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Sample records for delaying insulin initiation

  1. Insulin Secretion in Response to Glycemic Stimulus: Relation of Delayed Initial Release to Carbohydrate intolerance in Mild Diabetes Mellitus*

    PubMed Central

    Seltzer, Holbrooke S.; Allen, E. William; Herron, Arthur L.; Brennan, Mildred T.

    1967-01-01

    Insulin secretory responses to paired intravenous and oral glucose loads were determined in 38 nonobese individuals classified as normal (nondiabetic) subjects, “mild” diabetics (fasting blood glucose below 105 mg per 100 ml), or “moderate” diabetics (fasting glucose below 192 mg per 100 ml). Studies were also performed in 29 obese persons who were similarly grouped. The intravenous load was given to assess the alacrity of hormonal release after glycemic stimulus, and the oral glucose to determine how the speed of initial insulinogenesis modifies the disposition of ingested carbohydrate. In the nonobese group, normal subjects responded to massive hyperglycemia after rapid injection of glucose with immediate and maximal outpouring of insulin, in contrast to a desultory insulinogenic response in patients with mild diabetes, and no initial response at all in moderate diabetics. During oral glucose tolerance tests, the much faster clearance of blood sugar in nondiabetic subjects was actually associated with lower absolute insulin output than was found in mildly diabetic patients, since the latter exhibited delayed hyperinsulinemia in concert with prolonged hyperglycemia. Moderate diabetics never showed excessive insulin release despite even greater hyperglycemia. An empirical “insulinogenic index,” the ratio relating enhancement of circulating insulin to magnitude of corresponding glycemic stimulus, was used to compare the secretory capacities of respective groups. Despite the higher absolute hormonal output after oral glucose in mild diabetics, the index revealed that insulin release in normal subjects was proportionally more than twice as great. This relatively greater normal secretory response declared itself shortly after the administration of glucose by either route, and was maintained throughout both tests. In the 29 obese individuals, differences among groups were essentially the same as in persons of normal weight. Obese nondiabetics did show much

  2. Lessons learned from a pilot RCT of simultaneous versus delayed initiation of continuous glucose monitoring in children and adolescents with type 1 diabetes starting insulin pump therapy.

    PubMed

    Olivier, Patricia; Lawson, Margaret L; Huot, Celine; Richardson, Christine; Nakhla, Meranda; Romain, Judette

    2014-05-01

    Uncertainty remains about effectiveness of continuous glucose monitoring (CGM) in pediatric type 1 diabetes (T1D). Success with CGM is related to CGM adherence, which may relate to readiness to make the behavior changes required for effective use. We hypothesize that readiness for change will be greater at initiation of insulin pump therapy than in established pump users, and that this will predict CGM adherence. Our objective was to evaluate the feasibility of a randomized controlled trial (RCT) in children with established T1D comparing simultaneous pump and CGM initiation to standard pump therapy with delayed CGM initiation. We randomized participants to simultaneous pump and CGM initiation or to standard pump therapy with the option of adding CGM 4 months later. CGM adherence was tracked via web-based download and readiness for change assessed with the SOCRATES questionnaire. Of 41 eligible children, 20 agreed to participate; 15 subjects completed the study (7 males; baseline age 11.8 ± 4.0 years; T1D duration 2.7 ± 2.7 years; mean A1C 8.2 ± 0.8%). Six of 8 simultaneous group subjects used CGM > 60% of the time for 4 months compared to 1 of 7 delayed group subjects (P = .02). Using SOCRATES, we could assign 87-100% of subjects to a single motivation stage at baseline and 4 months. This pilot study demonstrates the feasibility of randomizing pump naïve children and adolescents with established T1D to simultaneous pump and CGM initiation versus standard pump therapy with delayed CGM initiation. Lessons from this pilot study were used to inform development of a full-scale multicenter RCT. © 2014 Diabetes Technology Society.

  3. Role of Emerging Insulin Technologies in the Initiation and Intensification of Insulin Therapy for Diabetes in Primary Care

    PubMed Central

    Kruger, Davida F.; Funnell, Martha M.

