insulin therapy, resulting in an oedematous condition. Peripheral or generalised oedema is an extremely rare complication of insulin therapy in the absence of heart, liver or renal involvement. It has been reported in newly diagnosed type 1 diabetes, in poorly controlled type 2 diabetes following the initiation of insulin therapy, and in underweight patients on large doses of insulin. The oedema occurs shortly after the initiation of intensive insulin therapy. We describe two adolescent girls with newly diagnosed type 1 diabetes, who presented with oedema of the lower extremities approximately one week after the initiation of insulin treatment; other causes of oedema were excluded. Spontaneous recovery was observed in both patients. Conflict of interest:None declared. PMID:21274337

Efficacy and safety of an insulin infusion protocol in a surgical ICU.

PubMed

Taylor, Beth E; Schallom, Marilyn E; Sona, Carrie S; Buchman, Timothy G; Boyle, Walter A; Mazuski, John E; Schuerer, Douglas E; Thomas, James M; Kaiser, Christy; Huey, Way Y; Ward, Myrna R; Zack, Jeanne E; Coopersmith, Craig M

2006-01-01

Hyperglycemia is associated with complications in the surgical intensive care unit. The purpose of this study was to determine the efficacy and safety of nurse-driven insulin infusion protocols in lowering blood glucose (BG) in critical illness. All patients in a 24-bed surgical intensive care unit who required i.v. insulin infusions during 3 noncontiguous 6-month periods from 2002 to 2004 were evaluated. In the preintervention phase, 71 patients received a physician-initiated insulin infusion without a developed protocol. They were compared with 95 patients who received a nurse-driven insulin infusion protocol with a target BG of 120 to 150 mg/dL and to 119 patients who received a more stringent protocol with a target BG of 80 to 110 mg/dL. There was a stepwise decrease in average daily BG levels, from 190 to 163 to 132 mg/dL (p < 0.001). The less stringent protocol decreased the time to achieve a BG level < 150 mg/dL from 14.1 to 7.4 hours compared with physician-driven management (p < 0.05) resulting in similar time on an insulin infusion (53 versus 48 hours). The more intensive protocol brought BG levels < 150 mg/dL in 7.2 hours and < 111 mg/dL in 13.6 hours, but increased the length of time a patient was on an insulin infusion to 77 hours. The incidence of severe hypoglycemia (BG < 40 mg/dL) was statistically similar between the groups, ranging between 1.1% and 3.4%. Implementation of a nurse-driven protocol led to more rapid and more effective BG control in critically ill surgical patients compared with physician management. Tighter BG control can be obtained without a significant increase in hypoglycemia, although this is associated with increased time on an insulin infusion.

Using insulin pen needles up to five times does not affect needle tip shape nor increase pain intensity.

PubMed

Puder, Jardena J; Atar, Michael; Muller, Beat; Pavan, Marco; Keller, Ulrich

2005-02-01

Reusing insulin pen needles could help to reduce the increasing economic burden of diabetes. We tested the hypothesis that reusing insulin pen needles leads to needle tip deformity and increased pain. Three blinded reviewers assessed 123 electron microscope pictures analyzing needle tip deformity of insulin pen needles used up to four times by diabetic subjects and up to five times by blinded non-diabetic volunteers. The estimated frequency of needle use was correlated to the actual number of needle use. Pain intensity and unpleasantness of each injection were measured by a visual analogue scale and their differences analyzed by Kruskal-Wallis analysis of variance. Unused needles could be differentiated visually from used needles. However, there was no correlation between the actual and guessed number of times a needle was used (r = 0.07, P = 0.2). Evaluating all 270 injections, neither pain intensity nor unpleasantness increased with repeated injections of the same needles in people with diabetes (P = 0.1 and 0.96) and in the volunteers (P = 0.63 and 0.92). Using pen needles four to five times does not lead to progressive needle tip deformity and does not increase pain intensity or unpleasantness, but could increase convenience and lead to substantial financial savings in Europe of around EUR 100 million/year.

The effect of sleep deprivation on vocal expression of emotion in adolescents and adults.

PubMed

McGlinchey, Eleanor L; Talbot, Lisa S; Chang, Keng-Hao; Kaplan, Katherine A; Dahl, Ronald E; Harvey, Allison G

2011-09-01

Investigate the impact of sleep deprivation on vocal expression of emotion. Within-group repeated measures analysis involving sleep deprivation and rested conditions. Experimental laboratory setting. Fifty-five healthy participants (24 females), including 38 adolescents aged 11-15 y and 17 adults aged 30-60 y. A multimethod approach was used to examine vocal expression of emotion in interviews conducted at 22:30 and 06:30. On that night, participants slept a maximum of 2 h. Interviews were analyzed for vocal expression of emotion via computerized text analysis, human rater judgments, and computerized acoustic properties. Computerized text analysis and human rater judgments indicated decreases in positive emotion in all participants at 06:30 relative to 22:30, and adolescents displayed a significantly greater decrease in positive emotion via computerized text analysis relative to adults. Increases in negative emotion were observed among all participants using human rater judgments. Results for the computerized acoustic properties indicated decreases in pitch, bark energy (intensity) in certain high frequency bands, and vocal sharpness (reduction in high frequency bands > 1000 Hz). These findings support the importance of sleep for healthy emotional functioning in adults, and further suggest that adolescents are differentially vulnerable to the emotional consequences of sleep deprivation.

Closed-Loop Insulin Delivery for Adults with Type 1 Diabetes Undertaking High-Intensity Interval Exercise Versus Moderate-Intensity Exercise: A Randomized, Crossover Study.

PubMed

Jayawardene, Dilshani C; McAuley, Sybil A; Horsburgh, Jodie C; Gerche, André La; Jenkins, Alicia J; Ward, Glenn M; MacIsaac, Richard J; Roberts, Timothy J; Grosman, Benyamin; Kurtz, Natalie; Roy, Anirban; O'Neal, David N

2017-06-01

We aimed to compare closed-loop glucose control for people with type 1 diabetes undertaking high-intensity interval exercise (HIIE) versus moderate-intensity exercise (MIE). Adults with type 1 diabetes established on insulin pumps undertook HIIE and MIE stages in random order during automated insulin delivery via a closed-loop system (Medtronic). Frequent venous sampling for glucose, lactate, ketones, insulin, catecholamines, cortisol, growth hormone, and glucagon levels was performed. The primary outcome was plasma glucose <4.0 mmol/L for ≥15 min, from exercise commencement to 120 min postexercise. Secondary outcomes included continuous glucose monitoring and biochemical parameters. Twelve adults (age mean ± standard deviation 40 ± 13 years) were recruited; all completed the study. Plasma glucose of one participant fell to 3.4 mmol/L following MIE completion; no glucose levels were <4.0 mmol/L for HIIE (primary outcome). There were no glucose excursions >15.0 mmol/L for either stage. Mean (±standard error) plasma glucose did not differ between stages pre-exercise; was higher during exercise in HIIE than MIE (11.3 ± 0.5 mmol/L vs. 9.7 ± 0.6 mmol/L, respectively; P < 0.001); and remained higher until 60 min postexercise. There were no differences in circulating free insulin before, during, or postexercise. During HIIE compared with MIE, there were greater increases in lactate (P < 0.001), catecholamines (all P < 0.05), and cortisol (P < 0.001). Ketones increased more with HIIE than MIE postexercise (P = 0.031). Preliminary findings suggest that closed-loop glucose control is safe for people undertaking HIIE and MIE. However, the management of the postexercise rise in ketones secondary to counter-regulatory hormone-induced insulin resistance observed with HIIE may represent a challenge for closed-loop systems.

A Pediatric Intensive Care Unit Bedside Computer Clinical Decision Support Protocol for Hyperglycemia Is Feasible, Safe and Offers Advantages

PubMed Central

Lanspa, Michael J.; Wilson, Emily L.; Sward, Katherine A.; Jephson, Al; Larsen, Gitte Y.; Morris, Alan H.

2017-01-01

Abstract Background: Computer clinical decision support (CDS) systems are uncommon in the pediatric intensive care unit (PICU), despite evidence suggesting they improve outcomes in adult ICUs. We reasoned that a bedside CDS protocol for intravenous insulin titration, eProtocol-insulin, would be feasible and safe in critically ill children. Methods: We retrospectively reviewed data from non-diabetic children admitted to the PICU with blood glucose (BG) ≥140 mg/dL who were managed with intravenous insulin by either unaided clinician titration or eProtocol-insulin. Primary outcomes were BG measurements in target range (80–110 mg/dL) and severe hypoglycemia (BG ≤40 mg/dL); secondary outcomes were 60-day mortality and PICU length of stay. We assessed bedside nurse satisfaction with the eProtocol-insulin protocol by using a 5-point Likert scale and measured clinician compliance with eProtocol-insulin recommendations. Results: Over 5 years, 69 children were titrated with eProtocol-insulin versus 104 by unaided clinicians. eProtocol-insulin achieved target range more frequently than clinician titration (41% vs. 32%, P < 0.001). Severe hypoglycemia was uncommon in both groups (4.3% of patients in eProtocol-insulin, 8.7% in clinician titration, P = 0.37). There were no differences in mean time to BG target or median BG between the groups. Mortality was 23% in both groups. Clinician compliance with eProtocol-insulin recommendations was 89%. Nurses believed that eProtocol-insulin was easy to understand and safer than clinician titration. Conclusions: eProtocol-insulin is safe for titration of intravenous insulin in critically ill children. Clinical research protocols and quality improvement initiatives aimed at optimizing BG control should utilize detailed computer protocols that enable replicable clinician decisions. PMID:28248127

[The use of continuous subcutaneous insulin infusion (CSII) with personal insulin pumps in the treatment of children and adolescents with diabetes type 1].

PubMed

Jarosz-Chobot, Przemysława

2004-01-01

This paper sums up recently published researches on the continuous subcutaneous insulin infusion (CSII) with the use of insulin pump in children and adolescents with diabetes type 1. Obtaining a balance in the organism metabolism in childhood and adolescence diabetology is nowadays one of the most important rules of the diabetes management in children. One of the modern ways to achieve that goal is the intensive insulin therapy model with use of the insulin pump. In this paper the advantages and disadvantages as well as the indications and contraindications for the CSII in children and adolescents with diabetes are widely discussed.

Efficacy of computerized discrimination between structure-related and non-structure-related echoes in ultrasonographic images for the quantitative evaluation of the structural integrity of superficial digital flexor tendons in horses.

PubMed

van Schie, H T; Bakker, E M; Jonker, A M; van Weeren, P R

2001-07-01

To evaluate effectiveness of computerized discrimination between structure-related and non-structure-related echoes in ultrasonographic images for quantitative evaluation of tendon structural integrity in horses. 4 superficial digital flexor tendons (2 damaged tendons, 2 normal tendons). Transverse ultrasonographic images that precisely matched histologic sections were obtained in fixed steps along the long axis of each tendon. Distribution, intensity, and delineation of structure-related echoes, quantitatively expressed as the correlation ratio and steadiness ratio , were compared with histologic findings in tissue that was normal or had necrosis, early granulation, late granulation, early fibrosis, or inferior repair. In normal tendon, the even distribution of structure-related echoes with high intensity and sharp delineation yielded high correlation ratio and steadiness ratio. In areas of necrosis, collapsed endotendon septa yielded solid but blurred structure-related echoes (high correlation ration and low steadiness ratio). In early granulation tissue, complete lack of organization caused zero values for both ratios. In late granulation tissue, reorganization and swollen endotendon septa yielded poorly delineated structure-related echoes (high correlation ratio, low steadiness ratio). In early fibrosis, rearrangement of bundles resulted in normal correlation ration and slightly low steadiness ratio. In inferior repair, the almost complete lack of structural reorganization resulted in heterogeneous poorly delineated low-intensity echoes (low correlation ratio and steadiness ratio). The combination of correlation ratio and steadiness ratio accurately reflects histopathologic findings, making computerized correlation of ultrasonographic images an efficient tool for quantitative evaluation of tendon structural integrity.

Electronic Chemotherapy Order Entry: A Major Cancer Center's Implementation

PubMed Central

Sklarin, Nancy T.; Granovsky, Svetlana; O'Reilly, Eileen M.; Zelenetz, Andrew D.

2011-01-01

Implementation of a computerized provider order entry system for complex chemotherapy regimens at a large cancer center required intense effort from a multidisciplinary team of clinical and systems experts with experience in all facets of the chemotherapy process. The online tools had to resemble the paper forms used at the time and parallel the successful established process as well as add new functionality. Close collaboration between the institution and the vendor was necessary. This article summarizes the institutional efforts, challenges, and collaborative processes that facilitated universal chemotherapy computerized electronic order entry across multiple sites during a period of several years. PMID:22043182

Electronic Chemotherapy Order Entry: A Major Cancer Center's Implementation.

PubMed

Sklarin, Nancy T; Granovsky, Svetlana; O'Reilly, Eileen M; Zelenetz, Andrew D

2011-07-01

Implementation of a computerized provider order entry system for complex chemotherapy regimens at a large cancer center required intense effort from a multidisciplinary team of clinical and systems experts with experience in all facets of the chemotherapy process. The online tools had to resemble the paper forms used at the time and parallel the successful established process as well as add new functionality. Close collaboration between the institution and the vendor was necessary. This article summarizes the institutional efforts, challenges, and collaborative processes that facilitated universal chemotherapy computerized electronic order entry across multiple sites during a period of several years.

Treatment of gestational diabetes mellitus: glyburide compared to subcutaneous insulin therapy and associated perinatal outcomes.

PubMed

Cheng, Yvonne W; Chung, Judith H; Block-Kurbisch, Ingrid; Inturrisi, Maribeth; Caughey, Aaron B

2012-04-01

To examine perinatal outcomes in women with gestational diabetes mellitus treated with glyburide compared to insulin injections. This is a retrospective cohort study of women diagnosed with gestational diabetes mellitus (GDM) who required pharmaceutical therapy and were enrolled in the Sweet Success California Diabetes and Pregnancy Program between 2001 and 2004, a California state-wide program. Women managed with glyburide were compared to women treated with insulin injections. Perinatal outcomes were compared using chi-square test and multivariable logistic regression models; statistical significance was indicated by p < 0.05 and 95% confidence intervals (CI). Among the 10,682 women with GDM who required medical therapy and met study criteria, 2073 (19.4%) received glyburide and 8609 (80.6%) received subcutaneous insulin injections. Compared to insulin therapy and controlling for confounders, oral hypoglycemic treatment was associated with increased risk of birthweight >4000 g (aOR = 1.29; 95% CI [1.03-1.64]), and admission to the intensive care nursery (aOR = 1.46 [1.07-2.00]). Neonates born to women with gestational diabetes managed on glyburide, and were more likely to be macrosomic and to be admitted to the intensive care unit compared to those treated with insulin injections. These findings should be examined in a large, prospective trial.

Effect of carbohydrate-electrolyte consumption on insulin, cortisol hormones and blood glucose after high-intensity exercise.

PubMed

Mor, Ahmet; Kayacan, Yildirim; Ipekoglu, Gokhan; Arslanoglu, Erkal

2018-04-21

This study aimed to examine the effect of CHO-E consumption after high-intensity exercise on insulin, cortisol hormones and blood glucose responses, which is important for performance and recovery in athletes. Sixteen volunteers, male athletes, participated into this study. Athletes were divided into two groups as experiment (CHO-E) and placebo (PLA). Blood was taken from the athletes three times as basal, post-exercise (PE) and 2 h after ingestion of supplement (PS). When inter-group comparisons, insulin was significantly higher in the CHO-E group than the PLA group at the PS phase (p < .05). Cortisol significantly decreased in the CHO-E group at the PS compared to the PE (p < .05). Carbohydrate-electrolyte consumption after high-intensity exercise, accelerates the recovery process by providing optimal recovery, and enable the metabolism to remain in the anabolic state by preventing it from entering in the catabolic process as well as provides hormonal balance in metabolism.

Relative effectiveness of insulin pump treatment over multiple daily injections and structured education during flexible intensive insulin treatment for type 1 diabetes: cluster randomised trial (REPOSE).

PubMed

2017-03-30

Objective  To compare the effectiveness of insulin pumps with multiple daily injections for adults with type 1 diabetes, with both groups receiving equivalent training in flexible insulin treatment. Design  Pragmatic, multicentre, open label, parallel group, cluster randomised controlled trial (Relative Effectiveness of Pumps Over MDI and Structured Education (REPOSE) trial). Setting  Eight secondary care centres in England and Scotland. Participants  Adults with type 1 diabetes who were willing to undertake intensive insulin treatment, with no preference for pumps or multiple daily injections. Participants were allocated a place on established group training courses that taught flexible intensive insulin treatment ("dose adjustment for normal eating," DAFNE). The course groups (the clusters) were then randomly allocated in pairs to either pump or multiple daily injections. Interventions  Participants attended training in flexible insulin treatment (using insulin analogues) structured around the use of pump or injections, followed for two years. Main outcome measures  The primary outcomes were a change in glycated haemoglobin (HbA1c) values (%) at two years in participants with baseline HbA1c value of ≥7.5% (58 mmol/mol), and the proportion of participants achieving an HbA1c value of <7.5%. Secondary outcomes included body weight, insulin dose, and episodes of moderate and severe hypoglycaemia. Ancillary outcomes included quality of life and treatment satisfaction. Results  317 participants (46 courses) were randomised (156 pump and 161 injections). 267 attended courses and 260 were included in the intention to treat analysis, of which 235 (119 pump and 116 injection) had baseline HbA1c values of ≥7.5%. Glycaemic control and rates of severe hypoglycaemia improved in both groups. The mean change in HbA1c at two years was -0.85% with pump treatment and -0.42% with multiple daily injections. Adjusting for course, centre, age, sex, and accounting for missing values, the difference was -0.24% (-2.7 mmol/mol) in favour of pump users (95% confidence interval -0.53 to 0.05, P=0.10). Most psychosocial measures showed no difference, but pump users showed greater improvement in treatment satisfaction and some quality of life domains (dietary freedom and daily hassle) at 12 and 24 months. Conclusions  Both groups showed clinically relevant and long lasting decreases in HbA1c, rates of severe hypoglycaemia, and improved psychological measures, although few participants achieved glucose levels currently recommended by national and international guidelines. Adding pump treatment to structured training in flexible intensive insulin treatment did not substantially enhance educational benefits on glycaemic control, hypoglycaemia, or psychosocial outcomes in adults with type 1 diabetes. These results do not support a policy of providing insulin pumps to adults with poor glycaemic control until the effects of training on participants' level of engagement in intensive self management have been determined. Trial registration  Current Controlled Trials ISRCTN61215213. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effect of standard (self-directed) training versus intensive training for Lilly/Alkermes human insulin inhalation powder delivery system on patient-reported outcomes and patient evaluation of the system.

PubMed

Hayes, Risa P; Nakano, Masako; Muchmore, Douglas; Schmitke, Jennifer

2007-02-01

Inhaled insulin may provide patients with diabetes a safe, efficacious method of insulin delivery without the burden of injection, but complexity of and time required for training in proper use of delivery systems have not been evaluated. This 4-week, multicenter, single-blind, randomized parallel-group study compared the effect of self-directed [written text-graphic directions for use (DFU) with patient-assistance phone number] or intensive (same DFU, personal training by study personnel, inspiratory flow rate coaching) training for the Lilly/Alkermes human insulin inhalation powder (HIIP) delivery system on patient-reported outcomes (PROs). Patients with type 2 diabetes poorly controlled on oral therapy (n = 102, mean hemoglobin A1C = 9.3%) were administered measures of vitality, diabetes-associated symptoms, fear of hypoglycemia, insulin-delivery system satisfaction, and a delivery system-specific evaluation questionnaire. Analysis of covariance models were used to compare the effect on PROs of treatment of diabetes for 1 month following the two training methods. Paired t tests were used to determine change in PROs after treatment with HIIP. PROs did not differ significantly between training groups. Patients in both groups positively evaluated the delivery system, but the intensive group agreed significantly (P < 0.05) more strongly that the DFU was easy to follow. Improvements in vitality and symptoms of fatigue and increases in fear of hypoglycemia were detected among all patients after using HIIP (P < 0.05). Training for this HIIP delivery system can be self-directed without detrimental effects on PROs, making it potentially a more patient-friendly insulin-delivery method that should appeal to both clinicians and patients.

Level of insulin adherence among diabetes mellitus patients in Felege Hiwot Referral Hospital, Bahir Dar, Northwest Ethiopia, 2017: a cross-sectional study.

PubMed

Tewabe, Tilahun; Kindie, Selamsew

2018-05-11

The objective of this study was to know the level of insulin adherence and to identify factors affecting insulin adherence among diabetes mellitus patients in Felege Hiwot Referral Hospital, Bahir Dar, Northwest Ethiopia. Prevalence of insulin adherence was 59.2%. Patients who are married [AOR = 0.3 (0.14-0.7)], have regular health care visit [AOR = 3.3 (1.5-7.5)] and accessing insulin with low cost [AOR = 2.9 (1.3-6.3)] were more likely to adhere insulin therapy than their counterparts. Recommendations to increase insulin adherence were: government and non-governmental organizations, volunteers and concerned bodies should support syringe and needles for diabetes patients, health care providers and responsible bodies should give intensive health education about the effect of stopping insulin medication.

Misadventures in insulin therapy: are you at risk?

PubMed Central

Grissinger, Matthew; Lease, Michael

2003-01-01

About dollar 1 out of every dollar 7 spent on health care is related to diabetes mellitus, a leading cause of blindness and kidney failure and a strong risk factor for heart disease. Prevalence of the disease has increased by a third among adults in general in the last decade, but intensive therapy has been shown to delay the onset and slow the progression of diabetes-related complications. While insulin therapy remains key in the management of type 1 diabetes, many patients with type 2, or insulin-resistant, diabetes encounter insulin administration errors that compromise the quality of insulin delivery. Insulin errors are a major, but modifiable, barrier to dosing accuracy and optimal diabetes control for many patients. Future trends to combat the problem include increased use of insulin inhalers and smaller doses of rapid- or short-acting insulin to supplement longer-acting injections. PMID:12653373

Hyperinsulinemia prevents prolonged hyperglycemia after intense exercise in insulin-dependent diabetic subjects.

PubMed

Sigal, R J; Purdon, C; Fisher, S J; Halter, J B; Vranic, M; Marliss, E B

1994-10-01

Hyperglycemia with accompanying hyperinsulinemia occurs after brief, greater than 85% maximum oxygen consumption exercise to exhaustion in normal subjects and persists up to 60 min of recovery. To determine the importance of endogenous insulin secretion during and after intense exercise, responses to exercise of lean fit male post-absorptive insulin-dependent diabetes mellitus (IDDM) subjects, aged 18-34 yr, were compared with those of control subjects (C; n = 6). Three iv insulin protocols were employed: hyperglycemic (HG; n = 7) and euglycemic (EG1; n = 6) with constant insulin infusion, and euglycemic with doubled insulin infusion during recovery (EG2; n = 6). Overnight iv insulin was adjusted to achieve prolonged euglycemia (5.4 +/- 0.3 mmol/L) or hyperglycemia (8.6 +/- 0.3 mmol/L) before exercise. This allowed for comparisons between HG and EG1 (constant infusion) and between C and EG2 (to approximate physiological hyperinsulinemia by doubling the infusion rates at exhaustion for 56 +/- 7 min during recovery). Subjects exercised to 89-98% of their individual maximum oxygen consumption for 12.8 +/- 0.3 min. Glycemia increased to maximum values at 6 min of recovery (9.8 +/- 0.5 in HG, 6.9 +/- 0.4 in EG1, 7.3 +/- 0.3 in EG2, and 6.9 +/- 0.4 mmol/L in C). Whereas in EG2 and C, glucose returned to resting values in 50-80 min, it remained elevated at 120 min recovery in HG and EG1. During exercise, [3-3H]-glucose-determined glucose production increased markedly and exceeded disappearance in all groups, but less so in the HG subjects than in the other groups. An early recovery decline in glucose production did not differ among groups, but MCR (rate of glucose disappearance/glycemia) were markedly lower in HG and EG1, in whom plasma free insulin remained unchanged from 15 min of recovery onward (MCR, 1.6-1.9 vs. 2.3-2.8 mL/kg.min in C). Doubling the insulin infusion rate in EG2 restored the MCR response to that of C subjects. In summary, constant insulin infusion is insufficient to prevent prolonged postexercise hyperglycemia in IDDM subjects, even when provided at a rate sufficient to maintain normal resting glycemia and glucose turnover. The finding that increasing the rate of insulin infusion restored plasma glucose to normal in IDDM subjects suggests that the postexercise increase in insulin levels observed in normal subjects is essential to return plasma glucose to resting levels. Therefore, special strategies, differing from those for less strenuous exercise, are required for the management of insulin therapy in IDDM during and after intense exercise.

Maternal low intensity physical exercise prevents obesity in offspring rats exposed to early overnutrition.

PubMed

Ribeiro, Tatiane Aparecida; Tófolo, Laize Peron; Martins, Isabela Peixoto; Pavanello, Audrei; de Oliveira, Júlio Cezar; Prates, Kelly Valério; Miranda, Rosiane Aparecida; da Silva Franco, Claudinéia Conationi; Gomes, Rodrigo Mello; Francisco, Flávio Andrade; Alves, Vander Silva; de Almeida, Douglas Lopes; Moreira, Veridiana Mota; Palma-Rigo, Kesia; Vieira, Elaine; Fabricio, Gabriel Sergio; da Silva Rodrigues, Marcos Ricardo; Rinaldi, Wilson; Malta, Ananda; de Freitas Mathias, Paulo Cezar

2017-08-09

Low intensity exercise during pregnancy and lactation may create a protective effect against the development of obesity in offspring exposed to overnutrition in early life. To test these hypotheses, pregnant rats were randomly assigned into 2 groups: Sedentary and Exercised, low intensity, on a rodent treadmill at 30% VO 2Max /30-minute/session/3x/week throughout pregnancy and the lactation. Male offspring were raised in small litters (SL, 3 pups/dam) and normal litters (NL, 9 pups/dam) as models of early overnutrition and normal feed, respectively. Exercised mothers showed low mesenteric fat pad stores and fasting glucose and improved glucose-insulin tolerance, VO 2max during lactation and sympathetic activity. Moreover, the breast milk contained elevated levels of insulin. In addition, SL of sedentary mothers presented metabolic dysfunction and glucose and insulin intolerance and were hyperglycemic and hyperinsulinemic in adulthood. SL of exercised mothers showed lower fat tissue accretion and improvements in glucose tolerance, insulin sensitivity, insulinemia and glycemia. The results suggest that maternal exercise during the perinatal period can have a possible reprogramming effect to prevent metabolic dysfunction in adult rat offspring exposed to early overnutrition, which may be associated with the improvement in maternal health caused by exercise.

High intensity aerobic exercise training improves chronic intermittent hypoxia-induced insulin resistance without basal autophagy modulation.

PubMed

Pauly, Marion; Assense, Allan; Rondon, Aurélie; Thomas, Amandine; Dubouchaud, Hervé; Freyssenet, Damien; Benoit, Henri; Castells, Josiane; Flore, Patrice

2017-03-03

Chronic intermittent hypoxia (IH) associated with obstructive sleep apnea (OSA) is a major risk factor for cardiovascular and metabolic diseases (insulin resistance: IR). Autophagy is involved in the pathophysiology of IR and high intensity training (HIT) has recently emerged as a potential therapy. We aimed to confirm IH-induced IR in a tissue-dependent way and to explore the preventive effect of HIT on IR-induced by IH. Thirty Swiss 129 male mice were randomly assigned to Normoxia (N), Intermittent Hypoxia (IH: 21-5% FiO 2 , 30 s cycle, 8 h/day) or IH associated with high intensity training (IH HIT). After 8 days of HIT (2*24 min, 50 to 90% of Maximal Aerobic Speed or MAS on a treadmill) mice underwent 14 days IH or N. We found that IH induced IR, characterized by a greater glycemia, an impaired insulin sensitivity and lower AKT phosphorylation in adipose tissue and liver. Nevertheless, MAS and AKT phosphorylation were greater in muscle after IH. IH associated with HIT induced better systemic insulin sensitivity and AKT phosphorylation in liver. Autophagy markers were not altered in both conditions. These findings suggest that HIT could represent a preventive strategy to limit IH-induced IR without change of basal autophagy.

High intensity aerobic exercise training improves chronic intermittent hypoxia-induced insulin resistance without basal autophagy modulation

PubMed Central

Pauly, Marion; Assense, Allan; Rondon, Aurélie; Thomas, Amandine; Dubouchaud, Hervé; Freyssenet, Damien; Benoit, Henri; Castells, Josiane; Flore, Patrice

2017-01-01

Chronic intermittent hypoxia (IH) associated with obstructive sleep apnea (OSA) is a major risk factor for cardiovascular and metabolic diseases (insulin resistance: IR). Autophagy is involved in the pathophysiology of IR and high intensity training (HIT) has recently emerged as a potential therapy. We aimed to confirm IH-induced IR in a tissue-dependent way and to explore the preventive effect of HIT on IR-induced by IH. Thirty Swiss 129 male mice were randomly assigned to Normoxia (N), Intermittent Hypoxia (IH: 21–5% FiO2, 30 s cycle, 8 h/day) or IH associated with high intensity training (IH HIT). After 8 days of HIT (2*24 min, 50 to 90% of Maximal Aerobic Speed or MAS on a treadmill) mice underwent 14 days IH or N. We found that IH induced IR, characterized by a greater glycemia, an impaired insulin sensitivity and lower AKT phosphorylation in adipose tissue and liver. Nevertheless, MAS and AKT phosphorylation were greater in muscle after IH. IH associated with HIT induced better systemic insulin sensitivity and AKT phosphorylation in liver. Autophagy markers were not altered in both conditions. These findings suggest that HIT could represent a preventive strategy to limit IH-induced IR without change of basal autophagy. PMID:28255159

Dietary fat acutely increases glucose concentrations and insulin requirements in patients with type 1 diabetes: implications for carbohydrate-based bolus dose calculation and intensive diabetes management.

PubMed

Wolpert, Howard A; Atakov-Castillo, Astrid; Smith, Stephanie A; Steil, Garry M

2013-04-01

Current guidelines for intensive treatment of type 1 diabetes base the mealtime insulin bolus calculation exclusively on carbohydrate counting. There is strong evidence that free fatty acids impair insulin sensitivity. We hypothesized that patients with type 1 diabetes would require more insulin coverage for higher-fat meals than lower-fat meals with identical carbohydrate content. We used a crossover design comparing two 18-h periods of closed-loop glucose control after high-fat (HF) dinner compared with low-fat (LF) dinner. Each dinner had identical carbohydrate and protein content, but different fat content (60 vs. 10 g). Seven patients with type 1 diabetes (age, 55 ± 12 years; A1C 7.2 ± 0.8%) successfully completed the protocol. HF dinner required more insulin than LF dinner (12.6 ± 1.9 units vs. 9.0 ± 1.3 units; P = 0.01) and, despite the additional insulin, caused more hyperglycemia (area under the curve >120 mg/dL = 16,967 ± 2,778 vs. 8,350 ± 1,907 mg/dL⋅min; P < 0001). Carbohydrate-to-insulin ratio for HF dinner was significantly lower (9 ± 2 vs. 13 ± 3 g/unit; P = 0.01). There were marked interindividual differences in the effect of dietary fat on insulin requirements (percent increase significantly correlated with daily insulin requirement; R(2) = 0.64; P = 0.03). This evidence that dietary fat increases glucose levels and insulin requirements highlights the limitations of the current carbohydrate-based approach to bolus dose calculation. These findings point to the need for alternative insulin dosing algorithms for higher-fat meals and suggest that dietary fat intake is an important nutritional consideration for glycemic control in individuals with type 1 diabetes.

Comparison of standard (self-directed) versus intensive patient training for the human insulin inhalation powder (HIIP) delivery system in patients with type 2 diabetes: efficacy, safety, and training measures.

PubMed

Rosenstock, Julio; Nakano, Masako; Silverman, Bernard L; Sun, Bin; de la Peña, Amparo; Suri, Ajit; Muchmore, Douglas B

2007-02-01

The Lilly/Alkermes human insulin inhalation powder (HIIP) delivery system [AIR (a registered trademark of Alkermes, Inc., Cambridge, MA) Inhaled Insulin System] was designed to be easy to use. Training methods were compared in insulin-naive patients with type 2 diabetes. Patients (n = 102) were randomized to standard or intensive training. With standard training, patients learned how to use the HIIP delivery system by reading directions for use (DFU) and trying on their own. Intensive training included orientation to the HIIP delivery system with individual coaching and inspiratory flow rate training. Both groups received preprandial HIIP + metformin with or without a thiazolidinedione for 4 weeks. Overall 2-h postprandial blood glucose (PPBG) excursion was the primary measure. Noninferiority was defined as the upper limit of the two-sided 95% confidence interval of the mean difference between groups being 1.2 < or = mmol/L. Overall 2-h PPBG excursions (least squares mean +/- SE) at endpoint were -0.11 +/- 0.38 (standard training) and 0.23 +/- 0.36 (intensive training) mmol/L. The mean difference (standard minus intensive training) and two-sided 95% confidence interval were -0.35 (-1.02, 0.33) mmol/L. No statistically or clinically significant differences were observed between training methods in premeal, postmeal, or bedtime blood glucose values, HIIP doses at endpoint, or blood glucose values after a test meal. No discontinuations occurred because of difficulty of use or dislike of the HIIP system. DFU compliance was >90% in both training groups. There were no significant differences between training methods in safety measures. The HIIP delivery system is easy to use, and most patients can learn to use it by reading the DFU without assistance from health care professionals.

Glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients.

PubMed

Lo, Clement; Jun, Min; Badve, Sunil V; Pilmore, Helen; White, Sarah L; Hawley, Carmel; Cass, Alan; Perkovic, Vlado; Zoungas, Sophia

2017-02-27

Kidney transplantation is the preferred form of kidney replacement therapy for patients with end-stage kidney disease (ESKD) and is often complicated by worsening or new-onset diabetes. Management of hyperglycaemia is important to reduce post-transplant and diabetes-related complications. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. To evaluate the efficacy and safety of pharmacological interventions for lowering glucose levels in patients who have undergone kidney transplantation and have diabetes. We searched the Cochrane Kidney and Transplant Specialised Register to 15 April 2016 through contact with the Information Specialist using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE, and EMBASE; handsearching conference proceedings; and searching the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. All randomised controlled trials (RCTs), quasi-RCTs and cross-over studies examining head-to-head comparisons of active regimens of glucose-lowering therapy or active regimen compared with placebo/standard care in patients who have received a kidney transplant and have diabetes were eligible for inclusion. Two authors independently assessed study eligibility and quality and performed data extraction. Continuous outcomes were expressed as post-treatment mean differences (MD) or standardised mean difference (SMD). Adverse events were expressed as post-treatment absolute risk differences (RD). Dichotomous clinical outcomes were presented as risk ratios (RR) with 95% confidence intervals (CI). We included seven studies that involved a total of 399 kidney transplant recipients. All included studies had observed heterogeneity in the patient population, interventions and measured outcomes or missing data (which was unavailable despite correspondence with authors). Many studies had incompletely reported methodology preventing meta-analysis and leading to low confidence in treatment estimates.Three studies with 241 kidney transplant recipients examined the use of more intensive compared to less intensive insulin therapy in kidney transplant recipients with pre-existing type 1 or 2 diabetes. Evidence for the effects of more intensive compared to less intensive insulin therapy on transplant graft survival, HbA1c, fasting blood glucose, all cause mortality and adverse effects including hypoglycaemia was of very low quality. More intensive versus less intensive insulin therapy resulted in no difference in transplant or graft survival over three to five years in one study while another study showed that more intensive versus less intensive insulin therapy resulted in more rejection events over the three year follow-up (11 events in total; 9 in the more intensive group, P = 0.01). One study showed that more intensive insulin therapy resulted in a lower mean HbA1c (10 ± 0.8% versus 13 ± 0.9%) and lower fasting blood glucose (7.22 ± 0.5 mmol/L versus 13.44 ± 1.22 mmol/L) at 13 months compared with standard insulin therapy. Another study showed no difference between more intensive compared to less intensive insulin therapy on all-cause mortality over a five year follow-up period. All studies showed either an increased frequency of hypoglycaemia or severe hypoglycaemia episodes.Three studies with a total of 115 transplant recipients examined the use of DPP4 inhibitors for new-onset diabetes after transplantation. Evidence for the treatment effect of DPP4 inhibitors on transplant or graft survival, HbA1c and fasting blood glucose levels, all cause mortality, and adverse events including hypoglycaemia was of low quality. One study comparing vildagliptin to placebo and another comparing sitagliptin to placebo showed no difference in transplant or graft survival over two to four months of follow-up. One study comparing vildagliptin to placebo showed no significant change in estimated glomerular filtration rate from baseline (1.9 ± 10.3 mL/min/1.73 m 2 , P = 0.48 and 2.1 ± 6.1 mL/min/1.73 m 2 , P = 0.22) and no deaths, in either treatment group over three months of follow-up. One study comparing vildagliptin to placebo showed a lower HbA1c level (mean ± SD) (6.3 ± 0.5% versus versus 6.7 ± 0.6%, P = 0.03) and trend towards a greater lowering of fasting blood glucose (-0.91 ± -0.92 mmol/L versus vs -0.19 ± 1.16 mmol/L, P = 0.08) with vildagliptin. One study comparing sitagliptin to insulin glargine showed an equivalent lowering of HbA1c (-0.6 ± 0.5% versus -0.6 ± 0.6%, P = NS) and fasting blood glucose (4.92 ± 1.42 versus 4.76 ± 1.09 mmol/L, P = NS) with sitagliptin. For the outcome of hypoglycaemia, one study comparing vildagliptin to placebo reported no episodes of hypoglycaemia, one study comparing sitagliptin to insulin glargine reported fewer episodes of hypoglycaemia with sitagliptin (3/28 patients; 10.7% versus 5/28; 17.9%) and one cross-over study of sitagliptin and placebo reported two episodes of asymptomatic moderate hypoglycaemia (2 to 3.9 mmol/L) when sitagliptin was administered with glipizide. All three studies reported no drug interactions between DPP4 inhibitors and the immunosuppressive agents taken.Evidence for the treatment effect of pioglitazone for treating pre-existing diabetes was of low quality. One study with 62 transplant recipients compared the use of pioglitazone with insulin to insulin alone for treating pre-existing diabetes. Pioglitazone resulted in a lower HbA1c level (mean ± SD) (-1.21 ± 1.2 versus 0.39 ± 1%, P < 0.001) but had no effects on fasting blood glucose (6.58 ± 2.71 versus 7.28 ± 2.78 mmol/L, P = 0.14 ), and change in creatinine (3.54 ± 15.03 versus 10.61 ± 18.56 mmol/L, P = 0.53) and minimal adverse effects (no episodes of hypoglycaemia, three dropped out due to mild to moderate lower extremity oedema, cyclosporin levels were not affected). Evidence concerning the efficacy and safety of glucose-lowering agents for treating pre-existing and new-onset diabetes in kidney transplant recipients is limited. Existing studies examine more intensive versus less intensive insulin therapy, and the use of DPP4 inhibitors and pioglitazone. The safety and efficacy of more intensive compared to less intensive insulin therapy is very uncertain and the safety and efficacy of DPP4 inhibitors and pioglitazone is uncertain, due to data being limited and of poor quality. Additional RCTs are required to clarify the safety and efficacy of current glucose-lowering agents for kidney transplant recipients with diabetes.

High-Intensity Interval Training Attenuates Insulin Resistance Induced by Sleep Deprivation in Healthy Males.

PubMed

de Souza, Jorge F T; Dáttilo, Murilo; de Mello, Marco T; Tufik, Sergio; Antunes, Hanna K M

2017-01-01

Introduction: Sleep deprivation can impair several physiological systems and recently, new evidence has pointed to the relationship between a lack of sleep and carbohydrate metabolism, consequently resulting in insulin resistance. To minimize this effect, High-Intensity Interval Training (HIIT) is emerging as a potential strategy. Objective: The aim of this study was to investigate the effects of HIIT on insulin resistance induced by sleep deprivation. Method: Eleven healthy male volunteers were recruited, aged 18-35 years, who declared taking 7-8 h sleep per night. All volunteers were submitted to four different conditions: a single night of regular sleep (RS condition), 24 h of total sleep deprivation ( SD condition), HIIT training followed by regular sleep (HIIT+RS condition), and HIIT training followed by 24 h of total sleep deprivation (HIIT+ SD condition). They performed six training sessions over 2 weeks and each session consisted of 8-12 × 60 s intervals at 100% of peak power output. In each experimental condition, tests for glucose, insulin, cortisol, free fatty acids, and insulin sensitivity, measured by oral glucose tolerance test (OGTT), were performed. Results: Sleep deprivation increased glycaemia and insulin levels, as well as the area under the curve. Furthermore, an increase in free fatty acids concentrations and basal metabolism was observed. There were no differences in the concentrations of cortisol. However, HIIT before 24 h of sleep deprivation attenuated the increase of glucose, insulin, and free fatty acids. Conclusion: Twenty-four hours of sleep deprivation resulted in acute insulin resistance. However, HIIT is an effective strategy to minimize the deleterious effects promoted by this condition.

The Role of Dietary Protein and Fat in Glycaemic Control in Type 1 Diabetes: Implications for Intensive Diabetes Management.

PubMed

Paterson, Megan; Bell, Kirstine J; O'Connell, Susan M; Smart, Carmel E; Shafat, Amir; King, Bruce

2015-09-01

A primary focus of the management of type 1 diabetes has been on matching prandial insulin therapy with carbohydrate amount consumed. However, even with the introduction of more flexible intensive insulin regimes, people with type 1 diabetes still struggle to achieve optimal glycaemic control. More recently, dietary fat and protein have been recognised as having a significant impact on postprandial blood glucose levels. Fat and protein independently increase the postprandial glucose excursions and together their effect is additive. This article reviews how the fat and protein in a meal impact the postprandial glycaemic response and discusses practical approaches to managing this in clinical practice. These insights have significant implications for patient education, mealtime insulin dose calculations and dosing strategies.

Gender differences in fat distribution and inflammatory markers among Arabs.

PubMed

Farooq, Abdulaziz; Knez, Wade L; Knez, Kelly; Al-Noaimi, Asma; Grantham, Justin; Mohamed-Ali, Vidya

2013-01-01

Recent studies from the Gulf region suggest that compared to men, women have a greater risk of developing metabolic syndrome (MeS). To investigate gender differences in body composition, adipokines, inflammatory markers, and aerobic fitness in a cohort of healthy Qatari adults. Participants. Healthy Qatari (n = 58) were matched for age, gender, and body mass index. Body composition and regional fat distribution were determined by dual-energy X-ray absorptiometry and computerized tomography. Laboratory assessments included serum levels of fasting glucose, insulin, lipid profile analysis, adipokines, and inflammatory markers. Subjects were also evaluated for aerobic fitness. Women had more adipose tissue in the total abdominal (P = 0.04) and abdominal subcutaneous (P = 0.07) regions compared to men. Waist circumference and indices of insulin sensitivity were similar; however, women had a more favourable lipid profile than men. Serum adiponectin and leptin levels were significantly higher in women, whereas inflammatory profiles were not different between men and women. Aerobic fitness was lower in women and was associated with abdominal fat accumulation. In premenopausal women, higher levels of adiponectin may support maintenance of insulin sensitivity and normolipidemia despite greater adiposity. However, poor aerobic fitness combined with abdominal fat accumulation may explain their greater future risk of MeS compared with men.

Gender Differences in Fat Distribution and Inflammatory Markers among Arabs

PubMed Central

Farooq, Abdulaziz; Knez, Wade L.; Knez, Kelly; Al-Noaimi, Asma; Grantham, Justin; Mohamed-Ali, Vidya

2013-01-01

Recent studies from the Gulf region suggest that compared to men, women have a greater risk of developing metabolic syndrome (MeS). Objective. To investigate gender differences in body composition, adipokines, inflammatory markers, and aerobic fitness in a cohort of healthy Qatari adults. Participants. Healthy Qatari (n = 58) were matched for age, gender, and body mass index. Methods. Body composition and regional fat distribution were determined by dual-energy X-ray absorptiometry and computerized tomography. Laboratory assessments included serum levels of fasting glucose, insulin, lipid profile analysis, adipokines, and inflammatory markers. Subjects were also evaluated for aerobic fitness. Results. Women had more adipose tissue in the total abdominal (P = 0.04) and abdominal subcutaneous (P = 0.07) regions compared to men. Waist circumference and indices of insulin sensitivity were similar; however, women had a more favourable lipid profile than men. Serum adiponectin and leptin levels were significantly higher in women, whereas inflammatory profiles were not different between men and women. Aerobic fitness was lower in women and was associated with abdominal fat accumulation. Conclusion. In premenopausal women, higher levels of adiponectin may support maintenance of insulin sensitivity and normolipidemia despite greater adiposity. However, poor aerobic fitness combined with abdominal fat accumulation may explain their greater future risk of MeS compared with men. PMID:24227909

Metformin as add-on to intensive insulin therapy in type 1 diabetes mellitus.

PubMed

Staels, Frederik; Moyson, Carolien; Mathieu, Chantal

2017-10-01

We aimed to evaluate the effect of adjuvant metformin to intensive insulin therapy in patients with type 1 diabetes mellitus (T1DM). A 10-year retrospective study in 2 cohorts was performed: the MET cohort (n = 181) consisted of patients with T1DM on adjuvant metformin for ≥6 months and the CTR cohort (n = 62) consisted of patients with T1DM who refused metformin (n = 25) or adhered to metformin for <6 months (n = 36). Data on glycated haemoglobin (HbA1c), body mass index (BMI) and daily insulin dose were recorded yearly. A third cross-sectional cohort, the REF cohort (n = 961), consisting of patients with T1DM not offered adjuvant metformin, was used as a reference for baseline comparison. At the study start, BMI was significantly higher and insulin doses were lower in patients in the MET cohort, while HbA1c levels were similar. In the first years of metformin therapy, small but non-significant decreases were seen in BMI and insulin dose in patients in the MET cohort, while after 10 years no persistent effect on HbA1c, insulin dose or BMI was seen. In conclusion, although metformin may have short-term effects on BMI and insulin dose when used as adjunct therapy in patients with T1DM, no long-term beneficial effects were observed when patients were followed for 10 years. © 2017 John Wiley & Sons Ltd.

Lower mean blood glucose during short-term intensive insulin therapy is associated with long-term glycemic remission in patients with newly diagnosed type 2 diabetes: Evidence-based recommendations for standardization.

PubMed

Liu, Liehua; Liu, Juan; Xu, Lijuan; Ke, Weijian; Wan, Xuesi; Li, Hai; He, Xiaoying; Wang, Liangjiao; Cao, Xiaopei; Xiao, Haipeng; Li, Yanbing

2017-11-30

Optimal glycemic targets during short-term intensive insulin therapy in patients with newly diagnosed type 2 diabetes are not standardized. The present study was carried out to determine the optimal glycemic targets during therapy by analyzing the impacts of glucose levels on therapeutic outcomes. A total of 95 individuals with newly diagnosed type 2 diabetes were enrolled. Short-term intensive insulin therapy was carried out using an insulin pump to achieve and maintain glycemic targets (fasting blood glucose ≤6.0 mmol/L, 2-h postprandial blood glucose ≤7.8 mmol/L) for 14 days, with daily eight-point capillary blood glucose profiles recorded. Patients were followed up for 1 year after discharge. In most participants, the mean blood glucose and glycemic excursion parameters during the therapy were controlled within the normal range. Mean blood glucose was independently associated with amelioration of acute insulin response (r = -0.25, P = 0.015) and 1-year remission (odds ratio 0.12, 95% confidence interval 0.034-0.426), but negatively associated with more level 1 hypoglycemia (r = -0.34, P = 0.001), although major hypoglycemia was rare. Among mean blood glucose tertiles, patients in the middle (68.7%) and lower (75.0%) tertiles had a higher 1-year remission rate compared with the upper tertile (32.3%, both P < 0.001), whereas only the middle tertile did not have increased hypoglycemia compared with the upper tertile (8.1 ± 5.4 vs 7.2 ± 3.9 events/person, P = 0.48). Stricter glycemic control during short-term intensive insulin therapy produced more remission despite self-manageable hypoglycemia. Based on glycemic parameters in the middle mean tertile, we propose new glycemic targets that are approximately 0.4 mmol/L lower than current the targets, as long-term benefit outweighs short-term risks. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Comparison of the effects of intensive insulin treatment modalities on cardiovascular biomarkers in type 1 diabetes mellitus.

PubMed

Cetinkalp, Sevki; Felekoglu, Canan; Karadeniz, Muammer; Boyacıoglu, Hayal; Delen, Yasemin; Yildirim, Eser; Yilmaz, Candeger

2015-01-01

To evaluate effects of intensive insulin treatment modalities on cardiovascular biomarkers in patients with type 1 diabetes mellitus (T1DM). A total of 25 patients with T1DM receiving intensive insulin therapy either in the form of continuous insulin pump (IP group; n=13) or as multiple daily injections (MDI group; n=12) and 13 controls (control group, n=13) were included. Data on demographics, anthropometrics, diabetes history, and laboratory findings including glycemic and lipid parameters, and cardiovascular biomarkers [C-reactive protein (mg/dL), homocysteine (μmol/L), fibrinogen (mg/dL), oxidized LDL (ng/dL), PAI-1 (ng/mL), MCP-1 (pg/mL) and VEGF (pg/mL)] were recorded in each group. Correlation of cardiovascular biomarkers to other parameters was also evaluated in T1DM patients. Apart from significantly higher mean (SD) values for HbA1c [6.1 (0.3) vs. 5.6 (0.5)% (43 (3) vs. 38 (5) mmol/mol), p<0.05)] and HDL-cholesterol [71.5 (13.6) vs. 58.2 (10.8), p<0.01) in the IP than in the MDI group, no significance difference was noted between insulin treatment modalities as well as between patient and control groups in terms of demographic, anthropometric and laboratory parameters. Negative correlation of MCP-1 to treatment duration (r=-0.615, p=0.025), and HDL-c to CRP (r=-0.685, p=0.010) and VEGF (r=-0.678, p=0.011) was noted in IP group, whereas positive correlation of PAI-1 to diabetes age (r=0.805, p=0.002) and treatment duration was noted in MDI group. Our findings in a cohort of T1DM patients with optimal glycemic control revealed that intensive insulin therapy was not associated with an increase in atherosclerotic markers in T1DM, regardless of whether continuous IP infusion or MDIs was administered. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Type 1 Diabetes and Sports Participation: Strategies for Training and Competing Safely.

ERIC Educational Resources Information Center

Draznin, Martin B.

2000-01-01

Athletes with type 1 diabetes require frequent blood glucose checks throughout the day and intensive diabetes management to balance insulin, carbohydrate intake, and the effects of exercise. Effective care begins with a targeted preparticipation examination. Decreasing insulin dosage may be necessary for heavier exercise programs. Analysis of…

Modification of insulin sensitivity and glycemic control by activity and exercise.

PubMed

Roberts, Christian K; Little, Jonathan P; Thyfault, John P

2013-10-01

Type 2 diabetes has progressed into a major contributor to preventable death, and developing optimal therapeutic strategies to prevent future type 2 diabetes and its primary clinical manifestation of cardiovascular disease is a major public health challenge. This article will provide a brief overview of the role of activity and exercise in modulating insulin sensitivity and will outline the effect of physical activity, high-intensity interval training, and resistance training on insulin sensitivity and glycemic control.

Treatment of gestational diabetes mellitus: glyburide compared to subcutaneous insulin therapy and associated perinatal outcomes

PubMed Central

Cheng, Yvonne W.; Chung, Judith H.; Block-Kurbisch, Ingrid; Inturrisi, Maribeth; Caughey, Aaron B.

2012-01-01

Objective To examine perinatal outcomes in women with gestational diabetes mellitus treated with glyburide compared to insulin injections. Study design This is a retrospective cohort study of women diagnosed with gestational diabetes mellitus (GDM) who required pharmaceutical therapy and were enrolled in the Sweet Success California Diabetes and Pregnancy Program between 2001 and 2004, a California state-wide program. Women managed with glyburide were compared to women treated with insulin injections. Perinatal outcomes were compared using chi-square test and multivariable logistic regression models; statistical significance was indicated by p < 0.05 and 95% confidence intervals (CI). Results Among the 10,682 women with GDM who required medical therapy and met study criteria, 2073 (19.4%) received glyburide and 8609 (80.6%) received subcutaneous insulin injections. Compared to insulin therapy and controlling for confounders, oral hypoglycemic treatment was associated with increased risk of birthweight >4000 g (aOR = 1.29; 95% CI [1.03–1.64]), and admission to the intensive care nursery (aOR = 1.46 [1.07–2.00]). Conclusion Neonates born to women with gestational diabetes managed on glyburide, and were more likely to be macrosomic and to be admitted to the intensive care unit compared to those treated with insulin injections. These findings should be examined in a large, prospective trial. PMID:21631239

Anti-inflammatory effects of insulin.

PubMed

Dandona, Paresh; Chaudhuri, Ajay; Mohanty, Priya; Ghanim, Husam

2007-07-01

This review deals with the recent observations on the pro-inflammatory effects of glucose and the anti-inflammatory actions of insulin. Apart from being novel, they are central to our understanding of why hyperglycemia is a prognosticator of bad clinical outcomes including patients with acute coronary syndromes, stroke and in patients in the intensive care unit. The pro-inflammatory effect of glucose as well as that of other macronutrients including fast food meals provides the basis of chronic oxidative stress and inflammation in the obese and their propensity to atherosclerotic disease. The anti-inflammatory action of insulin provides a neutralizing effect to balance macronutrient induced inflammation on the one hand and the possibility of using insulin as an anti-inflammatory drug on the other. The actions of macronutrients and insulin described above explain why insulin resistant states like obesity and type 2 diabetes are associated with oxidative stress, inflammation and atherosclerosis. They also suggest that insulin may be antiatherogenic.

Minimal Intensity Physical Activity (Standing and Walking) of Longer Duration Improves Insulin Action and Plasma Lipids More than Shorter Periods of Moderate to Vigorous Exercise (Cycling) in Sedentary Subjects When Energy Expenditure Is Comparable

PubMed Central

Duvivier, Bernard M. F. M.; Schaper, Nicolaas C.; Bremers, Michelle A.; van Crombrugge, Glenn; Menheere, Paul P. C. A.; Kars, Marleen; Savelberg, Hans H. C. M.

2013-01-01

Background Epidemiological studies suggest that excessive sitting time is associated with increased health risk, independent of the performance of exercise. We hypothesized that a daily bout of exercise cannot compensate the negative effects of inactivity during the rest of the day on insulin sensitivity and plasma lipids. Methodology/Principal Findings Eighteen healthy subjects, age 21±2 year, BMI 22.6±2.6 kgm−2 followed randomly three physical activity regimes for four days. Participants were instructed to sit 14 hr/day (sitting regime); to sit 13 hr/day and to substitute 1 hr of sitting with vigorous exercise 1 hr (exercise regime); to substitute 6 hrs sitting with 4 hr walking and 2 hr standing (minimal intensity physical activity (PA) regime). The sitting and exercise regime had comparable numbers of sitting hours; the exercise and minimal intensity PA regime had the same daily energy expenditure. PA was assessed continuously by an activity monitor (ActivPAL) and a diary. Measurements of insulin sensitivity (oral glucose tolerance test, OGTT) and plasma lipids were performed in the fasting state, the morning after the 4 days of each regime. In the sitting regime, daily energy expenditure was about 500 kcal lower than in both other regimes. Area under the curve for insulin during OGTT was significantly lower after the minimal intensity PA regime compared to both sitting and exercise regimes 6727.3±4329.4 vs 7752.0±3014.4 and 8320.4±5383.7 mU•min/ml, respectively. Triglycerides, non-HDL cholesterol and apolipoprotein B plasma levels improved significantly in the minimal intensity PA regime compared to sitting and showed non-significant trends for improvement compared to exercise. Conclusions One hour of daily physical exercise cannot compensate the negative effects of inactivity on insulin level and plasma lipids if the rest of the day is spent sitting. Reducing inactivity by increasing the time spent walking/standing is more effective than one hour of physical exercise, when energy expenditure is kept constant. PMID:23418444

Mechanisms behind the superior effects of interval vs continuous training on glycaemic control in individuals with type 2 diabetes: a randomised controlled trial.

PubMed

Karstoft, Kristian; Winding, Kamilla; Knudsen, Sine H; James, Noemi G; Scheel, Maria M; Olesen, Jesper; Holst, Jens J; Pedersen, Bente K; Solomon, Thomas P J

2014-10-01

By use of a parallel and partly crossover randomised, controlled trial design we sought to elucidate the underlying mechanisms behind the advantageous effects of interval walking training (IWT) compared with continuous walking training (CWT) on glycaemic control in individuals with type 2 diabetes. We hypothesised that IWT, more than CWT, would improve insulin sensitivity including skeletal muscle insulin signalling, insulin secretion and disposition index (DI). By simple randomisation (sequentially numbered, opaque sealed envelopes), eligible individuals (diagnosed with type 2 diabetes, no exogenous insulin treatment) were allocated to three groups: a control group (CON, n = 8), an IWT group (n = 12) and an energy expenditure-matched CWT group (n = 12). Training groups were prescribed free-living training, five sessions per week (60 min/session). A three-stage hyperglycaemic clamp, including glucose isotope tracers and skeletal muscle biopsies, was performed before and after a 4 month intervention in a hospitalised setting. No blinding was performed. The improved glycaemic control, which was only seen in the IWT group, was consistent with IWT-induced increases in insulin sensitivity index (49.8 ± 14.6%; p < 0.001), peripheral glucose disposal (14.5 ± 4.9%; p < 0.05) and DI (66.2 ± 21.8%; p < 0.001), with no changes in the CWT or CON group. Moreover, only IWT improved insulin signalling in skeletal muscle via increased insulin-stimulated phosphorylation of AS160 (29.0 ± 10.8%; p < 0.05). No changes were seen in insulin secretion during hyperglycaemia alone, hyperglycaemia + glucagon-like peptide 1 infusion or arginine injection. IWT maintains insulin secretion and improves insulin sensitivity and DI, in contrast to energy expenditure-matched CWT. These results suggest that training with alternating intensity, and not just training volume and mean intensity, is a key determinant of changes in whole body glucose disposal in individuals with type 2 diabetes. ClinicalTrials (NCT01234155).

High-Intensity Interval Training Attenuates Insulin Resistance Induced by Sleep Deprivation in Healthy Males

PubMed Central

de Souza, Jorge F. T.; Dáttilo, Murilo; de Mello, Marco T.; Tufik, Sergio; Antunes, Hanna K. M.

2017-01-01

Introduction: Sleep deprivation can impair several physiological systems and recently, new evidence has pointed to the relationship between a lack of sleep and carbohydrate metabolism, consequently resulting in insulin resistance. To minimize this effect, High-Intensity Interval Training (HIIT) is emerging as a potential strategy. Objective: The aim of this study was to investigate the effects of HIIT on insulin resistance induced by sleep deprivation. Method: Eleven healthy male volunteers were recruited, aged 18–35 years, who declared taking 7–8 h sleep per night. All volunteers were submitted to four different conditions: a single night of regular sleep (RS condition), 24 h of total sleep deprivation (SD condition), HIIT training followed by regular sleep (HIIT+RS condition), and HIIT training followed by 24 h of total sleep deprivation (HIIT+SD condition). They performed six training sessions over 2 weeks and each session consisted of 8–12 × 60 s intervals at 100% of peak power output. In each experimental condition, tests for glucose, insulin, cortisol, free fatty acids, and insulin sensitivity, measured by oral glucose tolerance test (OGTT), were performed. Results: Sleep deprivation increased glycaemia and insulin levels, as well as the area under the curve. Furthermore, an increase in free fatty acids concentrations and basal metabolism was observed. There were no differences in the concentrations of cortisol. However, HIIT before 24 h of sleep deprivation attenuated the increase of glucose, insulin, and free fatty acids. Conclusion: Twenty-four hours of sleep deprivation resulted in acute insulin resistance. However, HIIT is an effective strategy to minimize the deleterious effects promoted by this condition. PMID:29270126

Predictors for Mild and Severe Hypoglycemia in Insulin-Treated Japanese Diabetic Patients.

PubMed

Sonoda, Nao; Morimoto, Akiko; Ugi, Satoshi; Morino, Katsutaro; Sekine, Osamu; Nemoto, Ken-Ichi; Godai, Kayo; Maegawa, Hiroshi; Miyamatsu, Naomi

2015-01-01

The objective of this study was to explore predictors, including social factors, lifestyle factors, and factors relevant to glycemic control and treatment, for mild and severe hypoglycemia in insulin-treated Japanese diabetic patients. This study included 123 insulin-treated diabetic patients who were referred to the diabetes clinic between January and July 2013 at Shiga University of Medical Science Hospital. After a survey examining the various factors, patients were followed for 6 months. During the follow-up period, blood glucose was self-monitored. Mild hypoglycemia was defined as blood glucose level 50-69 mg/dl, and severe hypoglycemia was defined as blood glucose level ≤49 mg/dl. Multinomial logistic regression was used to estimate the adjusted odds ratio (OR) and 95% confidence interval (CI) of each factor for mild and severe hypoglycemia. During the 6-month follow-up period, 41 (33.3%) patients experienced mild hypoglycemia, and 20 (16.3%) experienced severe hypoglycemia. In multivariable-adjusted analyses, assistance from family members at the time of the insulin injection [presence/absence, OR (95% CI): 0.39 (0.16-0.97)] and drinking [current drinker/non- and ex-drinker, OR (95% CI): 4.89 (1.68-14.25)] affected mild hypoglycemia. Assistance from family members at the time of insulin injection [presence/absence, OR (95% CI): 0.19 (0.05-0.75)] and intensive insulin therapy [yes/no, OR (95% CI): 3.61 (1.06-12.26)] affected severe hypoglycemia. In conclusion, our findings suggest that not only a factor relevant to glycemic control and treatment (intensive insulin therapy) but also a social factor (assistance from family members) and a lifestyle factor (current drinking) were predictors for mild or severe hypoglycemia in Japanese insulin-treated diabetic patients.

Studies of the structure of insulin fibrils by Fourier transform infrared (FTIR) spectroscopy and electron microscopy.

PubMed

Nielsen, L; Frokjaer, S; Carpenter, J F; Brange, J

2001-01-01

Fibril formation (aggregation) of insulin was investigated in acid media by visual inspection, transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy. Insulin fibrillated faster in hydrochloric acid than in acetic acid at elevated temperatures, whereas the fibrillation tendencies were reversed at ambient temperatures. Electron micrographs showed that bovine insulin fibrils consisted of long fibers with a diameter of 5 to 10 nm and lengths of several microns. The fibrils appeared either as helical filaments (in hydrochloric acid) or arranged laterally in bundles (in acetic acid, NaCl). Freeze-thawing cycles broke the fibrils into shorter segments. FTIR spectroscopy showed that the native secondary structure of insulin was identical in hydrochloric acid and acetic acid, whereas the secondary structure of fibrils formed in hydrochloric acid was different from that formed in acetic acid. Fibrils of bovine insulin prepared by heating or agitating an acid solution of insulin showed an increased content of beta-sheet (mostly intermolecular) and a decrease in the intensity of the alpha-helix band. In hydrochloric acid, the frequencies of the beta-sheet bands depended on whether the fibrillation was induced by heating or agitation. This difference was not seen in acetic acid. Freeze-thawing cycles of the fibrils in hydrochloric acid caused an increase in the intensity of the band at 1635 cm(-1) concomitant with reduction of the band at 1622 cm(-1). The results showed that the structure of insulin fibrils is highly dependent on the composition of the acid media and on the treatment. Copyright 2001 Wiley-Liss Inc. and the American Pharmaceutical Association J Pharm Sci 90: 29-37, 2001

Color intensity projections: A rapid approach for evaluating four-dimensional CT scans in treatment planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cover, Keith S.; Lagerwaard, Frank J.; Senan, Suresh

2006-03-01

Purpose: Four-dimensional computerized tomography scans (4DCT) enable intrafractional motion to be determined. Because more than 1500 images can be generated with each 4DCT study, tools for efficient data visualization and evaluation are needed. We describe the use of color intensity projections (CIP) for visualizing mobility. Methods: Four-dimensional computerized tomography images of each patient slice were combined into a CIP composite image. Pixels largely unchanged over the component images appear unchanged in the CIP image. However, pixels whose intensity changes over the phases of the 4DCT appear in the CIP image as colored pixels, and the hue encodes the percentage ofmore » time the tissue was in each location. CIPs of 18 patients were used to study tumor and surrogate markers, namely the diaphragm and an abdominal marker block. Results: Color intensity projections permitted mobility of high-contrast features to be quickly visualized and measured. In three selected expiratory phases ('gating phases') that were reviewed in the sagittal plane, gating would have reduced mean tumor mobility from 6.3 {+-} 2.0 mm to 1.4 {+-} 0.5 mm. Residual tumor mobility in gating phases better correlated with residual mobility of the marker block than that of the diaphragm. Conclusion: CIPs permit immediate visualization of mobility in 4DCT images and simplify the selection of appropriate surrogates for gated radiotherapy.« less

Exercise and the Development of the Artificial Pancreas

PubMed Central

Riddell, Michael C.; Zaharieva, Dessi P.; Yavelberg, Loren; Cinar, Ali; Jamnik, Veronica K.

2015-01-01

Regular physical activity (PA) promotes numerous health benefits for people living with type 1 diabetes (T1D). However, PA also complicates blood glucose control. Factors affecting blood glucose fluctuations during PA include activity type, intensity and duration as well as the amount of insulin and food in the body at the time of the activity. To maintain equilibrium with blood glucose concentrations during PA, the rate of glucose appearance (Ra) to disappearance (Rd) in the bloodstream must be balanced. In nondiabetics, there is a rise in glucagon and a reduction in insulin release at the onset of mild to moderate aerobic PA. During intense aerobic -anaerobic work, insulin release first decreases and then rises rapidly in early recovery to offset a more dramatic increase in counterregulatory hormones and metabolites. An “exercise smart” artificial pancreas (AP) must be capable of sensing glucose and perhaps other physiological responses to various types and intensities of PA. The emergence of this new technology may benefit active persons with T1D who are prone to hypo and hyperglycemia. PMID:26428933

Clinical Impact of Accurate Point-of-Care Glucose Monitoring for Tight Glycemic Control in Severely Burned Children.

PubMed

Tran, Nam K; Godwin, Zachary R; Steele, Amanda N; Wolf, Steven E; Palmieri, Tina L

2016-09-01

The goal of this study was to retrospectively evaluate the clinical impact of an accurate autocorrecting blood glucose monitoring system in children with severe burns. Blood glucose monitoring system accuracy is essential for providing appropriate intensive insulin therapy and achieving tight glycemic control in critically ill patients. Unfortunately, few comparison studies have been performed to evaluate the clinical impact of accurate blood glucose monitoring system monitoring in the high-risk pediatric burn population. Retrospective analysis of an electronic health record system. Pediatric burn ICU at an academic medical center. Children (aged < 18 yr) with severe burns (≥ 20% total body surface area) receiving intensive insulin therapy guided by either a noncorrecting (blood glucose monitoring system-1) or an autocorrecting blood glucose monitoring system (blood glucose monitoring system-2). Patient demographics, insulin rates, and blood glucose monitoring system measurements were collected. The frequency of hypoglycemia and glycemic variability was compared between the two blood glucose monitoring system groups. A total of 122 patient charts from 2001 to 2014 were reviewed. Sixty-three patients received intensive insulin therapy using blood glucose monitoring system-1 and 59 via blood glucose monitoring system-2. Patient demographics were similar between the two groups. Mean insulin infusion rates (5.1 ± 3.8 U/hr; n = 535 paired measurements vs 2.4 ± 1.3 U/hr; n = 511 paired measurements; p < 0.001), glycemic variability, and frequency of hypoglycemic events (90 vs 12; p < 0.001) were significantly higher in blood glucose monitoring system-1-treated patients. Compared with laboratory measurements, blood glucose monitoring system-2 yielded the most accurate results (mean ± SD bias: -1.7 ± 6.9 mg/dL [-0.09 ± 0.4 mmol/L] vs 7.4 ± 13.5 mg/dL [0.4 ± 0.7 mmol/L]). Blood glucose monitoring system-2 patients achieve glycemic control more quickly (5.7 ± 4.3 vs 13.1 ± 6.9 hr; p< 0.001) and stayed within the target glycemic control range longer compared with blood glucose monitoring system-1 patients (85.2% ± 13.9% vs 57.9% ± 29.1%; p < 0.001). Accurate autocorrecting blood glucose monitoring system optimizes intensive insulin therapy, improves tight glycemic control, and reduces the risk of hypoglycemia and glycemic variability. The use of an autocorrecting blood glucose monitoring system for intensive insulin therapy may improve glycemic control in severely burned children.

Molecular aspects of glucose homeostasis in skeletal muscle--A focus on the molecular mechanisms of insulin resistance.

PubMed

Carnagarin, Revathy; Dharmarajan, Arun M; Dass, Crispin R

2015-12-05

Among all the varied actions of insulin, regulation of glucose homeostasis is the most critical and intensively studied. With the availability of glucose from nutrient metabolism, insulin action in muscle results in increased glucose disposal via uptake from the circulation and storage of excess, thereby maintaining euglycemia. This major action of insulin is executed by redistribution of the glucose transporter protein, GLUT4 from intracellular storage sites to the plasma membrane and storage of glucose in the form of glycogen which also involves modulation of actin dynamics that govern trafficking of all the signal proteins of insulin signal transduction. The cellular mechanisms responsible for these trafficking events and the defects associated with insulin resistance are largely enigmatic, and this review provides a consolidated overview of the various molecular mechanisms involved in insulin-dependent glucose homeostasis in skeletal muscle, as insulin resistance at this major peripheral site impacts whole body glucose homeostasis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Interaction of dipalmitoyl phosphatidylcholine (DPPC) liposomes and insulin

NASA Astrophysics Data System (ADS)

Mady, Mohsen M.; Elshemey, Wael M.

2011-06-01

Insulin, a peptide that has been used for decades in the treatment of diabetes, has well-defined properties and delivery requirements. Liposomes, which are lipid bilayer vesicles, have gained increasing attention as drug carriers which reduce the toxicity and increase the pharmacological activity of various drugs. The molecular interaction between (uncharged lipid) dipalmitoyl phosphatidylcholine (DPPC) liposomes and insulin has been characterized by using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction. The characteristic protein absorption band peaks, Amide I (at about 1660 cm-1) and Amide II band (at about 1546 cm-1) are potentially reduced in the liposome insulin complex. Wide-angle x-ray scattering measurements showed that the association of insulin with DPPC lipid of liposomes still maintains the characteristic DPPC diffraction peaks with almost no change in relative intensities or change in peak positions. The absence of any shift in protein peak positions after insulin being associated with DPPC liposomes indicates that insulin is successfully forming complex with DPPC liposomes with possibly no pronounced alterations in the structure of insulin molecule.

Lower dipeptidyl peptidase-4 following exercise training plus weight loss is related to increased insulin sensitivity in adults with metabolic syndrome.

PubMed

Malin, Steven K; Huang, Hazel; Mulya, Anny; Kashyap, Sangeeta R; Kirwan, John P

2013-09-01

Dipeptidyl peptidase-4 (DPP-4) is a circulating glycoprotein that impairs insulin-stimulated glucose uptake and is linked to obesity and metabolic syndrome. However, the effect of exercise on plasma DPP-4 in adults with metabolic syndrome is unknown. Therefore, we determined the effect of exercise on DPP-4 and its role in explaining exercise-induced improvements in insulin sensitivity. Fourteen obese adults (67.9±1.2 years, BMI: 34.2±1.1kg/m(2)) with metabolic syndrome (ATP III criteria) underwent a 12-week supervised exercise intervention (60min/day for 5 days/week at ∼85% HRmax). Plasma DPP-4 was analyzed using an enzyme-linked immunosorbent assay. Insulin sensitivity was measured using the euglycemic-hyperinsulinemic clamp (40mU/m(2)/min) and estimated by HOMA-IR. Visceral fat (computerized tomography), 2-h glucose levels (75g oral glucose tolerance), and basal fat oxidation as well as aerobic fitness (indirect calorimetry) were also determined before and after exercise. The intervention reduced visceral fat, lowered blood pressure, glucose and lipids, and increased aerobic fitness (P<0.05). Exercise improved clamp-derived insulin sensitivity by 75% (P<0.001) and decreased HOMA-IR by 15% (P<0.05). Training decreased plasma DPP-4 by 10% (421.8±30.1 vs. 378.3±32.5ng/ml; P<0.04), and the decrease in DPP-4 was associated with clamp-derived insulin sensitivity (r=-0.59; P<0.04), HOMA-IR (r=0.59; P<0.04) and fat oxidation (r=-0.54; P<0.05). Increased fat oxidation also correlated with lower 2-h glucose levels (r=-0.64; P<0.02). Exercise training reduces plasma DPP-4, which may be linked to elevated insulin sensitivity and fat oxidation. Maintaining low plasma DPP-4 concentrations is a potential mechanism whereby exercise plus weight loss prevents/delays the onset of type 2 diabetes in adults with metabolic syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

Lipid-induced mitochondrial stress and insulin action in muscle

PubMed Central

Muoio, Deborah M.; Neufer, P. Darrell

2012-01-01

Summary The interplay between mitochondrial energetics, lipid balance and muscle insulin sensitivity has remained a topic of intense interest and debate for decades. One popular view suggests that increased oxidative capacity benefits metabolic wellness; based on the premise that it is healthier to burn fat than glucose. Attempts to test this hypothesis using genetically-modified mouse models have produced contradictory results; and instead link muscle insulin resistance to excessive fat oxidation, acylcarnitine production and increased mitochondrial H2O2 emitting potential. Here, we consider emerging evidence that insulin action in muscle is driven principally by mitochondrial load and redox signaling rather than oxidative capacity. PMID:22560212

Effects of intensive glucose control on platelet reactivity in patients with acute coronary syndromes. Results of the CHIPS Study ("Control de Hiperglucemia y Actividad Plaquetaria en Pacientes con Sindrome Coronario Agudo").

PubMed

Vivas, David; García-Rubira, Juan C; Bernardo, Esther; Angiolillo, Dominick J; Martín, Patricia; Calle-Pascual, Alfonso; Núñez-Gil, Iván; Macaya, Carlos; Fernández-Ortiz, Antonio

2011-05-01

Hyperglycaemia has been associated with increased platelet reactivity and impaired prognosis in patients with acute coronary syndrome (ACS). Whether platelet reactivity can be reduced by lowering glucose in this setting is unknown. The aim of this study was to assess the functional impact of intensive glucose control with insulin on platelet reactivity in patients admitted with ACS and hyperglycaemia. This is a prospective, randomised trial evaluating the effects of either intensive glucose control (target glucose 80-120 mg/dl) or conventional control (target glucose 180 mg/dl or less) with insulin on platelet reactivity in patients with ACS and hyperglycaemia. The primary endpoint was platelet aggregation following stimuli with 20 μM ADP at 24 h and at hospital discharge. Aggregation following collagen, epinephrine and thrombin receptor-activated peptide, as well as P2Y₁₂ reactivity index and surface expression of glycoprotein IIb/IIIa and P-selectin were also measured. Of the 115 patients who underwent random assignment, 59 were assigned to intensive and 56 to conventional glucose control. Baseline platelet functions and inhospital management were similar in both groups. Maximal aggregation after ADP stimulation at hospital discharge was lower in the intensive group (47.9 ± 13.2% vs 59.1 ± 17.3%; p=0.002), whereas no differences were found at 24 h. Similarly all other parameters of platelet reactivity measured at hospital discharge were significantly reduced in the intensive glucose control group. In this randomised trial, early intensive glucose control with insulin in patients with ACS presenting with hyperglycaemia was found to decrease platelet reactivity. Clinical Trial Registration Number http://www.controlledtrials.com/ISRCTN35708451/ISRCTN35708451.

Management of type 2 diabetes with multiple oral hypoglycaemic agents or insulin in primary care: retrospective cohort study

PubMed Central

Calvert, Melanie J; McManus, Richard J; Freemantle, Nick

2007-01-01

Background Intensive glycaemic control can reduce the risk of microvascular complications in people with type 2 diabetes. Aim To examine the extent of monitoring and glycaemic control of patients with type 2 diabetes prescribed oral agents and/or insulin, and to investigate transition to insulin. Design of study Retrospective cohort study. Setting A total of 154 general practices in the UK contributing to the DIN-LINK database between 1995 and 2005. Method People with type 2 diabetes were identified using Read codes and prescribing data. Outcome measures were: glycaemic monitoring and control on multiple oral agents and/or insulin, and transition to insulin. Results A total of 14 824 people with type 2 diabetes were prescribed multiple oral agents concurrently, of whom 5064 (34.16%) had haemoglobin A1c (HbA1c) assessments 6 months before and following initiation of their last oral therapy. Mean HbA1c before therapy was 9.07%, which dropped to 8.16% following therapy (mean difference 0.91%, 95% confidence interval [CI] = 0.86 to 0.95, P<0.0001). Of the patients with HbA1c assessments, 3153 (62.26%) had evidence of poor glycaemic control following therapy. Median time to insulin for patients prescribed multiple oral agents was 7.7 years (95% CI = 7.4 to 8.5 years); 1513 people began insulin during the study and had HbA1c assessments 6 months before and following insulin. Mean HbA1c before insulin was 9.85% (standard deviation [SD] 1.96%) which decreased by 1.34%, (95% CI = 1.24% to 1.44%) following therapy, but 1110 people (73.36%) still had HbA1c ≥7.5%. Conclusion Many people with type 2 diabetes received inadequate monitoring and had poor glycaemic control. Intensive management is required to reduce the risk of microvascular complications. PMID:17550670

Influence of dietary protein on postprandial blood glucose levels in individuals with Type 1 diabetes mellitus using intensive insulin therapy.

PubMed

Paterson, M A; Smart, C E M; Lopez, P E; McElduff, P; Attia, J; Morbey, C; King, B R

2016-05-01

To determine the effects of protein alone (independent of fat and carbohydrate) on postprandial glycaemia in individuals with Type 1 diabetes mellitus using intensive insulin therapy. Participants with Type 1 diabetes mellitus aged 7-40 years consumed six 150 ml whey isolate protein drinks [0 g (control), 12.5, 25, 50, 75 and 100] and two 150 ml glucose drinks (10 and 20 g) without insulin, in randomized order over 8 days, 4 h after the evening meal. Continuous glucose monitoring was used to assess postprandial glycaemia. Data were collected from 27 participants. Protein loads of 12.5 and 50 g did not result in significant postprandial glycaemic excursions compared with control (water) throughout the 300 min study period (P > 0.05). Protein loads of 75 and 100 g resulted in lower glycaemic excursions than control in the 60-120 min postprandial interval, but higher excursions in the 180-300 min interval. In comparison with 20 g glucose, the large protein loads resulted in significantly delayed and sustained glucose excursions, commencing at 180 min and continuing to 5 h. Seventy-five grams or more of protein alone significantly increases postprandial glycaemia from 3 to 5 h in people with Type 1 diabetes mellitus using intensive insulin therapy. The glycaemic profiles resulting from high protein loads differ significantly from the excursion from glucose in terms of time to peak glucose and duration of the glycaemic excursion. This research supports recommendations for insulin dosing for large amounts of protein. © 2015 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.

BPN, a marine-derived PTP1B inhibitor, activates insulin signaling and improves insulin resistance in C2C12 myotubes.

PubMed

Xu, Qi; Luo, Jiao; Wu, Ning; Zhang, Renshuai; Shi, Dayong

2018-01-01

Insulin resistance is a key feature of type 2 diabetes mellitus (T2DM) and is characterized by defects in insulin signaling. Protein tyrosine phosphatase 1B (PTP1B) is a major negative regulator of insulin signaling cascade and has attracted intensive investigation in recent T2DM therapy study. BPN, a marine-derived bromophenol compound, was isolated from the red alga Rhodomela confervoides. This study investigated the effects of BPN on the insulin signaling pathway in insulin-resistant C2C12 myotubes by inhibiting PTP1B. Molecular docking study and analysis of small- molecule interaction with PTP1B all showed BPN inhibited PTP1B activity via binding to the catalytic site through hydrogen bonds. We then found that BPN permeated into C2C12 myotubes, on the one hand, activated insulin signaling in an insulin-independent manner in C2C12 cells; on the other hand, ameliorated palmitate-induced insulin resistance through augmenting insulin sensitivity. Moreover, our studies also showed that PTP1B inhibition by BPN increased glucose uptake in normal and insulin-resistant C2C12 myotubes through glucose transporter 4 (GLUT4) translocation. Taken together, BPN activates insulin signaling and alleviates insulin resistance and represents a potential candidate for further development as an antidiabetic agent. Copyright © 2017 Elsevier B.V. All rights reserved.

High-Intensity Interval Training and Isocaloric Moderate-Intensity Continuous Training Result in Similar Improvements in Body Composition and Fitness in Obese Individuals.

PubMed

Martins, Catia; Kazakova, Irina; Ludviksen, Marit; Mehus, Ingar; Wisloff, Ulrik; Kulseng, Bard; Morgan, Linda; King, Neil

2016-06-01

This study aimed to determine the effects of 12 weeks of isocaloric programs of high-intensity intermittent training (HIIT) or moderate-intensity continuous training (MICT) or a short-duration HIIT (1/2HIIT) inducing only half the energy deficit on a cycle ergometer, on body weight and composition, cardiovascular fitness, resting metabolism rate (RMR), respiratory exchange ratio (RER), nonexercise physical activity (PA) levels and fasting and postprandial insulin response in sedentary obese individuals. Forty-six sedentary obese individuals (30 women), with a mean BMI of 33.3 ± 2.9 kg/m2 and a mean age of 34.4 ± 8.8 years were randomly assigned to one of the three training groups: HIIT (n = 16), MICT (n = 14) or 1/2HIIT (n = 16) and exercise was performed 3 times/week for 12 weeks. Overall, there was a significant reduction in body weight, waist (p < .001) and hip (p < .01) circumference,, trunk and leg fat mass (FM; p < .01) and an increase in trunk and leg fat free mass (FFM; p < .01) and cardiovascular fitness (VO2max in ml/kg/min; p < .001) with exercise. However, no significant differences were observed between groups. There was no significant change in RMR, RER, nonexercise PA levels, fasting insulin or insulin sensitivity with exercise or between groups. There was a tendency for a reduction in AUC insulin with exercise (p = .069), but no differences between groups. These results indicate that isocaloric training protocols of HIIT or MICT (or 1/2HIIT inducing only half the energy deficit) exert similar metabolic and cardiovascular improvements in sedentary obese individuals.

The positive financial impact of using an Intensive Care Information System in a tertiary Intensive Care Unit.

PubMed

Levesque, Eric; Hoti, Emir; de La Serna, Sofia; Habouchi, Houssam; Ichai, Philippe; Saliba, Faouzi; Samuel, Didier; Azoulay, Daniel

2013-03-01

In the French healthcare system, the intensive care budget allocated is directly dependent on the activity level of the center. To evaluate this activity level, it is necessary to code the medical diagnoses and procedures performed on Intensive Care Unit (ICU) patients. The aim of this study was to evaluate the effects of using an Intensive Care Information System (ICIS) on the incidence of coding errors and its impact on the ICU budget allocated. Since 2005, the documentation on and monitoring of every patient admitted to our ICU has been carried out using an ICIS. However, the coding process was performed manually until 2008. This study focused on two periods: the period of manual coding (year 2007) and the period of computerized coding (year 2008) which covered a total of 1403 ICU patients. The time spent on the coding process, the rate of coding errors (defined as patients missed/not coded or wrongly identified as undergoing major procedure/s) and the financial impact were evaluated for these two periods. With computerized coding, the time per admission decreased significantly (from 6.8 ± 2.8 min in 2007 to 3.6 ± 1.9 min in 2008, p<0.001). Similarly, a reduction in coding errors was observed (7.9% vs. 2.2%, p<0.001). This decrease in coding errors resulted in a reduced difference between the potential and real ICU financial supplements obtained in the respective years (€194,139 loss in 2007 vs. a €1628 loss in 2008). Using specific computer programs improves the intensive process of manual coding by shortening the time required as well as reducing errors, which in turn positively impacts the ICU budget allocation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Atypical blood glucose response to continuous and interval exercise in a person with type 1 diabetes: a case report.