    2016-01-01

    In Brief This article explores some of the reasons for the delay in insulin initiation in primary care and evaluates new approaches to insulin therapy that may address these barriers and, therefore, improve insulin use by primary care providers. PMID:26807007

  4. Initiating insulin therapy in type 2 diabetes: benefits of insulin analogs and insulin pens.

    PubMed

    Brunton, Stephen

    2008-08-01

    Despite the development of alternative therapies in recent years, insulin injections remain essential treatment for type 2 diabetes once oral therapy alone becomes inadequate. However, neither patients nor physicians are proactive enough with regard to starting insulin, despite the well-known benefits of early insulin initiation and aggressive dose titration. Barriers to starting insulin therapy are being overcome by developments in insulin and delivery device technology and are the subject of this review. A literature search spanning the last 25 years was carried out to identify publications addressing issues of insulin initiation, how insulin analogs can help overcome barriers to initiation, and the advantages of pen-type insulin delivery systems. Seventy-five publications were identified. These references illustrate that the drawbacks associated with regular exogenous human insulins (soluble and NPH) are improved with modern insulin analogs. The more rapid absorption of prandial insulin analogs compared with human insulin eliminates the need for an injection-meal-interval, increasing convenience, while basal analogs have no discernible peak in activity. Modern insulin delivery devices also have advantages over the traditional vial and syringe. Currently available insulin pens are either durable (insulin cartridge is replaceable; e.g., HumaPen, Eli Lilly [Indianapolis, IN]; NovoPen series, Novo Nordisk [Bagsvaerd, Denmark]) or disposable (prefilled; e.g., FlexPen, Novo Nordisk; SoloSTAR, sanofi-aventis [Paris, France]), with features to aid ease-of-use. These include a large dose selector, dial-up and dial-down facility, and audible clicks when selecting the dose. The potential for dosing errors is thus reduced with pen-type devices, with other benefits including a discreet appearance, ease of learning, and greater user confidence. Collectively, these features contribute to overwhelming patient preference when compared with vials and syringes. Despite the greater

  5. SBASI: Actuated pyrotechnic time delay initiator

    NASA Technical Reports Server (NTRS)

    Salter, S. J.; Lundberg, R. E.; Mcdougal, G. L.

    1975-01-01

    A precision pyrotechnic time delay initiator for missile staging was developed and tested. Incorporated in the assembly is a single bridgewire Apollo standard initiator (SBASI) for initiation, a through-bulkhead-initiator to provide isolation of the SBASI output from the delay, the pyrotechnic delay, and an output charge. An attempt was made to control both primary and secondary variables affecting functional performance of the delay initiator. Design and functional limit exploration was performed to establish tolerance levels on manufacturing and assembling operations. The test results demonstrate a 2% coefficient of variation at any one temperature and an overall 2.7% coefficient of variation throughout the temperature range of 30 to 120 F. Tests were conducted at simulated operational altitude from sea level to 200,000 feet.

  6. Delayed Next Turn Repair Initiation.

    ERIC Educational Resources Information Center

    Wong, Jean

    A study examined a form of other-initiated repair which occurs later than next turn, a form which is produced by nonnative speakers of English whose native language is Mandarin. Data consists of transcriptions of naturally occurring conversations from 12 native speaker-nonnative speaker (NS-NNS) dyads, friends who ordinarily chat. Conversational…

  7. Demonstrating strategies for initiation of insulin therapy: matching the right insulin to the right patient.

    PubMed

    Meneghini, L

    2008-08-01

    To increase awareness regarding the different types of insulin available and provide discussion regarding how each type of insulin can address the needs of diverse patients in terms of their unique requirements, preferences, medical history and lifestyle concerns. New classes of antidiabetes medications, the development of insulin analogues and novel insulin delivery systems, provide more options for the management of type 2 diabetes. Given the inevitable progression of beta-cell dysfunction, along with the relatively limited glucose-lowering capacity of other agents, many patients will eventually require insulin for optimal glycaemic management. However, patients and physicians often fail to initiate insulin early enough during the progression of disease to maintain the recommended levels of glycaemic control. The inherent properties of the new insulin analogues, more physiological and user-friendly time-action profiles compared with older human insulin formulations, may partly address the barriers to insulin use. Insulin analogues include rapid acting (for prandial glycaemic control), long acting (for basal insulin coverage) and premixed insulin analogues, which combine both a rapid acting and an extended duration component in a single insulin formulation. Various case-based scenarios on initiating and intensifying therapy with insulin analogues will be presented. Development of an individualised treatment plan for initiation of insulin is a critical step in achieving target glycaemic levels in patients with type 2 diabetes.