PubMed

Moser, Othmar; Tschakert, Gerhard; Mueller, Alexander; Groeschl, Werner; Pieber, Thomas R; Koehler, Gerd; Eckstein, Max L; Bracken, Richard M; Hofmann, Peter

2017-06-30

Therapy must be adapted for people with type 1 diabetes to avoid exercise-induced hypoglycemia caused by increased exercise-related glucose uptake into muscles. Therefore, to avoid hypoglycemia, the preexercise short-acting insulin dose must be reduced for safety reasons. We report a case of a man with long-lasting type 1 diabetes in whom no blood glucose decrease during different types of exercise with varying exercise intensities and modes was found, despite physiological hormone responses. A Caucasian man diagnosed with type 1 diabetes for 24 years performed three different continuous high-intensity interval cycle ergometer exercises as part of a clinical trial (ClinicalTrials.gov identifier NCT02075567). Intensities for both modes of exercises were set at 5% below and 5% above the first lactate turn point and 5% below the second lactate turn point. Short-acting insulin doses were reduced by 25%, 50%, and 75%, respectively. Measurements taken included blood glucose, blood lactate, gas exchange, heart rate, adrenaline, noradrenaline, cortisol, glucagon, and insulin-like growth factor-1. Unexpectedly, no significant blood glucose decreases were observed during all exercise sessions (start versus end, 12.97 ± 2.12 versus 12.61 ± 2.66 mmol L -1 , p = 0.259). All hormones showed the expected response, dependent on the different intensities and modes of exercises. People with type 1 diabetes typically experience a decrease in blood glucose levels, particularly during low- and moderate-intensity exercises. In our patient, we clearly found no decline in blood glucose, despite a normal hormone response and no history of any insulin insensitivity. This report indicates that there might be patients for whom the recommended preexercise therapy adaptation to avoid exercise-induced hypoglycemia needs to be questioned because this could increase the risk of severe hyperglycemia and ketosis.

Development of Functional or Medical Foods for Oral Administration of Insulin for Diabetes Treatment: Gastroprotective Edible Microgels.

PubMed

Sun, Quancai; Zhang, Zipei; Zhang, Ruojie; Gao, Ruichang; McClements, David Julian

2018-05-16

Insulin and an antacid [Mg(OH) 2 ] were co-encapsulated inside calcium alginate microgels (diameter = 280 μm) using a vibrating nozzle injector. Confocal microscopy indicated that insulin was successfully encapsulated inside the microgels and remained inside them after they were exposed to simulated gastric conditions. Localized fluorescence intensity measurements indicated that the internal pH of the antacid-loaded microgels was around pH 7.4 after incubation in acidic gastric fluids but below the limit of detection (pH < 4) in the antacid-free microgels. After incubation in small intestine conditions, around 30% of the insulin was released from the antacid-loaded microgels over a 2 h period. Encapsulation of insulin within the antacid-loaded microgels increased its biological activity after exposure to simulated gastric conditions. In particular, the encapsulated insulin significantly increased Akt phosphorylation at both Thr308 and Ser473 in L6 myotubes when compared to free insulin.

An ultrasensitive photoelectrochemical immunosensor for insulin detection based on BiOBr/Ag2S composite by in-situ growth method with high visible-light activity.

PubMed

Fan, Dawei; Wang, Haoyuan; Khan, Malik Saddam; Bao, Chunzhu; Wang, Huan; Wu, Dan; Wei, Qin; Du, Bin

2017-11-15

A novel ultrasensitive label-free immunosensor based on BiOBr/Ag 2 S composite with high visible-light photoelectrochemical activity was prepared for the detection of insulin. After BiOBr was modified by thioglycolic acid, Ag 2 S nanoparticles were grown in-situ on the surface of BiOBr hierarchical microspheres to first form novel BiOBr/Ag 2 S composite. When ascorbic acid (AA) was used as an efficient electron donor for scavenging photo-generated holes, BiOBr/Ag 2 S composite material showed excellent photoelectrochemical activity. In order to immobilize insulin antibody, adhesive polydopamine (PDA) film formed by self-polymerization of dopamine was fabricated onto BiOBr/Ag 2 S modified electrode. Moreover, PDA film could further enhance the visible light absorption of BiOBr/Ag 2 S. When the solutions of 0.08molL -1 AgNO 3 and 0.1molL -1 AA were selected respectively during fabrication and detection process of this sensor, the best photocurrent singles were obtained. Under the optimum experimental condition, the specific binding between insulin and antibody resulted in a decrease in photocurrent intensity and the intensity decreased linearly with the logarithm of insulin concentration in the range of 0.001-20ngmL -1 with a detection limit of 0.2pgmL -1 . The photoelectrochemical sensor ITO/BiOBr/Ag 2 S/PDA/anti-Insulin/BSA/Insulin revealed facile preparation, high sensitivity, and acceptable reproducibility, which may have practical applications in the biosensor, clinical diagnosis of cancers, photocatalysis, and other related fields. Copyright © 2017 Elsevier B.V. All rights reserved.

The role of resistance and aerobic exercise training on insulin sensitivity measures in STZ-induced Type 1 diabetic rodents.

PubMed

Hall, Katharine E; McDonald, Matthew W; Grisé, Kenneth N; Campos, Oscar A; Noble, Earl G; Melling, C W James

2013-10-01

Individuals with Type 1 Diabetes Mellitus (T1DM) can develop insulin resistance. Regular exercise may improve insulin resistance partially through increased expression of skeletal muscle GLUT4 content. To examine if different exercise training modalities can alter glucose tolerance through changes in skeletal muscle GLUT4 content in T1DM rats. Fifty rats were divided into 5 groups; control, diabetic control, diabetic resistance exercised, and diabetic high and low intensity treadmill exercised. Diabetes was induced using multiple low dose Streptozotocin (20 mg/kg/day) injections and blood glucose concentrations were maintained moderately hyperglycemic through subcutaneous insulin pellets. Resistance trained rats climbed a ladder with incremental loads, while treadmill trained rats ran on a treadmill at 27 or 15 m/min, respectively, all for 6 weeks. At weeks 3 and 6, area under the curve measurements following an intravenous glucose tolerance test (AUC-IVGTT) in all diabetic groups were higher than control rats (p<0.05). At 6 weeks, all exercise groups had significantly lower AUC-IVGTT values than diabetic control animals (p<0.05). Treadmill trained rats had the lowest insulin dose requirement of the T1DM rats and the greatest reduction in insulin dosage was evident in high intensity treadmill exercise. Concomitant with improvements in glucose handling improvements, tissue-specific elevations in GLUT4 content were demonstrated in both red and white portions of vastus lateralis and gastrocnemius muscles, suggesting that glucose handling capacity was altered in the skeletal muscle of exercised T1DM rats. These results suggest that, while all exercise modalities can improve glucose tolerance, each mode leads to differential improvements in insulin requirements and protein content alterations. Copyright © 2013 Elsevier Inc. All rights reserved.

The role of new technologies in treating children and adolescents with type 1 diabetes mellitus.

PubMed

Shalitin, S; Phillip, M

2007-10-01

Given the physiological and psychological impact of type 1 diabetes in children and adolescents, these patients present special challenges to pediatric health care providers. The goals of intensive management of diabetes have been clearly established since the publication of the Diabetes Control and Complication Trial (DCCT) in 1993, which demonstrated that tight metabolic control achieved with intensive insulin therapy is superior to conventional treatment in reducing the risk of long-term microvascular complications. Thus, current recommendations mandate that youth with type 1 diabetes should aim to achieve metabolic control as close to normal as possible. However, strict glycemic control is hard to achieve requiring frequent blood glucose measurements and several insulin injections per day, and in addition is associated with an increased risk of severe hypoglycemia. Recurrent episodes of hypoglycemia, especially at young ages, may cause adverse effects on neurocognitive function, may lead to hypoglycemia unawareness, and may be associated with significant emotional morbidity for the child and parents. Since the discovery of insulin in 1921 there has been constant progress in the way patients with type 1 diabetes are treated. The introduction of recombinant insulin and insulin analogs as well as new insulin delivery systems and glucose monitoring devices enhanced the ability of both patients and medical teams to better define the therapeutic goals and to develop more effective therapeutic strategies. Recent advances in devices for insulin administration and glucose monitoring and the introduction of telemedicine are having a profound effect on the lives of youth with type 1 diabetes. This review focuses on the new technologies which have been developed for treating children and adolescents with type 1 diabetes.

Determinants of weight gain in the action to control cardiovascular risk in diabetes trial.

PubMed

Fonseca, Vivian; McDuffie, Roberta; Calles, Jorge; Cohen, Robert M; Feeney, Patricia; Feinglos, Mark; Gerstein, Hertzel C; Ismail-Beigi, Faramarz; Morgan, Timothy M; Pop-Busui, Rodica; Riddle, Matthew C

2013-08-01

Identify determinants of weight gain in people with type 2 diabetes mellitus (T2DM) allocated to intensive versus standard glycemic control in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. We studied determinants of weight gain over 2 years in 8,929 participants (4,425 intensive arm and 4,504 standard arm) with T2DM in the ACCORD trial. We used general linear models to examine the association between each baseline characteristic and weight change at the 2-year visit. We fit a linear regression of change in weight and A1C and used general linear models to examine the association between each medication at baseline and weight change at the 2-year visit, stratified by glycemia allocation. There was significantly more weight gain in the intensive glycemia arm of the trial compared with the standard arm (3.0 ± 7.0 vs. 0.3 ± 6.3 kg). On multivariate analysis, younger age, male sex, Asian race, no smoking history, high A1C, baseline BMI of 25-35, high waist circumference, baseline insulin use, and baseline metformin use were independently associated with weight gain over 2 years. Reduction of A1C from baseline was consistently associated with weight gain only when baseline A1C was elevated. Medication usage accounted for <15% of the variability of weight change, with initiation of thiazolidinedione (TZD) use the most prominent factor. Intensive participants who never took insulin or a TZD had an average weight loss of 2.9 kg during the first 2 years of the trial. In contrast, intensive participants who had never previously used insulin or TZD but began this combination after enrolling in the ACCORD trial had a weight gain of 4.6-5.3 kg at 2 years. Weight gain in ACCORD was greater with intensive than with standard treatment and generally associated with reduction of A1C from elevated baseline values. Initiation of TZD and/or insulin therapy was the most important medication-related factor associated with weight gain.

Lipid-induced mitochondrial stress and insulin action in muscle.

PubMed

Muoio, Deborah M; Neufer, P Darrell

2012-05-02

The interplay between mitochondrial energetics, lipid balance, and muscle insulin sensitivity has remained a topic of intense interest and debate for decades. One popular view suggests that increased oxidative capacity benefits metabolic wellness, based on the premise that it is healthier to burn fat than glucose. Attempts to test this hypothesis using genetically modified mouse models have produced contradictory results and instead link muscle insulin resistance to excessive fat oxidation, acylcarnitine production, and increased mitochondrial H(2)O(2)-emitting potential. Here, we consider emerging evidence that insulin action in muscle is driven principally by mitochondrial load and redox signaling rather than oxidative capacity. Copyright © 2012 Elsevier Inc. All rights reserved.

A randomized trial of therapies for type 2 diabetes and coronary artery disease.

PubMed

Frye, Robert L; August, Phyllis; Brooks, Maria Mori; Hardison, Regina M; Kelsey, Sheryl F; MacGregor, Joan M; Orchard, Trevor J; Chaitman, Bernard R; Genuth, Saul M; Goldberg, Suzanne H; Hlatky, Mark A; Jones, Teresa L Z; Molitch, Mark E; Nesto, Richard W; Sako, Edward Y; Sobel, Burton E

2009-06-11

Optimal treatment for patients with both type 2 diabetes mellitus and stable ischemic heart disease has not been established. We randomly assigned 2368 patients with both type 2 diabetes and heart disease to undergo either prompt revascularization with intensive medical therapy or intensive medical therapy alone and to undergo either insulin-sensitization or insulin-provision therapy. Primary end points were the rate of death and a composite of death, myocardial infarction, or stroke (major cardiovascular events). Randomization was stratified according to the choice of percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) as the more appropriate intervention. At 5 years, rates of survival did not differ significantly between the revascularization group (88.3%) and the medical-therapy group (87.8%, P=0.97) or between the insulin-sensitization group (88.2%) and the insulin-provision group (87.9%, P=0.89). The rates of freedom from major cardiovascular events also did not differ significantly among the groups: 77.2% in the revascularization group and 75.9% in the medical-treatment group (P=0.70) and 77.7% in the insulin-sensitization group and 75.4% in the insulin-provision group (P=0.13). In the PCI stratum, there was no significant difference in primary end points between the revascularization group and the medical-therapy group. In the CABG stratum, the rate of major cardiovascular events was significantly lower in the revascularization group (22.4%) than in the medical-therapy group (30.5%, P=0.01; P=0.002 for interaction between stratum and study group). Adverse events and serious adverse events were generally similar among the groups, although severe hypoglycemia was more frequent in the insulin-provision group (9.2%) than in the insulin-sensitization group (5.9%, P=0.003). Overall, there was no significant difference in the rates of death and major cardiovascular events between patients undergoing prompt revascularization and those undergoing medical therapy or between strategies of insulin sensitization and insulin provision. (ClinicalTrials.gov number, NCT00006305.) 2009 Massachusetts Medical Society

The nutritional and metabolic support of heart failure in the intensive care unit.

PubMed

Meltzer, Joseph S; Moitra, Vivek K

2008-03-01

Heart failure and cardiovascular disease are common causes of morbidity and mortality, contributing to many ICU admissions. Nutritional deficiencies have been associated with the development and worsening of chronic heart failure. Nutritional and metabolic support may improve outcomes in critically ill patients with heart failure. This review analyzes the role of this support in the acute care setting of the ICU. Cardiac cachexia is a complex pathophysiologic process. It is characterized by inflammation and anabolic-catabolic imbalance. Nutritional supplements containing selenium, vitamins and antioxidants may provide needed support to the failing myocardium. Evidence shows that there is utility in intensive insulin therapy in the critically ill. Finally, there is an emerging metabolic role for HMG-CoA reductase inhibition, or statin therapy, in the treatment of heart failure. Shifting the metabolic milieu from catabolic to anabolic, reducing free radicals, and quieting inflammation in addition to caloric supplementation may be the key to nutritional support in the heart failure patient. Tight glycemic control with intensive insulin therapy plays an expanding role in the care of the critically ill. Glucose-insulin-potassium therapy probably does not improve the condition of the patient with heart failure or acute myocardial infarction.

Maryland Department of Natural Resources Camp Initiatives Program

Treesearch

Kelly R. Schaeffer

1992-01-01

The Camp Initiatives Program was developed to increase revenue and visitation through a series of policy changes. During the summer of 1990, the program was evaluated at six Maryland State Parks and found to increase revenue and visitation by 3% and 16%, respectively. More intensive marketing efforts, implementation of a computerized reservation system, increased...

Exercise Training at Maximal Fat Oxidation Intensity for Older Women with Type 2 Diabetes.

PubMed

Tan, Sijie; Du, Ping; Zhao, Wanting; Pang, Jiaqi; Wang, Jianxiong

2018-05-01

The purpose of this study was to investigate the pleiotropic effects of 12 weeks of supervised exercise training at maximal fat oxidation (FATmax) intensity on body composition, lipid profile, glycemic control, insulin sensitivity and serum adipokine levels in older women with type 2 diabetes. Thirty-one women with type 2 diabetes, aged 60 to 69 years, were randomly allocated into exercise and control groups. Body composition, lipid profile, blood glucose, insulin resistance and serum leptin and adiponectin concentrations were measured before and after the intervention. Exercise group (n=16) walked at individualized FATmax intensities for 1 h/day for 3 days/week over 12 weeks. No dietary intervention was introduced during the experimental period. Maximal fat oxidation rate was 0.37±0.10 g/min, and occurred at 37.3±7.3% of the estimated VO 2 max. Within the exercise group, significant improvements were observed for most of the measured variables compared to non-exercising controls; in particular, the FATmax program reduced body fat% (p<0.001), visceral fat% (p<0.001), and insulin resistance (p<0.001). There was no significant change in daily energy intake for all participants during the intervention period. These results suggest that individualized FATmax training is an effective exercise training intensity for managing type 2 diabetes in older women. © Georg Thieme Verlag KG Stuttgart · New York.

Therapeutics of diabetes mellitus: focus on insulin analogues and insulin pumps.

PubMed

Valla, Vasiliki

2010-01-01

Inadequately controlled diabetes accounts for chronic complications and increases mortality. Its therapeutic management aims in normal HbA1C, prandial and postprandial glucose levels. This review discusses diabetes management focusing on the latest insulin analogues, alternative insulin delivery systems and the artificial pancreas. Intensive insulin therapy with multiple daily injections (MDI) allows better imitation of the physiological rhythm of insulin secretion. Longer-acting, basal insulin analogues provide concomitant improvements in safety, efficacy and variability of glycaemic control, followed by low risks of hypoglycaemia. Continuous subcutaneous insulin infusion (CSII) provides long-term glycaemic control especially in type 1 diabetic patients, while reducing hypoglycaemic episodes and glycaemic variability. Continuous subcutaneous glucose monitoring (CGM) systems provide information on postprandial glucose excursions and nocturnal hypo- and/or hyperglycemias. This information enhances treatment options, provides a useful tool for self-monitoring and allows safer achievement of treatment targets. In the absence of a cure-like pancreas or islets transplants, artificial "closed-loop" systems mimicking the pancreatic activity have been also developed. Individualized treatment plans for insulin initiation and administration mode are critical in achieving target glycaemic levels. Progress in these fields is expected to facilitate and improve the quality of life of diabetic patients.

A comparison of the health benefits of reduced-exertion high-intensity interval training (REHIT) and moderate-intensity walking in type 2 diabetes patients.

PubMed

Ruffino, José S; Songsorn, Preeyaphorn; Haggett, Malindi; Edmonds, Daniel; Robinson, Anthony M; Thompson, Dylan; Vollaard, Niels B J

2017-02-01

Reduced-exertion high-intensity interval training (REHIT) is a genuinely time-efficient intervention that can improve aerobic capacity and insulin sensitivity in sedentary individuals. The present study compared the effects of REHIT and moderate-intensity walking on health markers in patients with type 2 diabetes (T2D) in a counter-balanced crossover study. Sixteen men with T2D (mean ± SD age: 55 ± 5 years, body mass index: 30.6 ± 2.8 kg·m -2 , maximal aerobic capacity: 27 ± 4 mL·kg -1 ·min -1 ) completed 8 weeks of REHIT (three 10-min low-intensity cycling sessions/week with two "all-out" 10-20-s sprints) and 8 weeks of moderate-intensity walking (five 30-min sessions/week at an intensity corresponding to 40%-55% of heart-rate reserve), with a 2-month wash-out period between interventions. Before and after each intervention, participants underwent an incremental fitness test, an oral glucose tolerance test (OGTT), a whole-body dual-energy X-ray absorptiometry scan, and continuous glucose monitoring. REHIT was associated with a significantly larger increase in maximal aerobic capacity compared with walking (7% vs. 1%; time × intervention interaction effect: p < 0.05). Both REHIT and walking decreased resting mean arterial pressure (-4%; main effect of time: p < 0.05) and plasma fructosamine (-5%; main effect of time: p < 0.05). Neither intervention significantly improved OGTT-derived measures of insulin sensitivity, glycaemic control measured using continuous glucose monitors, blood lipid profile, or body composition. We conclude that REHIT is superior to a 5-fold larger volume of moderate-intensity walking in improving aerobic fitness, but similar to walking REHIT is not an effective intervention for improving insulin sensitivity or glycaemic control in T2D patients in the short term.

Uncovering the Path That Leads to Diabetes | Center for Cancer Research

Cancer.gov

The origins of diabetes have been the subject of intense scientific research, but the genetic factors that cause certain people to develop the disease have remained elusive. In healthy individuals, glucose levels in the bloodstream are transiently elevated after a meal. The increase in glucose triggers β cells in the pancreatic islet to release the hormone insulin. Insulin is

Important role of heparan sulfate in postnatal islet growth and insulin secretion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Takahashi, Iwao; Noguchi, Naoya; Nata, Koji

2009-05-22

Heparan sulfate (HS) binds with several signaling molecules and regulates ligand-receptor interactions, playing an essential role in embryonic development. Here we showed that HS was intensively expressed in pancreatic islet {beta}-cells after 1 week of age in mice. The enzymatic removal of HS in isolated islets resulted in attenuated glucose-induced insulin secretion with a concomitant reduction in gene expression of several key components in the insulin secretion machinery. We further depleted islet HS by inactivating the exostosin tumor-like 3 gene specifically in {beta}-cells. These mice exhibited abnormal islet morphology with reduced {beta}-cell proliferation after 1 week of age and glucosemore » intolerance due to defective insulin secretion. These results demonstrate that islet HS is involved in the regulation of postnatal islet maturation and required to ensure normal insulin secretion.« less

Effects of High-Intensity Interval Exercise versus Moderate Continuous Exercise on Glucose Homeostasis and Hormone Response in Patients with Type 1 Diabetes Mellitus Using Novel Ultra-Long-Acting Insulin

PubMed Central

Mueller, Alexander; Groeschl, Werner; Pieber, Thomas R.; Obermayer-Pietsch, Barbara; Koehler, Gerd; Hofmann, Peter

2015-01-01

Introduction We investigated blood glucose (BG) and hormone response to aerobic high-intensity interval exercise (HIIE) and moderate continuous exercise (CON) matched for mean load and duration in type 1 diabetes mellitus (T1DM). Material and Methods Seven trained male subjects with T1DM performed a maximal incremental exercise test and HIIE and CON at 3 different mean intensities below (A) and above (B) the first lactate turn point and below the second lactate turn point (C) on a cycle ergometer. Subjects were adjusted to ultra-long-acting insulin Degludec (Tresiba/ Novo Nordisk, Denmark). Before exercise, standardized meals were administered, and short-acting insulin dose was reduced by 25% (A), 50% (B), and 75% (C) dependent on mean exercise intensity. During exercise, BG, adrenaline, noradrenaline, dopamine, cortisol, glucagon, and insulin-like growth factor-1, blood lactate, heart rate, and gas exchange variables were measured. For 24 h after exercise, interstitial glucose was measured by continuous glucose monitoring system. Results BG decrease during HIIE was significantly smaller for B (p = 0.024) and tended to be smaller for A and C compared to CON. No differences were found for post-exercise interstitial glucose, acute hormone response, and carbohydrate utilization between HIIE and CON for A, B, and C. In HIIE, blood lactate for A (p = 0.006) and B (p = 0.004) and respiratory exchange ratio for A (p = 0.003) and B (p = 0.003) were significantly higher compared to CON but not for C. Conclusion Hypoglycemia did not occur during or after HIIE and CON when using ultra-long-acting insulin and applying our methodological approach for exercise prescription. HIIE led to a smaller BG decrease compared to CON, although both exercises modes were matched for mean load and duration, even despite markedly higher peak workloads applied in HIIE. Therefore, HIIE and CON could be safely performed in T1DM. Trial Registration ClinicalTrials.gov NCT02075567 http://www.clinicaltrials.gov/ct2/show/NCT02075567 PMID:26317981

Tools to Improve the Accuracy of Kidney Stone Sizing with Ultrasound

PubMed Central

Dunmire, Barbrina; Hsi, Ryan S.; Cunitz, Bryan W.; Paun, Marla; Bailey, Michael R.; Sorensen, Mathew D.; Harper, Jonathan D.

2015-01-01

Abstract Purpose: Ultrasound (US) overestimates stone size when compared with CT. The purpose of this work was to evaluate the overestimation of stone size with US in an in vitro water bath model and investigate methods to reduce overestimation. Materials and Methods: Ten human stones (3–12 mm) were measured using B-mode (brightness mode) US by a sonographer blinded to the true stone size. Images were captured and compared using both a commercial US machine and software-based research US device. Image gain was adjusted between moderate and high stone intensities, and the transducer-to-stone depth was varied from 6 to 10 cm. A computerized stone-sizing program was developed to outline the stone width based on a grayscale intensity threshold. Results: Overestimation with the commercial device increased with both gain and depth. Average overestimation at moderate and high gain was 1.9±0.8 and 2.1±0.9 mm, respectively (p=0.6). Overestimation increased an average of 22% with an every 2-cm increase in depth (p=0.02). Overestimation using the research device was 1.5±0.9 mm and did not vary with depth (p=0.28). Overestimation could be reduced to 0.02±1.1 mm (p<0.001) with the computerized stone-sizing program. However, a standardized threshold consistent across depth, system, or system settings could not be resolved. Conclusion: Stone size is consistently overestimated with US. Overestimation increased with increasing depth and gain using the commercial machine. Overestimation was reduced and did not vary with depth, using the software-based US device. The computerized stone-sizing program shows the potential to reduce overestimation by implementing a grayscale intensity threshold for defining the stone size. More work is needed to standardize the approach, but if successful, such an approach could significantly improve stone-sizing accuracy and lead to automation of stone sizing. PMID:25105243

Physical activity intensity and type 2 diabetes risk in overweight youth: a randomized trial.

PubMed

Hay, J; Wittmeier, K; MacIntosh, A; Wicklow, B; Duhamel, T; Sellers, E; Dean, H; Ready, E; Berard, L; Kriellaars, D; Shen, G X; Gardiner, P; McGavock, J

2016-04-01

The chronic effects of high-intensity endurance training on metabolic health outcomes in overweight adolescents remains poorly understood. To test the hypothesis that high-intensity endurance training (ET) is superior to moderate-intensity ET for improving risk factors for type 2 diabetes in overweight adolescents. In this randomized trial, 106 overweight and obese adolescents (15.2 years; 76% female; 62% Caucasian) were randomly assigned to high-intensity ET (70-85% of heart rate reserve, n=38), moderate-intensity ET (40-55% heart rate reserve; n=32) or control for 6 months (n=36). The primary and secondary outcome measures were insulin sensitivity assessed using a frequently sampled intravenous glucose tolerance test and hepatic triglyceride content with magnetic resonance spectroscopy. Exploratory outcomes were cardiorespiratory fitness, physical activity and MRI and dual x-ray absorptiometry-derived measures of adiposity. The study had 96% retention and attendance was 61±21% and 55±24% in the high- and moderate-intensity ET arms. Intention-to-treat analyses revealed that, at follow-up, insulin sensitivity was not different between high-intensity (-1.0 mU kg(-1) min(-1); 95% confidence interval (CI): -1.6, +1.4 mU kg(-1) min(-1)) and moderate-intensity (+0.26 mU kg(-1) min(-1); 95% CI: -1.3, +1.8 mU kg(-1) min(-1)) ET arms compared with controls (interaction, P=0.97). Similarly, hepatic triglyceride at follow-up was not different in high-intensity (-1.7% fat/water (F/W); 95% CI: -7.0, +3.6% F/W) and moderate-intensity (-0.40% FW; 95% CI: -6.0, +5.3% F/W) ET compared with controls. Both high intensity (+4.4 ml per kg-FFM (fat-free mass) per minute; 95% CI: 1.7, 7.1 ml kg-FFM(-1) min(-1)) and moderate intensity (+4.4 ml kg-FFM(-1) min(-1); 95% CI: 1.6, 7.3 ml kg-FFM(-1) min(-1)) increased cardiorespiratory fitness, relative to controls (interaction P<0.001). ET improves cardiorespiratory fitness among obese adolescents; however, owing to lack of compliance, the influence of exercise intensity on insulin sensitivity and hepatic triglycerides remains unclear.

Design and clinical pilot testing of the model-based dynamic insulin sensitivity and secretion test (DISST).

PubMed

Lotz, Thomas F; Chase, J Geoffrey; McAuley, Kirsten A; Shaw, Geoffrey M; Docherty, Paul D; Berkeley, Juliet E; Williams, Sheila M; Hann, Christopher E; Mann, Jim I

2010-11-01

Insulin resistance is a significant risk factor in the pathogenesis of type 2 diabetes. This article presents pilot study results of the dynamic insulin sensitivity and secretion test (DISST), a high-resolution, low-intensity test to diagnose insulin sensitivity (IS) and characterize pancreatic insulin secretion in response to a (small) glucose challenge. This pilot study examines the effect of glucose and insulin dose on the DISST, and tests its repeatability. DISST tests were performed on 16 subjects randomly allocated to low (5 g glucose, 0.5 U insulin), medium (10 g glucose, 1 U insulin) and high dose (20 g glucose, 2 U insulin) protocols. Two or three tests were performed on each subject a few days apart. Average variability in IS between low and medium dose was 10.3% (p=.50) and between medium and high dose 6.0% (p=.87). Geometric mean variability between tests was 6.0% (multiplicative standard deviation (MSD) 4.9%). Geometric mean variability in first phase endogenous insulin response was 6.8% (MSD 2.2%). Results were most consistent in subjects with low IS. These findings suggest that DISST may be an easily performed dynamic test to quantify IS with high resolution, especially among those with reduced IS. © 2010 Diabetes Technology Society.

Efficacy of octreotide-LAR in dieting women with abdominal obesity and polycystic ovary syndrome.

PubMed

Gambineri, Alessandra; Patton, Laura; De Iasio, Rosaria; Cantelli, Barbara; Cognini, Graciela Estela; Filicori, Marco; Barreca, Antonina; Diamanti-Kandarakis, Evanthia; Pagotto, Uberto; Pasquali, Renato

2005-07-01

Somatostatin reduces LH, GH, and insulin, and somatostatin receptors are present at the ovarian level; somatostatin analogs are thus potential candidates for treatment of the polycystic ovary syndrome (PCOS). The purpose of this study was to evaluate the effect of octreotide-LAR, a long-acting somatostatin analog, in anovulatory abdominal obese women with PCOS. A single-blind, placebo-controlled study was performed, lasting for 7 months. The patients were ambulatory throughout the study. Twenty PCOS subjects were enrolled. Eighteen completed the study. A low-calorie diet was given during the first month, a low-calorie diet plus octreotide-LAR (10 mg; n = 10 subjects) or placebo (n = 10 subjects) was then given, with one im injection every 28 d (for 6 months). The main outcome measures were clinical features, computerized tomography measurement of fat distribution, androgens, GH, IGF-I, IGF-binding proteins (IGFBPs), fasting and glucose-stimulated insulin, and ovulation. Octreotide had no additional effect in reducing body fat or improving fat distribution than placebo. Conversely, octreotide produced an additional decrease in fasting (P = 0.018) and glucose-stimulated (P = 0.038) insulin levels, an increase in IGFBP-2 (P = 0.042) and IGFBP-3 (P = 0.047), and an improvement in hirsutism (P = 0.004). Moreover, a trend toward greater reductions in testosterone (P = 0.061) and androstenedione (P = 0.069) was observed in women treated with octreotide-LAR compared with those given placebo. All women treated with octreotide ovulated at the end of the study compared with only one of those receiving placebo (P < 0.001). Octreotide-LAR may be usefully applied to hypocalorically dieting, abdominal obese PCOS women to improve hyperandrogenism and the insulin-IGF-I system. Restoration of ovulatory menstrual cycles appears to be another advantage of this treatment.

Computerized detection of unruptured aneurysms in MRA images: reduction of false positives using anatomical location features

NASA Astrophysics Data System (ADS)

Uchiyama, Yoshikazu; Gao, Xin; Hara, Takeshi; Fujita, Hiroshi; Ando, Hiromichi; Yamakawa, Hiroyasu; Asano, Takahiko; Kato, Hiroki; Iwama, Toru; Kanematsu, Masayuki; Hoshi, Hiroaki

2008-03-01

The detection of unruptured aneurysms is a major subject in magnetic resonance angiography (MRA). However, their accurate detection is often difficult because of the overlapping between the aneurysm and the adjacent vessels on maximum intensity projection images. The purpose of this study is to develop a computerized method for the detection of unruptured aneurysms in order to assist radiologists in image interpretation. The vessel regions were first segmented using gray-level thresholding and a region growing technique. The gradient concentration (GC) filter was then employed for the enhancement of the aneurysms. The initial candidates were identified in the GC image using a gray-level threshold. For the elimination of false positives (FPs), we determined shape features and an anatomical location feature. Finally, rule-based schemes and quadratic discriminant analysis were employed along with these features for distinguishing between the aneurysms and the FPs. The sensitivity for the detection of unruptured aneurysms was 90.0% with 1.52 FPs per patient. Our computerized scheme can be useful in assisting the radiologists in the detection of unruptured aneurysms in MRA images.

Consumer and provider responses to a computerized version of the Illness Management and Recovery Program.

PubMed

Wright-Berryman, Jennifer L; Salyers, Michelle P; O'Halloran, James P; Kemp, Aaron S; Mueser, Kim T; Diazoni, Amanda J

2013-12-01

To explore mental health consumer and provider responses to a computerized version of the Illness Management and Recovery (IMR) program. Semistructured interviews were conducted to gather data from 6 providers and 12 consumers who participated in a computerized prototype of the IMR program. An inductive-consensus-based approach was used to analyze the interview responses. Qualitative analysis revealed consumers perceived various personal benefits and ease of use afforded by the new technology platform. Consumers also highly valued provider assistance and offered several suggestions to improve the program. The largest perceived barriers to future implementation were lack of computer skills and access to computers. Similarly, IMR providers commented on its ease and convenience, and the reduction of time intensive material preparation. Providers also expressed that the use of technology creates more options for the consumer to access treatment. The technology was acceptable, easy to use, and well-liked by consumers and providers. Clinician assistance with technology was viewed as helpful to get clients started with the program, as lack of computer skills and access to computers was a concern. Access to materials between sessions appears to be desired; however, given perceived barriers of computer skills and computer access, additional supports may be needed for consumers to achieve full benefits of a computerized version of IMR. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Aspartame in conjunction with carbohydrate reduces insulin levels during endurance exercise

PubMed Central

2012-01-01

Background As most sport drinks contain some form of non-nutritive sweetener (e.g. aspartame), and with the variation in blood glucose regulation and insulin secretion reportedly associated with aspartame, a further understanding of the effects on insulin and blood glucose regulation during exercise is warranted. Therefore, the aim of this preliminary study was to profile the insulin and blood glucose responses in healthy individuals after aspartame and carbohydrate ingestion during rest and exercise. Findings Each participant completed four trials under the same conditions (45 min rest + 60 min self-paced intense exercise) differing only in their fluid intake: 1) carbohydrate (2% maltodextrin and 5% sucrose (C)); 2) 0.04% aspartame with 2% maltodextrin and 5% sucrose (CA)); 3) water (W); and 4) aspartame (0.04% aspartame with 2% maltodextrin (A)). Insulin levels dropped significantly for CA versus C alone (43%) between pre-exercise and 30 min, while W and A insulin levels did not differ between these time points. Conclusions Aspartame with carbohydrate significantly lowered insulin levels during exercise versus carbohydrate alone. PMID:22853297

Quasi-Steady-State Analysis based on Structural Modules and Timed Petri Net Predict System's Dynamics: The Life Cycle of the Insulin Receptor.

PubMed

Scheidel, Jennifer; Lindauer, Klaus; Ackermann, Jörg; Koch, Ina

2015-12-17

The insulin-dependent activation and recycling of the insulin receptor play an essential role in the regulation of the energy metabolism, leading to a special interest for pharmaceutical applications. Thus, the recycling of the insulin receptor has been intensively investigated, experimentally as well as theoretically. We developed a time-resolved, discrete model to describe stochastic dynamics and study the approximation of non-linear dynamics in the context of timed Petri nets. Additionally, using a graph-theoretical approach, we analyzed the structure of the regulatory system and demonstrated the close interrelation of structural network properties with the kinetic behavior. The transition invariants decomposed the model into overlapping subnetworks of various sizes, which represent basic functional modules. Moreover, we computed the quasi-steady states of these subnetworks and demonstrated that they are fundamental to understand the dynamic behavior of the system. The Petri net approach confirms the experimental results of insulin-stimulated degradation of the insulin receptor, which represents a common feature of insulin-resistant, hyperinsulinaemic states.

Computerized Dose Range Checking Using Hard and Soft Stop Alerts Reduces Prescribing Errors in a Pediatric Intensive Care Unit.

PubMed

Balasuriya, Lilanthi; Vyles, David; Bakerman, Paul; Holton, Vanessa; Vaidya, Vinay; Garcia-Filion, Pamela; Westdorp, Joan; Sanchez, Christine; Kurz, Rhonda

2017-09-01

An enhanced dose range checking (DRC) system was developed to evaluate prescription error rates in the pediatric intensive care unit and the pediatric cardiovascular intensive care unit. An enhanced DRC system incorporating "soft" and "hard" alerts was designed and implemented. Practitioner responses to alerts for patients admitted to the pediatric intensive care unit and the pediatric cardiovascular intensive care unit were retrospectively reviewed. Alert rates increased from 0.3% to 3.4% after "go-live" (P < 0.001). Before go-live, all alerts were soft alerts. In the period after go-live, 68% of alerts were soft alerts and 32% were hard alerts. Before go-live, providers reduced doses only 1 time for every 10 dose alerts. After implementation of the enhanced computerized physician order entry system, the practitioners responded to soft alerts by reducing doses to more appropriate levels in 24.7% of orders (70/283), compared with 10% (3/30) before go-live (P = 0.0701). The practitioners deleted orders in 9.5% of cases (27/283) after implementation of the enhanced DRC system, as compared with no cancelled orders before go-live (P = 0.0774). Medication orders that triggered a soft alert were submitted unmodified in 65.7% (186/283) as compared with 90% (27/30) of orders before go-live (P = 0.0067). After go-live, 28.7% of hard alerts resulted in a reduced dose, 64% resulted in a cancelled order, and 7.4% were submitted as written. Before go-live, alerts were often clinically irrelevant. After go-live, there was a statistically significant decrease in orders that were submitted unmodified and an increase in the number of orders that were reduced or cancelled.

Enhancing Japanese College Students' English Reading and Vocabulary Skills by Using CALL Innovations.

ERIC Educational Resources Information Center

Loucky, John Paul

This article summarizes software which can help to enhance both local and specific reading skills (often done through what is known as intensive reading) and global or general reading skills (known as extensive reading). Although the use of computerized bilingual dictionaries (CBDs) and translation websites of various types does not appear to…

Using Computers to Enable Self-Management of Aphasia Therapy Exercises for Word Finding: The Patient and Carer Perspective

ERIC Educational Resources Information Center

Palmer, Rebecca; Enderby, Pam; Paterson, Gail

2013-01-01

Background: Speech and language therapy (SLT) for aphasia can be difficult to access in the later stages of stroke recovery, despite evidence of continued improvement with sufficient therapeutic intensity. Computerized aphasia therapy has been reported to be useful for independent language practice, providing new opportunities for continued…

Long-term insulin glargine therapy in type 2 diabetes mellitus: a focus on cardiovascular outcomes

PubMed Central

Joseph, Joshua J; Donner, Thomas W

2015-01-01

Cardiovascular disease is the leading cause of mortality in type 2 diabetes mellitus. Hyperinsulinemia is associated with increased cardiovascular risk, but the effects of exogenous insulin on cardiovascular disease progression have been less well studied. Insulin has been shown to have both cardioprotective and atherosclerosis-promoting effects in laboratory animal studies. Long-term clinical trials using insulin to attain improved diabetes control in younger type 1 and type 2 diabetes patients have shown improved cardiovascular outcomes. Shorter trials of intensive diabetes control with high insulin use in higher risk patients with type 2 diabetes have shown either no cardiovascular benefit or increased all cause and cardiovascular mortality. Glargine insulin is a basal insulin analog widely used to treat patients with type 1 and type 2 diabetes. This review focuses on the effects of glargine on cardiovascular outcomes. Glargine lowers triglycerides, leads to a modest weight gain, causes less hypoglycemia when compared with intermediate-acting insulin, and has a neutral effect on blood pressure. The Outcome Reduction With Initial Glargine Intervention (ORIGIN trial), a 6.2 year dedicated cardiovascular outcomes trial of glargine demonstrated no increased cardiovascular risk. PMID:25657589

Managing hypoglycaemia.

PubMed

Iqbal, Ahmed; Heller, Simon

2016-06-01

Intensive glycaemic control reduces the diabetic microvascular disease burden but iatrogenic hypoglycaemia is a major barrier preventing tight glycaemic control because of the limitations of subcutaneous insulin preparations and insulin secretagogues. Severe hypoglycaemia is uncommon early in the disease as robust physiological defences, particularly glucagon and adrenaline release, limit falls in blood glucose whilst associated autonomic symptoms drive patients to take action by ingesting oral carbohydrate. With increasing diabetes duration, glucagon release is progressively impaired and sympatho-adrenal responses are activated at lower glucose levels. Repeated hypoglycaemic episodes contribute to impaired defences, increasing the risk of severe hypoglycaemia in a vicious downward spiral. Managing hypoglycaemia requires a systematic clinical approach with structured insulin self-management training and support of experienced diabetes educators. Judicious use of technologies includes insulin analogues, insulin pump therapy, continuous glucose monitoring, and in a few cases islet cell transplantation. Some individuals require specialist psychological support. Copyright © 2016. Published by Elsevier Ltd.

Dose Adjustment for Normal Eating: A Role for the Expert Patient?

PubMed Central

2014-01-01

The Dose Adjustment for Normal Eating (DAFNE) programme of intensive insulin therapy for type 1 diabetes provides a structured educational intervention to improve glycemic control, reduce hypoglycemia and improve quality of life. Enhancement of self-management skills is a key element of DAFNE and patients acquire detailed skills in insulin dose adjustment. Following DAFNE training, patients report improved confidence in their ability to manage their own insulin dosing, but generally still seek and require the assistance of health professionals when making substantial changes to their insulin regimens. Some DAFNE trained patients may be able to assist their peers in aspects of diabetes management within a group environment, but widespread introduction of the expert patient/peer educator role in the self-management of type 1 diabetes, in particular related to insulin dose management, would require formal and detailed evaluation, preferably in randomized controlled clinical trials, before being introduced into routine clinical practice. PMID:24851201

Effects of computerized decision support systems on blood glucose regulation in critically ill surgical patients.

PubMed

Fogel, Sandy L; Baker, Christopher C

2013-04-01

The use of computerized decision support systems (CDSS) in glucose control for critically ill surgical patients has been reported in both diabetic and nondiabetic patients. Prospective studies evaluating its effect on glucose control are, however, lacking. The objective of this study was to evaluate patient-specific computerized IV insulin dosing on blood glucose levels (BGLs) by comparing patients treated pre-CDSS with those treated post-CDSS. A prospective study was performed in 4 surgical ICUs and 1 progressive care unit comparing patient data pre- and post-implementation of CDSS. The primary outcomes measures were the impact of the CDSS on glycemic control in this population and on reducing the incidence of severe hypoglycemia. Data on 1,682 patient admissions were evaluated, which corresponded to 73,290 BGLs post-CDSS compared with 44,972 BGLs pre-CDSS. The percentage of hyperglycemic events improved, with BGLs of >150 mg/dL decreasing by 50% compared with 6-month historical controls during the 18-month study period from July 2010 through December 2011. This was true for all 5 units individually (p < 0.0001, by one sample sign test). In addition, severe hypoglycemia (defined as BGL <40 mg/dL) decreased from 1% to 0.05% after implementing CDSS (p < 0.0001 by 2-sided binomial test). Patients whose BGLs were managed using CDSS were statistically significantly more likely to have a glucose reading under control (<150 mg/dL) than in the 6-month historical controls and to avoid serious hypoglycemia (p < 0.0001). Copyright © 2013 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Energy-matched moderate and high intensity exercise training improves nonalcoholic fatty liver disease risk independent of changes in body mass or abdominal adiposity - A randomized trial.

PubMed

Winn, Nathan C; Liu, Ying; Rector, R Scott; Parks, Elizabeth J; Ibdah, Jamal A; Kanaley, Jill A

2018-01-01

Exercise training is commonly prescribed for individuals diagnosed with nonalcoholic fatty liver disease (NAFLD); however, consensus regarding the volume and intensity of exercise for optimal benefits is lacking. Thus, we determined whether high intensity interval exercise training (HIIT) produced greater reductions in intrahepatic lipid (IHL) content and NAFLD risk factors compared with energy-matched moderate intensity continuous exercise training (MICT) in obese adults with liver steatosis. Eighteen obese adults were randomized to either 4weeks of HIIT (4min 80% VO 2 peak/3min, 50% VO 2 peak) or MICT (55% VO 2 peak, ~60min), matched for energy expenditure (~400kcal/session) and compared to five non-exercising age-matched control subjects. IHL was measured by 1 H-MRS and frequent blood samples were analyzed for glucose, insulin, c-peptide, and NEFA levels during a liquid meal test (180min) to characterize metabolic phenotype. Baseline body weight, visceral abdominal adiposity, and fasting insulin concentrations were greater in the MICT vs HIIT group (P<0.05), while IHL was tightly matched between MICT and HIIT subjects (P>0.05), albeit higher than control subjects (P<0.01). Visceral abdominal adiposity, body mass, liver aminotransferases (ALT, AST), and hepatic apoptotic/inflammatory markers (cytokeratin 18 and fetuin a) were not reduced with either exercise training intervention (P>0.05). Both HIIT and MICT lowered IHL (HIIT, -37.0±12.4%; MICT, -20.1±6.6%, P<0.05); however, the reduction in IHL was not statistically different between exercise intensities (P=0.25). Furthermore, exercise training decreased postprandial insulin, c-peptide, and lipid peroxidation levels (iAUC, P<0.05). Collectively, these findings indicate that energy-matched high intensity and moderate intensity exercise are effective at decreasing IHL and NAFLD risk that is not contingent upon reductions in abdominal adiposity or body mass. Copyright © 2017 Elsevier Inc. All rights reserved.

Modern-Day Clinical Course of Type 1 Diabetes Mellitus After 30 Years’ Duration

PubMed Central

Nathan, David M.; Zinman, Bernard; Cleary, Patricia A.; Backlund, Jye-Yu C.; Genuth, Saul; Miller, Rachel; Orchard, Trevor J.

2010-01-01

Background Clinical treatment goals of type 1 diabetes mellitus (T1DM) have changed since the Diabetes Control and Complications Trial (DCCT) demonstrated reduced long-term complications with intensive diabetes therapy. There have been few longitudinal studies to describe the clinical course of T1DM in the age of intensive therapy. Our objective was to describe the current-day clinical course of T1DM. Methods An analysis of the cumulative incidence of long-term complications was performed. The DCCT (1983-1993) assigned patients to conventional or intensive therapy. Since 1993, the DCCT has been observational, and intensive therapy was recommended for all patients. The Pittsburgh Epidemiology of Diabetes Complications (EDC) study is an observational study of patients with T1DM from Allegheny County, Pennsylvania. The study population comprised the DCCT T1DM cohort (N=1441) and a subset of the EDC cohort (n=161) selected to match DCCT entry criteria. In the DCCT, intensive therapy aimed for a near-normal glycemic level with 3 or more daily insulin injections or an insulin pump. Conventional therapy, with 1 to 2 daily insulin injections, was not designed to achieve specific glycemic targets. Main outcome measures included the incidences of proliferative retinopathy, nephropathy (albumin excretion rate >300 mg/24 h, creatinine level ≥2 mg/dL [to convert to micromoles per liter, multiply by 88.4], or renal replacement), and cardiovascular disease. Results After 30 years of diabetes, the cumulative incidences of proliferative retinopathy, nephropathy, and cardiovascular disease were 50%, 25%, and 14%, respectively, in the DCCT conventional treatment group, and 47%, 17%, and 14%, respectively, in the EDC cohort. The DCCT intensive therapy group had substantially lower cumulative incidences (21%, 9%, and 9%) and fewer than 1% became blind, required kidney replacement, or had an amputation because of diabetes during that time. Conclusion The frequencies of serious complications in patients with T1DM, especially when treated intensively, are lower than that reported historically. PMID:19636033

Accurate screening for insulin resistance in PCOS women using fasting insulin concentrations.

PubMed

Lunger, Fabian; Wildt, Ludwig; Seeber, Beata

2013-06-01

The aims of this cross-sectional study were to evaluate the relative agreement of both static and dynamic methods of diagnosing IR in women with polycystic ovary syndrome (PCOS) and to suggest a simple screening method for IR. All participants underwent serial blood draws for hormonal profiling and lipid assessment, a 3 h, 75 g load oral glucose tolerance test (OGTT) with every 15 min measurements of glucose and insulin, and an ACTH stimulation test. The prevalence of IR ranged from 12.2% to 60.5%, depending on the IR index used. Based on largest area under the curve on receiver operating curve (ROC) analyses, the dynamic indices outperformed the static indices with glucose to insulin ratio and fasting insulin (fInsulin) demonstrating the best diagnostic properties. Applying two cut-offs representing fInsulin extremes (<7 and >13 mIU/l, respectively) gave the diagnosis in 70% of the patients with high accuracy. Currently utilized indices for assessing IR give highly variable results in women with PCOS. The most accurate indices based on dynamic testing can be time-consuming and labor-intensive. We suggest the use of fInsulin as a simple screening test, which can reduce the number of OGTTs needed to routinely assess insulin resistance in women with PCOS.

Different effects of low- and high-dose insulin on ROS production and VEGF expression in bovine retinal microvascular endothelial cells in the presence of high glucose.

PubMed

Wu, Haixiang; Jiang, Chunhui; Gan, Dekang; Liao, Yujie; Ren, Hui; Sun, Zhongcui; Zhang, Meng; Xu, Gezhi

2011-09-01

Clinical trials have demonstrated that acute intensive insulin therapy may cause transient worsening of retinopathy in type 1 and type 2 diabetes patients. However, the related mechanism still remains controversial. The purpose of the present study was to investigate the effect of insulin on the mitochondrial membrane potential (△Ψm), reactive oxygen species (ROS) production, UCP-2 and VEGF expression in bovine retinal microvascular endothelial cells (BRECs) in the presence of normal or high glucose and the related mechanisms. BRECs were isolated as primary cultures and identified by immunostaining. Passage BRECs were initially exposed to normal (5 mM) or high glucose (30 mM) for 3 days, with equimolar L: -glucose supplemented for osmotic equation. Then the cells were treated with 1 nM, 10 nM, or 100 nM insulin for 24 h: △Ψm and ROS production were determined by JC-1 and CM-H2DCFDA, respectively. Expression of UCP-2 and VEGF mRNA was determined by real-time RT-PCR; expression UCP-2 and VEGF protein was determined by Western-blotting analysis. A general ROS scavenger N-acetylcysteine (NAC, 10 mM) and an NADPH oxidase inhibitor apocynin (1 mmol/l) were added 1 h before treatment with 100 nM insulin. Insulin increased △Ψm, ROS production, and expression of UCP-2 and VEGF in BRECs at normal glucose (5 mM) in a dose-dependent manner. Low-dose insulin (1 nM) decreased △Ψm, ROS production, and UCP-2, VEGF expression in BRECs at high glucose (30 mM); and high-dose insulin (10 nM, 100nM) recovered △Ψm, ROS production, and UCP-2, VEGF expression. Pretreatment of cells with NADPH oxidase inhibitor apocynin significantly suppressed 100 nM insulin-induced ROS production (p < 0.01, one-way ANOVA). Pretreatment of cells with ROS scavenger N-acetylcysteine completely blocked insulin-induced UCP-2 expression (p < 0.01, one-way ANOVA) and significantly suppressed VEGF expression (p < 0.01, one-way ANOVA). High-dose insulin-induced ROS production and VEGF expression in BRECs in the presence of high glucose might be one of the reasons for the transient worsening of diabetic retinopathy during intensive insulin treatment.

Accurately Diagnosing Uric Acid Stones from Conventional Computerized Tomography Imaging: Development and Preliminary Assessment of a Pixel Mapping Software.

PubMed

Ganesan, Vishnu; De, Shubha; Shkumat, Nicholas; Marchini, Giovanni; Monga, Manoj

2018-02-01

Preoperative determination of uric acid stones from computerized tomography imaging would be of tremendous clinical use. We sought to design a software algorithm that could apply data from noncontrast computerized tomography to predict the presence of uric acid stones. Patients with pure uric acid and calcium oxalate stones were identified from our stone registry. Only stones greater than 4 mm which were clearly traceable from initial computerized tomography to final composition were included in analysis. A semiautomated computer algorithm was used to process image data. Average and maximum HU, eccentricity (deviation from a circle) and kurtosis (peakedness vs flatness) were automatically generated. These parameters were examined in several mathematical models to predict the presence of uric acid stones. A total of 100 patients, of whom 52 had calcium oxalate and 48 had uric acid stones, were included in the final analysis. Uric acid stones were significantly larger (12.2 vs 9.0 mm, p = 0.03) but calcium oxalate stones had higher mean attenuation (457 vs 315 HU, p = 0.001) and maximum attenuation (918 vs 553 HU, p <0.001). Kurtosis was significantly higher in each axis for calcium oxalate stones (each p <0.001). A composite algorithm using attenuation distribution pattern, average attenuation and stone size had overall 89% sensitivity, 91% specificity, 91% positive predictive value and 89% negative predictive value to predict uric acid stones. A combination of stone size, attenuation intensity and attenuation pattern from conventional computerized tomography can distinguish uric acid stones from calcium oxalate stones with high sensitivity and specificity. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A Comparison of the Effects of Aerobic and Intense Exercise on the Type 2 Diabetes Mellitus Risk Marker Adipokines, Adiponectin and Retinol Binding Protein-4

PubMed Central

Phillips, Amy

2014-01-01

With a more sedentary population comes growing rates of obesity and increased type 2 diabetes mellitus (T2DM) risk. Exercise generally induces positive changes in traditional T2DM risk markers such as lipids, glucose tolerance, and insulin sensitivity; however alterations in concentrations of many circulating cytokines and their respective receptors are also becoming apparent. These cytokines may be early-response health risk factors otherwise overlooked in traditional T2DM risk marker analysis. Plasma levels of two adipocyte-originating cytokines, adiponectin and retinol binding protein 4 (RBP-4), alter following exercise. Adiponectin has anti-inflammatory, anti-atherosclerotic, and anti-insulin resistance roles and its secretion increases with physical activity, whilst elevated RBP-4 leads to increased insulin resistance, and secretion decreases with increasing physical activity; thus these plasma adipokine levels alter favourably following exercise. Although current data are limited, they do suggest that the more intense the exercise, the greater the positive effect on plasma RBP-4 levels, whilst lower intensity aerobic exercise may positively improve adiponectin concentrations. Therefore short-duration, high intensity training may provide a time-efficient alternative to the recommended 150 min moderate aerobic exercise per week in providing positive changes in RBP-4 and other traditional T2DM risk markers and due to increased compliance give greater health benefits over the longer term. PMID:26464853

Dose comparison of ultrasonic transdermal insulin delivery to subcutaneous insulin injection

NASA Astrophysics Data System (ADS)

Park, Eun-Joo; Dodds, Jeff; Barrie Smith, Nadine

2010-03-01

Prior studies have demonstrated the effectiveness of noninvasive transdermal insulin delivery using a cymbal transducer array. In this study the physiologic response to ultrasound mediated transdermal insulin delivery is compared to that of subcutaneously administered insulin. Anesthetized rats (350-550 g) were divided into four groups of four animals; one group representing ultrasound mediated insulin delivery and three representing subcutaneously administered insulin (0.15, 0.20, and 0.25 U/kg). The cymbal array was operated for 60 minutes at 20 kHz with 100 mW/cm2 spatial-peak temporal-peak intensity and a 20% duty cycle. The blood glucose level was determined at the beginning of the experiment and, following insulin administration, every 15 minutes for 90 minutes for both the ultrasound and injection groups. The change in blood glucose from baseline was compared between groups. When administered by subcutaneous injection at insulin doses of 0.15 and 0.20 U/kg, there was little change in the blood glucose levels over the 90 minute experiment. Following subcutaneous administration of insulin at a dose of 0.25 U/kg, blood glucose decreased by 190±96 mg/dl (mean±SD) at 90 minutes. The change in blood glucose following ultrasound mediated insulin delivery was -262±40 mg/dl at 90 minutes. As expected, the magnitude of change in blood glucose between the three injection groups was dependant on the dose of insulin administered. The change in blood glucose in the ultrasound group was greater than that observed in the injection groups suggesting that a higher effective dose of insulin was delivered.

Insulin requirement profiles of short-term intensive insulin therapy in patients with newly diagnosed type 2 diabetes and its association with long-term glycemic remission.

PubMed

Liu, Liehua; Ke, Weijian; Wan, Xuesi; Zhang, Pengyuan; Cao, Xiaopei; Deng, Wanping; Li, Yanbing

2015-05-01

To investigate the insulin requirement profiles during short-term intensive continuous subcutaneous insulin infusion (CSII) in patients with newly diagnosed type 2 diabetes and its relationship with long-term glycemic remission. CSII was applied in 104 patients with newly diagnosed type 2 diabetes. Daily insulin doses were titrated and recorded to achieve and maintain euglycemia for 2 weeks. Measurements of blood glucose, lipid profiles as well as intravenous glucose tolerance tests were performed before and after the therapy. Afterwards, patients were followed up for 1 year. Total daily insulin dose (TDD) was 56.6±16.1IU at the first day when euglycemia was achieved (TDD-1). Thereafter, TDD progressively decreased at a rate of 1.4±1.0IU/day to 36.2±16.5IU at the end of the therapy. TDD-1 could be estimated with body weight, FPG, triglyceride and waist circumference in a multiple linear regression model. Decrement of TDD after euglycemia was achieved (ΔTDD) was associated with reduction of HOMA-IR (r=0.27, P=0.008) but not with improvement in β cell function. Patients in the lower tertile of ΔTDD had a significantly higher risk of hyperglycemia relapse than those in the upper tertile within 1 year (HR 3.4, 95%CI [1.4, 8.4], P=0.008). There is a steady decline of TDD after euglycemia is achieved in patients with newly diagnosed type 2 diabetes treated with CSII, and ΔTDD is associated with a better long-term glycemic outcome. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A new table for prevention of hypoglycaemia during physical activity in type 1 diabetic patients.

PubMed

Grimm, J J; Ybarra, J; Berné, C; Muchnick, S; Golay, A

2004-11-01

The ability to adjust both insulin and nutrition to allow safe participation in physical activity and high performance has recently been recognized as an important management strategy in these patients. In particular, the important role played by the patient in self-monitoring blood glucose during physical activity and then using these data to improve performance and decrease hypoglycaemias is now fully accepted. The primary objective of this study is to compare different therapeutic options in exercising Type 1 diabetic patients (n=67) with or without CHO compensation and/or with or without insulin dosage reduction in order to prevent hypoglycaemias during and after exercise. Sixty-seven type 1 diabetic patients were aggregated into four treatment categories according to four strategies to prevent hypoglycaemia episodes, with or without carbohydrate compensation and/or with or without insulin dosage reduction. The protocol included 7 different disciplines and 9 subgroups according to 3 different durations (<20 min., 20-60 min., > 60 min.) and 3 intensity degrees (<60% of Maximal Heart Rate, 60-75% and > 75%). Our study shows that by replacing adequately the carbohydrates during the practice of physical exercise it is possible to prevent almost all hypoglycaemia episodes, independently of the insulin dosage adjustments. Furthermore, the amount of extra-carbohydrates correlates well with the number of hypoglycaemia while the decrease in insulin dosage does not. Adequate carbohydrate replacement during and after exercise seems to be the most important measure to prevent hypoglycaemia. However, the insulin dosage adjustment does not play such an important role. A decrease from 20 to 30% seems reasonable only for a long duration exercise (> 60 min.). Finally, a new user-friendly table for prevention of hypoglycaemia is proposed for physical activity of different intensity and duration.

High intensity interval exercise is an effective alternative to moderate intensity exercise for improving glucose tolerance and insulin sensitivity in adolescent boys.

PubMed

Cockcroft, Emma J; Williams, Craig A; Tomlinson, Owen W; Vlachopoulos, Dimitris; Jackman, Sarah R; Armstrong, Neil; Barker, Alan R

2015-11-01

High-intensity interval exercise (HIIE) may offer a time efficient means to improve health outcomes compared to moderate-intensity exercise (MIE). This study examined the acute effect of HIIE compared to a work-matched bout of MIE on glucose tolerance, insulin sensitivity (IS), resting fat oxidation and exercise enjoyment in adolescent boys. Within-measures design with counterbalanced experimental conditions. Nine boys (14.2 ± 0.4 years) completed three conditions on separate days in a counterbalanced order: (1) HIIE; (2) work matched MIE, both on a cycle ergometer; and (3) rest (CON). An oral glucose tolerance test (OGTT) was performed after exercise or rest and the area under curve (AUC) responses for plasma [glucose] and [insulin] were calculated, and IS estimated (Cederholm index). Energy expenditure and fat oxidation were measured following the OGTT using indirect calorimetry. Exercise enjoyment was assessed using the Physical Activity Enjoyment Scale. The incremental AUC (iAUC) for plasma [glucose] was reduced following both MIE (-23.9%, P = 0.013, effect size [ES] = -0.64) and HIIE (-28.9%, P=0.008, ES = -0.84) compared to CON. The iAUC for plasma [insulin] was lower for HIIE (-24.2%, P = 0.021, ES = -0.71) and MIE (-29.1%, P = 0.012, ES = -0.79) compared to CON. IS increased by 11.2% after HIIE (P = 0.03, ES = 0.76) and 8.4% after MIE (P = 0.10, ES = 0.58). There was a trend for an increase in fat oxidation following HIIE (P = 0.097, ES = 0.70). Both HIIE and MIE were rated as equally enjoyable (P > 0.05, ES < 0.01). A single bout of time efficient HIIE is an effective alternative to MIE for improving glucose tolerance and IS in adolescent boys immediately after exercise. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Short-term HIIT and Fat max training increase aerobic and metabolic fitness in men with class II and III obesity.

PubMed

Lanzi, Stefano; Codecasa, Franco; Cornacchia, Mauro; Maestrini, Sabrina; Capodaglio, Paolo; Brunani, Amelia; Fanari, Paolo; Salvadori, Alberto; Malatesta, Davide

2015-10-01

To compare the effects of two different 2-week-long training modalities [continuous at the intensity eliciting the maximal fat oxidation (Fatmax) versus high-intensity interval training (HIIT)] in men with class II and III obesity. Nineteen men with obesity (BMI ≥ 35 kg · m(-2)) were assigned to Fatmax group (GFatmax) or to HIIT group (GHIIT). Both groups performed eight cycling sessions matched for mechanical work. Aerobic fitness and fat oxidation rates (FORs) during exercise were assessed prior and following the training. Blood samples were drawn to determine hormones and plasma metabolites levels. Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA2-IR). Aerobic fitness and FORs during exercise were significantly increased in both groups after training (P ≤ 0.001). HOMA2-IR was significantly reduced only for GFatmax (P ≤ 0.001). Resting non-esterified fatty acids (NEFA) and insulin decreased significantly only in GFatmax (P ≤ 0.002). Two weeks of HIIT and Fatmax training are effective for the improvement of aerobic fitness and FORs during exercise in these classes of obesity. The decreased levels of resting NEFA only in GFatmax may be involved in the decreased insulin resistance only in this group. © 2015 The Obesity Society.

Two-year efficacy and safety of AIR inhaled insulin in patients with type 1 diabetes: An open-label randomized controlled trial.

PubMed

Garg, Satish K; Mathieu, Chantal; Rais, Nadeem; Gao, Haitao; Tobian, Janet A; Gates, Jeffrey R; Ferguson, Jeffrey A; Webb, David M; Berclaz, Pierre-Yves

2009-09-01

Patients with type 1 diabetes require intensive insulin therapy for optimal glycemic control. AIR((R)) inhaled insulin (system from Eli Lilly and Company, Indianapolis, IN) (AIR is a registered trademark of Alkermes, Inc., Cambridge, MA) may be an efficacious and safe alternative to subcutaneously injected (SC) mealtime insulin. This was a Phase 3, 2-year, randomized, open-label, active-comparator, parallel-group study in 385 patients with type 1 diabetes who were randomly assigned to receive AIR insulin or SC insulin (regular human insulin or insulin lispro) at mealtimes. Both groups received insulin glargine once daily. Efficacy measures included mean change in hemoglobin A1C (A1C) from baseline to end point, eight-point self-monitored blood glucose profiles, and insulin dosage. Safety assessments included hypoglycemic events, pulmonary function tests, adverse events, and insulin antibody levels. In both treatment groups, only 20% of subjects reached the target of A1C <7.0%. A significant A1C difference of 0.44% was seen favoring SC insulin, with no difference between the groups in insulin doses or hypoglycemic events at end point. Patients in both treatment groups experienced progressive decreases in lung function, but larger (reversible) decrements in diffusing capacity of the lung for carbon monoxide (DL(CO)) were associated with AIR insulin treatment. Greater weight gain was seen with SC insulin treatment. The AIR inhaled insulin program was terminated by the sponsor prior to availability of any Phase 3 data for reasons unrelated to safety or efficacy. Despite early termination, this trial provides evidence that AIR insulin was less efficacious in lowering A1C and was associated with a greater decrease in DL(CO) and increased incidence of cough than SC insulin in patients with type 1 diabetes.

Changes in end-user satisfaction with Computerized Provider Order Entry over time among nurses and providers in intensive care units.

PubMed

Hoonakker, Peter L T; Carayon, Pascale; Brown, Roger L; Cartmill, Randi S; Wetterneck, Tosha B; Walker, James M

2013-01-01

Implementation of Computerized Provider Order Entry (CPOE) has many potential advantages. Despite the potential benefits of CPOE, several attempts to implement CPOE systems have failed or met with high levels of user resistance. Implementation of CPOE can fail or meet high levels of user resistance for a variety of reasons, including lack of attention to users' needs and the significant workflow changes required by CPOE. User satisfaction is a critical factor in information technology implementation. Little is known about how end-user satisfaction with CPOE changes over time. To examine ordering provider and nurse satisfaction with CPOE implementation over time. We conducted a repeated cross-sectional questionnaire survey in four intensive care units of a large hospital. We analyzed the questionnaire data as well as the responses to two open-ended questions about advantages and disadvantages of CPOE. Users were moderately satisfied with CPOE and there were interesting differences between user groups: ordering providers and nurses. User satisfaction with CPOE did not change over time for providers, but it did improve significantly for nurses. Results also show that nurses and providers are satisfied with different aspects of CPOE.

Low intensity vs. self-guided Internet-delivered psychotherapy for major depression: a multicenter, controlled, randomized study

PubMed Central

2013-01-01

Background Major depression will become the second most important cause of disability in 2020. Computerized cognitive-behaviour therapy could be an efficacious and cost-effective option for its treatment. No studies on cost-effectiveness of low intensity vs self-guided psychotherapy has been carried out. The aim of this study is to assess the efficacy of low intensity vs self-guided psychotherapy for major depression in the Spanish health system. Methods The study is made up of 3 phases: 1.- Development of a computerized cognitive-behaviour therapy for depression tailored to Spanish health system. 2.- Multicenter controlled, randomized study: A sample (N=450 patients) with mild/moderate depression recruited in primary care. They should have internet availability at home, not receive any previous psychological treatment, and not suffer from any other severe somatic or psychological disorder. They will be allocated to one of 3 treatments: a) Low intensity Internet-delivered psychotherapy + improved treatment as usual (ITAU) by GP, b) Self-guided Internet-delivered psychotherapy + ITAU or c) ITAU. Patients will be diagnosed with MINI psychiatric interview. Main outcome variable will be Beck Depression Inventory. It will be also administered EuroQol 5D (quality of life) and Client Service Receipt Inventory (consume of health and social services). Patients will be assessed at baseline, 3 and 12 months. An intention to treat and a per protocol analysis will be performed. Discussion The comparisons between low intensity and self-guided are infrequent, and also a comparative economic evaluation between them and compared with usual treatment in primary. The strength of the study is that it is a multicenter, randomized, controlled trial of low intensity and self-guided Internet-delivered psychotherapy for depression in primary care, being the treatment completely integrated in primary care setting. Trial registration Clinical Trials NCT01611818 PMID:23312003

Uncovering the Path That Leads to Diabetes | Center for Cancer Research

Cancer.gov

The origins of diabetes have been the subject of intense scientific research, but the genetic factors that cause certain people to develop the disease have remained elusive. In healthy individuals, glucose levels in the bloodstream are transiently elevated after a meal. The increase in glucose triggers β cells in the pancreatic islet to release the hormone insulin. Insulin is delivered to tissues throughout the body, and stimulates to import of glucose into cells. If a person does not produce insulin, or their cells have become insensitive to the hormone, glucose uptake does not occur and the level of glucose in the bloodstream remains elevated.  

Computerized nursing process in the Intensive Care Unit: ergonomics and usability.

PubMed

Almeida, Sônia Regina Wagner de; Sasso, Grace Teresinha Marcon Dal; Barra, Daniela Couto Carvalho

2016-01-01

Analyzing the ergonomics and usability criteria of the Computerized Nursing Process based on the International Classification for Nursing Practice in the Intensive Care Unit according to International Organization for Standardization(ISO). A quantitative, quasi-experimental, before-and-after study with a sample of 16 participants performed in an Intensive Care Unit. Data collection was performed through the application of five simulated clinical cases and an evaluation instrument. Data analysis was performed by descriptive and inferential statistics. The organization, content and technical criteria were considered "excellent", and the interface criteria were considered "very good", obtaining means of 4.54, 4.60, 4.64 and 4.39, respectively. The analyzed standards obtained means above 4.0, being considered "very good" by the participants. The Computerized Nursing Processmet ergonomic and usability standards according to the standards set by ISO. This technology supports nurses' clinical decision-making by providing complete and up-to-date content for Nursing practice in the Intensive Care Unit. Analisar os critérios de ergonomia e usabilidade do Processo de Enfermagem Informatizado a partir da Classificação Internacional para as Práticas de Enfermagem, em Unidade de Terapia Intensiva, de acordo com os padrões da InternationalOrganization for Standardization (ISO). Pesquisa quantitativa, quase-experimental do tipo antes e depois, com uma amostra de 16 participantes, realizada em uma Unidade de Terapia Intensiva. Coleta de dados realizada por meio da aplicação de cinco casos clínicos simulados e instrumento de avaliação. A análise dos dados foi realizada pela estatística descritiva e inferencial. Os critérios organização, conteúdo e técnico foram considerados "excelentes", e o critério interface "muito bom", obtendo médias 4,54, 4,60, 4,64 e 4,39, respectivamente. Os padrões analisados obtiveram médias acima de 4,0, sendo considerados "muito bons" pelos participantes. O Processo de Enfermagem Informatizado possui padrões ergonômicos e de usabilidade de acordo com os padrões estabelecidos pela ISO. Esta tecnologia apoia a decisão clínica do enfermeiro fornecendo conteúdo completo e atualizado para a prática de Enfermagem em Unidade de Terapia Intensiva.

The function of androgen/androgen receptor and insulin growth factor‑1/insulin growth factor‑1 receptor on the effects of Tribulus terrestris extracts in rats undergoing high intensity exercise.

PubMed

Wu, Yin; Yang, Hongfang; Wang, Xiaohui

2017-09-01

Our previous study demonstrated that treatment with Tribulus terrestris (TT) extracts (120 mg/kg) promoted the muscle weight gain and performance of rats undergoing high intensity exercise. The present study was designed to explore the mechanisms underlying the effect of treatment with TT extracts and the involvement of androgens, the androgen receptor (AR), insulin growth factor‑1 (IGF‑1) and the IGF‑1 receptor (IGF‑1R). A total of 32 Sprague‑Dawley rats were randomly divided into groups as follows: Control; TT, treated with TT extracts, E, high intensity exercise; E+TT, high intensity exercise plus TT treatment. The rats of the E and E+TT groups underwent high intensity exercise with a progressively increasing load for 5 weeks, and TT extracts were intragastrically administered in the TT and E+TT rats 30 min prior to training. TT extract composition was analyzed using ultra‑high performance liquid chromatography‑quadrupole‑time of flight mass spectrometry. Testosterone and IGF‑1 plasma levels and AR, IGF‑1R and myosin heavy chain (MHC) protein levels in muscles were determined by ELISA and western blotting, respectively. The saponins tigogenin and diosgenin comprised ~71.35% of the total peak area. Compared with the E group, TT extracts increased the testosterone and IGF‑1 plasma levels, and AR, IGF‑1R and MHC protein levels in the gastrocnemius of rats undergoing high intensity exercise, accompanied with increased body weight and gastrocnemius weight. In conclusion, the effect of TT extracts on the performance of high intensity exercise rats may be attributed to increased levels of circulating testosterone and IGF‑1 and increased AR and IGF‑1R protein expression levels in the gastrocnemius, resulting in increased muscle weight and increased MHC in the gastrocnemius. The present study provided preliminary evidence supporting the use of TT extracts as a dietary supplement for the promotion of skeletal muscle mass increase and the enhancement of athletic performance in humans performing high intensity exercise.

Effects of High Intensity Interval Training and Strength Training on Metabolic, Cardiovascular and Hormonal Outcomes in Women with Polycystic Ovary Syndrome: A Pilot Study.

PubMed

Almenning, Ida; Rieber-Mohn, Astrid; Lundgren, Kari Margrethe; Shetelig Løvvik, Tone; Garnæs, Kirsti Krohn; Moholdt, Trine

2015-01-01

Polycystic ovary syndrome is a common endocrinopathy in reproductive-age women, and associates with insulin resistance. Exercise is advocated in this disorder, but little knowledge exists on the optimal exercise regimes. We assessed the effects of high intensity interval training and strength training on metabolic, cardiovascular, and hormonal outcomes in women with polycystic ovary syndrome. Three-arm parallel randomized controlled trial. Thirty-one women with polycystic ovary syndrome (age 27.2 ± 5.5 years; body mass index 26.7 ± 6.0 kg/m2) were randomly assigned to high intensity interval training, strength training, or a control group. The exercise groups exercised three times weekly for 10 weeks. The main outcome measure was change in homeostatic assessment of insulin resistance (HOMA-IR). HOMA-IR improved significantly only after high intensity interval training, by -0.83 (95% confidence interval [CI], -1.45, -0.20), equal to 17%, with between-group difference (p = 0.014). After high intensity interval training, high-density lipoprotein cholesterol increased by 0.2 (95% CI, 0.02, 0.5) mmol/L, with between group difference (p = 0.04). Endothelial function, measured as flow-mediated dilatation of the brachial artery, increased significantly after high intensity interval training, by 2.0 (95% CI, 0.1, 4.0) %, between-group difference (p = 0.08). Fat percentage decreased significantly after both exercise regimes, without changes in body weight. After strength training, anti-Müllarian hormone was significantly reduced, by -14.8 (95% CI, -21.2, -8.4) pmol/L, between-group difference (p = 0.04). There were no significant changes in high-sensitivity C-reactive protein, adiponectin or leptin in any group. High intensity interval training for ten weeks improved insulin resistance, without weight loss, in women with polycystic ovary syndrome. Body composition improved significantly after both strength training and high intensity interval training. This pilot study indicates that exercise training can improve the cardiometabolic profile in polycystic ovary syndrome in the absence of weight loss. ClinicalTrial.gov NCT01919281.

Exubera® (inhaled insulin): an evidence-based review of its effectiveness in the management of diabetes

PubMed Central

Profit, Louise

2005-01-01

Introduction: Inadequate glycemic control contributes to the development and progression of complications, which are associated with a significant economic burden on healthcare systems. However, optimal glycemic control is difficult to sustain with oral antidiabetic agents and adherence to intensive insulin regimens is compromised by patient compliance to multiple daily injections. Therefore, alternative delivery systems are required to improve the acceptability of insulin therapy. Aims: This review assesses the evidence for the therapeutic value of inhaled insulin (Exubera®) in the management of type 1 and type 2 diabetes. Evidence review: Evidence indicates that glycemic control, as measured by plasma HbA1c levels, with Exubera is as effective as subcutaneous insulin in patients with type 1 or type 2 diabetes. There is also good evidence that Exubera provides improved patient satisfaction and ease of use compared with subcutaneous insulin. However, the cost effectiveness of Exubera and its place in therapy compared with other inhaled insulin delivery systems currently in development remain to be determined. Outcomes summary: Exubera is an alternative treatment option for the management of diabetes which provides effective glycemic control with improved patient satisfaction. PMID:22500147

Insulin regulates the novel adipokine adipolin/CTRP12: in vivo and ex vivo effects.

PubMed

Tan, Bee K; Lewandowski, Krzysztof C; O'Hare, Joseph Paul; Randeva, Harpal S

2014-04-01

There has been intense interest in the adipokines of the C1q complement/TNF-related protein (CTRP) superfamily. Adipolin (CTRP12) has been described as a novel adipokine, abundantly expressed in adipose tissue with insulin-sensitising and anti-inflammatory effects. We wanted to investigate the effects of acute and chronic hyperinsulinaemia on circulating adipolin concentrations (ELISA) via a prolonged insulin-glucose infusion in humans. We also examined the effects of insulin and the insulin sensitiser, rosiglitazone, on adipolin concentrations (western blotting) in human adipose tissue explants. We found that hyperinsulinaemic induction in healthy lean human subjects significantly increased circulating levels of adipolin (P<0.05 and P<0.01). Furthermore, in subcutaneous adipose tissue explants, insulin significantly increased adipolin protein expression and secretion (P<0.05 and P<0.01). This effect was attenuated by the phosphatidylinositol 3-kinase inhibitor, LY294002 (P<0.05). Moreover, the insulin-sensitising peroxisome proliferator-activated receptor γ (PPARγ) agonist, rosiglitazone, significantly increased adipolin protein expression and secretion in subcutaneous adipose tissue explants (P<0.05 and P<0.01). This effect was inhibited by the PPARγ antagonist, GW9662 (P<0.05). Our data provide novel insights into adipolin physiology in human subjects.

The effects of exenatide twice daily compared to insulin lispro added to basal insulin in Latin American patients with type 2 diabetes: A retrospective analysis of the 4B trial.

PubMed

de Lapertosa, Silvia Beatriz Gorban; Frechtel, Gustavo; Hardy, Elise; Sauque-Reyna, Leobardo

2016-12-01

Socioeconomic changes in Latin American countries have led to an increased prevalence of type 2 diabetes (T2D). We examined the effects of exenatide twice daily (BID) or insulin lispro, each added to insulin glargine, in Latin American patients with T2D. This was a subgroup analysis of patients from Argentina and Mexico in the 4B study (N=114). Patients with glycated hemoglobin (HbA1c) of 7.0-10.0% (53-86mmol/mol) after 12weeks of intensive basal insulin optimization were randomized to exenatide BID or thrice-daily insulin lispro added to insulin glargine and metformin. After 30weeks, addition of exenatide BID or insulin lispro resulted in significant (P<0.0001) reductions in HbA1c (exenatide BID: -0.9% [-10mmol/mol]; insulin lispro: -1.2% [-13mmol/mol]). Weight was stable in the exenatide BID group (-0.1kg) and increased significantly (+3.4kg; P<0.0001) with insulin lispro. Major and minor hypoglycemia occurred less frequently (40 vs. 253 events) with exenatide BID compared with insulin lispro. Gastrointestinal adverse events of nausea, diarrhea, and vomiting occurred more frequently with exenatide BID than with insulin lispro. Both exenatide BID and prandial insulin lispro, each added to basal insulin glargine, were effective at reducing HbA1c in Latin American patients. Treatment with exenatide BID resulted in stable weight but more gastrointestinal adverse events. Treatment with insulin lispro resulted in weight gain and an increased risk of hypoglycemia. These findings support the addition of exenatide BID to insulin glargine as an option for Latin American patients unable to achieve glycemic control on basal insulin alone. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

[Increasing cost of insulin therapy in Belgium. From a critical analysis of the situation to a search for practical solutions].

PubMed

Scheen, A J

2006-09-01

Cost related to insulin therapy is markedly increasing in Belgium, as in other Eucopean countries. In the present paper, we will briefly analyze the main reasons for such aa increase, integrate such observation withIn the global context of diabetes management and suggest some solutions to provide best care to insulin-treated diabetic patients at a reasonable cost. The rise of the cost of insulin therapy has a multifactorial origin. It mainly results from an increase in the number of diabetic patients, a more intensive management, In both type 1 and type 2 diabetes, and a greater use of more expansive insulin analogues. It is important to analyze the increase of the cost of insulin therapy within the global burden of diabetes melitus. Only a better responsibility of all health care partners, patients, physicians, pharmaceutical companies, public health authorities, could provide solutions allowing diabetic people to profit from best treatments they should receive in order to prevent diabetic complications, by far the main cause of expenses.

Computerized symptom and quality-of-life assessment for patients with cancer part I: development and pilot testing.

PubMed

Berry, Donna L; Trigg, Lisa J; Lober, William B; Karras, Bryant T; Galligan, Mary L; Austin-Seymour, Mary; Martin, Stephanie

2004-09-01

To develop and test an innovative computerized symptom and quality-of-life (QOL) assessment for patients with cancer who are evaluated for and treated with radiation therapy. Descriptive, longitudinal prototype development and cross-sectional clinical data. Department of radiation oncology in an urban, academic medical center. 101 outpatients who were evaluated for radiation therapy, able to communicate in English (or through one of many interpreters available at the University of Washington), and competent to understand the study information and give informed consent. Six clinicians caring for the patients in the sample were enrolled. Iterative prototype development was conducted using a standing focus group of clinicians. The software was developed based on survey markup language and implemented in a wireless, Web-based format. Patient participants completed the computerized assessment prior to consultation with the radiation physician. Graphical output pages with flagged areas of symptom distress or troublesome QOL issues were made available to consulting physicians and nurses. Pain intensity, symptoms, QOL, and demographics. Computerized versions of a 0 to 10 Pain Intensity Numerical Scale (PINS), Symptom Distress Scale, and Short Form-8. Focus group recommendations included clinician priorities of brevity, flexibility, and simplicity for both input interface and output and that the assessment output contain color graphic display. Patient participants included 45 women and 56 men with a mean age of 52.7 years (SD = 13.8). Fewer than half of the participants (40%) reported using a computer on a regular basis (weekly or daily). Completion time averaged 7.8 minutes (SD = 3.7). Moderate to high levels of distress were reported more often for fatigue, pain, and emotional issues than for other symptoms or concerns. Computerized assessment of cancer symptoms and QOL is technically possible and feasible in an ambulatory cancer clinic. A wireless, Web-based system facilitates access to results and data entry and retrieval. The symptom and QOL profiles of these patients new to radiation therapy were comparable to other samples of outpatients with cancer. The ability to capture an easily interpreted illustration of a patients symptom and QOL experience in less than 10 minutes is a potentially useful adjunct to traditional face-to-face interviewing. Ultimately, electronic patient-generated data could produce automated red flags directed to the most appropriate clinicians (e.g., nurse, pain specialist, social worker, nutritionist) for further evaluation. Such system enhancement could greatly facilitate oncology nurses coordination role in caring for complex patients with cancer.

Metabolomic Response of Skeletal Muscle to Aerobic Exercise Training in Insulin Resistant Type 1 Diabetic Rats.

PubMed

Dotzert, Michelle S; Murray, Michael R; McDonald, Matthew W; Olver, T Dylan; Velenosi, Thomas J; Hennop, Anzel; Noble, Earl G; Urquhart, Brad L; Melling, C W James

2016-05-20

The etiology of insulin resistance in Type 1 Diabetes (T1D) is unknown, however it affects approximately 20% of T1D patients. Intramyocellular lipids (IMCL) have been identified as a mechanism of insulin resistance. We examined skeletal muscle of T1D rats to determine if alterations in lipid metabolism were evident and whether aerobic exercise training improves IMCL and insulin resistance. To do so, 48 male Sprague-Dawley rats were divided into control (C), sedentary diabetes (D) and diabetes exercise (DX) groups. Following multiple low-dose Streptozotocin (STZ) injections (20 mg/kg), glycemia (9-15 mM) was maintained using insulin treatment. DX were treadmill trained at high intensity (~75% V02max; 5days/week) for 10 weeks. The results demonstrate that D exhibited insulin resistance compared with C and DX, indicated by decreased glucose infusion rate during a hyperinsulinemic-euglycemic clamp (p < 0.05). There were no differences between C and DX, suggesting that exercise improved insulin resistance (p < 0.05). Metabolomics analysis revealed a significant shift in lipid metabolism whereby notable fatty acid metabolites (arachidonic acid, palmitic acid and several polyunsaturated fatty acids) were significantly elevated in D compared to C and DX. Based on the intermediates observed, insulin resistance in T1D is characterized by an insulin-desensitizing intramyocellular fatty acid metabolite profile that is ameliorated with exercise training.

Insulin requirements in late pregnancy in women with type 1 diabetes mellitus: a retrospective review.

PubMed

Achong, N; Callaway, L; d'Emden, M; McIntyre, H D; Lust, K; Barrett, H L

2012-12-01

Pregnancy in women with type 1 diabetes mellitus (T1DM) is generally associated with increased insulin requirements. To determine the frequency and significance of declining insulin requirements in late gestation in women with T1DM. We conducted a retrospective review of 54 women seen at our institution from 2006 to 2010 with a diagnosis of T1DM pre-pregnancy and presentation for antenatal care prior to 28 weeks. Information was collected regarding patient demographics, insulin dose and pregnancy outcome. A 15% difference in weight-adjusted basal insulin from 30 weeks gestation to delivery was considered significant. Five women (9.3%) had a fall of 15% or more and 23 (42.5%) had a rise of 15% or more rise in insulin requirements. There were fewer neonatal intensive care admissions but more infants with an APGAR <8 at 5 min in women with a fall in insulin requirements. These differences were not evident when the data were re-analysed by quartiles of change. In most women with T1DM, insulin requirements show little change from 30 weeks gestation until delivery. Almost 10% of women had a significant fall in insulin requirements which did not correlate with adverse neonatal outcome. These results require validation in a larger, prospective trial. Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

Effect of intensive insulin therapy on macular biometrics, plasma VEGF and its soluble receptor in newly diagnosed diabetic patients.

PubMed

Hernández, Cristina; Zapata, Miguel A; Losada, Eladio; Villarroel, Marta; García-Ramírez, Marta; García-Arumí, José; Simó, Rafael

2010-07-01

To evaluate whether intensive insulin therapy leads to changes in macular biometrics (volume and thickness) in newly diagnosed diabetic patients with acute hyperglycaemia and its relationship with serum levels of vascular endothelial growth factor (VEGF) and its soluble receptor (sFlt-1). Twenty-six newly diagnosed diabetic patients admitted to our hospital to initiate intensive insulin treatment were prospectively recruited. Examinations were performed on admission (day 1) and during follow-up (days 3, 10 and 21) and included a questionnaire regarding the presence of blurred vision, standardized refraction measurements and optical coherence tomography. Plasma VEGF and sFlt-1 were assessed by ELISA at baseline and during follow-up. At study entry seven patients (26.9%) complained of blurred vision and five (19.2%) developed burred vision during follow-up. Macular volume and thickness increased significantly (p = 0.008 and p = 0.04, respectively) in the group with blurred vision at day 3 and returned to the baseline value at 10 days. This pattern was present in 18 out of the 24 eyes from patients with blurred vision. By contrast, macular biometrics remained unchanged in the group without blurred vision. We did not detect any significant changes in VEGF levels during follow-up. By contrast, a significant reduction of sFlt-1 was observed in those patients with blurred vision at day 3 (p = 0.03) with normalization by day 10. Diabetic patients with blurred vision after starting insulin therapy present a significant transient increase in macular biometrics which is associated with a decrease in circulating sFlt-1. Copyright (c) 2010 John Wiley & Sons, Ltd.

Sustained, Low-Intensity Exercise Achieved by a Dynamic Feeding System Decreases Body Fat in Ponies.

PubMed

de Laat, M A; Hampson, B A; Sillence, M N; Pollitt, C C

2016-09-01

Obesity in horses is increasing in prevalence and can be associated with insulin insensitivity and laminitis. Current treatment strategies for obesity include dietary restriction and exercise. However, whether exercise alone is effective for decreasing body fat is uncertain. Our hypothesis was that twice daily use of a dynamic feeding system for 3 months would induce sustained, low-intensity exercise thereby decreasing adiposity and improving insulin sensitivity (SI). Eight, university-owned, mixed-breed, adult ponies with body condition scores (BCS) ≥5/9 were used. Two treatments ("feeder on" or "feeder off") were administered for a 3-month period by a randomized, crossover design (n = 4/treatment). An interim equilibration period of 6 weeks at pasture separated the 2 study phases. Measurements of body mass (body weight, BCS, cresty neck score [CrNS], and morphometry), body fat (determined before and after the "feeder on" treatment only), triglycerides, and insulin sensitivity (SI; combined glucose-insulin test) were undertaken before and after treatments. The dynamic feeding system induced a 3.7-fold increase in the daily distance travelled (n = 6), compared to with a stationary feeder, which significantly decreased mean BCS (6.53 ± 0.94 to 5.38 ± 1.71), CrNS (2.56 ± 1.12 to 1.63 ± 1.06) and body fat (by 4.95%). An improvement in SI did not occur in all ponies. A dynamic feeding system can be used to induce sustained (daily), low-intensity exercise that promotes weight loss in ponies. However, this exercise may not be sufficient to substantially improve SI. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

[New developments in the treatment and monitoring of type 1 diabetes mellitus].

PubMed

Otto-Buczkowska, Ewa; Jarosz-Chobot, Przemysława; Tucholski, Krzysztof

2008-01-01

In recent years, insulin analogues are the benefits of the use in functional intensive insulin therapy for the treatment of diabetes. Shortacting insulin (lispro, aspart and glulisine) and long-acting insulin (glargine and detemir) have been developed for the management of diabetes. Short-acting insulin analogues are an alternative to regular human insulin before meals. These new short-acting insulin analogues show more rapid onset of activity and a shorter duration of action. As a result of these pharmacokinetic differences, an improved postprandial glycemic control is achieved, without increasing the risk of hypoglycemia. In addition, these insulin analogues can be administered immediately before a meal. The long-acting insulin analogues provide basal insulin levels for 24 h when administered once (glargine) or two (detemir) daily. Compared with previous intermediate- or long-acting conventional insulin, these insulins shows a flat profile of plasma insulin levels . The use of these long-acting insulin analogues appears to be associated with a reduced incidence of hypoglycemia, especially at night. The availability of these new insulin analogues has the potential to significantly improve long-term control over blood glucose in diabetic patients. In recent years more and more frequently the method of multiple daily injections (MDI) of insulin is being replaced by the method of continuous subcutaneous insulin infusion (CSII). It is the most physiological way to administer insulin. In recent years treatment with insulin pumps has been used more frequently in the pediatric patients and in the treatment of diabetes in pregnancy. Use of continuous glucose monitoring systems enables detection of glycemia fluctuations unrevealed by selfmonitoring of blood glucose, such as night hypoglycemias and early postprandial hyperglycemias. Real-time systems allow to reduce HbA1c levels and limit number of excursions. Non-invasive glucose measurement devices are introduced. Fully automated continuous glucose monitoring systems integrated with insulin pumps operating in closed-loop model, requiring no patient assistance, are still being researched. Commercially available systems operate in open-loop model, where the patient has to decide on administration and dose of insulin.

Associations of Low- and High-Intensity Light Activity with Cardiometabolic Biomarkers.

PubMed

Howard, Bethany; Winkler, Elisabeth A H; Sethi, Parneet; Carson, Valerie; Ridgers, Nicola D; Salmon, J O; Healy, Genevieve N; Owen, Neville; Dunstan, David W

2015-10-01

Light-intensity physical activity (LIPA) accounts for much of adults' waking hours (≈40%) and substantially contributes to overall daily energy expenditure. Encompassing activity behaviors of low intensity (standing with little movement) to those of higher intensity (slow walking), LIPA is ubiquitous, yet little is known about how associations with health may vary depending on its intensity. We examined the associations of objectively assessed LIPA (categorized as either low LIPA [LLPA] or high LIPA [HLPA]) and moderate- to vigorous-intensity activity with cardiometabolic risk biomarkers. Cardiometabolic biomarkers were measured in 4614 US adults (47 ± 17 yr) who participated in the 2003-2004 and 2005-2006 National Health and Nutrition Examination Survey cycles. Multiple linear regression analyses examined the associations of three accelerometer-derived physical activity (SD increment per day) intensity categories (LLPA, 100-761 counts per minute; HLPA, 762-1951 counts per minute; moderate-intensity physical activity [MPA], 1952-5724 counts per minute; vigorous-intensity physical activity [VPA], ≥5725 counts per minute) with cardiometabolic biomarkers, adjusting for potential sociodemographic, behavioral, and medical confounders. All intensities of physical activity were beneficially associated with waist circumference, C-reactive protein, triglycerides, fasting insulin, β-cell function, and insulin sensitivity (P < 0.05); only some activity intensities showed significant associations with systolic blood pressure (LLPA), body mass index, HDL cholesterol, fasting glucose, and 2-h plasma glucose (HLPA, MPA, and VPA). Generally, effect size increased with intensity of physical activity. Overall, further adjustment for waist circumference attenuated associations with MPA and VPA to a greater extent than associations with LLPA and HLPA. The cross-sectional findings provide novel evidence for the potential benefits of increasing both LLPA and HLPA. They further reinforce the established importance of moderate- to vigorous-intensity activity, the mainstay of public health recommendations.

Detecting insulin resistance in polycystic ovary syndrome: purposes and pitfalls.

PubMed

Legro, Richard S; Castracane, V Daniel; Kauffman, Robert P

2004-02-01

Approximately 50% to 70% of all women with polycystic ovary syndrome (PCOS) have some degree of insulin resistance, and this hormone insensitivity probably contributes to the hyperandrogenism that is responsible for the signs and symptoms of PCOS. Although uncertainty exists, early detection and treatment of insulin resistance in this population could ultimately reduce the incidence or severity of diabetes mellitus, dyslipidemia, hypertension, and cardiovascular disease. Even if that proves to be the case, there are still several problems with our current approach to insulin sensitivity assessment in PCOS, including the apparent lack of consensus on what defines PCOS and "normal" insulin sensitivity, ethnic and genetic variability, the presence of other factors contributing to insulin resistance such as obesity, stress, and aging, and concern about whether simplified models of insulin sensitivity have the precision to predict treatment needs, responses, and future morbidity. Although the hyperinsulinemic-euglycemic clamp technique is the gold standard for measuring insulin sensitivity, it is too expensive, time-consuming, and labor-intensive to be of practical use in an office setting. Homeostatic measurements (fasting glucose/insulin ratio or homeostatic model assessment [HOMA] value) and minimal model tests (particularly the oral glucose tolerance test [OGTT]) represent the easiest office-based assessments of insulin resistance in the PCOS patient. The OGTT is probably the best simple, office-based method to assess women with PCOS because it provides information about both insulin resistance and glucose intolerance. The diagnosis of glucose intolerance holds greater prognostic and treatment implications. All obese women with PCOS should be screened for the presence of insulin resistance by looking for other stigmata of the insulin resistance syndrome such as hypertension, dyslipidemia, central obesity, and glucose intolerance.

Effects of menopause and high-intensity training on insulin sensitivity and muscle metabolism.

PubMed

Mandrup, Camilla M; Egelund, Jon; Nyberg, Michael; Enevoldsen, Lotte Hahn; Kjær, Andreas; Clemmensen, Andreas E; Christensen, Anders Nymark; Suetta, Charlotte; Frikke-Schmidt, Ruth; Steenberg, Dorte Enggaard; Wojtaszewski, Jørgen F P; Hellsten, Ylva; Stallknecht, Bente M

2018-02-01

To investigate peripheral insulin sensitivity and skeletal muscle glucose metabolism in premenopausal and postmenopausal women, and evaluate whether exercise training benefits are maintained after menopause. Sedentary, healthy, normal-weight, late premenopausal (n = 21), and early postmenopausal (n = 20) women were included in a 3-month high-intensity exercise training intervention. Body composition was assessed by magnetic resonance imaging and dual-energy x-ray absorptiometry, whole body glucose disposal rate (GDR) by hyperinsulinemic euglycemic clamp (40 mU/m/min), and femoral muscle glucose uptake by positron emission tomography/computed tomography, using the glucose analog fluorodeoxyglucose, expressed as estimated metabolic rate (eMR). Insulin signaling was investigated in muscle biopsies. Age difference between groups was 4.5 years, and no difference was observed in body composition. Training increased lean body mass (estimate [95% confidence interval] 0.5 [0.2-0.9] kg, P < 0.01) and thigh muscle mass (0.2 [-0.1 to 0.6] kg, P < 0.01), and decreased fat percentage (1.0 [0.5-1.5]%, P < 0.01) similarly in the two groups. The postmenopausal women had lower eMR in vastus lateralis muscle than the premenopausal women (-14.0 [-26.0 to -2.0] μmol/min/kg, P = 0.02), and tended to have lower eMR in femoral muscles (-11.2 [-22.7 to 0.4] μmol/min/kg, P = 0.06), and also GDR (-59.3 [-124.8 to 6.3] mg/min, P = 0.08), but increased similarly in both groups with training (eMR vastus lateralis muscle: 27.8 [19.6-36.0] μmol/min/kg, P < 0.01; eMR femoral muscle: 20.0 [13.1-26.7] μmol/min/kg, P < 0.01, respectively; GDR: 43.6 [10.4-76.9] mg/min, P = 0.01). Potential mechanisms underlying the training-induced increases in insulin sensitivity included increased expression of hexokinase (19.2 [5.0-24.7] AU, P = 0.02) and glycogen synthase (32.4 [15.0-49.8] AU, P < 0.01), and also increased insulin activation of Akt2 (20.6 [3.4-29.0], P = 0.03) and dephosphorylation of glycogen synthase (-41.8 [-82.9 to -0.7], P = 0.05). Insulin sensitivity was reduced in early postmenopausal women. However, postmenopausal women increased peripheral insulin sensitivity, skeletal muscle insulin-stimulated glucose uptake, and skeletal muscle mass to the same extent as premenopausal women after 3 months of high-intensity exercise training.

Effects and prevalence of nonresponders after 12 weeks of high-intensity interval or resistance training in women with insulin resistance: a randomized trial.

PubMed

Álvarez, Cristian; Ramírez-Campillo, Rodrigo; Ramírez-Vélez, Robinson; Izquierdo, Mikel

2017-04-01

Our aim was to investigate the effects and prevalence of nonresponders (NR) to high-intensity interval training (HIIT) and resistance training (RT) in women with insulin resistance on cardiometabolic health parameters. Sedentary overweight/obese insulin-resistant women (age = 33.5 ± 6.5 yr; body mass index = 29.9 ± 3.7 kg/m 2 ) were randomly assigned to a triweekly HIIT program (HIIT; n = 18) or resistance training (RT; n = 17). Anthropometry (body mass, fat mass, muscle mass, waist circumference, and skinfold thickness), cardiovascular (blood pressure), metabolic [fasting glucose, fasting insulin, and homeostatic model of insulin resistance (HOMA-IR)], as well as muscle strength, and endurance performance covariables were measured before and after 12 wk in both intervention groups. The interindividual variability to exercise training of the subjects was categorized as responders and NR using as cut points two times the typical error of measurement in mean outcomes. After intervention, significant reduction in waist circumference, skinfold thicknesses, fat mass, blood pressure, fasting glucose, insulin, and HOMA-IR ( P < 0.05) were identified to HIIT and RT group, respectively. Both HIIT and RT groups exhibited a significant decrease in the endurance performance, whereas only RT exhibited increased muscle strength. Significant differences in the NR prevalence between the HIIT and RT groups were identified for a decrease in fat mass (HIIT 33.3% vs. RT 70.5%; P = 0.028), muscle mass (HIIT 100% vs. RT 52.9%; P = 0.001), and tricipital skinfold (HIIT 5.5% vs. RT 29.4%; P < 0.041). For diastolic blood pressure, significant differences were observed in the NR prevalence between the HIIT and RT groups (55.5% vs. 94.1; P = 0.009). However, there were no differences in the NR prevalence between HIIT and RT for decreasing fasting glucose. Twelve weeks of HIIT and RT have similar effects and NR prevalence to improve glucose control variables; however, there is different NR prevalence in other anthropometric, cardiovascular, strength, and endurance performance measurements in insulin-resistant women. These findings were displayed with a similar time investment per week of 114 vs. 108 min, respectively, to HIIT and RT. NEW & NOTEWORTHY The effects and prevalence of nonresponders (NR) to improve glucose control variables have predominately been reported by endurance training. A uniqueness of the present study was to examine the NR prevalence in women with insulin resistance after high-intensity interval (HIIT) and resistance training (RT). This study demonstrates that 12 wk of HIIT and RT have similar effects and NR prevalence to improve glucose control variables. However, significantly different NR prevalence were observed in other anthropometric, cardiovascular, strength, and endurance performance measurements. Copyright © 2017 the American Physiological Society.

Prolonged sitting and markers of cardiometabolic disease risk in children and youth: a randomized crossover study.

PubMed

Saunders, Travis J; Chaput, Jean-Philippe; Goldfield, Gary S; Colley, Rachel C; Kenny, Glen P; Doucet, Eric; Tremblay, Mark S

2013-10-01

Recent evidence suggests that short bouts of uninterrupted sedentary behavior reduce insulin sensitivity and glucose tolerance while increasing triglyceride levels in both healthy and overweight/obese adults. To date no study has examined the acute impact of uninterrupted sitting in children and youth. The objective of the present study was to determine whether 8 h of uninterrupted sitting increases markers of cardiometabolic disease risk in healthy children and youth, in comparison to 8 h of sitting interrupted by light intensity walk breaks or structured physical activity. 11 healthy males and 8 healthy females between the ages of 10 and 14 years experienced 3 conditions in random order: (1) 8 h of uninterrupted sitting (Sedentary); (2) 8 h of sitting interrupted with a 2-min light-intensity walk break every 20 min (Breaks); and (3) 8 h of sitting interrupted with a 2-min light-intensity walk break every 20 min as well as 2×20 min of moderate-intensity physical activity (Breaks+Physical Activity). Insulin, glucose, triglyceride, HDL and LDL cholesterol area under the curve were calculated for each condition. We observed no significant differences in the area under the curve for any marker of cardiometabolic disease risk across the 3 study conditions (all p>0.09). These results suggest that in comparison to interrupted sitting or structured physical activity, a single bout of 8 h of uninterrupted sitting does not result in measurable changes in circulating levels of insulin, glucose, or lipids in healthy children and youth. Copyright © 2013 Elsevier Inc. All rights reserved.

Role of O-GlcNAcylation in nutritional sensing, insulin resistance and in mediating the benefits of exercise.

PubMed

Myslicki, Jason P; Belke, Darrell D; Shearer, Jane

2014-11-01

The purpose of this review is to highlight the role of O-linked β-N-acetylglucosamine (O-GlcNAc) protein modification in metabolic disease states and to summarize current knowledge of how exercise affects this important post-translational signalling pathway. O-GlcNAc modification is an intracellular tool capable of integrating energy supply with demand. The accumulation of excess energy associated with obesity and insulin resistance is mediated, in part, by the hexosamine biosynthetic pathway (HBP), which results in the O-GlcNAcylation of a myriad of proteins, thereby affecting their respective function, stability, and localization. Insulin resistance is related to the excessive O-GlcNAcylation of key metabolic proteins causing a chronic blunting of insulin signalling pathways and precipitating the accompanying pathologies, such as heart and kidney disease. Lifestyle modifications such as diet and exercise also modify the pathway. Exercise is a front-line and cost-effective therapeutic approach for insulin resistance, and recent work shows that the intervention can alter O-GlcNAc gene expression, signalling, and protein modification. However, there is currently no consensus on the effect of frequency, intensity, type, and duration of exercise on O-GlcNAc modification, the HBP, and its related enzymes. On one end of the spectrum, mild, prolonged swim training reduces O-GlcNAcylation, while on the other end, higher intensity treadmill running increases cardiac protein O-GlcNAc modification. Clearly, a balance between acute and chronic stress of exercise is needed to reap the benefits of the intervention on O-GlcNAc signalling.

The effects of high-intensity interval training on glucose regulation and insulin resistance: a meta-analysis.

PubMed

Jelleyman, C; Yates, T; O'Donovan, G; Gray, L J; King, J A; Khunti, K; Davies, M J

2015-11-01

The aim of this meta-analysis was to quantify the effects of high-intensity interval training (HIIT) on markers of glucose regulation and insulin resistance compared with control conditions (CON) or continuous training (CT). Databases were searched for HIIT interventions based upon the inclusion criteria: training ≥2 weeks, adult participants and outcome measurements that included insulin resistance, fasting glucose, HbA1c or fasting insulin. Dual interventions and participants with type 1 diabetes were excluded. Fifty studies were included. There was a reduction in insulin resistance following HIIT compared with both CON and CT (HIIT vs. CON: standardized mean difference [SMD] = -0.49, confidence intervals [CIs] -0.87 to -0.12, P = 0.009; CT: SMD = -0.35, -0.68 to -0.02, P = 0.036). Compared with CON, HbA1c decreased by 0.19% (-0.36 to -0.03, P = 0.021) and body weight decreased by 1.3 kg (-1.9 to -0.7, P < 0.001). There were no statistically significant differences between groups in other outcomes overall. However, participants at risk of or with type 2 diabetes experienced reductions in fasting glucose (-0.92 mmol L(-1), -1.22 to -0.62, P < 0.001) compared with CON. HIIT appears effective at improving metabolic health, particularly in those at risk of or with type 2 diabetes. Larger randomized controlled trials of longer duration than those included in this meta-analysis are required to confirm these results. © 2015 World Obesity.

Diabetes management: optimizing roles for nurses in insulin initiation

PubMed Central

Levich, Bridget R

2011-01-01

Type 2 diabetes is a major public health concern. Screening and early diagnosis followed by prompt and aggressive treatment interventions can help control progression of diabetes and its complications. Nurses are often the first healthcare team members to interact with patients and are being called on to apply their specialized knowledge, training, and skills to educate and motivate patients with diabetes about insulin use and practical ways to achieve treatment goals. Clinical nurse specialists possess specific training and skills to provide this level of care, while staff or office-based nurses may be trained by physicians to fulfill a task-specific role. This manuscript reviews the benefits of intensive glycemic control in type 2 diabetes, therapeutic goals and guidelines, advances in insulin therapy, and contribution of nurses in overcoming barriers to insulin initiation and related aspects of diabetes care. Nurses are particularly well positioned to fill the gap and improve efficiency in diabetes-related healthcare by assisting patients with insulin initiation and other aspects of glycemic self-management. PMID:21468244

[New insulin types in type 1 diabetes mellitus].

PubMed

Mesa, Jordi

2015-07-20

Since its discovery almost a century ago, insulin remains the mainstay of treatment of patients with type 1 diabetes mellitus. Although progress in the synthesis of new formulations has been remarkable, the physiological profile of insulin is still different from that observed with preparations available nowadays. In the last decade, the introduction into clinical practice of insulin analogues has allowed significantly improvement in glycemic control and has facilitated the spread of basal/bolus patterns, the most physiological ones until now. Despite the benefits of basal analogues, glycemia often varies considerably when used as a single daily injection and this is why new molecules have been further investigated. Improvement has been achieved especially in terms of duration and rate of hypoglycemia, the main limiting factor of intensive therapy. This article reviews the available data concerning the new basal insulin analogues, degludec, pegylated lispro and glargine U300, and new formulations currently under development. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Dynamic insulin sensitivity index: importance in diabetes.

PubMed

Pillonetto, Gianluigi; Caumo, Andrea; Cobelli, Claudio

2010-03-01

The classical minimal model (MM) index of insulin sensitivity, S(I), does not account for how fast or slow insulin action takes place. In a recent work, we proposed a new dynamic insulin sensitivity index, S(I)(D), which is able to take into account the dynamics of insulin action as well. The new index is a function of two MM parameters, namely S(I) and p(2), the latter parameter governing the speed of rise and decay of insulin action. We have previously shown that in normal glucose tolerant subjects S(I)(D) provides a more comprehensive picture of insulin action on glucose metabolism than S(I). The aim of this study is to show that resorting to S(I)(D) rather S(I) is even more appropriate when studying diabetic patients who have a low and slow insulin action. We analyzed insulin-modified intravenous glucose tolerance test studies performed in 10 diabetic subjects and mixed meal glucose tolerance test studies exploiting the triple tracer technique in 14 diabetic subjects. We derived both S(I) and S(I)(D) resorting to Bayesian and Fisherian identification strategies. The results show that S(I)(D) is estimated more precisely than S(I) when using the Bayesian approach. In addition, the less labor-intensive Fisherian approach can still be used to obtain reliable point estimates of S(I)(D) but not of S(I). These results suggest that S(I)(D) yields a comprehensive, precise, and cost-effective assessment of insulin sensitivity in subjects with impaired insulin action like impaired glucose tolerant subjects or diabetic patients.

A multiplet table for Mn I (Adelman, Svatek, Van Winkler, Warren 1989): Documentation for the machine-readable version

NASA Technical Reports Server (NTRS)

Warren, Wayne H., Jr.; Adelman, Saul J.

1989-01-01

The machine-readable version of the multiplet table, as it is currently being distributed from the Astronomical Data Center, is described. The computerized version of the table contains data on excitation potentials, J values, multiplet terms, intensities of the transitions, and multiplet numbers. Files ordered by multiplet and by wavelength are included in the distributed version.

A contrast enhancement method for improving the segmentation of breast lesions on ultrasonography.

PubMed

Flores, Wilfrido Gómez; Pereira, Wagner Coelho de Albuquerque

2017-01-01

This paper presents an adaptive contrast enhancement method based on sigmoidal mapping function (SACE) used for improving the computerized segmentation of breast lesions on ultrasound. First, from the original ultrasound image an intensity variation map is obtained, which is used to generate local sigmoidal mapping functions related to distinct contextual regions. Then, a bilinear interpolation scheme is used to transform every original pixel to a new gray level value. Also, four contrast enhancement techniques widely used in breast ultrasound enhancement are implemented: histogram equalization (HEQ), contrast limited adaptive histogram equalization (CLAHE), fuzzy enhancement (FEN), and sigmoid based enhancement (SEN). In addition, these contrast enhancement techniques are considered in a computerized lesion segmentation scheme based on watershed transformation. The performance comparison among techniques is assessed in terms of both the quality of contrast enhancement and the segmentation accuracy. The former is quantified by the measure, where the greater the value, the better the contrast enhancement, whereas the latter is calculated by the Jaccard index, which should tend towards unity to indicate adequate segmentation. The experiments consider a data set with 500 breast ultrasound images. The results show that SACE outperforms its counterparts, where the median values for the measure are: SACE: 139.4, SEN: 68.2, HEQ: 64.1, CLAHE: 62.8, and FEN: 7.9. Considering the segmentation performance results, the SACE method presents the largest accuracy, where the median values for the Jaccard index are: SACE: 0.81, FEN: 0.80, CLAHE: 0.79, HEQ: 77, and SEN: 0.63. The SACE method performs well due to the combination of three elements: (1) the intensity variation map reduces intensity variations that could distort the real response of the mapping function, (2) the sigmoidal mapping function enhances the gray level range where the transition between lesion and background is found, and (3) the adaptive enhancing scheme for coping with local contrasts. Hence, the SACE approach is appropriate for enhancing contrast before computerized lesion segmentation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Short-Term Treatment with Bisphenol-A Leads to Metabolic Abnormalities in Adult Male Mice

PubMed Central

Batista, Thiago M.; Alonso-Magdalena, Paloma; Vieira, Elaine; Amaral, Maria Esmeria C.; Cederroth, Christopher R.; Nef, Serge; Quesada, Ivan; Carneiro, Everardo M.; Nadal, Angel

2012-01-01

Bisphenol-A (BPA) is one of the most widespread endocrine disrupting chemicals (EDC) used as the base compound in the manufacture of polycarbonate plastics. Although evidence points to consider exposure to BPA as a risk factor for insulin resistance, its actions on whole body metabolism and on insulin-sensitive tissues are still unclear. The aim of the present work was to study the effects of low doses of BPA in insulin-sensitive peripheral tissues and whole body metabolism in adult mice. Adult mice were treated with subcutaneous injection of 100 µg/kg BPA or vehicle for 8 days. Whole body energy homeostasis was assessed with in vivo indirect calorimetry. Insulin signaling assays were conducted by western blot analysis. Mice treated with BPA were insulin resistant and had increased glucose-stimulated insulin release. BPA-treated mice had decreased food intake, lower body temperature and locomotor activity compared to control. In skeletal muscle, insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit was impaired in BPA-treated mice. This impairment was associated with a reduced insulin-stimulated Akt phosphorylation in the Thr308 residue. Both skeletal muscle and liver displayed an upregulation of IRS-1 protein by BPA. The mitogen-activated protein kinase (MAPK) signaling pathway was also impaired in the skeletal muscle from BPA-treated mice. In the liver, BPA effects were of lesser intensity with decreased insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit. In conclusion, short-term treatment with low doses of BPA slows down whole body energy metabolism and disrupts insulin signaling in peripheral tissues. Thus, our findings support the notion that BPA can be considered a risk factor for the development of type 2 diabetes. PMID:22470480

Insulin degludec/insulin aspart combination for the treatment of type 1 and type 2 diabetes

PubMed Central

Dardano, Angela; Bianchi, Cristina; Del Prato, Stefano; Miccoli, Roberto

2014-01-01

Glycemic control remains the major therapeutic objective to prevent or delay the onset and progression of complications related to diabetes mellitus. Insulin therapy represents a cornerstone in the treatment of diabetes and has been used widely for achieving glycemic goals. Nevertheless, a large portion of the population with diabetes does not meet the internationally agreed glycemic targets. Moreover, insulin treatment, especially if intensive, may be associated with emergency room visits and hospitalization due to hypoglycemic events. Therefore, fear of hypoglycemia or hypoglycemic events represents the main barriers to the attainment of glycemic targets. The burden associated with multiple daily injections also remains a significant obstacle to initiating and maintaining insulin therapy. The most attractive insulin treatment approach should meet the patients’ preference, rather than demanding patients to change or adapt their lifestyle. Insulin degludec/insulin aspart (IDegAsp) is a new combination, formulated with ultra-long-acting insulin degludec and rapid-acting insulin aspart, with peculiar pharmacological features, clinical efficacy, safety, and tolerability. IDegAsp provides similar, noninferior glycemic control to a standard basal–bolus regimen in patients with type 1 diabetes mellitus, with additional benefits of significantly lower episodes of hypoglycemia (particularly nocturnal) and fewer daily insulin injections. Moreover, although treatment strategy and patients’ viewpoint are different in type 1 and type 2 diabetes, trial results suggest that IDegAsp may be an appropriate and reasonable option for initiating insulin therapy in patients with type 2 diabetes inadequately controlled on maximal doses of conventional oral agents. This paper will discuss the role of IDegAsp combination as a novel treatment option in diabetic patients. PMID:25143741

An in silico method to identify computer-based protocols worthy of clinical study: An insulin infusion protocol use case

PubMed Central

Wong, Anthony F; Pielmeier, Ulrike; Haug, Peter J; Andreassen, Steen

2016-01-01

Objective Develop an efficient non-clinical method for identifying promising computer-based protocols for clinical study. An in silico comparison can provide information that informs the decision to proceed to a clinical trial. The authors compared two existing computer-based insulin infusion protocols: eProtocol-insulin from Utah, USA, and Glucosafe from Denmark. Materials and Methods The authors used eProtocol-insulin to manage intensive care unit (ICU) hyperglycemia with intravenous (IV) insulin from 2004 to 2010. Recommendations accepted by the bedside clinicians directly link the subsequent blood glucose values to eProtocol-insulin recommendations and provide a unique clinical database. The authors retrospectively compared in silico 18 984 eProtocol-insulin continuous IV insulin infusion rate recommendations from 408 ICU patients with those of Glucosafe, the candidate computer-based protocol. The subsequent blood glucose measurement value (low, on target, high) was used to identify if the insulin recommendation was too high, on target, or too low. Results Glucosafe consistently provided more favorable continuous IV insulin infusion rate recommendations than eProtocol-insulin for on target (64% of comparisons), low (80% of comparisons), or high (70% of comparisons) blood glucose. Aggregated eProtocol-insulin and Glucosafe continuous IV insulin infusion rates were clinically similar though statistically significantly different (Wilcoxon signed rank test P = .01). In contrast, when stratified by low, on target, or high subsequent blood glucose measurement, insulin infusion rates from eProtocol-insulin and Glucosafe were statistically significantly different (Wilcoxon signed rank test, P < .001), and clinically different. Discussion This in silico comparison appears to be an efficient nonclinical method for identifying promising computer-based protocols. Conclusion Preclinical in silico comparison analytical framework allows rapid and inexpensive identification of computer-based protocol care strategies that justify expensive and burdensome clinical trials. PMID:26228765

Examining mealtime behaviors in families of young children with type 1 diabetes on intensive insulin therapy.

PubMed

Patton, Susana R; Dolan, Lawrence M; Smith, Laura B; Brown, Morton B; Powers, Scott W

2013-12-01

This study examined mealtime behaviors in families of young children with type 1 diabetes (T1DM) on intensive insulin therapy. Behaviors were compared to published data for children on conventional therapy and examined for correlations with glycemic control. Thirty-nine families participated and had at least three home meals videotaped while children wore a continuous glucose monitor. Videotaped meals were coded for parent, child, and child eating behaviors using a valid coding system. A group difference was found for child request for food only. There were also associations found between children's glycemic control and child play and away. However, no associations were found between parent and child behaviors within meals and children's corresponding post-prandial glycemic control. Results reinforce existing research indicating that mealtime behavior problems exist for families of young children even in the context of intensive therapy and that some child behaviors may relate to glycemic control. © 2013.

Pancreas Islet Transplantation for Patients With Type 1 Diabetes Mellitus: A Clinical Evidence Review.

PubMed

2015-01-01

Type 1 diabetes mellitus is caused by the autoimmune destruction of pancreatic beta (β) cells, resulting in severe insulin deficiency. Islet transplantation is a β-cell replacement therapeutic option that aims to restore glycemic control in patients with type 1 diabetes. The objective of this study was to determine the clinical effectiveness of islet transplantation in patients with type 1 diabetes, with or without kidney disease. We conducted a systematic review of the literature on islet transplantation for type 1 diabetes, including relevant health technology assessments, systematic reviews, meta-analyses, and observational studies. We used a two-step process: first, we searched for systematic reviews and health technology assessments; second, we searched primary studies to update the chosen health technology assessment. The Assessment of Multiple Systematic Reviews measurement tool was used to examine the methodological quality of the systematic reviews and health technology assessments. We assessed the quality of the body of evidence and the risk of bias according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. Our searched yielded 1,354 citations. One health technology assessment, 11 additional observational studies to update the health technology assessment, one registry report, and four guidelines were included; the observational studies examined islet transplantation alone, islet-after-kidney transplantation, and simultaneous islet-kidney transplantation. In general, low to very low quality of evidence exists for islet transplantation in patients with type 1 diabetes with difficult-to-control blood glucose levels, with or without kidney disease, for these outcomes: health-related quality of life, secondary complications of diabetes, glycemic control, and adverse events. However, high quality of evidence exists for the specific glycemic control outcome of insulin independence compared with intensive insulin therapy. For patients without kidney disease, islet transplantation improves glycemic control and diabetic complications for patients with type 1 diabetes when compared with intensive insulin therapy. However, results for health-related quality of life outcomes were mixed, and adverse events were increased compared with intensive insulin therapy. For patients with type 1 diabetes with kidney disease, islet-after-kidney transplantation or simultaneous islet-kidney transplantation also improved glycemic control and secondary diabetic complications, although the evidence was more limited for this patient group. Compared with intensive insulin therapy, adverse events for islet-after-kidney transplantation or simultaneous islet-kidney transplantation were increased, but were in general less severe than with whole pancreas transplantation. For patients with type 1 diabetes with difficult-to-control blood glucose levels, islet transplantation may be a beneficial β-cell replacement therapy to improve glycemic control and secondary complications of diabetes. However, there is uncertainty in the estimates of effectiveness because of the generally low to very low quality of evidence for all outcomes of interest.

International Congress for the Assessment of Stress Intensity and Stress Compatibility in Large Groups. Held in Bad Radkersburg, Austria on November 25-27, 1999

DTIC Science & Technology

1999-11-01

comparison between their products , whereby increased stress upon the diagnostical value of magnesium dynamics could be helpful. Such an agreement would...as sudden cardiac death when magnesium (Mg) deficiency exists. The stress hormones mediate release and utilization of substrates for production of...would be increased [28]. Since insulin sensitivity relates to mi- crovascular function, the presence of insulin resistance during space flights

Validation of insulin sensitivity and secretion indices derived from the liquid meal tolerance test.

PubMed

Maki, Kevin C; Kelley, Kathleen M; Lawless, Andrea L; Hubacher, Rachel L; Schild, Arianne L; Dicklin, Mary R; Rains, Tia M

2011-06-01

A liquid meal tolerance test (LMTT) has been proposed as a useful alternative to more labor-intensive methods of assessing insulin sensitivity and secretion. This substudy, conducted at the conclusion of a randomized, double-blind crossover trial, compared insulin sensitivity indices from a LMTT (Matsuda insulin sensitivity index [MISI] and LMTT disposition index [LMTT-DI]) with indices derived from minimal model analysis of results from the insulin-modified intravenous glucose tolerance test (IVGTT) (insulin sensitivity index [S(I)] and disposition index [DI]). Participants included men (n = 16) and women (n = 8) without diabetes but with increased abdominal adiposity (waist circumference ≥102 cm and ≥89 cm, respectively) and mean age of 48.9 years. The correlation between S(I) and the MISI was 0.776 (P < 0.0001). The respective associations between S(I) and MISI with waist circumference (r = -0.445 and -0.554, both P < 0.05) and body mass index were similar (r = -0.500 and -0.539, P < 0.05). The correlation between DI and LMTT-DI was 0.604 (P = 0.002). These results indicate that indices of insulin sensitivity and secretion derived from the LMTT correlate well with those from the insulin-modified IVGTT with minimal model analysis, suggesting that they may be useful for application in clinical and population studies of glucose homeostasis.

Degradation rate of lyophilized insulin, exhibiting an apparent Arrhenius behavior around glass transition temperature regardless of significant contribution of molecular mobility.

PubMed

Yoshioka, Sumie; Miyazaki, Tamaki; Aso, Yukio

2006-12-01

The relative influences of chemical activation energy and molecular mobility in determining chemical reactivity were evaluated for insulin lyophilized with alpha,beta-poly(N-hydroxyethyl)-L-aspartamide (PHEA), and compared with that for insulin lyophilized with trehalose, which had been found to have the ability to decrease the molecular mobility of insulin at low humidity. The ratio of the observed rate constant k(obs) to the chemical activation energy-controlled rate constant k(act) (k(obs)/k(act)) at glass transition temperature (T(g)) was estimated to be approximately 0.6 and 0.8 at 6% RH and 12% RH, respectively, indicating that the degradation rate is significantly affected by molecular mobility at lower humidity conditions. However, these k(obs)/k(act) values at T(g) were larger than those for the insulin-trehalose system, and changes in the temperature-dependent slope around T(g) were less obvious than those for the insulin-trehalose system. Thus, the contribution of molecular mobility to the degradation rate in the insulin-PHEA system appeared to be less intense than that in the insulin-trehalose system. The subtle change in the temperature-dependent slope around T(g) observed in the insulin-PHEA system brought about a significant bias in shelf-life estimation when the reaction rate was extrapolated from temperatures above T(g) according to the Arrhenius equation. (c) 2006 Wiley-Liss, Inc. and the American Pharmacists Association

Effect of strong electric field on the conformational integrity of insulin.

PubMed

Wang, Xianwei; Li, Yongxiu; He, Xiao; Chen, Shude; Zhang, John Z H

2014-10-02

A series of molecular dynamics (MD) simulations up to 1 μs for bovine insulin monomer in different external electric fields were carried out to study the effect of external electric field on conformational integrity of insulin. Our results show that the secondary structure of insulin is kept intact under the external electric field strength below 0.15 V/nm, but disruption of secondary structure is observed at 0.25 V/nm or higher electric field strength. Although the starting time of secondary structure disruption of insulin is not clearly correlated with the strength of the external electric field ranging between 0.15 and 0.60 V/nm, long time MD simulations demonstrate that the cumulative effect of exposure time under the electric field is a major cause for the damage of insulin's secondary structure. In addition, the strength of the external electric field has a significant impact on the lifetime of hydrogen bonds when it is higher than 0.60 V/nm. The fast evolution of some hydrogen bonds of bovine insulin in the presence of the 1.0 V/nm electric field shows that different microwaves could either speed up protein folding or destroy the secondary structure of globular proteins deponding on the intensity of the external electric field.

Relationships of the systolic blood pressure response during exercise with insulin resistance, obesity, and endurance fitness in men with type 2 diabetes mellitus.

PubMed

Kumagai, S; Kai, Y; Hanada, H; Uezono, K; Sasaki, H

2002-10-01

The purpose of the present study was to investigate the relationships among the resting systolic (SBP) and diastolic blood pressure (DBP) or SBP response during exercise with insulin resistance evaluated by a homeostasis model (HOMA-IR), abdominal fat accumulation (visceral fat area [VFA], subcutaneous fat area [SFA]) by computed tomography (CT), and an estimation of the maximal oxygen uptake (V*O2max) in 63 Japanese middle-aged male patients with type 2 diabetes mellitus (type 2 DM). Body mass index (BMI) and waist-to-hip ratio (WHR) in type 2 DM subjects were significantly higher than in age-matched healthy male control subjects (n = 135) with normal glucose tolerance. Resting SBP (127.7 +/- 16.2 mm Hg v 119.4 +/- 13.0 mm Hg) and DBP (82.2 +/- 11.9mmHg v 76.8 +/- 9.4 mm Hg) levels, and the percentage of hypertension (20.6% v 1.5%) in type 2 DM subjects were significantly higher than in the control subjects (P <.05). According to a multiple regression analysis for resting blood pressure in type 2 DM, VFA was found to be an independent predictor of SBP, while V*O2max and HOMA-IR were independent predictors of DBP. In the controls, however, HOMA-IR was not found to be a significantly independent predictor for either resting SBP or resting DBP. Measurement of the SBP response during graded exercise using a ramp test was performed by an electrical braked cycle ergometer in 54 patients with type 2 DM only. The SBP was measured at 15-second intervals during exercise. The exercise intensity at the double product breaking point (DPBP), which strongly correlated with the exercise intensity at the lactate threshold, was used as an index for the SBP response to standardized exercise intensity. The SBP corresponding to exercise intensity at DPBP (SBP@DPBP) was evaluated as an index of the SBP response to standardized exercise intensity. The change in SBP (deltaSBP = SBP@DPBP - resting SBP) was significantly and positively associated with log area under the curve for glucose (log AUCPG) during a 75-g oral glucose tolerance test (OGTT). In addition, deltaSBP significantly and negatively correlated with the log area under the curve for insulin (log AUCIRI) and log AUCIRI/log AUCPG. Based on these results, insulin resistance was suggested to be independently associated with the resting DBP and SBP response to standardized exercise intensity in type 2 DM patients. Copyright 2002, Elsevier Science (USA). All rights reserved.

Simulation and qualitative analysis of glucose variability, mean glucose, and hypoglycemia after subcutaneous insulin therapy for stress hyperglycemia.

PubMed

Strilka, Richard J; Stull, Mamie C; Clemens, Michael S; McCaver, Stewart C; Armen, Scott B

2016-01-27

The critically ill can have persistent dysglycemia during the "subacute" recovery phase of their illness because of altered gene expression; it is also not uncommon for these patients to receive continuous enteral nutrition during this time. The optimal short-acting subcutaneous insulin therapy that should be used in this clinical scenario, however, is unknown. Our aim was to conduct a qualitative numerical study of the glucose-insulin dynamics within this patient population to answer the above question. This analysis may help clinicians design a relevant clinical trial. Eight virtual patients with stress hyperglycemia were simulated by means of a mathematical model. Each virtual patient had a different combination of insulin resistance and insulin deficiency that defined their unique stress hyperglycemia state; the rate of gluconeogenesis was also doubled. The patients received 25 injections of subcutaneous regular or Lispro insulin (0-6 U) with 3 rates of continuous nutrition. The main outcome measurements were the change in mean glucose concentration, the change in glucose variability, and hypoglycemic episodes. These end points were interpreted by how the ultradian oscillations of glucose concentration were affected by each insulin preparation. Subcutaneous regular insulin lowered both mean glucose concentrations and glucose variability in a linear fashion. No hypoglycemic episodes were noted. Although subcutaneous Lispro insulin lowered mean glucose concentrations, glucose variability increased in a nonlinear fashion. In patients with high insulin resistance and nutrition at goal, "rebound hyperglycemia" was noted after the insulin analog was rapidly metabolized. When the nutritional source was removed, hypoglycemia tended to occur at higher Lispro insulin doses. Finally, patients with severe insulin resistance seemed the most sensitive to insulin concentration changes. Subcutaneous regular insulin consistently lowered mean glucose concentrations and glucose variability; its linear dose-response curve rendered the preparation better suited for a sliding-scale protocol. The longer duration of action of subcutaneous regular insulin resulted in better glycemic-control metrics for patients who were continuously postprandial. Clinical trials are needed to examine whether these numerical results represent the glucose-insulin dynamics that occur in intensive care units; if present, their clinical effects should be evaluated.

Comparing errors in ED computer-assisted vs conventional pediatric drug dosing and administration.

PubMed

Yamamoto, Loren; Kanemori, Joan

2010-06-01

Compared to fixed-dose single-vial drug administration in adults, pediatric drug dosing and administration requires a series of calculations, all of which are potentially error prone. The purpose of this study is to compare error rates and task completion times for common pediatric medication scenarios using computer program assistance vs conventional methods. Two versions of a 4-part paper-based test were developed. Each part consisted of a set of medication administration and/or dosing tasks. Emergency department and pediatric intensive care unit nurse volunteers completed these tasks using both methods (sequence assigned to start with a conventional or a computer-assisted approach). Completion times, errors, and the reason for the error were recorded. Thirty-eight nurses completed the study. Summing the completion of all 4 parts, the mean conventional total time was 1243 seconds vs the mean computer program total time of 879 seconds (P < .001). The conventional manual method had a mean of 1.8 errors vs the computer program with a mean of 0.7 errors (P < .001). Of the 97 total errors, 36 were due to misreading the drug concentration on the label, 34 were due to calculation errors, and 8 were due to misplaced decimals. Of the 36 label interpretation errors, 18 (50%) occurred with digoxin or insulin. Computerized assistance reduced errors and the time required for drug administration calculations. A pattern of errors emerged, noting that reading/interpreting certain drug labels were more error prone. Optimizing the layout of drug labels could reduce the error rate for error-prone labels. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Changes in metformin use and other antihyperglycemic therapies after insulin initiation in patients with type 2 diabetes.

PubMed

Pilla, Scott J; Dotimas, James R; Maruthur, Nisa M; Clark, Jeanne M; Yeh, Hsin-Chieh

2018-05-01

When patients with type 2 diabetes initiate insulin, metformin should be continued while continuation of other antihyperglycemics has unclear benefit. We aimed to identify practice patterns in antihyperglycemic therapy during the insulin transition, and determine factors associated with metformin continuation. We performed a retrospective analysis of the Look AHEAD (Action for Health in Diabetes) trial which randomized overweight/obese adults under ambulatory care for type 2 diabetes to an intensive lifestyle intervention or diabetes support and education. Among the 931 participants who initiated insulin over ten years, we described longitudinal changes in antihyperglycemic medications during the insulin transition, and performed multivariable logistic regression to estimate the association between patient characteristics and metformin continuation. Before insulin initiation, 81.0% of patients used multiple antihyperglycemics, the most common being metformin, sulfonylureas, and thiazolidinediones. After insulin initiation, metformin was continued in 80.3% of patients; other antihyperglycemics were continued less often, yet 58.0% of patients were treated with multiple non-insulin antihyperglycemics. Metformin continuation was inversely associated with age (fully adjusted (a) OR 0.60 per 10 years [0.42-0.86]), serum creatinine above safety thresholds (aOR 0.09 [0.02-0.36]), lower income (P = 0.025 for trend), taking more medications (aOR 0.92 per medication [0.86-0.98]), and initiating rapid, short, or premixed insulin (aOR 0.59 [0.39-0.89]). The vast majority of patients with type 2 diabetes continue metformin after insulin initiation, consistent with guidelines. Other antihyperglycemics are frequently continued along with insulin, and further research is needed to determine which, if any, patients may benefit from this. Copyright © 2018 Elsevier B.V. All rights reserved.

Is the current standard of care leading to cost-effective outcomes for patients with type 2 diabetes requiring insulin? A long-term health economic analysis for the UK.

PubMed

Valentine, W J; Curtis, B H; Pollock, R F; Van Brunt, K; Paczkowski, R; Brändle, M; Boye, K S; Kendall, D M

2015-07-01

The aim of the analysis was to investigate whether insulin intensification, based on the use of intensive insulin regimens as recommended by the current standard of care in routine clinical practice, would be cost-effective for patients with type 2 diabetes in the UK. Clinical data were derived from a retrospective analysis of 3185 patients with type 2 diabetes on basal insulin in The Health Improvement Network (THIN) general practice database. In total, 48% (614 patients) intensified insulin therapy, defined by adding bolus or premix insulin to a basal regimen, which was associated with a reduction in HbA1c and an increase in body mass index. Projections of clinical outcomes and costs (2011 GBP) over patients' lifetimes were made using a recently validated type 2 diabetes model. Immediate insulin intensification was associated with improvements in life expectancy, quality-adjusted life expectancy and time to onset of complications versus no intensification or delaying intensification by 2, 4, 6, or 8 years. Direct costs were higher with the insulin intensification strategy (due to the acquisition costs of insulin). Incremental cost-effectiveness ratios for insulin intensification were GBP 32,560, GBP 35,187, GBP 40,006, GBP 48,187 and GBP 55,431 per QALY gained versus delaying intensification 2, 4, 6 and 8 years, and no intensification, respectively. Although associated with improved clinical outcomes, insulin intensification as practiced in the UK has a relatively high cost per QALY and may not lead to cost-effective outcomes for patients with type 2 diabetes as currently defined by UK cost-effectiveness thresholds. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effects of glargine insulin on glycemic control in patients with diabetes mellitus type II undergoing off-pump coronary artery bypass graft.

PubMed

Gandhi, Hemang; Sarvaia, Alpesh; Malhotra, Amber; Acharya, Himanshu; Shah, Komal; Rajavat, Jeevraj

2018-01-01

The prevalence of diabetes mellitus in patients requiring coronary artery bypass grafting (CABG) is noticeably high (20%-30%). These patients have inferior perioperative outcome, reduced long-term survival, and high risk of recurrent episodes of angina. To improve perioperative outcome surgical unit defined satisfactory glycemic control is desired during this period. Hence, the aim of our study is to compare the efficacy of glargine insulin combination with continuous human insulin infusion for perioperative glycemic control in patients with diabetes undergoing CABG. Fifty Patients, who were posted for off-pump CABG with diabetes mellitus type II, were randomized in two group, Group I normal saline + human insulin infusion during the perioperative period, Group II (glargine group): Glargine + human insulin infusion during perioperative period. During surgery and in the postoperative period, random blood sugar and human insulin requirement are significantly higher in control group than glargine group. Other infection, step-up antibiotics, intensive care unit (ICU) stay, and hospital stay were significantly higher in control groups in postoperative period. Our study results suggest that glargine effectively manages blood glucose level with significantly greater control over postoperative morbidity.

Differential Impact of Acute High-Intensity Exercise on Circulating Endothelial Microparticles and Insulin Resistance between Overweight/Obese Males and Females

PubMed Central

Durrer, Cody; Robinson, Emily; Wan, Zhongxiao; Martinez, Nic; Hummel, Michelle L.; Jenkins, Nathan T.; Kilpatrick, Marcus W.; Little, Jonathan P.

2015-01-01

Background An acute bout of exercise can improve endothelial function and insulin sensitivity when measured on the day following exercise. Our aim was to compare acute high-intensity continuous exercise (HICE) to high-intensity interval exercise (HIIE) on circulating endothelial microparticles (EMPs) and insulin sensitivity in overweight/obese men and women. Methods Inactive males (BMI = 30 ± 3, 25 ± 6 yr, n = 6) and females (BMI = 28 ± 2, 21 ± 3 yr, n = 7) participated in three experimental trials in a randomized counterbalanced crossover design: 1) No exercise control (Control); 2) HICE (20 min cycling @ just above ventilatory threshold); 3) HIIE (10 X 1-min @ ∼90% peak aerobic power). Exercise conditions were matched for external work and diet was controlled post-exercise. Fasting blood samples were obtained ∼18 hr after each condition. CD62E+ and CD31+/CD42b- EMPs were assessed by flow cytometry and insulin resistance (IR) was estimated by homeostasis model assessment (HOMA-IR). Results There was a significant sex X exercise interaction for CD62E+ EMPs, CD31+/CD42b- EMPs, and HOMA-IR (all P<0.05). In males, both HICE and HIIE reduced EMPs compared to Control (P≤0.05). In females, HICE increased CD62E+ EMPs (P<0.05 vs. Control) whereas CD31+/CD42b- EMPs were unaltered by either exercise type. There was a significant increase in HOMA-IR in males but a decrease in females following HIIE compared to Control (P<0.05). Conclusions Overweight/obese males and females appear to respond differently to acute bouts of high-intensity exercise. A single session of HICE and HIIE reduced circulating EMPs measured on the morning following exercise in males but in females CD62E+ EMPs were increased following HICE. Next day HOMA-IR paradoxically increased in males but was reduced in females following HIIE. Future research is needed to investigate mechanisms responsible for potential differential responses between males and females. PMID:25710559

A pilot crossover study: effects of an intervention using an activity monitor with computerized game functions on physical activity and body composition.

PubMed

Nishiwaki, Masato; Kuriyama, Akinori; Ikegami, Yumi; Nakashima, Nana; Matsumoto, Naoyuki

2014-12-02

Wearing an activity monitor as a motivational tool and incorporating a behavior-based reward system or a computerized game element might have a synergistic effect on an increase in daily physical activity, thereby inducing body fat reduction. This pilot crossover study aimed to examine the effects of a short-term lifestyle intervention using an activity monitor with computerized game functions on physical activity and body composition. Twenty healthy volunteers (31 ± 3 years) participated in a 12-week crossover study. The participants were randomly assigned to either Group A (a 6-week game intervention followed by a 6-week normal intervention) or Group B (a 6-week normal intervention followed by a 6-week game intervention). The participants wore both a normal activity monitor (Lifecorder EX) and an activity monitor with computerized game functions (Yuuhokei) during the game intervention, whereas they only wore a normal activity monitor during the normal intervention. Before, during, and after the intervention, body composition was assessed. Significantly more daily steps were recorded for the game intervention than for the normal intervention (10,520 ± 562 versus 8,711 ± 523 steps/day, P < 0.01). The participants performed significantly more physical activity at an intensity of ≥ 3 metabolic equivalents (METs) in the game intervention than in the normal intervention (3.1 ± 0.2 versus 2.4 ± 0.2 METs · hour/day, P < 0.01). Although body mass and fat were significantly reduced in both periods (P < 0.01), the difference in body fat reduction was significantly greater in the game intervention than in the normal intervention (P < 0.05). A short-term intervention using an activity monitor with computerized game functions increases physical activity and reduces body fat more effectively than an intervention using a standard activity monitor.

Technologic advances in aural rehabilitation: applications and innovative methods of service delivery.

PubMed

Sweetow, Robert W; Sabes, Jennifer Henderson

2007-06-01

The level of interest in aural rehabilitation has increased recently, both in clinical use and in research presentations and publications. Advances in aural rehabilitation have seen previous techniques such as speech tracking and analytic auditory training reappear in computerized forms. These new delivery methods allow for a consistent, cost-effective, and convenient training program. Several computerized aural rehabilitation programs for hearing aid wearers and cochlear implant recipients have recently been developed and were reported on at the 2006 State of the Science Conference of the Rehabilitation Engineering Research Center on Hearing Enhancement at Gallaudet University. This article reviews these programs and outlines the similarities and differences in their design. Another promising area of aural rehabilitation research is the use of pharmaceuticals in the rehabilitation process. The results from a study of the effect of d-amphetamine in conjunction with intensive aural rehabilitation with cochlear implant patients are also described.

Technologic Advances in Aural Rehabilitation: Applications and Innovative Methods of Service Delivery

PubMed Central

Sweetow, Robert W.; Sabes, Jennifer Henderson

2007-01-01

The level of interest in aural rehabilitation has increased recently, both in clinical use and in research presentations and publications. Advances in aural rehabilitation have seen previous techniques such as speech tracking and analytic auditory training reappear in computerized forms. These new delivery methods allow for a consistent, cost-effective, and convenient training program. Several computerized aural rehabilitation programs for hearing aid wearers and cochlear implant recipients have recently been developed and were reported on at the 2006 State of the Science Conference of the Rehabilitation Engineering Research Center on Hearing Enhancement at Gallaudet University. This article reviews these programs and outlines the similarities and differences in their design. Another promising area of aural rehabilitation research is the use of pharmaceuticals in the rehabilitation process. The results from a study of the effect of d-amphetamine in conjunction with intensive aural rehabilitation with cochlear implant patients are also described. PMID:17494876

Factors Associated with Nocturnal Hypoglycemia in At-Risk Adolescents and Young Adults with Type 1 Diabetes

PubMed Central

Wilson, Darrell M.; Calhoun, Peter M.; Maahs, David M.; Chase, H. Peter; Messer, Laurel; Buckingham, Bruce A.; Aye, Tandy; Clinton, Paula K.; Hramiak, Irene; Kollman, Craig

2015-01-01

Abstract Background: Hypoglycemia remains an impediment to good glycemic control, with nocturnal hypoglycemia being particularly dangerous. Information on major contributors to nocturnal hypoglycemia remains critical for understanding and mitigating risk. Materials and Methods: Continuous glucose monitoring (CGM) data for 855 nights were studied, generated by 45 subjects 15–45 years of age with hemoglobin A1c (HbA1c) levels of ≤8.0% who participated in a larger randomized study. Factors assessed for potential association with nocturnal hypoglycemia (CGM measurement of <60 mg/dL for ≥30 min) included bedtime blood glucose (BG), exercise intensity, bedtime snack, insulin on board, day of the week, previous daytime hypoglycemia, age, gender, HbA1c level, diabetes duration, daily basal insulin, and daily insulin dose. Results: Hypoglycemia occurred during 221 of 885 (25%) nights and was more frequent with younger age (P<0.001), lower HbA1c levels (P=0.006), medium/high-intensity exercise during the preceding day (P=0.003), and the occurrence of antecedent daytime hypoglycemia (P=0.001). There was a trend for lower bedtime BG levels to be associated with more frequent nocturnal hypoglycemia (P=0.10). Bedtime snack, before bedtime insulin bolus, weekend versus weekday, gender, and daily basal and bolus insulin were not associated with nocturnal hypoglycemia. Conclusions: Awareness that HbA1c level, exercise, bedtime BG level, and daytime hypoglycemia are all modifiable factors associated with nocturnal hypoglycemia may help patients and providers decrease the risk of hypoglycemia at night. Risk for nocturnal hypoglycemia increased in a linear fashion across the range of variables, with no clear-cut thresholds to guide clinicians or patients for any particular night. PMID:25761202

Intensive postoperative glucose control reduces the surgical site infection rates in gynecologic oncology patients.

PubMed

Al-Niaimi, Ahmed N; Ahmed, Mostafa; Burish, Nikki; Chackmakchy, Saygin A; Seo, Songwon; Rose, Stephen; Hartenbach, Ellen; Kushner, David M; Safdar, Nasia; Rice, Laurel; Connor, Joseph

2015-01-01

SSI rates after gynecologic oncology surgery vary from 5% to 35%, but are up to 45% in patients with diabetes mellitus (DM). Strict postoperative glucose control by insulin infusion has been shown to lower morbidity, but not specifically SSI rates. Our project studied continuous postoperative insulin infusion for 24h for gynecologic oncology patients with DM and hyperglycemia with a target blood glucose of <139 mL/dL and a primary outcome of the protocol's impact on SSI rates. We compared SSI rates retrospectively among three groups. Group 1 was composed of patients with DM whose blood glucose was controlled with intermittent subcutaneous insulin injections. Group 2 was composed of patients with DM and postoperative hyperglycemia whose blood glucose was controlled by insulin infusion. Group 3 was composed of patients with neither DM nor hyperglycemia. We controlled for all relevant factors associated with SSI. We studied a total of 372 patients. Patients in Group 2 had an SSI rate of 26/135 (19%), similar to patients in Group 3 whose rate was 19/89 (21%). Both were significantly lower than the SSI rate (43/148, 29%) of patients in Group 1. This reduction of 35% is significant (p = 0.02). Multivariate analysis showed an odd ratio = 0.5 (0.28-0.91) in reducing SSI rates after instituting this protocol. Initiating intensive glycemic control for 24h after gynecologic oncology surgery in patients with DM and postoperative hyperglycemia lowers the SSI rate by 35% (OR = 0.5) compared to patients receiving intermittent sliding scale insulin and to a rate equivalent to non-diabetics. Copyright © 2014. Published by Elsevier Inc.

Targeted Adherence Intervention to Reach Glycemic Control with Insulin Therapy for patients with Diabetes (TARGIT-Diabetes): rationale and design of a pragmatic randomised clinical trial

PubMed Central

Lewey, Jennifer; Wei, Wenhui; Makanji, Sagar; Chant, Alan; DiGeronimo, Jeff; Nanchanatt, Gina; Jan, Saira; Choudhry, Niteesh K

2017-01-01

Introduction Adherence to and persistence of medications for chronic diseases remains poor and many interventions to improve medication use have only been modestly effective. Targeting interventions to patients who are most likely to benefit should improve their efficiency and clinical impact. This study aims to test the impact of three cost-equivalent pharmacist-led interventions on insulin persistence and glycaemic control among patients with diabetes. Methods and analysis TARGIT-Diabetes (Targeted Adherence Intervention to Reach Glycemic Control with Insulin Therapy for patients with Diabetes) is a randomised controlled trial that will evaluate three different multifaceted pharmacist-outreach strategies for improving long-term insulin use among individuals with diabetes. We will randomise 6000 patients in a large insurer to one of three arms. The arms are designed to deliver an increasingly intensive intervention to a progressively targeted population, identified using predictive analytics. The central component of the intervention in all arms is a tailored telephone consultation with a pharmacist which varies across arms based on the: (A) proportion of patients offered the intervention and (B) intervention intensity, including follow-up frequency and cointerventions such as text reminders and interactions with patients’ providers. The primary outcome is insulin persistence, assessed using pharmacy claims data, and the secondary outcomes are glycaemic control as measured by glycosylated haemoglobin values, healthcare utilisation and healthcare spending. Ethics and dissemination This protocol has been approved by the Institutional Review Board of Brigham and Women’s Hospital and the Privacy Board of Horizon Blue Cross Blue Shield of New Jersey. We plan to present the results of this trial at national meetings and in manuscripts submitted to peer-reviewed journals. Trial registration number NCT 02846779. PMID:29084790

Factors associated with nocturnal hypoglycemia in at-risk adolescents and young adults with type 1 diabetes.

PubMed

Wilson, Darrell M; Calhoun, Peter M; Maahs, David M; Chase, H Peter; Messer, Laurel; Buckingham, Bruce A; Aye, Tandy; Clinton, Paula K; Hramiak, Irene; Kollman, Craig; Beck, Roy W

2015-06-01

Hypoglycemia remains an impediment to good glycemic control, with nocturnal hypoglycemia being particularly dangerous. Information on major contributors to nocturnal hypoglycemia remains critical for understanding and mitigating risk. Continuous glucose monitoring (CGM) data for 855 nights were studied, generated by 45 subjects 15-45 years of age with hemoglobin A1c (HbA1c) levels of ≤8.0% who participated in a larger randomized study. Factors assessed for potential association with nocturnal hypoglycemia (CGM measurement of <60 mg/dL for ≥30 min) included bedtime blood glucose (BG), exercise intensity, bedtime snack, insulin on board, day of the week, previous daytime hypoglycemia, age, gender, HbA1c level, diabetes duration, daily basal insulin, and daily insulin dose. Hypoglycemia occurred during 221 of 885 (25%) nights and was more frequent with younger age (P<0.001), lower HbA1c levels (P=0.006), medium/high-intensity exercise during the preceding day (P=0.003), and the occurrence of antecedent daytime hypoglycemia (P=0.001). There was a trend for lower bedtime BG levels to be associated with more frequent nocturnal hypoglycemia (P=0.10). Bedtime snack, before bedtime insulin bolus, weekend versus weekday, gender, and daily basal and bolus insulin were not associated with nocturnal hypoglycemia. Awareness that HbA1c level, exercise, bedtime BG level, and daytime hypoglycemia are all modifiable factors associated with nocturnal hypoglycemia may help patients and providers decrease the risk of hypoglycemia at night. Risk for nocturnal hypoglycemia increased in a linear fashion across the range of variables, with no clear-cut thresholds to guide clinicians or patients for any particular night.

[The optimal blood glucose target in critically ill patient: comparison of two intensive insulin therapy protocols].

PubMed

Raurell Torredà, Marta; del Llano Serrano, César; Almirall Solsona, Dolors; Catalan Ibars, Rosa María; Nicolás Arfelis, José María

2014-03-04

Recent studies in critically ill patients receiving insulin intravenous therapy (IIT) have shown an increased incidence of severe hypoglycemia, while intermittent subcutaneous insulin «sliding scales» (conventional insulin therapy [CIT]) is associated with hyperglycemia. The objective of this study is to assess whether glycemic control range IIT can affect glucose levels and their variability and to compare it with CIT. Prospective comparative cohort study in intensive care unit, with 2 study periods: Period 1, IIT with glycemic target range 110-140 mg/dL, and Period 2, IIT of 140-180 mg/dL. In both periods CIT glycemic target was 110-180 mg/dL. We assessed severe hypoglycemia (< 50 mg/dL), moderate hypoglycemia (51-79 mg/dL), hyperglycemia (> 216 mg/L) and the variability of blood glucose. We studied 221 patients with 12.825 blood glucose determinations. Twenty-six and 17% of patients required IIT for glycemic control in Period 1 and 2, respectively. Hypoglycemia was associated with a discontinuous nutritional intake, glycemic target 110-140 mg/dL and low body mass index (BMI) (P = .002). Hyperglycemia was exclusively associated with a history of diabetes mellitus (OR 2.6 [95% CI 1.6 to 4.5]). Glycemic variability was associated with a discontinuous nutritional intake, low BMI, CIT insulinization, diabetes mellitus, elderly and high APACHE II (P < .001). The use of IIT is useful to reduce the variability of blood glucose. Although the 140-180 mg/dL range would be more secure as to presenting greater variability and hyperglycemia, the 110-140 mg/dL range is most suitable. Copyright © 2012 Elsevier España, S.L. All rights reserved.

The effects of short-term continuous subcutaneous insulin infusion treatment on fasting glucagon-like peptide-1 concentrations in newly diagnosed type 2 diabetes.

PubMed

Huang, Xiaofei; Li, Sha; Yang, Mei; Fu, Xuquan; Li, Huaqi; Yan, Tong; Liu, Yidong; Chen, Lihong; Lan, Lingsheng; Li, Libo; Zhong, Xiaowei

2018-04-01

Early short-term intensive insulin therapy in newly diagnosed type 2 diabetes patients shows benefit in glycemic control and β-cell function. Glucagon-like peptide-1 (GLP-1) plays an important role in glucose metabolism and development of type 2 diabetes. We did a study to observe the changes of GLP-1 and β-cell function after short-term continuous subcutaneous insulin infusion (CSII) treatment. A total of 66 subjects were enrolled, including 30 normal glucose tolerance controls (NGT) and 36 patients with newly diagnosed type 2 diabetes between October 2015 and July 2016. Fasting plasma glucose (FPG), insulin, and GLP-1 were measured in each subject. The patients underwent CSII treatment for 2 weeks, and then FBG, insulin, and GLP-1 were measured. HOMA-IR and HOMA-B were then calculated. All patients achieved target glycemic control in two weeks. HOMA-IR and HOMA-B improved significantly after intensive interventions (p < 0.05). The GLP-1 concentration increased significantly in patients after treatment (p < 0.05). When grouped according to bodyweight and age in all patients, the HOMA-IR changed significantly in overweight and old age subgroups, the HOMA-B increased significantly in normal weight, overweight and middle age subgroups, and the GLP-1 concentration also increased significantly in overweight and middle age subgroups respectively (p < 0.05). Short-term CSII treatment can obtain glycemic control target and recover β-cell function and GLP-1 secretion in newly diagnosed type 2 diabetes patients. The overweight and middle-aged patients may get more benefit from this treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Impact of computerized information systems on workload in operating room and intensive care unit.

PubMed

Bosman, R J

2009-03-01

The number of operating rooms and intensive care departments equipped with a clinical information system (CIS) is rapidly expanding. Amongst the putative advantages of such an installation, reduction in workload for the clinician is one of the most appealing. The scarce studies looking at workload variations associated with the implementation of a CIS, only focus on direct workload discarding indirect changes in workload. Descriptions of the various methods to quantify workload are provided. The hypothesis that a third generation CIS can reduce documentation time for ICU nurses and increase time they spend on patient care, is supported by recent literature. Though it seems obvious to extrapolate these advantages of a CIS to the anesthesiology department or physicians in the intensive care, studies examining this assumption are scarce.

Age influence on attitudes of office workers faced with new computerized technologies: a questionnaire analysis.

PubMed

Marquié, J C; Thon, B; Baracat, B

1994-06-01

The study of Bue and Gollac (1988) provided evidence that a significantly lower proportion of workers aged 45 years and over make use of computer technology compared with younger ones. The aim of the present survey was to explain this fact by a more intensive analysis of the older workers' attitude with respect to the computerization of work situations in relation to other individual and organizational factors. Six hundred and twenty office workers from 18 to 70 years old, either users or non-users of computerized devices, were asked to complete a questionnaire. The questions allowed the assessment of various aspects of the workers' current situation, such as the computer training they had received, the degree of consultation they were subjected to during the computerization process, their representation of the effects of these new technologies on working conditions and employment, the rate of use of new technologies outside the work context, and the perceived usefulness of computers for their own work. The analysis of the questionnaire revealed that as long as the step towards using computer tools, even minimally, has not been taken, then attitudes with respect to computerization are on the whole not very positive and are a source of anxiety for many workers. Age, and even more, seniority in the department, increase such negative representations. The effects of age and seniority were also found among users, as well as the effects of other factors such as qualification, education level, type and rate of computer use, and size of the firm. For the older workers, the expectation of less positive consequences for their career, or even the fear that computerization might be accompanied by threats to their own employment and the less clear knowledge of how computers operate, appeared to account for a significant part of the observed age and seniority differences in attitudes. Although the difference in the amount of computer training between age groups was smaller than expected, the study revealed that one third of the users never received any specific training, and that many of those who benefited from it were trained for only a few days. Consultation of the staff during the computerization process also appeared to be poor, to apply mostly to the best trained and qualified workers, and to be more highly developed in small companies. The results are discussed in the light of more qualitative data recorded during the survey. They suggest the need to increase information, training and involvement of all personnel from the very first stages of computerization (or other technical changes) in order to lessen fears and the feeling of disruption, which are particularly obvious among the oldest workers.

Effects of insulin under normal and low glucose on retinal electrophysiology in the perfused cat eye.

PubMed

Lansel, N; Niemeyer, G

1997-04-01

To investigate the short-term effects of fast-acting insulin on the electroretinogram-b-wave, optic nerve response, standing potential, and flow rate in the arterially perfused cat eye under normal conditions and during low glucose levels. Enucleated cat eyes were perfused with a glucose- and insulin-free tissue culture medium, to which glucose was applied at normal (5.5 mM) and reduced (2 and 1 mM) concentrations. Photic stimulation was performed in the rod-matched intensity range before, during, and after insulin application at postprandial (5 ng/ml) and at 10 and 20 x higher concentrations. Insulin failed to affect retinal signals at normal glucose levels. However, insulin enhanced the low glucose-induced decrease in rod-driven b-wave amplitude (P < 0.05 at 2 mM; P < 0.01 at 1 mM) without affecting the corresponding changes in the optic nerve response. The standing potential increased by as much as 0.75 mV in response to insulin. The perfusate flow rate was not altered by insulin. Insulin was not required for normal retinal function as observed during 10 hours of perfusion. The differential responsiveness to insulin under low glucose of the b-wave versus the optic nerve response is thought to reflect suppression of glucose use by Müller (glial) cells rather than neuromodulation, as the neuronal optic nerve response is unaffected. The postulated insulin sensitivity of Müller cells (changes in b-wave amplitude) indicates a possible difference in the mechanism of glucose metabolism of glia versus neurons. The electrophysiological effect of insulin under low glucose suggests its passage across the blood-retina barrier. The increase in the standing potential is likely to be a receptor-mediated retinal pigment epithelium effect. These results provide evidence in the retina for the reported multifunctional nature of the insulin receptor.

A multifaceted program for improving quality of care in intensive care units: IATROREF study.

PubMed

Garrouste-Orgeas, Maite; Soufir, Lilia; Tabah, Alexis; Schwebel, Carole; Vesin, Aurelien; Adrie, Christophe; Thuong, Marie; Timsit, Jean Francois

2012-02-01

To test the effects of three multifaceted safety programs designed to decrease insulin administration errors, anticoagulant prescription and administration errors, and errors leading to accidental removal of endotracheal tubes and central venous catheters, respectively. Medical errors and adverse events are associated with increased mortality in intensive care patients, indicating an urgent need for prevention programs. Multicenter cluster-randomized study. One medical intensive care unit in a university hospital and two medical-surgical intensive care units in community hospitals belonging to the Outcomerea Study Group. Consecutive patients >18 yrs admitted from January 2007 to January 2008 to the intensive care units. We tested three multifaceted safety programs vs. standard care in random order, each over 2.5 months, after a 1.5-month observation period. Incidence rates of medical errors/1000 patient-days in the multifaceted safety program and standard-care groups were compared using adjusted hierarchical models. In 2117 patients with 15,014 patient-days, 8520 medical errors (567.5/1000 patient-days) were reported, including 1438 adverse events (16.9%, 95.8/1000 patient-days). The insulin multifaceted safety program significantly decreased errors during implementation (risk ratio 0.65; 95% confidence interval [CI] 0.52-0.82; p = .0003) and after implementation (risk ratio 0.51; 95% CI 0.35-0.73; p = .0004). A significant Hawthorne effect was found. The accidental tube/catheter removal multifaceted safety program decreased errors significantly during implementation (odds ratio [OR] 0.34; 95% CI 0.15-0.81; p = .01]) and nonsignificantly after implementation (OR 1.65; 95% CI 0.78-3.48). The anticoagulation multifaceted safety program was not significantly effective (OR 0.64; 95% CI 0.26-1.59) but produced a significant Hawthorne effect. A multifaceted program was effective in preventing insulin errors and accidental tube/catheter removal. Significant Hawthorne effects occurred, emphasizing the need for appropriately designed studies before definitively implementing strategies. clinicaltrials.gov Identifier: NCT00461461.

Effects of food texture change on metabolic parameters: short- and long-term feeding patterns and body weight.

PubMed

Labouré, H; Saux, S; Nicolaidis, S

2001-03-01

A complete diet was prepared with cooked pieces of meat, beans, cream starch, and water and presented to the rats in two different textures: a blended purée and a rough mixture that required a lot of chewing. We hypothesized that this texture modification might change both anticipatory reflexes and feeding behavior. Feeding rate, meal size, intermeal intervals, and their correlation were monitored in response to each texture. The long-term (6 wk) effect on body weight was assessed. Periprandial plasma glucose, insulin, glucagon, and lipid concentrations were assayed. Whole and background metabolism, respiratory quotient, and locomotion were measured using a computerized calorimeter of original design. In the short term, rats preferred the mixture. However, after 3 wk, they ingested more purée than mixture and gained more body weight per gram of food ingested as purée. Insulin response declined earlier with the mixture. During meals, glycerol and free fatty acid increased earlier with purée, whereas in the postprandial period, glycerol increased earlier with mixture. The metabolic rate, however, was not significantly affected. We concluded that texture, an everyday manipulation performed on food for human consumption, affects not only palatability of ingestants but also their metabolic management in the short and long term.

Major depressive disorder and type II diabetes mellitus: mechanisms underlying risk for Alzheimer's disease.

PubMed

Cha, Danielle S; Carvalho, Andre F; Rosenblat, Joshua D; Ali, Muna M; McIntyre, Roger S

2014-01-01

Objectives/Introduction: Major Depressive Disorder is associated age-related medical conditions (e.g., diabetes mellitus type II, Alzheimer's disease) that frequently manifest at an earlier age, contributing to excess and premature mortality. The foregoing observation provides the impetus to further refine potential mechanisms and molecular pathways subserving these disorders in order to more effectively treat these clinical populations by aiming to reduce and prevent cognitive impairment as well as downstream neurodegeneration. A review of computerized databases was performed to identify original studies that investigated the impact of the independent and comorbid association of major depressive disorder and type II diabetes mellitus on cognitive function and conversion to Alzheimer's disease. English-written articles were selected for review based on the adequacy of sample size, the use of standardized diagnostic instruments, and validated assessment measures. Individuals with persistent neuropsychiatric illness account for a disproportionate overall burden of disability mediated largely by decrements in cognitive performance. Mixed results from epidemiological and clinical studies suggest that insulin may mediate and/or moderate risk for cognitive dysfunction in subsets of individuals. Moreover, physiological changes, such as insulin resistance and the activation of neuroimmunoinflammatory systems result in glial and neuroendangerment. Disturbances in the metabolic milieu exert a neurotoxic effect on the central nervous system and poses a hazard to other organ systems.

Computerized Cognitive Training with Older Adults: A Systematic Review

PubMed Central

Kueider, Alexandra M.; Parisi, Jeanine M.; Gross, Alden L.; Rebok, George W.

2012-01-01

A systematic review to examine the efficacy of computer-based cognitive interventions for cognitively healthy older adults was conducted. Studies were included if they met the following criteria: average sample age of at least 55 years at time of training; participants did not have Alzheimer’s disease or mild cognitive impairment; and the study measured cognitive outcomes as a result of training. Theoretical articles, review articles, and book chapters that did not include original data were excluded. We identified 151 studies published between 1984 and 2011, of which 38 met inclusion criteria and were further classified into three groups by the type of computerized program used: classic cognitive training tasks, neuropsychological software, and video games. Reported pre-post training effect sizes for intervention groups ranged from 0.06 to 6.32 for classic cognitive training interventions, 0.19 to 7.14 for neuropsychological software interventions, and 0.09 to 1.70 for video game interventions. Most studies reported older adults did not need to be technologically savvy in order to successfully complete or benefit from training. Overall, findings are comparable or better than those from reviews of more traditional, paper-and-pencil cognitive training approaches suggesting that computerized training is an effective, less labor intensive alternative. PMID:22792378

Association of Adverse Pregnancy Outcomes With Glyburide vs Insulin in Women With Gestational Diabetes.

PubMed

Camelo Castillo, Wendy; Boggess, Kim; Stürmer, Til; Brookhart, M Alan; Benjamin, Daniel K; Jonsson Funk, Michele

2015-05-01

Glyburide is thought to be safe for use during pregnancy for treatment of gestational diabetes mellitus (GDM). However, there are limited data on the effectiveness of glyburide when compared with insulin as used in a real-world setting. To estimate the risk of adverse maternal and neonatal outcomes in women with GDM treated with glyburide compared with insulin. Retrospective cohort study of a population-based cohort from a nationwide US employer-based insurance claims database from January 1, 2000, to December 31, 2011. We identified women with GDM and their newborns. We excluded those with type 1 or 2 diabetes and those younger than 15 years or older than 45 years. Treatment with glyburide or insulin during pregnancy within 150 days before delivery. We used binomial regression to estimate risk ratios (RRs) and risk differences with 95% confidence intervals for the association of glyburide with diagnosis codes for obstetric trauma, cesarean delivery, birth injury, preterm birth, hypoglycemia, respiratory distress, jaundice, large for gestational age, and hospitalization in the neonatal intensive care unit. Inverse probability of treatment weights were used to adjust for maternal characteristics that differed between the treatment groups. Among 110,879 women with GDM, 9173 women (8.3%) were treated with glyburide (n = 4982) or insulin (n = 4191). After adjusting for differences at baseline, newborns of women treated with glyburide were at increased risk for neonatal intensive care unit admission (RR = 1.41; 95% CI, 1.23-1.62), respiratory distress (RR = 1.63; 95% CI, 1.23-2.15), hypoglycemia (RR = 1.40; 95% CI, 1.00-1.95), birth injury (RR = 1.35; 95% CI, 1.00-1.82), and large for gestational age (RR = 1.43; 95% CI, 1.16-1.76) compared with those treated with insulin; they were not at increased risk for obstetric trauma (RR = 0.92; 95% CI, 0.71-1.20), preterm birth (RR = 1.06; 95% CI, 0.93-1.21), or jaundice (RR = 0.96; 95% CI, 0.48-1.91). The risk of cesarean delivery was 3% lower in the glyburide group (adjusted RR = 0.97; 95% CI, 0.93-1.00). The risk difference associated with glyburide was 2.97% (95% CI, 1.82-4.12) for neonatal intensive care unit admission, 1.41% (95% CI, 0.61-2.20) for large for gestational age, and 1.11% (95% CI, 0.50-1.72) for respiratory distress. Newborns from privately insured mothers treated with glyburide were more likely to experience adverse outcomes than those from mothers treated with insulin. Given the widespread use of glyburide, further investigation of these differences in pregnancy outcomes is a public health priority.

Methods for quantifying adipose tissue insulin resistance in overweight/obese humans.

PubMed

Ter Horst, K W; van Galen, K A; Gilijamse, P W; Hartstra, A V; de Groot, P F; van der Valk, F M; Ackermans, M T; Nieuwdorp, M; Romijn, J A; Serlie, M J

2017-08-01

Insulin resistance of adipose tissue is an important feature of obesity-related metabolic disease. However, assessment of lipolysis in humans requires labor-intensive and expensive methods, and there is limited validation of simplified measurement methods. We aimed to validate simplified methods for the quantification of adipose tissue insulin resistance against the assessment of insulin sensitivity of lipolysis suppression during hyperinsulinemic-euglycemic clamp studies. We assessed the insulin-mediated suppression of lipolysis by tracer-dilution of [1,1,2,3,3- 2 H 5 ]glycerol during hyperinsulinemic-euglycemic clamp studies in 125 overweight or obese adults (85 men, 40 women; age 50±11 years; body mass index 38±7 kg m -2 ). Seven indices of adipose tissue insulin resistance were validated against the reference measurement method. Low-dose insulin infusion resulted in suppression of the glycerol rate of appearance ranging from 4% (most resistant) to 85% (most sensitive), indicating a good range of adipose tissue insulin sensitivity in the study population. The reference method correlated with (1) insulin-mediated suppression of plasma glycerol concentrations (r=0.960, P<0.001), (2) suppression of plasma non-esterified fatty acid (NEFA) concentrations (r=0.899, P<0.001), (3) the Adipose tissue Insulin Resistance (Adipo-IR) index (fasting plasma insulin-NEFA product; r=-0.526, P<0.001), (4) the fasting plasma insulin-glycerol product (r=-0.467, P<0.001), (5) the Adipose Tissue Insulin Resistance Index (fasting plasma insulin-basal lipolysis product; r=0.460, P<0.001), (6) the Quantitative Insulin Sensitivity Check Index (QUICKI)-NEFA index (r=0.621, P<0.001), and (7) the QUICKI-glycerol index (r=0.671, P<0.001). Bland-Altman plots showed no systematic errors for the suppression indices but proportional errors for all fasting indices. Receiver-operator characteristic curves confirmed that all indices were able to detect adipose tissue insulin resistance (area under the curve ⩾0.801, P<0.001). Adipose tissue insulin sensitivity (that is, the antilipolytic action of insulin) can be reliably quantified in overweight and obese humans by simplified index methods. The sensitivity and specificity of the Adipo-IR index and the fasting plasma insulin-glycerol product, combined with their simplicity and acceptable agreement, suggest that these may be most useful in clinical practice.

Insulin and glucose responses during bed rest with isotonic and isometric exercise

NASA Technical Reports Server (NTRS)

Dolkas, C. B.; Greenleaf, J. E.