  8. Computational modeling and analysis of insulin induced eukaryotic translation initiation.

    PubMed

    Lequieu, Joshua; Chakrabarti, Anirikh; Nayak, Satyaprakash; Varner, Jeffrey D

    2011-11-01

    Insulin, the primary hormone regulating the level of glucose in the bloodstream, modulates a variety of cellular and enzymatic processes in normal and diseased cells. Insulin signals are processed by a complex network of biochemical interactions which ultimately induce gene expression programs or other processes such as translation initiation. Surprisingly, despite the wealth of literature on insulin signaling, the relative importance of the components linking insulin with translation initiation remains unclear. We addressed this question by developing and interrogating a family of mathematical models of insulin induced translation initiation. The insulin network was modeled using mass-action kinetics within an ordinary differential equation (ODE) framework. A family of model parameters was estimated, starting from an initial best fit parameter set, using 24 experimental data sets taken from literature. The residual between model simulations and each of the experimental constraints were simultaneously minimized using multiobjective optimization. Interrogation of the model population, using sensitivity and robustness analysis, identified an insulin-dependent switch that controlled translation initiation. Our analysis suggested that without insulin, a balance between the pro-initiation activity of the GTP-binding protein Rheb and anti-initiation activity of PTEN controlled basal initiation. On the other hand, in the presence of insulin a combination of PI3K and Rheb activity controlled inducible initiation, where PI3K was only critical in the presence of insulin. Other well known regulatory mechanisms governing insulin action, for example IRS-1 negative feedback, modulated the relative importance of PI3K and Rheb but did not fundamentally change the signal flow.

  9. Delayed insulin transport across endothelium in insulin-resistant JCR:LA-cp rats.

    PubMed

    Wascher, T C; Wölkart, G; Russell, J C; Brunner, F

    2000-05-01

    /min per 1, respectively). These data show, for the first time in a genetic animal model of insulin resistance, that transfer of insulin across the endothelium is substantially delayed in obese insulin-resistant rats and that it likely contributes to the postprandial alterations of glucose metabolism observed in the metabolic syndrome.

  10. A retrospective database analysis of insulin use patterns in insulin-naïve patients with type 2 diabetes initiating basal insulin or mixtures

    PubMed Central

    Bonafede, Machaon MK; Kalsekar, Anupama; Pawaskar, Manjiri; Ruiz, Kimberly M; Torres, Amelito M; Kelly, Karen R; Curkendall, Suellen M

    2010-01-01

    Objective: To describe insulin persistence among patients with type 2 diabetes initiating insulin therapy with basal insulin or insulin mixtures and determine factors associated with nonpersistence. Research design and methods: The Thomson Reuters MarketScan® databases were used to retrospectively analyze insulin-naïve patients with type 2 diabetes by initiating insulin therapy. Insulin use was described using a variety of measures. The persistence to insulin was described using both a gap-based measure and the number of claims measure. Results: Patients in the basal insulin cohort (N = 15,255) primarily used insulin analogs (88.1%) and vial and syringe (97%). Patients in the mixture cohort (N = 2,732) were more likely to initiate on human insulin mixtures (62.5%) and vial and syringe (68.1%). Average time between insulin refills was 80 and 71 days for basal and mixture initiators, respectively. Nearly, 75% of basal insulin initiators and 65% of insulin mixture initiators had a 90-day gap in insulin prescriptions. More than half of all the patients had at least one insulin prescription per quarter. Patients initiating with insulin analogs were more likely to be persistent compared with those initiating with human insulin across both cohorts and measures of persistence (P < 0.001). Conclusion: Persistence to insulin therapy is poorer than one would anticipate, but appears to be higher in users of insulin analogs and insulin mixtures. PMID:20622915

  11. Economic analysis of insulin initiation by pharmacists in a Canadian setting

    PubMed Central

    Brown, Stephen; Al Hamarneh, Yazid N.; Tsuyuki, Ross T.; Nehme, Kimberley; Sauriol, Luc