1977-01-01

The effects of daily intensive isotonic (68% maximum oxygen uptake) and isometric (21% maximum extension force) leg exercise on plasma insulin and glucose responses to an oral glucose tolerance test (OGTT) during 14-day bed-rest (BR) periods were investigated in seven young healthy men. The OGTT was given during ambulatory control and on day 10 of the no-exercise, isotonic, and isometric exercise BR periods during the 15-wk study. The subjects were placed on a controlled diet starting 10 days before each BR period. During BR, basal plasma glucose concentration remained unchanged with no exercise, but increased (P less 0.05) to 87-89 mg/100 ml with both exercise regimens on day 2, and then fell slightly below control levels on day 13. The fall in glucose content during BR was independent of the exercise regimen and was an adjustment for the loss of plasma volume. The intensity of the responses of insulin and glucose to the OGTT was inversely proportional to the total daily energy expenditure during BR. It was estimated that at least 1020 kcal/day must be provided by supplemental exercise to restore the hyperinsulinemia to control levels.

Prevalence of Non-responders for Glucose Control Markers after 10 Weeks of High-Intensity Interval Training in Adult Women with Higher and Lower Insulin Resistance.

PubMed

Álvarez, Cristian; Ramírez-Campillo, Rodrigo; Ramírez-Vélez, Robinson; Izquierdo, Mikel

2017-01-01

Background: Exercise training improves performance and biochemical parameters on average, but wide interindividual variability exists, with individuals classified as responders (R) or non-responders (NRs), especially between populations with higher or lower levels of insulin resistance. This study assessed the effects of high-intensity interval training (HIIT) and the prevalence of NRs in adult women with higher and lower levels of insulin resistance. Methods: Forty adult women were assigned to a HIIT program, and after training were analyzed in two groups; a group with higher insulin resistance (H-IR, 40 ± 6 years; BMI: 29.5 ± 3.7 kg/m 2 ; n = 20) and a group with lower insulin resistance (L-IR, 35 ± 9 years; 27.8 ± 2.8 kg/m 2 ; n = 20). Anthropometric, cardiovascular, metabolic, and performance variables were measured at baseline and after 10 weeks of training. Results: There were significant training-induced changes [delta percent (Δ%)] in fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) scores in the H-IR group (-8.8, -26.5, -32.1%, p < 0.0001), whereas no significant changes were observed in the L-IR. Both groups showed significant pre-post changes in other anthropometric variables [waist circumference (-5.2, p < 0.010, and -3.8%, p = 0.046) and tricipital (-13.3, p < 0.010, and -13.6%, p < 0.0001), supra-iliac (-19.4, p < 0.0001, and -13.6%, p < 0.0001), and abdominal (-18.2, p < 0.0001, and -15.6%, p < 0.010) skinfold measurements]. Systolic blood pressure decreased significantly only in the L-IR group (-3.2%, p < 0.010). Both groups showed significant increases in 1RM LE (+12.9, p < 0.010, and +14.7%, p = 0.045). There were significant differences in the prevalence of NRs between the H-IR and L-IR groups for fasting glucose (25 vs. 95%, p < 0.0001) and fasting insulin ( p = 0.025) but not for HOMA-IR (25 vs. 45%, p = 0.185). Conclusion: Independent of the "magnitude" of the cardiometabolic disease (i.e., higher vs. lower insulin resistance), no differences were observed in the NRs prevalence with regard to improved HOMA-IR or to anthropometric, cardiovascular, and muscle performance co-variables after 10 weeks of HIIT in sedentary adult women. This research demonstrates the protective effect of HIIT against cardiometabolic disease progression in a sedentary population.

Prevalence of Non-responders for Glucose Control Markers after 10 Weeks of High-Intensity Interval Training in Adult Women with Higher and Lower Insulin Resistance

PubMed Central

Álvarez, Cristian; Ramírez-Campillo, Rodrigo; Ramírez-Vélez, Robinson; Izquierdo, Mikel

2017-01-01

Background: Exercise training improves performance and biochemical parameters on average, but wide interindividual variability exists, with individuals classified as responders (R) or non-responders (NRs), especially between populations with higher or lower levels of insulin resistance. This study assessed the effects of high-intensity interval training (HIIT) and the prevalence of NRs in adult women with higher and lower levels of insulin resistance. Methods: Forty adult women were assigned to a HIIT program, and after training were analyzed in two groups; a group with higher insulin resistance (H-IR, 40 ± 6 years; BMI: 29.5 ± 3.7 kg/m2; n = 20) and a group with lower insulin resistance (L-IR, 35 ± 9 years; 27.8 ± 2.8 kg/m2; n = 20). Anthropometric, cardiovascular, metabolic, and performance variables were measured at baseline and after 10 weeks of training. Results: There were significant training-induced changes [delta percent (Δ%)] in fasting glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) scores in the H-IR group (−8.8, −26.5, −32.1%, p < 0.0001), whereas no significant changes were observed in the L-IR. Both groups showed significant pre-post changes in other anthropometric variables [waist circumference (−5.2, p < 0.010, and −3.8%, p = 0.046) and tricipital (−13.3, p < 0.010, and −13.6%, p < 0.0001), supra-iliac (−19.4, p < 0.0001, and −13.6%, p < 0.0001), and abdominal (−18.2, p < 0.0001, and −15.6%, p < 0.010) skinfold measurements]. Systolic blood pressure decreased significantly only in the L-IR group (−3.2%, p < 0.010). Both groups showed significant increases in 1RMLE (+12.9, p < 0.010, and +14.7%, p = 0.045). There were significant differences in the prevalence of NRs between the H-IR and L-IR groups for fasting glucose (25 vs. 95%, p < 0.0001) and fasting insulin (p = 0.025) but not for HOMA-IR (25 vs. 45%, p = 0.185). Conclusion: Independent of the “magnitude” of the cardiometabolic disease (i.e., higher vs. lower insulin resistance), no differences were observed in the NRs prevalence with regard to improved HOMA-IR or to anthropometric, cardiovascular, and muscle performance co-variables after 10 weeks of HIIT in sedentary adult women. This research demonstrates the protective effect of HIIT against cardiometabolic disease progression in a sedentary population. PMID:28729841

Changes in the heart rate recovery to endurance effort after high intensity interval, strength, and concurrent exercise training in patients with insulin resistance.

PubMed

Álvarez, Cristian; Ramírez-Campillo, Rodrigo; Martínez, Cristian; Castro-Sepúlveda, Mauricio; Cano-Montoya, Johnathan; Mancilla, Rodrigo; Flores-Opazo, Marcelo

2017-11-01

The aim of this study was to assess the effects of three exercise training programs in the adaptation of the heart rate recovery of patients with insulin resistance. We studied 43 women with insulin resistance, which were assigned to three training groups: 1) high intensity interval training (HIT, age 39.0±10 years); 2) strength training (ST, age 33.9±9.4 years); 3) HIT+ST (MIXT, age 43.3±8.1 years); and 4) control group (CG, age 40.1±11 years). Heart rate was measured at rest (HRrest), during the 2-km-walking-test (UKKT) for mean (HRDE), and maximum (HRMDE) values, and during the recovery at one, two, and three minutes after the UKKT. Additionally, anthropometric measurements (body mass and body mass index) were assessed. HIT significantly decreased HRrest and HRDE (-4.5% and -2% respectively, P<0.05). MIXT training also decreased HRDE in -3% whilst both average and maximal HR during UKK were significantly increased in the control group HRDE (+2% and +3% respectively). Moreover, there were significant reductions in HR recovery at 1, 2 and 3 minutes after both HIT and MIXT training, whereas these values were increased in control group. Our findings suggest that HIT induces meaningful cardiovascular adaptations in patient with insulin resistance, reducing heart rate at rest, as well as during and after exercise, and that complementary strength training increases these adaptations.

Safety and metabolic impact of Ramadan fasting in children and adolescents with type 1 diabetes.

PubMed

El-Hawary, Amany; Salem, Nanees; Elsharkawy, Ashraf; Metwali, Abdelhameed; Wafa, Alaa; Chalaby, Nehad; El-Gilany, Abelhady; Abo-Elmagd, Megahed; El-Ziny, Magdy

2016-05-01

Annually, many children and adolescents with type 1 diabetes mellitus (T1DM) insist on fasting for Ramadan despite being exempted and despite knowing all the risks. We aimed to assess the safety and metabolic impact of Ramadan fasting in children with T1DM using different insulin regimens. Children with T1DM who choose to fast during Ramadan 1434/2013 (29 days) were recruited 3 months before Ramadan. They received pre-Ramadan intensive education. Three insulin regimens were included; Regimen-I (regular insulin/NPH); Regimen-II (regular insulin/insulin glargine) and Regimen-III (premixed insulin). Changes in weight, insulin dose, HbA1c, fructosamine and lipid profile were evaluated. Out of total 53 patients (24 male), 28 patients (52.8%) completed Ramadan fasting (fasting group). The remaining 25 patients were included in (broke-fasting group). Positive correlation between fructosamine changes and number of days fasted during Ramadan. Significant decrease in post-Ramadan fructosamine (<0.001) and increase in post-Ramadan total cholesterol and low density lipoprotein (LDL) levels were detected within fasting, broke-fasting and insulin regimen groups. Significant higher blood glucose at three time points, pre-Iftar, pre-Sohur and midday in Regimen-I compared to Regimen-II and Regimen-III (p=0.004). Fasting during Ramadan is feasible and is associated with significant improvement in fructosamine level in children with T1DM using different insulin regimens. Mandatory consideration to the quality and quantity of food offered to patients with T1DM during Ramadan to guard against adverse changes in lipid profile.

Statin Intake Is Associated With Decreased Insulin Sensitivity During Cardiac Surgery

PubMed Central

Sato, Hiroaki; Carvalho, George; Sato, Tamaki; Hatzakorzian, Roupen; Lattermann, Ralph; Codere-Maruyama, Takumi; Matsukawa, Takashi; Schricker, Thomas

2012-01-01

OBJECTIVE Surgical trauma impairs intraoperative insulin sensitivity and is associated with postoperative adverse events. Recently, preprocedural statin therapy is recommended for patients with coronary artery disease. However, statin therapy is reported to increase insulin resistance and the risk of new-onset diabetes. Thus, we investigated the association between preoperative statin therapy and intraoperative insulin sensitivity in nondiabetic, dyslipidemic patients undergoing coronary artery bypass grafting. RESEARCH DESIGN AND METHODS In this prospective, nonrandomized trial, patients taking lipophilic statins were assigned to the statin group and hypercholesterolemic patients not receiving any statins were allocated to the control group. Insulin sensitivity was assessed by the hyperinsulinemic-normoglycemic clamp technique during surgery. The mean, SD of blood glucose, and the coefficient of variation (CV) after surgery were calculated for each patient. The association between statin use and intraoperative insulin sensitivity was tested by multiple regression analysis. RESULTS We studied 120 patients. In both groups, insulin sensitivity gradually decreased during surgery with values being on average ∼20% lower in the statin than in the control group. In the statin group, the mean blood glucose in the intensive care unit was higher than in the control group (153 ± 20 vs. 140 ± 20 mg/dL; P < 0.001). The oscillation of blood glucose was larger in the statin group (SD, P < 0.001; CV, P = 0.001). Multiple regression analysis showed that statin use was independently associated with intraoperative insulin sensitivity (β = −0.16; P = 0.03). CONCLUSIONS Preoperative use of lipophilic statins is associated with increased insulin resistance during cardiac surgery in nondiabetic, dyslipidemic patients. PMID:22829524

Characteristics of hand tremor and postural sway in patients with fetal-type Minamata disease.

PubMed

Iwata, Toyoto; Takaoka, Shigeru; Sakamoto, Mineshi; Maeda, Eri; Nakamura, Masaaki; Liu, Xiao-Jie; Murata, Katsuyuki

2016-01-01

About forty certified patients aged around 50 years old existed as living witnesses to fetal-type Minamata disease (methylmercury poisoning due to in utero exposure) in Minamata, Japan in 2006. Computerized hand tremor and postural sway tests with spectral analysis were conducted for 24 of them and in matched control subjects to examine the pathophysiological feature of neuromotor function. The tremor intensities of the patients with fetal-type Minamata disease were significantly larger than those of the 67 controls at every frequency band for both hands. In the patients, proportions for intensity at 1-6 Hz of both hands were larger, but those of the intensity at 6-10 Hz were smaller compared with the controls. The center frequency of a tremor was significantly lower in the patients than in the controls. Only eight males of the 24 patients were examined to evaluate postural sway because of extremely low scores in activities of daily living in the remaining. Most of the postural sway parameters obtained with eyes open and closed were significantly larger in the patients than in the male controls. Likewise, Romberg quotients of postural sway in anterior-posterior direction were significantly higher in the patients. In conclusion, the patients with fetal-type Minamata disease of our study showed a larger tremor of low frequency at less than 6 Hz and postural instability. Spectral analyses of computerized hand tremor and postural sway are suggested to be useful for assessing the pathophysiological change, related to a lesion of the cerebellum, resulting from prenatal methylmercury exposure.

[A contribution safety on using low molecular weight heparin in patients with renal failure].

PubMed

Gea Rodríguez, E; Barral Viñals, N; Manso Mardones, P; Indo Berges, O

2004-01-01

1. To promote safe and appropriate use of low molecular weight heparins in patients with renal failure. 2. To analyze results from a pharmaceutical intervention program. Data from a prospective, 16-month study are presented. The entire adult population of a general hospital with 41,792 stays/year is included. An intensive monitoring program for low molecular weight heparin prescriptions in patients with renal failure is implemented. This program identifies patients using a computerized unit dose system, and is aided by a software able to calculate creatinine clearance using the Cockroft-Gault formula from an interphase between laboratory, pharmacy and admissions data, and by an algorithm to establish a recommended pharmaceutical intervention according to renal failure severity and low molecular weight heparin indication, either with prophylactic or therapeutic purposes. In all, 221 patients were identified, corresponding to 2.9% of admitted patients and 25.5% of patients with renal failure. Answers were assessable for 128 patients (61%). Extent of program acceptance according to physician-accepted pharmaceutical interventions was proportional to renal failure severity and therapy intensiveness. An acceptance of 70% was obtained for treatments with clearance < 30 mL/min, of 41.8% for treatments with 30-60 mL/min, of 31.5% for prophylaxis, and of 21.4% for low-risk patients. 1. Program repercussions improve prescription safety. 2. Scarce literature and a belief in low molecular weight heparin safety account for responses regarding pharmaceutical intervention. 3. Integrated computerized systems are essential for the implementation of intensive pharmaceutical care programs.

Photoelectrochemical sensitive detection of insulin based on CdS/polydopamine co-sensitized WO3 nanorod and signal amplification of carbon nanotubes@polydopamine.

PubMed

Wang, Rongyu; Ma, Hongmin; Zhang, Yong; Wang, Qi; Yang, Zhongping; Du, Bin; Wu, Dan; Wei, Qin

2017-10-15

An ultrasensitive photoelectrochemical sandwich immunosensor was designed for detection of insulin based on WO 3 /CdS/polydopamine (WO 3 /CdS/PDA) co-sensitized and PDA@carbon nanotubes (PDA@CNT) conjugates for signal amplification. The CdS nanoparticles were first deposited on the WO 3 nanorods via sequential chemical bath deposition to form the WO 3 /CdS structure to enhance photocurrent. Then equipped with PDA to form the WO 3 /CdS/PDA photosensitive structure. The PDA was used not only to reduce the toxicity of CdS but also adsorb insulin primary antibodies (Ab 1 ). Meanwhile, insulin secondary antibodies (Ab 2 ) were decorated by PDA@CNT conjugates for signal amplification and further enhance photocurrent. Different photocurrent intensities were obtained by the photoelectrochemical workstation at applied bias of 0V due to the different amount of the PDA@CNT conjugates introduced by the different concentrations of insulin. A good linear relationship was obtained between the increased photocurrent and insulin concentrations range from 0.01ngmL -1 to 50ngmL -1 . And a detection limit of 2.8pgmL -1 was obtained. The proposed sensor was applied to the determination of the insulin in human serum sample, and satisfactory results were obtained. The sensor presented good specificity, reproducibility and stability, thus it might find application in the clinical diagnosis of insulin or other biomarkers in the near future. Copyright © 2017 Elsevier B.V. All rights reserved.

High-Intensity Interval vs. Continuous Endurance Training: Preventive Effects on Hormonal Changes and Physiological Adaptations in Prediabetes Patients.

PubMed

Safarimosavi, Saleh; Mohebbi, Hamid; Rohani, Hadi

2018-06-22

Safarimosavi, S, Mohebbi, H, and Rohani, H. High-intensity interval vs. continuous endurance training: Preventive effects on hormonal changes and physiological adaptations in prediabetes patients. J Strength Cond Res XX(X): 000-000, 2018-The aim of this study was to examine the effects of a 12-week high-intensity interval training (HIIT) intervention, or an isocaloric continuous endurance training (CET) intervention on insulin resistance indices and change in irisin and preptin in patients with prediabetes. Thirty-two prediabetic male patients (age = 38.7 ± 4; body mass index = 26.9 ± 1.4 kg·m; and V[Combining Dot Above]O2peak = 2.49 ± 0.22 L·min) were randomly assigned into 3 training groups (N = 8). These groups were matched based on the required energy expenditure (EE) for completing each protocol: (a) HIIT (10 × 60 seconds at 90% peak oxygen uptake [V[Combining Dot Above]O2peak], 1: 1 work to recovery at 50 W), (b) CET at an intensity equivalent to maximal fat oxidation (Fatmax) (CETFAT) (pedaling for a duration that expends an equivalent EE to an HIIT session [E ≈ HIIT]), (c) CET at an intensity equivalent to anaerobic threshold (CETAT) (E ≈ HIIT), and (d) the control group (CON): continued to perform their daily activities. After intervention, blood glucose levels were significantly (p < 0.05) lower in the HIIT group compared with CETAT group. Exercise training improved the insulin resistance index by 35, 28, and 37% in CETFAT, CETAT, and HIIT groups, respectively. Irisin concentrations in the HIIT and CETAT groups was significantly (p < 0.05) decreased compared with the pre-training values. Also, HIIT and CETFAT resulted in significant (p < 0.05) changes in preptin concentration compared with baseline. This study demonstrated that both HIIT and CETFAT protocols had similar effects on the insulin resistance index of prediabetic patients. Also, the intensity and type of exercise were effective factors in changing irisin and preptin concentrations.

Comprehensive intensive therapy for Chinese gestational diabetes benefits both newborns and mothers.

PubMed

Cao, Xiaopei; Wang, Zilian; Yang, Chijiao; Mo, Xiaoqing; Xiu, Lingling; Li, Yangbing; Xiao, Haipeng

2012-11-01

This study identified the impact of intensive therapy on neonatal outcomes in women with gestational diabetes mellitus (GDM) and determined the effects on the postpartum metabolic status of the mothers. In total, 127 pregnant women with GDM were randomly selected to receive an intensive treatment regimen, which included one-to-one education, lifestyle intervention, scheduled clinic visits, strict glucose control, and frequent glucose self-monitoring. Meanwhile, 148 age-matched pregnant women with GDM were selected as controls and given the standard treatment regimen. Pregnancy outcomes including parameters related to the GDM mothers and to their neonates were comparatively analyzed between the two treatment groups. GDM patient follow-up (range, 1-3 years after delivery) included an oral glucose tolerance test and measurements of lipid concentration and insulin secretion. The insulinogenic index (ΔInsulin(30 min)/ΔBlood glucose(30 min)) and homeostasis model assessment index of β-cell function and insulin resistance were calculated. The patients' demographic and anthropometric data were also recorded for comparative analysis. Compared with GDM patients receiving standard treatment, GDM patients receiving intensive treatment had lower instances of premature delivery (2.4% vs. 8.3%, P<0.05) and neonatal care unit admission (21.3% vs. 33.3%, P<0.05) and lower neonatal birth weight (3.26±0.53 vs. 3.45±0.55 kg, P<0.0001). At follow-up, GDM patients from the intensive treatment group had a smaller waist circumference (75.83±3.11 vs. 78.34±4.20 cm, P<0.01), lower 30-min glucose levels after a 75-g glucose load (8.26±1.85 vs. 9.46±2.74 mmol/L, P<0.05), and higher high-density lipoprotein levels (1.30±0.24 vs. 1.18±0.23 mmol/L, P<0.05). The intensive GDM treatment regimen led to healthier outcomes for the women, the neonates, and the birth event and was associated with better maternal metabolic situations in the months and years after delivery.

Functional high intensity exercise training ameliorates insulin resistance and cardiometabolic risk factors in type 2 diabetes.

PubMed

Fealy, Ciarán E; Nieuwoudt, Stephan; Foucher, Julie A; Scelsi, Amanda R; Malin, Steve K; Pagadala, Mangesh; Cruz, Lauren A; Li, Miranda; Rocco, Michael; Burguera, Bartolome; Kirwan, John P

2018-05-15

Functional high intensity training (F-HIT) is a novel fitness paradigm that integrates simultaneous aerobic and resistance training in sets of constantly varied movements, based on real-world situational exercises, performed at high intensity in workouts that range from ∼8-20 min/session. We hypothesized that F-HIT would be an effective exercise mode for reducing insulin resistance in type 2 diabetes (T2D). We recruited 13 overweight/obese adults (5 males, 8 females; 53 ± 7 years; BMI 34.5 ± 3.6 kg•m -2 , Mean ± SD) with T2D to participate in a 6 week (3d/wk) supervised F-HIT program. An oral glucose tolerance test was used to derive measures of insulin sensitivity. F-HIT significantly reduced fat mass (43.8 ± 83.8 vs 41.6 ± 7.9 kg; P < 0.01), diastolic blood pressure (80.2 ± 7.1 vs 74.5 ± 5.8; P < 0.01), blood lipids (triglyceride and VLDL, both P < 0.05) and metabolic syndrome z-score (6.4 ± 4.5 vs -0.2 ± 5.2 AU; P < 0.001), and increased basal fat oxidation (FOX: 0.08 ± 0.03 vs 0.10 ± 0.04 g•min -1 ; P = 0.05), and HMW adiponectin (214.4 ± 88.9 vs 288.8 ± 127.4 ng•mL -1 ; P < 0.01). Importantly, F-HIT also increased insulin sensitivity (0.037 ± 0.010 vs 0.042 ± 0.010 AU; P < 0.05). Increases in HMW adiponectin and FOX correlated with the change in insulin sensitivity (rho: 0.75; P < 0.05, rho: 0.81; P < 0.01, respectively). Compliance with the training program was > 95% and no injuries or adverse events were reported. These data suggest that F-HIT may be an effective exercise mode for managing T2D. The increase in insulin sensitivity addresses a key defect in T2D and is consistent with improvements observed after more traditional aerobic exercise programs in overweight/obese adults with T2D. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Pancreas Islet Transplantation for Patients With Type 1 Diabetes Mellitus: A Clinical Evidence Review

PubMed Central

2015-01-01

Background Type 1 diabetes mellitus is caused by the autoimmune destruction of pancreatic beta (β) cells, resulting in severe insulin deficiency. Islet transplantation is a β-cell replacement therapeutic option that aims to restore glycemic control in patients with type 1 diabetes. The objective of this study was to determine the clinical effectiveness of islet transplantation in patients with type 1 diabetes, with or without kidney disease. Methods We conducted a systematic review of the literature on islet transplantation for type 1 diabetes, including relevant health technology assessments, systematic reviews, meta-analyses, and observational studies. We used a two-step process: first, we searched for systematic reviews and health technology assessments; second, we searched primary studies to update the chosen health technology assessment. The Assessment of Multiple Systematic Reviews measurement tool was used to examine the methodological quality of the systematic reviews and health technology assessments. We assessed the quality of the body of evidence and the risk of bias according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. Results Our searched yielded 1,354 citations. One health technology assessment, 11 additional observational studies to update the health technology assessment, one registry report, and four guidelines were included; the observational studies examined islet transplantation alone, islet-after-kidney transplantation, and simultaneous islet-kidney transplantation. In general, low to very low quality of evidence exists for islet transplantation in patients with type 1 diabetes with difficult-to-control blood glucose levels, with or without kidney disease, for these outcomes: health-related quality of life, secondary complications of diabetes, glycemic control, and adverse events. However, high quality of evidence exists for the specific glycemic control outcome of insulin independence compared with intensive insulin therapy. For patients without kidney disease, islet transplantation improves glycemic control and diabetic complications for patients with type 1 diabetes when compared with intensive insulin therapy. However, results for health-related quality of life outcomes were mixed, and adverse events were increased compared with intensive insulin therapy. For patients with type 1 diabetes with kidney disease, islet-after-kidney transplantation or simultaneous islet-kidney transplantation also improved glycemic control and secondary diabetic complications, although the evidence was more limited for this patient group. Compared with intensive insulin therapy, adverse events for islet-after-kidney transplantation or simultaneous islet-kidney transplantation were increased, but were in general less severe than with whole pancreas transplantation. Conclusions For patients with type 1 diabetes with difficult-to-control blood glucose levels, islet transplantation may be a beneficial β-cell replacement therapy to improve glycemic control and secondary complications of diabetes. However, there is uncertainty in the estimates of effectiveness because of the generally low to very low quality of evidence for all outcomes of interest. PMID:26644812

Breaking sitting with light activities vs structured exercise: a randomised crossover study demonstrating benefits for glycaemic control and insulin sensitivity in type 2 diabetes.

PubMed

Duvivier, Bernard M F M; Schaper, Nicolaas C; Hesselink, Matthijs K C; van Kan, Linh; Stienen, Nathalie; Winkens, Bjorn; Koster, Annemarie; Savelberg, Hans H C M

2017-03-01

We aimed to examine the effects of breaking sitting with standing and light-intensity walking vs an energy-matched bout of structured exercise on 24 h glucose levels and insulin resistance in patients with type 2 diabetes. In a randomised crossover study, 19 patients with type 2 diabetes (13 men/6 women, 63 ± 9 years old) who were not using insulin each followed three regimens under free-living conditions, each lasting 4 days: (1) Sitting: 4415 steps/day with 14 h sitting/day; (2) Exercise: 4823 steps/day with 1.1 h/day of sitting replaced by moderate- to vigorous-intensity cycling (at an intensity of 5.9 metabolic equivalents [METs]); and (3) Sit Less: 17,502 steps/day with 4.7 h/day of sitting replaced by standing and light-intensity walking (an additional 2.5 h and 2.2 h, respectively, compared with the hours spent doing these activities in the Sitting regimen). Blocked randomisation was performed using a block size of six regimen orders using sealed, non-translucent envelopes. Individuals who assessed the outcomes were blinded to group assignment. Meals were standardised during each intervention. Physical activity and glucose levels were assessed for 24 h/day by accelerometry (activPAL) and a glucose monitor (iPro2), respectively. The incremental AUC (iAUC) for 24 h glucose (primary outcome) and insulin resistance (HOMA2-IR) were assessed on days 4 and 5, respectively. The iAUC for 24 h glucose (mean ± SEM) was significantly lower during the Sit Less intervention than in Sitting (1263 ± 189 min × mmol/l vs 1974 ± 324 min × mmol/l; p = 0.002), and was similar between Sit Less and Exercise (Exercise: 1383 ± 194 min × mmol/l; p = 0.499). Exercise failed to improve HOMA2-IR compared with Sitting (2.06 ± 0.28 vs 2.16 ± 0.26; p = 0.177). In contrast, Sit Less (1.89 ± 0.26) significantly reduced HOMA2-IR compared with Exercise (p = 0.015) as well as Sitting (p = 0.001). Breaking sitting with standing and light-intensity walking effectively improved 24 h glucose levels and improved insulin sensitivity in individuals with type 2 diabetes to a greater extent than structured exercise. Thus, our results suggest that breaking sitting with standing and light-intensity walking may be an alternative to structured exercise to promote glycaemic control in patients type 2 diabetes. Clinicaltrials.gov NCT02371239 FUNDING: : The study was supported by a Kootstra grant from Maastricht University Medical Centre + , and the Dutch Heart Foundation. Financial support was also provided by Novo Nordisk BV, and Medtronic and Roche made the equipment available for continuous glucose monitoring.

Long-term impact of a structured group-based inpatient-education program for intensive insulin therapy in patients with diabetes mellitus.

PubMed

Göbl, Christian S; Dobes, Barbara; Luger, Anton; Bischof, Martin G; Krebs, Michael

2010-06-01

Structured patient education aiming to improve self-management strategies might be beneficial for insulin-treated diabetic patients. However, in previous studies the extent of the benefit has been inconsistent in different subgroups of patients. The aim of the present study was to assess the potential benefit of a structured inpatient-education program for intensive insulin therapy according to the basal-bolus concept with particular emphasis on self-management strategies. We included 81 diabetic patients (59 with type 1, 14 with type 2, eight with other forms) in this retrospective longitudinal study; all had completed the training program on eight consecutive days at a university clinic between 2003 and 2005. Data assessment included HbA1c, LDL-cholesterol, HDL-cholesterol and BMI at baseline (0-15 months before the training) and after 0-5, 5-10 and 10-20 months. A transient decrease of HbA1c (0.2%, 95% CI: 0.04-0.37, P = 0.017) and LDL-cholesterol levels (9.95 mg/dl, 95% CI: 2.24-17.76, P = 0.013) between baseline and the first follow-up examination was observed in the group overall. Thereafter, HbA1c and LDL-cholesterol were similar to baseline, whereas a persistent increase in HDL-cholesterol (P = 0.025) was evident in the multivariable analysis. No changes in BMI were observed. A significant type-by-time interaction (P = 0.008) in HbA1c suggests a long-term benefit in glycemic control in patients with type 2 diabetes. A diabetes training program for intensive insulin therapy with particular emphasis on self-management skills was followed by a moderate and transient improvement of glycemic control and LDL-cholesterol and by a persistent increase in HDL-cholesterol. Long-term improvement in glycemic control was observed only in patients with type 2 diabetes.

Impact of long-term high-intensity interval and moderate-intensity continuous training on subclinical inflammation in overweight/obese adults.

PubMed

Gerosa-Neto, José; Antunes, Barbara M M; Campos, Eduardo Z; Rodrigues, Jhennyfer; Ferrari, Gustavo D; Rosa Neto, José C; Bueno, Carlos R; Lira, Fábio S

2016-12-01

Obesity is a risk factor able to trigger several inflammatory alterations and the imbalance between pro- and anti-inflammatory cytokine productions. Physical exercise is an important strategy for reduction of inflammatory established process. The aim of this study was to evaluate the effect of 16 weeks of three exercise training programs in the inflammatory profile and insulin resistance in overweight/obesity. Thirty two men and women (46.4±10.1 years; 162.0±9.1 cm; 82.0±13.6 kg) were divided into three groups for training on a treadmill: continuous at 70% maximum heart rate (HRmax) 5 times a week (CONT); 1×4 min (1-bout) and 4×4 min (high intensity interval training, HIIT) at 90% HRmax 3 times a week. Interleukin (IL) 6 and IL-10, tumor necrosis factor-alpha (TNF-α), insulin and adiponectin levels were analyzed by enzyme-linked immunosorbent assay, and homeostasis model assessment insulin resistance was calculated. After 16 weeks of training blood concentrations of IL-6 decreased in the HIIT group ( P =0.035), TNF-α decreased in the CONT ( P =0.037) and increased in HIIT ( P =0.001) and adiponectin decreased in the three training models. There was a trend towards decreased body weight and body mass index (BMI) after HIIT only ( P =0.059 and P =0.060, respectively). Despite the decrease of adiponectin and the increase of TNF-α in HIIT group, insulin sensitivity showed a trend for improvement ( P =0.08). HIIT program decreased IL-6 at rest and although not significant was the only who tended to decrease total body weight and BMI. Taken together, our data suggest that both HIIT as well as CONT exercises training program promotes changes in inflammatory profile in overweight/obesity, but dissimilar response is seen in TNF-α levels.

Functional high-intensity training improves pancreatic β-cell function in adults with type 2 diabetes.

PubMed

Nieuwoudt, Stephan; Fealy, Ciarán E; Foucher, Julie A; Scelsi, Amanda R; Malin, Steven K; Pagadala, Mangesh; Rocco, Michael; Burguera, Bartolome; Kirwan, John P

2017-09-01

Type 2 diabetes (T2D) is characterized by reductions in β-cell function and insulin secretion on the background of elevated insulin resistance. Aerobic exercise has been shown to improve β-cell function, despite a subset of T2D patients displaying "exercise resistance." Further investigations into the effectiveness of alternate forms of exercise on β-cell function in the T2D patient population are needed. We examined the effect of a novel, 6-wk CrossFit functional high-intensity training (F-HIT) intervention on β-cell function in 12 sedentary adults with clinically diagnosed T2D (54 ± 2 yr, 166 ± 16 mg/dl fasting glucose). Supervised training was completed 3 days/wk, comprising functional movements performed at a high intensity in a variety of 10- to 20-min sessions. All subjects completed an oral glucose tolerance test and anthropometric measures at baseline and following the intervention. The mean disposition index, a validated measure of β-cell function, was significantly increased (PRE: 8.4 ± 3.1, POST: 11.5 ± 3.5, P = 0.02) after the intervention. Insulin processing inefficiency in the β-cell, expressed as the fasting proinsulin-to-insulin ratio, was also reduced (PRE: 2.40 ± 0.37, POST: 1.78 ± 0.30, P = 0.04). Increased β-cell function during the early-phase response to glucose correlated significantly with reductions in abdominal body fat ( R 2 = 0.56, P = 0.005) and fasting plasma alkaline phosphatase ( R 2 = 0.55, P = 0.006). Mean total body-fat percentage decreased significantly (Δ: -1.17 0.30%, P = 0.003), whereas lean body mass was preserved (Δ: +0.05 ± 0.68 kg, P = 0.94). We conclude that F-HIT is an effective exercise strategy for improving β-cell function in adults with T2D. Copyright © 2017 the American Physiological Society.

Impact of race/ethnicity on the efficacy and safety of commonly used insulin regimens: a post hoc analysis of clinical trials in type 2 diabetes mellitus.

PubMed

Davidson, Jaime A; Lacaya, Lyndon B; Jiang, Honghua; Heilmann, Cory R; Scism-Bacon, Jamie L; Gates, Jeffrey R; Jackson, Jeffrey A

2010-01-01

To explore the impact of race/ethnicity on the efficacy and safety of commonly used insulin regimens in patients with type 2 diabetes mellitus. In this post hoc analysis, pooled data from 11 multinational clinical trials involving 1455 patients with type 2 diabetes were used to compare specific insulin treatments in Latino/Hispanic, Asian, African-descent, and Caucasian patients. Insulin treatments included once daily insulin glargine or neutral protamine Hagedorn (BASAL), insulin lispro mix 75/25 twice daily (LMBID), or insulin lispro mix 50/50 three times daily (LMTID). Race/ethnicity was associated with significant outcome differences for each of the insulin regimens. BASAL therapy was associated with greater improvement in several measures of glycemic control among Latino/Hispanic patients compared with Caucasian patients (lower end point hemoglobin A1c, greater reduction in hemoglobin A1c from baseline, and a larger proportion of patients achieving hemoglobin A1c level <7%). In contrast, LMBID therapy was associated with higher end point hemoglobin A1c and a smaller decrease in hemoglobin A1c from baseline in Latino/Hispanic and Asian patients than in Caucasian patients. Furthermore, fewer Asian patients attained a hemoglobin A1c level <7% than did Caucasians patients. For LMTID therapy, hemoglobin A1c outcomes were comparable across patient groups. Fasting blood glucose and glycemic excursions varied among racial/ethnic groups for the 3 insulin regimens. Weight change was comparable among racial/ethnic groups in each insulin regimen. During treatment with LMTID, Asian patients experienced higher incidence and rate of severe hypoglycemia than Caucasian patients. Latino/Hispanic, Asian, and African-descent patients with type 2 diabetes show different metabolic responses to insulin therapy, dependent in part on insulin type and regimen intensity.

Does IGF-1 play a role in the etiopathogenesis of non-functioning adrenocortical adenoma?

PubMed

Bahadir, C T; Ecemis, G C; Atmaca, H

2018-03-14

The aim of this study was to investigate the possible association of insulin-like growth factor-1 (IGF-1) with the pathogenesis of non-functioning adrenocortical adenomas (NFAs). This study included 50 female patients (mean age 54 years) with NFAs, 55 patients (mean age 48 years; 20 male, 35 female) with acromegaly and 38 female control subjects (mean age 58 years). Body mass index (BMI) and waist circumference (WC) of the subjects were recorded and blood samples for IGF-1 were taken. Insulin resistance was calculated using the homeostatic model assessment (HOMA) score. Since most of the acromegaly patients had been using medicine that could have effected insulin resistance, HOMA scores were calculated only in patients with NFAs and the controls. Computerized tomography or magnetic resonance imaging was taken of the acromegalics and controls to detect adrenal mass frequency. The mean age was similar among the groups. As expected, the serum IGF-1 levels were significantly higher in patients with acromegaly than in patients with NFAs and the controls (p < 0.001). Although BMI, WC, and serum IGF-1 levels were significantly higher (p < 0.001) in patients with NFAs, the HOMA scores were similar between patients with NFAs and control groups. Although none of the control subjects had adrenal masses, NFAs were detected in 14 (25%) out of 55 acromegalic patients. Higher serum IGF-1 levels in patients with NFAs compared to the control group and an increased prevalence of NFAs in acromegaly patients compared to control subjects and the general population suggest an association of IGF-1 with the etiopathogenesis of NFA.

The role of dietary fat in obesity-induced insulin resistance.

PubMed

Lackey, Denise E; Lazaro, Raul G; Li, Pingping; Johnson, Andrew; Hernandez-Carretero, Angelina; Weber, Natalie; Vorobyova, Ivetta; Tsukomoto, Hidekazu; Osborn, Olivia

2016-12-01

Consumption of excess calories results in obesity and insulin resistance and has been intensively studied in mice and humans. The objective of this study was to determine the specific contribution of dietary fat rather than total caloric intake to the development of obesity-associated insulin resistance. We used an intragastric feeding method to overfeed excess calories from a low-fat diet (and an isocalorically matched high-fat diet) through a surgically implanted gastric feeding tube to generate obesity in wild-type mice followed by hyperinsulinemic-euglycemic clamp studies to assess the development of insulin resistance. We show that overfeeding a low-fat diet results in levels of obesity similar to high-fat diet feeding in mice. However, despite a similar body weight, obese high-fat diet-fed mice are more insulin resistant than mice fed an isocaloric low-fat diet. Therefore, increased proportion of calories from dietary fat further potentiates insulin resistance in the obese state. Furthermore, crossover diet studies revealed that reduction in dietary fat composition improves glucose tolerance in obesity. In the context of the current obesity and diabetes epidemic, it is particularly important to fully understand the role of dietary macronutrients in the potentiation and amelioration of disease. Copyright © 2016 the American Physiological Society.

An evaluation of the effectiveness of adaptive histogram equalization for contrast enhancement.

PubMed

Zimmerman, J B; Pizer, S M; Staab, E V; Perry, J R; McCartney, W; Brenton, B C

1988-01-01

Adaptive histogram equalization (AHE) and intensity windowing have been compared using psychophysical observer studies. Experienced radiologists were shown clinical CT (computerized tomographic) images of the chest. Into some of the images, appropriate artificial lesions were introduced; the physicians were then shown the images processed with both AHE and intensity windowing. They were asked to assess the probability that a given image contained the artificial lesion, and their accuracy was measured. The results of these experiments show that for this particular diagnostic task, there was no significant difference in the ability of the two methods to depict luminance contrast; thus, further evaluation of AHE using controlled clinical trials is indicated.

Computer-supported weight-based drug infusion concentrations in the neonatal intensive care unit.

PubMed

Giannone, Gay

2005-01-01

This article addresses the development of a computerized provider order entry (CPOE)-embedded solution for weight-based neonatal drug infusion developed during the transition from a legacy CPOE system to a customized application of a neonatal CPOE product during a hospital-wide information system transition. The importance of accurate fluid management in the neonate is reviewed. The process of tailoring the system that eventually resulted in the successful development of a computer application enabling weight-based medication infusion calculation for neonates within the CPOE information system is explored. In addition, the article provides guidelines on how to customize a vendor solution for hospitals with neonatal intensive care unit.

Effects of exercise at individual anaerobic threshold and maximal fat oxidation intensities on plasma levels of nesfatin-1 and metabolic health biomarkers.

PubMed

Mohebbi, Hamid; Nourshahi, Maryam; Ghasemikaram, Mansour; Safarimosavi, Saleh

2015-03-01

Exercise is recognized as an effective method of weight management and short-term appetite regulation tool. The effect of different exercise intensities on appetite regulation hormones in healthy overweight participants has not been intensively studied. The aim of this study was to examine the influence of exercise at individual anaerobic threshold (IAT) and maximal fat oxidation (Fatmax) intensities on the nesfatin-1 response and metabolic health biomarkers in overweight men. Nine healthy overweight males (age, 23.1 ± 1.1 years) volunteered in this study in a counterbalanced order. Blood samples were obtained before, immediately after, and following the first 45 min of recovery for measuring plasma variables. There was significant decrease in plasma levels of nesfatin-1 and leptin after exercise at the IAT intensity which remained lower than baseline following 45 min of recovery. However, nesfatin-1 and leptin levels did not change significantly in any time courses of Fatmax intensity (P > 0.09). Plasma interleukin-6 (IL-6) concentration increased during exercise in both intensities (P < 0.05), whereas changes in free fatty acids (FFAs) and epinephrine concentrations were significant only at the IAT. In addition, a significant correlation was found among nesfatin-1 levels with insulin (r = 0.39, P < 0.05) and glucose (r = 0.41, P < 0.05) at basal and in response to exercise. These results indicate that IAT has a greater exercise-induced appetite regulation effect compared with Fat(max). Based on these data, the intensity of exercise may have an important role in changes of nesfatin-1, leptin, FFA, and epinephrine concentrations even though this was not the case for IL-6 and insulin resistance.

The Role of Hyperglycemia in Burned Patients: Evidence-Based Studies

PubMed Central

Mecott, Gabriel A.; Al-Mousawi, Ahmed M.; Gauglitz, Gerd G.; Herndon, David N.; Jeschke, Marc G.

2013-01-01

Severely burned patients typically experience a systemic response expressed as increased metabolism, inflammation, alteration of cardiac and immune function, and associated hyperglycemia. Hyperglycemia has been associated with an increased risk of morbidity and mortality in critically ill patients. Until recently and for many years, hyperglycemia has been expectantly managed and considered a normal and desired response of an organism to stress. However, findings reported from recent studies now suggest beneficial effects of intensive insulin treatment for critically-ill patients. The literature on the management of hyperglycemia in severely burned patients is sparse, with most of the available studies involving only small numbers of burned patients. The purpose of this article is to describe the pathophysiology of hyperglycemia following severe burns and review the available literature on the outcome of intensive insulin treatment and other anti-hyperglycemic modalities in burned patients in an evidence-based-medicine approach. PMID:19503020

The effect of different volumes of high-intensity interval training on proinsulin in participants with the metabolic syndrome: a randomised trial.

PubMed

Ramos, Joyce S; Dalleck, Lance C; Borrani, Fabio; Mallard, Alistair R; Clark, Bronwyn; Keating, Shelley E; Fassett, Robert G; Coombes, Jeff S

2016-11-01

The continuous demand for insulin in the face of insulin resistance, coupled with the glucolipotoxic environment associated with the metabolic syndrome (MetS), adversely affects the quality of insulin produced and secreted by the pancreatic beta cells. This is depicted by increased circulating intact proinsulin concentration, which is associated with increased MetS severity and risk of cardiovascular (CV) mortality. High-intensity interval training (HIIT) has been shown to reduce insulin resistance and other CV disease risk factors to a greater degree than moderate-intensity continuous training (MICT). We therefore aimed to investigate the impact of MICT and different volumes of HIIT on circulating intact proinsulin concentration. This was a substudy of the 'Exercise in prevention of Metabolic Syndrome' (EX-MET) multicentre trial. Sixty-six individuals with MetS were randomised to 16 weeks of: (1) MICT (n = 21, 30 min at 60-70% peak heart rate [HRpeak], five times/week); (2) 4HIIT (n = 22, 4 × 4 min bouts at 85-95% HRpeak, interspersed with 3 min of active recovery at 50-70% HRpeak, three times/week); or (3) 1HIIT (n = 23, 1 × 4 min bout at 85-95% HRpeak, three times/week). A subanalysis investigated the differential impact of these training programmes on intact proinsulin concentration in MetS individuals with type 2 diabetes (MICT, n = 6; 4HIIT, n = 9; 1HIIT, n = 12) and without type 2 diabetes (MICT, n = 15; 4HIIT, n = 13; 1HIIT, n = 11). Intact proinsulin, insulin and C-peptide concentrations were measured in duplicate via ELISA, following a 12 h fast, before and after the exercise programme. Fasting intact proinsulin concentration was also expressed relative to insulin and C-peptide concentrations. Following the exercise training, there were no significant (p > 0.05) changes in fasting intact proinsulin concentration indices in all participants (pre- vs post-programme proinsulin, proinsulin:insulin, proinsulin:C-peptide: MICT 19% decrease, 6% increase, 4% increase; 4HIIT 19% decrease, 8% decrease, 11% decrease; 1HIIT 34% increase, 49% increase, 36% increase). In participants who did not have type 2 diabetes, only 4HIIT significantly (p < 0.05) reduced fasting intact proinsulin concentration indices from pre to post intervention (pre- vs post-programme proinsulin, proinsulin:insulin, proinsulin:C-peptide: 4HIIT 32% decrease, 26% decrease, 32% decrease, p < 0.05; 1HIIT, 14% increase, 32% increase, 16% increase, p > 0.05; MICT 27% decrease, 17% decrease, 11% decrease), with a group × time interaction effect, indicating a greater reduction in intact proinsulin indices following 4HIIT compared with MICT and 1HIIT. There were no significant (p > 0.05) changes in intact proinsulin concentration indices in participants with type 2 diabetes. Higher-volume HIIT (4HIIT) improved insulin quality in MetS participants without type 2 diabetes. ClinicalTrials.gov NCT01676870 FUNDING: The study was funded by the Norwegian University of Science and Technology and from an unrestricted research grant from the Coca-Cola company. Funding for the collection of physical activity data was derived from a 'UQ New Staff Start Up' grant awarded to B. Clark.

Insulin therapy in children and adolescents with type 1 diabetes.

PubMed

Malik, Faisal S; Taplin, Craig E

2014-04-01

Treatment of type 1 diabetes mellitus (T1DM) requires lifelong administration of exogenous insulin. The primary goal of treatment of T1DM in children and adolescents is to maintain near-normoglycemia through intensive insulin therapy, avoid acute complications, and prevent long-term microvascular and macrovascular complications, while facilitating as close to a normal life as possible. Effective insulin therapy must, therefore, be provided on the basis of the needs, preferences, and resources of the individual and the family for optimal management of T1DM. To achieve target glycemic control, the best therapeutic option for patients with T1DM is basal-bolus therapy either with multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII). Many formulations of insulin are available to help simulate endogenous insulin secretion as closely as possible in an effort to eliminate the symptoms and complications of hyperglycemia, while minimizing the risk of hypoglycemia secondary to therapy. When using MDI, basal insulin requirements are given as an injection of long- or intermediate-acting insulin analogs, while meal-related glucose excursions are controlled with bolus injections of rapid-acting insulin analogs. Alternatively, CSII can be used, which provides a 24-h preselected but adjustable basal rate of rapid-acting insulin, along with patient-activated mealtime bolus doses, eliminating the need for periodic injections. Both MDI treatment and CSII therapy must be supported by comprehensive education that is appropriate for the individual needs of the patient and family before and after initiation. Current therapies still do not match the endogenous insulin profile of pancreatic β-cells, and all still pose risks of suboptimal control, hypoglycemia, and ketosis in children and adolescents. The safety and success of a prescribed insulin regimen is, therefore, dependent on self-monitoring of blood glucose and/or a continuous glucose monitoring system to avoid critical hypoglycemia and glucose variability. Regardless of the mode of insulin therapy, doses should be adapted on the basis of the daily pattern of blood glucose, through regular review and reassessment, and patient factors such as exercise and pubertal status. New therapy options such as sensor-augmented insulin pump therapy, which integrates CSII with a continuous glucose sensor, along with emerging therapies such as the artificial pancreas, will likely continue to improve safe insulin therapy in the near future.

Methods for insulin delivery and glucose monitoring in diabetes: summary of a comparative effectiveness review.

PubMed

Golden, Sherita Hill; Sapir, Tamar

2012-08-01

Diabetes mellitus is defined as a group of metabolic diseases characterized by hyperglycemia, which when untreated can lead to long-term complications, including micro- and macrovascular complications. Tight glycemic control with intensive insulin therapy has been suggested to reduce the risk of such complications in several diabetes populations; however, such an approach can also be associated with risks and challenges. There are currently several modalities available to deliver insulin and monitor glucose levels to achieve glycemic goals in diabetic patients. In July 2012, the Agency for Healthcare Research and Quality (AHRQ) published a systematic review on the comparative effectiveness of insulin delivery systems and glucose-monitoring modalities in diabetic patients receiving intensive insulin therapy. Studies from 44 publications included in the review compared the effects of continuous subcutaneous insulin infusion (CSII) with multiple daily injections (MDI) and/or real time-continuous glucose monitoring (rt-CGM) with self-monitoring of blood glucose (SMBG) among children, adolescents, or adults with either type 1 (T1DM) or type 2 diabetes (T2DM), or pregnant women with pre-existing diabetes (either T1DM or T2DM). This comparative effectiveness review evaluated which modality results in improved glycemic control, less hypoglycemia, better quality of life, and/or improved clinical outcomes. The numerous technologies and the challenges that clinicians face when determining which patient population may benefit from different insulin delivery systems and glucose-monitoring approaches motivated AHRQ to synthesize the available information to assist health professionals in making evidence-based practice decisions for their patients. The review also delineates advances in insulin delivery and glucose-monitoring systems, practical methods to achieve tight glycemic control and strategies to minimize associated risks, as well as highlights gaps in research and areas that need to be addressed in the future.  To (a) educate health care professionals on the findings from AHRQ's 2012 comparative effectiveness review on insulin delivery and glucose-monitoring modalities in patients with diabetes; (b) apply review findings to make treatment decisions in clinical practice; and (c) identify shortcomings in the current research and future directions relating to the comparative effectiveness of insulin delivery and glucose-monitoring modalities for patients with diabetes. The AHRQ systematic review of randomized clinical trials reveals that both insulin delivery modalities (CSII and MDI) demonstrate similar effectiveness on glycemic control and severe hypoglycemia in children and adolescents with T1DM and in adults with T2DM. In adults with T1DM, hemoglobin A1c decreased more with CSII than with MDI with low strength of evidence, but one study heavily influenced these results. In children and adults with T1DM, the use of CSII was associated with improved quality of life compared with MDI, with low strength of evidence, while there was insufficient strength of evidence to make conclusions regarding the quality of life for adults with T2DM. The study investigators suggest that the modality to deliver intensive insulin therapy can be individualized to patient preference in order to maximize quality of life. On all measured outcomes, there was insufficient or low strength of evidence regarding pregnant women with pre-existing diabetes.The AHRQ investigators found studies comparing the effectiveness of glucose-monitoring modalities in individuals with T1DM only. The systematic review demonstrates that rt-CGM is associated with greater lowering of A1c compared with SMBG (high strength of evidence) without affecting the risk of severe hypoglycemia (low strength of evidence) or quality of life (low strength of evidence) in nonpregnant individuals with T1DM, particularly when compliance with device use is high. Additional findings suggest that the use of sensor-augmented insulin pumps (rt-CGM + CSII) is superior to the use of MDI/SMBG use in lowering A1c in nonpregnant individuals with T1DM (moderate strength of evidence). Comparison of other outcome measures did not yield firm conclusions due to low or insufficient evidence.

Relationship between hyperglycemia, hormone disturbances, and clinical evolution in severely hyperglycemic post surgery critically ill children: an observational study

PubMed Central

2014-01-01

Background To study hormonal changes associated with severe hyperglycemia in critically ill children and the relationship with prognosis and length of stay in intensive care. Methods Observational study in twenty-nine critically ill children with severe hyperglycemia defined as 2 blood glucose measurements greater than 180 mg/dL. Severity of illness was assessed using pediatric index of mortality (PIM2), pediatric risk of mortality (PRISM) score, and pediatric logistic organ dysfunction (PELOD) scales. Blood glucose, glycosuria, insulin, C-peptide, cortisol, corticotropin, insulinlike growth factor-1, growth hormone, thyrotropin, thyroxine, and treatment with insulin were recorded. β-cell function and insulin sensitivity and resistance were determined on the basis of the homeostatic model assessment (HOMA), using blood glucose and C-peptide levels. Results The initial blood glucose level was 249 mg/dL and fell gradually to 125 mg/dL at 72 hours. Initial β-cell function (49.2%) and insulin sensitivity (13.2%) were low. At the time of diagnosis of hyperglycemia, 50% of the patients presented insulin resistance and β-cell dysfunction, 46% presented isolated insulin resistance, and 4% isolated β-cell dysfunction. β-cell function improved rapidly but insulin resistance persisted. Initial glycemia did not correlate with any other factor, and there was no relationship between glycemia and mortality. Patients who died had higher cortisol and growth hormone levels at diagnosis. Length of stay was correlated by univariate analysis, but not by multivariate analysis, with C-peptide and glycemic control at 24 hours, insulin resistance, and severity of illness scores. Conclusions Critically ill children with severe hyperglycemia initially present decreased β-cell function and insulin sensitivity. Nonsurvivors had higher cortisol and growth hormone levels and developed hyperglycemia later than survivors. PMID:24628829

Qualitative analysis of subcutaneous Lispro and regular insulin injections for stress hyperglycemia: a pilot numerical study.

PubMed

Strilka, Richard J; Armen, Scott B; Indeck, Matthew C

2014-09-07

Increased glucose variability (GV) is an independent risk factor for mortality in the critically ill; unfortunately, the optimal insulin therapy that minimizes GV is not known. We simulate the glucose-insulin feedback system to study how stress hyperglycemia (SH) states, taken to be a non-uniform group of physiologic disorders with varying insulin resistance (IR) and similar levels of hyperglycemia, respond to the type and dose of subcutaneous (SQ) insulin. Two groups of 100 virtual patients are studied: those receiving and those not receiving continuous enteral feeds. Stress hyperglycemia was facilitated by doubling the gluconeogenesis rate and IR was stepwise varied from a borderline to a high value. Lispro and regular insulin were simulated with dosages that ranged from 0 to 6 units; the resulting GV was analyzed after each insulin injection. The numerical model used consists of a set of non-linear differential equations with two time delays and five adjustable parameters. The results show that regular insulin decreased GV in both patient groups and rarely caused hypoglycemia. With continuous enteral feeds and borderline to mild IR, Lispro showed minimal effect on GV; however, rebound hyperglycemia that increased GV occurred when the IR was moderate to high. Without a nutritional source, Lispro worsened GV through frequent hypoglycemia episodes as the injection dose increased. The inferior performance of Lispro is a result of its rapid absorption profile; half of its duration of action is similar to the glucose ultradian period. Clinical trials are needed to examine whether these numerical results represent the glucose-insulin dynamics that occur in intensive care units, and if such dynamics are present, their clinical effects should be evaluated. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

The adipogenic potential of Cr(III). A molecular approach exemplifying metal-induced enhancement of insulin mimesis in diabetes mellitus II.

PubMed

Tsave, O; Yavropoulou, M P; Kafantari, M; Gabriel, C; Yovos, J G; Salifoglou, A

2016-10-01

Insulin resistance is identified through numerous pathophysiological conditions, such as Diabetes mellitus II, obesity, hypertension and other metabolic syndromes. Enhancement of insulin action and\\or its complete replacement by insulin-enhancing or insulin-mimetic agents seems to improve treatment of metabolic diseases. Over the last decades, intensive research has targeted the investigation of such agents, with chromium emerging as an important inorganic cofactor involved in the requisite metabolic chemistry. Chromium in its trivalent state has been shown to play a central role in carbohydrate metabolism by enhancing insulin signaling, action, and thus the sensitivity of insulin-sensitive tissues. A very likely link between diabetes and obesity is the adipose tissue, which stores energy in the form of triglycerides and releases free fatty acids. To date, there is paucity of information on the exact mechanism of the chromium effect concerning insulin-activated molecular paths, such as adipogenesis. The aim of the present study is to delve into such an effect by employing a well-defined form of chromium (Cr(III)-citrate) on the a) survival of pre- and mature adipocytes (3T3-L1), b) endogenous cell motility, and c) insulin-enhancing adipogenic capacity. The emerging results suggest that Cr(III)-citrate a) is (a)toxic in a concentration- and time-dependent manner, b) has no influence on cell motility, c) can induce 3T3-L1 pre-adipocyte differentiation into mature adipocytes through elevation of tissue specific biomarker levels (PPAR-γ, GLUT 4 and GCK), and d) exemplifies structurally-based metal-induced adipogenesis as a key process contributing to the development of future antidiabetic metallodrugs. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of Interrupting Children's Sedentary Behaviors With Activity on Metabolic Function: A Randomized Trial.

PubMed

Belcher, Britni R; Berrigan, David; Papachristopoulou, Alexia; Brady, Sheila M; Bernstein, Shanna B; Brychta, Robert J; Hattenbach, Jacob D; Tigner, Ira L; Courville, Amber B; Drinkard, Bart E; Smith, Kevin P; Rosing, Douglas R; Wolters, Pamela L; Chen, Kong Y; Yanovski, Jack A

2015-10-01

Limited data suggest that interrupting sedentary behaviors with activity improves metabolic parameters in adults. We tested whether interrupting sitting with short, moderate-intensity walking bouts improved glucose tolerance in children. Participants underwent two experimental conditions in random order on different days: continuous sitting for 3 hours or sitting interrupted by walking (3 min of moderate-intensity walking every 30 min). Insulin, C-peptide, glucose, and free fatty acids were measured every 30 minutes for 3 hours during an oral glucose tolerance test. Area under the curve (AUC) was calculated from hormone and substrate measurements. Children were given a buffet meal after each condition. The study was conducted at the National Institutes of Health Hatfield Clinical Research Center. Twenty-eight normal-weight 7-11 year olds participated. Patterns of substrate/hormone secretion and AUC, as well as energy intake, were examined by experimental condition. Interrupting sitting resulted in a 32% lower insulin AUC (P < .001), 17% lower C-peptide AUC (P < .001), and 7% lower glucose AUC (P = .018) vs continuous sitting. Mixed model results indicated that insulin (P = .036) and free fatty acid concentrations (P = .009) were significantly lower in the interrupted vs the continuous sitting condition. Lunchtime buffet meal energy intake did not significantly differ between the conditions (975 ± 387 vs 963 ± 309 kcal; P = .85). Interrupting sedentary time with brief moderate-intensity walking improved short-term metabolic function in non-overweight children without increasing subsequent energy intake. These findings suggest that interrupting sedentary behavior may be a promising prevention strategy for reducing cardiometabolic risk in children.

Using Neuroplasticity-Based Auditory Training to Improve Verbal Memory in Schizophrenia

PubMed Central

Fisher, Melissa; Holland, Christine; Merzenich, Michael M.; Vinogradov, Sophia

2009-01-01

Objective Impaired verbal memory in schizophrenia is a key rate-limiting factor for functional outcome, does not respond to currently available medications, and shows only modest improvement after conventional behavioral remediation. The authors investigated an innovative approach to the remediation of verbal memory in schizophrenia, based on principles derived from the basic neuroscience of learning-induced neuroplasticity. The authors report interim findings in this ongoing study. Method Fifty-five clinically stable schizophrenia subjects were randomly assigned to either 50 hours of computerized auditory training or a control condition using computer games. Those receiving auditory training engaged in daily computerized exercises that placed implicit, increasing demands on auditory perception through progressively more difficult auditory-verbal working memory and verbal learning tasks. Results Relative to the control group, subjects who received active training showed significant gains in global cognition, verbal working memory, and verbal learning and memory. They also showed reliable and significant improvement in auditory psychophysical performance; this improvement was significantly correlated with gains in verbal working memory and global cognition. Conclusions Intensive training in early auditory processes and auditory-verbal learning results in substantial gains in verbal cognitive processes relevant to psychosocial functioning in schizophrenia. These gains may be due to a training method that addresses the early perceptual impairments in the illness, that exploits intact mechanisms of repetitive practice in schizophrenia, and that uses an intensive, adaptive training approach. PMID:19448187

INSULIN RESISTANCE POST-BURN: UNDERLYING MECHANISMS AND CURRENT THERAPEUTIC STRATEGIES

PubMed Central

Gauglitz, Gerd G.; Herndon, David N.; Jeschke, Marc G.

2014-01-01

The profound hypermetabolic response to burn injury is associated with insulin resistance and hyperglycemia, significantly contributing to the incidence of morbidity and mortality in this patient population. These responses are present in all trauma, surgical, or critically ill patients, but the severity, length, and magnitude is unique for burn patients. Although advances in therapeutic strategies to attenuate the post-burn hypermetabolic response have significantly improved the clinical outcome of these patients over the past years, therapeutic approaches to overcome stress-induced hyperglycemia have remained challenging. Intensive insulin therapy has been shown to significantly reduce morbidity and mortality in critically ill patients. High incidence of hypoglycemic events and difficult blood glucose titrations have led to investigation of alternative strategies, including the use of metformin, a biguanide, or fenofibrate, a PPAR-γ agonist. Nevertheless, weaknesses and potential side affects of these drugs reinforces the need for better understanding of the molecular mechanisms underlying insulin resistance post-burn that may lead to novel therapeutic strategies further improving the prognosis of these patients. This review aims to discuss the mechanisms underlying insulin resistance induced hyperglycemia post-burn and outlines current therapeutic strategies that are being used to modulate hyperglycemia following thermal trauma. PMID:18695610

Impact of the aspirated volume of fat tissue in the insulin resistance after liposuction.

PubMed

Oliveira, Sérgio de Souza; Cibantos, Jubert Sanches; Ripari, Wagner Targa; Aguilar-Nascimento, José Eduardo de

2013-01-01

To investigate insulin resistance imposed by liposuction, correlating its intensity with the extent of the operation. The sample consisted of 20 female patients without comorbidities, aged between 21 and 43 years, body mass index between 19 and 27 kg/m², undergoing liposuction alone or associated with breasts' prosthesis. We assessed insulin resistance at the beginning and end of the procedure by calculating the Homeostasis Model Assessment (HOMA-IR). The operative variables were length of liposuction, breast prosthesis time, body areas submitted to liposuction and total fat aspirated. The liposuction time was 94-278 min (mean = 174 min), duration of breast prosthesis 20-140 min (mean = 65 min) and total fat aspirated 680-4280 g (mean = 1778 g). Statistical analysis was performed by considering a division line of 1500 g of aspirated fat and there was a significantly increased insulin resistance by HOMA index greater in the group > 1500 g (123% increase) than in the group d" 1500 g (an increase of 53 %) from the baseline data (p = 0.02). Other operative variables showed no significant correlation. Insulin resistance shows significant increase in liposuction, and it is correlated to the volume of aspirated fat.

Insulin-Responsive Compartments Containing GLUT4 in 3T3-L1 and CHO Cells: Regulation by Amino Acid Concentrations

PubMed Central

Bogan, Jonathan S.; McKee, Adrienne E.; Lodish, Harvey F.

2001-01-01

In fat and muscle, insulin stimulates glucose uptake by rapidly mobilizing the GLUT4 glucose transporter from a specialized intracellular compartment to the plasma membrane. We describe a method to quantify the relative proportion of GLUT4 at the plasma membrane, using flow cytometry to measure a ratio of fluorescence intensities corresponding to the cell surface and total amounts of a tagged GLUT4 reporter in individual living cells. Using this assay, we demonstrate that both 3T3-L1 and CHO cells contain intracellular compartments from which GLUT4 is rapidly mobilized by insulin and that the initial magnitude and kinetics of redistribution to the plasma membrane are similar in these two cell types when they are cultured identically. Targeting of GLUT4 to a highly insulin-responsive compartment in CHO cells is modulated by culture conditions. In particular, we find that amino acids regulate distribution of GLUT4 to this kinetically defined compartment through a rapamycin-sensitive pathway. Amino acids also modulate the magnitude of insulin-stimulated translocation in 3T3-L1 adipocytes. Our results indicate a novel link between glucose and amino acid metabolism. PMID:11416153

Diabetic ketoacidosis producing extreme hyperkalemia in a patient with type 1 diabetes on hemodialysis.

PubMed

Yamada, Hodaka; Funazaki, Shunsuke; Kakei, Masafumi; Hara, Kazuo; Ishikawa, San-E

2017-01-01

Diabetic ketoacidosis (DKA) is a critical complication of type 1 diabetes associated with water and electrolyte disorders. Here, we report a case of DKA with extreme hyperkalemia (9.0 mEq/L) in a patient with type 1 diabetes on hemodialysis. He had a left frontal cerebral infarction resulting in inability to manage his continuous subcutaneous insulin infusion pump. Electrocardiography showed typical changes of hyperkalemia, including absent P waves, prolonged QRS interval and tented T waves. There was no evidence of total body water deficit. After starting insulin and rapid hemodialysis, the serum potassium level was normalized. Although DKA may present with hypokalemia, rapid hemodialysis may be necessary to resolve severe hyperkalemia in a patient with renal failure. Patients with type 1 diabetes on hemodialysis may develop ketoacidosis because of discontinuation of insulin treatment.Patients on hemodialysis who develop ketoacidosis may have hyperkalemia because of anuria.Absolute insulin deficit alters potassium distribution between the intracellular and extracellular space, and anuria abolishes urinary excretion of potassium.Rapid hemodialysis along with intensive insulin therapy can improve hyperkalemia, while fluid infusions may worsen heart failure in patients with ketoacidosis who routinely require hemodialysis.

Use of HOMA-IR in hepatitis C.

PubMed

Eslam, M; Kawaguchi, T; Del Campo, J A; Sata, M; Khattab, M Abo-Elneen; Romero-Gomez, M

2011-10-01

Chronic infection with hepatitis C virus (HCV) can induce insulin resistance (IR) in a genotype-dependent manner and contributes to steatosis, progression of fibrosis and resistance to interferon plus ribavirin therapy. Our understanding of HCV-induced IR has improved considerably over the years, but certain aspects concerning its evaluation still remain elusive to clinical researchers. One of the most important issues is elucidating the ideal method for assessment of IR in the setting of hepatitis C. The hyperinsulinaemic euglycaemic clamp is the gold standard method for determining insulin sensitivity, but is impractical as it is labour intensive and time-consuming. To date, all human studies except for four where IR was evaluated in the HCV setting, an estimation of IR has been used rather than direct measurements of insulin-mediated glucose uptake. The most commonly used estimation in the HCV population is the homeostasis model assessment of insulin resistance (HOMA-IR) which is calculated from a single measurement of fasting insulin and glucose. In this article, we review the use and reporting of HOMA in the literature and provide guidance on its appropriate as well as inappropriate use in the hepatitis setting. © 2011 Blackwell Publishing Ltd.

Eight-Week Training Cessation Suppresses Physiological Stress but Rapidly Impairs Health Metabolic Profiles and Aerobic Capacity in Elite Taekwondo Athletes.

PubMed

Liao, Yi-Hung; Sung, Yu-Chi; Chou, Chun-Chung; Chen, Chung-Yu

2016-01-01

Changes in an athlete's physiological and health metabolic profiles after detraining have not been studied in elite Taekwondo (TKD) athletes. To enable a better understanding of these physiological changes to training cessation, this study examined the effects of 8-weeks detraining on the aerobic capacity, body composition, inflammatory status and health metabolic profile in elite TKD athletes. Sixteen elite TKD athletes (age: 21.0 ± 0.8 yrs, BMI: 22.4 ± 3.9 kg/m2; Mean ± SD; 11 males and 5 females) participated in this study. Physical activity level assessment using computerized physical activity logs was performed during the competitive preparation season (i.e. one-week before national competition) and at two week intervals throughout the detraining period. Participant aerobic capacity, body fat, and blood biomarkers were measured before and after detraining, and the blood biomarker analyses included leukocyte subpopulations, blood glucose, insulin, dehydroepiandrosterone-sulfate (DHEA-S), and cortisol. Eight-week detraining increased DHEA-S/cortisol ratio (+57.3%, p = 0.004), increased insulin/cortisol ratio (+59.9%, p = 0.004), reduced aerobic power (-2.43%, p = 0.043), increased body fat accumulation (body fat%: +21.3%, p < 0.001), decreased muscle mass (muscle mass%: -4.04%, p < 0.001), and elevated HOMA-IR (the biomarker of systemic insulin resistance; +34.2%, p = 0.006). The neutrophil-to-lymphocyte ratio (NLR), a systemic inflammatory index, increased by 48.2% (p = 0.005). The change in aerobic capacity was correlated with the increased fat mass (r = -0.429, p = 0.049) but not with muscle loss. An increase in the NLR was correlated to the changes in HOMA-IR (r = 0.44, p = 0.044) and aerobic capacity (r = -0.439, p = 0.045). We demonstrate that 8-week detraining suppresses physiological stress but rapidly results in declines in athletic performance and health metabolic profiles, including reduced aerobic capacity, increased body fat, muscle loss, insulin resistance development and elevated systemic inflammatory status in these young elite TKD athletes. The inflammation state was positively associated with insulin resistance development, fat mass, WHR (the index for central fat accumulation), and the decline in VO2max.

Decreased insulin-stimulated brown adipose tissue glucose uptake after short-term exercise training in healthy middle-aged men.

PubMed

Motiani, Piryanka; Virtanen, Kirsi A; Motiani, Kumail K; Eskelinen, Joonas J; Middelbeek, Roeland J; Goodyear, Laurie J; Savolainen, Anna M; Kemppainen, Jukka; Jensen, Jørgen; Din, Mueez U; Saunavaara, Virva; Parkkola, Riitta; Löyttyniemi, Eliisa; Knuuti, Juhani; Nuutila, Pirjo; Kalliokoski, Kari K; Hannukainen, Jarna C

2017-10-01

To test the hypothesis that high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) improve brown adipose tissue (BAT) insulin sensitivity. Healthy middle-aged men (n = 18, age 47 years [95% confidence interval {CI} 49, 43], body mass index 25.3 kg/m 2 [95% CI 24.1-26.3], peak oxygen uptake (VO 2peak ) 34.8 mL/kg/min [95% CI 32.1, 37.4] ) were recruited and randomized into six HIIT or MICT sessions within 2 weeks. Insulin-stimulated glucose uptake was measured using 2-[ 18 F]flouro-2-deoxy-D-glucose positron-emission tomography in BAT, skeletal muscle, and abdominal and femoral subcutaneous and visceral white adipose tissue (WAT) depots before and after the training interventions. Training improved VO 2peak (P = .0005), insulin-stimulated glucose uptake into the quadriceps femoris muscle (P = .0009) and femoral subcutaneous WAT (P = .02) but not into BAT, with no difference between the training modes. Using pre-intervention BAT glucose uptake, we next stratified subjects into high BAT (>2.9 µmol/100 g/min; n = 6) or low BAT (<2.9 µmol/100 g/min; n = 12) groups. Interestingly, training decreased insulin-stimulated BAT glucose uptake in the high BAT group (4.0 [2.8, 5.5] vs 2.5 [1.7, 3.6]; training*BAT, P = .02), whereas there was no effect of training in the low BAT group (1.5 [1.2, 1.9] vs 1.6 [1.2, 2.0] µmol/100 g/min). Participants in the high BAT group had lower levels of inflammatory markers compared with those in the low BAT group. Participants with functionally active BAT have an improved metabolic profile compared with those with low BAT activity. Short-term exercise training decreased insulin-stimulated BAT glucose uptake in participants with active BAT, suggesting that training does not work as a potent stimulus for BAT activation. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Metabolic syndrome marks early risk for cognitive decline with APOE4 gene variation: A case study.

PubMed

Brown, Dawson; Gibas, Kelly J

2018-04-20

A vast amount of research has been done on the APOE4 genetic marker for Alzheimer's disease (AD), but its connection to metabolic processes associated with peripheral insulin resistance and cerebral glucose metabolism is still relatively unknown. The APOE4 allele is the strongest genetic risk factor for developing late-onset Alzheimer's disease, particularly in individuals who have inherited two copies of the gene (Zhao et al., 2017). In this case study, a 38 year old male with metabolic syndrome (MetS), the APOE4 gene, early stage memory problems and a family history of Alzheimer's Disease (AD) was placed on a ketogenic diet combined with high intensity interval training (HIIT) for 10 weeks. The primary intervention goal was reduce insulin defect, impaired cerebral and peripheral insulin signaling, associated with metabolic syndrome. Recent research demonstrates that insulin defect competes for space with APOE4 in brain cells, thus exacerbating amyloid pathology (Zhao et al., 2017). Primary biomarkers for metabolic syndrome were measured at baseline and after 10 weeks. The MoCA (Montreal Cognitive Assessment) was administered at baseline and after 10 weeks. The results were statistically significant. The HOMA-IR (homeostatic measure of insulin resistance) decreased by 59% from 4.3 to 1.8. The triglyceride/HDL ratio decreased by 77% from 14.7 to 3.4. Fasting triglycerides were reduced from 573 mg/dL to 167 mg/dL (71% reduction); VLDL decreased from 114.6 mg/dL to 33.4 mg/dL (71% decrease); and fasting insulin was reduced by 55% from 15.6 mU/L to 7.1 mU/L. The baseline MoCA score was 22/30; post treatment score was 30/30. If APOEE4 is the strongest genetic risk factor for developing late-onset Alzheimer's Disease, then implementing a ketogenic diet and high intensity exercise could essentially turn "off" the effects of this APOE4 gene earlier in life for prevention of future neurodegeneration. Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Third Exposure to a Reduced Carbohydrate Meal Lowers Evening Postprandial Insulin and GIP Responses and HOMA-IR Estimate of Insulin Resistance.

PubMed

Lin, Po-Ju; Borer, Katarina T

2016-01-01

Postprandial hyperinsulinemia, hyperglycemia, and insulin resistance increase the risk of type 2 diabetes (T2D) and cardiovascular disease mortality. Postprandial hyperinsulinemia and hyperglycemia also occur in metabolically healthy subjects consuming high-carbohydrate diets particularly after evening meals and when carbohydrate loads follow acute exercise. We hypothesized the involvement of dietary carbohydrate load, especially when timed after exercise, and mediation by the glucose-dependent insulinotropic peptide (GIP) in this phenomenon, as this incretin promotes insulin secretion after carbohydrate intake in insulin-sensitive, but not in insulin-resistant states. Four groups of eight metabolically healthy weight-matched postmenopausal women were provided with three isocaloric meals (a pre-trial meal and two meals during the trial day) containing either 30% or 60% carbohydrate, with and without two-hours of moderate-intensity exercise before the last two meals. Plasma glucose, insulin, glucagon, GIP, glucagon-like peptide 1 (GLP-1), free fatty acids (FFAs), and D-3-hydroxybutyrate concentrations were measured during 4-h postprandial periods and 3-h exercise periods, and their areas under the curve (AUCs) were analyzed by mixed-model ANOVA, and insulin resistance during fasting and meal tolerance tests within each diet was estimated using homeostasis-model assessment (HOMA-IR). The third low-carbohydrate meal, but not the high-carbohydrate meal, reduced: (1) evening insulin AUC by 39% without exercise and by 31% after exercise; (2) GIP AUC by 48% without exercise and by 45% after exercise, and (3) evening insulin resistance by 37% without exercise and by 24% after exercise. Pre-meal exercise did not alter insulin-, GIP- and HOMA-IR- lowering effects of low-carbohydrate diet, but exacerbated evening hyperglycemia. Evening postprandial insulin and GIP responses and insulin resistance declined by over 30% after three meals that limited daily carbohydrate intake to 30% compared to no such changes after three 60%-carbohydrate meals, an effect that was independent of pre-meal exercise. The parallel timing and magnitude of postprandial insulin and GIP changes suggest their dependence on a delayed intestinal adaptation to a low-carbohydrate diet. Pre-meal exercise exacerbated glucose intolerance with both diets most likely due to impairment of insulin signaling by pre-meal elevation of FFAs.

Endocrine abnormalities in critical care patients with moderate-to-severe head trauma: incidence, pattern and predisposing factors.

PubMed

Dimopoulou, Ioanna; Tsagarakis, Stylianos; Theodorakopoulou, Maria; Douka, Evangelia; Zervou, Maria; Kouyialis, Andreas T; Thalassinos, Nikolaos; Roussos, Charis

2004-06-01

To investigate the incidence and type of endocrine abnormalities in critical care patients with traumatic brain injury (TBI) and to examine their relationships to possible predisposing factors. Prospective study. General intensive care unit in a university hospital. Thirty-four TBI patients (27 men, 7 women), having a mean age of 37+/-16 years, were studied after weaning from mechanical ventilation. Baseline endocrine assessment was carried out by measuring cortisol, corticotropin, dehydroepiandrosterone sulfate, free thyroxine, thyrotropin (TSH), testosterone, oestradiol, follicle stimulating hormone (FSH), luteinizing hormone, prolactin, growth hormone and insulin-like growth factor I. Dynamic evaluation was performed by human corticotropin releasing hormone and growth hormone releasing hormone in all patients. Male patients underwent additional investigation with gonadotropin-releasing hormone. Severity of neurological derangement was graded according to Glasgow Coma Scale (GCS), Marshall Computerized Tomographic Classification and intracranial pressure (ICP) levels. Eighteen of the 34 patients (53%) had an abnormal result in at least one hormonal axis tested, with cortisol hyporesponsiveness and gonadal dysfunction being equally common, affecting 24% of patients. Endocrine abnormalities were associated with a higher brain CT-scan classification score ( p=0.02). The GCS on admission correlated positively with baseline FSH (r=0.37, p=0.03), peak FSH (r=0.41, p=0.03), testosterone (r=0.44, p=0.02) and TSH (r=0.39, p=0.03). There were no relations between ICP(max) and any baseline or dynamic hormone measurements. Patients with TBI receiving critical care show changes in their neuroendocrine responses, which depend upon clinical and radiological measures of head injury severity. Most common abnormalities include cortisol hyporesponsiveness and hypogonadism.

Using computers to enable self-management of aphasia therapy exercises for word finding: the patient and carer perspective.

PubMed

Palmer, Rebecca; Enderby, Pam; Paterson, Gail

2013-01-01

Speech and language therapy (SLT) for aphasia can be difficult to access in the later stages of stroke recovery, despite evidence of continued improvement with sufficient therapeutic intensity. Computerized aphasia therapy has been reported to be useful for independent language practice, providing new opportunities for continued rehabilitation. The success of this option depends on its acceptability to patients and carers. To investigate factors that affect the acceptability of independent home computerized aphasia therapy practice. An acceptability study of computerized therapy was carried out alongside a pilot randomized controlled trial of computer aphasia therapy versus usual care for people more than 6 months post-stroke. Following language assessment and computer exercise prescription by a speech and language therapist, participants practised three times a week for 5 months at home with monthly volunteer support. Semi-structured interviews were conducted with 14 participants who received the intervention and ten carers (n = 24). Questions from a topic guide were presented and answered using picture, gesture and written support. Interviews were audio recorded, transcribed verbatim and analysed thematically. Three research SLTs identified and cross-checked themes and subthemes emerging from the data. The key themes that emerged were benefits and disadvantages of computerized aphasia therapy, need for help and support, and comparisons with face-to-face therapy. The independence, flexibility and repetition afforded by the computer was viewed as beneficial and the personalized exercises motivated participants to practise. Participants and carers perceived improvements in word-finding and confidence-talking. Computer practice could cause fatigue and interference with other commitments. Support from carers or volunteers for motivation and technical assistance was seen as important. Although some participants preferred face-to-face therapy, using a computer for independent language practice was perceived to be an acceptable alternative. Independent computerized aphasia therapy is acceptable to stroke survivors. Acceptability can be maximized by tailoring exercises to personal interests of the individual, ensuring access to support and giving consideration to fatigue and life style when recommending practice schedules. © 2013 Royal College of Speech and Language Therapists.

Role of tDCS in potentiating poststroke computerized cognitive rehabilitation: Lessons learned from a case study.

PubMed

Leo, Antonino; De Luca, Rosario; Russo, Margherita; Naro, Antonino; Bramanti, Placido; Calabrò, Rocco S

2016-01-01

Cognitive impairment after stroke is quite common and can cause important disability with a relevant impact on quality of life. Cognitive rehabilitation (CR) and related assistive technology may improve functional outcomes. A 30-year-old woman came to our research institute for an intensive CR cycle following a right parieto-temporal stroke. Because the patient was in the chronic phase, we decided to use 3 different rehabilitative protocols: (a) traditional cognitive training (TCT), (b) computerized cognitive training (CCT), and (c) CCT combined with transcranial direct stimulation (CCT plus) with a 2-week interval separating each session. Cognitive and language deficits were investigated using an ad-hoc psychometric battery at baseline (T0), post-TCT (T1), post-CCT (T2), and post-CCT plus (T3). Our patient showed the best neuropsychological improvement, with regard to attention processes and language domain, after T3. Our data showed that CCT plus should be considered a promising tool in the treatment of poststroke neuropsychological deficits.

Measurement of myocardial perfusion and infarction size using computer-aided diagnosis system for myocardial contrast echocardiography.

PubMed

Du, Guo-Qing; Xue, Jing-Yi; Guo, Yanhui; Chen, Shuang; Du, Pei; Wu, Yan; Wang, Yu-Hang; Zong, Li-Qiu; Tian, Jia-Wei

2015-09-01

Proper evaluation of myocardial microvascular perfusion and assessment of infarct size is critical for clinicians. We have developed a novel computer-aided diagnosis (CAD) approach for myocardial contrast echocardiography (MCE) to measure myocardial perfusion and infarct size. Rabbits underwent 15 min of coronary occlusion followed by reperfusion (group I, n = 15) or 60 min of coronary occlusion followed by reperfusion (group II, n = 15). Myocardial contrast echocardiography was performed before and 7 d after ischemia/reperfusion, and images were analyzed with the CAD system on the basis of eliminating particle swarm optimization clustering analysis. The myocardium was quickly and accurately detected using contrast-enhanced images, myocardial perfusion was quantitatively calibrated and a color-coded map calibrated by contrast intensity and automatically produced by the CAD system was used to outline the infarction region. Calibrated contrast intensity was significantly lower in infarct regions than in non-infarct regions, allowing differentiation of abnormal and normal myocardial perfusion. Receiver operating characteristic curve analysis documented that -54-pixel contrast intensity was an optimal cutoff point for the identification of infarcted myocardium with a sensitivity of 95.45% and specificity of 87.50%. Infarct sizes obtained using myocardial perfusion defect analysis of original contrast images and the contrast intensity-based color-coded map in computerized images were compared with infarct sizes measured using triphenyltetrazolium chloride staining. Use of the proposed CAD approach provided observers with more information. The infarct sizes obtained with myocardial perfusion defect analysis, the contrast intensity-based color-coded map and triphenyltetrazolium chloride staining were 23.72 ± 8.41%, 21.77 ± 7.8% and 18.21 ± 4.40% (% left ventricle) respectively (p > 0.05), indicating that computerized myocardial contrast echocardiography can accurately measure infarct size. On the basis of the results, we believe the CAD method can quickly and automatically measure myocardial perfusion and infarct size and will, it is hoped, be very helpful in clinical therapeutics. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

The skeletal structure of insulin-like growth factor I-deficient mice

NASA Technical Reports Server (NTRS)

Bikle, D.; Majumdar, S.; Laib, A.; Powell-Braxton, L.; Rosen, C.; Beamer, W.; Nauman, E.; Leary, C.; Halloran, B.

2001-01-01

The importance of insulin-like growth factor I (IGF-I) for growth is well established. However, the lack of IGF-I on the skeleton has not been examined thoroughly. Therefore, we analyzed the structural properties of bone from mice rendered IGF-I deficient by homologous recombination (knockout [k/o]) using histomorphometry, peripheral quantitative computerized tomography (pQCT), and microcomputerized tomography (muCT). The k/o mice were 24% the size of their wild-type littermates at the time of study (4 months). The k/o tibias were 28% and L1 vertebrae were 26% the size of wild-type bones. Bone formation rates (BFR) of k/o tibias were 27% that of the wild-type littermates. The k/o bones responded normally to growth hormone (GH; 1.7-fold increase) and supranormally to IGF-I (5.2-fold increase) with respect to BFR. Cortical thickness of the proximal tibia was reduced 17% in the k/o mouse. However, trabecular bone volume (bone volume/total volume [BV/TV]) was increased 23% (male mice) and 88% (female mice) in the k/o mice compared with wild-type controls as a result of increased connectivity, increased number, and decreased spacing of the trabeculae. These changes were either less or not found in L1. Thus, lack of IGF-I leads to the development of a bone structure, which, although smaller, appears more compact.