    2016-01-01

    Background: Conducted in Alberta, the RxING study examined the effect of a community pharmacist prescribing intervention on glycemic control in patients with uncontrolled type 2 diabetes mellitus (T2DM) using insulin glargine. The objective of this study was to assess the cost-effectiveness of pharmacists’ prescribing of insulin glargine as an early intervention in uncontrolled patients with T2DM vs usual clinical practice. Methods: The IMS CORE diabetes Markov model was used to project long-term clinical outcomes, costs and cost-effectiveness of interventions. The efficacy of insulin glargine, in terms of hemoglobin A1c reduction and hypoglycemia rates, was obtained from the RxING study. Health utility and cost data were found in Canadian publications. The base-case analyses examined the economic and clinical effects of having pharmacists initiate insulin therapy in patients with uncontrolled T2DM in comparison to a physician initiate it up to 3 years later. Results: Insulin initiation by pharmacists with uncontrolled T2DM patients is cost-effective. Having pharmacists prescribe insulin 1 year earlier than usual clinical practice resulted in an incremental cost savings of $805 (CDN$) and a gain of 0.048 QALYs per patient. Pharmacists prescribing insulin 2 years earlier resulted in an incremental cost savings of $624 (CDN$) per year and a gain of 0.075 quality-adjusted life-years (QALYs). Prescribing 3 years earlier allowed for a minor increase of $26 and a gain of 0.086 QALYs. Conclusion: Earlier initiation of insulin by pharmacists, in uncontrolled T2DM patients, resulted in cost savings and delays in the development of diabetes-related complications, leading to an improved quality of life and increased survival rates. PMID:27212963

  12. Gallbladder edema in type 1 diabetic patient due to delayed-type insulin allergy.

    PubMed

    Kawasaki, Fumiko; Kamei, Shinji; Tatsumi, Fuminori; Hamamoto, Sumiko; Shimoda, Masashi; Tawaramoto, Kazuhito; Shigeto, Makoto; Kanda, Yukiko; Hashiramoto, Mitsuru; Matsuki, Michihiro; Kaku, Kohei

    2009-01-01

    A 29-year-old woman was diagnosed as having type 1 diabetes mellitus and received insulin aspart and NPH insulin (NovolinN). On day 22, she had leg edema and right abdominal pain. The serum hepatobiliary enzyme levels were markedly elevated. Computed tomography revealed gallbladder edema. After an injection of human regular insulin and NPH insulin (HumacartN), the elevated liver enzyme levels were no longer observed. Challenge testing demonstrated that protamine was the cause of her allergy. Furthermore, tests revealed increased VEGF levels. This is an extremely rare case with a delayed-type protamine allergy caused by NovolinN resulting in gallbladder edema.

  13. Delayed puberty but normal fertility in mice with selective deletion of insulin receptors from Kiss1 cells.

    PubMed

    Qiu, Xiaoliang; Dowling, Abigail R; Marino, Joseph S; Faulkner, Latrice D; Bryant, Benjamin; Brüning, Jens C; Elias, Carol F; Hill, Jennifer W

    2013-03-01

    Pubertal onset only occurs in a favorable, anabolic hormonal environment. The neuropeptide kisspeptin, encoded by the Kiss1 gene, modifies GnRH neuronal activity to initiate puberty and maintain fertility, but the factors that regulate Kiss1 neurons and permit pubertal maturation remain to be clarified. The anabolic factor insulin may signal nutritional status to these neurons. To determine whether insulin sensing plays an important role in Kiss1 neuron function, we generated mice lacking insulin receptors in Kiss1 neurons (IR(ΔKiss) mice). IR(ΔKiss) females showed a delay in vaginal opening and in first estrus, whereas IR(ΔKiss) males also exhibited late sexual maturation. Correspondingly, LH levels in IR(ΔKiss) mice were reduced in early puberty in both sexes. Adult reproductive capacity, body weight, fat composition, food intake, and glucose regulation were comparable between the 2 groups. These data suggest that impaired insulin sensing by Kiss1 neurons delays the initiation of puberty but does not affect adult fertility. These studies provide insight into the mechanisms regulating pubertal timing in anabolic states.

  14. Initial symptoms and delay in patients with penile carcinoma.

    PubMed

    Skeppner, Elisabet; Andersson, Swen-Olof; Johansson, Jan-Erik; Windahl, Torgny

    2012-10-01

    This study aimed to assess initial symptoms and factors associated with patients' and doctors' delay in penile carcinoma. Fifty consecutive patients with penile carcinoma treated with an organ-sparing technique and nine with partial amputation were enrolled in a prospective study at the Department of Urology, Örebro University Hospital, between 2005 and 2009. Face-to-face structured interviews in combination with self-assessment forms were used for the patients' descriptions of clinical symptoms, treatment seeking and reasons for delay. Data were also extracted from the medical records confirming time-lag between GP assessment, specialist care and time for diagnosis. Erythema, rash and eczema were the most common initial symptoms (35%). In total, 65% had a patients' delay of more than 6 months, and among these there was a small, but not statistically significant, predominance for pT1 and pTis tumours. Living with a stable partner did not affect the delay. The most common reason for patients' delay was the feeling of embarrassment over symptoms localized in a sexual body area. Nine patients had a doctors' delay of more than 3 months from first special visit to diagnosis. Eight of these patients consulted dermatologists and were subjected to repeated biopsies, leaving premalignant results. A considerable proportion of the patients had a patients' delay of more than 6 months, perhaps due to benign initial symptoms as erythema, rash or eczema. Psychological factors such as embarrassment and denial may also be involved, as well as insufficient awareness or knowledge.

  15. Short-term subcutaneous insulin treatment delays but does not prevent diabetes in NOD mice.

    PubMed

    Brezar, Vedran; Culina, Slobodan; Gagnerault, Marie-Claude; Mallone, Roberto

    2012-06-01

    Despite encouraging results in the NOD mouse, type 1 diabetes prevention trials using subcutaneous insulin have been unsuccessful. To explain these discrepancies, 3-week-old NOD mice were treated for 7 weeks with subcutaneous insulin at two different doses: a high dose (0.5 U/mouse) used in previous mouse studies; and a low dose (0.005 U/mouse) equivalent to that used in human trials. Effects on insulitis and diabetes were monitored along with immune and metabolic modifications. Low-dose insulin did not have any effect on disease incidence. High-dose treatment delayed but did not prevent diabetes, with reduced insulitis reappearing once insulin discontinued. This effect was not associated with significant immune changes in islet infiltrates, either in terms of cell composition or frequency and IFN-γ secretion of islet-reactive CD8(+) T cells recognizing the immunodominant epitopes insulin B(15-23) and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP)(206-214). Delayed diabetes and insulitis were associated with lower blood glucose and endogenous C-peptide levels, which rapidly returned to normal upon treatment discontinuation. In conclusion, high- but not low-dose prophylactic insulin treatment delays diabetes onset and is associated with metabolic changes suggestive of β-cell "rest" which do not persist beyond treatment. These findings have important implications for designing insulin-based prevention trials.

  16. The Longitudinal Association between Depressive Symptoms and Initiation of Insulin Therapy in People with Type 2 Diabetes in Primary Care

    PubMed Central

    Nefs, Giesje; Pop, Victor J. M.; Denollet, Johan; Pouwer, François

    2013-01-01

    Objective To examine whether depressive symptoms are associated with time to insulin initiation in insulin-naïve people with type 2 diabetes in primary care. Methods 1,389 participants completed the Edinburgh Depression Scale (EDS) in 2005 and were followed until: 1) insulin therapy was started, 2) death, 3) an oral antihyperglycemic drug (OAD) prescription gap >1 year, 4) last OAD prescription in 2010 or 5) the end of the study (December 31, 2010). Cox regression analyses were used to determine whether there was a difference in time to insulin initiation between people with a low versus a high depression score at baseline, adjusting for potential demographic and clinical confounders, including HbA1c levels. Results The prevalence of depression (EDS≥12) was 12% (n = 168). After a mean follow-up of 1,597±537 days, 253 (18%) participants had started insulin therapy. The rate of insulin initiation did not differ between depressed and non-depressed participants. People with depression were not more likely to start insulin therapy earlier or later than their non-depressed counterparts (HR = 0.98, 95% CI 0.66–1.45), also after adjustment for sex and age (HR = 0.95, 0.64–1.42). The association remained non-significant when individual candidate confounders were added to the age- and sex-adjusted base model. Conclusions In the present study, depression was not associated with time to insulin initiation. The hypothesis that depression is associated with delayed initiation of insulin therapy merits more thorough testing, preferably in studies where more information is available about patient-, provider- and health care system factors that may influence the decision to initiate insulin. PMID:24223860

  17. Pityriasis rubra pilaris-like eruption following insulin therapy initiation

    PubMed Central

    Badri, Talel; Zaouak, Anissa; Lakhoua, Ghozlane; Koubaa, Wafaa; Fennich, Sami; Zaiem, Ahmed