Glucose regulation and cognitive function after bariatric surgery.

PubMed

Galioto, Rachel; Alosco, Michael L; Spitznagel, Mary Beth; Strain, Gladys; Devlin, Michael; Cohen, Ronald; Crosby, Ross D; Mitchell, James E; Gunstad, John

2015-01-01

Obesity is associated with cognitive impairment, and bariatric surgery has been shown to improve cognitive functioning. Rapid improvements in glycemic control are common after bariatric surgery and likely contribute to these cognitive gains. We examined whether improvements in glucose regulation are associated with better cognitive function following bariatric surgery. A total of 85 adult bariatric surgery patients underwent computerized cognitive testing and fasting blood draw for glucose, insulin, and glycated hemoglobin (HbA1c) at baseline and 12 months postoperatively. Significant improvements in both cognitive function and glycemic control were observed among patients. After controlling for baseline factors, 12-month homeostatic model assessment of insulin resistance HOMA-IR predicted 12-month digits backward (β = -.253, p < .05), switching of attention-A (β = .156, p < .05), and switching of attention-B (β = -.181, p < .05). Specifically, as HOMA-IR decreased over time, working memory, psychomotor speed, and cognitive flexibility improved. Decreases in HbA1c were not associated with postoperative cognitive improvements. After controlling for baseline cognitive test performance, changes in body mass index (BMI) were also not associated with 12-month cognitive function. Small effects of improved glycemic control on improved aspects of attention and executive function were observed following bariatric surgery among severely obese individuals. Future research is needed to identify the underlying mechanisms for the neurocognitive benefits of these procedures.

Factors associated with reaching or not reaching target HbA1c after initiation of basal or premixed insulin in patients with type 2 diabetes.

PubMed

Scheen, A J; Schmitt, H; Jiang, H H; Ivanyi, T

2017-02-01

To evaluate factors associated with reaching or not reaching target glycated haemoglobin (HbA 1c ) levels by analysing the respective contributions of fasting hyperglycaemia (FHG), also referred to as basal hyperglycaemia, vs postprandial hyperglycaemia (PHG) before and after initiation of a basal or premixed insulin regimen in patients with type 2 diabetes. This post-hoc analysis of insulin-naïve patients in the DURABLE study randomised to receive either insulin glargine or insulin lispro mix 25 evaluated the percentages of patients achieving a target HbA 1c of <7.0% (<53mmol/mol) per baseline HbA 1c quartiles, and the effect of each insulin regimen on the relative contributions of PHG and FHG to overall hyperglycaemia. Patients had comparable demographic characteristics and similar HbA 1c and FHG values at baseline in each HbA 1c quartile regardless of whether they reached the target HbA 1c . The higher the HbA 1c quartile, the greater was the decrease in HbA 1c , but also the smaller the percentage of patients achieving the target HbA 1c . HbA 1c and FHG decreased more in patients reaching the target, resulting in significantly lower values at endpoint in all baseline HbA 1c quartiles with either insulin treatment. Patients not achieving the target HbA 1c had slightly higher insulin doses, but lower total hypoglycaemia rates. Smaller decreases in FHG were associated with not reaching the target HbA 1c , suggesting a need to increase basal or premixed insulin doses to achieve targeted fasting plasma glucose and improve patient response before introducing more intensive prandial insulin regimens. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Acute exercise alters skeletal muscle mitochondrial respiration and H2O2 emission in response to hyperinsulinemic-euglycemic clamp in middle-aged obese men

PubMed Central

Trewin, Adam J.; Levinger, Itamar; Parker, Lewan; Shaw, Christopher S.; Serpiello, Fabio R.; Anderson, Mitchell J.; McConell, Glenn K.; Hare, David L.

2017-01-01

Obesity, sedentary lifestyle and aging are associated with mitochondrial dysfunction and impaired insulin sensitivity. Acute exercise increases insulin sensitivity in skeletal muscle; however, whether mitochondria are involved in these processes remains unclear. The aim of this study was to investigate the effects of insulin stimulation at rest and after acute exercise on skeletal muscle mitochondrial respiratory function (JO2) and hydrogen peroxide emission (JH2O2), and the associations with insulin sensitivity in obese, sedentary men. Nine men (means ± SD: 57 ± 6 years; BMI 33 ± 5 kg.m2) underwent hyperinsulinemic-euglycemic clamps in two separate trials 1–3 weeks apart: one under resting conditions, and another 1 hour after high-intensity exercise (4x4 min cycling at 95% HRpeak). Muscle biopsies were obtained at baseline, and pre/post clamp to measure JO2 with high-resolution respirometry and JH2O2 via Amplex UltraRed from permeabilized fibers. Post-exercise, both JO2 and JH2O2 during ADP stimulated state-3/OXPHOS respiration were lower compared to baseline (P<0.05), but not after subsequent insulin stimulation. JH2O2 was lower post-exercise and after subsequent insulin stimulation compared to insulin stimulation in the rest trial during succinate supported state-4/leak respiration (P<0.05). In contrast, JH2O2 increased during complex-I supported leak respiration with insulin after exercise compared with resting conditions (P<0.05). Resting insulin sensitivity and JH2O2 during complex-I leak respiration were positively correlated (r = 0.77, P<0.05). We conclude that in obese, older and sedentary men, acute exercise modifies skeletal muscle mitochondrial respiration and H2O2 emission responses to hyperinsulinemia in a respiratory state-specific manner, which may have implications for metabolic diseases involving insulin resistance. PMID:29161316

Metformin in gestational diabetes: An emerging contender

PubMed Central

Singh, Awadhesh Kumar; Singh, Ritu

2015-01-01

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance occurring first time during pregnancy. Its prevalence is simultaneously increasing with the global rise of diabesity. GDM commonly develops, when maternal glucose metabolism is unable to compensate for the progressive development of insulin resistance, arising primarily from the consistently rising diabetogenic placental hormones. It classically develops during the second or third trimester. Theoretically, insulin sensitizers should have been the ideal agent in its treatment, given the insulin resistance, the major culprit in its pathogenesis. Fortunately, majority of women can be treated satisfactorily with lifestyle modification, and approximately 20% requires more intensive treatment. For several decades, insulin has been the most reliable treatment strategy and the gold standard in GDM. Metformin is effective insulin sensitizing agent and an established first line drug in type 2 diabetes currently. As it crosses the placenta, a safety issue remains an obstacle and, therefore, metformin is currently not recommended in the treatment of GDM. Nevertheless, given the emerging clinically equivalent safety and efficacy data of metformin compared to insulin, it appears that it may perhaps open a rather new door in managing GDM. The aim of this review is to critically analyze, the safety and efficacy data of metformin regarding its use in GDM and pregnant mothers with polycystic ovarian disease, which has emerged in past decades. PMID:25729685

Short-term intensive insulin therapy could be the preferred option for new onset Type 2 diabetes mellitus patients with HbA1c > 9.

PubMed

Weng, Jianping

2017-10-01

Type 2 diabetes mellitus (T2DM) is a heterogeneous disease. Currently, the typical clinical therapeutic pathway for the disease consists of the stepwise addition of antihyperglycemic preparations over time, followed lastly by insulin therapy when functional β-cell capacity is severely deteriorated. Recognizing the complexity of disease management, personalized (precision) medicine approaches may enable the physician to tailor diabetes treatment based on HbA1c levels, body mass index (BMI), efficacy, risk of hypoglycemia, risk of weight gain, age, safety, cost, and even genetic characteristics. Although insulin therapy has traditionally been recommended as the last option in the sequential treatment algorithm of T2DM, it is notable that several guidelines and consensus statements suggest consideration of insulin as part of a first-line regimen. In the American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) comprehensive T2DM 2017 management algorithm, insulin is recommended for T2DM patients presenting with symptoms and an HbA1c >9.0%. In addition, the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) consensus statement recommends initial insulin therapy as an option when HbA1c ≥9%, and definite consideration with HbA1c ≥10-12%, and mentions that it may be possible to taper off insulin once initial glucotoxicity is reversed and to consider transfer to other types of non-insulin therapies. Based on accumulating evidence, an expert group has endorsed the concept of short-term intensive insulin (STII) therapy as an option for some patients with T2DM at the time of diagnosis. Notably, the latest Israeli guidelines suggest considering immediate, sometimes short-term, insulin treatment for patients with HbA1c >9% or with symptoms. It has been reported that nearly one-quarter (23%) of newly diagnosed T2DM patients in the US had an HbA1c ≥9.0% prior to initiation of treatment. For such patients, initiating insulin is difficult, although it has been almost 10 years since the ACE/AACE Diabetes Road Map suggested insulin therapy for treatment-naïve patients with high HbA1c. Lack of patient education resources in primary care and of provider knowledge as to approaches to insulin treatment (insulin initiation dosage, multiple daily injection or basal insulin supplement, insulin treatment duration) are major obstacles to selecting appropriately intensive but also timely therapy for newly diagnosed T2DM patients in clinical practice so as to minimize avoidable glycemic exposure. Treatment with STII early in the course of T2DM is of considerable interest. There is a wide range of evidence currently available supporting the use of STII therapy in newly diagnosed T2DM. For example, STII can quickly normalize glycemic control, improve β-cell function, restore first-phase insulin secretion, and even reduce glucagonemia in newly diagnosed T2DM, suggesting that it may provide unique capacity for modification of the natural process of diabetes. The largest and most robust clinical trial of STII therapy enrolled 382 newly diagnosed people with T2DM at nine centers in China and randomized them to either insulin (short-term continuous subcutaneous insulin infusion [CSII] or multiple daily injections [MDI]) or oral anti-hyperglycemic therapy. First-phase insulin secretion was increased in all three groups after 2 weeks of normoglycemia. Remission rates at 1 year were higher in the two insulin-treated groups (51.1% in the CSII group, 44.9% in the MDI group) than in the oral therapy group (26.7%). Furthermore, the increase in first-phase insulin response was maintained at 1 year in the two insulin-treated groups, but declined in the group allocated to oral medication (Fig. ). A beneficial effect of insulin therapy over oral anti-diabetic agents was also observed by Chen et al. [Figure: see text] A meta-analysis, including seven studies and 839 participants, further underscored the robustness of the evidence supporting STII therapy by showing that the proportion of patients in drug-free remission was 66.2% at 3 months, 58.9% at 6 months, 46.3% at 12 months, and 42.1% at 24 months. All but one study showed an improvement in β-cell function, as assessed by homeostatic model assessment of β-cell function (HOMA-B), and all but one study showed a decrease in insulin resistance, as assessed by homeostasis model assessment of insulin resistance (HOMA-IR). Therefore, STII has beneficial effects on both the fundamental pathophysiological mechanisms of T2DM (β-cell dysfunction and insulin resistance). Recent animal studies suggest a potential mechanism for such clinical benefits: β-cells dedifferentiate to endocrine progenitor-like cells during stress-induced hyperglycemia, and strictly normalizing blood glucose by insulin therapy could induce dedifferentiated cell redifferentiation to mature β-cells, and hence restoration of drug responsivity. In addition to its glucose-lowering activity, insulin may contribute to improved β-cell function by its antilipolytic, anti-inflammatory, and antiapoptotic effects. We recognized that not all newly diagnosed people with T2DM would experience improved β-cell function or achieve long-term remission following cessation of STII. It would be worthwhile to precisely identify the subpopulation more likely to benefit from this strategy. Previous studies have suggested that lower baseline fasting glucose, higher BMI, better early phase insulin secretion, and lower exogenous insulin requirements may be predictors of diabetes remission in newly diagnosed patients treated with STII therapy. A recent study demonstrated that a shorter duration of diabetes supplanted baseline HbA1c and β-cell function as an independent predictor of remission. In particular, diabetes duration <2 years predicted sustained remission, suggesting that the key determinant of inducing persistent drug-free diabetes remission with STII is early intervention. Although reluctance to initiate insulin treatment in T2DM is well described, it is interesting to see that when introduced early in the course of the disease as a short-term treatment, STII resulted in significant improvement in patient-reported quality of life and treatment satisfaction, demonstrating the patient acceptability of early insulin therapy. In our clinical experience, patients often request insulin resumption after a trial has ended because of the good clinical outcomes and the recognition that such treatment is much easier and better tolerated than expected. The pros and cons of STII therapy for new-onset T2DM patients with HbA1c >9%, based on current evidence and our understanding, are listed in Table . It is important that STII be considered an option at this early stage of the disease. Existing studies and clinical experience do indicate that this concept is very well received by patients and clinicians alike, especially when they realize that insulin only needs to be used for a few weeks, and that STII at that point in time does not necessarily require continuing long-term insulin therapy. Numerous public health, clinical efficacy and effectiveness, and cost-effectiveness questions need to be better understood before widespread adoption of this novel treatment regimen can be more endorsed. [Table: see text]. © 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Insulin during pregnancy, labour and delivery.

PubMed

de Valk, Harold W; Visser, Gerard H A

2011-02-01

Optimal glycaemic control is of the utmost importance to achieve the best possible outcome of a pregnancy complicated by diabetes. This holds for pregnancies in women with preconceptional type 1 or type 2 diabetes as well as for pregnancies complicated by gestational diabetes. Glycaemic control is conventionally expressed in the HbA1c value but the HbA1c value does not completely capture the complexity of glycaemic control. The daily glucose profile measured by the patients themselves through measurements performed in capillary blood obtained by finger stick provides valuable information needed to adjust insulin therapy. Hypoglycaemia is the major threat to the pregnant woman or the woman with tight glycaemic control in the run-up to pregnancy. Repetitive hypoglycaemia can lead to hypoglycaemia unawareness, which is reversible with prevention of hypoglycaemia. A delicate balance should be struck between preventing hyperglycaemia and hypoglycaemia. Insulin requirements are not uniform across the day: it is low during the night with a more or less pronounced rise at dawn, followed by a gradual decrease during the remainder of the day. A basal amount of insulin is needed to regulate the endogenous glucose production, short-acting insulin shots are needed to handle exogenous glucose loads. Insulin therapy means two choices: the type of insulin used and the method of insulin administration. Regarding the type of insulin, the choice is between human and analogue insulins. The analogue short-acting insulin aspart has been shown to be safe during pregnancy in a randomised trial and has received registration for this indication; the short-acting analogue insulin lispro has been shown to be safe in observational studies. No such information is available on the long-acting insulin analogues detemir and glargine and both are prescribed off-label with human long-acting insulin as obvious alternatives. Randomised trials have not been able to show superiority of continuous subcutaneous insulin administration (CSII (insulin pump)) over intensive insulin injection therapy (multiple-dose insulin (MDI)) on any maternal or foeto-neonatal end point. However, group sizes were far too small to allow assessment of superiority and issues such as manageability of the disease and quality of life were never assessed. These two issues are of major importance to patients. The first trimester is often the period of most hypoglycaemic events, and insulin therapy should be especially closely monitored and adjusted in this period. After midterm, insulin requirements increase. Continuous glucose monitoring can offer better insights into the glycaemic profile than self-monitoring of blood glucose levels by the patients but the place of these new monitoring techniques has yet to be established more clearly. Insulin therapy during labour means short-acting insulin adjusted to achieve glucose levels between 4 and 8 mmol l(-1) to prevent neonatal hypoglycaemia as much as possible. After delivery, glycaemic control must be relaxed to prevent hypoglycaemia, especially in women who breastfeed. Copyright © 2010 Elsevier Ltd. All rights reserved.

Twenty-four hour hyperinsulinemic-euglycemic clamp improves postoperative nitrogen balance only in low insulin sensitivity patients following cardiac surgery.

PubMed

Donatelli, F; Nafi, M; Di Nicola, M; Macchitelli, V; Mirabile, C; Lorini, L; Carli, F

2015-07-01

Critically ill patients often suffer from a protein catabolic state. The aim of this study was to demonstrate that nitrogen balance (NB) in cardiac patients admitted to the intensive care unit (ICU) is related to their insulin sensitivity level and that supraphysiologic doses of insulin can restore anabolism. Twenty-eight patients that were admitted to ICU in enteral and/or parenteral nutrition have been enrolled in this study. All patients received a standard nutrition protocol for at least 3 days before starting the study. These patients received either enteral or parenteral nutrition based on 1.4 kcal/kg/h and 1.1 g/kg/24 h of proteins. Participants were studied for three 24 h periods (P1 , P2 , and P3 ). Twenty-four hour NB was calculated from urinary urea nitrogen excretion, fixed protein and energy intake during each of the three periods (P1 , P2 , and P3 ). Simultaneous to P2, a 24 h hyperinsulinemic-euglycemic clamp (HEC) was performed to determine patients' insulin sensitivity (IS) or insulin resistance (IR), as well as the impact of high doses of insulin on NB. Nitrogen balance remained consistently positive in the IS group regardless of the clamp. In IR patients, NB was negative before the clamp and became positive during P2 and P3 . Insulin sensitivity improved during the HEC in IR patients (P < 0.001). A negative NB was found only in insulin resistant patients admitted to the ICU for more than 7 days. A 24-h period HEC improved NB in these patients. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Insulin Responsiveness in Metabolic Syndrome after Eight Weeks of Cycle Training

PubMed Central

Stuart, Charles A.; South, Mark A.; Lee, Michelle L.; McCurry, Melanie P.; Howell, Mary E. A.; Ramsey, Michael W.; Stone, Michael H.

2013-01-01

Introduction Insulin resistance in obesity is decreased after successful diet and exercise. Aerobic exercise training alone was evaluated as an intervention in subjects with the metabolic syndrome. Methods Eighteen non-diabetic, sedentary subjects, eleven with the metabolic syndrome, participated in eight weeks of increasing intensity stationary cycle training. Results Cycle training without weight loss did not change insulin resistance in metabolic syndrome subjects or sedentary control subjects. Maximal oxygen consumption (VO2max), activated muscle AMP-dependent kinase, and muscle mitochondrial marker ATP synthase all increased. Strength, lean body mass, and fat mass did not change. Activated mammalian target of rapamycin was not different after training. Training induced a shift in muscle fiber composition in both groups but in opposite directions. The proportion of 2x fibers decreased with a concomitant increase in 2a mixed fibers in the control subjects, but in metabolic syndrome, 2x fiber proportion increased and type 1 fibers decreased. Muscle fiber diameters increased in all three fiber types in metabolic syndrome subjects. Muscle insulin receptor expression increased in both groups and GLUT4 expression increased in the metabolic syndrome subjects. Excess phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser337 in metabolic syndrome muscle tended to increase further after training in spite of a decrease in total IRS-1. Conclusion In the absence of weight loss, cycle training of metabolic syndrome subjects resulted in enhanced mitochondrial biogenesis, and increased expression of insulin receptors and GLUT4 in muscle, but did not decrease the insulin resistance. The failure for the insulin signal to proceed past IRS-1 tyrosine phosphorylation may be related to excess serine phosphorylation at IRS-1 Ser337 and this is not ameliorated by eight weeks of endurance exercise training. PMID:23669880

Benefits of three-month continuous glucose monitoring for persons with diabetes using insulin pumps and sensors.

PubMed

Peterson, Karolina; Zapletalova, Jana; Kudlova, Pavla; Matuskova, Veronika; Bartek, Josef; Novotny, Dalibor; Chlup, Rudolf

2009-03-01

The latest Paradigm 722 insulin pump, Medtronic MiniMed, USA, enables daily reading of 288 interstitial fluid glucose concentrations determined by a sensor inserted into subcutaneous tissue; the sensor signals are transmitted into the insulin pump, enabling the patient to see real-time glucose concentration on the display and adapt further treatment. To assess the evolution of HbA1c over the course of a 3-month period in two cohorts of persons with type 1 (n=39) or type 2 (n=3) diabetes (PWD): 1) PWD on Paradigm 722 using sensors for continuous glucose monitoring (CGM group), 2) PWD on other types of insulin pumps performing intensive self-monitoring as before (3 to 6 times/d) on glucometer Linus, Wellion, Agamatrix (control group). Compliant PWDs using insulin pump with insulin aspart for several previous months were included in the study. Seventeen were put on Paradigm 722 with CGM and 25 were included in the control group. Paired t-test and the statistical program SPSS v.15.0 were used to analyze the data. There was no significant difference in age between the two groups (P=0.996), in diabetes duration (P=0.482) or in daily insulin dose (P=0.469). In the CGM group (but not in the control group) HbA1c/IFCC dropped from 6.98+/-0.43 % to 5.98+/-0.36 % (P=0.006) within 1 month and remained reduced. The use of the Paradigm 722 insulin pump with CGM resulted in significant improvement in HbA1c which appeared within one month and remained throughout the whole 3-month study period. No significant improvement in HbA1c was seen in the control group.

The effect of dietary fiber and other factors on insulin response: role in obesity.

PubMed

Ullrich, I H; Albrink, M J

1985-07-01

Epidemiologic evidence favors the hypothesis that obesity may result from the fiber-depleted diet of industrialized societies. Since hyperinsulinemia is a universal characteristic and perhaps causal of obesity, the possibility is considered that dietary factors causing excess insulin secretion might lead to obesity. Dietary glucose causes a slightly greater insulin rise than cooked starch containing an equal amount of carbohydrate, and high fiber starchy foods cause a much lesser insulin response than does glucose in solution. Doubling the dose of carbohydrate in a meal causes only a small increase in glucose response but a large increase in insulin response. Dietary fiber could act by displacing some of the carbohydrate that would normally be absorbable in the small intestine, or could translocate the carbohydrate to a point lower in the intestinal tract where less effect on insulin secretion would be observed. Evidence is presented that a higher fiber diet is associated with a higher concentration of fasting circulating free fatty acids, a lesser post-cibal decrease in circulating free fatty acids and triglycerides and less chronic increase in fasting triglycerides than a low fiber diet. These differences are associated with a lesser insulin response to high fiber meals. The extreme fluctuations between the fed and fasted states seen with low fiber diets are thus dampened by high fiber diets. The less complete inhibition of lipolysis during the fed state, and more intense lipolysis during fasting, suggested by the above data, might tend to prevent obesity. The mechanisms of the lesser insulin response to high rather than low fiber meals are not known, but the possibility that dietary fiber decreases the GIP response is considered.

Differential response between diabetes and stress-induced hyperglycaemia to algorithmic use of detemir and flexible mealtime aspart among stable postcardiac surgery patients requiring intravenous insulin.

PubMed

Dungan, K; Hall, C; Schuster, D; Osei, K

2011-12-01

To determine whether an insulin algorithm could be used in a similar manner in the setting of diabetes and stress hyperglycaemia following cessation of intravenous (IV) insulin after cardiac surgery. Subjects who were clinically stable, requiring ≥ 1 unit/h of IV insulin 48 h after surgery, were randomized to once daily detemir at 50, 65 or 80% of IV insulin requirements and received aspart according to carbohydrate intake. Diabetes was defined as any history of diabetes or preoperative HbA1c 6.5%. The morning glucose in patients with diabetes was 143 mg/dl (n = 61) vs. 124 mg/dl in those with stress hyperglycaemia (n = 21,p = 0.05) on day 1 and 127 vs. 110 mg/dl over 72 h (p = 0.01). This was unaffected by adjustment for initial dosing group. At 72 h, 56% of patients with stress hyperglycaemia reached AM (80-130 mg/dl) and 87% reached overall (80-180 mg/dl) glucose targets, compared to 90 and 100% of patients with stress hyperglycaemia, respectively. There was no difference in hypoglycaemia in patients with stress hyperglycaemia or diabetes. The percentage of patients with diabetes receiving insulin was 46% on admission and 77% at discharge, compared to 0 and 42% of patients with stress hyperglycaemia. Following cardiac surgery, patients with stress hyperglycaemia may be converted from IV insulin to detemir with a 50% conversion factor, while patients with diabetes may require a higher conversion factor. Stress hyperglycaemia may be prolonged; the intensity and duration of insulin therapy required for optimal outcomes warrants further examination. © 2011 Blackwell Publishing Ltd.

Insulin responsiveness in metabolic syndrome after eight weeks of cycle training.

PubMed

Stuart, Charles A; South, Mark A; Lee, Michelle L; McCurry, Melanie P; Howell, Mary E A; Ramsey, Michael W; Stone, Michael H

2013-11-01

Insulin resistance in obesity is decreased after successful diet and exercise. Aerobic exercise training alone was evaluated as an intervention in subjects with the metabolic syndrome. Eighteen nondiabetic, sedentary subjects, 11 with the metabolic syndrome, participated in 8 wk of increasing intensity stationary cycle training. Cycle training without weight loss did not change insulin resistance in metabolic syndrome subjects or sedentary control subjects. Maximal oxygen consumption (V·O 2max), activated muscle AMP-dependent kinase, and muscle mitochondrial marker ATP synthase all increased. Strength, lean body mass, and fat mass did not change. The activated mammalian target of rapamycin was not different after training. Training induced a shift in muscle fiber composition in both groups but in opposite directions. The proportion of type 2× fibers decreased with a concomitant increase in type 2a mixed fibers in the control subjects, but in metabolic syndrome, type 2× fiber proportion increased and type 1 fibers decreased. Muscle fiber diameters increased in all three fiber types in metabolic syndrome subjects. Muscle insulin receptor expression increased in both groups, and GLUT4 expression increased in the metabolic syndrome subjects. The excess phosphorylation of insulin receptor substrate 1 (IRS-1) at Ser337 in metabolic syndrome muscle tended to increase further after training in spite of a decrease in total IRS-1. In the absence of weight loss, the cycle training of metabolic syndrome subjects resulted in enhanced mitochondrial biogenesis and increased the expression of insulin receptors and GLUT4 in muscle but did not decrease the insulin resistance. The failure for the insulin signal to proceed past IRS-1 tyrosine phosphorylation may be related to excess serine phosphorylation at IRS-1 Ser337, and this is not ameliorated by 8 wk of endurance exercise training.

The diabetes drug liraglutide reverses cognitive impairment in mice and attenuates insulin receptor and synaptic pathology in a non-human primate model of Alzheimer's disease.

PubMed

Batista, Andre F; Forny-Germano, Leticia; Clarke, Julia R; Lyra E Silva, Natalia M; Brito-Moreira, Jordano; Boehnke, Susan E; Winterborn, Andrew; Coe, Brian C; Lablans, Ann; Vital, Juliana F; Marques, Suelen A; Martinez, Ana Mb; Gralle, Matthias; Holscher, Christian; Klein, William L; Houzel, Jean-Christophe; Ferreira, Sergio T; Munoz, Douglas P; De Felice, Fernanda G

2018-05-01

Alzheimer's disease (AD) is a devastating neurological disorder that still lacks an effective treatment, and this has stimulated an intense pursuit of disease-modifying therapeutics. Given the increasingly recognized link between AD and defective brain insulin signaling, we investigated the actions of liraglutide, a glucagon-like peptide-1 (GLP-1) analog marketed for treatment of type 2 diabetes, in experimental models of AD. Insulin receptor pathology is an important feature of AD brains that impairs the neuroprotective actions of central insulin signaling. Here, we show that liraglutide prevented the loss of brain insulin receptors and synapses, and reversed memory impairment induced by AD-linked amyloid-β oligomers (AβOs) in mice. Using hippocampal neuronal cultures, we determined that the mechanism of neuroprotection by liraglutide involves activation of the PKA signaling pathway. Infusion of AβOs into the lateral cerebral ventricle of non-human primates (NHPs) led to marked loss of insulin receptors and synapses in brain regions related to memory. Systemic treatment of NHPs with liraglutide provided partial protection, decreasing AD-related insulin receptor, synaptic, and tau pathology in specific brain regions. Synapse damage and elimination are amongst the earliest known pathological changes and the best correlates of memory impairment in AD. The results illuminate mechanisms of neuroprotection by liraglutide, and indicate that GLP-1 receptor activation may be harnessed to protect brain insulin receptors and synapses in AD. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Effects of antihypertensive drugs losartan and levamlodipine besylate on insulin resistance in patients with essential hypertension combined with isolated impaired fasting glucose.

PubMed

Xiao, Wei-Yin; Ning, Ning; Tan, Ming-Hong; Jiang, Xue-Shu; Zhou, Liang; Liu, Ling; Yi, Dong; Wei, Ping

2016-05-01

The objective of this study was to observe the antihypertensive effect of losartan and levamlodipine besylate on insulin resistance in patients with essential hypertension (EH) combined with isolated impaired fasting glucose (i-IFG). Patients (n=244) were randomly assigned to losartan potassium tablets (50-100 mg per day) or levamlodipine besylate tablets (2.5-5.0 mg per day) for intensive antihypertensive treatment with no lifestyle interventions for 3 years. The changes in fasting plasma glucose, fasting insulin (FINS) and insulin sensitivity index (ISI) from before to after treatment were observed. Blood pressure (BP) in each group was significantly reduced by treatment (P<0.05). After 12 months of treatment, the FINS level in the losartan potassium group was significantly decreased and ISI was significantly increased compared with before treatment (P<0.05) and compared with the levamlodipine besylate group (P<0.05). After 24 and 36 months of treatment, FINS was significantly decreased and ISI was significantly improved in both groups compared with baseline (P<0.05), and there was no difference between the groups (P>0.05). The incidence of new-onset diabetes mellitus was not significantly different between two groups. The antihypertensive effect of losartan and levamlodipine besylate could amoliorate insulin resistance in patients with EH combined with i-IFG. The improvement of insulin resistance by losartan potassium at 12 months might be better than that by levamlodipine besylate; however, after 24 and 36 months of follow-up, both agents significantly alleviated insulin resistance. These results suggest that the effects of these two drugs on insulin resistance are not significantly different.

Effect of exercise intensity on abdominal fat loss during calorie restriction in overweight and obese postmenopausal women: a randomized, controlled trial1234

PubMed Central

Nicklas, Barbara J; Wang, Xuewen; You, Tongjian; Lyles, Mary F; Demons, Jamehl; Easter, Linda; Berry, Michael J; Lenchik, Leon; Carr, J Jeffrey

2009-01-01

Background: Exercise intensity may affect the selective loss of abdominal adipose tissue. Objective: This study showed whether aerobic exercise intensity affects the loss of abdominal fat and improvement in cardiovascular disease risk factors under conditions of equal energy deficit in women with abdominal obesity. Design: This was a randomized trial in 112 overweight and obese [body mass index (in kg/m2): 25–40; waist circumference >88 cm], postmenopausal women assigned to one of three 20-wk interventions of equal energy deficit: calorie restriction (CR only), CR plus moderate-intensity aerobic exercise (CR + moderate-intensity), or CR plus vigorous-intensity exercise (CR + vigorous-intensity). The diet was a controlled program of underfeeding during which meals were provided at individual calorie levels (≈400 kcal/d). Exercise (3 d/wk) involved treadmill walking at an intensity of 45–50% (moderate-intensity) or 70–75% (vigorous-intensity) of heart rate reserve. The primary outcome was abdominal visceral fat volume. Results: Average weight loss for the 95 women who completed the study was 12.1 kg (±4.5 kg) and was not significantly different across groups. Maximal oxygen uptake (O2max) increased more in the CR + vigorous-intensity group than in either of the other groups (P < 0.05). The CR-only group lost relatively more lean mass than did either exercise group (P < 0.05). All groups showed similar decreases in abdominal visceral fat (≈25%; P < 0.001 for all). However, changes in visceral fat were inversely related to increases in O2max (P < 0.01). Changes in lipids, fasting glucose or insulin, and 2-h glucose and insulin areas during the oral-glucose-tolerance test were similar across treatment groups. Conclusion: With a similar amount of total weight loss, lean mass is preserved, but there is not a preferential loss of abdominal fat when either moderate- or vigorous-intensity aerobic exercise is performed during caloric restriction. This trial was registered at clinicaltrials.gov as NCT00664729. PMID:19211823

Cost calculation for a flash glucose monitoring system for UK adults with type 1 diabetes mellitus receiving intensive insulin treatment.

PubMed

Hellmund, Richard; Weitgasser, Raimund; Blissett, Deirdre

2018-04-01

To estimate the costs associated with a flash glucose monitoring system as a replacement for routine self-monitoring of blood glucose (SMBG) in patients with type 1 diabetes mellitus (T1DM) using intensive insulin, from a UK National Health Service (NHS) perspective. The base-case cost calculation was created using the maximum frequency of glucose monitoring recommended by the 2015 National Institute for Health and Care Excellence guidelines (4-10 tests per day). Scenario analyses considered SMBG at the frequency observed in the IMPACT clinical trial (5.6 tests per day) and at the frequency of flash monitoring observed in a real-world analysis (16 tests per day). A further scenario included potential costs associated with severe hypoglycaemia. In the base case, the annual cost per patient using flash monitoring was £234 (19%) lower compared with routine SMBG (10 tests per day). In scenario analyses, the annual cost per patient of flash monitoring compared with 5.6 and 16 SMBG tests per day was £296 higher and £957 lower, respectively. The annual cost of severe hypoglycaemia for flash monitoring users was estimated to be £221 per patient, compared with £428 for routine SMBG users (based on 5.6 tests/day), corresponding to a reduction in costs of £207. The flash monitoring system has a modest impact on glucose monitoring costs for the UK NHS for patients with T1DM using intensive insulin. For people requiring frequent tests, flash monitoring may be cost saving, especially when taking into account potential reductions in the rate of severe hypoglycaemia. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Calorically restricted diets decrease PCSK9 in overweight adolescents.

PubMed

Levenson, A E; Milliren, C E; Biddinger, S B; Ebbeling, C B; Feldman, H A; Ludwig, D S; de Ferranti, S D

2017-04-01

Nutritional therapy is the first line approach to treatment of hyperlipidemia in childhood. Proprotein convertase subtilisin kexin type 9 (PCSK9) is a key regulator of plasma cholesterol levels and a target of novel lipid-lowering pharmacotherapies. We examined the effects of an intensive nutritional intervention on PCSK9 levels in overweight adolescents with cardiovascular disease (CVD) risk factors. Twenty seven obese and overweight adolescents with CVD risk factors were assigned to either a low fat or low glycemic load diet. During an 8-week "Intensive Phase," assigned meals were delivered to the home, and all participants received weekly in-person home nutrition counseling and phone calls. The subjects then underwent a 4-month "Maintenance Phase" without food provision and with no in-person contact. Anthropometric measurements, laboratory data, and serum PCSK9 protein levels were measured at baseline, 8 weeks, and 6 months. PCSK9 decreased by 16.5% at 8 weeks (201.2 ± 56.3 vs 165.6 ± 58.4 ng/mL; p < 0.001); PCSK9 levels returned to baseline levels at 6 months, after the Maintenance Phase. Change in PCSK9 was associated with change in fasting insulin, HOMA-IR, and AUC insulin, independent of weight loss. PCSK9 decreased in youth participating in an intensive dietary intervention. Change in HOMA-IR was associated with change in PCSK9, independent of weight loss, suggesting an important relationship with insulin sensitivity. ClinicalTrials.gov Identifier: NCT01080339. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Creatine kinase and alpha-actin mRNA levels decrease in diabetic rat hearts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Popovich, B.; Barrieux, A.; Dillmann, W.H.

1987-05-01

Diabetic cardiomyopathy is associated with cardiac atrophy and isoenzyme redistribution. To determine if tissue specific changes occur in mRNAs coding for ..cap alpha..-actin and creatine kinase (CK), they performed RNA blot analysis. Total ventricular RNA from control (C) and 4 wk old diabetic (D) rats were hybridized with /sup 32/P cDNA probes for ..cap alpha..-actin and CK. A tissue independent cDNA probe, CHOA was also used. Signal intensity was quantified by photodensitometry. D CK mRNA was 47 +/- 16% lower in D vs C. Insulin increases CK mRNA by 20% at 1.5 hs, and completely reverses the deficit after 4more » wks. D ..cap alpha..-actin mRNA is 66 +/- 18% lower in D vs C. Insulin normalized ..cap alpha..-actin mRNA by 5 hs. CHOA mRNA is unchanged in D vs C, but D + insulin CHOA mRNA is 30 +/- 2% lower than C. In rats with diabetic cardiomyopathy, muscle specific CK and ..cap alpha..-actin mRNAs are decreased. Insulin treatment reverses these changes.« less

Dietary glucose regulates yeast consumption in adult Drosophila males

PubMed Central

Lebreton, Sébastien; Witzgall, Peter; Olsson, Marie; Becher, Paul G.

2014-01-01

The adjustment of feeding behavior in response to hunger and satiety contributes to homeostatic regulation in animals. The fruit fly Drosophila melanogaster feeds on yeasts growing on overripe fruit, providing nutrients required for adult survival, reproduction and larval growth. Here, we present data on how the nutritional value of food affects subsequent yeast consumption in Drosophila adult males. After a period of starvation, flies showed intensive yeast consumption. In comparison, flies stopped feeding after having access to a nutritive cornmeal diet. Interestingly, dietary glucose was equally efficient as the complex cornmeal diet. In contrast, flies fed with sucralose, a non-metabolizable sweetener, behaved as if they were starved. The adipokinetic hormone and insulin-like peptides regulate metabolic processes in insects. We did not find any effect of the adipokinetic hormone pathway on this modulation. Instead, the insulin pathway was involved in these changes. Flies lacking the insulin receptor (InR) did not respond to nutrient deprivation by increasing yeast consumption. Together these results show the importance of insulin in the regulation of yeast consumption in response to starvation in adult D. melanogaster males. PMID:25566097

Dietary glucose regulates yeast consumption in adult Drosophila males.

PubMed

Lebreton, Sébastien; Witzgall, Peter; Olsson, Marie; Becher, Paul G

2014-01-01

The adjustment of feeding behavior in response to hunger and satiety contributes to homeostatic regulation in animals. The fruit fly Drosophila melanogaster feeds on yeasts growing on overripe fruit, providing nutrients required for adult survival, reproduction and larval growth. Here, we present data on how the nutritional value of food affects subsequent yeast consumption in Drosophila adult males. After a period of starvation, flies showed intensive yeast consumption. In comparison, flies stopped feeding after having access to a nutritive cornmeal diet. Interestingly, dietary glucose was equally efficient as the complex cornmeal diet. In contrast, flies fed with sucralose, a non-metabolizable sweetener, behaved as if they were starved. The adipokinetic hormone and insulin-like peptides regulate metabolic processes in insects. We did not find any effect of the adipokinetic hormone pathway on this modulation. Instead, the insulin pathway was involved in these changes. Flies lacking the insulin receptor (InR) did not respond to nutrient deprivation by increasing yeast consumption. Together these results show the importance of insulin in the regulation of yeast consumption in response to starvation in adult D. melanogaster males.

Insulin regimens and insulin adjustments in diabetic children, adolescents and young adults: personal experience.

PubMed

Dorchy, H

2000-12-01

Because recent multicenter studies, even those performed in developed countries without financial restriction, show that treatment of childhood diabetes is inadequate in general and that levels of glycated hemoglobin (HbA1c) are very different, diabetes treatment teams should individually explore the reasons for failure, without any prejudice or bias. The "good" treatment is signed by good HbA1c associated with good quality of life, and is not necessarily exportable without adjustment to the local way of life. HbA1c must be under 7%, if the upper normal limit is about 6%, which is possible, in our experience, even in diabetic children and adolescents. Our "recipes" are summarized. The number of daily insulin injections, 2 or 4, by itself does not necessarily give better results, but the 4-injection regimen allows greater freedom, taking into account that the proper insulin adjustment is difficult before adolescence. Successful glycemic control in young patients depends mainly on the quality and intensity of diabetes education. Any dogmatism must be avoided; only the objective result is important.

Ultrasound Stimulation of Insulin Release from Pancreatic Beta Cells

NASA Astrophysics Data System (ADS)

Suarez Castellanos, Ivan M.

Type 2 diabetes (T2D) mellitus is a complex metabolic disease that has reached epidemic proportions in the United States and around the world. Controlling T2D is often difficult as pharmacological management routinely requires complex therapy with multiple medications, and loses its effectiveness over time. The objective of this dissertation was to explore a novel, non-pharmacological approach that utilizes the application of ultrasound energy to stimulate insulin release. Our experiments have focused on determination of effectiveness and safety of ultrasound application in stimulation of insulin release from the pancreatic beta cells. Our results showed that ultrasound treatment, applied at frequencies of 800 kHz and 1 MHz and intensities of 0.5 W/cm2 and 1 W/cm2, did not produce any significant effects on cell viability compared to sham group as assessed with trypan blue dye exclusion test and MTT cytotoxicity assay. ELISA quantification of insulin release from beta cells resulting from ultrasound treatment showed clinically-significant amounts of released insulin as compared to sham-treated beta cells. Carbon fiber amperometry detection of secretory events from dopamine-loaded beta cells treated with ultrasound showed that release of secretory content could be temporally controlled by careful selection of ultrasound parameters. Both ELISA and amperometry experiments demonstrated that ultrasound-stimulated insulin release is a calcium-dependent process, potentially mediated by the mechanical effects of ultrasound. This study demonstrated that therapeutic ultrasound is a technique capable of stimulating the release of insulin from pancreatic beta cells in a safe, effective and controlled manner.

Treating type 1 diabetes: from strategies for insulin delivery to dual hormonal control

PubMed Central

McCall, A. L.; Farhy, L. S.

2014-01-01

Type 1 diabetes is a disorder where slow destruction of pancreatic β-cells occurs through autoimmune mechanisms. The result is a progressive and ultimately complete lack of endogenous insulin. Due to β-cell lack, secondary abnormalities in glucagon and likely in incretins occur. These multiple hormonal abnormalities cause metabolic instability and extreme glycemic variability, which is the primary phenotype. As the disease progresses patients often develop hypoglycemia unawareness and defects in their counterregulatory defenses. Intensive insulin therapy may thus lead to 3-fold excess of severe hypoglycemia and severely hinder the effective and safe control of hyperglycemia. The main goal of the therapy for type 1 diabetes has long been physiological mimicry of normal insulin secretion based on monitoring which requires considerable effort and understanding of the underlying physiology. Attainment of this goal is challenged by the nature of the disease and our current lack of means to fully repair the abnormal endocrine pancreas interactive functions. As a result, various insulin preparations has been developed to partially compensate for the inability to deliver timely exogenous insulin directly to the portal/intrapancreatic circulation. It remains an ongoing task to identify the ideal routes and regimens of their delivery and potentially that of other hormones to restore the deficient and disordered hormonal environment of the pancreas to achieve a near normal metabolic state. Several recent technological advances help addressing these goals, including the rapid progress in insulin pumps, continuous glucose sensors, and ultimately the artificial pancreas closed-loop technology and the recent start of dual-hormone therapies. PMID:23732369

A unified Hyperglycemia and Diabetic ketoacidosis (DKA) insulin infusion protocol based on an Excel algorithm and implemented via Electronic Medical Record (EMR) in Intensive Care Units.

PubMed

Gupta, Deepashree; Kirn, Meredith; Jamkhana, Zafar A; Lee, Richard; Albert, Stewart G; Rollins, Kimberly M

To assess the efficacy of a unified hyperglycemia and diabetic ketoacidosis (DKA) insulin infusion protocol (IIP), based on an Excel algorithm and implemented as an electronic order set, in achieving glycemic targets and minimizing hypoglycemia. An IIP was instituted in medical and surgical intensive care units for post-cardiac surgery (PCS) and other stress hyperglycemia (SH), diabetes hyperglycemia (DH), and DKA. The IIP initiated therapeutic insulin rates at elevated blood glucose (BG), and decreased insulin when target range was achieved. A convenience sample (n=62) was studied; 20 PCS, 15 with DH, 9 with SH, 8 with diabetes on vasopressors, 7 with diabetes on glucocorticoids and 3 with DKA were assessed. The protocol maintained BG at 144±24.7mg/dL for PCS and 167±36mg/dL for patients with diabetes mellitus. It maintained acceptable target range (ATR) (100mg/dL-180mg/dL) 89% of the time for PCS and 67% of the time for patients with diabetes mellitus. There were no measurements of BG<70mg/dL. The protocol lowered the BG at a similar rate and time period in those with diabetes, DKA and those with or without vasopressors or glucocorticoids. To determine long-term efficacy, a retrospective review of Point of Care (POC) RALS (Remote Automated Data System) BG data 2 years post implementation demonstrated fewer episodes of hypoglycemia<70mg/dL and hyperglycemia>240mg/dL and more BG values within ATR. This IIP maintained ATR without hypoglycemia for patients in the ICU setting without requiring complex nursing calculations. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Effectiveness of a Predictive Algorithm in the Prevention of Exercise-Induced Hypoglycemia in Type 1 Diabetes.

PubMed

Abraham, Mary B; Davey, Raymond; O'Grady, Michael J; Ly, Trang T; Paramalingam, Nirubasini; Fournier, Paul A; Roy, Anirban; Grosman, Benyamin; Kurtz, Natalie; Fairchild, Janice M; King, Bruce R; Ambler, Geoffrey R; Cameron, Fergus; Jones, Timothy W; Davis, Elizabeth A

2016-09-01

Sensor-augmented pump therapy (SAPT) with a predictive algorithm to suspend insulin delivery has the potential to reduce hypoglycemia, a known obstacle in improving physical activity in patients with type 1 diabetes. The predictive low glucose management (PLGM) system employs a predictive algorithm that suspends basal insulin when hypoglycemia is predicted. The aim of this study was to determine the efficacy of this algorithm in the prevention of exercise-induced hypoglycemia under in-clinic conditions. This was a randomized, controlled cross-over study in which 25 participants performed 2 consecutive sessions of 30 min of moderate-intensity exercise while on basal continuous subcutaneous insulin infusion on 2 study days: a control day with SAPT alone and an intervention day with SAPT and PLGM. The predictive algorithm suspended basal insulin when sensor glucose was predicted to be below the preset hypoglycemic threshold in 30 min. We tested preset hypoglycemic thresholds of 70 and 80 mg/dL. The primary outcome was the requirement for hypoglycemia treatment (symptomatic hypoglycemia with plasma glucose <63 mg/dL or plasma glucose <50 mg/dL) and was compared in both control and intervention arms. Results were analyzed in 19 participants. In the intervention arm with both thresholds, only 6 participants (32%) required treatment for hypoglycemia compared with 17 participants (89%) in the control arm (P = 0.003). In participants with a 2-h pump suspension on intervention days, the plasma glucose was 84 ± 12 and 99 ± 24 mg/dL at thresholds of 70 and 80 mg/dL, respectively. SAPT with PLGM reduced the need for hypoglycemia treatment after moderate-intensity exercise in an in-clinic setting.

Plasma chemerin in young untrained men: association with cardio-metabolic traits and physical performance, and response to intensive interval training.

PubMed

Ouerghi, Nejmeddine; Fradj, Mohamed Kacem Ben; Khammassi, Marwa; Feki, Moncef; Kaabachi, Naziha; Bouassida, Anissa

2017-02-01

Chemerin is an adipose tissue-derived adipokine thought to decrease insulin sensitivity and increase cardiometabolic risk. This study aimed to assess the association of chemerin with cardiometabolic risk and physical performance and examine its response to high-intensity interval training (HIIT). Eighteen young men have been applied a HIIT program during 8 weeks. Plasma chemerin together with several cardiometabolic factors and physical performance indices were determined before and after the training program. Plasma chemerin and insulin were assessed using immunoenzymatic methods. The homeostasis model assessment (HOMA-IR) index was calculated as an estimate of insulin resistance. Basal plasma chemerin was positively correlated with body mass index (r=0.782, p<0.001), body fat (r=0.767, p<0.001), total (r=0.686, p=0.002) and LDL (r=0.587, p=0.010) cholesterol, triglycerides (r=0.775, p<0.001), HOMA-IR (r=0.673, p=0.002) and C-reactive protein (r=0.765, p<0.001). With regards to physical performance, chemerin was negatively correlated with maximal oxygen uptake (r=-0.572, p=0.013) and squat jump (r=-0.627, p=0.005), but positively related to 10-m sprint (r=0.716, p=0.001) and 30-m sprint (r=0.667, p=0.002) times. HIIT program resulted in significant improvements in body composition, plasma lipids and insulin sensitivity. However, no significant change was detected for plasma chemerin in response to HIIT (134±50.7 ng/mL vs. 137±51.9 ng/mL, p=0.750). Basal plasma chemerin is associated with cardiometabolic health and physical performance in young men. Following HIIT, cardiometabolic health and physical performance had improved, but no significant change had occurred for plasma chemerin.

The effects of a 2 week modified high intensity interval training program on the homeostatic model of insulin resistance (HOMA-IR) in adults with type 2 diabetes.

PubMed

Shaban, N; Kenno, K A; Milne, K J

2014-04-01

High intensity interval training (HIIT) induces similar metabolic adaptations to traditional steady state aerobic exercise training. Until recently, most HIIT studies have examined maximum efforts in healthy populations. The current study aimed to examine the effects of a 2 week modified HIIT program on the homeostatic model of insulin resistance (HOMA-IR) in individuals with type 2 diabetes (T2D). It was hypothesized that HIIT would improve HOMA-IR. Nine individuals with T2D (age=40.2±9.7 y; BMI=33.9±5.3; fasting plasma glucose [FPG]=8.7±2.9 mmol/L; HbA1C=7.3±1.2%; [mean±SD]) performed 6 individualized training sessions of HIIT (4x30 seconds at 100% of estimated maximum workload followed by 4 minutes of active rest) over 2 weeks. HOMA-IR was calculated from FPG and serum insulin and compared against a prior 2 week baseline period. Blood glucose was reduced immediately after each HIIT session (P<0.05). Anthropometrics, FPG, serum insulin, and HOMA-IR were unchanged after training. However, 6 of the 9 individuals exhibited reduced HOMA-IR values after the training period and there was a significant negative correlation between HOMA-IR value prior to training and change in HOMA-IR after HIIT. These observations tend to support the positive health benefits of HITT for individuals with T2D reported in recently published data using a modified HIIT protocol. However, they suggest that the magnitude of the disease should be assessed when examining the effects of exercise interventions in individuals with T2D.

Intensive insulin treatment increases donor site wound protein synthesis in burn patients

PubMed Central

Tuvdendorj, Demidmaa; Zhang, Xiao-Jun; Chinkes, David L.; Aarsland, Asle; Kulp, Gabriela A.; Jeschke, Marc G.; Herndon, David N.

2013-01-01

Background In the treatment of burns, patients’ own skin is the preferred material to cover burn wounds, resulting in the need to create a donor site wound. Enhancement of healing of the donor site wound would be beneficial in burn patients. Insulin, an anabolic agent, is routinely used to treat hyperglycemia after injury. We investigated whether intensive insulin treatment (INS) increases fractional synthesis rate (FSR) of the donor site wound protein and decreases the length of hospitalization normalized for total body surface area burned (LOS/TBSA). Methods FSR of the donor site wound protein was measured in pediatric patients randomized to control (CNT) (n = 13) and INS (n = 10) treatments. Depending on the postoperative day when the tracer study was done studies were divided into “Early” (days < 5) and “Late” (days >=5) periods. Results FSR of the donor site wound protein was greater in the INS group at the “Early” period of wound healing (CNT vs. INS, 8.2±3.8 vs. 13.1±6.9 %/day, p: < 0.05); but not at the “Late” (CNT vs. INS, 19.7±4.6 vs. 16.6±4.0 %/day, p > 0.05). Despite these differences LOS/TBSA was not decreased in the INS group. Correlation analyses demonstrated that independently of the treatment regimen FSR positively correlated (p < 0.05) with time post creation of the donor site and negatively correlated (p < 0.05) with LOS/TBSA. Conclusions Insulin treatment increased FSR of the donor site wound protein in the early period of wound healing; FSR correlated with LOS/TBSA independently of the treatment regimen. PMID:21236451

Exercise Training Reduces Intrathoracic Fat Regardless of Defective Glucose Tolerance.

PubMed

Honkala, Sanna M; Motiani, Kumail K; Eskelinen, Jari-Joonas; Savolainen, Anna; Saunavaara, Virva; Virtanen, Kirsi A; Löyttyniemi, Eliisa; Kapanen, Jukka; Knuuti, Juhani; Kalliokoski, Kari K; Hannukainen, Jarna C

2017-07-01

Epicardial (EAT) and pericardial (PAT) fat masses and myocardial triglyceride content (MTC) are enlarged in obesity and insulin resistance. We studied whether the high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) similarly decrease ectopic fat in and around the heart and whether the decrease is similar in healthy subjects and subjects with defective glucose tolerance (DGT). A total of 28 healthy men (body mass index = 20.7-30.0 kg·m, age = 40-55 yr) and 16 men with DGT (body mass index = 23.8-33.5 kg·m, age = 43-53 yr) were randomized into HIIT and MICT interventions for 2 wk. EAT and PAT were determined by computed tomography and MTC by H-MRS. At baseline, DGT subjects had impaired aerobic capacity and insulin sensitivity and higher levels of whole body fat, visceral fat, PAT, and EAT (P < 0.05, all) compared with healthy subjects. In the whole group, HIIT increased aerobic capacity (HIIT = 6%, MICT = 0.3%; time × training P = 0.007) and tended to improve insulin sensitivity (HIIT = 24%, MICT = 8%) as well as reduce MTC (HIIT = -42%, MICT = +23%) (time × training P = 0.06, both) more efficiently compared with MICT, and without differences in the training response between the healthy and the DGT subjects. However, both training modes decreased EAT (-5%) and PAT (-6%) fat (time P < 0.05) and not differently between the healthy and the DGT subjects. Whole body fat, visceral fat, PAT, and EAT masses are enlarged in DGT. Both HIIT and MICT effectively reduce EAT and PAT in healthy and DGT subjects, whereas HIIT seems to be superior as regards improving aerobic capacity, whole-body insulin sensitivity, and MTC.

Defining the Adipose Tissue Proteome of Dairy Cows to Reveal Biomarkers Related to Peripartum Insulin Resistance and Metabolic Status.

PubMed

Zachut, Maya

2015-07-02

Adipose tissue is a central regulator of metabolism in dairy cows; however, little is known about the association between various proteins in adipose tissue and the metabolic status of peripartum cows. Therefore, the objectives were to (1) examine total protein expression in adipose tissue of dairy cows and (2) identify biomarkers in adipose that are linked to insulin resistance and to cows' metabolic status. Adipose tissue biopsies were obtained from eight multiparous cows at -17 and +4 days relative to parturition. Proteins were analyzed by intensity-based, label-free, quantitative shotgun proteomics (nanoLC-MS/MS). Cows were divided into groups with insulin-resistant (IR) and insulin-sensitive (IS) adipose according to protein kinase B phosphorylation following insulin stimulation. Cows with IR adipose lost more body weight postpartum compared with IS cows. Differential expression of 143 out of 586 proteins was detected in prepartum versus postpartum adipose. Comparing IR to IS adipose revealed differential expression of 18.9% of the proteins; those related to lipolysis (hormone-sensitive lipase, perilipin, monoglycerol lipase) were increased in IR adipose. In conclusion, we found novel biomarkers related to IR in adipose and to metabolic status that could be used to characterize high-yielding dairy cows that are better adapted to peripartum metabolic stress.

Amino group of salicylic acid exhibits enhanced inhibitory potential against insulin amyloid fibrillation with protective aptitude toward amyloid induced cytotoxicity.

PubMed

Zaman, Masihuz; Khan, Mohsin Vahid; Zakariya, Syed Mohammad; Nusrat, Saima; Meeran, Syed Mustapha; Alam, Parvez; Ajmal, Mohammad Rehan; Wahiduzzaman, Wahiduzzaman; Shahein, Yasser E; Abouelella, Amira M; Khan, Rizwan Hasan

2018-05-01

Protein misfolding and aggregation lead to amyloid generation that in turn may induce cell membrane disruption and leads to cell apoptosis. In an effort to prevent or treat amyloidogenesis, large number of studies has been paying attention on breakthrough of amyloid inhibitors. In the present work, we aim to access the effect of two drugs, that is, acetylsalicylic acid and 5-amino salicylic acid on insulin amyloids by using various biophysical, imaging, cell viability assay, and computational approaches. We established that both drugs reduce the turbidity, light scattering and fluorescence intensity of amyloid indicator dye thioflavin T. Premixing of drugs with insulin inhibited the nucleation phase and inhibitory potential was boosted by increasing the concentration of the drug. Moreover, addition of drugs at the studied concentrations attenuated the insulin fibril induced cytotoxicity in breast cancer cell line MDA-MB-231. Our results highlight the amino group of salicylic acid exhibited enhanced inhibitory effects on insulin fibrillation in comparison to acetyl group. It may be due to presence of amino group that helps it to prolong the nucleation phase with strong binding as well as disruption of aromatic and hydrophobic stacking that plays a key role in amyloid progression. © 2017 Wiley Periodicals, Inc.

Diabetic management in high risk patients (pregnancy, insulin pumps).

PubMed

Vanhaverbeke, G; Mertens, A; Mathieu, C

2004-01-01

During the past decades our understanding about the clinical impact of diabetes has changed. We now know for certain that a good (read : near normal) glycemic control is necessary to prevent chronic complications of this disease in women regardless of the type of diabetes. Pregnancy is a specific situation whereby a "near normal" control is wanted not only for the patient but also for the fetus. Several studies have shown a correlation beween glycemic control and complications of pregnancy. Reaching optimal glycemic control is mandatory even before the pregnancy starts, considering the time window of occurance of the severe foetal congenital malformations (first weeks of pregnancy). The role of pre-conception care is emphasized. Optimal control in type 1 and type 2 diabetic patients can best be reached through intensive insulin therapy, but reaching normoglycemia is mainly limited by the occurence of hypoglycemia. The introduction of the new insulin analogues is an important step in our arsenal to achieve control using multiple daily insulin injections, but Novorapid and Lantus have not yet been approved for use in pregnancy. Insulin pumps are often used in pregnant patients, allowing an even better glycemic control with less hypoglycemia. An absolute requirement for CSII therapy to be successful is patient education and motivation by an experienced team.

Endothelial function and its relationship to leptin, homocysteine, and insulin resistance in lean and overweight eumenorrheic women and PCOS patients: a pilot study.

PubMed

Mancini, Fulvia; Cianciosi, Arianna; Reggiani, Giulio Marchesini; Facchinetti, Fabio; Battaglia, Cesare; de Aloysio, Domenico

2009-06-01

To verify if patients with polycystic ovarian syndrome (PCOS), have an increased cardiovascular risk compared with healthy controls. Prospective case-control study. University-based practice. Twenty eumenorrheic controls (ten lean [group A] and ten overweight [group B]) and 24 PCOS women (14 lean [group C] and ten overweight [group D]). Cardiovascular risk markers and hormonal parameters were assessed. Androgens, fasting glucose, insulin, leptin, fibrinogen, homocysteine, endothelin-1 and flow-mediated dilatation of the brachial artery were measured to investigate their relationship to weight and to PCOS. The brachial artery diameter and the pulsatility index, after the reactive hyperemia, showed in group A the most intense vasodilatation compared with the other groups. Homocysteine levels did not differ among the groups. Endothelin-1 was significantly higher in group A compared with groups B and D. Leptin was significantly lower in groups A and C compared with groups B and D. Insulin resistance was higher in groups B and D. Group A had significantly higher glucose-insulin ratio compared with all of the other groups; group C had significantly higher glucose-insulin ratio only compared with group D. Weight and PCOS are two independent variables affecting the endothelial function.

Effect of moderate- and high-intensity acute exercise on appetite in obese individuals.

PubMed

Martins, Catia; Stensvold, Dorthe; Finlayson, Graham; Holst, Jens; Wisloff, Ulrik; Kulseng, Bård; Morgan, Linda; King, Neil A

2015-01-01

The effect of acute exercise, and exercise intensity, on appetite control in obese individuals requires further study. The aim of this study was to compare the effects of acute isocaloric bouts (250 kcal) of high-intensity intermittent cycling (HIIC) and moderate-intensity continuous cycling (MICC) or short-duration HIIC (S-HIIC) (125 kcal) and a resting control condition on the appetite hormone responses, subjective feelings of appetite, energy intake (EI), and food reward in overweight/obese individuals. This study is a randomized crossover study on 12 overweight/obese volunteers. Participants were assigned to the control, MICC, HIIC, and S-HIIC conditions, 1 wk apart, in a counterbalanced order. Exercise was performed 1 h after a standard breakfast. An ad libitum test lunch was served 3 h after breakfast. Fasting/postprandial plasma samples of insulin, acylated ghrelin, polypeptide YY3-36, and glucagon-like peptide 1 and subjective feelings of appetite were measured every 30 min for 3 h. Nutrient and taste preferences were measured at the beginning and end of each condition using the Leeds Food Preference Questionnaire. Insulin levels were significantly reduced, and glucagon-like peptide 1 levels significantly increased during all exercise bouts compared with those during rest. Acylated ghrelin plasma levels were lower in the MICC and HIIC, but not in S-HIIC, compared with those in control. There were no significant differences for polypeptide YY3-36 plasma levels, hunger or fullness ratings, EI, or food reward. Our findings suggest that, in overweight/obese individuals, isocaloric bouts of moderate- or high-intensity exercise lead to a similar appetite response. This strengthens previous findings in normal-weight individuals that acute exercise, even at high intensity, does not induce any known physiological adaptation that would lead to increased EI.

Effectiveness of early intensive therapy on β-cell preservation in type 1 diabetes.

PubMed

Buckingham, Bruce; Beck, Roy W; Ruedy, Katrina J; Cheng, Peiyao; Kollman, Craig; Weinzimer, Stuart A; DiMeglio, Linda A; Bremer, Andrew A; Slover, Robert; Tamborlane, William V

2013-12-01

To assess effectiveness of inpatient hybrid closed-loop control (HCLC) followed by outpatient sensor-augmented pump (SAP) therapy initiated within 7 days of diagnosis of type 1 diabetes on the preservation of β-cell function at 1 year. Sixty-eight individuals (mean age 13.3 ± 5.7 years; 35% female, 92% Caucasian) were randomized to HCLC followed by SAP therapy (intensive group; N = 48) or to the usual-care group treated with multiple daily injections or insulin pump therapy (N = 20). Primary outcome was C-peptide concentrations during mixed-meal tolerance tests at 12 months. Intensive-group participants initiated HCLC a median of 6 days after diagnosis for a median duration of 71.3 h, during which median participant mean glucose concentration was 140 mg/dL (interquartile range 134-153 mg/dL). During outpatient SAP, continuous glucose monitor (CGM) use decreased over time, and at 12 months, only 33% of intensive participants averaged sensor use ≥6 days/week. In the usual-care group, insulin pump and CGM use were initiated prior to 12 months by 15 and 5 participants, respectively. Mean HbA1c levels were similar in both groups throughout the study. At 12 months, the geometric mean (95% CI) of C-peptide area under the curve was 0.43 (0.34-0.52) pmol/mL in the intensive group and 0.52 (0.32-0.75) pmol/mL in the usual-care group (P = 0.49). Thirty-seven (79%) intensive and 16 (80%) usual-care participants had a peak C-peptide concentration ≥0.2 pmol/mL (P = 0.30). In new-onset type 1 diabetes, HCLC followed by SAP therapy did not provide benefit in preserving β-cell function compared with current standards of care.

Intermediary Variables and Algorithm Parameters for an Electronic Algorithm for Intravenous Insulin Infusion

PubMed Central

Braithwaite, Susan S.; Godara, Hemant; Song, Julie; Cairns, Bruce A.; Jones, Samuel W.; Umpierrez, Guillermo E.

2009-01-01

Background Algorithms for intravenous insulin infusion may assign the infusion rate (IR) by a two-step process. First, the previous insulin infusion rate (IRprevious) and the rate of change of blood glucose (BG) from the previous iteration of the algorithm are used to estimate the maintenance rate (MR) of insulin infusion. Second, the insulin IR for the next iteration (IRnext) is assigned to be commensurate with the MR and the distance of the current blood glucose (BGcurrent) from target. With use of a specific set of algorithm parameter values, a family of iso-MR curves is created, each giving IR as a function of MR and BG. Method To test the feasibility of estimating MR from the IRprevious and the previous rate of change of BG, historical hyperglycemic data points were used to compute the “maintenance rate cross step next estimate” (MRcsne). Historical cases had been treated with intravenous insulin infusion using a tabular protocol that estimated MR according to column-change rules. The mean IR on historical stable intervals (MRtrue), an estimate of the biologic value of MR, was compared to MRcsne during the hyperglycemic iteration immediately preceding the stable interval. Hypothetically calculated MRcsne-dependent IRnext was compared to IRnext assigned historically. An expanded theory of an algorithm is developed mathematically. Practical recommendations for computerization are proposed. Results The MRtrue determined on each of 30 stable intervals and the MRcsne during the immediately preceding hyperglycemic iteration differed, having medians with interquartile ranges 2.7 (1.2–3.7) and 3.2 (1.5–4.6) units/h, respectively. However, these estimates of MR were strongly correlated (R2 = 0.88). During hyperglycemia at 941 time points the IRnext assigned historically and the hypothetically calculated MRcsne-dependent IRnext differed, having medians with interquartile ranges 4.0 (3.0–6.0) and 4.6 (3.0–6.8) units/h, respectively, but these paired values again were correlated (R2 = 0.87). This article describes a programmable algorithm for intravenous insulin infusion. The fundamental equation of the algorithm gives the relationship among IR; the biologic parameter MR; and two variables expressing an instantaneous rate of change of BG, one of which must be zero at any given point in time and the other positive, negative, or zero, namely the rate of change of BG from below target (rate of ascent) and the rate of change of BG from above target (rate of descent). In addition to user-definable parameters, three special algorithm parameters discoverable in nature are described: the maximum rate of the spontaneous ascent of blood glucose during nonhypoglycemia, the glucose per daily dose of insulin exogenously mediated, and the MR at given patient time points. User-assignable parameters will facilitate adaptation to different patient populations. Conclusions An algorithm is described that estimates MR prior to the attainment of euglycemia and computes MR-dependent values for IRnext. Design features address glycemic variability, promote safety with respect to hypoglycemia, and define a method for specifying glycemic targets that are allowed to differ according to patient condition. PMID:20144334

Dipeptidyl peptidase-4 inhibitors or sodium glucose co-transporter-2 inhibitors as an add-on to insulin therapy: A comparative review

PubMed Central

Singh, Awadhesh Kumar; Singh, Ritu

2016-01-01

The gradual decline in β-cell function is inevitable in type 2 diabetes mellitus and therefore, substantial proportions of patients require insulin subsequently, in order to achieve optimal glucose control. While weight gain, hypoglycemia, and fluid retention especially during dose intensification is a known limitation to insulin therapy, these adverse effects also reduce patient satisfaction and treatment adherence. It is also possible that the benefits of intensive control achieved by insulin therapy, perhaps get nullified by the weight gain and hypoglycemia. In addition, improvement in plasma glucose or glycated hemoglobin (HbA1c) itself is associated with weight gain. Notably, studies have already suggested that reduction in body weight by ~3–5%, may allow a significantly better glycemic control. Thus, a class of drugs, which can reduce HbA1c effectively, yet are weight neutral or preferably reduce body weight, could be the most sought out strategy as an add-on therapy to insulin. While sulfonylureas (SUs) are associated with weight gain and hypoglycemia, pioglitazone increases body weight and fluid retention. Moreover, SUs are not recommended once premix or prandial insulin is commenced. The addition of newer agents, such as glucagon-like peptide-1 receptor agonist to insulin certainly appears to be an effective tool in reducing both HbA1c and body weight as is evident across the studies; however, this approach incurs an additional injection as well as cost. Dipeptidyl peptidase-4 inhibitors (DPP-4I) and sodium-glucose co-transporter-2 inhibitors (SGLT-2I) are other exciting options, as an add-on to insulin therapy primarily because these are oral drugs and do not possess any intrinsic potential of hypoglycemia. Furthermore, these are either weight neutral or induce significant weight loss. This review article aims to comparatively analyze the safety and efficacy of DPP-4I and SGLT-2I, as an add-on therapy to insulin. PMID:26904466

Insulin Pump and Continuous Glucose Monitor Initiation in Hospitalized Patients with Type 2 Diabetes Mellitus.

PubMed

Levitt, David L; Spanakis, Elias K; Ryan, Kathleen A; Silver, Kristi D

2018-01-01

Insulin pumps and continuous glucose monitoring (CGM) are commonly used by patients with diabetes mellitus in the outpatient setting. The efficacy and safety of initiating inpatient insulin pumps and CGM in the nonintensive care unit setting is unknown. In a prospective pilot study, inpatients with type 2 diabetes were randomized to receive standard subcutaneous basal-bolus insulin and blinded CGM (group 1, n = 5), insulin pump and blinded CGM (group 2, n = 6), or insulin pump and nonblinded CGM (group 3, n = 5). Feasibility, glycemic control, and patient satisfaction were evaluated among groups. Group 1 had lower mean capillary glucose levels, 144.5 ± 19.5 mg/dL, compared with groups 2 and 3, 191.5 ± 52.3 and 182.7 ± 59.9 mg/dL (P 1 vs. 2+3  = 0.05). CGM detected 19 hypoglycemic episodes (glucose <70 mg/dL) among all treatment groups, compared with 12 episodes detected by capillary testing, although not statistically significant. No significant differences were found for the total daily dose of insulin or percentage of time spent below target glucose range (<90 mg/dL), in target glucose range (90-180 mg/dL), or above target glucose range (>180 mg/dL). On the Diabetes Treatment Satisfaction Questionnaire-Change, group 3 reported increased hyperglycemia and decreased hypoglycemia frequency compared with the other two groups, although the differences did not reach statistical significance. Insulin pump and CGM initiation are feasible during hospitalization, although they are labor intensive. Although insulin pump initiation may not lead to improved glycemic control, there is a trend toward CGM detecting a greater number of hypoglycemic episodes. Larger studies are needed to determine whether use of this technology can lower inpatient morbidity and mortality.

Coordinated Basal–Bolus Infusion for Tighter Postprandial Glucose Control in Insulin Pump Therapy

PubMed Central

Bondia, Jorge; Dassau, Eyal; Zisser, Howard; Calm, Remei; Vehí, Josep; Jovanovič, Lois; Doyle, Francis J.

2009-01-01

Background Basal and bolus insulin determination in intensive insulin therapy for type 1 diabetes mellitus (T1DM) are currently considered independently of each other. A new strategy that coordinates basal and bolus insulin infusion to cope with postprandial glycemia in pump therapy is proposed. Superior performance of this new strategy is demonstrated through a formal analysis of attainable performances in an in silico study. Methods The set inversion via interval analysis algorithm has been applied to obtain the feasible set of basal and bolus doses that, for a given meal, mathematically guarantee a postprandial response fulfilling the International Diabetes Federation (IDF) guidelines (i.e., no hypoglycemia and 2 h postprandial glucose below 140 mg/dl). Hypoglycemia has been defined as a glucose value below 70 mg/dl. A 5 h time horizon has been considered for a 70 kg in silico T1DM subject consuming meals in the range of 30 to 80 g of carbohydrates. Results The computed feasible sets demonstrate that current separated basal/bolus strategy dramatically limits the attainable performance. For a nominal basal of 0.8 IU/h leading to a basal glucose of approximately 100 mg/dl, IDF guidelines cannot be fulfilled for meals greater than 50 g of carbohydrates, independent of the bolus insulin computed. However, coordinating the basal and bolus insulin delivery can achieve this. A decrement of basal insulin during the postprandial period is required together with an increase in bolus insulin, in appropriate percentages, which is meal dependent. After 3 h, basal insulin can be restored to its nominal value. Conclusions The new strategy meets IDF guidelines in a typical day, contrary to the standard basal/bolus strategy, yielding a mean 2 h postprandial glucose reduction of 36.4 mg/dl without late hypoglycemia. The application of interval analysis for the computation of feasible sets is demonstrated to be a powerful tool for the analysis of attainable performance in glucose control. PMID:20046653

Diabetes and cardiovascular disease: pathophysiology of a life-threatening epidemic.

PubMed

King, R J; Grant, P J

2016-05-01

Diabetes is associated with the development of premature cardiovascular disease (CVD), which relates to the clustering of risk factors such as dyslipidaemia, hypertension, obesity and hyperglycaemia in the presence of insulin resistance. In addition, diabetes is associated with an inflammatory and pro-thrombotic environment, exacerbating the development of atherothrombosis. Insulin resistance and hyperglycaemia both contribute to the development of endothelial cell dysfunction and increased oxidative stress, culminating in accelerated atherosclerosis. Clot formation and function are also directly affected by insulin resistance and hyperglycaemia, with increased levels of coagulation factors and anti-fibrinolytic proteins and a fibrin network that is more resistant to lysis, coupled with increased platelet activation.It is well recognised that the intensification of glycaemic control leads to a reduction in microvascular complications in type 1 and type 2 diabetes; however, the same is less clear with macrovascular disease. Several randomised studies have attempted to address the effect of short-, medium- and long-term glycaemic control on cardiovascular outcomes, with mixed results. The overall interpretation of these trials suggests that intensive glycaemic control in patients with a relatively short duration of diabetes, without very poor control and with no CVD, might be safe and associated with fewer cardiovascular events.This review will summarise the effects of hyperglycaemia on the development of atherothrombosis and examine key cardiovascular outcome trials following intensive glucose control.

Validation of an electronic surveillance system for acute lung injury.

PubMed

Herasevich, Vitaly; Yilmaz, Murat; Khan, Hasrat; Hubmayr, Rolf D; Gajic, Ognjen

2009-06-01

Early detection of acute lung injury (ALI) is essential for timely implementation of evidence-based therapies and enrollment into clinical trials. We aimed to determine the accuracy of computerized syndrome surveillance for detection of ALI in hospitalized patients and compare it with routine clinical assessment. Using a near-real time copy of the electronic medical records, we developed and validated a custom ALI electronic alert (ALI "sniffer") based on the European-American Consensus Conference Definition and compared its performance against provider-derived documentation. A total of 3,795 consecutive critically ill patients admitted to nine multidisciplinary intensive care units (ICUs) of a tertiary care teaching institution were included. ALI developed in 325 patients and was recognized by bedside clinicians in only 86 (26.5%). Under-recognition of ALI was associated with not implementing protective mechanical ventilation (median tidal volumes of 9.2 vs. 8.0 ml/kg predicted body weight, P < 0.001). ALI "sniffer" demonstrated excellent sensitivity of 96% (95% CI 94-98) and moderate specificity of 89% (95% CI 88-90) with a positive predictive value ranging from 24% (95% CI 13-40) in the heart-lung transplant ICU to 64% (95% CI 55-71) in the medical ICU. The computerized surveillance system accurately identifies critically ill patients who develop ALI syndrome. Since the lack of ALI recognition is a barrier to the timely implementation of best practices and enrollment into research studies, computerized syndrome surveillance could be a useful tool to enhance patient safety and clinical research.

Computerized assessment of placental calcification post-ultrasound: a novel software tool.

PubMed

Moran, M; Higgins, M; Zombori, G; Ryan, J; McAuliffe, F M

2013-05-01

Placental calcification is associated with an increased risk of perinatal morbidity and mortality. The subjectivity of current ultrasound methods of assessment of placental calcification indicates that a more objective method is required. The aim of this study was to correlate the percentage of calcification defined by the clinician using a new software tool for calculating the extent of placental calcification with traditional ultrasound methods and with pregnancy outcome. Ninety placental images were individually assessed. An upper threshold was defined, based on high intensity, to quantify calcification within the placenta. Output metrics were then produced including the overall percentage of calcification with respect to the total number of pixels within the region of interest. The results were correlated with traditional ultrasound methods of assessment of placental calcification and with pregnancy outcome. The results demonstrate a significant correlation between placental calcification, as defined using the software, and traditional methods of Grannum grading of placental calcification. Whilst correlation with perinatal outcome and cord pH was not significant as a result of small numbers, patients with placental calcification assessed using the computerized software at the upper quartile had higher rates of poor perinatal outcome when compared with those at the lower quartile (8/22 (36%) vs 3/23 (13%); P = 0.069). These results suggest that this computerized software tool has the potential to become an alternative method of assessing placental calcification. Copyright © 2012 ISUOG. Published by John Wiley & Sons Ltd.

Parameters of glucose metabolism and the aging brain: a magnetization transfer imaging study of brain macro- and micro-structure in older adults without diabetes.

PubMed

Akintola, Abimbola A; van den Berg, Annette; Altmann-Schneider, Irmhild; Jansen, Steffy W; van Buchem, Mark A; Slagboom, P Eline; Westendorp, Rudi G; van Heemst, Diana; van der Grond, Jeroen

2015-08-01

Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain MRI was used to detect macro-structural damage (atrophy, white matter hyper-intensities, infarcts and/or micro-bleeds) and magnetization transfer imaging (MTI) to detect loss of micro-structural homogeneity that remains otherwise invisible on conventional MRI. Macro-structurally, higher fasted glucose was significantly associated with white matter atrophy (P = 0.028). Micro-structurally, decreased magnetization transfer ratio (MTR) peak height in gray matter was associated with higher fasted insulin (P = 0.010), AUCinsulin (P = 0.001), insulinogenic index (P = 0.008) and lower HOMA-IS index (P < 0.001). Similar significant associations were found for white matter. Thus, while higher glucose was associated with macro-structural damage, impaired insulin action was associated more strongly with reduced micro-structural brain parenchymal homogeneity. These findings offer some insight into the association between different parameters of glucose metabolism (impairment of which is characteristic of diabetes mellitus) and brain aging.

Effects of intravitreal insulin and insulin signaling cascade inhibitors on emmetropization in the chick

PubMed Central

Penha, Alexandra Marcha; Burkhardt, Eva; Schaeffel, Frank

2012-01-01

Purpose Intravitreal insulin has been shown to be a powerful stimulator of myopia in chickens, in particular if the retinal image is degraded or defocused. In most tissues, the insulin receptor activates two main signaling pathways: a) the mitogen-activated protein kinase (MAPK) cascade (e.g., mitogen-activated protein kinasem kinase [MEK] and extracellular regulated kinase [ERK]) and b) the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. In the current study, insulin was injected, and these pathways were separately inhibited to determine which is activated when the retinal image is defocused by spectacle lenses. Methods Chicks were treated with either +7 D, −7 D, or no lenses. They were intravitreally injected with insulin, the MEK inhibitor U0126, the PI3K inhibitor Ly294002, or a combination of insulin and one of the inhibitors. Refractions and ocular dimension were measured at the beginning and after four days of treatment. The retinal proteins of the chicks were measured with western blots after 2 h and four days of treatment. Incubation occurred with anti-Akt1, anti-Erk1/2, anti-phospho-AktThr308, and anti-phospho-Erk1/2(Thr202/Tyr204) antibodies, and the ratio between the relative intensity of the phospho-form and the total-form was calculated. Results Chicks wearing positive lenses and injected with saline and with PI3K inhibitor compensated for the imposed defocus and became hyperopic. Insulin injections and insulin plus PI3K inhibitor injections prevented lens-induced hyperopia, whereas the MEK inhibitor alone and insulin plus MEK inhibitor had no effect. Obviously, the MEK inhibitor suppressed the effect of insulin on eye growth in the plus lens–treated animals. Chicks treated with negative lenses and injected with insulin, or with insulin plus MEK inhibitor, overcompensated for the imposed defocus. This effect of insulin was not detected in eyes injected with PI3K inhibitor plus insulin, suggesting that the PI3K inhibitor suppressed the effects of insulin in minus lens–treated animals. Insulin increased the ratio of phospho-Akt/total-Akt in animals with normal visual exposure but even more so in chicks wearing plus or minus lenses. The increase was blocked by simultaneous PI3K inhibitor injections in control eyes but not in lens-treated eyes. Insulin also increased the ratio of phospho-ERK/total-ERK in animals with normal visual exposure and in animals wearing positive lenses, compared to U0126- and Ly294002-injected eyes. In contrast, no significant activation of the MEK/ERK pathway was observed in the negative lens–treated animals. Conclusions Intravitreal insulin promoted axial eye growth and stimulated both signaling pathways. The PI3K/Akt pathway was activated in control and plus and minus lens–treated eyes, but the MEK/ERK pathway was activated only with positive lenses or no lenses. With negative lenses, insulin did not stimulate the MEK/ERK signaling cascade. Independent of the pathway stimulated after insulin binding, the effect on insulin was always the same: an increase in eye growth. PMID:23112573

Effects of intravitreal insulin and insulin signaling cascade inhibitors on emmetropization in the chick.

PubMed

Penha, Alexandra Marcha; Burkhardt, Eva; Schaeffel, Frank; Feldkaemper, Marita P

2012-01-01

Intravitreal insulin has been shown to be a powerful stimulator of myopia in chickens, in particular if the retinal image is degraded or defocused. In most tissues, the insulin receptor activates two main signaling pathways: a) the mitogen-activated protein kinase (MAPK) cascade (e.g., mitogen-activated protein kinasem kinase [MEK] and extracellular regulated kinase [ERK]) and b) the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. In the current study, insulin was injected, and these pathways were separately inhibited to determine which is activated when the retinal image is defocused by spectacle lenses. Chicks were treated with either +7 D, -7 D, or no lenses. They were intravitreally injected with insulin, the MEK inhibitor U0126, the PI3K inhibitor Ly294002, or a combination of insulin and one of the inhibitors. Refractions and ocular dimension were measured at the beginning and after four days of treatment. The retinal proteins of the chicks were measured with western blots after 2 h and four days of treatment. Incubation occurred with anti-Akt1, anti-Erk1/2, anti-phospho-Akt(Thr308), and anti-phospho-Erk1/2((Thr202/Tyr204)) antibodies, and the ratio between the relative intensity of the phospho-form and the total-form was calculated. Chicks wearing positive lenses and injected with saline and with PI3K inhibitor compensated for the imposed defocus and became hyperopic. Insulin injections and insulin plus PI3K inhibitor injections prevented lens-induced hyperopia, whereas the MEK inhibitor alone and insulin plus MEK inhibitor had no effect. Obviously, the MEK inhibitor suppressed the effect of insulin on eye growth in the plus lens-treated animals. Chicks treated with negative lenses and injected with insulin, or with insulin plus MEK inhibitor, overcompensated for the imposed defocus. This effect of insulin was not detected in eyes injected with PI3K inhibitor plus insulin, suggesting that the PI3K inhibitor suppressed the effects of insulin in minus lens-treated animals. Insulin increased the ratio of phospho-Akt/total-Akt in animals with normal visual exposure but even more so in chicks wearing plus or minus lenses. The increase was blocked by simultaneous PI3K inhibitor injections in control eyes but not in lens-treated eyes. Insulin also increased the ratio of phospho-ERK/total-ERK in animals with normal visual exposure and in animals wearing positive lenses, compared to U0126- and Ly294002-injected eyes. In contrast, no significant activation of the MEK/ERK pathway was observed in the negative lens-treated animals. Intravitreal insulin promoted axial eye growth and stimulated both signaling pathways. The PI3K/Akt pathway was activated in control and plus and minus lens-treated eyes, but the MEK/ERK pathway was activated only with positive lenses or no lenses. With negative lenses, insulin did not stimulate the MEK/ERK signaling cascade. Independent of the pathway stimulated after insulin binding, the effect on insulin was always the same: an increase in eye growth.

Acute regulation of IGF-I by alterations in post-exercise macronutrients

USDA-ARS?s Scientific Manuscript database

This investigation sought to examine the contributions of exercise and nutrient replenishment on in vivo regulation of the insulin-like growth factor-I (IGF-I) axis components. Eight college-aged males completed three high-intensity interval training (HIIT) protocols followed by three post-exercise ...

The Effects of Basal Insulin Suspension at the Start of Exercise on Blood Glucose Levels During Continuous Versus Circuit-Based Exercise in Individuals with Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion.