    2016-01-01

    Pityriasis rubra pilaris (PRP) is a chronic disorder of keratinization of unclear pathogenesis. PRP-like eruptions induced by drugs have rarely been described. A previously healthy 29-year-old man presented with a generalized, rapidly spreading, erythematosquamous dermatosis, that started three days after initiation of subcutaneous insulin therapy for diabetes mellitus type 1. Clinical and histopathological features were consistent with a PRP-like eruption, possibly due to insulin therapy. The patient was switched to insulin analogue therapy and a complete healing of all lesions was achieved after two months. No recurrence was seen after one year of follow-up. Other possible etiologies of PRP were excluded. The mechanism leading to the occurrence of drug-induced PRP-like eruptions are not clear. Since PRP may occur in the context of immunological anomalies, it is possible that diabetes mellitus type 1 may have been a predisposing condition for the development of PRP in this case. PMID:27867741

  18. Enhanced insulin sensitivity in prepubertal children with constitutional delay of growth and development.

    PubMed

    Wilson, Dyanne A; Hofman, Paul L; Miles, Harriet L; Sato, Tim A; Billett, Nathalie E; Robinson, Elizabeth M; Cutfield, Wayne S

    2010-02-01

    To test the hypothesis that prepubertal children with presumed constitutional delay of growth and development (CDGD) have enhanced insulin sensitivity and, therefore, insulin sensitivity is associated with later onset of puberty. Twenty-one prepubertal children with presumed CDGD and 23 prepubertal control children, underwent a frequently sampled intravenous glucose tolerance test to evaluate insulin sensitivity and other markers of insulin, glucose, and growth regulation. Children in the CDGD group were shorter and leaner than control subjects. Children with presumed CDGD were 40% more insulin sensitive (17.0 x 10(-4) min(-1)/[mU/L] versus 12.1 x 10(-4) min(-1)/[mU/L]; P = .0006) and had reduced acute insulin response, thus maintaining euglycemia (216 mU/L versus 330 mU/L; P = .02) compared with control subjects. In addition, the CDGD group had lower serum insulin-like growth factor binding protein 3 levels (3333 ng/mL versus 3775 ng/mL; P = .0004) and a trend toward lower serum insulin-like growth factor-II levels (794 ng/mL versus 911 ng/mL; P = .06). Prepubertal children with presumed CDGD have enhanced insulin sensitivity, supporting the hypothesis that insulin sensitivity is associated with timing of puberty. It may signify long-term biological advantages with lower risk of metabolic syndrome and malignancy. Copyright 2010 Mosby, Inc. All rights reserved.

  19. Infantile-onset saccade initiation delay (congenital ocular motor apraxia).

    PubMed

    Salman, Michael S

    2015-05-01

    Infantile-onset saccade initiation delay, also known as congenital ocular motor apraxia, typically presents in early infancy with horizontal head thrusts once head control is achieved. Defective initiation of horizontal saccades and saccade hypometria with normal saccadic velocity are characteristic findings. Isolated impairment of vertical saccades is rare. Impaired smooth ocular pursuit may be seen. Other relatively common features include developmental delay, hypotonia, ataxia, or clumsiness. Brain MRI may be normal or show a diverse range of abnormalities, most commonly involving the cerebellum. Defective slow phases of the optokinetic response are commonly associated with brain MRI abnormalities. Isolated defect of vertical saccade initiation may indicate supratentorial brain abnormalities on MRI. Joubert syndrome, a developmental midbrain-hindbrain malformation, and ataxia telangiectasia are both commonly associated with defective volitional and reflexive saccade initiation, saccade hypometria, and head thrusts. Both horizontal and vertical saccades are impaired in these two disorders.