PubMed

Zaharieva, Dessi; Yavelberg, Loren; Jamnik, Veronica; Cinar, Ali; Turksoy, Kamuran; Riddell, Michael C

2017-06-01

Exercise causes glycemic disturbances in individuals with type 1 diabetes (T1D). Continuous moderate-intensity aerobic exercise (CON) generally lowers blood glucose (BG) levels and often leads to hypoglycemia. In comparison, circuit-based exercise (CIRC) may attenuate the drop in BG. The goal of this study is to contrast the effects of basal insulin suspension at the onset of two different forms of exercise (CON vs. CIRC). Twelve individuals (six men and six women) with T1D on insulin pump therapy were recruited for the study. All participants completed a maximal aerobic fitness test and two 40-min exercise sessions, consisting of either continuous treadmill walking or a circuit workout. Basal insulin infusion was stopped at the onset of exercise and resumed in recovery. After providing an initial reference value, volunteers were blinded to their [BG] and were asked to estimate their levels during exercise. Oxygen consumption (47.5 ± 7.5 vs. 54.5 ± 13.5 mL·kg -1 ·min -1 , P = 0.03) and heart rate (122 ± 20 vs. 144 ± 20 bpm, P = 0.003) were lower in CON vs. CIRC. Despite the lower workload, BG levels dropped more with CON vs. CIRC (delta BG = -3.8 ± 1.5 vs. -0.5 ± 3.0 mmol/L for CON vs. CIRC, respectively, P = 0.001). Participants were able to estimate their BG more accurately during CON (r = 0.83) vs. CIRC (r = 0.33) based on a regression analysis. Despite a lower intensity of exercise, with full basal insulin suspension at the start of exercise, CON results in a larger drop in BG vs. CIRC. These findings have implications for single hormone-based artificial pancreas development for exercise. While this study does not negate the importance of frequent capillary BG monitoring during exercise, it does suggest that if persons are knowledgeable about their pre-exercise BG levels, they can accurately perceive the changes in BG during CON, but not during CIRC.

Associations between facial emotion recognition and young adolescents’ behaviors in bullying

PubMed Central

Gini, Gianluca; Altoè, Gianmarco

2017-01-01

This study investigated whether different behaviors young adolescents can act during bullying episodes were associated with their ability to recognize morphed facial expressions of the six basic emotions, expressed at high and low intensity. The sample included 117 middle-school students (45.3% girls; mean age = 12.4 years) who filled in a peer nomination questionnaire and individually performed a computerized emotion recognition task. Bayesian generalized mixed-effects models showed a complex picture, in which type and intensity of emotions, students’ behavior and gender interacted in explaining recognition accuracy. Results were discussed with a particular focus on negative emotions and suggesting a “neutral” nature of emotion recognition ability, which does not necessarily lead to moral behavior but can also be used for pursuing immoral goals. PMID:29131871

[Estimated glucose disposal rate in patients under 18 years of age with type 1 diabetes mellitus and overweight or obesity].

PubMed

Palomo Atance, Enrique; Ballester Herrera, M José; Giralt Muiña, Patricio; Ruiz Cano, Rafael; León Martín, Alberto; Giralt Muiña, Juan

2013-01-01

To assess the estimated glucose disposal rate (eGDR), insulin dose, and lipoprotein profile in children with type 1 diabetes mellitus (T1DM) and overweight or obesity as compared to children with T1DM and normal weight. A total of 115 patients (aged 5-16 years) with T1DM on intensive insulin therapy were recruited. The following parameters were measured: weight, height, body mass index, waist and hip circumference, insulin dose, eGDR, glycosylated hemoglobin, blood pressure, and lipoprotein profile. Results were stratified by sex and age. No significant differences were found in eGDR between children with normal weight, overweight, and obesity. However, obese children older than 11 years had lower eGDR values (9.3±1.3 vs 10.1±0.8 mg kg(-1)min(-1); p<0.01). Insulin dose was higher in overweight and obese children, especially in IU/m2/day (37.7 vs 36.1 vs. 29.4 respectively; p<0.01). Obese children had higher low-density lipoprotein cholesterol levels than children with overweight and normal weight (106.5 vs 91.7 vs 91.5mg/dL respectively; p<0.01). No correlation was found between waist circumference and the different markers of insulin resistance. Values of eGDR values were lower in obese children with T1DM older than 11 years, and this may therefore be considered a marker of insulin resistance. Insulin dose was higher in diabetic patients with overweight or obesity, specially in IU/m2/day. Obese children with T1DM had a lipoprotein profile of cardiovascular risk. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

The relationship between the metabolic syndrome and energy-utilization deficit in the pathogenesis of obesity-induced osteoarthritis.

PubMed

Rojas-Rodríguez, Jorge; Escobar-Linares, Luis E; Garcia-Carrasco, Mario; Escárcega, Ricardo O; Fuentes-Alexandro, Salvador; Zamora-Ustaran, Alfonso

2007-01-01

We propose that the pathogenesis of obesity-induced osteoarthritis may be explained by the metabolic changes in the striated muscle induced by the interaction of insulin resistance and systemic inflammation in obese individuals with metabolic syndrome being osteoarthritis the latest consequence by the physiological changes seen in the metabolic syndrome. Increased levels of TH1 cytokines are produced by activated macrophages in the presence of an acute or chronic infectious disease and suppress the sensitivity of insulin receptors on the membrane of muscle cell and adipocytes. Both cells are activated by inflammatory cytokines and contribute to enhance acute inflammation and to maintain a state of chronic, low-grade inflammation in apparently healthy obese individuals. The increased number of macrophage in the adipose tissue of obese individuals acts as an amplifier of inflammation. Patients with osteoarthritis and metabolic syndrome frequently are complaining about hotness and recurrent edema of feet and hands. It is probable that hyperinsulinemia in the presence of insulin resistance and inflammation, induce vasodilation through the TNF mediated-iNOS overexpression. Patients with metabolic syndrome express clinically the consequence of a poor uptake, storage and energy expenditure by the muscle and any other insulin dependent tissue and the consequence of high insulin plasma levels are vasodilation and increased protein synthesis. The fatigue and muscle weakness induced by insulin resistance and inflammation in obese patients with metabolic syndrome increase the frequency and the intensity of traumatic events of peripheral or axial joints that result in stretch and breaking of tenoperiosteal junction and abrasive damage of cartilage and therefore in these patients with metabolic syndrome and pro-inflammatory state the reparative process of cartilage and periarticular tissues would be severely modified by the growth factor activity in presence of high levels of insulin.

Brain Insulin Resistance and Deficiency as Therapeutic Targets in Alzheimer's Disease

PubMed Central

de la Monte, Suzanne M

2012-01-01

Alzheimer's disease [AD] is the most common cause of dementia in North America. Despite 30+ years of intense investigation, the field lacks consensus regarding the etiology and pathogenesis of sporadic AD, and therefore we still do not know the best strategies for treating and preventing this debilitating and costly disease. However, growing evidence supports the concept that AD is fundamentally a metabolic disease with substantial and progressive derangements in brain glucose utilization and responsiveness to insulin and insulin-like growth factor [IGF] stimulation. Moreover, AD is now recognized to be heterogeneous in nature, and not solely the end-product of aberrantly processed, misfolded, and aggregated oligomeric amyloid-beta peptides and hyperphosphorylated tau. Other factors, including impairments in energy metabolism, increased oxidative stress, inflammation, insulin and IGF resistance, and insulin/IGF deficiency in the brain should be incorporated into all equations used to develop diagnostic and therapeutic approaches to AD. Herein, the contributions of impaired insulin and IGF signaling to AD-associated neuronal loss, synaptic disconnection, tau hyperphosphorylation, amyloid-beta accumulation, and impaired energy metabolism are reviewed. In addition, we discuss current therapeutic strategies and suggest additional approaches based on the hypothesis that AD is principally a metabolic disease similar to diabetes mellitus. Ultimately, our ability to effectively detect, monitor, treat, and prevent AD will require more efficient, accurate and integrative diagnostic tools that utilize clinical, neuroimaging, biochemical, and molecular biomarker data. Finally, it is imperative that future therapeutic strategies for AD abandon the concept of uni-modal therapy in favor of multi-modal treatments that target distinct impairments at different levels within the brain insulin/IGF signaling cascades. PMID:22329651

Regulation of insulin secretion from islets of Langerhans rendered permeable by electric discharge

PubMed Central

Yaseen, M. Adel; Pedley, Kevin C.; Howell, Simon L.

1982-01-01

1. High-voltage electric discharge has been used to increase the permeability of B-cells of isolated islets of Langerhans to facilitate studies of the effects of normally impermeable substances on insulin secretion. 2. The application of an intense electric field increased the [14C]sucrose space of the islets from 37.8±3.1% to 86.2±5.2% of their total volume as assessed by 3H2O content. The cells remained permeable for at least 40min. 3. Ultrastructural studies showed no deleterious changes in the structure of the B-cells after discharge. 4. Insulin secretion from normal islets was unaffected by increasing the medium [Ca2+] from 10nm to 10μm. In the islets that had been rendered permeable by discharge, insulin secretion was significantly increased under these conditions, without any alteration in the release of lactate dehydrogenase, a cytoplasmic marker enzyme. 5. Studies of the dynamics of insulin release during perifusion showed that the response to increased (10μm) Ca2+ concentration was rapid and sustained over a period of at least 13min. 6. Secretion responses to Ca2+ in perifusion established that maximum release in permeabilized islets occurs at approx. 1μm-Ca2+ and half-maximum release occurs at approx. 0.6μm-Ca2+. 7. The study of the effect of agents that interfere with the microtubular microfilamentous system in B-cells using a perifusion system revealed that cytochalasin B caused a considerable increase, whereas vinblastine sulphate caused a significant inhibition, in insulin release in response to 1μm-Ca2+. 8. This technique should facilitate the study of the role of normally impermeable ions and metabolic intermediates in the regulation of insulin secretion. ImagesPLATE 1 PMID:6751326

Ontogeny of polycystic ovary syndrome and insulin resistance in utero and early childhood

USDA-ARS?s Scientific Manuscript database

Polycystic ovary syndrome (PCOS) is a prevalent hyperandrogenic infertility and cardiometabolic disorder that increases a woman's lifetime risk of type 2 diabetes mellitus. It is heritable and intensely familial. Progress toward a cure has been delayed by absence of an etiology. Evidence is mounting...

Current Trends in the Management of Blunt Solid Organ Injuries.

PubMed

Taviloglu, Korhan; Yanar, Hakan

2009-04-01

The management of patients with solid organ injuries has changed since the introduction of technically advanced imaging tools, such as ultrasonography and multiple scan computerized tomography, interventional radiological techniques and modern intensive care units. In spite of this development in the management of these patients, major solid organ traumas can still be challenging. There has been great improvement in the non-operative management (NOM) of intra-abdominal solid organ injury in recent decades. In most cases treatment of injuries has shifted from early surgical treatment to NOM.

Design and rationale of Heart and Lung Failure – Pediatric INsulin Titration Trial (HALF-PINT): A randomized clinical trial of tight glycemic control in hyperglycemic critically ill children☆

PubMed Central

Agus, Michael SD; Hirshberg, Ellie; Srinivasan, Vijay; Faustino, Edward Vincent; Luckett, Peter M; Curley, Martha AQ; Alexander, Jamin; Asaro, Lisa A; Coughlin-Wells, Kerry; Duva, Donna; French, Jaclyn; Hasbani, Natalie; Sisko, Martha T; Soto-Rivera, Carmen L; Steil, Garry; Wypij, David; Nadkarni, Vinay M

2017-01-01

Objectives Test whether hyperglycemic critically ill children with cardiovascular and/or respiratory failure experience more ICU-free days when assigned to tight glycemic control with a normoglycemic versus hyperglycemic blood glucose target range. Design Multi-center randomized clinical trial. Setting Pediatric ICUs at 35 academic hospitals. Patients Children aged 2 weeks to 17 years receiving inotropic support and/or acute mechanical ventilation, excluding cardiac surgical patients. Interventions Patients receive intravenous insulin titrated to either 80–110 mg/dL (4.4–6.1 mmol/L) or 150–180 mg/dL (8.3–10.0 mmol/L). The intervention begins upon confirmed hyperglycemia and ends when the patient meets study-defined ICU discharge criteria or after 28 days. Continuous glucose monitoring, a minimum glucose infusion, and an explicit insulin infusion algorithm are deployed to achieve the BG targets while minimizing hypoglycemia risk. Measurements and main results The primary outcome is ICU-free days (equivalent to 28-day hospital mortality-adjusted ICU length of stay). Secondary outcomes include 90-day hospital mortality, organ dysfunction scores, ventilator-free days, nosocomial infection rate, neurodevelopmental outcomes, and nursing workload. To detect an increase of 1.25 ICU-free days (corresponding to a 20% relative reduction in 28-day hospital mortality and a one-day reduction in ICU length of stay), 1414 patients are needed for 80% power using a two-sided 0.05 level test. Conclusions This trial tests whether hyperglycemic critically ill children randomized to 80–110 mg/dL benefit more than those randomized to 150–180 mg/dL. This study implements validated bedside support tools including continuous glucose monitoring and a computerized algorithm to enhance patient safety and ensure reproducible bedside decision-making in achieving glycemic control. PMID:28042054

Plasma Irisin Modestly Increases during Moderate and High-Intensity Afternoon Exercise in Obese Females

PubMed Central

Winn, Nathan C.; Grunewald, Zachary I.; Liu, Ying; Heden, Timothy D.; Nyhoff, Lauren M.; Kanaley, Jill A.

2017-01-01

Background and Purpose Irisin is an exercise-responsive myokine that has been proposed to exert anti-obesity benefits; yet its response during exercise in obese women is not described. This study characterized plasma irisin levels during a single bout of afternoon isocaloric-exercise of different intensities (moderate- vs high-intensity) in obese females. Methods Eleven obese females participated in 3 randomized study days beginning at 1600h: 1) no exercise (NoEx), 2) moderate exercise (ModEx; 55%VO2max) and 3) high intensity interval exercise (IntEx; 4 min (80%VO2max)/3 min (50% VO2max). Frequent blood samples were analyzed for glucose and lactate (whole-blood), and insulin, c-peptide, glucagon, and irisin (plasma) throughout 190 min of testing. Results Plasma irisin increased above baseline during ModEx and IntEx (P<0.05), but not NoEx (P>0.05). Peak irisin levels during ModEx and IntEx exercise were 11.9± 3.4% and 12.3 ± 4.1% relative to baseline (P<0.05), respectively, with no differences between exercise intensities (P>0.05). Irisin levels remained elevated above resting for 125 minutes post-exercise during ModEx, whereas levels returned to baseline within 15 minutes post-exercise during IntEx. Similarly, no associations were found between plasma irisin levels and circulating lactate, glucose, insulin, c-peptide, or glucagon among study days (P>0.05). However, there was an inverse association between basal irisin and lean mass (r = -0.70, P = 0.01). Conclusion A single bout of moderate and high intensity afternoon exercise induces modest increases in circulating irisin concentrations during exercise; however the regulation post-exercise appears to be dimorphic between exercise intensity in obese females. Future studies are needed to compare morning and afternoon exercise on irisin secretion. PMID:28125733

Rebound hyperglycaemia in diabetic cats.

PubMed

Roomp, Kirsten; Rand, Jacquie

2016-08-01

Rebound hyperglycaemia (also termed Somogyi effect) is defined as hyperglycaemia caused by the release of counter-regulatory hormones in response to insulin-induced hypoglycaemia, and is widely believed to be common in diabetic cats. However, studies in human diabetic patients over the past quarter century have rejected the common occurrence of this phenomenon. Therefore, we evaluated the occurrence and prevalence of rebound hyperglycaemia in diabetic cats. In a retrospective study, 10,767 blood glucose curves of 55 cats treated with glargine using an intensive blood glucose regulation protocol with a median of five blood glucose measurements per day were evaluated for evidence of rebound hyperglycaemic events, defined in two different ways (with and without an insulin resistance component). While biochemical hypoglycaemia occurred frequently, blood glucose curves consistent with rebound hyperglycaemia with insulin resistance was confined to four single events in four different cats. In 14/55 cats (25%), a median of 1.5% (range 0.32-7.7%) of blood glucose curves were consistent with rebound hyperglycaemia without an insulin resistance component; this represented 0.42% of blood glucose curves in both affected and unaffected cats. We conclude that despite the frequent occurrence of biochemical hypoglycaemia, rebound hyperglycaemia is rare in cats treated with glargine on a protocol aimed at tight glycaemic control. For glargine-treated cats, insulin dose should not be reduced when there is hyperglycaemia in the absence of biochemical or clinical evidence of hypoglycaemia. © ISFM and AAFP 2015.

Immunohistochemical differentiation of reactive from malignant mesothelium as a diagnostic aid in canine pericardial disease.

PubMed

Milne, E; Martinez Pereira, Y; Muir, C; Scase, T; Shaw, D J; McGregor, G; Oldroyd, L; Scurrell, E; Martin, M; Devine, C; Hodgkiss-Geere, H

2018-05-01

To develop a provisional immunohistochemistry panel for distinguishing reactive pericardium, atypical mesothelial proliferation and mesothelioma in dogs. Archived pericardial biopsies were subject to haematoxylin and eosin staining, immunohistochemistry for cytokeratin, vimentin, insulin-like growth factor II mRNA-binding protein 3, glucose transporter 1 and desmin. Samples were scored for intensity and number of cells stained. Ten biopsies of reactive mesothelium, 17 of atypical mesothelial proliferation, 26 of mesothelioma and five of normal pericardium were identified on the basis of haematoxylin and eosin staining. Cytokeratin and vimentin were expressed in all biopsies, confirming mesothelial origin. Normal pericardial samples had the lowest scores for insulin-like growth factor II mRNA-binding protein 3, glucose transporter 1 and desmin. Mesothelioma and atypical proliferative samples were similar to each other, with higher scores for insulin-like growth factor II mRNA-binding protein 3 and glucose transporter 1 than the reactive samples. Desmin staining was variable. Insulin-like growth factor II mRNA-binding protein 3 was the best to distinguish between disease groups. An immunohistochemistry panel of cytokeratin, vimentin, insulin-like growth factor II mRNA-binding protein 3 and glucose transporter 1 could provide superior information compared with haematoxylin and eosin staining alone in the diagnosis of cases of mesothelial proliferation in canine pericardium, but further validation is warranted. © 2018 British Small Animal Veterinary Association.

Insulin Therapy for the Management of Hyperglycemia in Hospitalized Patients

PubMed Central

McDonnell, Marie E.; Umpierrez, Guillermo E.

2013-01-01

It has long been established that hyperglycemia with or without a prior diagnosis of diabetes increases both mortality and disease-specific morbidity in hospitalized patients1–4 and that goal-directed insulin therapy can improve outcomes.5–9 During the past decade, since the widespread institutional adoption of intensified insulin protocols after the publication of a landmark trial,5,10 the pendulum in the inpatient diabetes literature has swung away from achieving intensive glucose control and toward more moderate and individualized glycemic targets.11,12 This change in clinical practice is the result of several factors, including challenges faced by hospitals to coordinate glycemic control across all levels of care,13,14 publication of negative prospective trials,15,16 revised recommendations from professional organizations,17,18 and increasing evidence on the deleterious effect of hypoglycemia.19–22 This article reviews the pathophysiology of hyperglycemia during illness, the mechanisms for increased complications and mortality due to hyperglycemia and hypoglycemia, beneficial mechanistic effects of insulin therapy and provides updated recommendations for the inpatient management of diabetes in the critical care setting and in the general medicine and surgical settings.23,24 PMID:22575413

Houttuynia cordata Facilitates Metformin on Ameliorating Insulin Resistance Associated with Gut Microbiota Alteration in OLETF Rats.

PubMed

Wang, Jing-Hua; Bose, Shambhunath; Lim, Soo-Kyoung; Ansari, AbuZar; Chin, Young-Won; Choi, Han Seok; Kim, Hojun

2017-09-22

Metformin and Houttuynia cordata are representative anti-diabetic therapeutics in western and oriental medicine, respectively. The current study examined the synergistic anti-diabetic effect of Houttuynia cordata extraction (HCE) and metformin combination in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Fecal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE) and real-time PCR. Combining HCE + metformin resulted in significantly ameliorated glucose tolerance (oral glucose tolerance test (OGTT))-the same as metformin alone. Particularly, results of the insulin tolerance test (ITT) showed that combining HCE + metformin dramatically improved insulin sensitivity as compared to metformin treatment alone. Both fecal and serum endotoxin, as well as cytokines (tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6)) were significantly ameliorated by HCE + metformin compared to metformin alone. Meanwhile, the activation of AMPK (adenosine monophosphate-activated protein kinase) by metformin was distinctly enhanced by HCE. Both of HCE and metformin evidently changed the gut microbiota composition, causing the alteration of bacterial metabolite, like short-chain fatty acids. H. cordata , together with metformin, exerts intensive sensibilization to insulin; the corresponding mechanisms are associated with alleviation of endotoxemia via regulation of gut microbiota, particularly Roseburia , Akkermansia , and Gram-negative bacterium.

Houttuynia cordata Facilitates Metformin on Ameliorating Insulin Resistance Associated with Gut Microbiota Alteration in OLETF Rats

PubMed Central

Bose, Shambhunath; Lim, Soo-Kyoung; Ansari, AbuZar; Chin, Young-Won; Choi, Han Seok; Kim, Hojun

2017-01-01

Metformin and Houttuynia cordata are representative anti-diabetic therapeutics in western and oriental medicine, respectively. The current study examined the synergistic anti-diabetic effect of Houttuynia cordata extraction (HCE) and metformin combination in Otsuka Long–Evans Tokushima Fatty (OLETF) rats. Fecal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE) and real-time PCR. Combining HCE + metformin resulted in significantly ameliorated glucose tolerance (oral glucose tolerance test (OGTT))—the same as metformin alone. Particularly, results of the insulin tolerance test (ITT) showed that combining HCE + metformin dramatically improved insulin sensitivity as compared to metformin treatment alone. Both fecal and serum endotoxin, as well as cytokines (tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6)) were significantly ameliorated by HCE + metformin compared to metformin alone. Meanwhile, the activation of AMPK (adenosine monophosphate-activated protein kinase) by metformin was distinctly enhanced by HCE. Both of HCE and metformin evidently changed the gut microbiota composition, causing the alteration of bacterial metabolite, like short-chain fatty acids. H. cordata, together with metformin, exerts intensive sensibilization to insulin; the corresponding mechanisms are associated with alleviation of endotoxemia via regulation of gut microbiota, particularly Roseburia, Akkermansia, and Gram-negative bacterium. PMID:28937612

The effect of aerobic training on CXL5, tumor necrosis factor α and insulin resistance index (HOMA-IR) in sedentary obese women.

PubMed

Zehsaz, Farzad; Farhangi, Negin; Mirheidari, Lamia

2014-01-01

The purpose of the present study was to investigate the effects of a 12-week training program on serum CXC ligand 5, tumor necrosis factor α (TNF-α) and insulin resistance index in obese sedentary women. To this end, twenty-four obese sedentary women were evaluated before and after a 12-week exercise program including a brief warm-up, followed by ~45 min per session of aerobic exercise at an intensity of 60-75% of age-predicted maximum heart rate (~300 kcal/day), followed by a brief cool down, five times per week. After the exercise program, body weight, waist circumference, waist to hip ratio, percentage body fat mass, fasting glucose and insulin of participants were decreased. Furthermore, serum CXCL5 levels were significantly decreased from 2693.2 ±375.8 to 2290.2 ±345.9 pg/ml (p < 0.001) after the training program, which was accompanied with significantly decreased HOMA-IR (p < 0.001) and TNF-α (p < 0.001). Exercise training induced weight loss resulted in a significant reduction in serum CXCL5 concentrations and caused an improvement in insulin resistance in obese sedentary women.

A Method of Porcine Pancreatic Islet Isolation for Microencapsulation.

PubMed

Kendall, William F; Opara, Emmanuel C

2017-01-01

Since the discovery of insulin by Banting and Best in 1921, the prognosis and treatment options for individuals with diabetes have improved. The development of various insulin types, various oral agents, and insulin pumps have improved the available medical options for individuals afflicted with diabetes. The current need for frequent blood glucose monitoring imposed by multiple daily insulin injections, result in significant life-style challenges for in individuals afflicted with Type 1 diabetes (T1D). In contrast the use of surgical interventions, such as whole organ pancreas transplantation (PT) requires less-intensive glucose monitoring while the organ is viable. Also, isolated human pancreatic islet transplantation (IT) holds similar promise as PT; however, the limited availability of human pancreata exacerbated by, the need for multiple pancreata per individual IT recipient, and issues with prolonged viability, still hamper widespread successful, and routine use of IT. The use of porcine pancreata holds promise as a viable alternative to human pancreas to significantly increase the volume of islets available to meet the needs of millions of patients afflicted with T1D. This chapter outlines our protocol utilized to reliably isolate and microencapsulate porcine islets.

Pharmacokinetics, efficacy and safety of glyburide for treatment of gestational diabetes mellitus.

PubMed

Malek, Rana; Davis, Stephen N

2016-06-01

Gestational diabetes mellitus (GDM) complicates 10% of all pregnancies and is defined as hyperglycemia first noted during pregnancy. Rates of GDM are rising and untreated GDM results in complications for both mother and fetus. GDM is often managed by diet and exercise but 30-40% of women will require pharmacological intervention. Insulin has traditionally been the treatment of choice but since 2007, glyburide, a second generation sulfonylurea has become the most prescribed medication for GDM. This review will cover the pharmacokinetics, efficacy, and safety of glyburide for the management of GDM. Management of GDM is challenging secondary to the stringent glycemic goals that mimic the lower glucose levels in pregnancy. Glyburide is generally effective in treating hyperglycemia. However, several studies have raised safety concerns showing higher neonatal intensive care unit (NICU) admissions, higher rates of macrosomia, large for gestational age and pre-eclampsia in the mother. For this reason, insulin should be first-line therapy for GDM. In areas of limited resources where the self-monitoring needed for accurate insulin dosing is not possible, where access to refrigeration for insulin storage is not universal, or severe needle phobia then the benefits of glyburide (controlling hyperglycemia) outweighs the harm of NICU admissions and macrosomia.

Targeted proteomics reveals strain-specific changes in the mouse insulin and central metabolic pathways after a sustained high-fat diet.

PubMed

Sabidó, Eduard; Wu, Yibo; Bautista, Lucia; Porstmann, Thomas; Chang, Ching-Yun; Vitek, Olga; Stoffel, Markus; Aebersold, Ruedi

2013-07-16

The metabolic syndrome is a collection of risk factors including obesity, insulin resistance and hepatic steatosis, which occur together and increase the risk of diseases such as diabetes, cardiovascular disease and cancer. In spite of intense research, the complex etiology of insulin resistance and its association with the accumulation of triacylglycerides in the liver and with hepatic steatosis remains not completely understood. Here, we performed quantitative measurements of 144 proteins involved in the insulin-signaling pathway and central metabolism in liver homogenates of two genetically well-defined mouse strains C57BL/6J and 129Sv that were subjected to a sustained high-fat diet. We used targeted mass spectrometry by selected reaction monitoring (SRM) to generate accurate and reproducible quantitation of the targeted proteins across 36 different samples (12 conditions and 3 biological replicates), generating one of the largest quantitative targeted proteomics data sets in mammalian tissues. Our results revealed rapid response to high-fat diet that diverged early in the feeding regimen, and evidenced a response to high-fat diet dominated by the activation of peroxisomal β-oxidation in C57BL/6J and by lipogenesis in 129Sv mice.

Addressing hyperglycemia from hospital admission to discharge.

PubMed

Moghissi, Etie S

2010-03-01

This review examines glycemia management practices in hospitalized patients. Optimal glycemic control remains a challenge among hospitalized patients. Recent studies have questioned the benefit of tight glycemic control and have raised concerns regarding the safety of this approach. As a result, medical societies have updated glycemic targets and have published new consensus guidelines for management of glycemia in hospitalized patients. This review highlights recent inpatient glycemic trials, the new glycemic targets and recommended strategies for management of glycemia in hospitalized patients. Medline and PubMed searches (diabetes, hyperglycemia, hypoglycemia, intensive therapy insulin, tight glycemic control, and hospital patients) were performed for English-language articles on treatment of diabetes, insulin therapy, hyperglycemia or hypoglycemia in hospitalized patients published from 2004 to present. Earlier works cited in these papers were surveyed. Clinical studies, reviews, consensus/guidelines statements, and meta-analyses relevant to the identification and management of diabetes and hyperglycemia in hospitalized patients were included and selected. This is not an exhaustive review of the published literature. Insulin remains the most appropriate agent for a majority of hospitalized patients. In critically ill patients insulin is given as a continuous intravenous (IV) infusion and in non-critically ill inpatients hyperglycemia is best managed using scheduled subcutaneous (SC) basal-bolus insulin regimens supplemented with correction doses as needed and adjusted daily with the guidance of frequent blood glucose monitoring. Prevention of hypoglycemia is equally as important to patient outcomes and is an equally necessary part of any effective glucose control program. Modern insulin analogs offer advantages over the older human insulins (e.g., regular and neutral protamine Hagedorn [NPH] insulin) because their time-action profiles more closely correspond to physiological basal and prandial insulin requirements, and have a lower propensity for inducing hypoglycemia than human insulin formulations. Long-acting basal insulin analogs (glargine, detemir) are suitable and preferred for the basal component of therapy; rapid-acting insulin analogs (aspart, lispro, glulisine) are recommended for bolus and correction doses. Sliding-scale insulin (SSI) regimens are not effective and should not be used, especially as this excludes a basal insulin component from the therapy. Optimal glycemic management in the hospital setting requires judicious treatment of hyperglycemia while avoiding hypoglycemia. Insulin is the most appropriate agent for management of hyperglycemia for the majority of hospitalized patients. Intravenous insulin infusion is still preferred during and immediately after surgery, but s.c. basal insulin analogs with prandial or correction doses should be used after the immediate post-operative period, and also should be used in non-critically ill patients. Frequent and effective glucose monitoring is critical for avoiding wide deviations from acceptable glucose levels, which under a recently promulgated consensus guideline currently range between 140 mg/dL and 180 mg/dL. Glucose targets near 140 mg/dL are recommended as being the most appropriate for all hospitalized patients.

PPARgamma gene polymorphism is associated with exercise-mediated changes of insulin resistance in healthy men.

PubMed

Kahara, Toshio; Takamura, Toshinari; Hayakawa, Tetsuo; Nagai, Yukihiro; Yamaguchi, Hiromi; Katsuki, Tatsuo; Katsuki, Ken-Ichi; Katsuki, Michio; Kobayashi, Ken-Ichi

2003-02-01

Exercise training improves insulin sensitivity, but individual responses vary greatly. Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a regulator of adipose cell differentiation and plays an important role in systemic insulin action. We investigated whether PPARgamma gene polymorphism affects insulin resistance in response to exercise in Japanese healthy men. The exercise program at an individual intensity of 50% of the maximal heart rate was performed for 20 to 60 min/d, and 2 to 3 days per week to attain a level of physical activity of 700 kcal/wk. The program was conducted for 3 months without any dietary intervention, and the clinical and metabolic characteristics were examined before and after the exercise program. Body mass index (BMI) did not change significantly after the exercise program, whereas percentage of body fat (% body fat), fasting plasma glucose (FPG), and serum leptin levels decreased significantly. Pro12Ala polymorphism in PPARgamma gene was performed on genomic DNA isolated from human leukocytes and examined with polymerase chain reaction (PCR) and subsequent restriction enzyme analysis using BstU-I. In this study, the Ala allele did not correlate with fasting immunoreactive insulin (IRI) and homeostasis model assessment-insulin resistance index (HOMA-R) at baseline, but did so with the changes in IRI and HOMA-R after exercise (DeltaIRI, Pro/Pro 0.55 +/- 3.49 microU/mL v Pro/Ala -2.83 +/- 1.47 microU/mL, P <.05; DeltaHOMA-R, Pro/Pro 0.09 +/- 0.86 v Pro/Ala -0.61 +/- 0.32, P <.05). This result suggests that the Ala allele is associated with improvement in insulin resistance after exercise. We conclude that PPARgamma gene polymorphism may be a reliable indicator of whether exercise will have a beneficial effect as part of the treatment of insulin resistance syndrome. Copyright 2003, Elsevier Science (USA). All rights reserved.

The importance of declining insulin requirements during pregnancy in patients with pre-gestational gestational diabetes mellitus.

PubMed

Ram, Maya; Feinmesser, Larissa; Shinar, Shiri; Maslovitz, Sharon

2017-08-01

In patients with pre-gestational and gestational diabetes mellitus (GDM), insulin requirements often increase during the third trimester of pregnancy in order to maintain proper glycemic control. However, a fraction of patients demonstrate a significant decrease in insulin requirements in late gestation. We aimed to evaluate the clinical significance of decreasing insulin requirements in patients with pre-gestational diabetes and GDM with respect to fetal wellbeing and pregnancy outcome. We performed a retrospective cohort study in a single referral center for gestational diabetes between 1/2010 and 12/2014. Healthy pregnant women with pre-gestational diabetes and GDMA2 and a decrease of at least 30% in insulin requirements over a period of two weeks during the third trimester (group A) were compared to women with stable or increasing insulin requirements (group B). The primary outcome was a composite of situations associated with feto-placental dysfunction (fetal growth restriction, oligohydramnios and cesarean section due to category 2-3 monitor). Secondary outcomes were maternal oral glucose tolerance test (OGTT) results 6 weeks postpartum, neonatal intensive care unit (NICU) admission rates, Apgar scores ≤7 at 5min, arterial blood pH≤7.1, macrosomia, neonatal hypoglycemia and a composite adverse neonatal outcomes (defined as one or more of the following: respiratory morbidity, cerebral morbidity, phototherapy, need for blood transfusion, necrotizing enterocolitis or death). Group A consisted of 101 women and group B - of 203 women. There were no differences between the groups in demographic characteristics or diagnostic characteristics of diabetes. The frequency of conditions related to feto-placental dysfunction did not differ between the groups (7.9% vs. 8.4%, p=0.61). Secondary outcome measures also did not differ between the groups, regardless of insulin requirements. Decreasing insulin requirements during the third trimester are not associated with adverse perinatal outcome related to placental dysfunction. Copyright © 2017 Elsevier B.V. All rights reserved.

Ultrasound Stimulation of Insulin Release from Pancreatic Beta Cells as a Potential Novel Treatment for Type 2 Diabetes.

PubMed

Suarez Castellanos, Ivan; Jeremic, Aleksandar; Cohen, Joshua; Zderic, Vesna

2017-06-01

Type 2 diabetes mellitus is a complex metabolic disease that has reached epidemic proportions in the United States and around the world. This disease is characterized by loss of insulin secretion and, eventually, destruction of insulin-producing pancreatic beta cells. Controlling type 2 diabetes is often difficult as pharmacological management routinely requires complex therapy with multiple medications, and loses its effectiveness over time. The objective of this study was to explore the effectiveness of a novel, non-pharmacological approach that uses the application of ultrasound energy to augment insulin release from rat INS 832/13 beta cells. The cells were exposed to unfocused ultrasound for 5 min at a peak intensity of 1 W/cm 2 and frequencies of 400 kHz, 600 kHz, 800 kHz and 1 MHz. Insulin release was measured with enzyme-linked immunosorbent assay and cell viability was assessed via the trypan blue dye exclusion test. A marked release (approximately 150 ng/10 6  cells, p < 0.05) of insulin was observed when beta cells were exposed to ultrasound at 400 and 600 kHz as compared with their initial control values; however, this release was accompanied by a substantial loss in cell viability. Ultrasound application at frequencies of 800 kHz resulted in 24 ng/10 6  cells released insulin (p < 0.05) as compared with its unstimulated base level, while retaining cell viability. Insulin release from beta cells caused by application of 800-kHz ultrasound was comparable to that reported by the secretagogue glucose, thus operating within physiological secretory capacity of these cells. Ultrasound has potential as a novel and alternative method to current approaches aimed at correcting secretory deficiencies in patients with type 2 diabetes. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Comparison between surrogate indexes of insulin sensitivity/resistance and hyperinsulinemic euglycemic clamp estimates in rats

PubMed Central

Muniyappa, Ranganath; Chen, Hui; Muzumdar, Radhika H.; Einstein, Francine H.; Yan, Xu; Yue, Lilly Q.; Barzilai, Nir

2009-01-01

Assessing insulin resistance in rodent models gives insight into mechanisms that cause type 2 diabetes and the metabolic syndrome. The hyperinsulinemic euglycemic glucose clamp, the reference standard for measuring insulin sensitivity in humans and animals, is labor intensive and technically demanding. A number of simple surrogate indexes of insulin sensitivity/resistance have been developed and validated primarily for use in large human studies. These same surrogates are also frequently used in rodent studies. However, in general, these indexes have not been rigorously evaluated in animals. In a recent validation study in mice, we demonstrated that surrogates have a weaker correlation with glucose clamp estimates of insulin sensitivity/resistance than in humans. This may be due to increased technical difficulties in mice and/or intrinsic differences between human and rodent physiology. To help distinguish among these possibilities, in the present study, using data from rats substantially larger than mice, we compared the clamp glucose infusion rate (GIR) with surrogate indexes, including QUICKI, HOMA, 1/HOMA, log (HOMA), and 1/fasting insulin. All surrogates were modestly correlated with GIR (r = 0.34–0.40). Calibration analyses of surrogates adjusted for body weight demonstrated similar predictive accuracy for GIR among all surrogates. We conclude that linear correlations of surrogate indexes with clamp estimates and predictive accuracy of surrogate indexes in rats are similar to those in mice (but not as substantial as in humans). This additional rat study (taken with the previous mouse study) suggests that application of surrogate insulin sensitivity indexes developed for humans may not be appropriate for determining primary outcomes in rodent studies due to intrinsic differences in metabolic physiology. However, use of surrogates may be appropriate in rodents, where feasibility of clamps is an obstacle and measurement of insulin sensitivity is a secondary outcome. PMID:19706785

11 CFR 9033.12 - Production of computerized information.

Code of Federal Regulations, 2011 CFR

2011-01-01

... magnetic media, such as magnetic tapes or magnetic diskettes, containing the computerized information at.... The computerized magnetic media shall be prepared and delivered at the committee's expense and shall... Commission's Computerized Magnetic Media Requirements for title 26 Candidates/Committees Receiving Federal...

Heparanase augments insulin receptor signaling in breast carcinoma

PubMed Central

Goldberg, Rachel; Sonnenblick, Amir; Hermano, Esther; Hamburger, Tamar; Meirovitz, Amichay; Peretz, Tamar; Elkin, Michael

2017-01-01

Recently, growing interest in the potential link between metabolic disorders (i.e., diabetes, obesity, metabolic syndrome) and breast cancer has mounted, including studies which indicate that diabetic/hyperinsulinemic women have a significantly higher risk of bearing breast tumors that are more aggressive and associated with higher death rates. Insulin signaling is regarded as a major contributor to this phenomenon; much less is known about the role of heparan sulfate-degrading enzyme heparanase in the link between metabolic disorders and cancer. In the present study we analyzed clinical samples of breast carcinoma derived from diabetic/non-diabetic patients, and investigated effects of heparanase on insulin signaling in breast carcinoma cell lines, as well as insulin-driven growth of breast tumor cells. We demonstrate that heparanase activity leads to enhanced insulin signaling and activation of downstream tumor-promoting pathways in breast carcinoma cells. In agreement, heparanase enhances insulin-induced proliferation of breast tumor cells in vitro. Moreover, analyzing clinical data from diabetic breast carcinoma patients, we found that concurrent presence of both diabetic state and heparanase in tumor tissue (as opposed to either condition alone) was associated with more aggressive phenotype of breast tumors in the patient cohort analyzed in our study (two-sided Fisher's exact test; p=0.04). Our findings highlight the emerging role of heparanase in powering effect of hyperinsulinemic state on breast tumorigenesis and imply that heparanase targeting, which is now under intensive development/clinical testing, could be particularly efficient in a growing fraction of breast carcinoma patients suffering from metabolic disorders. PMID:28038446

International trade and determinants of price differentials of insulin medicine.

PubMed

Helble, Matthias; Aizawa, Toshiaki

2017-02-01

Empirical studies on pharmaceutical pricing across countries have found evidence that prices vary according to per capita income. These studies are typically based on survey data from a subset of countries and cover only one year. In this paper, we study the international trade and price of insulin by using detailed trade data for 186 importing countries from 1995 to 2013. With almost 12,000 observations, our study constitutes the largest comparative study on pharmaceutical pricing conducted so far. The large dataset allows us to uncover new determinants of price differentials. Our analysis shows that the international trade of insulin increased substantially over this time period, clearly outpacing the increasing prevalence of diabetes. Using the unit values of imports, we also study the determinants of price differentials between countries. Running various panel regressions, we find that the differences in prices across countries can be explained by the following factors: First, corroborating earlier studies, we find that per capita GDP is positively correlated with the unit price of insulin. Second, the price of insulin drugs originating from Organisation for Economic Co-operation and Development countries tends to be substantially higher than for those imported from developing countries. Third, more intense competition among suppliers leads to lower insulin prices. Fourth, higher out-of-pocket payments for health care are associated with higher prices. Finally, higher volumes and tariffs seem to result in lower unit prices. © The Author 2016. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Agenesis of the dorsal pancreas: a rare cause of insulin-dependent diabetes without abdominal pain: Case report.

PubMed

Liang, Kaiyong; Ou, Xiaojuan; Huang, Xukai; Lan, Qunfang

2018-03-01

Agenesis of the dorsal pancreas is a very rare condition with an unknown pathology and etiology, although it may be associated with autosomal dominant or X-linked dominant inheritance or retinoic acid and hedgehog signaling pathway alterations. This condition usually manifests with abdominal pain or pancreatitis, although some cases are asymptomatic. Approximately 50% of affected patients with this disorder present with hyperglycemia or various other anomalies. We report the case of a 23-year-old Chinese woman who visited the Department of Endocrinology and Metabolism with insulin-dependent diabetes but no specific symptoms, signs, or other deformities. Severe diabetic retinopathy indicated a long period of hyperglycemia. Agenesis of the dorsal pancreas was observed incidentally during the common diagnosis of diabetes, and the diagnosis was established using magnetic resonance imaging, diffusion-weighted imaging, and magnetic resonance cholangiopancreatography. Following the diagnosis of diabetes, insulin replacement therapy was initiated at a dosage of up to 45 U per day. The patient's blood glucose level was monitored, and the insulin dosage was adjusted accordingly. The patient's blood glucose levels gradually normalized after insulin treatment and were subsequently maintained with intensive insulin therapy. Treatment for diabetic retinopathy was provided by the Ophthalmology Department. Agenesis of the dorsal pancreas should be considered in a young patient diagnosed with diabetes who presents with obvious diabetes-related complications (e.g., renal, retinal, or neurological) inconsistent with the course of the disease or a history of other congenital anomalies. We recommend the routine use of computed tomography or magnetic resonance imaging when examining young patients with diabetes.

Interactions between metabolic and reproductive functions in the resumption of postpartum fecundity

PubMed Central

Valeggia, Claudia; Ellison, Peter T.

2012-01-01

Lactation has long been recognized as a major determinant of interbirth intervals. The temporal pattern of nursing has been proposed as the mechanism behind lactational amenorrhea. We present a new model of the dynamic regulation of lactational amenorrhea that identifies maternal energy availability as the main determinant of ovarian resumption. Variation in the intensity of lactation remains a component of the model as a determinant of the absolute energetic cost of milk production. But maternal energy supply determines net energy availability; a larger energy supply leaves a greater net energy surplus than a smaller energy supply (lactation costs being equal). We characterize the hormonal postpartum profile of 70 lactating Toba women of Argentina. We use C-peptide, which reflects maternal insulin production, as a measure of energy availability. Initially low, insulin production rises as the postpartum period progresses, reflecting the declining metabolic load of lactation. A short period of supernormal insulin production precedes menstrual resumption. The high levels of insulin may play a role in stimulating the resumption of ovarian activity, which in turn may help to resolve the transient period of insulin resistance. The dynamics of insulin sensitivity during lactation would aid in synchronizing the resumption of ovarian function with a reduction in the energy demands of milk production. This hypothesis is supported by the sustained weight gain experienced by lactating women during the months preceding the first postpartum menses. The link between fecundity and energy balance could serve as a mechanism for adjusting the duration of lactational amenorrhea to the relative metabolic load of lactation. PMID:19298003

The management of type 1 diabetes in primary school: review of the literature.

PubMed

Marks, Anne; Wilson, Valerie; Crisp, Jackie

2013-01-01

Type 1 diabetes is one of the most common chronic health conditions in childhood. The introduction of intensive insulin therapy and the rising prevalence of diabetes in younger children has increased the need for involvement of diabetes educators and school personnel in school diabetes care. School encompasses a significant proportion of a child's day, therefore diabetes treatment at school needs to be optimal or the child will have poor metabolic control. The aim of this literature review is to examine diabetes management in the early primary school setting. The main areas of diabetes management explored are: type, provision, and location of treatment, the impact on the child, and the role of the credentialed diabetes educator. The review identifies that the majority of children are not receiving intensive diabetes treatment at school. Younger children require more assistance with care and may be disadvantaged due to lack of appropriate school staff support. Most schools do not have nurses to assist with diabetes care, therefore teaching and administration staff are utilized. The use of insulin pump therapy may increase access to insulin at school, as children and teaching staff appear more confident with this method of delivery than injections. Treatment is frequently performed away from the classroom and can impact on class attendance, metabolic control, and emergencies. Diabetes educators need to work in collaboration with children, parents, and school personnel to ensure diabetes care is fully integrated into the school day.

Effects of exercise intensity on plasma concentrations of appetite-regulating hormones: Potential mechanisms.

PubMed

Hazell, Tom J; Islam, Hashim; Townsend, Logan K; Schmale, Matt S; Copeland, Jennifer L

2016-03-01

The physiological control of appetite regulation involves circulating hormones with orexigenic (appetite-stimulating) and anorexigenic (appetite-inhibiting) properties that induce alterations in energy intake via perceptions of hunger and satiety. As the effectiveness of exercise to induce weight loss is a controversial topic, there is considerable interest in the effect of exercise on the appetite-regulating hormones such as acylated ghrelin, peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and pancreatic polypeptide (PP). Research to date suggests short-term appetite regulation following a single exercise session is likely affected by decreases in acylated ghrelin and increases in PYY, GLP-1, and PP. Further, this exercise-induced response may be intensity-dependent. In an effort to guide future research, it is important to consider how exercise alters the circulating concentrations of these appetite-regulating hormones. Potential mechanisms include blood redistribution, sympathetic nervous system activity, gastrointestinal motility, cytokine release, free fatty acid concentrations, lactate production, and changes in plasma glucose and insulin concentrations. This review of relevant research suggests blood redistribution during exercise may be important for suppressing ghrelin, while other mechanisms involving cytokine release, changes in plasma glucose and insulin concentrations, SNS activity, and muscle metabolism likely mediate changes in the anorexigenic signals PYY and GLP-1. Overall, changes in appetite-regulating hormones following acute exercise appear to be intensity-dependent, with increasing intensity leading to a greater suppression of orexigenic signals and greater stimulation of anorexigenic signals. However, there is less research on how exercise-induced responses in appetite-regulating hormones differ between sexes or different age groups. A better understanding of how exercise intensity and workload affect appetite across the sexes and life stages will be a powerful tool in developing more successful strategies for managing weight. Copyright © 2015 Elsevier Ltd. All rights reserved.

Light at night acutely impairs glucose tolerance in a time-, intensity- and wavelength-dependent manner in rats.

PubMed

Opperhuizen, Anne-Loes; Stenvers, Dirk J; Jansen, Remi D; Foppen, Ewout; Fliers, Eric; Kalsbeek, Andries

2017-07-01

Exposure to light at night (LAN) has increased dramatically in recent decades. Animal studies have shown that chronic dim LAN induced obesity and glucose intolerance. Furthermore, several studies in humans have demonstrated that chronic exposure to artificial LAN may have adverse health effects with an increased risk of metabolic disorders, including type 2 diabetes. It is well-known that acute exposure to LAN affects biological clock function, hormone secretion and the activity of the autonomic nervous system, but data on the effects of LAN on glucose homeostasis are lacking. This study aimed to investigate the acute effects of LAN on glucose metabolism. Male Wistar rats were subjected to i.v. glucose or insulin tolerance tests while exposed to 2 h of LAN in the early or late dark phase. In subsequent experiments, different light intensities and wavelengths were used. LAN exposure early in the dark phase at ZT15 caused increased glucose responses during the first 20 min after glucose infusion (p < 0.001), whereas LAN exposure at the end of the dark phase, at ZT21, caused increased insulin responses during the first 10 min (p < 0.01), indicating that LAN immediately induces glucose intolerance in rats. Subsequent experiments demonstrated that the effect of LAN was both intensity- and wavelength-dependent. White light of 50 and 150 lx induced greater glucose responses than 5 and 20 lx, whereas all intensities other than 5 lx reduced locomotor activity. Green light induced glucose intolerance, but red and blue light did not, suggesting the involvement of a specific retina-brain pathway. Together, these data show that exposure to LAN has acute adverse effects on glucose metabolism in a time-, intensity- and wavelength-dependent manner.

VEMP responses are not affected in non-insulin-dependent diabetes mellitus patients with or without polyneuropathy.

PubMed

Bektas, Devrim; Gazioglu, Sibel; Arslan, Selcuk; Cobanoglu, Bengu; Boz, Cavit; Caylan, Refik

2008-07-01

Vestibular evoked myogenic responses (VEMPs) are not affected in non-insulin-dependent diabetes mellitus (NIDDM) patients with or without polyneuropathy. To compare VEMP responses of NIDDM patients and healthy subjects. VEMP responses were collected from 25 NIDDM patients with polyneuropathy (PNP), 13 NIDDM patients without PNP and 21 healthy subjects using click stimulation. After excluding ears with hearing loss (HL) (worse than 25 dB) the VEMP responses (p13 and n21 latencies and amplitude) recorded in 105 dB stimulus intensity were compared. There was no statistically significant difference between groups. VEMP responses were found to be normal in NIDDM patients with or without PNP.

Critical factors influencing physicians' intention to use computerized clinical practice guidelines: an integrative model of activity theory and the technology acceptance model.

PubMed

Hsiao, Ju-Ling; Chen, Rai-Fu

2016-01-16

With the widespread use of information communication technologies, computerized clinical practice guidelines are developed and considered as effective decision supporting tools in assisting the processes of clinical activities. However, the development of computerized clinical practice guidelines in Taiwan is still at the early stage and acceptance level among major users (physicians) of computerized clinical practice guidelines is not satisfactory. This study aims to investigate critical factors influencing physicians' intention to computerized clinical practice guideline use through an integrative model of activity theory and the technology acceptance model. The survey methodology was employed to collect data from physicians of the investigated hospitals that have implemented computerized clinical practice guidelines. A total of 505 questionnaires were sent out, with 238 completed copies returned, indicating a valid response rate of 47.1 %. The collected data was then analyzed by structural equation modeling technique. The results showed that attitudes toward using computerized clinical practice guidelines (γ = 0.451, p < 0.001), organizational support (γ = 0.285, p < 0.001), perceived usefulness of computerized clinical practice guidelines (γ = 0.219, p < 0.05), and social influence (γ = 0.213, p < 0.05) were critical factors influencing physicians' intention to use computerized clinical practice guidelines, and these factors can explain 68.6 % of the variance in intention to use computerized clinical practice guidelines. This study confirmed that some subject (human) factors, environment (organization) factors, tool (technology) factors mentioned in the activity theory should be carefully considered when introducing computerized clinical practice guidelines. Managers should pay much attention on those identified factors and provide adequate resources and incentives to help the promotion and use of computerized clinical practice guidelines. Through the appropriate use of computerized clinical practice guidelines, the clinical benefits, particularly in improving quality of care and facilitating the clinical processes, will be realized.

39 CFR 501.15 - Computerized Meter Resetting System.

Code of Federal Regulations, 2010 CFR

2010-07-01

... AND DISTRIBUTE POSTAGE EVIDENCING SYSTEMS § 501.15 Computerized Meter Resetting System. (a) Description. The Computerized Meter Resetting System (CMRS) permits customers to reset their postage meters at... 39 Postal Service 1 2010-07-01 2010-07-01 false Computerized Meter Resetting System. 501.15...

Consensus recommendations for the management of hyperglycaemia in critically ill patients in the Indian setting.

PubMed

Mukherjee, J J; Chatterjee, P S; Saikia, M; Muruganathan, A; Das, Ashok Kumar

2014-07-01

Hyperglycaemia occurs frequently in critically-ill patients. Not only does it occur among patients with pre-existing diabetes mellitus but elevated blood glucose values during an acute illness can also be seen in previously glucose-tolerant individuals (stress hyperglycaemia). Numerous observational studies have shown an increase in morbidity and mortality in critically ill patients with hyperglycaemia. Interestingly, outcomes in individuals with stress hyperglycaemia are worse than that in critically ill hyperglycaemic patients with pre-existing diabetes. Proper management of hyperglycaemia has been shown to result in improved clinical outcomes. Critically ill patients with hyperglycaemia should primarily be managed with intravenous insulin infusion to allow dynamic adjustment of treatment to suit the rapid changes in blood glucose values in these patients. Currently, there are in existence a fair number of published protocols to administer intensive intravenous insulin therapy that range from the relatively simple to the fairly complex. Different management strategies have been proposed depending upon whether the critically ill hyperglycaemic patient is stationed in the emergency department, the medical intensive care unit (ICU), the surgical ICU or the coronary care unit. Moreover, the ideal target blood glucose value to maintain in this group of patients remains controversial. Keeping these issues in mind, a group of leading experts in the fields of diabetes and critical care extensively reviewed the literature and framed recommendations with special attention to clinical practice in India. The aim was to formulate recommendations which are based on sound evidence and yet are simple and easy to understand and implement across the ICU throughout the country. In the current recommendations, intensive intravenous insulin therapy has been suggested as the preferred mode of managing hyperglycaemia in patients admitted to critical care settings. The current recommendations suggest using a simple and similar protocol for managing hyperglycaemia in critically-ill patients irrespective of their location among the various critical care units in a hospital. Recommendations have also been made for transition from intravenous to subcutaneous administration of insulin when the patient is transferred out of the critical care setting. It is hoped that the current recommendations shall form the basis for the management of hyperglycaemia in critically ill patients across the country.

The cognitive cost of anticholinergic burden: decreased response to cognitive training in schizophrenia.

PubMed

Vinogradov, Sophia; Fisher, Melissa; Warm, Heather; Holland, Christine; Kirshner, Margaret A; Pollock, Bruce G

2009-09-01

Schizophrenia is treated with medications that raise serum anticholinergic activity and are known to adversely affect cognition. The authors examined the relationship between serum anticholinergic activity and baseline cognitive performance and response to computerized cognitive training in outpatients with schizophrenia. Fifty-five patients were randomly assigned to either computerized cognitive training or a computer games control condition. A neurocognitive battery based on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative was performed at baseline and after the intervention. Serum anticholinergic activity, measured at study entry by radioreceptor assay, was available for 49 patients. Serum anticholinergic activity showed a significant negative correlation with baseline performance in verbal working memory and verbal learning and memory, accounting for 7% of the variance in these measures, independent of age, IQ, or symptom severity. Patients in the cognitive training condition (N=25) showed a significant gain in global cognition compared to those in the control condition, but this improvement was negatively correlated with anticholinergic burden. Serum anticholinergic activity uniquely accounted for 20% of the variance in global cognition change, independent of age, IQ, or symptom severity. Serum anticholinergic activity in schizophrenia patients shows a significant association with impaired performance in MATRICS-based measures of verbal working memory and verbal learning and memory and is significantly associated with a lowered response to an intensive course of computerized cognitive training. These findings underscore the cognitive cost of medications that carry a high anticholinergic burden. The findings also have implications for the design and evaluation of cognitive treatments for schizophrenia.

Validation of an electronic surveillance system for acute lung injury

PubMed Central

Herasevich, Vitaly; Yilmaz, Murat; Khan, Hasrat; Hubmayr, Rolf D.; Gajic, Ognjen

2009-01-01

Objective Early detection of acute lung injury (ALI) is essential for timely implementation of evidence-based therapies and enrollment into clinical trials. We aimed to determine the accuracy of computerized syndrome surveillance for detection of ALI in hospitalized patients and compare it with routine clinical assessment. Design Using a near-real time copy of the electronic medical records we developed and validated a custom ALI electronic alert (ALI “sniffer”) based on the European-American Consensus Conference Definition and compared its performance against provider derived documentation. Patients and setting Consecutive 3795 critically ill patients admitted to 9 multidisciplinary intensive care units (ICUs) of a tertiary care teaching institution. Measurements and main results ALI developed in 325 patients and was recognized by bedside clinicians in only 86 (26.5%). Under-recognition of ALI was associated with not implementing protective mechanical ventilation (median tidal volumes of 9.2 vs 8.0 mL/kg predicted body weight, p<0.001). ALI “sniffer” demonstrated excellent sensitivity, 96% (95% CI 94 to 98) and moderate specificity, 89% (95% CI 88 to 90) with a positive predictive value ranging from 24% (95% CI 13 to 40) in the heart-lung transplant ICU to 64% (95% CI 55 to 71) in the medical ICU. Conclusions Computerized surveillance system accurately identifies critically ill patients who develop ALI syndrome. Since the lack of ALI recognition is a barrier to the timely implementation of best practices and enrollment into research studies, computerized syndrome surveillance could be a useful tool to enhance patient safety and clinical research. PMID:19280175

Transcriptomic and metabolomic profiling of chicken adipose tissue in response to insulin neutralization and fasting

PubMed Central

2012-01-01

Background Domestic broiler chickens rapidly accumulate adipose tissue due to intensive genetic selection for rapid growth and are naturally hyperglycemic and insulin resistant, making them an attractive addition to the suite of rodent models used for studies of obesity and type 2 diabetes in humans. Furthermore, chicken adipose tissue is considered as poorly sensitive to insulin and lipolysis is under glucagon control. Excessive fat accumulation is also an economic and environmental concern for the broiler industry due to the loss of feed efficiency and excessive nitrogen wasting, as well as a negative trait for consumers who are increasingly conscious of dietary fat intake. Understanding the control of avian adipose tissue metabolism would both enhance the utility of chicken as a model organism for human obesity and insulin resistance and highlight new approaches to reduce fat deposition in commercial chickens. Results We combined transcriptomics and metabolomics to characterize the response of chicken adipose tissue to two energy manipulations, fasting and insulin deprivation in the fed state. Sixteen to 17 day-old commercial broiler chickens (ISA915) were fed ad libitum, fasted for five hours, or fed but deprived of insulin by injections of anti-insulin serum. Pair-wise contrasts of expression data identified a total of 2016 genes that were differentially expressed after correction for multiple testing, with the vast majority of differences due to fasting (1780 genes). Gene Ontology and KEGG pathway analyses indicated that a short term fast impacted expression of genes in a broad selection of pathways related to metabolism, signaling and adipogenesis. The effects of insulin neutralization largely overlapped with the response to fasting, but with more modest effects on adipose tissue metabolism. Tissue metabolomics indicated unique effects of insulin on amino acid metabolism. Conclusions Collectively, these data provide a foundation for further study into the molecular basis for adipose expansion in commercial poultry and identify potential pathways through which fat accretion may be attenuated in the future through genetic selection or management practices. They also highlight chicken as a useful model organism in which to study the dynamic relationship between food intake, metabolism, and adipose tissue biology. PMID:22938590

Studies of insulin resistance in patients with clinical and subclinical hyperthyroidism.

PubMed

Maratou, Eirini; Hadjidakis, Dimitrios J; Peppa, Melpomeni; Alevizaki, Maria; Tsegka, Katerina; Lambadiari, Vaia; Mitrou, Panayota; Boutati, Eleni; Kollias, Anastasios; Economopoulos, Theofanis; Raptis, Sotirios A; Dimitriadis, George

2010-10-01

Although clinical hyperthyroidism (HR) is associated with insulin resistance, the information on insulin action in subclinical hyperthyroidism (SHR) is limited. To investigate this, we assessed the sensitivity of glucose metabolism to insulin in vivo (by an oral glucose tolerance test) and in vitro (by measuring insulin-stimulated rates of glucose transport in isolated monocytes) in 12 euthyroid subjects (EU), 16 patients with HR, and 10 patients with SHR. HR and SHR patients displayed higher postprandial glucose levels (area under the curve, AUC(0)(-)(300) 32,190±1067 and 31,497±716,mg/dl min respectively) versus EU (27,119±1156 mg/dl min, P<0.05). HR but not SHR patients displayed higher postprandial insulin levels (AUC(0)(-)(300) 11,020±985 and 9565±904 mU/l min respectively) compared with EU subjects (AUC(0)(-)(300) 7588±743 mU/l min, P<0.05). Homeostasis model assessment index was increased in HR and SHR patients (2.81±0.3 and 2.43±0.38 respectively) compared with EU subjects (1.27±0.16, P<0.05), while Matsuda and Belfiore indices were decreased in HR (4.21±0.41 and 0.77±0.05 respectively, P<0.001) and SHR patients (4.47±0.33 and 0.85±0.05 respectively, P<0.05 versus EU (7.76±0.87 and 1 respectively). At 100 μU/ml insulin, i) GLUT3 levels on the monocyte plasma membrane were increased in HR (468.8±7 mean fluorescence intensity (MFI)) and SHR patients (522.2±25 MFI) compared with EU subjects (407±18 MFI, P<0.01 and P<0.05 respectively), ii) glucose transport rates in monocytes (increases from baseline) were decreased in HR patients (37.8±5%) versus EU subjects (61.26±10%, P<0.05). Insulin-stimulated glucose transport in isolated monocytes of patients with HR was decreased compared with EU subjects. Insulin resistance was comparable in patients with both HR and SHR.

Computer-determined dosage of insulin in the management of neonatal hyperglycaemia (HINT2): protocol of a randomised controlled trial.

PubMed

Alsweiler, Jane; Williamson, Kathryn; Bloomfield, Frank; Chase, Geoffrey; Harding, Jane

2017-03-06

Neonatal hyperglycaemia is frequently treated with insulin, which may increase the risk of hypoglycaemia. Computer-determined dosage of insulin (CDD) with the STAR-GRYPHON program uses a computer model to predict an effective dose of insulin to treat hyperglycaemia while minimising the risk of hypoglycaemia. However, CDD models can require more frequent blood glucose testing than common clinical protocols. The aim of this trial is to determine if CDD using STAR-GRYPHON reduces hypoglycaemia in hyperglycaemic preterm babies treated with insulin independent of the frequency of blood glucose testing. Design: Multicentre, non-blinded, randomised controlled trial. Neonatal intensive care units in New Zealand and Australia. 138 preterm babies ≤30 weeks' gestation or ≤1500 g at birth who develop hyperglycaemia (two consecutive blood glucose concentrations ≥10 mmol/L, at least 4 hours apart) will be randomised to one of three groups: (1) CDD using the STAR-GRYPHON model-based decision support system: insulin dose and frequency of blood glucose testing advised by STAR-GRYPHON, with a maximum testing interval of 4 hours; (2) bedside titration: insulin dose determined by medical staff, maximum blood glucose testing interval of 4 hours; (3) standard care: insulin dose and frequency of blood glucose testing determined by medical staff. The target range for blood glucose concentrations is 5-8 mmol/L in all groups. A subset of babies will have masked continuous glucose monitoring. is the number of babies with one or more episodes of hypoglycaemia (blood glucose concentration <2.6 mmol/L), during treatment with insulin. This protocol has been approved by New Zealand's Health and Disability Ethics Committee: 14/STH/26. A data safety monitoring committee has been appointed to oversee the trial. Findings will be disseminated to participants and carers, peer-reviewed journals, guideline developers and the public. 12614000492651. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Adipokines, cytokines and body fat stores in hepatitis C virus liver steatosis

PubMed Central

González-Reimers, Emilio; López-Prieto, Javier; Quintero-Platt, Geraldine; Pelazas-González, Ricardo; Alemán-Valls, M Remedios; Pérez-Hernández, Onán; de-la-Vega-Prieto, M José; Gómez-Rodríguez, M Angeles; Martín-González, Candelaria; Santolaria-Fernández, Francisco

2016-01-01

AIM: To identify patients with or without liver steatosis and its severity in treatment-naïve patients affected by hepatitis C virus (HCV) infection. METHODS: We included 56 HCV infected patients, and assessed the amount of liver fat by histomorphometry, and its relationships with fat and lean mass at different parts of the body (by densitometry), hormones [insulin, homeostatic model assessment (HOMA)], adipokines (resistin, adiponectin, leptin), and cytokines (tumor necrosis factor α, interleukin-6). RESULTS: Although the intensity of liver steatosis is related to trunk fat mass and HOMA, 33% of patients showed no liver steatosis, and this finding was not related to body mass index or genotype. Besides trunk fat mass, no other factor was related to the presence or not of liver steatosis, or to the intensity of it, by multivariate analysis. Lean mass was not related to liver steatosis. Adiponectin levels were lower among patients. No differences were observed in leptin and resistin. CONCLUSION: Steatosis in HCV infection is common (67.2%), and closely related to trunk fat, and insulin resistance, but not with leg fat mass or adipokines. PMID:26783423

Adipokines, cytokines and body fat stores in hepatitis C virus liver steatosis.

PubMed

González-Reimers, Emilio; López-Prieto, Javier; Quintero-Platt, Geraldine; Pelazas-González, Ricardo; Alemán-Valls, M Remedios; Pérez-Hernández, Onán; de-la-Vega-Prieto, M José; Gómez-Rodríguez, M Angeles; Martín-González, Candelaria; Santolaria-Fernández, Francisco

2016-01-08

To identify patients with or without liver steatosis and its severity in treatment-naïve patients affected by hepatitis C virus (HCV) infection. We included 56 HCV infected patients, and assessed the amount of liver fat by histomorphometry, and its relationships with fat and lean mass at different parts of the body (by densitometry), hormones [insulin, homeostatic model assessment (HOMA)], adipokines (resistin, adiponectin, leptin), and cytokines (tumor necrosis factor α, interleukin-6). Although the intensity of liver steatosis is related to trunk fat mass and HOMA, 33% of patients showed no liver steatosis, and this finding was not related to body mass index or genotype. Besides trunk fat mass, no other factor was related to the presence or not of liver steatosis, or to the intensity of it, by multivariate analysis. Lean mass was not related to liver steatosis. Adiponectin levels were lower among patients. No differences were observed in leptin and resistin. Steatosis in HCV infection is common (67.2%), and closely related to trunk fat, and insulin resistance, but not with leg fat mass or adipokines.

Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells

PubMed Central

Lee, Jonghyeob; Sugiyama, Takuya; Liu, Yinghua; Wang, Jing; Gu, Xueying; Lei, Ji; Markmann, James F; Miyazaki, Satsuki; Miyazaki, Jun-ichi; Szot, Gregory L; Bottino, Rita; Kim, Seung K

2013-01-01

Pancreatic islet β-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional β-cell replacement from renewable sources is the focus of intensive worldwide effort. However, in vitro production of progeny that secrete insulin in response to physiological cues from primary human cells has proven elusive. Here we describe fractionation, expansion and conversion of primary adult human pancreatic ductal cells into progeny resembling native β-cells. FACS-sorted adult human ductal cells clonally expanded as spheres in culture, while retaining ductal characteristics. Expression of the cardinal islet developmental regulators Neurog3, MafA, Pdx1 and Pax6 converted exocrine duct cells into endocrine progeny with hallmark β-cell properties, including the ability to synthesize, process and store insulin, and secrete it in response to glucose or other depolarizing stimuli. These studies provide evidence that genetic reprogramming of expandable human pancreatic cells with defined factors may serve as a general strategy for islet replacement in diabetes. DOI: http://dx.doi.org/10.7554/eLife.00940.001 PMID:24252877

Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells.

PubMed

Lee, Jonghyeob; Sugiyama, Takuya; Liu, Yinghua; Wang, Jing; Gu, Xueying; Lei, Ji; Markmann, James F; Miyazaki, Satsuki; Miyazaki, Jun-Ichi; Szot, Gregory L; Bottino, Rita; Kim, Seung K

2013-11-19

Pancreatic islet β-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional β-cell replacement from renewable sources is the focus of intensive worldwide effort. However, in vitro production of progeny that secrete insulin in response to physiological cues from primary human cells has proven elusive. Here we describe fractionation, expansion and conversion of primary adult human pancreatic ductal cells into progeny resembling native β-cells. FACS-sorted adult human ductal cells clonally expanded as spheres in culture, while retaining ductal characteristics. Expression of the cardinal islet developmental regulators Neurog3, MafA, Pdx1 and Pax6 converted exocrine duct cells into endocrine progeny with hallmark β-cell properties, including the ability to synthesize, process and store insulin, and secrete it in response to glucose or other depolarizing stimuli. These studies provide evidence that genetic reprogramming of expandable human pancreatic cells with defined factors may serve as a general strategy for islet replacement in diabetes. DOI: http://dx.doi.org/10.7554/eLife.00940.001.

Strategies for searching medical natural language text. Distribution of words in the anatomic diagnoses of 7000 autopsy subjects.

PubMed Central

Moore, G. W.; Hutchins, G. M.; Miller, R. E.

1984-01-01

Computerized indexing and retrieval of medical records is increasingly important; but the use of natural language versus coded languages (SNOP, SNOMED) for this purpose remains controversial. In an effort to develop search strategies for natural language text, the authors examined the anatomic diagnosis reports by computer for 7000 consecutive autopsy subjects spanning a 13-year period at The Johns Hopkins Hospital. There were 923,657 words, 11,642 of them distinct. The authors observed an average of 1052 keystrokes, 28 lines, and 131 words per autopsy report, with an average 4.6 words per line and 7.0 letters per word. The entire text file represented 921 hours of secretarial effort. Words ranged in frequency from 33,959 occurrences of "and" to one occurrence for each of 3398 different words. Searches for rare diseases with unique names or for representative examples of common diseases were most readily performed with the use of computer-printed key word in context (KWIC) books. For uncommon diseases designated by commonly used terms (such as "cystic fibrosis"), needs were best served by a computerized search for logical combinations of key words. In an unbalanced word distribution, each conjunction (logical and) search should be performed in ascending order of word frequency; but each alternation (logical inclusive or) search should be performed in descending order of word frequency. Natural language text searches will assume a larger role in medical records analysis as the labor-intensive procedure of translation into a coded language becomes more costly, compared with the computer-intensive procedure of text searching. PMID:6546837

A Computerized Microelectrode Recording to Magnetic Resonance Imaging Mapping System for Subthalamic Nucleus Deep Brain Stimulation Surgery.

PubMed

Dodani, Sunjay S; Lu, Charles W; Aldridge, J Wayne; Chou, Kelvin L; Patil, Parag G

2018-06-01

Accurate electrode placement is critical to the success of deep brain stimulation (DBS) surgery. Suboptimal targeting may arise from poor initial target localization, frame-based targeting error, or intraoperative brain shift. These uncertainties can make DBS surgery challenging. To develop a computerized system to guide subthalamic nucleus (STN) DBS electrode localization and to estimate the trajectory of intraoperative microelectrode recording (MER) on magnetic resonance (MR) images algorithmically during DBS surgery. Our method is based upon the relationship between the high-frequency band (HFB; 500-2000 Hz) signal from MER and voxel intensity on MR images. The HFB profile along an MER trajectory recorded during surgery is compared to voxel intensity profiles along many potential trajectories in the region of the surgically planned trajectory. From these comparisons of HFB recordings and potential trajectories, an estimate of the MER trajectory is calculated. This calculated trajectory is then compared to actual trajectory, as estimated by postoperative high-resolution computed tomography. We compared 20 planned, calculated, and actual trajectories in 13 patients who underwent STN DBS surgery. Targeting errors for our calculated trajectories (2.33 mm ± 0.2 mm) were significantly less than errors for surgically planned trajectories (2.83 mm ± 0.2 mm; P = .01), improving targeting prediction in 70% of individual cases (14/20). Moreover, in 4 of 4 initial MER trajectories that missed the STN, our method correctly indicated the required direction of targeting adjustment for the DBS lead to intersect the STN. A computer-based algorithm simultaneously utilizing MER and MR information potentially eases electrode localization during STN DBS surgery.

21 CFR 884.2800 - Computerized Labor Monitoring System.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Computerized Labor Monitoring System. 884.2800... Devices § 884.2800 Computerized Labor Monitoring System. (a) Identification. A computerized labor monitoring system is a system intended to continuously measure cervical dilation and fetal head descent and...

45 CFR 307.15 - Approval of advance planning documents for computerized support enforcement systems.

Code of Federal Regulations, 2010 CFR

2010-10-01

... computerized support enforcement systems. 307.15 Section 307.15 Public Welfare Regulations Relating to Public... CHILDREN AND FAMILIES, DEPARTMENT OF HEALTH AND HUMAN SERVICES COMPUTERIZED SUPPORT ENFORCEMENT SYSTEMS § 307.15 Approval of advance planning documents for computerized support enforcement systems. (a...

Arkansas' Curriculum Guide. Competency Based Computerized Accounting.

ERIC Educational Resources Information Center

Arkansas State Dept. of Education, Little Rock. Div. of Vocational, Technical and Adult Education.

This guide contains the essential parts of a total curriculum for a one-year secondary-level course in computerized accounting. Addressed in the individual sections of the guide are the following topics: the complete accounting cycle, computer operations for accounting, computerized accounting and general ledgers, computerized accounts payable,…

Novel All-Extremity High-Intensity Interval Training Improves Aerobic Fitness, Cardiac Function and Insulin Resistance in Healthy Older Adults

PubMed Central

Hwang, Chueh-Lung; Yoo, Jeung-Ki; Kim, Han-Kyul; Hwang, Moon-Hyon; Handberg, Eileen M.; Petersen, John W.; Christou, Demetra D.

2016-01-01

Aging is associated with decreased aerobic fitness and cardiac remodeling leading to increased risk for cardiovascular disease. High-intensity interval training (HIIT) on the treadmill has been reported to be more effective in ameliorating these risk factors compared with moderate-intensity continuous training (MICT) in patients with cardiometabolic disease. In older adults, however, weight-bearing activities are frequently limited due to musculoskeletal and balance problems. The purpose of this study was to examine the feasibility and safety of non-weight-bearing all-extremity HIIT in older adults. In addition, we tested the hypothesis that all-extremity HIIT will be more effective in improving aerobic fitness, cardiac function, and metabolic risk factors compared with all-extremity MICT. Fifty-one healthy sedentary older adults (age: 65±1 years) were randomized to HIIT (n=17), MICT (n=18) or non-exercise control (CONT; n=16). HIIT (4×4 minutes 90% of peak heart rate; HRpeak) and isocaloric MICT (70% of HRpeak) were performed on a non-weight-bearing all-extremity ergometer, 4x/week for 8 weeks under supervision. All-extremity HIIT was feasible in older adults and resulted in no adverse events. Aerobic fitness (peak oxygen consumption; VO2peak) and ejection fraction (echocardiography) improved by 11% (P<0.0001) and 4% (P=0.001) respectively in HIIT, while no changes were observed in MICT and CONT (P≥0.1). Greater improvements in ejection fraction were associated with greater improvements in VO2peak (r=0.57; P<0.0001). Insulin resistance (homeostatic model assessment) decreased only in HIIT by 26% (P=0.016). Diastolic function, body composition, glucose and lipids were unaffected (P≥0.1). In conclusion, all-extremity HIIT is feasible and safe in older adults. HIIT, but not MICT, improved aerobic fitness, ejection fraction, and insulin resistance. PMID:27346646

Novel all-extremity high-intensity interval training improves aerobic fitness, cardiac function and insulin resistance in healthy older adults.

PubMed

Hwang, Chueh-Lung; Yoo, Jeung-Ki; Kim, Han-Kyul; Hwang, Moon-Hyon; Handberg, Eileen M; Petersen, John W; Christou, Demetra D

2016-09-01

Aging is associated with decreased aerobic fitness and cardiac remodeling leading to increased risk for cardiovascular disease. High-intensity interval training (HIIT) on the treadmill has been reported to be more effective in ameliorating these risk factors compared with moderate-intensity continuous training (MICT) in patients with cardiometabolic disease. In older adults, however, weight-bearing activities are frequently limited due to musculoskeletal and balance problems. The purpose of this study was to examine the feasibility and safety of non-weight-bearing all-extremity HIIT in older adults. In addition, we tested the hypothesis that all-extremity HIIT will be more effective in improving aerobic fitness, cardiac function, and metabolic risk factors compared with all-extremity MICT. Fifty-one healthy sedentary older adults (age: 65±1years) were randomized to HIIT (n=17), MICT (n=18) or non-exercise control (CONT; n=16). HIIT (4×4min 90% of peak heart rate; HRpeak) and isocaloric MICT (70% of HRpeak) were performed on a non-weight-bearing all-extremity ergometer, 4×/week for 8weeks under supervision. All-extremity HIIT was feasible in older adults and resulted in no adverse events. Aerobic fitness (peak oxygen consumption; VO2peak) and ejection fraction (echocardiography) improved by 11% (P<0.0001) and 4% (P=0.001), respectively in HIIT, while no changes were observed in MICT and CONT (P≥0.1). Greater improvements in ejection fraction were associated with greater improvements in VO2peak (r=0.57; P<0.0001). Insulin resistance (homeostatic model assessment) decreased only in HIIT by 26% (P=0.016). Diastolic function, body composition, glucose and lipids were unaffected (P≥0.1). In conclusion, all-extremity HIIT is feasible and safe in older adults. HIIT, but not MICT, improved aerobic fitness, ejection fraction, and insulin resistance. Copyright © 2016 Elsevier Inc. All rights reserved.

Exercise Training Reduces Intrathoracic Fat Regardless of Defective Glucose Tolerance

PubMed Central

HONKALA, SANNA M.; MOTIANI, KUMAIL K.; ESKELINEN, JARI-JOONAS; SAVOLAINEN, ANNA; SAUNAVAARA, VIRVA; VIRTANEN, KIRSI A.; LÖYTTYNIEMI, ELIISA; KAPANEN, JUKKA; KNUUTI, JUHANI; KALLIOKOSKI, KARI K.; HANNUKAINEN, JARNA C.

2017-01-01

ABSTRACT Purpose Epicardial (EAT) and pericardial (PAT) fat masses and myocardial triglyceride content (MTC) are enlarged in obesity and insulin resistance. We studied whether the high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) similarly decrease ectopic fat in and around the heart and whether the decrease is similar in healthy subjects and subjects with defective glucose tolerance (DGT). Methods A total of 28 healthy men (body mass index = 20.7–30.0 kg·m−2, age = 40–55 yr) and 16 men with DGT (body mass index = 23.8–33.5 kg·m−2, age = 43–53 yr) were randomized into HIIT and MICT interventions for 2 wk. EAT and PAT were determined by computed tomography and MTC by 1H-MRS. Results At baseline, DGT subjects had impaired aerobic capacity and insulin sensitivity and higher levels of whole body fat, visceral fat, PAT, and EAT (P < 0.05, all) compared with healthy subjects. In the whole group, HIIT increased aerobic capacity (HIIT = 6%, MICT = 0.3%; time × training P = 0.007) and tended to improve insulin sensitivity (HIIT = 24%, MICT = 8%) as well as reduce MTC (HIIT = −42%, MICT = +23%) (time × training P = 0.06, both) more efficiently compared with MICT, and without differences in the training response between the healthy and the DGT subjects. However, both training modes decreased EAT (−5%) and PAT (−6%) fat (time P < 0.05) and not differently between the healthy and the DGT subjects. Conclusion Whole body fat, visceral fat, PAT, and EAT masses are enlarged in DGT. Both HIIT and MICT effectively reduce EAT and PAT in healthy and DGT subjects, whereas HIIT seems to be superior as regards improving aerobic capacity, whole-body insulin sensitivity, and MTC. PMID:28628064

Discrete Features of Sedentary Behavior Impact Cardiometabolic Risk Factors

PubMed Central

Lyden, Kate; Keadle, Sarah Kozey; Staudenmayer, John; Braun, Barry; Freedson, Patty S.

2014-01-01

Sedentary behavior is linked to numerous poor health outcomes. Purpose To determine the effects of 7 days of increased sitting in free-living individuals on markers of cardiometabolic risk. Methods Ten, recreationally active participants (>150 min of moderate intensity physical activity per week, mean (SD) age; 25.2 y (5.7), BMI 24.9 m˙kg−2 (4.3)) completed a 7-day baseline period and a 7-day sedentary condition in their free-living environment. During baseline participants maintained normal activity. Following baseline, participants completed a 7-day sedentary condition. Participants were instructed to sit as much as possible, limit standing and walking and refrain from structured exercise and leisure time physical activity. The activPAL™ was used to assess sedentary behavior and physical activity. Fasting lipids, glucose and insulin were measured and an oral glucose tolerance test (OGTT) was performed following baseline and sedentary conditions. Results In comparison to baseline, total sedentary time (mean change (95% CI); 14.9% (10.2, 19.6)), and time in prolonged/uninterrupted sedentary bouts significantly increased, while the rate of breaks from sedentary time was significantly reduced (21.4% (6.9, 35.9)). For the OGTT, 2 h plasma insulin (mean change (95% CI); 38.8 uU˙ml−1 (10.9, 66.8)) and area under the insulin curve (3074.1 uU˙ml−1˙120 min−1 (526.0, 5622.3)) were significantly elevated after the sedentary condition. Lipid concentrations did not change. Change in 2 h insulin was negatively associated with change in light intensity activity (r=-0.62) and positively associated with change in time in sitting bouts longer than 30 (r=0.82) and 60 min (r=0.83). Conclusion Increased free-living sitting negatively impacts markers of cardiometabolic health and specific features of sedentary behavior (e.g. time in prolonged sitting bouts) may be particularly important. PMID:25202848

Discrete features of sedentary behavior impact cardiometabolic risk factors.

PubMed

Lyden, Kate; Keadle, Sarah Kozey; Staudenmayer, John; Braun, Barry; Freedson, Patty S

2015-05-01

Sedentary behavior is linked to numerous poor health outcomes. This study aims to determine the effects of 7 d of increased sitting on markers of cardiometabolic risk among free-living individuals. Ten recreationally active participants (>150 min of moderate-intensity physical activity per week; mean ± SD age, 25.2 ± 5.7 yr; mean ± SD body mass index, 24.9 ± 4.3 kg·m(-2)) completed a 7-d baseline period and a 7-d sedentary condition in their free-living environment. At baseline, participants maintained normal activity. After baseline, participants completed a 7-d sedentary condition. Participants were instructed to sit as much as possible, to limit standing and walking, and to refrain from structured exercise and leisure time physical activity. ActivPAL monitor was used to assess sedentary behavior and physical activity. Fasting lipids, glucose, and insulin were measured, and oral glucose tolerance test was performed after baseline and sedentary condition. In comparison to baseline, total sedentary time (mean Δ, 14.9%; 95% CI, 10.2-19.6) and time in prolonged/uninterrupted sedentary bouts significantly increased, whereas the rate of breaks from sedentary time was significantly reduced (mean Δ, 21.4%; 95% CI, 6.9-35.9). For oral glucose tolerance test, 2-h plasma insulin (mean Δ, 38.8 μU·mL(-1); 95% CI, 10.9-66.8) and area under the insulin curve (mean Δ, 3074.1 μU·mL(-1) per 120 min; 95% CI, 526.0-5622.3) were significantly elevated after the sedentary condition. Lipid concentrations did not change. Change in 2-h insulin was negatively associated with change in light-intensity activity (r = -0.62) and positively associated with change in time in sitting bouts longer than 30 min (r = 0.82) and 60 min (r = 0.83). Increased free-living sitting negatively impacts markers of cardiometabolic health, and specific features of sedentary behavior (e.g., time in prolonged sitting bouts) may be particularly important.

[Role of physical activity in the therapy and prevention of Type II diabetes mellitus].

PubMed

Lehmann, R; Spinas, G A

1996-12-01

Increased physical activity should be part of the treatment for non insulin-dependent diabetic patients. Increased physical activity delays the onset of non insulin-dependent diabetes mellitus (NIDDM) or even prevents the disease in about 50% of susceptible individuals (positive family history of NIDDM, body-mass index > 25, hypertension or gestational diabetes). Regular exercise has been shown to lower plasma triglyceride and to increase high-density lipoprotein cholesterol levels. Exercise has also beneficial effects on hypertension, body composition and fat distribution. Improved glucose tolerance has been achieved in type II diabetic patients in as little as one week with an exercise program. The beneficial effect of regular exercise on glucose control appears to reflect the cumulative effect of transient improvement in glucose tolerance following each individual bout of exercise. Increased insulin sensitivity is lost after as little as three days of inactivity. Most studies suggest that the maximum benefit from exercise is most likely to occur in patients with mild diabetes in whom insulin resistance and hyperinsulinemia are present (i.e. patients with fasting blood glucose of < 11 mM). The recommended frequency and duration of exercise is three times per week or every other day and, as adjunct for weight reduction, five to seven times per week for 30 to 45 min. at an intensity of 50 to 70% VO2max (or 60 to 80% of maximal the heart rate). Because of the high incidence of ischemic heart disease in type II diabetic patients, patients older than 35 years of age should undergo a graded exercise stress electrocardiogram. Attention should be paid to foot-care and the use of appropriate footwear and diabetic late complications, such as autonomic and peripheral neuropathy. Older obese NIDDM patients can achieve significant metabolic benefits from low-intensity programs, such as daily walking, which can be easily incorporated into daily living. Taking the necessary precautions, most patients with diabetes can take part in a monitored exercise program safely.

Circulating natriuretic peptide concentrations reflect changes in insulin sensitivity over time in the Diabetes Prevention Program.

PubMed

Walford, Geoffrey A; Ma, Yong; Christophi, Costas A; Goldberg, Ronald B; Jarolim, Petr; Horton, Edward; Mather, Kieren J; Barrett-Connor, Elizabeth; Davis, Jaclyn; Florez, Jose C; Wang, Thomas J

2014-05-01

We aimed to study the relationship between measures of adiposity, insulin sensitivity and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the Diabetes Prevention Program (DPP). The DPP is a completed clinical trial. Using stored samples from this resource, we measured BMI, waist circumference (WC), an insulin sensitivity index (ISI; [1/HOMA-IR]) and NT-proBNP at baseline and at 2 years of follow-up in participants randomised to placebo (n = 692), intensive lifestyle intervention (n = 832) or metformin (n = 887). At baseline, log NT-proBNP did not differ between treatment arms and was correlated with baseline log ISI (p < 0.0001) and WC (p = 0.0003) but not with BMI (p = 0.39). After 2 years of treatment, BMI decreased in the lifestyle and metformin groups (both p < 0.0001); WC decreased in all three groups (p < 0.05 for all); and log ISI increased in the lifestyle and metformin groups (both p < 0.001). The change in log NT-proBNP did not differ in the lifestyle or metformin group vs the placebo group (p > 0.05 for both). In regression models, the change in log NT-proBNP was positively associated with the change in log ISI (p < 0.005) in all three study groups after adjusting for changes in BMI and WC, but was not associated with the change in BMI or WC after adjusting for changes in log ISI. Circulating NT-proBNP was associated with a measure of insulin sensitivity before and during preventive interventions for type 2 diabetes in the DPP. This relationship persisted after adjustment for measures of adiposity and was consistent regardless of whether a participant was treated with placebo, intensive lifestyle intervention or metformin.

Effects of Feeding Milk Replacer Ad Libitum or in Restricted Amounts for the First Five Weeks of Life on the Growth, Metabolic Adaptation, and Immune Status of Newborn Calves

PubMed Central

Schäff, Christine T.; Gruse, Jeannine; Maciej, Josefine; Mielenz, Manfred; Wirthgen, Elisa; Hoeflich, Andreas; Schmicke, Marion; Pfuhl, Ralf; Jawor, Paulina; Stefaniak, Tadeusz

2016-01-01

The pre-weaning period is critical for calf health and growth, and intensive milk feeding programs may assist postnatal development by improving body growth and organ maturation. The aim of the present work was to study the effects of ad libitum milk replacer (MR) feeding on the growth, metabolic adaptation, health, and immune status of newborn calves. Twenty-eight newborn Holstein and Holstein x Charolais crossbred calves were fed ad libitum (ADLIB) or in restricted amounts (6 liters per day; RES) during the first five weeks of life. The MR intake in the ADLIB treatment was gradually reduced at weeks 6 and 7, and all calves then received 6 liters of MR per day until day 60. Blood samples were collected to measure the plasma concentrations of metabolites, insulin, insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBP), immunoglobulins, and acute phase proteins. The expression of mRNA associated with both the somatotropic axis and gluconeogenic enzymes was measured in the liver on day 60. Intensive feeding improved MR intake and growth in ADLIB without influencing concentrate intake. Carcass weight, perirenal fat, and muscle mass were greater in ADLIB. Plasma concentrations of glucose, triglycerides, insulin, and IGF-I were greater, whereas plasma concentrations of β-hydroxybutyrate, total protein, albumin, urea, IGFBP-2 and -4, and fibrinogen were lower at distinct time points in ADLIB. The hepatic mRNA expression of cytosolic phosphoenolpyruvate carboxykinase was greater in ADLIB. Most metabolic and endocrine differences occurred during the MR feeding period, but a slightly greater concentrate intake was associated with increased plasma IGF-I and insulin at the end of the study. The immune and health status of the calves were not affected by MR feeding. However, increased plasma fibrinogen in the RES group suggested differences in the acute phase response. PMID:28036351

Effects of Feeding Milk Replacer Ad Libitum or in Restricted Amounts for the First Five Weeks of Life on the Growth, Metabolic Adaptation, and Immune Status of Newborn Calves.

PubMed

Schäff, Christine T; Gruse, Jeannine; Maciej, Josefine; Mielenz, Manfred; Wirthgen, Elisa; Hoeflich, Andreas; Schmicke, Marion; Pfuhl, Ralf; Jawor, Paulina; Stefaniak, Tadeusz; Hammon, Harald M

2016-01-01

The pre-weaning period is critical for calf health and growth, and intensive milk feeding programs may assist postnatal development by improving body growth and organ maturation. The aim of the present work was to study the effects of ad libitum milk replacer (MR) feeding on the growth, metabolic adaptation, health, and immune status of newborn calves. Twenty-eight newborn Holstein and Holstein x Charolais crossbred calves were fed ad libitum (ADLIB) or in restricted amounts (6 liters per day; RES) during the first five weeks of life. The MR intake in the ADLIB treatment was gradually reduced at weeks 6 and 7, and all calves then received 6 liters of MR per day until day 60. Blood samples were collected to measure the plasma concentrations of metabolites, insulin, insulin-like growth factor (IGF)-I and IGF binding proteins (IGFBP), immunoglobulins, and acute phase proteins. The expression of mRNA associated with both the somatotropic axis and gluconeogenic enzymes was measured in the liver on day 60. Intensive feeding improved MR intake and growth in ADLIB without influencing concentrate intake. Carcass weight, perirenal fat, and muscle mass were greater in ADLIB. Plasma concentrations of glucose, triglycerides, insulin, and IGF-I were greater, whereas plasma concentrations of β-hydroxybutyrate, total protein, albumin, urea, IGFBP-2 and -4, and fibrinogen were lower at distinct time points in ADLIB. The hepatic mRNA expression of cytosolic phosphoenolpyruvate carboxykinase was greater in ADLIB. Most metabolic and endocrine differences occurred during the MR feeding period, but a slightly greater concentrate intake was associated with increased plasma IGF-I and insulin at the end of the study. The immune and health status of the calves were not affected by MR feeding. However, increased plasma fibrinogen in the RES group suggested differences in the acute phase response.

Computerized Adaptive Personality Testing: A Review and Illustration With the MMPI-2 Computerized Adaptive Version.

ERIC Educational Resources Information Center

Forbey, Johnathan D.; Ben-Porath, Yossef S.

2007-01-01

Computerized adaptive testing in personality assessment can improve efficiency by significantly reducing the number of items administered to answer an assessment question. Two approaches have been explored for adaptive testing in computerized personality assessment: item response theory and the countdown method. In this article, the authors…

A Randomized Controlled Trial of the "Cool Teens" CD-ROM Computerized Program for Adolescent Anxiety

ERIC Educational Resources Information Center

Wuthrich, Viviana M.; Rapee, Ronald M.; Cunningham, Michael J.; Lyneham, Heidi J.; Hudson, Jennifer L.; Schniering, Carolyn A.

2012-01-01

Objective: Computerized cognitive behavioral interventions for anxiety disorders in adults have been shown to be efficacious, but limited data are available on the use of computerized interventions with young persons. Adolescents in particular are difficult to engage in treatment and may be especially suited to computerized technologies. This…

Experience with the high-intensity sweetener saccharin impairs glucose homeostasis and GLP-1 release in rats

PubMed Central

Swithers, Susan E.; Laboy, Alycia F.; Clark, Kiely; Cooper, Stephanie; Davidson, T.L.

2012-01-01

Previous work from our lab has demonstrated that experience with high-intensity sweeteners in rats leads to increased food intake, body weight gain and adiposity, along with diminished caloric compensation and decreased thermic effect of food. These changes may occur as a result of interfering with learned relations between the sweet taste of food and the caloric or nutritive consequences of consuming those foods. The present experiments determined whether experience with the high-intensity sweetener saccharin versus the caloric sweetener glucose affected blood glucose homeostasis. The results demonstrated that during oral glucose tolerance tests, blood glucose levels were more elevated in animals that had previously consumed the saccharin-sweetened supplements. In contrast, during glucose tolerance tests when a glucose solution was delivered directly into the stomach, no differences in blood glucose levels between the groups were observed. Differences in oral glucose tolerance responses were not accompanied by differences in insulin release; insulin release was similar in animals previously exposed to saccharin and those previously exposed to glucose. However, release of GLP-1 in response to an oral glucose tolerance test, but not to glucose tolerance tests delivered by gavage, was significantly lower in saccharin-exposed animals compared to glucose-exposed animals. Differences in both blood glucose and GLP-1 release in saccharin animals were rapid and transient, and suggest that one mechanism by which exposure to high-intensity sweeteners that interfere with a predictive relation between sweet tastes and calories may impair energy balance is by suppressing GLP-1 release, which could alter glucose homeostasis and reduce satiety. PMID:22561130

Greater effects of high- compared with moderate-intensity interval training on cardio-metabolic variables, blood leptin concentration and ratings of perceived exertion in obese adolescent females.

PubMed

Racil, G; Coquart, J B; Elmontassar, W; Haddad, M; Goebel, R; Chaouachi, A; Amri, M; Chamari, K

2016-06-01

This study examined the effects of high- vs. moderate-intensity interval training on cardiovascular fitness, leptin levels and ratings of perceived exertion (RPE) in obese female adolescents. Forty-seven participants were randomly assigned to one of three groups receiving either a 1:1 ratio of 15 s of effort comprising moderate-intensity interval training (MIIT at 80% maximal aerobic speed: MAS) or high-intensity interval training (HIIT at 100% MAS), with matched 15 s recovery at 50% MAS, thrice weekly, or a no-training control group. The HIIT and MIIT groups showed improved (p < 0.05) body mass (BM), BMI Z-score, and percentage of body fat (%BF). Only the HIIT group showed decreased waist circumference (WC) (p = 0.017). The effect of exercise on maximal oxygen uptake (VO2max) was significant (p = 0.019, ES = 0.48 and p = 0.010, ES = 0.57, HIIT and MIIT, respectively). The decrease of rate-pressure product (RPP) (p < 0.05, ES = 0.53 and ES = 0.46, HIIT and MIIT, respectively) followed the positive changes in resting heart rate and blood pressures. Blood glucose, insulin level and the homeostasis model assessment index for insulin decreased (p < 0.05) in both training groups. Significant decreases occurred in blood leptin (p = 0.021, ES = 0.67 and p = 0.011, ES = 0.73) and in RPE (p = 0.001, ES = 0.76 and p = 0.017, ES = 0.57) in HIIT and MIIT, respectively. In the post-intervention period, blood leptin was strongly associated with %BF (p < 0.001) and VO2max (p < 0.01) in the HIIT and MIIT groups, respectively, while RPE was strongly associated with BM (p < 0.01) in the HIIT group. The results suggest that high-intensity interval training may produce more positive effects on health determinants in comparison with the same training mode at a moderate intensity.

Similar magnitude of post-exercise hyperglycemia despite manipulating resistance exercise intensity in type 1 diabetes individuals.

PubMed

Turner, D; Gray, B J; Luzio, S; Dunseath, G; Bain, S C; Hanley, S; Richards, A; Rhydderch, D C; Ayles, M; Kilduff, L P; Campbell, M D; West, D J; Bracken, R M

2016-04-01

The aim of this study was to compare the glycemic and glucoregulatory hormone responses to low- and moderate-intensity morning resistance exercise (RE) sessions in type 1 diabetes (T1DM). Following maximal strength assessments (1RM), eight T1DM (HbA1C :72 ± 12 mmol/mol, age:34 ± 7 years, body mass index:25.7 ± 1.6 kg/m(2) ) participants attended the research facility on two separate occasions, having fasted and taken their usual basal insulin but omitting rapid-acting insulin. Participants performed six exercises for two sets of 20 repetitions at 30%1RM during one session [low-intensity RE session (LOW)] and two sets of 10 repetitions at 60%1RM during another session [moderate-intensity RE session (MOD)], followed by 65-min recovery. Sessions were matched for total mass lifted (kg). Venous blood samples were taken before and after exercise. Data (mean ± SEM) were analyzed using analysis of variance (P ≤ 0.05). There were no hypoglycemic occurrences throughout the study. Blood glucose rose similarly between sessions during exercise (P = 0.382), remaining comparable between sessions throughout recovery (P > 0.05). There was no effect of RE intensity on metabolic acidosis (P > 0.05) or peak growth hormone responses (P = 0.644), but a tendency for greater catecholamine responses under LOW (individualized peak concentrations: adrenaline MOD 0.55 ± 0.13 vs LOW 1.04 ± 0.37 nmol/L, P = 0.155; noradrenaline MOD 4.59 ± 0.86 vs LOW 7.11 ± 1.82 nmol/L, P = 0.082). The magnitude of post-exercise hyperglycemia does not differ between equal volume low and moderate intensity RE sessions performed in the morning. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Greater effects of high- compared with moderate-intensity interval training on cardio-metabolic variables, blood leptin concentration and ratings of perceived exertion in obese adolescent females

PubMed Central

Coquart, JB; Elmontassar, W; Haddad, M; Goebel, R; Chaouachi, A; Amri, M; Chamari, K

2016-01-01

This study examined the effects of high- vs. moderate-intensity interval training on cardiovascular fitness, leptin levels and ratings of perceived exertion (RPE) in obese female adolescents. Forty-seven participants were randomly assigned to one of three groups receiving either a 1:1 ratio of 15 s of effort comprising moderate-intensity interval training (MIIT at 80% maximal aerobic speed: MAS) or high-intensity interval training (HIIT at 100% MAS), with matched 15 s recovery at 50% MAS, thrice weekly, or a no-training control group. The HIIT and MIIT groups showed improved (p < 0.05) body mass (BM), BMI Z-score, and percentage of body fat (%BF). Only the HIIT group showed decreased waist circumference (WC) (p = 0.017). The effect of exercise on maximal oxygen uptake (VO2max) was significant (p = 0.019, ES = 0.48 and p = 0.010, ES = 0.57, HIIT and MIIT, respectively). The decrease of rate-pressure product (RPP) (p < 0.05, ES = 0.53 and ES = 0.46, HIIT and MIIT, respectively) followed the positive changes in resting heart rate and blood pressures. Blood glucose, insulin level and the homeostasis model assessment index for insulin decreased (p < 0.05) in both training groups. Significant decreases occurred in blood leptin (p = 0.021, ES = 0.67 and p = 0.011, ES = 0.73) and in RPE (p = 0.001, ES = 0.76 and p = 0.017, ES = 0.57) in HIIT and MIIT, respectively. In the post-intervention period, blood leptin was strongly associated with %BF (p < 0.001) and VO2max (p < 0.01) in the HIIT and MIIT groups, respectively, while RPE was strongly associated with BM (p < 0.01) in the HIIT group. The results suggest that high-intensity interval training may produce more positive effects on health determinants in comparison with the same training mode at a moderate intensity. PMID:27274107

Computerized Automated Reminder Diabetes System (CARDS): E-Mail and SMS Cell Phone Text Messaging Reminders to Support Diabetes Management

PubMed Central

Hanauer, David A.; Wentzell, Katherine; Laffel, Nikki

2009-01-01

Abstract Background: Cell phone text messaging, via the Short Messaging Service (SMS), offers the promise of a highly portable, well-accepted, and inexpensive modality for engaging youth and young adults in the management of their diabetes. This pilot and feasibility study compared two-way SMS cell phone messaging with e-mail reminders that were directed at encouraging blood glucose (BG) monitoring. Methods: Forty insulin-treated adolescents and young adults with diabetes were randomized to receive electronic reminders to check their BG levels via cell phone text messaging or e-mail reminders for a 3-month pilot study. Electronic messages were automatically generated, and participant replies with BG results were processed by the locally developed Computerized Automated Reminder Diabetes System (CARDS). Participants set their schedule for reminders on the secure CARDS website where they could also enter and review BG data. Results: Of the 40 participants, 22 were randomized to receive cell phone text message reminders and 18 to receive e-mail reminders; 18 in the cell phone group and 11 in the e-mail group used the system. Compared to the e-mail group, users in the cell phone group received more reminders (180.4 vs. 106.6 per user) and responded with BG results significantly more often (30.0 vs. 6.9 per user, P=0.04). During the first month cell phone users submitted twice as many BGs as e-mail users (27.2 vs. 13.8 per user); by month 3, usage waned. Conclusions: Cell phone text messaging to promote BG monitoring is a viable and acceptable option in adolescents and young adults with diabetes. However, maintaining interest levels for prolonged intervals remains a challenge. PMID:19848576

Computerized Automated Reminder Diabetes System (CARDS): e-mail and SMS cell phone text messaging reminders to support diabetes management.

PubMed

Hanauer, David A; Wentzell, Katherine; Laffel, Nikki; Laffel, Lori M

2009-02-01

Cell phone text messaging, via the Short Messaging Service (SMS), offers the promise of a highly portable, well-accepted, and inexpensive modality for engaging youth and young adults in the management of their diabetes. This pilot and feasibility study compared two-way SMS cell phone messaging with e-mail reminders that were directed at encouraging blood glucose (BG) monitoring. Forty insulin-treated adolescents and young adults with diabetes were randomized to receive electronic reminders to check their BG levels via cell phone text messaging or e-mail reminders for a 3-month pilot study. Electronic messages were automatically generated, and participant replies with BG results were processed by the locally developed Computerized Automated Reminder Diabetes System (CARDS). Participants set their schedule for reminders on the secure CARDS website where they could also enter and review BG data. Of the 40 participants, 22 were randomized to receive cell phone text message reminders and 18 to receive e-mail reminders; 18 in the cell phone group and 11 in the e-mail group used the system. Compared to the e-mail group, users in the cell phone group received more reminders (180.4 vs. 106.6 per user) and responded with BG results significantly more often (30.0 vs. 6.9 per user, P = 0.04). During the first month cell phone users submitted twice as many BGs as e-mail users (27.2 vs. 13.8 per user); by month 3, usage waned. Cell phone text messaging to promote BG monitoring is a viable and acceptable option in adolescents and young adults with diabetes. However, maintaining interest levels for prolonged intervals remains a challenge.

Combining computerized social cognitive training with neuroplasticity-based auditory training in schizophrenia.

PubMed

Sacks, Stephanie; Fisher, Melissa; Garrett, Coleman; Alexander, Phillip; Holland, Christine; Rose, Demian; Hooker, Christine; Vinogradov, Sophia

2013-01-01

Social cognitive deficits are an important treatment target in schizophrenia, but it is unclear to what degree they require specialized interventions and which specific components of behavioral interventions are effective. In this pilot study, we explored the effects of a novel computerized neuroplasticity-based auditory training delivered in conjunction with computerized social cognition training (SCT) in patients with schizophrenia. Nineteen clinically stable schizophrenia subjects performed 50 hours of computerized exercises that place implicit, increasing demands on auditory perception, plus 12 hours of computerized training in emotion identification, social perception, and theory of mind tasks. All subjects were assessed with MATRICS-recommended measures of neurocognition and social cognition, plus a measure of self-referential source memory before and after the computerized training. Subjects showed significant improvements on multiple measures of neurocognition. Additionally, subjects showed significant gains on measures of social cognition, including the MSCEIT Perceiving Emotions, MSCEIT Managing Emotions, and self-referential source memory, plus a significant decrease in positive symptoms. Computerized training of auditory processing/verbal learning in schizophrenia results in significant basic neurocognitive gains. Further, addition of computerized social cognition training results in significant gains in several social cognitive outcome measures. Computerized cognitive training that directly targets social cognitive processes can drive improvements in these crucial functions.

Improving the utility of the fine motor skills subscale of the comprehensive developmental inventory for infants and toddlers: a computerized adaptive test.

PubMed

Huang, Chien-Yu; Tung, Li-Chen; Chou, Yeh-Tai; Chou, Willy; Chen, Kuan-Lin; Hsieh, Ching-Lin

2017-07-27

This study aimed at improving the utility of the fine motor subscale of the comprehensive developmental inventory for infants and toddlers (CDIIT) by developing a computerized adaptive test of fine motor skills. We built an item bank for the computerized adaptive test of fine motor skills using the fine motor subscale of the CDIIT items fitting the Rasch model. We also examined the psychometric properties and efficiency of the computerized adaptive test of fine motor skills with simulated computerized adaptive tests. Data from 1742 children with suspected developmental delays were retrieved. The mean scores of the fine motor subscale of the CDIIT increased along with age groups (mean scores = 1.36-36.97). The computerized adaptive test of fine motor skills contains 31 items meeting the Rasch model's assumptions (infit mean square = 0.57-1.21, outfit mean square = 0.11-1.17). For children of 6-71 months, the computerized adaptive test of fine motor skills had high Rasch person reliability (average reliability >0.90), high concurrent validity (rs = 0.67-0.99), adequate to excellent diagnostic accuracy (area under receiver operating characteristic = 0.71-1.00), and large responsiveness (effect size = 1.05-3.93). The computerized adaptive test of fine motor skills used 48-84% fewer items than the fine motor subscale of the CDIIT. The computerized adaptive test of fine motor skills used fewer items for assessment but was as reliable and valid as the fine motor subscale of the CDIIT. Implications for Rehabilitation We developed a computerized adaptive test based on the comprehensive developmental inventory for infants and toddlers (CDIIT) for assessing fine motor skills. The computerized adaptive test has been shown to be efficient because it uses fewer items than the original measure and automatically presents the results right after the test is completed. The computerized adaptive test is as reliable and valid as the CDIIT.

Insulin Sensitivity and Plasma Glucose Response to Aerobic Exercise in Pregnant Women at Risk for Gestational Diabetes Mellitus.

PubMed

Embaby, Heba; Elsayed, Enas; Fawzy, Mohamed

2016-09-01

Gestational diabetes mellitus (GDM) is one of the common complications that occur during pregnancy. Early intervention is essential to prevent the development of the disease in the non-pregnant state but also helpful in preventing the occurrence of GDM. The aim of the study was to assess the effect of aerobic exercises on insulin sensitivity and fasting plasma glucose level in pregnant women with risk for gestational diabetes mellitus. Forty multigravidae women between 20-24 weeks of gestation with risk for GDM were randomly selected (age range was 25-35 years), body mass index ranged from 30-35 kg/m 2 . Women were divided into two equal groups: intervention group (A), which followed an aerobic exercise program in the form of walking on treadmill, three times weekly until the end of 37 weeks of gestation in addition to diet control. Control group (B) which received diet control with usual care given by obstetricians and midwives. Evaluation of the women in both groups was carried out before and after treatment program through assessment of fasting blood glucose and insulin levels. There was a highly statistically significance decrease in fasting blood glucose level, fasting insulin level in both groups where the p value was 0.0001 favoring group (A). Moderate intensity of aerobic exercises were effective in reducing fasting blood glucose level and fasting insulin level in pregnant women with risk for gestational diabetes mellitus.

Moving beyond subcutaneous insulin: the application of adjunctive therapies to the treatment of type 1 diabetes.

PubMed

Ang, Kathleen H; Sherr, Jennifer L

2017-09-01

With the discovery of insulin nearly a century ago, the diagnosis of Type 1 Diabetes (T1D) transformed from a death sentence to a chronic medical condition. Despite the advances that have been made, the vast majority of those living with T1D still struggle to achieve targeted control. Yet, a plethora of agents have been developed to treat those with Type 2 Diabetes. Exploration of how these agents may benefit those with T1D has been an area of intense investigation, especially due to the overweight/obesity epidemic, which now afflicts more than 60% of those living with T1D. Areas covered: This review focuses on agents that have been utilized, including inhaled insulin preparations, pramlintide, metformin, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and dual SGLT1/2 inhibitors. Furthermore, with approval of the first hybrid closed loop (CL) system, the development of dual hormone CL systems is being explored. While the most common agent applied to these dual systems has been glucagon, research has been conducted to assess how some of the adjunctive therapies described above could aide with achieving postprandial glucose control while on CL insulin delivery. Expert opinion: By becoming less insulin-centric and incorporating some of these other agents, it is possible we may be able to better combat T1D.

Influence of a mini-trampoline rebound exercise program on insulin resistance, lipid profile and central obesity in individuals with type 2 diabetes.

PubMed

Nuhu, Jibril M; Maharaj, Sonill S

2018-04-01

Exercises are important as an adjuvant for managing diabetes but due to fatigue and time constraints, individuals with diabetes may not engage in them. Jumping on a mini-trampoline referred to as rebound exercise is an aerobic activity used for exercise training benefits but only little research is available on its effects in diabetes. The purpose of this study was to determine the effect of mini-trampoline rebound exercise on insulin resistance, lipid profile and central obesity in type 2 diabetics. Sixty non-insulin dependent type 2 diabetics (median age: 39.0 years, median body mass index: 25.2 kg/m2) recruited using convenience sampling were randomized to a rebound exercise group (N.=30) or a control group (N.=30). The control group read health magazines or watched television while the rebound exercise group jumped on a mini-trampoline at moderate intensity for 30 minutes three times per week for 12 weeks. Postrebound exercise, significant improvements in insulin resistance, lipid profile and waist circumference were noted when compared to the control (P<0.05). The values for high density lipoprotein cholesterol increased with low density lipoprotein cholesterol, triglycerides, insulin resistance decreasing significantly from baseline (P<0.05). The findings suggest that mini-trampoline rebound exercise is beneficial for individuals with type 2 diabetes and can serve as a useful exercise approach in the management of cardiovascular risk in diabetes.

Differences in self-monitored, blood glucose test strip utilization by therapy for type 2 diabetes mellitus.

PubMed

Tavares, Ruben; Duclos, Marc; Brabant, Marie-Josée; Checchin, Daniella; Bosnic, Nevzeta; Turvey, Katherine; Terres, Jorge Alfonso Ross

2016-06-01

To determine whether blood glucose test strip (BGTS) utilization in patients with type 2 diabetes (T2D) is associated with the type of diabetes therapy, classified according to hypoglycemic risk. A retrospective, longitudinal (2006-2012) study of Canadian private drug plans (PDP) and Ontario Public Drug Programs (OPDP) prescription claims was conducted. Analyses were restricted to patients with T2D with or without a claim for BGTS. Daily BGTS utilization (TS/patient/day) was evaluated by diabetes therapy classified by hypoglycemic risk. Multivariate analyses were conducted to identify determinants of BGTS utilization. The T2D cohort comprised 5,759,591 observations from 1,949,129 claimants. Mean BGTS utilization was 0.84 TS/patient/day and differed between PDP and OPDP (0.66 vs. 1.00). Daily utilization was greatest in patients receiving therapy associated with a pre-defined high risk of hypoglycemia [insulin: basal + bolus (2.16), premixed (1.65), basal (1.16), other insulin regimens (2.13), and sulfonylureas (0.74)] versus non-sulfonylurea non-insulin-based regimens (0.52). For non-insulin therapy, BGTS utilization was greater for patients on multiple non-insulin therapies versus monotherapy (0.74 vs. 0.53 TS/patient/day). In multivariate analyses, drivers for BGTS utilization included insulin use, previous BGTS use, and female gender. Previous diabetes therapy and duration of therapy were negatively correlated with BGTS utilization. BGTS utilization varies depending on the type of therapy used to treat T2D according to hypoglycemic risk. Decision making regarding BGTS needs to account for robust analyses of current utilization and its value in those settings, including in patients not receiving diabetes therapy and the prevalence of circumstances conducive to more intensive monitoring.

Clinical review: insulin pump-associated adverse events in adults and children.

PubMed

Ross, P L; Milburn, J; Reith, D M; Wiltshire, E; Wheeler, B J

2015-12-01

Insulin pumps are a vital and rapidly developing tool in the treatment of type 1 diabetes mellitus in both adults and children. Many studies have highlighted outcomes and assessed their potential advantages, but much of the data on adverse outcomes are limited and often based on outdated technology. We aimed to review and summarize the available literature on insulin pump-associated adverse events in adults and children. A literature search was undertaken using PubMed, EMBASE, and the Cochrane library. Articles were then screened by title, followed by abstract, and full text as needed. A by-hand search of reference lists in identified papers was also utilised. All searches were limited to English language material, but no time limits were used. Current and past literature regarding insulin pump-associated adverse events is discussed, including potential metabolic and non-metabolic adverse events, in particular: pump malfunction; infusion set/site issues; and cutaneous problems. We show that even with modern technology, adverse events are common, occurring in over 40 % of users per year, with a minority, particularly in children, requiring hospital management. Hyperglycaemia and ketosis are now the most common consequences of adverse events and are usually associated with infusion set failure. This differs from older technology where infected infusion sites predominated. This timely review covers all potential insulin pump-associated adverse events, including their incidence, features, impacts, and contributory factors such as the pump user. The importance of ongoing anticipatory education and support for patients and families using this intensive insulin technology is highlighted, which if done well should improve the overall experience of pump therapy for users, and hopefully reduce the incidence and impact of severe adverse events.

Dietary tartary buckwheat intake attenuates insulin resistance and improves lipid profiles in patients with type 2 diabetes: a randomized controlled trial.

PubMed

Qiu, Ju; Liu, Yanping; Yue, Yanfen; Qin, Yuchang; Li, Zaigui

2016-12-01

Tartary buckwheat (TB) is rich in protein, dietary fiber, and flavonoids and has been reported to affect type 2 diabetes mellitus (T2DM) in animal experiments, but limited information on the benefit of TB as a whole food in T2DM patients is available. Thus, we tested the hypothesis that a daily replacement of a portion of the staple food with TB will improve risk factors of T2DM, including fasting glucose, insulin resistance, and lipid profile. In a parallel, randomized, open-label, controlled trial, 165 T2DM patients were randomly assigned to a control diet group (DC group; systematic diet plans and intensive nutritional education) or a TB intervention group (TB group; daily replacement of a portion of staple food with TB food). Blood samples and diet information were collected at baseline and after 4 weeks of intervention. The TB group decreased fasting insulin (2.46-2.39 Ln mU/L), total cholesterol (5.08-4.79 mmol/L), and low-density lipoprotein cholesterol (3.00-2.80 mmol/L) compared with the DC group at 4 weeks (P<.05). No significant differences in blood glucose or glycated hemoglobin levels were noted between the TB and DC groups. In addition, subgroup analyses based on daily TB intake dose showed a reduction in insulin, total cholesterol, and low-density lipoprotein cholesterol, but also insulin resistance was observed when TB intake dose was greater than 110 g/d. These results support the hypothesis that TB may improve insulin resistance and lipid profile in T2DM patients. Copyright © 2016 Elsevier Inc. All rights reserved.

45 CFR 310.40 - What requirements apply for accessing systems and records for monitoring Computerized Tribal IV-D...

Code of Federal Regulations, 2010 CFR

2010-10-01

... records for monitoring Computerized Tribal IV-D Systems and Office Automation? 310.40 Section 310.40... COMPUTERIZED TRIBAL IV-D SYSTEMS AND OFFICE AUTOMATION Accountability and Monitoring Procedures for... monitoring Computerized Tribal IV-D Systems and Office Automation? In accordance with Part 95 of this title...

Colocalization of insulin-like growth factor-binding protein with insulin-like growth factor I.

PubMed

Kobayashi, S; Clemmons, D R; Venkatachalam, M A

1991-07-01

We report the localization of insulin-like growth factor I (IGF-I) and a 25-kDa form of insulin-like growth factor-binding protein (IGF-BP-1) in adult rat kidney. The antigens were localized using a rabbit anti-human IGF-I antibody, and a rabbit anti-human IGF-BP-1 antibody raised against human 25-kDa IGF-BP-1 purified from amniotic fluid. Immunohistochemistry by the avidin-biotin peroxidase conjugate technique showed that both peptides are located in the same nephron segments, in the same cell types. The most intense staining was in papillary collecting ducts. There was moderate staining also in cortical collecting ducts and medullary thick ascending limbs of Henle's loop. In collecting ducts the antigens were shown to be present in principal cells but not in intercalated cells. In distal convoluted tubules, cortical thick ascending limbs, and in structures presumptively identified as thin limbs of Henle's loops there was only modest staining. The macula densa, however, lacked immunoreactivity. Colocalization of IGF-I and IGF-BP-1 in the same cells supports the notion, derived from studies on cultured cells, that the actions of IGF-I may be modified by IGF-BPs that are present in the same location.

Redox Homeostasis in Pancreatic β Cells

PubMed Central

Ježek, Petr; Dlasková, Andrea; Plecitá-Hlavatá, Lydie

2012-01-01

We reviewed mechanisms that determine reactive oxygen species (redox) homeostasis, redox information signaling and metabolic/regulatory function of autocrine insulin signaling in pancreatic β cells, and consequences of oxidative stress and dysregulation of redox/information signaling for their dysfunction. We emphasize the role of mitochondrion in β cell molecular physiology and pathology, including the antioxidant role of mitochondrial uncoupling protein UCP2. Since in pancreatic β cells pyruvate cannot be easily diverted towards lactate dehydrogenase for lactate formation, the respiration and oxidative phosphorylation intensity are governed by the availability of glucose, leading to a certain ATP/ADP ratio, whereas in other cell types, cell demand dictates respiration/metabolism rates. Moreover, we examine the possibility that type 2 diabetes mellitus might be considered as an inevitable result of progressive self-accelerating oxidative stress and concomitantly dysregulated information signaling in peripheral tissues as well as in pancreatic β cells. It is because the redox signaling is inherent to the insulin receptor signaling mechanism and its impairment leads to the oxidative and nitrosative stress. Also emerging concepts, admiting participation of redox signaling even in glucose sensing and insulin release in pancreatic β cells, fit in this view. For example, NADPH has been firmly established to be a modulator of glucose-stimulated insulin release. PMID:23304259

Synergic effects of sugar and caffeine on insulin-mediated metabolomic alterations after an acute consumption of soft drinks.

PubMed

González-Domínguez, Raúl; Mateos, Rosa María; Lechuga-Sancho, Alfonso María; González-Cortés, José Joaquín; Corrales-Cuevas, Manuel; Rojas-Cots, Juan Alberto; Segundo, Carmen; Schwarz, Mónica

2017-09-01

High sugar consumption elicits numerous deleterious effects on health by inducing insulin resistance, which is closely associated with the development of metabolic disorders such as obesity or type-2 diabetes. Furthermore, there is also growing evidence that caffeine may play an important role in the regulation of insulin release and the appearance of related metabolic impairments. Thus, the aim of this work was to investigate the impact of acute sugar and caffeine intake on the metabolic health status by using a metabolomic multi-platform based on the combination of flow injection mass spectrometry and ultra-high performance liquid chromatography mass spectrometry. To this end, we performed a randomized, crossover and double-blind intervention study with different soft drinks from the same brand. Numerous metabolomic changes were detected in serum samples over time after the intake of sugar-sweetened beverages, including energy-related metabolites, amino acids and lipids, thus demonstrating the intense effects provoked by acute sugar consumption on the organism during 3 h of follow-up. However, the most significant findings were observed after the co-ingestion of caffeine, which could be indicative of a synergic effect of this psychostimulant on insulin-mediated perturbations. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The role of adding metformin in insulin-resistant diabetic pregnant women: a randomized controlled trial.

PubMed

Ibrahim, Moustafa Ibrahim; Hamdy, Ahmed; Shafik, Adel; Taha, Salah; Anwar, Mohammed; Faris, Mohammed

2014-05-01

The aim of the present study is to assess the impact of adding oral metformin to insulin therapy in pregnant women with insulin-resistant diabetes mellitus. The current non-inferiority randomized controlled trial was conducted at Ain Shams University Maternity Hospital. The study included pregnant women with gestational or pre-existing diabetes mellitus at gestations between 20 and 34 weeks, who showed insulin resistance (defined as poor glycemic control at a daily dose of ≥1.12 units/kg). Recruited women were randomized into one of two groups: group I, including women who received oral metformin without increasing the insulin dose; and group II, including women who had their insulin dose increased. The primary outcome was maternal glycemic control. Secondary outcomes included maternal bouts of hypoglycemia, need for another hospital admission for uncontrolled diabetes during pregnancy, gestational age at delivery, mode of delivery, birth weight, birth trauma, congenital anomalies, 1- and 5-min Apgar score, neonatal hypoglycemia, need for neonatal intensive care unit (NICU) admission and adverse neonatal outcomes. A total number of 154 women with diabetes mellitus with pregnancy were approached; of them 90 women were eligible and were randomly allocated and included in the final analysis. The recruited 90 women were randomized into one of two groups: group I (metformin group) (n = 46), including women who received oral metformin in addition to the same initial insulin dose; and group II (control group) (n = 44), including women who had their insulin dose increased according to the standard protocol. The mean age of included women was 29.84 ± 5.37 years (range 20-42 years). The mean gestational age at recruitment was 28.7 ± 3.71 weeks (range 21-34 weeks). Among the 46 women of group I, 17 (36.9 %) women reached proper glycemic control at a daily metformin dose of 1,500 mg, 18 (39.2 %) at a daily dose of 2,000 mg, while 11 (23.9 %) received metformin at a daily dose of 2,000 mg without reaching proper glycemic control and needed raising the dose of insulin dose. Adding metformin to insulin therapy in women with insulin-resistant diabetes mellitus with pregnancy seems to be effective in proper glycemic control in a considerable proportion of women, along with benefits of reduced hospital stay, reduced frequency of maternal hypoglycemia as well as reduced frequency of neonatal hypoglycemia, NICU admission and neonatal respiratory distress syndrome.

Treatment of mild-to-moderate hypoglycemia in patients with type 1 diabetes treated with insulin pump therapy: are current recommendations effective?

PubMed

Gingras, Véronique; Desjardins, Katherine; Smaoui, Mohamed Raef; Savard, Valérie; Messier, Virginie; Haidar, Ahmad; Legault, Laurent; Rabasa-Lhoret, Rémi

2018-03-01

Mild-to-moderate hypoglycemia (blood glucose < 4.0 mmol/L) is recommended to be treated with 15 g of carbohydrates and to repeat the treatment if hypoglycemia persists after 15 min. This recommendation was established before intensive insulin therapy and based on studies using insulin with different pharmacokinetic profiles from actual insulin analogs showing that 15 g of glucose increases blood glucose by ~ 1.5 mmol/L in 15 min. We aimed to explore the effect of current recommended treatment of mild-to-moderate hypoglycemia in type 1 diabetes (T1D) participants and factors associated with treatment effectiveness. This is a secondary analysis from three observational inpatient studies with a standardized and supervised treatment (16 g carbohydrates) of hypoglycemia (< 3.3 mmol/L with symptoms or < 3.0 mmol/L without symptom) in participants (47 adults-10 adolescents) with T1D using continuous subcutaneous insulin infusion ("insulin pumps"; CSII)). Twenty-seven participants presented a total of 48 hypoglycemia episodes treated by a single intake of 16 g of carbohydrates. Time required for normoglycemia recovery was 19.5 ± 12.0 min. The rise in plasma glucose following treatment was 0.85 ± 0.66 mmol/L in 15 min. Eighteen episodes (38%) were resolved (> 4.0 mmol/L) 15-min post-treatment. Glycemia at the time of treatment (< 3.2 mmol/L; p < 0.001) and a higher proportion of total daily insulin from basal doses (p = 0.03) were associated with a slower post-treatment plasma glucose rise. These results raise the possibility that sixteen grams of carbohydrates could be insufficient to treat a large proportion of hypoglycemia episodes in T1D patients treated with CSII. Factors affecting treatment effectiveness need to be investigated.

In type 1 diabetics, high-dose biotin may compensate for low hepatic insulin exposure, promoting a more normal expression of glycolytic and gluconeogenic enyzymes and thereby aiding glycemic control.

PubMed

McCarty, Mark F

2016-10-01

In type 1 diabetics, hepatic exposure to insulin is chronically subnormal even in the context of insulin therapy; as a result, expression of glycolytic enzymes is decreased, and that of gluconeogenic enzymes is enhanced, resulting in a physiologically inappropriate elevation of hepatic glucose output. Subnormal expression of glucokinase (GK) is of particular importance in this regard. Possible strategies for correcting this perturbation of hepatic enzyme expression include administration of small molecule allosteric activators of GK, as well as a procedure known as chronic intermittent intravenous insulin therapy (CIIIT); however, side effects accompany the use of GK activators, and CIIIT is time and labor intensive. Alternatively, administration of high-dose biotin has potential for modulating hepatic enzyme expression in a favorable way. Studies in rodents and in cultured hepatocytes demonstrate that, in the context of low insulin exposure, supra-physiological levels of biotin induce increased expression of GK while suppressing that of the key gluconeogenic enzyme phosphoenolpyruvate carboxykinase. These effects may be a downstream consequence of the fact that biotin down-regulates mRNA expression of FOXO1; insulin's antagonism of the activity of this transcription factor is largely responsible for its modulatory impact on hepatic glycolysis and gluconeogenesis. Hence, high-dose biotin may compensate for subnormal insulin exposure by suppressing FOXO1 levels. High-dose biotin also has the potential to oppose hepatic steatosis by down-regulating SREBP-1 expression. Two pilot trials of high-dose biotin (16 or 2mg per day) in type 1 diabetics have yielded promising results. There is also some reason to suspect that high-dose biotin could aid control of diabetic neuropathy and nephropathy via its stimulatory effect on cGMP production. Owing to the safety, good tolerance, moderate expense, and current availability of high-dose biotin, this strategy merits more extensive evaluation in type 1 diabetes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Falling insulin requirements are associated with adverse obstetric outcomes in women with preexisting diabetes.

PubMed

Padmanabhan, Suja; McLean, Mark; Cheung, N Wah

2014-10-01

To investigate the clinical significance of falling insulin requirements in women with preexisting or overt diabetes in pregnancy. A retrospective review of 139 pregnancies was conducted in women, with preexisting diabetes, delivering between January 2010 and January 2013. Women with falling insulin requirements of 15% or more from the peak total daily dose in late pregnancy were considered case subjects (n = 35). The primary outcome consisted of a composite of clinical markers of placental dysfunction, including preeclampsia, small for gestational age (SGA, ≤5th percentile for gestational age), stillbirth (>20 weeks), and premature delivery (≤30 weeks). A total of 25.2% of women had >15% fall in insulin requirements with nulliparity as the only predictor at baseline (odds ratio [OR] 2.5 [95% CI 1.1-5.7], P = 0.03). Falling insulin requirements were associated with an increased risk of preeclampsia (OR 3.5 [1.1-10.7], P < 0.05) and the composite of clinical markers of placental dysfunction (4.4 [1.73-11.26], P = 0.002). Although falling insulin requirements were associated with higher rates of SGA (3.4 [1.0-11.3], P = 0.048), they were not associated with other adverse neonatal outcomes. However, there was a higher incidence of neonatal intensive care unit admission (15.5 [3.1-77.6], P = 0.001) and earlier delivery in this group (median 37.7 weeks [IQR 34.3-38.4] vs. 38.3 weeks [37.4-38.9], P = 0.014). Falling insulin requirements, in women with preexisting diabetes, are associated with an increased risk of complications related to placental dysfunction. Further prospective studies are needed to guide clinical management. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Fields of application of continuous subcutaneous insulin infusion in the treatment of diabetes and implications in the use of rapid-acting insulin analogues.

PubMed

Pitocco, D; Rizzi, A; Scavone, G; Tanese, L; Zaccardi, F; Manto, A; Ghirlanda, G

2013-09-01

In western countries, diabetes mellitus, because of macrovascular and microvascular complications related to it, is still an important cause of death. Patients with type 1 diabetes mellitus (T1DM) have a six-time higher risk of mortality than healthy patients. Since the Diabetes Control and Complications Trial (DCCT) established how an intensive therapy is necessary to prevent diabetes mellitus complications, many studies have been conducted to understand which method is able to reach an optimal metabolic control. In the past 30 years continuous subcutaneous insulin infusion established/introduced as a validate alternative to multiple daily injections. Several trials demonstrated that, when compared to MDI, CSII brings to a better metabolic control, in terms of a reduction of glycated hemoglobin and blood glucose variability, hypoglycemic episodes and improvement in quality of life. Because of their pharmacokinetic and pharmacodynamic characteristics, rapid-action insulin analogues are imposed as best insulin to be used in CSII. The rapid onset and the fast reached peak make them better mimic the way how pancreas secretes insulin. CSII by pump is not free from issues. Catheter occlusions, blockages, clogs can arrest insulin administration. The consequent higher levels of glycemic values, can easily bring to the onset of ketoacidosis, with an high risk for patients' life. Aspart is a rapid analogue obtained by aminoacidic substitution. It is as effective as lispro and glulisine in gaining a good metabolic control and even better in reducing glucose variability. Some studies tried to compare rapid analogues in terms of stability. Obtained data are controversial. An in vivo study evidenced higher stability or glulisine, while studies in vitro highlighted a higher safety of aspart. Nowadays it is not possible to assess which analogues is safer. When the infusion set is changed every 48 hours equivalent rates of occlusions have been observed.

Closed-loop controlled noninvasive ultrasonic glucose sensing and insulin delivery

NASA Astrophysics Data System (ADS)

Park, Eun-Joo; Werner, Jacob; Jaiswal, Devina; Smith, Nadine Barrie

2010-03-01

To prevent complications in diabetes, the proper management of blood glucose levels is essential. Previously, ultrasonic transdermal methods using a light-weight cymbal transducer array has been studied for noninvasive methods of insulin delivery for Type-1 diabetes and glucose level monitoring. In this study, the ultrasound systems of insulin delivery and glucose sensing have been combined by a feedback controller. This study was designed to show the feasibility of the feedback controlled ultrasound system for the noninvasive glucose control. For perspective human application, in vivo experiments were performed on large animals that have a similar size to humans. Four in vivo experiments were performed using about 200 lbs pigs. The cymbal array of 3×3 pattern has been used for insulin delivery at 30 kHz with the spatial-peak temporal-peak intensity (Isptp) of 100 mW/cm2. For glucose sensing, a 2×2 array was operated at 20 kHz with Isptp = 100 mW/cm2. Based on the glucose level determined by biosensors after the ultrasound exposure, the ultrasound system for the insulin delivery was automatically operated. The glucose level of 115 mg/dl was set as a reference value for operating the insulin delivery system. For comparison, the glucose levels of blood samples collected from the ear vein were measured by a commercial glucose meter. Using the ultrasound system operated by the close-loop, feed-back controller, the glucose levels of four pigs were determined every 20 minutes and continuously controlled for 120 minutes. In comparison to the commercial glucose meter, the glucose levels determined by the biosensor were slightly higher. The results of in vivo experiments indicate the feasibility of the feedback controlled ultrasound system using the cymbal array for noninvasive glucose sensing and insulin delivery. Further studies on the extension of the glucose control will be continued for the effective method of glucose control.

Alpha-Mangostin Improves Insulin Secretion and Protects INS-1 Cells from Streptozotocin-Induced Damage.

PubMed

Lee, Dahae; Kim, Young-Mi; Jung, Kiwon; Chin, Young-Won; Kang, Ki Sung

2018-05-16

Alpha (α)-mangostin, a yellow crystalline powder with a xanthone core structure, is isolated from mangosteen ( Garcinia mangostana ), which is a tropical fruit of great nutritional value. The aim of the present study was to investigate the anti-diabetic effects of α-mangostin and to elucidate the molecular mechanisms underlying its effect on pancreatic beta (β)-cell dysfunction. To assess the effects of α-mangostin on insulin production, rat pancreatic INS-1 cells were treated with non-toxic doses of α-mangostin (1⁻10 μM) and its impact on insulin signaling was examined by Western blotting. In addition, the protective effect of α-mangostin against pancreatic β-cell apoptosis was verified by using the β-cell toxin streptozotocin (STZ). Our results showed that α-mangostin stimulated insulin secretion in INS-1 cells by activating insulin receptor (IR) and pancreatic and duodenal homeobox 1 (Pdx1) followed by phosphorylation of phospho-phosphatidylinositol-3 kinase (PI3K), Akt, and extracellular signal regulated kinase (ERK) signaling cascades, whereas it inhibited the phosphorylation of insulin receptor substrate (IRS-1) (Ser1101). Moreover, α-mangostin was found to restore the STZ-induced decrease in INS-1 cell viability in a dose-dependent manner. In addition, treatment of INS-1 cells with 50 μM STZ resulted in an increase in intracellular reactive oxygen species (ROS) levels, which was represented by the fluorescence intensity of 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). This oxidative stress was decreased by co-treatment with 5 μM α-mangostin. Similarly, marked increases in the phosphorylation of P38, c-Jun N-terminal kinase (JNK), and cleavage of caspase-3 by STZ were decreased significantly by co-treatment with 5 μM α-mangostin. These results suggest that α-mangostin is capable of improving insulin secretion in pancreatic β-cells and protecting cells from apoptotic damage.

A cluster randomised trial, cost-effectiveness analysis and psychosocial evaluation of insulin pump therapy compared with multiple injections during flexible intensive insulin therapy for type 1 diabetes: the REPOSE Trial.

PubMed

Heller, Simon; White, David; Lee, Ellen; Lawton, Julia; Pollard, Daniel; Waugh, Norman; Amiel, Stephanie; Barnard, Katharine; Beckwith, Anita; Brennan, Alan; Campbell, Michael; Cooper, Cindy; Dimairo, Munyaradzi; Dixon, Simon; Elliott, Jackie; Evans, Mark; Green, Fiona; Hackney, Gemma; Hammond, Peter; Hallowell, Nina; Jaap, Alan; Kennon, Brian; Kirkham, Jackie; Lindsay, Robert; Mansell, Peter; Papaioannou, Diana; Rankin, David; Royle, Pamela; Smithson, W Henry; Taylor, Carolin

2017-04-01

Insulin is generally administered to people with type 1 diabetes mellitus (T1DM) using multiple daily injections (MDIs), but can also be delivered using infusion pumps. In the UK, pumps are recommended for patients with the greatest need and adult use is less than in comparable countries. Previous trials have been small, of short duration and have failed to control for training in insulin adjustment. To assess the clinical effectiveness and cost-effectiveness of pump therapy compared with MDI for adults with T1DM, with both groups receiving equivalent structured training in flexible insulin therapy. Pragmatic, multicentre, open-label, parallel-group cluster randomised controlled trial, including economic and psychosocial evaluations. After participants were assigned a group training course, courses were randomly allocated in pairs to either pump or MDI. Eight secondary care diabetes centres in the UK. Adults with T1DM for > 12 months, willing to undertake intensive insulin therapy, with no preference for pump or MDI, or a clinical indication for pumps. Pump or MDI structured training in flexible insulin therapy, followed up for 2 years. MDI participants used insulin analogues. Pump participants used a Medtronic Paradigm ® Veo TM (Medtronic, Watford, UK) with insulin aspart (NovoRapid, Novo Nordisk, Gatwick, UK). Primary outcome - change in glycated haemoglobin (HbA 1c ) at 2 years in participants whose baseline HbA 1c was ≥ 7.5% (58 mmol/mol). Key secondary outcome - proportion of participants with HbA 1c ≤ 7.5% at 2 years. Other outcomes at 6, 12 and 24 months - moderate and severe hypoglycaemia; insulin dose; body weight; proteinuria; diabetic ketoacidosis; quality of life (QoL); fear of hypoglycaemia; treatment satisfaction; emotional well-being; qualitative interviews with participants and staff (2 weeks), and participants (6 months); and ICERs in trial and modelled estimates of cost-effectiveness. We randomised 46 courses comprising 317 participants: 267 attended a Dose Adjustment For Normal Eating course (132 pump; 135 MDI); 260 were included in the intention-to-treat analysis, of which 235 (119 pump; 116 MDI) had baseline HbA 1c of ≥ 7.5%. HbA 1c and severe hypoglycaemia improved in both groups. The drop in HbA 1c % at 2 years was 0.85 on pump and 0.42 on MDI. The mean difference (MD) in HbA 1c change at 2 years, at which the baseline HbA 1c was ≥ 7.5%, was -0.24% [95% confidence interval (CI) -0.53% to 0.05%] in favour of the pump ( p  = 0.098). The per-protocol analysis showed a MD in change of -0.36% (95% CI -0.64% to -0.07%) favouring pumps ( p  = 0.015). Pumps were not cost-effective in the base case and all of the sensitivity analyses. The pump group had greater improvement in diabetes-specific QoL diet restrictions, daily hassle plus treatment satisfaction, statistically significant at 12 and 24 months and supported by qualitative interviews. Blinding of pump therapy was not possible, although an objective primary outcome was used. Adding pump therapy to structured training in flexible insulin therapy did not significantly enhance glycaemic control or psychosocial outcomes in adults with T1DM. To understand why few patients achieve a HbA 1c of < 7.5%, particularly as glycaemic control is worse in the UK than in other European countries. Current Controlled Trials ISRCTN61215213. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 21, No. 20. See the NIHR Journals Library website for further project information.

The cost effectiveness of rapid-acting insulin aspart compared with human insulin in type 2 diabetes patients: an analysis from the Japanese third-party payer perspective.

PubMed

Pollock, R F; Valentine, W J; Pilgaard, T; Nishimura, H

2011-01-01

The Nippon Ultra-Rapid Insulin and Diabetic Complication Evaluation Study (NICE Study) (NCT00575172) was a 5-year, open-label, randomised controlled trial which compared cardiovascular outcomes in Japanese type 2 diabetes patients intensively treated with regular human insulin or insulin aspart (NovoRapid; Novo Nordisk A/S, Bagsvaerd, Denmark), a rapid-acting insulin analogue. The aim of the present analysis was to evaluate the cost effectiveness of insulin aspart versus regular human insulin from the perspective of a Japanese third-party healthcare payer. A discrete event-simulation model was developed in Microsoft Excel to assess the within-trial cost effectiveness and make longer-term clinical projections in patients treated with regular human insulin or insulin aspart. In addition to severe hypoglycaemia, the model captured myocardial and cerebral infarction events and percutaneous coronary intervention and coronary artery bypass graft procedures. Within-trial mortality, incidence of severe hypoglycaemia and cardiovascular event probabilities were derived from the annual rates observed during the trial period, while post-trial outcomes were calculated using the event rates from the trial, adjusted for increasing patient age. Event costs were accounted from the healthcare payer perspective and expressed in 2008 Japanese yen (JPY), while health-related quality of life (HRQoL) was captured using event and state utilities. Future costs and clinical benefits were discounted at 3% annually. Life expectancy, quality-adjusted life expectancy, cardiovascular event rates and costs were evaluated over 5- and 10-year time horizons and sensitivity analyses were performed to assess variability in model outcomes. Over 5 years of treatment, insulin aspart dominated human insulin both in incremental life expectancy and in incremental quality-adjusted life-years (QALYS). Insulin aspart was associated with a small improvement in discounted life expectancy of 0.005 years (4.688 vs. 4.684 years) and an increase of 0.023 quality-adjusted life-years (QALYs) (3.800 vs. 3.776 QALYs) when compared with regular human insulin. Insulin aspart also incurred lower costs (JPY 481,586 vs. 594,717, difference -113,131) which resulted from the decreased incidence of cardiovascular events with insulin aspart (0.013 events per patient year vs. 0.030 on regular human insulin). Breakdown of costs indicated that pharmacy costs were higher with insulin aspart (JPY 346,608 vs. 278,468), but these costs were more than offset by the reduced costs associated with cardiovascular complications and hypoglycaemia over 5 years of treatment (JPY 134,978 vs. 316,249). Sensitivity analysis showed that insulin aspart was still cost-effective in the case where only 18% of the within-trial cardiovascular and mortality benefit over regular human insulin was captured in the model (assuming a willingness-to-pay threshold of JPY 5,000,000). The NICE study cohort was relatively small (n = 325), meaning that caution should be exercised when calculating and interpreting the incremental cost-effectiveness ratio. Also, despite the differences in cardiovascular risk profile between the Japanese and UK populations, UKPDS-derived risk equations were used to project MI outcomes and PCI and CABG procedures and UKPDS HRQoL scores were applied to all health states. While these risk formulas and HRQoL utilities may not be directly applicable to the Japanese population, no equivalent Japanese-specific data are currently available. In a Japanese type 2 diabetes population, prescribing rapid-acting insulin aspart significantly reduced cardiovascular complications over 5- and 10-year time horizons, resulting in increased quality of life and decreased costs when compared with human insulin.

Creatine Monohydrate Supplementation Does Not Augment Fitness, Performance, or Body Composition Adaptations in Response to Four Weeks of High-Intensity Interval Training in Young Females.

PubMed

Forbes, Scott C; Sletten, Nathan; Durrer, Cody; Myette-Côté, Étienne; Candow, D; Little, Jonathan P

2017-06-01

High-intensity interval training (HIIT) has been shown to improve cardiorespiratory fitness, performance, body composition, and insulin sensitivity. Creatine (Cr) supplementation may augment responses to HIIT, leading to even greater physiological adaptations. The purpose of this study was to determine the effects of 4 weeks of HIIT (three sessions/week) combined with Cr supplementation in recreationally active females. Seventeen females (age = 23 ± 4 yrs; BMI = 23.4 ± 2.4) were randomly assigned to either Cr (Cr; 0.3 g・kg -1 ・d -1 for 5 d followed by 0.1 g・kg -1 ・d -1 for 23 days; n = 9) or placebo (PLA; n = 8). Before and after the intervention, VO 2peak , ventilatory threshold (VT), time-trial performance, lean body mass and fat mass, and insulin sensitivity were assessed. HIIT improved VO 2peak (Cr = +10.2%; PLA = +8.8%), VT (Cr = +12.7%; PLA = +9.9%), and time-trial performance (Cr = -11.5%; PLA = -11.6%) with no differences between groups (time main effects, all p < .001). There were no changes over time for fat mass (Cr = -0.3%; PLA = +4.3%), whole-body lean mass (Cr = +0.5%; PLA = -0.9%), or insulin resistance (Cr = +3.9%; PLA = +18.7%). In conclusion, HIIT is an effective way to improve cardiorespiratory fitness, VT, and time-trial performance. The addition of Cr to HIIT did not augment improvements in cardiorespiratory fitness, performance or body composition in recreationally active females.

Exercise associated hormonal signals as powerful determinants of an effective fat mass loss.

PubMed

Bajer, B; Vlcek, M; Galusova, A; Imrich, R; Penesova, A

2015-07-01

Obesity management for achieving an effective weight loss includes dietary modification and exercise [resistance (strength), endurance (cardiovascular) or intervals training (high-intensity intermittent exercise)]. Regular exercise acutely increases fat oxidation, which induces loss of fat mass and increases energy expenditure. Moreover, it has a positive effect on the physical (improved insulin sensitivity, lipid profile, etc.) and mental health (mood, cognition, memory, sleep, etc.). Endocrine responses to muscle actions are affected by many factors, including the exercise muscle groups (lower and upper body), load/volume, time-under tension, and rest-period intervals between sets, training status, gender, and age. The aim of this review is to summarize, evaluate, and clarify the literature data focusing on the endocrine responses to different types of exercise, including the frequency, intensity, and type of movement with regard to the fat loss strategies. Many studies have investigated anabolic [growth hormone, insulin-like growth factor-1 (IGF-1), testosterone] and gluco- and appetite- regulatory (insulin, cortisol, ghrelin) hormone responses and adaptations of skeletal muscles to exercise. Muscle tissue is a critical endocrine organ, playing important role in the regulation of several physiological and metabolic events. Moreover, we are also describing the response of some other substances to exercise, such as myokines [irisin, apelin, brain-derived neurotrophic factor (BDNF), myostatin, and fibroblast growth factor 21 (FGF21)]. It is proposed that reducing intra-abdominal fat mass and increasing cardiorespiratory fitness through improving nutritional quality, reducing sedentary behavior, and increase the participation in physical activity/exercise, might be associated with clinical benefits, sometimes even in the absence of weight loss.

Challenges and opportunities for genomic developmental neuropsychology: examples from the Penn-Drexel collaborative battery.

PubMed

Gur, Ruben C; Irani, Farzin; Seligman, Sarah; Calkins, Monica E; Richard, Jan; Gur, Raquel E

2011-08-01

Genomics has been revolutionizing medicine over the past decade by offering mechanistic insights into disease processes and engendering the age of "individualized medicine." Because of the sheer number of measures generated by gene sequencing methods, genomics requires "Big Science" where large datasets on genes are analyzed in reference to electronic medical record data. This revolution has largely bypassed the behavioral neurosciences, mainly because of the paucity of behavioral data in medical records and the labor-intensity of available neuropsychological assessment methods. We describe the development and implementation of an efficient neuroscience-based computerized battery, coupled with a computerized clinical assessment procedure. This assessment package has been applied to a genomic study of 10,000 children aged 8-21, of whom 1000 also undergo neuroimaging. Results from the first 3000 participants indicate sensitivity to neurodevelopmental trajectories. Sex differences were evident, with females outperforming males in memory and social cognition domains, while for spatial processing males were more accurate and faster, and they were faster on simple motor tasks. The study illustrates what will hopefully become a major component of the work of clinical and research neuropsychologists as invaluable participants in the dawning age of Big Science neuropsychological genomics.

Analysis of rocket beacon transmissions for computerized reconstruction of ionospheric densities

NASA Technical Reports Server (NTRS)

Bernhardt, P. A.; Huba, J. D.; Chaturvedi, P. K.; Fulford, J. A.; Forsyth, P. A.; Anderson, D. N.; Zalesak, S. T.

1993-01-01

Three methods are described to obtain ionospheric electron densities from transionospheric, rocket-beacon TEC data. First, when the line-of-sight from a ground receiver to the rocket beacon is tangent to the flight trajectory, the electron concentration can be obtained by differentiating the TEC with respect to the distance to the rocket. A similar method may be used to obtain the electron-density profile if the layer is horizontally stratified. Second, TEC data obtained during chemical release experiments may be interpreted with the aid of physical models of the disturbed ionosphere to yield spatial maps of the modified regions. Third, computerized tomography (CT) can be used to analyze TEC data obtained along a chain of ground-based receivers aligned along the plane of the rocket trajectory. CT analysis of TEC data is used to reconstruct a 2D image of a simulated equatorial plume. TEC data is computed for a linear chain of nine receivers with adjacent spacings of either 100 or 200 km. The simulation data are analyzed to provide an F region reconstruction on a grid with 15 x 15 km pixels. Ionospheric rocket tomography may also be applied to rocket-assisted measurements of amplitude and phase scintillations and airglow intensities.

The quality case for information technology in healthcare

PubMed Central

Bates, David W

2002-01-01

Background As described in the Institute of Medicine's Crossing the Quality Chasm report, the quality of health care in the U.S. today leaves much to be desired. Discussion One major opportunity for improving quality relates to increasing the use of information technology, or IT. Health care organizations currently invest less in IT than in any other information-intensive industry, and not surprisingly current systems are relatively primitive, compared with industries such as banking or aviation. Nonetheless, a number of organizations have demonstrated that quality can be substantially improved in a variety of ways if IT use is increased in ways that improve care. Specifically, computerization of processes that are error-prone and computerized decision support may substantially improve both efficiency and quality, as well as dramatically facilitate quality measurement. This report discusses the current levels of IT and quality in health care, how quality improvement and management are currently done, the evidence that more IT might be helpful, a vision of the future, and the barriers to getting there. Summary This report suggests that there are five key policy domains that need to be addressed: standards, incentives, security and confidentiality, professional involvement, and research, with financial incentives representing the single most important lever. PMID:12396233

Sarcoidosis Occurring After Lymphoma

PubMed Central

London, Jonathan; Grados, Aurélie; Fermé, Christophe; Charmillon, Alexandre; Maurier, François; Deau, Bénédicte; Crickx, Etienne; Brice, Pauline; Chapelon-Abric, Catherine; Haioun, Corinne; Burroni, Barbara; Alifano, Marco; Le Jeunne, Claire; Guillevin, Loïc; Costedoat-Chalumeau, Nathalie; Schleinitz, Nicolas; Mouthon, Luc; Terrier, Benjamin

2014-01-01

Abstract Sarcoidosis is a granulomatous disease that most frequently affects the lungs with pulmonary infiltrates and/or bilateral hilar and mediastinal lymphadenopathy. An association of sarcoidosis and lymphoproliferative disease has previously been reported as the sarcoidosis-lymphoma syndrome. Although this syndrome is characterized by sarcoidosis preceding lymphoma, very few cases of sarcoidosis following lymphoma have been reported. We describe the clinical, biological, and radiological characteristics and outcome of 39 patients presenting with sarcoidosis following lymphoproliferative disease, including 14 previously unreported cases and 25 additional patients, after performing a literature review. Hodgkin lymphoma and non-Hodgkin lymphoma were equally represented. The median delay between lymphoma and sarcoidosis was 18 months. Only 16 patients (41%) required treatment. Sarcoidosis was of mild intensity or self-healing in most cases, and overall clinical response to sarcoidosis was excellent with complete clinical response in 91% of patients. Sarcoidosis was identified after a follow-up computerized tomography scan (CT-scan) or 18fluorodeoxyglucose-positron emission tomography/computerized tomography (18FDG-PET/CT) evaluation in 18/34 patients (53%). Sarcoidosis is therefore a differential diagnosis to consider when lymphoma relapse is suspected on a CT-scan or 18FDG-PET/CT, emphasizing the necessity to rely on histological confirmation of lymphoma relapse. PMID:25380084

The impact of high-intensity interval training versus moderate-intensity continuous training on vascular function: a systematic review and meta-analysis.

PubMed

Ramos, Joyce S; Dalleck, Lance C; Tjonna, Arnt Erik; Beetham, Kassia S; Coombes, Jeff S

2015-05-01

Vascular dysfunction is a precursor to the atherosclerotic cascade, significantly increasing susceptibility to cardiovascular events such as myocardial infarction or stroke. Previous studies have revealed a strong relationship between vascular function and cardiorespiratory fitness (CRF). Thus, since high-intensity interval training (HIIT) is a potent method of improving CRF, several small randomized trials have investigated the impact on vascular function of HIIT relative to moderate-intensity continuous training (MICT). The aim of this study was to systematically review the evidence and quantify the impact on vascular function of HIIT compared with MICT. Three electronic databases (PubMed, Embase, and MEDLINE) were searched (until May 2014) for randomized trials comparing the effect of at least 2 weeks of HIIT and MICT on vascular function. HIIT protocols involved predominantly aerobic exercise at a high intensity, interspersed with active or passive recovery periods. We performed a meta-analysis to compare the mean difference in the change in vascular function assessed via brachial artery flow-mediated dilation (FMD) from baseline to post-intervention between HIIT and MICT. The impact of HIIT versus MICT on CRF, traditional cardiovascular disease (CVD) risk factors, and biomarkers associated with vascular function (oxidative stress, inflammation, and insulin resistance) was also reviewed across included studies. Seven randomized trials, including 182 patients, met the eligibility criteria and were included in the meta-analysis. A commonly used HIIT prescription was four intervals of 4 min (4 × 4 HIIT) at 85-95% of maximum or peak heart rate (HRmax/peak), interspersed with 3 min of active recovery at 60-70% HRmax/peak, three times per week for 12-16 weeks. Brachial artery FMD improved by 4.31 and 2.15% following HIIT and MICT, respectively. This resulted in a significant (p < 0.05) mean difference of 2.26%. HIIT also had a greater tendency than MICT to induce positive effects on secondary outcome measures, including CRF, traditional CVD risk factors, oxidative stress, inflammation, and insulin sensitivity. HIIT is more effective at improving brachial artery vascular function than MICT, perhaps due to its tendency to positively influence CRF, traditional CVD risk factors, oxidative stress, inflammation, and insulin sensitivity. However, the variability in the secondary outcome measures, coupled with the small sample sizes in these studies, limits this finding. Nonetheless, this review suggests that 4 × 4 HIIT, three times per week for at least 12 weeks, is a powerful form of exercise to enhance vascular function.

Tension pneumocephalus secondary to non-invasive mechanical ventilation in a patient with severe traumatic brain injury.

PubMed

Andreu-Ruiz, Antonio; Ros-Argente Del Castillo, Tomas; Moya-Sánchez, José; Garcia-Ortega, Ana Azahara

The presence of air inside intracranial cavity is a rare entity known as pneumocephalus and in most cases doesńt present any clinical repercussion except in case of elevated intracranial pressure that can lead to a decreasing level of consciousness, coma and even death. We present a rare case of a young male, without medical precedents of interest, hospitalized in an intensive care unit for vigilance after a traffic accident with asymptomatic crane encephalic trauma and cranial computerized tomography without meaningful findings. During the intensive care unit stay positive pressure is applied in airway with non-invasive mechanical ventilation that produces air entrance in cranial cavity (pneumocephalus) causing neurological deterioration and necessity of urgent surgery. Copyright © 2017 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.

Image analysis for dental bone quality assessment using CBCT imaging

NASA Astrophysics Data System (ADS)

Suprijanto; Epsilawati, L.; Hajarini, M. S.; Juliastuti, E.; Susanti, H.

2016-03-01

Cone beam computerized tomography (CBCT) is one of X-ray imaging modalities that are applied in dentistry. Its modality can visualize the oral region in 3D and in a high resolution. CBCT jaw image has potential information for the assessment of bone quality that often used for pre-operative implant planning. We propose comparison method based on normalized histogram (NH) on the region of inter-dental septum and premolar teeth. Furthermore, the NH characteristic from normal and abnormal bone condition are compared and analyzed. Four test parameters are proposed, i.e. the difference between teeth and bone average intensity (s), the ratio between bone and teeth average intensity (n) of NH, the difference between teeth and bone peak value (Δp) of NH, and the ratio between teeth and bone of NH range (r). The results showed that n, s, and Δp have potential to be the classification parameters of dental calcium density.

Lokomat training in vascular dementia: motor improvement and beyond!

PubMed

Calabrò, Rocco Salvatore; De Luca, Rosaria; Leo, Antonino; Balletta, Tina; Marra, Angela; Bramanti, Placido

2015-12-01

Vascular dementia (VaD) is a general term describing problems with reasoning, planning, judgment, memory, and other thought processes caused by brain damage from impaired blood flow to the brain. Cognitive rehabilitation and physical therapy are the mainstays of dementia treatment, although often ineffective because of the scarce collaboration of the patients. However, emerging data suggest that physical activity may reduce the risk of cognitive impairment, mainly VaD, in older people living independently. Herein, we describe a 72-year-old male affected by VaD, in which traditional cognitive training in addition to intensive gait robotic rehabilitation (by using Lokomat device) led to a significant improvement in the motor and cognitive function. This promising finding may be related either to the intensive and repetitive aerobic exercises or to the task-oriented training with computerized visual feedback, which can be considered as a relevant tool to increase patients' motor output, involvement, and motivation during robotic training.

Islet transplantation versus insulin therapy in patients with type 1 diabetes with severe hypoglycaemia or poorly controlled glycaemia after kidney transplantation (TRIMECO): a multicentre, randomised controlled trial.

PubMed

Lablanche, Sandrine; Vantyghem, Marie-Christine; Kessler, Laurence; Wojtusciszyn, Anne; Borot, Sophie; Thivolet, Charles; Girerd, Sophie; Bosco, Domenico; Bosson, Jean-Luc; Colin, Cyrille; Tetaz, Rachel; Logerot, Sophie; Kerr-Conte, Julie; Renard, Eric; Penfornis, Alfred; Morelon, Emmanuel; Buron, Fanny; Skaare, Kristina; Grguric, Gwen; Camillo-Brault, Coralie; Egelhofer, Harald; Benomar, Kanza; Badet, Lionel; Berney, Thierry; Pattou, François; Benhamou, Pierre-Yves

2018-05-15

Islet transplantation is indicated for patients with type 1 diabetes with severe hypoglycaemia or after kidney transplantation. We did a randomised trial to assess the efficacy and safety of islet transplantation compared with insulin therapy in these patients. In this multicentre, open-label, randomised controlled trial, we randomly assigned (1:1) patients with type 1 diabetes at 15 university hospitals to receive immediate islet transplantation or intensive insulin therapy (followed by delayed islet transplantation). Eligible patients were aged 18-65 years and had severe hypoglycaemia or hypoglycaemia unawareness, or kidney grafts with poor glycaemic control. We used computer-generated randomisation, stratified by centre and type of patient. Islet recipients were scheduled to receive 11 000 islet equivalents per kg bodyweight in one to three infusions. The primary outcome was proportion of patients with a modified β-score (in which an overall score of 0 was not allocated when stimulated C-peptide was negative) of 6 or higher at 6 months after first islet infusion in the immediate transplantation group or 6 months after randomisation in the insulin group. The primary analysis included all patients who received the allocated intervention; safety was assessed in all patients who received islet infusions. This trial is registered with ClinicalTrials.gov, number NCT01148680, and is completed. Between July 8, 2010, and July 29, 2013, 50 patients were randomly assigned to immediate islet transplantation (n=26) or insulin treatment (n=24), of whom three (one in the immediate islet transplantation group and two in the insulin therapy group) did not receive the allocated intervention. Median follow-up was 184 days (IQR 181-186) in the immediate transplantation group and 185 days (172-201) in the insulin therapy group. At 6 months, 16 (64% [95% CI 43-82]) of 25 patients in the immediate islet transplantation group had a modified β-score of 6 or higher versus none (0% [0-15]) of the 22 patients in the insulin group (p<0·0001). At 12 months after first infusion, bleeding complications had occurred in four (7% [2-18]) of 55 infusions, and a decrease in median glomerular filtration rate from 90·5 mL/min (IQR 76·6-94·0) to 71·8 mL/min (59·0-89·0) was observed in islet recipients who had not previously received a kidney graft and from 63·0 mL/min (55·0-71·0) to 57·0 mL/min (45·5-65·1) in islet recipients who had previously received a kidney graft. For the indications assessed in this study, islet transplantation effectively improves metabolic outcomes. Although studies with longer-term follow-up are needed, islet transplantation seems to be a valid option for patients with severe, unstable type 1 diabetes who are not responding to intensive medical treatments. However, immunosuppression can affect kidney function, necessitating careful selection of patients. Programme Hospitalier de Recherche Clinique grant from the French Government. Copyright © 2018 Elsevier Ltd. All rights reserved.

Comparative effectiveness and safety of methods of insulin delivery and glucose monitoring for diabetes mellitus: a systematic review and meta-analysis.

PubMed

Yeh, Hsin-Chieh; Brown, Todd T; Maruthur, Nisa; Ranasinghe, Padmini; Berger, Zackary; Suh, Yong D; Wilson, Lisa M; Haberl, Elisabeth B; Brick, Jessica; Bass, Eric B; Golden, Sherita Hill

2012-09-04

Patients with diabetes mellitus need information about the effectiveness of innovations in insulin delivery and glucose monitoring. To review how intensive insulin therapy (multiple daily injections [MDI] vs. rapid-acting analogue-based continuous subcutaneous insulin infusion [CSII]) or method of monitoring (self-monitoring of blood glucose [SMBG] vs. real-time continuous glucose monitoring [rt-CGM]) affects outcomes in types 1 and 2 diabetes mellitus. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through February 2012 without language restrictions. 33 randomized, controlled trials in children or adults that compared CSII with MDI (n=19), rt-CGM with SMBG (n=10), or sensor-augmented insulin pump use with MDI and SMBG (n=4). 2 reviewers independently evaluated studies for eligibility and quality and serially abstracted data. In randomized, controlled trials, MDI and CSII showed similar effects on hemoglobin A1c (HbA1c) levels and severe hypoglycemia in children or adults with type 1 diabetes mellitus and adults with type 2 diabetes mellitus. In adults with type 1 diabetes mellitus, HbA1c levels decreased more with CSII than with MDI, but 1 study heavily influenced these results. Compared with SMBG, rt-CGM achieved a lower HbA1c level (between-group difference of change, 0.26% [95% CI, 0.33% to 0.19%]) without any difference in severe hypoglycemia. Sensor-augmented insulin pump use decreased HbA1c levels more than MDI and SMBG did in persons with type 1 diabetes mellitus (between-group difference of change, 0.68% [CI, 0.81% to 0.54%]). Little evidence was available on other outcomes. Many studies were small, of short duration, and limited to white persons with type 1 diabetes mellitus. Continuous subcutaneous insulin infusion and MDI have similar effects on glycemic control and hypoglycemia, except CSII has a favorable effect on glycemic control in adults with type 1 diabetes mellitus. For glycemic control, rt-CGM is superior to SMBG and sensor-augmented insulin pumps are superior to MDI and SMBG without increasing the risk for hypoglycemia. Agency for Healthcare Research and Quality.

A two year observational study of nicotinamide and intensive insulin therapy in patients with recent onset type 1 diabetes mellitus.

PubMed

Crinó, A; Schiaffini, R; Ciampalini, P; Suraci, M C; Manfrini, S; Visalli, N; Matteoli, M C; Patera, P; Buzzetti, R; Guglielmi, C; Spera, S; Costanza, F; Fioriti, E; Pitocco, D; Pozzilli, P

2005-08-01

A number of trials have evaluated residual beta-cell function in patients with recent onset type 1 diabetes mellitus (DM1) treated with nicotinamide in addition to intensive insulin therapy (IIT). In most studies, only a slight decline of C-peptide secretion was observed 12 months after diagnosis; however, no data is available on C-peptide secretion and metabolic control in patients continuing nicotinamide and IIT for up to 2 years after diagnosis. We retrospectively analysed data from 25 patients (mean age 14.7 years +/- 5 SD) with DM1 in whom nicotinamide at a dose of 25 mg/kg b. wt. was added from diagnosis (< 4 weeks) to IIT (three injections of regular insulin at meals + one NPH at bed time) and continued for up to 2 years after diagnosis. Data were also analysed from patients (n = 27) in whom IIT was introduced at diagnosis and who were similarly followed for 2 years. Baseline C-peptide as well as insulin dose and HbA1c levels were evaluated at 12 and 24 months after diagnosis. In the course of the follow-up, patients on nicotinamide + IIT or IIT alone did not significantly differ in terms of C-peptide secretion (values at 24 months in the two groups were 0.19 +/- 0.24 nM vs 0.19 +/- 0.13 nM, respectively). Insulin requirement (0.6 +/- 0.3 U/kg/day vs 0.7 +/- 0.2 U/kg/day at 24 months, respectively) did not differ between the two groups. However, HbA1c was significantly lower 2 years after diagnosis in patients treated with nicotinamide + IIT (6.09 +/- 0.9% vs 6.98 +/- 0.9%, respectively, p < 0.01). No adverse effects were observed in patients receiving nicotinamide for 2 years. Implementation of IIT with the addition of nicotinamide at diagnosis continued for 2 years improves metabolic control as assessed by HbA1c. In both nicotinamide and control patients, no decline in C-peptide was detected 2 years after diagnosis, indicating that IIT preserves C-peptide secretion. We conclude that nicotinamide + IIT at diagnosis of DM1 prolonged for up to 2 years can be recommended, but longer follow-up is required to determine whether nicotinamide should be continued beyond this period.

Computerized adaptive control weld skate with CCTV weld guidance project

NASA Technical Reports Server (NTRS)

Wall, W. A.

1976-01-01

This report summarizes progress of the automatic computerized weld skate development portion of the Computerized Weld Skate with Closed Circuit Television (CCTV) Arc Guidance Project. The main goal of the project is to develop an automatic welding skate demonstration model equipped with CCTV weld guidance. The three main goals of the overall project are to: (1) develop a demonstration model computerized weld skate system, (2) develop a demonstration model automatic CCTV guidance system, and (3) integrate the two systems into a demonstration model of computerized weld skate with CCTV weld guidance for welding contoured parts.

Deleterious effects of increased body weight associated with intensive insulin therapy for type 1 diabetes: increased blood pressure and worsened lipid profile partially negate improvements in life expectancy.

PubMed

Palmer, Andrew J; Roze, Stéphane; Valentine, William J; Minshall, Michael E; Lammert, Morten; Nicklasson, Lars; Spinas, Giatgen A

2004-08-01

Weight gain is an unwanted side effect of improved glycaemic control in type 1 diabetes, associated with increased blood pressure (BP) and worsening lipid profiles. While improved glycaemic control per se should improve long-term patient outcomes, increases in BP and worsening lipid profiles may counteract these benefits. The aim of this modelling study was to assess whether the increased body weight and associated worsening of lipid profile and blood pressure would negate the improvements in glycaemic control seen with intensive therapy in patients with type 1 diabetes. A validated diabetes model projected life expectancy (LE), quality-adjusted LE (QALE) and total lifetime costs of complications in type 1 diabetes cohorts with the characteristics of patients from the Diabetes Control and Complications Trial (DCCT). The following four cohorts (A-D) were created based on increased body weight under either conventional or intensive therapy: A) conventional glycaemic control in the subgroup with lowest weight-gain quartile after 6.5 years (HbA1c increased by 11% from baseline); B) conventional control in the highest weight-gain quartile (no change in HbA1c from baseline); C) intensive control in the lowest quartile of weight gain (with 16.1% decrease in HbA1c, but no increase in weight or associated BP, and improved lipid profile); D) intensive control in the highest quartile of weight gain (with 21% decrease in HbA1c, increased systolic BP of 6 mmHg, and worsened lipid profile). Data were derived from DCCT and other published sources. Intensive control, even with weight gain, led to major improvements in LE and QALE, and reduction in costs of complications versus conventional therapy. Intensive therapy with no weight increase led to a higher LE (increased by 0.57 years) and higher QALE (increased by 0.28 years) and lower costs of complications (reduced by 523 dollars/patient), compared to intensive therapy with the highest quartile of weight gain. Concerns about weight gain should not deter intensive insulin therapy. However, the value of improving glycaemic control without increasing body weight (and associated increased BP and worsening of lipid profile) has been confirmed.

An Application of Computerized Axial Tomography (CAT) Technology to Mass Raid Tracking

DTIC Science & Technology

1989-08-01

ESD-TR-89-305 MTR-10542 An Application of Computerized Axial Tomography ( CAT ) Technology to Mass Raid Tracking By John K. Barr August 1989...NO 11. TITLE (Include Security Classification) An Application of Computerized Axial Tomography ( CAT ) Technology to Mass Raid Tracking 12...by block number) Computerized Axial Tomography ( CAT ) Scanner Electronic Support Measures (ESM) Fusion (continued) 19. ABSTRACT (Continue on

Increasing profitability through computerization.

PubMed

Sokol, D J

1988-01-01

The author explores the pragmatic or financial justification for computerizing a dental practice and discusses a computerized approach to precollection and collection for the dental office. The article also deals with the use of computerized correspondence to augment the recall policy of the office and to help generate new patient referrals and discusses the pros and cons of utilizing a dental computer service bureau in implementing these policies.

Feasibility of computerized working memory training in individuals with Huntington disease

PubMed Central

Sadeghi, Mahsa; Barlow-Krelina, Emily; Gibbons, Clare; Shaikh, Komal T.; Fung, Wai Lun Alan; Meschino, Wendy S.; Till, Christine

2017-01-01

Objectives Huntington disease (HD) is associated with a variety of cognitive deficits, with prominent difficulties in working memory (WM). WM deficits are notably compromised in early-onset and prodromal HD patients. This study aimed to determine the feasibility of a computerized WM training program (Cogmed QM), novel to the HD population. Methods Nine patients, aged 26–62, with early stage HD underwent a 25-session (5 days/week for 5 weeks) WM training program (Cogmed QM). Training exercises involved the manipulation and storage of verbal and visuospatial information, with difficulty adapted as a function of individual performance. Neuropsychological testing was conducted before and after training, and performance on criterion WM measures (Digit Span and Spatial Span), near-transfer WM measures (Symbol Span and Auditory WM), and control measures were evaluated. Post-training interviews about patient experience were thematically analyzed using NVivo software. Results Seven of nine patients demonstrated adherence to the training and completed all sessions within the recommended timeframe of 5 weeks. All adherent patients showed improvement on the Cogmed tasks as defined by the Improvement Index (M = 22.17, SD = 8.84, range = 13–36). All adherent patients reported that they found training helpful (n = 7), and almost all felt that their memory improved (n = 6). Participants also expressed that the training was difficult, sometimes frustrating, and time consuming. Conclusions This pilot study provides support for feasibility of computerized WM training in early-stage patients with HD. Results suggest that HD patients perceive benefits of intensive WM training, though a full-scale and controlled intervention project is needed to understand the size of the effect and reliability of changes over time. Trial registration ClinicalTrials.gov, Registry number NCT02926820 PMID:28453532

Renal calyceal anatomy characterization with 3-dimensional in vivo computerized tomography imaging.

PubMed

Miller, Joe; Durack, Jeremy C; Sorensen, Mathew D; Wang, James H; Stoller, Marshall L

2013-02-01

Calyceal selection for percutaneous renal access is critical for safe, effective performance of percutaneous nephrolithotomy. Available anatomical evidence is contradictory and incomplete. We present detailed renal calyceal anatomy obtained from in vivo 3-dimentional computerized tomography renderings. A total of 60 computerized tomography urograms were randomly selected. The renal collecting system was isolated and 3-dimensional renderings were constructed. The primary plane of each calyceal group of 100 kidneys was determined. A coronal maximum intensity projection was used for simulated percutaneous access. The most inferior calyx was designated calyx 1. Moving superiorly, the subsequent calyces were designated calyx 2 and, when present, calyx 3. The surface rendering was rotated to assess the primary plane of the calyceal group and the orientation of the select calyx. The primary plane of the upper pole calyceal group was mediolateral in 95% of kidneys and the primary plane of the lower pole calyceal group was anteroposterior in 95%. Calyx 2 was chosen in 90 of 97 simulations and it was appropriate in 92%. Calyx 3 was chosen in 7 simulations but it was appropriate in only 57%. Calyx 1 was not selected in any simulation and it was anteriorly oriented in 75% of kidneys. Appropriate lower pole calyceal access can be reliably accomplished with an understanding of the anatomical relationship between individual calyceal orientation and the primary plane of the calyceal group. Calyx 2 is most often appropriate for accessing the anteroposterior primary plane of the lower pole. Calyx 1 is most commonly oriented anterior. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Effects of a computerized working memory training program on working memory, attention, and academics in adolescents with severe LD and comorbid ADHD: a randomized controlled trial.

PubMed

Gray, S A; Chaban, P; Martinussen, R; Goldberg, R; Gotlieb, H; Kronitz, R; Hockenberry, M; Tannock, R

2012-12-01

Youths with coexisting learning disabilities (LD) and attention deficit hyperactivity disorder (ADHD) are at risk for poor academic and social outcomes. The underlying cognitive deficits, such as poor working memory (WM), are not well targeted by current treatments for either LD or ADHD. Emerging evidence suggests that WM might be improved by intensive and adaptive computerized training, but it remains unclear whether this intervention would be effective for adolescents with severe LD and comorbid ADHD. A total of sixty 12- to 17-year olds with LD/ADHD (52 male, 8 female, IQ > 80) were randomized to one of two computerized intervention programs: working memory training (Cogmed RM) or math training (Academy of Math) and evaluated before and 3 weeks after completion. The criterion measures of WM included auditory-verbal and visual-spatial tasks. Near and far transfer measures included indices of cognitive and behavioral attention and academic achievement. Adolescents in the WM training group showed greater improvements in a subset of WM criterion measures compared with those in the math-training group, but no training effects were observed on the near or far measures. Those who showed the most improvement on the WM training tasks at school were rated as less inattentive/hyperactive at home by parents. Results suggest that WM training may enhance some aspects of WM in youths with LD/ADHD, but further development of the training program is required to promote transfer effects to other domains of function. © 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.

The effect of a computerized prescribing and calculating system on hypo- and hyperglycemias and on prescribing time efficiency in neonatal intensive care patients.

PubMed

Maat, Barbara; Rademaker, Carin M A; Oostveen, Marloes I; Krediet, Tannette G; Egberts, Toine C G; Bollen, Casper W

2013-01-01

Prescribing glucose requires complex calculations because glucose is present in parenteral and enteral nutrition and drug vehicles, making it error prone and contributing to the burden of prescribing errors. Evaluation of the impact of a computerized physician order entry (CPOE) system with clinical decision support (CDS) for glucose control in neonatal intensive care patients (NICU) focusing on hypo- and hyperglycemic episodes and prescribing time efficiency. An interrupted time-series design to examine the effect of CPOE on hypo- and hyperglycemias and a crossover simulation study to examine the influence of CPOE on prescribing time efficiency. NICU patients at risk for glucose imbalance hospitalized at the University Medical Center Utrecht during 2001-2007 were selected. The risks of hypo- and hyperglycemias were expressed as incidences per 100 patient days in consecutive 3-month intervals during 3 years before and after CPOE implementation. To assess prescribing time efficiency, time needed to calculate glucose intake with and without CPOE was measured. No significant difference was found between pre- and post-CPOE mean incidences of hypo- and hyperglycemias per 100 hospital days of neonates at risk in every 3-month period (hypoglycemias, 4.0 [95% confidence interval, 3.2-4.8] pre-CPOE and 3.1 [2.7-3.5] post-CPOE, P = .88; hyperglycemias, 6.0 [4.3-7.7] pre-CPOE and 5.0 [3.7-6.3] post-CPOE, P = .75). CPOE led to a significant time reduction of 16% (1.3 [0.3-2.3] minutes) for simple and 60% (8.6 [5.1-12.1] minutes) for complex calculations. CPOE including a special CDS tool preserved accuracy for calculation and control of glucose intake and increased prescribing time efficiency.

Effect of shivering on brain tissue oxygenation during induced normothermia in patients with severe brain injury.

PubMed

Oddo, Mauro; Frangos, Suzanne; Maloney-Wilensky, Eileen; Andrew Kofke, W; Le Roux, Peter D; Levine, Joshua M

2010-02-01

We analyzed the impact of shivering on brain tissue oxygenation (PbtO(2)) during induced normothermia in patients with severe brain injury. We studied patients with severe brain injury who developed shivering during induced normothermia. Induced normothermia was applied to treat refractory fever (body temperature [BT] > or =38.3 degrees C, refractory to conventional treatment) using a surface cooling device with computerized adjustment of patient BT target to 37 +/- 0.5 degrees C. PbtO(2), intracranial pressure, mean arterial pressure, cerebral perfusion pressure, and BT were monitored continuously. Circulating water temperature of the device system was measured to assess the intensity of cooling. Fifteen patients (10 with severe traumatic brain injury, 5 with aneurysmal subarachnoid hemorrhage) were treated with induced normothermia for an average of 5 +/- 2 days. Shivering caused a significant decrease in PbtO(2) levels both in SAH and TBI patients. Compared to baseline, shivering was associated with an overall reduction of PbtO(2) from 34.1 +/- 7.3 to 24.4 +/- 5.5 mmHg (P < 0.001). A significant correlation was found between the magnitude of shivering-associated decrease of PbtO(2) (DeltaPbtO(2)) and circulating water temperature (R = 0.82, P < 0.001). In patients with severe brain injury treated with induced normothermia, shivering was associated with a significant decrease of PbtO(2), which correlated with the intensity of cooling. Monitoring of therapeutic cooling with computerized thermoregulatory systems may help prevent shivering and optimize the management of induced normothermia. The clinical significance of shivering-induced decrease in brain tissue oxygenation remains to be determined.

Influence of computerized sounding out on spelling performance for children who do and do not rely on AAC.

PubMed

McCarthy, Jillian H; Hogan, Tiffany P; Beukelman, David R; Schwarz, Ilsa E

2015-05-01

Spelling is an important skill for individuals who rely on augmentative and alternative communication (AAC). The purpose of this study was to investigate how computerized sounding out influenced spelling accuracy of pseudo-words. Computerized sounding out was defined as a word elongated, thus providing an opportunity for a child to hear all the sounds in the word at a slower rate. Seven children with cerebral palsy, four who use AAC and three who do not, participated in a single subject AB design. The results of the study indicated that the use of computerized sounding out increased the phonologic accuracy of the pseudo-words produced by participants. The study provides preliminary evidence for the use of computerized sounding out during spelling tasks for children with cerebral palsy who do and do not use AAC. Future directions and clinical implications are discussed. We investigated how computerized sounding out influenced spelling accuracy of pseudowords for children with complex communication needs who did and did not use augmentative and alternative communication (AAC). Results indicated that the use of computerized sounding out increased the phonologic accuracy of the pseudo-words by participants, suggesting that computerized sounding out might assist in more accurate spelling for children who use AAC. Future research is needed to determine how language and reading abilities influence the use of computerized sounding out with children who have a range of speech intelligibility abilities and do and do not use AAC.

Evaluation of nuclear chromatin using grayscale intensity and thresholded percentage area in liquid-based cervical cytology.

PubMed

Lee, Hyekyung; Han, Myungein; Yoo, Taejo; Jung, Chanho; Son, Hyun-Jin; Cho, Migyung

2018-05-01

Development of computerized image analysis techniques has opened up the possibility for the quantitative analysis of nuclear chromatin in pathology. We hypothesized that the features extracted from digital images could be used to determine specific cytomorphological findings for nuclear chromatin that may be applicable for establishing a medical diagnosis. Three parameters were evaluated from nuclear chromatin images obtained from the liquid-based cervical cytology samples of patients with biopsy-proven high-grade squamous intraepithelial lesion (HGSIL), and compared between non-neoplastic squamous epithelia and dysplastic epithelia groups: (1) standard deviation (SD) of the grayscale intensity; (2) difference between the maximum and minimum grayscale intensity (M-M); and (3) thresholded area percentage. Each parameter was evaluated at the mean, mean-1SD, and mean-2SD thresholding intensity levels. Between the mean and mean-1SD levels, the thresholded nuclear chromatin pattern was most similar to the chromatin granularity of the unthresholded grayscale images. The SD of the gray intensity and the thresholded area percentage differed significantly between the non-neoplastic squamous epithelia and dysplastic epithelia of HGSIL images at all three thresholding intensity levels (mean, mean-1SD, and mean-2SD). However, the M-M significantly differed between the two sample types for only two of the thresholding intensity levels (mean-1SD and mean-2SD). The digital parameters SD and M-M of the grayscale intensity, along with the thresholded area percentage could be useful in automated cytological evaluations. Further studies are needed to identify more valuable parameters for clinical application. © 2018 Wiley Periodicals, Inc.

Managing type 1 diabetes in school: Recommendations for policy and practice

PubMed Central

Lawrence, Sarah E; Cummings, Elizabeth A; Pacaud, Danièle; Lynk, Andrew; Metzger, Daniel L

2015-01-01

Diabetes requiring insulin is increasingly common and likely to impact students in most, if not all, schools. Diabetes and its complications have major personal, social and economic impact, and improved diabetes control reduces the risk of both short- and long-term complications. Evidence shows that more intensive management of diabetes – through frequent blood glucose monitoring, insulin administration with injections and/or insulin pumps, and careful attention to diet and exercise – leads to better control. Since children spend 30 to 35 hours per week at school, effectively managing their diabetes while there is integral to their short- and long-term health. The Canadian Paediatric Society and the Canadian Pediatric Endocrine Group recommend that minimum standards for supervision and care be established across Canada to support children and youth with type 1 diabetes in schools. These recommendations are derived from evidence-based clinical practice guidelines, with input from diabetes care providers from across Canada, and are consistent with the Canadian Diabetes Association’s Guidelines for the Care of Students Living with Diabetes at School. PMID:25722642

Influence of Acute and Chronic Exercise on Glucose Uptake

PubMed Central

Röhling, Martin; Herder, Christian; Stemper, Theodor; Müssig, Karsten

2016-01-01

Insulin resistance plays a key role in the development of type 2 diabetes. It arises from a combination of genetic predisposition and environmental and lifestyle factors including lack of physical exercise and poor nutrition habits. The increased risk of type 2 diabetes is molecularly based on defects in insulin signaling, insulin secretion, and inflammation. The present review aims to give an overview on the molecular mechanisms underlying the uptake of glucose and related signaling pathways after acute and chronic exercise. Physical exercise, as crucial part in the prevention and treatment of diabetes, has marked acute and chronic effects on glucose disposal and related inflammatory signaling pathways. Exercise can stimulate molecular signaling pathways leading to glucose transport into the cell. Furthermore, physical exercise has the potential to modulate inflammatory processes by affecting specific inflammatory signaling pathways which can interfere with signaling pathways of the glucose uptake. The intensity of physical training appears to be the primary determinant of the degree of metabolic improvement modulating the molecular signaling pathways in a dose-response pattern, whereas training modality seems to have a secondary role. PMID:27069930

Exercise and dietary change ameliorate high fat diet induced obesity and insulin resistance via mTOR signaling pathway.

PubMed

Bae, Ju Yong; Shin, Ki Ok; Woo, Jinhee; Woo, Sang Heon; Jang, Ki Soeng; Lee, Yul Hyo; Kang, Sunghwun

2016-06-01

The purpose of this study was to investigate the effect of exercise and dietary change on obesity and insulin resistance and mTOR signaling protein levels in skeletal muscles of obese rats. Sixty male Sprague-Dawley rats were divided into CO (Normal diet) and HF (High Fat diet) groups in order to induce obesity for 15 weeks. The rats were then subdivided into CO, COT (CO + Training), HF, HFT (HF + Training), HFND (Dietary change), and HFNDT (HFND + Training) groups (10 rats / group). The training groups underwent moderate-intensity treadmill exercise for 8 weeks, after which soleus muscles were excised and analyzed. Data was statistically analyzed by independent t-test and One-way ANOVA tests with a 0.05 significance level. Fasting blood glucose, plasma insulin, and HOMA-IR in the HF group were significantly higher, as compared with other groups (p <.05). Protein levels of insulin receptor subunit-1 (IRS-1), IRS-2, and p-Akt were significantly higher in the HFT, HFND, and HFNDT groups, as compared with HF group. In addition, the protein levels of the mammalian target of rapamycin complex 1 (mTORC1) and ribosomal S6 protein kinase 1 were significantly decreased by exercise and dietary change (p <.05). However, mTORC2 and phosphoinositide 3-kinase were significantly increased (p <.05). In summary, despite the negative impact of continuous high fat intake, regular exercise and dietary change showed a positive effect on insulin resistance and mTOR signaling protein levels.

Effect of acute exercise on glycogen synthase in muscle from obese and diabetic subjects

PubMed Central

Jensen, Jørgen; Tantiwong, Puntip; Stuenæs, Jorid T.; Molina-Carrion, Marjorie; DeFronzo, Ralph A.; Sakamoto, Kei

2012-01-01

Insulin stimulates glycogen synthase (GS) through dephosphorylation of serine residues, and this effect is impaired in skeletal muscle from insulin-resistant [obese and type 2 diabetic (T2DM)] subjects. Exercise also increases GS activity, yet it is not known whether the ability of exercise to affect GS is impaired in insulin-resistant subjects. The objective of this study was to examine the effect of acute exercise on GS phosphorylation and enzyme kinetic properties in muscle from insulin-resistant individuals. Lean normal glucose-tolerant (NGT), obese NGT, and obese T2DM subjects performed 40 min of moderate-intensity cycle exercise (70% of V̇o2max). GS kinetic properties and phosphorylation were measured in vastus lateralis muscle before exercise, immediately after exercise, and 3.5 h postexercise. In lean subjects, GS fractional activity increased twofold after 40 min of exercise, and it remained elevated after the 3.5-h rest period. Importantly, exercise also decreased GS Km for UDP-glucose from ≈0.5 to ≈0.2 mM. In lean subjects, exercise caused significant dephosphorylation of GS by 50–70% (Ser641, Ser645, and Ser645,649,653,657), and phosphorylation of these sites remained decreased after 3.5 h; Ser7 phosphorylation was not regulated by exercise. In obese NGT and T2DM subjects, exercise increased GS fractional activity, decreased Km for UDP-glucose, and decreased GS phosphorylation as effectively as in lean NGT subjects. We conclude that the molecular regulatory process by which exercise promotes glycogen synthesis in muscle is preserved in insulin-resistant subjects. PMID:22510711

Performing a cure for schizophrenia: insulin coma therapy on the wards.

PubMed

Doroshow, Deborah Blythe

2007-04-01

Most historians of psychiatry regard insulin coma therapy (ICT) either as an embarrassing stumble on the path to modern biological psychiatry or as one member of a long line of somatic therapies used to treat mental illness in the mid-twentieth century. This article explores the ICT era, roughly 1933-60, as a key moment in the development of American psychiatry. Developed only ten years after insulin had been embraced as a "miracle drug" for the treatment of diabetes, ICT was perceived by psychiatrists as a means of bringing their field closer to mainstream medicine, particularly to neurology. In addition, the story of ICT reveals how a treatment never quite proven on paper was unquestionably efficacious in the local world in which it was performed. An institutionally-based treatment, ICT was administered in a specific area of the mental hospital deemed the insulin unit, a room with its own staff, practices, and attitudes toward mental illness. There, psychiatrists often experienced wondrous recoveries of individual, formerly intractable patients. These intense personal experiences allowed psychiatrists to feel truly efficacious, enabling them to reinvent themselves as medical doctors rather than behavioral and disciplinary supervisors. The confidence they derived from this capacity, along with the operating room-like setting of the insulin unit, the unit's specialized staffing and group bond, and the availability of both risk-assessment tests and a medley of treatments that countered side effects and complications, allowed ICT to be understood as an efficacious treatment for schizophrenia within the local world in which it was administered.

Morphological assessment of pancreatic islet hormone content following aerobic exercise training in rats with poorly controlled Type 1 diabetes mellitus.

PubMed

McDonald, Matthew W; Murray, Michael R; Hall, Katharine E; Noble, Earl G; Melling, C W James

2014-01-01

Regular exercise has been shown to improve many complications of Type 1 diabetes mellitus (T1DM) including enhanced glucose tolerance and increased cardiac function. While exercise training has been shown to increase insulin content in pancreatic islets of rats with T1DM, experimental models were severely hyperglycemic and not undergoing insulin treatment. Further, research to date has yet to determine how exercise training alters glucagon content in pancreatic islets. The purpose of the present investigation was to determine the impact of a 10-week aerobic training program on pancreatic islet composition in insulin-treated rats with T1DM. Second, it was determined whether the acute, exercise-mediated reduction in blood glucose experienced in rats with T1DM would become larger in magnitude following aerobic exercise training. Diabetes was induced in male Sprague-Dawley rats by multiple low dose injections of streptozotocin (20mg/kg i.p.) and moderate intensity aerobic exercise training was performed on a motorized treadmill for one hour per day for a total of 10 weeks. Rats with T1DM demonstrated significantly less islet insulin, and significantly more islet glucagon hormone content compared with non-T1DM rats, which did not significantly change following aerobic training. The reduction in blood glucose in response to a single exercise bout was similar across 10 weeks of training. Results also support the view that different subpopulations of islets exist, as small islets (<50 μm diameter) had significantly more insulin and glucagon in rats with and without T1DM.

Effect of acute exercise on glycogen synthase in muscle from obese and diabetic subjects.

PubMed

Jensen, Jørgen; Tantiwong, Puntip; Stuenæs, Jorid T; Molina-Carrion, Marjorie; DeFronzo, Ralph A; Sakamoto, Kei; Musi, Nicolas

2012-07-01

Insulin stimulates glycogen synthase (GS) through dephosphorylation of serine residues, and this effect is impaired in skeletal muscle from insulin-resistant [obese and type 2 diabetic (T2DM)] subjects. Exercise also increases GS activity, yet it is not known whether the ability of exercise to affect GS is impaired in insulin-resistant subjects. The objective of this study was to examine the effect of acute exercise on GS phosphorylation and enzyme kinetic properties in muscle from insulin-resistant individuals. Lean normal glucose-tolerant (NGT), obese NGT, and obese T2DM subjects performed 40 min of moderate-intensity cycle exercise (70% of Vo(2max)). GS kinetic properties and phosphorylation were measured in vastus lateralis muscle before exercise, immediately after exercise, and 3.5 h postexercise. In lean subjects, GS fractional activity increased twofold after 40 min of exercise, and it remained elevated after the 3.5-h rest period. Importantly, exercise also decreased GS K(m) for UDP-glucose from ≈0.5 to ≈0.2 mM. In lean subjects, exercise caused significant dephosphorylation of GS by 50-70% (Ser(641), Ser(645), and Ser(645,649,653,657)), and phosphorylation of these sites remained decreased after 3.5 h; Ser⁷ phosphorylation was not regulated by exercise. In obese NGT and T2DM subjects, exercise increased GS fractional activity, decreased K(m) for UDP-glucose, and decreased GS phosphorylation as effectively as in lean NGT subjects. We conclude that the molecular regulatory process by which exercise promotes glycogen synthesis in muscle is preserved in insulin-resistant subjects.

[Ultrasonographic evaluation of selected parameters of the endothelial function in brachial arteries and IMT measurements in carotid arteries in children with diabetes type 1 using personal insulin pumps--preliminary report].

PubMed

Tołwińska, Joanna; Głowińska-Olszewska, Barbara; Urban, Mirosława; Florys, Bozena; Peczyńska, Jadwiga

2006-01-01

Type 1 diabetes is a known risk factor for arterial atherosclerosis. The first symptoms can be found even in childhood. The ultrasonographic measurements of intimal plus medial thickness in carotid arteries (IMT) and flow mediated dilatation (FMD) evaluated in brachial arteries, play a known role in the detection in these cases. The diabetes treatment intensification is an important factor in delaying early atherosclerotic changes. Currently, intensive treatment of children's diabetes with use of continuous subcutaneous insulin infusion with personal insulin pumps is gaining more and more popularity. THE AIM OF THIS STUDY was the evaluation of IMT and FMD indexes in children suffering from type 1 diabetes in the context of treatment intensification (multidose insulin injections v. personal insulin pumps). We examined 64 children (29 boys and 35 girls) in the mean age 15.5 years treated with the multidose insulin injections method and 10 children using personal insulin pumps (4 girls and 6 boys) in the mean age 14.5 years. Using high resolution ultrasonography we evaluated IMT values in carotid arteries and FMD parameters in brachial arteries. In our analysis we estimated the blood concentration of lipid parameters, values of systolic and diastolic blood pressure, the age of diabetes onset, duration time of the illness and the values of HbA1c as a marker of metabolic control. We noticed significantly higher FMD values in patients treated with personal insulin pumps (13.7 vs. 5.5%, p=0.001). IMT values were similar in both groups (0.52 vs. 0.5 mm, p=0. 41). The level of HDL cholesterol was higher and triglycerides lower in the group with treatment intensification. The metabolic control was the same in both groups. In patients treated by the multidose insulin injections IMT correlated with systolic blood pressure values. We didn't notice any correlation between IMT and FMD in any group. 1. Treatment intensification (personal insulin pumps) influences better vascular endothelial function in type 1 diabetic children and seems to be a significant tool in delaying the atherosclerotic process. 2. We need more examinations to explain the role of treatment intensification in common carotid arteries wall morphology in type 1 diabetic children. 3. The ultrasonographic detection of atherosclerotic changes in arterial vessels can help in the evaluation of the changes due to different methods of diabetes treatment.

Effects of a low-glycemic load vs low-fat diet in obese young adults: a randomized trial.

PubMed

Ebbeling, Cara B; Leidig, Michael M; Feldman, Henry A; Lovesky, Margaret M; Ludwig, David S

2007-05-16

The results of clinical trials involving diet in the treatment of obesity have been inconsistent, possibly due to inherent physiological differences among study participants. To determine whether insulin secretion affects weight loss with 2 popular diets. Randomized trial of obese young adults (aged 18-35 years; n = 73) conducted from September 2004 to December 2006 in Boston, Mass, and consisting of a 6-month intensive intervention period and a 12-month follow-up period. Serum insulin concentration at 30 minutes after a 75-g dose of oral glucose was determined at baseline as a measure of insulin secretion. Outcomes were assessed at 6, 12, and 18 months. Missing data were imputed conservatively. A low-glycemic load (40% carbohydrate and 35% fat) vs low-fat (55% carbohydrate and 20% fat) diet. Body weight, body fat percentage determined by dual-energy x-ray absorptiometry, and cardiovascular disease risk factors. Change in body weight and body fat percentage did not differ between the diet groups overall. However, insulin concentration at 30 minutes after a dose of oral glucose was an effect modifier (group x time x insulin concentration at 30 minutes: P = .02 for body weight and P = .01 for body fat percentage). For those with insulin concentration at 30 minutes above the median (57.5 microIU/mL; n = 28), the low-glycemic load diet produced a greater decrease in weight (-5.8 vs -1.2 kg; P = .004) and body fat percentage (-2.6% vs -0.9%; P = .03) than the low-fat diet at 18 months. There were no significant differences in these end points between diet groups for those with insulin concentration at 30 minutes below the median level (n = 28). Insulin concentration at 30 minutes after a dose of oral glucose was not a significant effect modifier for cardiovascular disease risk factors. In the full cohort, plasma high-density lipoprotein cholesterol and triglyceride concentrations improved more on the low-glycemic load diet, whereas low-density lipoprotein cholesterol concentration improved more on the low-fat diet. Variability in dietary weight loss trials may be partially attributable to differences in hormonal response. Reducing glycemic load may be especially important to achieve weight loss among individuals with high insulin secretion. Regardless of insulin secretion, a low-glycemic load diet has beneficial effects on high-density lipoprotein cholesterol and triglyceride concentrations but not on low-density lipoprotein cholesterol concentration. clinicaltrials.gov Identifier: NCT00130299.

A review of 25 years' experience with the NovoPen family of insulin pens in the management of diabetes mellitus.

PubMed

Hyllested-Winge, Jacob; Jensen, Klaus H; Rex, Jørn

2010-01-01

NovoPen, the first insulin pen, was introduced in 1985. This review article is an update of a review paper published in 2006 on 20 years' use of the NovoPen family of insulin pens in the management of diabetes mellitus. The literature searches conducted in the earlier review article were updated with search results for new articles published since April 2005. This was followed by an iterative search of references cited in identified publications and by searches of abstracts from proceedings of major international diabetes conferences since 2005. Most of the original studies identified in the 2006 review showed that insulin regimens using the NovoPen family of insulin pens were at least as effective (and in some cases superior) in maintaining glycaemic control and were as safe (in terms of hypoglycaemia) as conventional insulin regimens employing vials and syringes. Most patients preferred the various NovoPen insulin pens over vials and syringes, with some evidence suggesting that the use of discreet devices, such as those of the NovoPen family, facilitates intensive insulin therapy regimens, thereby helping to improve lifestyle flexibility. The new search results showed that the current generation of the device for the adult population, NovoPen 4, retains these benefits and further meets patients' needs by improving ease of use, convenience and discretion, which may be particularly important for those with manual dexterity, visual or auditory impairments. There was also evidence that healthcare professionals would be more likely to recommend NovoPen 4 to their patients than other devices. The recently introduced NovoPen Echo, designed specifically for the paediatric population, combines half-increment dosing with a memory function that can be used to retrieve information about the time and amount of the last dose, potentially reducing the fear of double dosing or missing a dose. Evidence obtained from the new searches suggested that paediatric patients, their parents and healthcare professionals were highly satisfied with NovoPen Echo overall, with most paediatric patients rating it their favourite pen compared with other insulin pens. In conclusion, new data published over the last 5 years on the use of NovoPen devices add to the large body of published evidence supporting the patient-related benefits of durable insulin injection pens in the treatment of diabetes since the first such pen was introduced in 1985. Together, the benefits of NovoPen are considered likely to improve both patients' quality of life and their compliance with therapy.

11 CFR 9033.12 - Production of computerized information.

Code of Federal Regulations, 2012 CFR

2012-01-01

... conform to the technical specifications, including file requirements, described in the Federal Election Commission's Computerized Magnetic Media Requirements for title 26 Candidates/Committees Receiving Federal... outstanding campaign obligations. (b) Organization of computerized information and technical specifications...

11 CFR 9033.12 - Production of computerized information.

Code of Federal Regulations, 2014 CFR

2014-01-01

... conform to the technical specifications, including file requirements, described in the Federal Election Commission's Computerized Magnetic Media Requirements for title 26 Candidates/Committees Receiving Federal... outstanding campaign obligations. (b) Organization of computerized information and technical specifications...

11 CFR 9033.12 - Production of computerized information.

Code of Federal Regulations, 2013 CFR

2013-01-01

... conform to the technical specifications, including file requirements, described in the Federal Election Commission's Computerized Magnetic Media Requirements for title 26 Candidates/Committees Receiving Federal... outstanding campaign obligations. (b) Organization of computerized information and technical specifications...

Microcomputer Network for Computerized Adaptive Testing (CAT)

DTIC Science & Technology

1984-03-01

PRDC TR 84-33 \\Q.�d-33- \\ MICROCOMPUTER NETWOJlt FOR COMPUTERIZED ADAPTIVE TESTING ( CAT ) Baldwin Quan Thomas A . Park Gary Sandahl John H...ACCEIIION NO NPRDC TR 84-33 4. TITLE (-d Sul>tlllo) MICROCOMP UTER NETWORK FOR COMPUTERIZED ADA PTIVE TESTING ( CAT ) 1. Q B. uan T. A . Park...adaptive testing ( CAT ) Bayesian sequential testing 20. ABSTitACT (Continuo on ro•••• aide II noco .. _, _., ld-tlly ,.,. t.loclt _._.) DO Computerized

Computerized Adaptive Testing (CAT): A User Manual

DTIC Science & Technology

1984-03-12

NPRDC TR 84-32 COMPUTERIZED ADAPTIVE TESTING ( CAT ): A USER MANUAL Susan Hardwick Lawrence Eastman Ross Cooper Rehab Group, Incorporated San...a ~EI’IOD COVIRED COMPUTERIZED ADAPTIVE TESTING ( CAT ) Final Report Aug 1981-June 1982 A USER MANUAL 1. ~l:l’t,ORMINCI ORCI. RE~ORT NUM.I:R 62-83...II nee• .. _, entl ldentll)’ ,,. llloclr _,.,) A joint-service effort is underway to develop a computerized adaptive testing ( CAT ) system and to

Clinical and scientific results in perinatal care of pregnancy complicated by insulin dependent diabetes mellitus in Croatia.

PubMed

Djelmis, J

1998-01-01

At the Department of Obstetrics and Gynecology, Perinatal Unit for Diabetes and Fetal Growth, School of Medicine, Zagreb, perinatal care of pregnancies complicated with insulin dependent diabetes melitus (IDDM), has been performed for more than 36 years. The intention of this review is to show our own results in the management of IDDM pregnancies and the latest clinical advances in perinatal care of such pregnancies. Pregnancy complicated with IDDM is at risk because of numerous maternal, fetal and neonatal complications. Recent advances in medicine, especially in diabetology and perinatology, helps clinician avoid or lessen antenatal or perinatal complications in IDDM pregnancies. The main result of improved perinatal care is that today fetal and neonatal mortality in IDDM pregnancy is almost equal to that of healthy pregnant population. Intensive preconceptual care and optimal regulation of IDDM have resulted not only in decreased perinatal mortality but also in a decreased rate of congenital malformation. Tight glycemia control during pregnancy has a beneficial effect on fetal growth. Intensive control of fetal growth, verification of lung maturation at term by amniocenthesis, and control of fetal oxygenation will result in delivery of a mature eutrophic newborn with the lowest rate of neonatal complications possible. Perinatal mortality of less than 2% in IDDM pregnancy can be obtained by planned delivery between 38 and 39 weeks of gestation by either vaginal route or cesarean section, depending on indications. After delivery, intensive care of the newborn is necessary.

High Intensity Exercise: Can It Protect You from A Fast Food Diet?

PubMed

Duval, Christian; Rouillier, Marc-Antoine; Rabasa-Lhoret, Rémi; Karelis, Antony D

2017-08-26

The purpose of this study was to assess the ability of high intensity exercise to counteract the deleterious effects of a fast food diet on the cardiometabolic profile of young healthy men. Fifteen men were subjected to an exclusive fast food diet from a popular fast food restaurant chain (three extra value meals/day + optional snack) for 14 consecutive days. Simultaneously, participants were asked to perform each day high intensity interval training (HIIT) (15 × 60 sec sprint intervals (~90% of maximal heart rate)) on a treadmill. Fast food diet and energy expenditure profiles of the participants during the intervention were assessed as well as body composition (DXA), cardiometabolic profile (lipid, hepatic enzymes, glycated hemoglobin, glucose, insulin, hsC-reactive protein (hsCRP) and blood pressure) and estimated maximal oxygen consumption (VO2 max) pre- and post-experiment. We found significant improvements for fat mass, lean body mass, estimated VO₂ max, fasting glucose, serum lipoprotein(a) and hsCRP after the intervention ( p < 0.05). HDL-cholesterol significantly decreased ( p < 0.002), but the triglycerides/HDL-cholesterol ratio did not change. All other cardiometabolic variables measured remained stable, which includes the primary outcome: the HOMA index (pre: 1.83 ± 1.2 vs. post: 1.54 ± 0.7 values; p = 0.35). In conclusion, in large part, insulin resistance and the cardiometabolic profile of young healthy individuals seems to be protected by HIIT from a fast food diet.

Adherence to a behavioral weight loss treatment program enhances weight loss and improvements in biomarkers

PubMed Central

Acharya, Sushama D; Elci, Okan U; Sereika, Susan M; Music, Edvin; Styn, Mindi A; Turk, Melanie Warziski; Burke, Lora E

2009-01-01

Objectives: To describe participants’ adherence to multiple components (attendance, energy intake, fat gram, exercise goals, and self-monitoring eating and exercise behaviors) of a standard behavioral treatment program (SBT) for weight loss and how adherence to these components may influence weight loss and biomarkers (triglycerides, low density lipoproteins [LDL], high density lipoprotein, and insulin) during the intensive and less-intensive intervention phases. Methods: A secondary analysis of a randomized clinical trial consisting of a SBT with either fat-restricted standard or lacto-ovo vegetarian diet. The 12-month intervention was delivered in 33 group sessions. The first six months reflected the intensive phase; the second six months, the less-intensive intervention phase. We conducted the analysis without regard to treatment assignment. Eligible participants included overweight/obese adults (N = 176; mean body mass index = 34.0 kg/m2). The sample was 86.9% female, 70.5% White, and 44.4 ± 8.6 years old. The outcome measures included weight and biomarkers. Results: There was a significant decline in adherence to each treatment component over time (P < 0.0001). In the first six months, adherence to attendance, self-monitoring and the energy goal were significantly associated with greater weight loss (P < 0.05). Adherence to attendance and exercise remained significantly associated with weight loss in the second six months (P < 0.05). Adherence to attendance, self-monitoring and exercise had indirect effects through weight loss on LDL, triglycerides, and insulin (P < 0.05). Conclusions: We observed a decline in adherence to each treatment component as the intervention intensity was reduced. Adherence to multiple treatment components was associated with greater weight loss and improvements in biomarkers. Future research needs to focus on improving and maintaining adherence to all components of the treatment protocol to promote weight loss and maintenance. PMID:19936157

Intensive lifestyle intervention improves cardiometabolic and exercise parameters in metabolically healthy obese and metabolically unhealthy obese individuals.

PubMed

Dalzill, Claudie; Nigam, Anil; Juneau, Martin; Guilbeault, Valérie; Latour, Elise; Mauriège, Pascale; Gayda, Mathieu

2014-04-01

The effects of an intensive lifestyle intervention including Mediterranean diet nutritional counselling and high-intensity interval training (HIIT) on body composition, cardiometabolic, and exercise parameters were studied in metabolically unhealthy obese (NMHO) and metabolically healthy but obese (MHO) subjects. Fifty-five MHO (51 ± 8 years; waist circumference, 109 ± 13 cm) and 79 NMHO subjects (54 ± 9 years; waist circumference, 112 ± 13 cm) participated in an intensive lifestyle modification program based on Mediterranean diet nutritional counselling and HIIT 2-3 times per week. Body composition, cardiometabolic, and exercise parameters were measured at baseline and after 9 months. Initially, MHO patients had a lower blood pressure (BP), fasting glycemia, triglycerides, and a higher high-density lipoprotein cholesterol and peak oxygen uptake (VO2 peak) (P < 0.05) vs NMHO patients. Body mass (P < 0.05), waist circumference (P < 0.0001), total and trunk fat mass (P < 0.001), systolic and diastolic BP (P < 0.001), fasting glucose (P < 0.0001), insulin sensitivity (P < 0.05), VO2 peak and muscle endurance (P < 0.0001) were similarly improved in both groups after the program. Prevalence of NMHO was reduced by 17.91% (P < 0.01) after the program. Similar improvements in body composition, BP, and exercise parameters were found for MHO and NMHO men and women (P < 0.05). In all patients, improvement of VO2 peak was negatively correlated with improvements in body composition, systolic blood pressure, and resting heart rate (HR) (R = -0.61 to -0.24; P < 0.05). A long-term intensive lifestyle program including Mediterranean diet nutritional counselling and HIIT is an appropriate intervention in MHO and NMHO subjects with similar potential clinical health benefits including an improved body composition, BP, fasting glycemia, insulin sensitivity, VO2 peak, and muscle endurance. Copyright © 2014 Canadian Cardiovascular Society. All rights reserved.

Clinical benefits of tight glycaemic control: focus on the intensive care unit.

PubMed

Mesotten, Dieter; Van den Berghe, Greet

2009-12-01

While stress hyperglycaemia has traditionally been regarded as an adaptive, beneficial response, it is clear that hyperglycaemia and hypoglycaemia are associated with increased risk of death in critically ill intensive care unit (ICU) patients. Recent studies on blood-glucose control failed to fully clarify whether this association is causal. Early proof-of-concept single-centre randomised controlled studies found that maintaining normoglycaemia by intensive insulin therapy, as compared with tolerating hyperglycaemia as an adaptive response, improved patient outcome. However, recent large multicentre studies VISEP, GLUCONTROL and NICE-SUGAR) could not confirm this survival benefit. Methodological disparity in the execution of the complex intervention of tight glycaemic control may have contributed significantly to the contradicting results. First, different target ranges for blood glucose were used in the control group of the GLUCONTROL and 'Normoglycemia in intensive care evaluation and survival using glucose algorithm' regulation' (NICE-SUGAR) studies. Second, problems to steer blood-glucose levels within target range in the intervention group resulted in a significant overlap of the treatment groups. Third, allowing inaccurate blood-glucose measurement devices, in combination with different blood sampling sites and types of infusion pumps, may have led to unnoticed swings in blood-glucose levels. Fourth, the level of expertise of the intensive care nurses with the therapy may have been variable due to low number of study patients per centre. Finally, the studies on tight blood-glucose control were done with vastly different nutritional and end-of-life strategies. The currently available studies do not allow to confidently recommend one optimal target for glucose in heterogeneous ICU patient groups and settings. Provided that adequate devices for blood-glucose measurement and insulin administration are available, together with an extensive experience of the nursing staff, blood-glucose levels should be controlled as close to normal as possible, without evoking unacceptable fluctuations and hypoglycaemia.

[Transplantation in diabetes type 1--current problems and perspectives].

PubMed

Wasikowa, Renata; Noczyńska, Anna; Basiak, Aleksander

2004-01-01

Diabetes type 1 is, as we know, a chronic progressive disease, which requires a substitutional therapy with insulin for the whole life. The cause is a definite destruction of the pancreatic beta cells. For many years there have been intensive investigations on the possibility to obtain a complete, persistent withdrawal of the symptoms. Substitution of the destroyed, not active cells, could take place after transplantation of the whole pancreas, transplantation of pancreatic islets or transplantation of stem cells. This is now the only method which may cause an independence from exogenous insulin, persistent normoglycemia, normal HbA1c level, without risk of hypoglycemia. Pancreas and islets transplantations, however, are connected till now with the necessity of an immunosuppressive therapy for the whole life, with the toxicity of the drugs, incidence of frequent infections and malignancy. Pancreas transplantation is a serious surgical intervention, connected with numerous risks and complications, considerably less risk appears in islet cell transplantations. Since 2000 exclusively islet cell transplantations have been performed. One of the leading centers is Edmonton, where professor Shapiro prepared the so called. Edmonton protocol which is characterized by using corticosteroid-free immunosuppressive drugs, islet cells from two or more donors, repeated till the attainment of insulin dependence. A problem now is that the islets are obtained from cadavers. Therefore intensive research is conducted for alternative sources of beta cells. At this moment it is mostly preferred for receiving a sufficient number of insulin producing cells to develop stem cells with a subsequent differentiation to insulin producing cells. The mentioned cells have an unlimited ability of reproduction, in this case also immunosuppressive therapy is not necessary. Alternative sources of beta cells are cells achieved on the genetic engineering, embryonic or adult somatic stem cells. It is however important to stress, that adult stem cells as insulin producing cells are not unequivocally identified. For obtaining better, permanent results after transplantation the following are important: optimalization of "islands growth" in the liver, prevention of the early inflammations, further development of highly selective, well tolerated, corticosteroid-free immunosuppressive drugs, identification of rejecting markers, induction of immunotolerance, micro- and macro-capsulation of the islets to protect the recipient against the immunological attack. Several multicenter studies in important scientific centers are opened, there is also Juvenile Research Foundation International. In spite of a permanent progress there are still many important problems to solve. It is necessary to institute further multicenter, international research to ascertain the effect of transplantation concerning the normalisation of glycemia, prevention or inhibition of the progress of diabetic complications and to prolong the life span in patients with type 1 diabetes after transplantation.

Resources for Improving Computerized Learning Environments.

ERIC Educational Resources Information Center

Yeaman, Andrew R. J.

1989-01-01

Presents an annotated review of human factors literature that discusses computerized environments. Topics discussed include the application of office automation practices to educational environments; video display terminal (VDT) workstations; health and safety hazards; planning educational facilities; ergonomics in computerized offices; and…

The effect of auditory memory load on intensity resolution in individuals with Parkinson's disease

NASA Astrophysics Data System (ADS)

Richardson, Kelly C.

Purpose: The purpose of the current study was to investigate the effect of auditory memory load on intensity resolution in individuals with Parkinson's disease (PD) as compared to two groups of listeners without PD. Methods: Nineteen individuals with Parkinson's disease, ten healthy age- and hearing-matched adults, and ten healthy young adults were studied. All listeners participated in two intensity discrimination tasks differing in auditory memory load; a lower memory load, 4IAX task and a higher memory load, ABX task. Intensity discrimination performance was assessed using a bias-free measurement of signal detectability known as d' (d-prime). Listeners further participated in a continuous loudness scaling task where they were instructed to rate the loudness level of each signal intensity using a computerized 150mm visual analogue scale. Results: Group discrimination functions indicated significantly lower intensity discrimination sensitivity (d') across tasks for the individuals with PD, as compared to the older and younger controls. No significant effect of aging on intensity discrimination was observed for either task. All three listeners groups demonstrated significantly lower intensity discrimination sensitivity for the higher auditory memory load, ABX task, compared to the lower auditory memory load, 4IAX task. Furthermore, a significant effect of aging was identified for the loudness scaling condition. The younger controls were found to rate most stimuli along the continuum as significantly louder than the older controls and the individuals with PD. Conclusions: The persons with PD showed evidence of impaired auditory perception for intensity information, as compared to the older and younger controls. The significant effect of aging on loudness perception may indicate peripheral and/or central auditory involvement.

An overview of selected information storage and retrieval issues in computerized document processing

NASA Technical Reports Server (NTRS)

Dominick, Wayne D. (Editor); Ihebuzor, Valentine U.

1984-01-01

The rapid development of computerized information storage and retrieval techniques has introduced the possibility of extending the word processing concept to document processing. A major advantage of computerized document processing is the relief of the tedious task of manual editing and composition usually encountered by traditional publishers through the immense speed and storage capacity of computers. Furthermore, computerized document processing provides an author with centralized control, the lack of which is a handicap of the traditional publishing operation. A survey of some computerized document processing techniques is presented with emphasis on related information storage and retrieval issues. String matching algorithms are considered central to document information storage and retrieval and are also discussed.

High-protein hypocaloric vs normocaloric enteral nutrition in critically ill patients: A randomized clinical trial.

PubMed

Rugeles, Saúl; Villarraga-Angulo, Luis Gabriel; Ariza-Gutiérrez, Aníbal; Chaverra-Kornerup, Santiago; Lasalvia, Pieralessandro; Rosselli, Diego

2016-10-01

Appropriate caloric intake in critically ill patients receiving enteral nutrition is controversial. This study evaluates the impact of different caloric regimens on severity of organ failure measured with Sequential Organ Failure Assessment (SOFA). We conducted a randomized prospective controlled trial. Study population included adult intensive care unit (ICU) patients expected to require enteral nutrition for more than 96 hours. Goals in the intervention group were hypocaloric (15 kcal/kg per day) enteral nutrition compared to normocaloric (25 kcal/kg per day) enteral nutrition, both with hyperproteic intake (1.7 g of protein/kg per day). Primary end point was change in SOFA score (ΔSOFA) from baseline at 48 hours. Secondary end points were ΔSOFA at 96 hours, insulin requirements, hyperglycemia or hypoglycemic episodes, length of ICU stay, days on ventilator, and 28-day mortality. After screening 443 patients, 120 patients were analyzed. There were no differences between groups in baseline characteristics. We did not find a statistically significant difference in ΔSOFA at 48 hours. Patients in the hypocaloric group showed lower average daily insulin requirements and percentage of patients requiring any insulin. Hyperproteic, hypocaloric nutrition did not show different outcomes compared to normocaloric nutrition, except lower insulin requirements. Hypocaloric nutrition could provide a more physiologic approach with lower need for care and metabolic impact. Copyright © 2016 Elsevier Inc. All rights reserved.

Geriatric patient profile in the cardiovascular surgery intensive care unit.

PubMed

Korhan, Esra Akin; Hakverdioglu, Gulendam; Ozlem, Maryem; Ozlem, Maryem; Yurekli, Ismail; Gurbuz, Ali; Alp, Nilgun Akalin

2013-11-01

To determine hospitalization durations and mortalities of elderly in the Cardiovascular Surgery Intensive Care Unit. The retrospective study was conducted in a Cardiovascular Surgery Intensive Care Unit in Turkey and comprised patient records from January 1 to December 31, 2011. Computerized epicrisis reports of 255, who had undergone a cardiac surgery were collected. The patients were grouped according to their ages, Group I aged 65-74 and Group II aged 75 and older. European society for Cardiac Operative Risk Evaluation scores of the two groups were compared using SPSS 17. Overall, there were 80 (31.37%) females and 175 (68.62%) males. There were 138 (54.1%) patients in Group I and 117 (45.9%) in Group II. Regarding their hospitalization reasons, it was determined that 70 (27.5%) patients in Group I and 79 (30.9%) patients in Group II were treated with the diagnosis ofcoronary artery disease. The average hospitalization duration of patients in the intensive care unit was determined to be 11.57 +/- 0.40 days. Regarding the EuroSCORE score intervals of patients, 132 (51.8%) had 3-5 and 225 (88.2%) patients were transferred to the Cardiovascular Surgery and then all of them were discharged; 5 (4.1%) had a mortal course; and 11 (7.7%) were transferred to the anaesthesia intensive care unit. The general mortality rates are very low in the Cardiovascular Surgery Intensive Care Unit and the patients have a good prognosis.

Practical measures of cognitive function and promotion of their performance in the context of research.

PubMed

Gujski, Mariusz; Juńczyk, Tomasz; Pinkas, Jaroslaw; Owoc, Alfred; Bojar, Iwona

2016-09-01

The aging of the population generates a number of very interesting research questions in the fields of medicine, psychology, sociology, demography, and many others. One of the issues subject to both intensive research by scientists and exploration by practitioners is associated with cognitive functions. The article presents current knowledge regarding practical actions in the field of promoting cognitive function using diagnostic programmes and training using modern technologies. An important aspect presented in this study is also related to the welfare of the maintenance or improvement of cognitive function. Information and communication technologies will contribute to the dissemination of computerized cognitive training, also personalized.

Intense Exercise Promotes Adult Hippocampal Neurogenesis But Not Spatial Discrimination

PubMed Central

So, Ji H.; Huang, Chao; Ge, Minyan; Cai, Guangyao; Zhang, Lanqiu; Lu, Yisheng; Mu, Yangling

2017-01-01

Hippocampal neurogenesis persists throughout adult life and plays an important role in learning and memory. Although the influence of physical exercise on neurogenesis has been intensively studied, there is controversy in regard to how the impact of exercise may vary with its regime. Less is known about how distinct exercise paradigms may differentially affect the learning behavior. Here we found that, chronic moderate treadmill running led to an increase of cell proliferation, survival, neuronal differentiation, and migration. In contrast, intense running only promoted neuronal differentiation and migration, which was accompanied with lower expressions of vascular endothelial growth factor, brain-derived neurotrophic factor, insulin-like growth factor 1, and erythropoietin. In addition, the intensely but not mildly exercised animals exhibited a lower mitochondrial activity in the dentate gyrus. Correspondingly, neurogenesis induced by moderate but not intense exercise was sufficient to improve the animal’s ability in spatial pattern separation. Our data indicate that the effect of exercise on spatial learning is intensity-dependent and may involve mechanisms other than a simple increase in the number of new neurons. PMID:28197080

Computerized Sociometric Assessment for Preschool Children

ERIC Educational Resources Information Center

Endedijk, Hinke M.; Cillessen, Antonius H. N.

2015-01-01

In preschool classes, sociometric peer ratings are used to measure children's peer relationships. The current study examined a computerized version of preschool sociometric ratings. The psychometric properties were compared of computerized sociometric ratings and traditional peer ratings for preschoolers. The distributions, inter-item…

Effect of High-Intensity Interval Training on Plasma Omentin-1 Concentration in Overweight/Obese and Normal-Weight Youth

PubMed Central

Ouerghi, Nejmeddine; Fradj, Mohamed Kacem Ben; Bezrati, Ikram; Feki, Moncef; Kaabachi, Naziha; Bouassida, Anissa

2017-01-01

Objectives Omentin-1 is a recently discovered adipokine, mainly produced by visceral adipose tissue, which is thought to improve insulin sensitivity. The study aimed to assess the association of plasma omentin-1 with cardiometabolic traits and physical performance and to test its response to high-intensity interval training (HIIT) in obese and normal-weight subjects. Methods Nine overweight/obese (OG) and 9 normal-weight (NWG) young men performed an 8-week HIIT program. Body composition, physical performance, homeostasis model assessment index for insulin resistance (HOMA-IR) as well as plasma omentin-1and lipid levels were assessed before and after the HIIT program. Results Baseline plasma omentin-1 was lower in OG than NWG men (359 ± 138 vs. 470 ± 114 ng/ml; p = 0.052). Plasma omentin-1 was related to body fat (r = −0.57; p = 0.03) and LDL-cholesterol (r = −0.49; p = 0.04). There was a trend towards significant association of omentin-1 with BMI (r = −0.47; p = 0.06) and VO2max (r = 0.41; p = 0.09). However, no association was observed with HOMA-IR. Following the HIIT program, omentin-1 concentrations have significantly (p < 0.01) increased in OG (359 ± 138 to 455 ± 126 ng/ml) and NWG men (470 ± 114 to 572 ± 115 ng/ml). In parallel, the cardiometabolic profile has improved with a significant decrease of HOMA-IR in OG. Conclusions HIIT resulted in a plasma omentin-1 increase and an improvement with regard to cardiometabolic traits in the OG men, which may contribute to modulate insulin sensitivity. PMID:28787708

Wolfram syndrome 1 gene (WFS1) product localizes to secretory granules and determines granule acidification in pancreatic beta-cells.

PubMed

Hatanaka, Masayuki; Tanabe, Katsuya; Yanai, Akie; Ohta, Yasuharu; Kondo, Manabu; Akiyama, Masaru; Shinoda, Koh; Oka, Yoshitomo; Tanizawa, Yukio

2011-04-01

Wolfram syndrome is an autosomal recessive disorder characterized by juvenile-onset insulin-dependent diabetes mellitus and optic atrophy. The gene responsible for the syndrome (WFS1) encodes an endoplasmic reticulum (ER) resident transmembrane protein. The Wfs1-null mouse exhibits progressive insulin deficiency causing diabetes. Previous work suggested that the function of the WFS1 protein is connected to unfolded protein response and to intracellular Ca(2+) homeostasis. However, its precise molecular function in pancreatic β-cells remains elusive. In our present study, immunofluorescent and electron-microscopic analyses revealed that WFS1 localizes not only to ER but also to secretory granules in pancreatic β-cells. Intragranular acidification was assessed by measuring intracellular fluorescence intensity raised by the acidotrophic agent, 3-[2,4-dinitroanilino]-3'-amino-N-methyldipropyramine. Compared with wild-type β-cells, there was a 32% reduction in the intensity in WFS1-deficient β-cells, indicating the impairment of granular acidification. This phenotype may, at least partly, account for the evidence that Wfs1-null islets have impaired proinsulin processing, resulting in an increased circulating proinsulin level. Morphometric analysis using electron microscopy evidenced that the density of secretory granules attached to the plasma membrane was significantly reduced in Wfs1-null β-cells relative to that in wild-type β-cells. This may be relevant to the recent finding that granular acidification is required for the priming of secretory granules preceding exocytosis and may partly explain the fact that glucose-induced insulin secretion is profoundly impaired in young prediabetic Wfs1-null mice. These results thus provide new insights into the molecular mechanisms of β-cell dysfunction in patients with Wolfram syndrome.

Acute Exercise and Insulin Sensitivity in Boys: A Time-Course Study.

PubMed

Cockcroft, Emma J; Williams, Craig A; Weaver, Hayley; O'Connor, Amy; Jackman, Sarah R; Armstrong, Neil; Barker, Alan R

2017-11-01

This study examined the time course of adaptions in insulin sensitivity (IS) in adolescent boys after acute high-intensity interval exercise (HIIE) and moderate-intensity exercise (MIE). Eight boys (15.1±0.4 y) completed three 3-day experimental trials in a randomised order: 1) 8×1 min cycling at 90% peak power with 75 s recovery (HIIE); 2) cycling at 90% of gas exchange threshold for a duration to match work during HIIE (MIE); and 3) rest (CON). Plasma [glucose] and [insulin] were measured before (PRE-Ex), 24 and 48 h post (24 h-POST, 48 h-POST) in a fasted state, and 40 min (POST-Ex) and 24 h (24 h-POST) post in response to an oral glucose tolerance test (OGTT). IS was estimated using the Cederholm (OGTT) and HOMA (fasted) indices. There was no change to HOMA at 24 h or 48 h-POST (all P> 0.05). IS from the OGTT was higher POST-EX for HIIE compared to CON (17.4%, P =0.010, ES=1.06), and a non-significant increase in IS after MIE compared to CON (9.0%, P =0.14, ES=0.59). At 24 h-POST, IS was higher following both HIIE and MIE compared to CON (HIIE: P =0.019, 13.2%, ES=0.88; MIE: 9.7%, P =0.024, ES=0.65). In conclusion, improvements to IS after a single bout of HIIE and MIE persist up to 24 h after exercise when assessed by OGTT. © Georg Thieme Verlag KG Stuttgart · New York.

High-intensity interval training improves insulin sensitivity in older individuals.

PubMed

Søgaard, D; Lund, M T; Scheuer, C M; Dehlbaek, M S; Dideriksen, S G; Abildskov, C V; Christensen, K K; Dohlmann, T L; Larsen, S; Vigelsø, A H; Dela, F; Helge, J W

2018-04-01

Metabolic health may deteriorate with age as a result of altered body composition and decreased physical activity. Endurance exercise is known to counter these changes delaying or even preventing onset of metabolic diseases. High-intensity interval training (HIIT) is a time efficient alternative to regular endurance exercise, and the aim of this study was to investigate the metabolic benefit of HIIT in older subjects. Twenty-two sedentary male (n = 11) and female (n = 11) subjects aged 63 ± 1 years performed HIIT training three times/week for 6 weeks on a bicycle ergometer. Each HIIT session consisted of five 1-minute intervals interspersed with 1½-minute rest. Prior to the first and after the last HIIT session whole-body insulin sensitivity, measured by a hyperinsulinaemic-euglycaemic clamp, plasma lipid levels, HbA1c, glycaemic parameters, body composition and maximal oxygen uptake were assessed. Muscle biopsies were obtained wherefrom content of glycogen and proteins involved in muscle glucose handling were determined. Insulin sensitivity (P = .011) and maximal oxygen uptake increased (P < .05) in both genders, while plasma cholesterol (P < .05), low-density lipoprotein (P < .05), visceral fat mass (P < .05) and per cent body fat (P < .05) decreased after 6 weeks of HIIT. HbA1c decreased only in males (P = .001). Muscle glycogen content increased in both genders (P = .001) and in line GLUT4 (P < .05), glycogen synthase (P = .001) and hexokinase II (P < .05) content all increased. Six weeks of HIIT significantly improves metabolic health in older males and females by reducing age-related risk factors for cardiometabolic disease. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Effect of High-Intensity Interval Training on Plasma Omentin-1 Concentration in Overweight/Obese and Normal-Weight Youth.

PubMed

Ouerghi, Nejmeddine; Ben Fradj, Mohamed Kacem; Bezrati, Ikram; Feki, Moncef; Kaabachi, Naziha; Bouassida, Anissa

2017-01-01

Omentin-1 is a recently discovered adipokine, mainly produced by visceral adipose tissue, which is thought to improve insulin sensitivity. The study aimed to assess the association of plasma omentin-1 with cardiometabolic traits and physical performance and to test its response to high-intensity interval training (HIIT) in obese and normal-weight subjects. Nine overweight/obese (OG) and 9 normal-weight (NWG) young men performed an 8-week HIIT program. Body composition, physical performance, homeostasis model assessment index for insulin resistance (HOMA-IR) as well as plasma omentin-1and lipid levels were assessed before and after the HIIT program. Baseline plasma omentin-1 was lower in OG than NWG men (359 ± 138 vs. 470 ± 114 ng/ml; p = 0.052). Plasma omentin-1 was related to body fat (r = -0.57; p = 0.03) and LDL-cholesterol (r = -0.49; p = 0.04). There was a trend towards significant association of omentin-1 with BMI (r = -0.47; p = 0.06) and VO2max (r = 0.41; p = 0.09). However, no association was observed with HOMA-IR. Following the HIIT program, omentin-1 concentrations have significantly (p < 0.01) increased in OG (359 ± 138 to 455 ± 126 ng/ml) and NWG men (470 ± 114 to 572 ± 115 ng/ml). In parallel, the cardiometabolic profile has improved with a significant decrease of HOMA-IR in OG. HIIT resulted in a plasma omentin-1 increase and an improvement with regard to cardiometabolic traits in the OG men, which may contribute to modulate insulin sensitivity. © 2017 The Author(s) Published by S. Karger GmbH, Freiburg.

Glucose counterregulation, hypoglycemia, and intensive insulin therapy in diabetes mellitus.

PubMed

Cryer, P E; Gerich, J E

1985-07-25

The prevention or correction of hypoglycemia is the result of both dissipation of insulin and activation of counterregulatory systems. In the models studied to date, glucagon and epinephrine have been shown to be the key counterregulatory factors; the potential roles of other hormones, neural factors, or substrate mechanisms in other models and during more gradual recovery from hypoglycemia remain to be defined. Deficient glucagon responses to decrements in plasma glucose, which are common in patients with IDDM and occur in some patients with NIDDM, result in altered counterregulation. But counterregulation is generally adequate, because epinephrine compensates for it. Defective glucose counterregulation due to combined deficiencies of glucagon and epinephrine secretory responses occurs in many patients, typically those with longstanding diabetes, and must be added to the list of factors known to increase the risk of hypoglycemia, at least during intensive therapy. From the material reviewed, it should be apparent that much has been learned about glucose counterregulation. It should be equally clear that much remains to be learned. Among the many possibilities, we consider four worthy of emphasis. First of all, we need to examine the physiology and pathophysiology of glucose counterregulation in additional models (e.g., during exercise) and over longer periods. Secondly, we need to determine whether central nervous system adaptation to antecedent glycemia occurs and, if so, identify its mechanisms. Thirdly, we need to develop better methods of insulin delivery or learn to correct or compensate for defective counterregulatory systems, if we are to achieve euglycemia safely in diabetic patients with defective glucose counterregulation. Finally, we need to know whether effective control of diabetes mellitus prevents development of defective glucose counterregulation.

Effect of cortisol infusion patterns and castration on metabolic and immunological indices of stress response in cattle.

PubMed

Ting, S T L; Earley, B; Crowe, M A

2004-05-01

This study tested the hypotheses that: (1) either acute stress induced by Burdizzo castration, or cortisol infusion would modulate plasma glucose, insulin and growth hormone (GH) concentrations; and (2) immune modulation induced by cortisol would be dependent on the pattern, intensity and duration of circulating cortisol concentrations. Fifty 9.2-month-old Holstein x Friesian bulls (232 +/- 2.0 kg) were blocked by weight and randomly assigned to one of five treatments (n = 10 per treatment): (1) sham handled control; (2) Burdizzo castration; (3) hydrocortisone infusion to mimic the castration-induced secretion pattern of cortisol; (4) hourly pulse infusion of hydrocortisone; and (5) sustained infusion of hydrocortisone for 8h. Blood samples were collected intensively on day 0, and weekly from days 1 to 35. Castration acutely increased plasma cortisol, GH and haptoglobin concentrations, suppressed lymphocyte in vitro interferon-gamma (IFN-gamma) production, but had no effect on plasma glucose and insulin concentrations. Cortisol infusion to simulate the castration-induced secretion pattern of cortisol, and pulse infusion of cortisol did not suppress the IFN-gamma production. A sustained infusion of cortisol resulted in the transient suppression of IFN-gamma production. Moreover, the sustained cortisol infusion resulted in increased plasma glucose, insulin and GH concentrations. The overall 14-day feed intakes and 35-day growth rates were not affected by treatments. In conclusion, cortisol infusion to induce immune suppression in vivo occurred only at pharmacological doses. Within physiological ranges, cortisol was not associated with the suppression of immune function, indicating that during castration cortisol per se is not responsible for the suppression of in vitro IFN-gamma production.

Evaluation of computerized health management information system for primary health care in rural India

PubMed Central

2010-01-01

Background The Comprehensive Rural Health Services Project Ballabgarh, run by All India Institute of Medical Sciences (AIIMS), New Delhi has a computerized Health Management Information System (HMIS) since 1988. The HMIS at Ballabgarh has undergone evolution and is currently in its third version which uses generic and open source software. This study was conducted to evaluate the effectiveness of a computerized Health Management Information System in rural health system in India. Methods The data for evaluation were collected by in-depth interviews of the stakeholders i.e. program managers (authors) and health workers. Health Workers from AIIMS and Non-AIIMS Primary Health Centers were interviewed to compare the manual with computerized HMIS. A cost comparison between the two methods was carried out based on market costs. The resource utilization for both manual and computerized HMIS was identified based on workers' interviews. Results There have been no major hardware problems in use of computerized HMIS. More than 95% of data was found to be accurate. Health workers acknowledge the usefulness of HMIS in service delivery, data storage, generation of workplans and reports. For program managers, it provides a better tool for monitoring and supervision and data management. The initial cost incurred in computerization of two Primary Health Centers was estimated to be Indian National Rupee (INR) 1674,217 (USD 35,622). Equivalent annual incremental cost of capital items was estimated as INR 198,017 (USD 4213). The annual savings is around INR 894,283 (USD 11,924). Conclusion The major advantage of computerization has been in saving of time of health workers in record keeping and report generation. The initial capital costs of computerization can be recovered within two years of implementation if the system is fully operational. Computerization has enabled implementation of a good system for service delivery, monitoring and supervision. PMID:21078203

Nil Whey Protein Effect on Glycemic Control after Intense Mixed-Mode Training in Type 2 Diabetes.

PubMed

Gaffney, Kim Alexander; Lucero, Adam; Stoner, Lee; Faulkner, James; Whitfield, Patricia; Krebs, Jeremy; Rowlands, David Stephen

2018-01-01

Although intense endurance and resistance exercise training and whey protein supplementation have both been shown to independently improve glycemic control, no known studies have examined the effect of high-intensity mixed-mode interval training (MMIT) and whey supplementation in adults with Type 2 diabetes (T2D). This study aimed to determine if peritraining whey protein supplementation combined with MMIT can improve glycemic control. In a double-blind, randomized, placebo-controlled trial, 24 men (55.7 ± 5.6 yr) with T2D performed MMIT with whey (20 g) or placebo control for 10 wk. Glycemic control was assessed via glucose disposal rate during a euglycemic insulin clamp, fasting blood glucose concentration, and homeostatic model assessment of insulin resistance. Changes in peak oxygen consumption, 1-repetition maximum strength, vastus lateralis muscle, and subcutaneous adipose thicknesses, and waist circumference were also assessed. Ten weeks of MMIT substantially improved glucose disposal rate by 27.5% (90% confidence interval, 1.2%-60.7%) and 24.8% (-5.4% to 64.8%) in the whey and control groups, respectively. There were likely and possible reductions in fasting blood glucose by -17.4% (-30.6% to -1.6%) and homeostatic model assessment of insulin resistance by -14.1% (-25.3% to 1.08%) in the whey group; however, whey effects were not clearly beneficial to glycemic outcomes relative to the control. MMIT also clearly substantially improved 1-repetition maximum by 20.6% (16.3%-24.9%) and 22.7% (18.4%-27.2%), peak oxygen consumption by 22.6% (12.0%-26.2%) and 18.5% (10.5%-27.4%), and vastus lateralis muscle thickness by 18.9% (12.0%-26.2%) and 18.6% (10.5%-27.4%) and possibly reduced waist circumference by -2.1% (-3.1% to -1.0%) and -1.9% (-3.7% to -0.1%) in the control and whey groups, respectively, but the whey-control outcome was trivial or unclear. A clinically meaningful enhancement in glycemic control after 10 wk of MMIT was not clearly advanced with peritraining whey protein supplementation in middle-age men with T2D.

78 FR 17940 - Certain Computerized Orthopedic Surgical Devices, Software, Implants, and Components Thereof...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-25

..., Software, Implants, and Components Thereof; Notice of Receipt of Complaint; Solicitation of Comments... Certain Computerized Orthopedic Surgical Devices, Software, Implants, and Components Thereof, DN 2945; the... importation of certain computerized orthopedic surgical devices, software, implants, and components thereof...

Designing a Computerized Presentation Center.

ERIC Educational Resources Information Center

Christopher, Doris A.

1995-01-01

The Office Systems and Business Education Department at California State University (Los Angeles) developed a computerized presentation center, with multimedia classrooms and a multipurpose room, where students learn computerized presentation design skills, faculty can develop materials for class, and local business can do videoconferencing and…

Endurance, interval sprint, and resistance exercise training: impact on microvascular dysfunction in type 2 diabetes

PubMed Central

Laughlin, M. Harold

2015-01-01

Type 2 diabetes (T2D) alters capillary hemodynamics, causes capillary rarefaction in skeletal muscle, and alters endothelial and vascular smooth muscle cell phenotype, resulting in impaired vasodilatory responses. These changes contribute to altered blood flow responses to physiological stimuli, such as exercise and insulin secretion. T2D-induced microvascular dysfunction impairs glucose and insulin delivery to skeletal muscle (and other tissues such as skin and nervous), thereby reducing glucose uptake and perpetuating hyperglycemia and hyperinsulinemia. In patients with T2D, exercise training (EX) improves microvascular vasodilator and insulin signaling and attenuates capillary rarefaction in skeletal muscle. EX-induced changes subsequently augment glucose and insulin delivery as well as glucose uptake. If these adaptions occur in a sufficient amount of tissue, and skeletal muscle in particular, chronic exposure to hyperglycemia and hyperinsulinemia and the risk of microvascular complications in all vascular beds will decrease. We postulate that EX programs that engage as much skeletal muscle mass as possible and recruit as many muscle fibers within each muscle as possible will generate the greatest improvements in microvascular function, providing that the duration of the stimulus is sufficient. Primary improvements in microvascular function occur in tissues (skeletal muscle primarily) engaged during exercise, and secondary improvements in microvascular function throughout the body may result from improved blood glucose control. We propose that the added benefit of combined resistance and aerobic EX programs and of vigorous intensity EX programs is not simply “more is better.” Rather, we believe the additional benefit is the result of EX-induced adaptations in and around more muscle fibers, resulting in more muscle mass and the associated microvasculature being changed. Thus, to acquire primary and secondary improvements in microvascular function and improved blood glucose control, EX programs should involve upper and lower body exercise and modulate intensity to augment skeletal muscle fiber recruitment. Under conditions of limited mobility, it may be necessary to train skeletal muscle groups separately to maximize whole body skeletal muscle fiber recruitment. PMID:26408541

Changes in aerobic capacity and glycaemic control in response to reduced-exertion high-intensity interval training (REHIT) are not different between sedentary men and women.

PubMed

Metcalfe, Richard S; Tardif, Nicolas; Thompson, Dylan; Vollaard, Niels B J

2016-11-01

Previously it has been reported that reduced-exertion high-intensity interval training (REHIT; total training time of 3 × 10 min per week) improves maximal aerobic capacity in both sedentary men and women, but improves insulin sensitivity in men only. The aim of the present study was to determine whether there is a true sex difference in response to REHIT, or that these findings can be explained by the large interindividual variability in response inherent to all exercise training. Thirty-five sedentary participants (18 women; mean ± SD age for men and women, respectively: age, 33 ± 9 and 36 ± 9 years; body mass index, 25.1 ± 2.1 and 24.1 ± 3.5 kg·m -2 ; maximal aerobic capacity, 38.6 ± 8.3 and 31.6 ± 4.6 mL·kg -1 ·min -1 ) completed a 6-week REHIT programme consisting of eighteen 10-min unloaded cycling sessions with 1 (first session) or 2 (all other sessions) "all-out" 10-20-s sprints against a resistance of 5% of body mass. Maximal aerobic capacity and oral glucose tolerance test-derived insulin sensitivity were determined before and after training. REHIT was associated with an increase in maximal aerobic capacity (2.54 ± 0.65 vs. 2.78 ± 0.68 L·min -1 , main effect of time: p < 0.01), a trend toward reduced plasma insulin area-under-the-curve (AUC; 6.7 ± 4.8 vs. 6.1 ± 4.0 IU·min -1 ·mL -1 , p = 0.096), but no significant change in plasma glucose AUC or the Cederholm index of insulin sensitivity. Substantial interindividual variability in response to REHIT was observed for all variables, but there was no significant effect of sex. In conclusion, REHIT improves the key health marker of aerobic capacity within a minimal total training time-commitment. There is large interindividual variability in responses to REHIT, but sex differences in the responses are not apparent.

Incentives and Barriers That Influence Clinical Computerization in Hong Kong: A Population-based Physician Survey

PubMed Central

Leung, Gabriel M.; Yu, Philip L. H.; Wong, Irene O. L.; Johnston, Janice M.; Tin, Keith Y. K.

2003-01-01

Objective: Given the slow adoption of medical informatics in Hong Kong and Asia, we sought to understand the contributory barriers and potential incentives associated with information technology implementation. Design and Measurements: A representative sample of 949 doctors (response rate = 77.0%) was asked through a postal survey to rank a list of nine barriers associated with clinical computerization according to self-perceived importance. They ranked seven incentives or catalysts that may influence computerization. We generated mean rank scores and used multidimensional preference analysis to explore key explanatory dimensions of these variables. A hierarchical cluster analysis was performed to identify homogenous subgroups of respondents. We further determined the relationships between the sets of barriers and incentives/catalysts collectively using canonical correlation. Results: Time costs, lack of technical support and large capital investments were the biggest barriers to computerization, whereas improved office efficiency and better-quality care were ranked highest as potential incentives to computerize. Cost vs. noncost, physician-related vs. patient-related, and monetary vs. nonmonetary factors were the key dimensions explaining the barrier variables. Similarly, within-practice vs external and “push” vs “pull” factors accounted for the incentive variables. Four clusters were identified for barriers and three for incentives/catalysts. Canonical correlation revealed that respondents who were concerned with the costs of computerization also perceived financial incentives and government regulation to be important incentives/catalysts toward computerization. Those who found the potential interference with communication important also believed that the promise of improved care from computerization to be a significant incentive. Conclusion: This study provided evidence regarding common barriers associated with clinical computerization. Our findings also identified possible incentive strategies that may be employed to accelerate uptake of computer systems. PMID:12595409

Can computerized tomography accurately stage childhood renal tumors?

PubMed

Abdelhalim, Ahmed; Helmy, Tamer E; Harraz, Ahmed M; Abou-El-Ghar, Mohamed E; Dawaba, Mohamed E; Hafez, Ashraf T

2014-07-01

Staging of childhood renal tumors is crucial for treatment planning and outcome prediction. We sought to identify whether computerized tomography could accurately predict the local stage of childhood renal tumors. We retrospectively reviewed our database for patients diagnosed with childhood renal tumors and treated surgically between 1990 and 2013. Inability to retrieve preoperative computerized tomography, intraoperative tumor spillage and nonWilms childhood renal tumors were exclusion criteria. Local computerized tomography stage was assigned by a single experienced pediatric radiologist blinded to the pathological stage, using a consensus similar to the Children's Oncology Group Wilms tumor staging system. Tumors were stratified into up-front surgery and preoperative chemotherapy groups. The radiological stage of each tumor was compared to the pathological stage. A total of 189 tumors in 179 patients met inclusion criteria. Computerized tomography staging matched pathological staging in 68% of up-front surgery (70 of 103), 31.8% of pre-chemotherapy (21 of 66) and 48.8% of post-chemotherapy scans (42 of 86). Computerized tomography over staged 21.4%, 65.2% and 46.5% of tumors in the up-front surgery, pre-chemotherapy and post-chemotherapy scans, respectively, and under staged 10.7%, 3% and 4.7%. Computerized tomography staging was more accurate in tumors managed by up-front surgery (p <0.001) and those without extracapsular extension (p <0.001). The validity of computerized tomography staging of childhood renal tumors remains doubtful. This staging is more accurate for tumors treated with up-front surgery and those without extracapsular extension. Preoperative computerized tomography can help to exclude capsular breach. Treatment strategy should be based on surgical and pathological staging to avoid the hazards of inaccurate staging. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

15 CFR 950.9 - Computerized Environmental Data and Information Retrieval Service.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Information Retrieval Service. 950.9 Section 950.9 Commerce and Foreign Trade Regulations Relating to Commerce... Computerized Environmental Data and Information Retrieval Service. The Environmental Data Index (ENDEX... computerized, information retrieval service provides a parallel subject-author-abstract referral service. A...

15 CFR 950.9 - Computerized Environmental Data and Information Retrieval Service.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Information Retrieval Service. 950.9 Section 950.9 Commerce and Foreign Trade Regulations Relating to Commerce... Computerized Environmental Data and Information Retrieval Service. The Environmental Data Index (ENDEX... computerized, information retrieval service provides a parallel subject-author-abstract referral service. A...

15 CFR 950.9 - Computerized Environmental Data and Information Retrieval Service.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Information Retrieval Service. 950.9 Section 950.9 Commerce and Foreign Trade Regulations Relating to Commerce... Computerized Environmental Data and Information Retrieval Service. The Environmental Data Index (ENDEX... computerized, information retrieval service provides a parallel subject-author-abstract referral service. A...

15 CFR 950.9 - Computerized Environmental Data and Information Retrieval Service.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Information Retrieval Service. 950.9 Section 950.9 Commerce and Foreign Trade Regulations Relating to Commerce... Computerized Environmental Data and Information Retrieval Service. The Environmental Data Index (ENDEX... computerized, information retrieval service provides a parallel subject-author-abstract referral service. A...

15 CFR 950.9 - Computerized Environmental Data and Information Retrieval Service.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Information Retrieval Service. 950.9 Section 950.9 Commerce and Foreign Trade Regulations Relating to Commerce... Computerized Environmental Data and Information Retrieval Service. The Environmental Data Index (ENDEX... computerized, information retrieval service provides a parallel subject-author-abstract referral service. A...

Innovations in Computerized Assessment.

ERIC Educational Resources Information Center

Drasgow, Fritz, Ed.; Olson-Buchanan, Julie B., Ed.

Chapters in this book present the challenges and dilemmas faced by researchers as they created new computerized assessments, focusing on issues addressed in developing, scoring, and administering the assessments. Chapters are: (1) "Beyond Bells and Whistles; An Introduction to Computerized Assessment" (Julie B. Olson-Buchanan and Fritz Drasgow);…

Advanced Composition and the Computerized Library.

ERIC Educational Resources Information Center

Hult, Christine

1989-01-01

Discusses four kinds of computerized access tools: online catalogs; computerized reference; online database searching; and compact disks and read only memory (CD-ROM). Examines how these technologies are changing research. Suggests how research instruction in advanced writing courses can be refocused to include the new technologies. (RS)

Chromium (D-phenylalanine)3 improves obesity-induced cardiac contractile defect in ob/ob mice.

PubMed

Dong, Feng; Yang, Xiaoping; Sreejayan, Nair; Ren, Jun

2007-11-01

Low-molecular weight chromium compounds, such as chromium picolinate [Cr(pic)(3)], improve insulin sensitivity, although toxicity is a concern. We synthesized a novel chromium complex, chromium (d-phenylalanine)(3) [Cr(d-phe)(3)], in an attempt to improve insulin sensitivity with reduced toxicity. The aim of this study was to compare the two chromium compounds on cardiac contractile function in ob/ob obese mice. C57BL lean and ob/ob obese mice were randomly divided into three groups: H(2)O, Cr(d-phe)(3), or Cr(pic)(3) (45 mug/kg per day orally for 6 months). The glucose tolerance test displayed improved glucose clearance by Cr(d-phe)(3) but not Cr(pic)(3). Myocytes from ob/ob mice exhibited depressed peak shortening (PS) and maximal velocity of shortening/relengthening (+/-dL/dt), prolonged time-to-PS and time-to-90% relengthening (TR90), reduced electrically stimulated rise in intracellular Ca(2+) (Deltafura-2 fluorescence intensity), and slowed intracellular Ca(2+) decay. Although a 3-month Cr(d-phe)(3) treatment for a separate group of ob/ob and lean 2-month-old mice only rectified reduced +/-dL/dt in ob/ob mice, all mechanical and intracellular Ca(2+) abnormalities were significantly attenuated or ablated by 6 months of Cr(d-phe)(3) but not Cr(pic)(3) treatment (except TR90). Sarco(endo)plasmic reticulum Ca(2+) ATPase activity and Na(+)-Ca(2+) exchanger expression were depressed in ob/ob mice, which were reversed by both Cr(d-phe)(3) and Cr(pic)(3), with a more pronounced effect from Cr(d-phe)(3). Cr(d-phe)(3) corrected reduced insulin-stimulated glucose uptake and improved basal phosphorylation of Akt and insulin receptor, as well as insulin-stimulated phosphorylation of Akt and insulin receptor in ob/ob myocytes. Heart homogenates from ob/ob mice had enhanced oxidative stress and protein carbonyl formation compared with the lean group, which were attenuated by both Cr(d-phe)(3) and Cr(pic)(3). Our data suggest that the new Cr(d-phe)(3) compound possesses better cardio-protective and insulin-sensitizing properties against obesity.

Validation of a Self-Administered Computerized System to Detect Cognitive Impairment in Older Adults

PubMed Central

Brinkman, Samuel D.; Reese, Robert J.; Norsworthy, Larry A.; Dellaria, Donna K.; Kinkade, Jacob W.; Benge, Jared; Brown, Kimberly; Ratka, Anna; Simpkins, James W.

2015-01-01

There is increasing interest in the development of economical and accurate approaches to identifying persons in the community who have mild, undetected cognitive impairments. Computerized assessment systems have been suggested as a viable approach to identifying these persons. The validity of a computerized assessment system for identification of memory and executive deficits in older individuals was evaluated in the current study. Volunteers (N = 235) completed a 3-hr battery of neuropsychological tests and a computerized cognitive assessment system. Participants were classified as impaired (n = 78) or unimpaired (n = 157) on the basis of the Mini Mental State Exam, Wechsler Memory Scale-III and the Trail Making Test (TMT), Part B. All six variables (three memory variables and three executive variables) derived from the computerized assessment differed significantly between groups in the expected direction. There was also evidence of temporal stability and concurrent validity. Application of computerized assessment systems for clinical practice and for identification of research participants is discussed in this article. PMID:25332303

Computerized neurocognitive testing in the management of sport-related concussion: an update.

PubMed

Resch, Jacob E; McCrea, Michael A; Cullum, C Munro

2013-12-01

Since the late nineties, computerized neurocognitive testing has become a central component of sport-related concussion (SRC) management at all levels of sport. In 2005, a review of the available evidence on the psychometric properties of four computerized neuropsychological test batteries concluded that the tests did not possess the necessary criteria to warrant clinical application. Since the publication of that review, several more computerized neurocognitive tests have entered the market place. The purpose of this review is to summarize the body of published studies on psychometric properties and clinical utility of computerized neurocognitive tests available for use in the assessment of SRC. A review of the literature from 2005 to 2013 was conducted to gather evidence of test-retest reliability and clinical validity of these instruments. Reviewed articles included both prospective and retrospective studies of primarily sport-based adult and pediatric samples. Summaries are provided regarding the available evidence of reliability and validity for the most commonly used computerized neurocognitive tests in sports settings.

Effects of rhythmic aerobic exercise plus core stability training on serum omentin, chemerin and vaspin levels and insulin resistance of overweight women.

PubMed

Faramarzi, Mohammad; Banitalebi, Ebrahim; Nori, Saba; Farzin, Shiva; Taghavian, Zohreh

2016-04-01

Omentin, chemerin and vaspin are novel adipokines that are secreted from adipose tissue and improved insulin sensitive. The purpose of this study was to examine the effects of rhythmic aerobic exercise plus core stability training on serum omentin, chemerin and vaspin levels and insulin resistance (IR) of overweight women. Forty aged healthy women (age; 25-45 years old, waist circumference [WC]>88 cm; Body Mass Index (BMI)>25 kg/m2) were selected purposely and divided in two control (N.=16) and experimental (N.=19) groups. Five dropped out during the study. The experimental group trained 12 weeks (3 sessions per week, one hr/session). The exercise program consisted of rhythmic aerobic exercise (55-85% maximum heart rate) along with core stability training. Serum chemerin, omentin, vaspin and insulin concentration were assayed by commercially ELISA kit. IR was evaluated according to the Homeostasis Model Assessment of Insulin Resistance Index (HOMA-IR). Data were analyzed by dependent and independent t-test to compare pre-test and post-test in each group and to compare the amount of changes in experimental and control training groups after twelve weeks. The result showed that exercise training had significant effect on BMI (P=0.00), WC (P=0.00), body fat (P=0.05), chemerin (P=0.041) and vaspin (P=0.045). But, this training had non-significant effect on plasma omentin level (P=0.090), plasma glucose level (P=0.670), insulin (P=0.11) and IR (P=0.07). Despite the fact that this kind of intervention could be an effective treatment to improve some adipokine levels and was accompanied by decreased body fat and waist circumference. However, more intense training is required to significantly change IR and serum omentin level in overweight women.

Skipping meals or carbohydrate-free meals in order to determine Basal insulin requirements in subjects with type 1 diabetes mellitus?

PubMed

Uthoff, H; Lehmann, R; Sprenger, M; Wiesli, P

2010-05-01

Basal insulin dose requirements in patients with type 1 diabetes may be derived from the course of glucose concentrations in the fasting state; i. e. by skipping meals. The present study examined whether fasting tests could be replaced by carbohydrate-free meals. 16 adult patients with type 1 diabetes (10 male) on intensive insulin therapy participated in this prospective intervention study. Mean age (+/-SD) was 44+/-12 years, BMI 24+/-3 kg/m (2), mean HbA1c was 7.5+/-0.6% and duration of diabetes 15+/-12 years. All participants skipped dinner and plasma glucose concentrations were hourly monitored from 7 p.m. to 11 p.m. This blood glucose profile was compared with three test meals given at 7 p.m. at day 2-4, consumed either in the hospital (meal 1) or at home (meal 2 and 3). No insulin injection (except to basal insulin) was allowed. Test meals consisted of 2.5 g carbohydrate, 32.4 g protein, 52.0 g fat (according to 612 kcal). During 16 fasting tests plasma glucose concentration remained stable between 7.2+/-2.4 mmol/l at 7 p.m. and 6.8+/-2.8 mmol/l at 11 p.m. (p=0.461). Following the intake of near carbohydrate-free meals (48 tests), plasma glucose concentrations rose within 4 h from 6.7+/-2.0 at 7 p.m. to 9.8+/-3.4 mmol/l at 11 p.m. (p<0.0001). The increase in plasma glucose concentrations was similar in all three different meals tested. Plasma glucose concentrations significantly increase in patients with type 1 diabetes following the intake of carbohydrate-free meals. Carbohydrate-free meal-tests cannot replace skipping meal tests to determine the basal insulin requirement in patients with type 1 diabetes.