  20. Dihydrotestosterone treatment in adolescents with delayed puberty: does it explain insulin resistance of puberty?

    PubMed

    Saad, R J; Keenan, B S; Danadian, K; Lewy, V D; Arslanian, S A

    2001-10-01

    Puberty is characterized by temporary insulin resistance, which subsides with the completion of pubertal development. This insulin resistance is manifested by lower rates of insulin-stimulated glucose metabolism and compensatory hyperinsulinemia in pubertal compared with prepubertal children. Whether or not pubertal insulin resistance is the result of sex steroids or GH or a combination of both has been investigated in our laboratory. Previously, we demonstrated that T treatment in adolescents with delayed puberty was not associated with the deterioration of insulin action. The present investigation evaluated the effects of 4 months of dihydrotestosterone administration (50 mg im every 2 wk) on body composition, glucose, fat, and protein metabolism, and insulin sensitivity. Ten adolescents with delayed puberty were evaluated before and after 4 months of DHT administration. Body composition was assessed by dual energy x-ray absorptiometry. Insulin-stimulated glucose metabolism was measured during a 3-h hyperinsulinemic (40 mU/m(2).min)-euglycemic clamp procedure. Lipolysis and proteolysis were evaluated by stable isotopes of [(2)H(5)]glycerol and [1-(13)C]leucine. After 4 months of dihydrotestosterone treatment, height, weight, and fat free mass increased and percentage of body fat decreased. IGF-I and nocturnal GH levels did not change. There was no significant change in insulin-stimulated glucose metabolism (57.2 +/- 3.9 vs. 58.3 +/- 3.9 micromol/kg.min). Total body proteolysis and lipolysis did not change. In summary, based on the present and past studies, we conclude that during puberty insulin resistance/hyperinsulinemia is not attributable to gonadal sex steroids in boys.

  1. Studying the Hurdles of Insulin Prescription (SHIP©): development, scoring and initial validation of a new self-administered questionnaire

    PubMed Central

    Martinez, Luc; Consoli, Silla M; Monnier, Louis; Simon, Dominique; Wong, Olivier; Yomtov, Bernard; Guéron, Béatrice; Benmedjahed, Khadra; Guillemin, Isabelle; Arnould, Benoit

    2007-01-01

    Background Although insulin therapy is well-accepted by symptomatic diabetic patients, it is still often delayed in less severe patients, in whom injectable insulin remains under-used. A better understanding of patients' perception of insulin would eventually help physicians to adopt the most appropriate dialogue when having to motivate patients to initiate or to intensify insulin injection. Methods The 'Studying the Hurdles of Insulin Prescription' (SHIP) questionnaire was developed based on a list of concepts derived from three diabetic patients' focus groups, and was included into two cross-sectional studies with similar design: SHIP Oral study and SHIP Premix study. Diabetic patients treated with oral hypoglycaemic agents (OHA; n = 1,494) and patients already treated with insulin (n = 1,150) completed the questionnaire at baseline, 6- and 12 months. Psychometric properties were assessed: 1) structure analysis by Principal Component Analysis (PCA) with Varimax rotation, 2) internal consistency reliability (Cronbach's alpha), and 3) concurrent validity (Spearman correlation coefficients with the Fear of Self-Injecting (FSI) score of the Diabetes Fear of Injecting and Self-testing Questionnaire. Reluctance/motivation towards insulin was assessed. Scores' ability to predict patients' insulin injection reluctance/motivation and initiation/intensification was evaluated with the Area Under the Receiver Operating Characteristic (ROC) Curve (AUC). Results PCA analysis confirmed the structure of the 14 items grouped into 3 dimensions: 'acceptance and motivation', 'fear and constraints', and 'restraints and barriers' towards insulin injection. Internal consistency reliability was excellent (Cronbach's alpha > 0.70); concurrent validity was good. The three scores were significantly predictive of patients' reluctance/motivation towards insulin injection initiation, as they were of patients' actual switch, except for the 'restraints and barriers' dimension. 'Acceptance and

  2. Early versus delayed initiation of adjuvant treatment for pancreatic cancer

    PubMed Central

    Kim, Hyoung Woo; Lee, Jong-Chan; Lee, Jongchan; Kim, Jin Won; Kim, Jaihwan; Hwang, Jin-Hyeok

    2017-01-01

    Background Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive tumor showing a tendency for early recurrence, even after curative resection. Although adjuvant treatment improves survival, it is unclear whether early adjuvant treatment initiation yields better outcomes in patients with PDAC. Methods We retrospectively enrolled 113 patients who underwent chemotherapy or chemoradiotherapy after curative resection of PDAC: Fifty-six and 57 patients were in the early and delayed groups, respectively based on the median time of treatment initiation (35 days [range, 20–83 days]). Results Patient baseline characteristics were comparable in both groups, except for grade III or IV postoperative complications (5.4% in the early group vs. 22.8% in the delayed group). With a median 20.3-month follow-up, the overall survival (OS) and disease-free survival (DFS) times were 29.5 and 14.7 months, respectively. The early group had significantly prolonged OS (39.1 vs. 21.1 months, p = 0.018) and DFS (18.8 vs. 10.0 months, p = 0.034), compared to the delayed group. Among 71 patients who completed planned adjuvant treatment, patients in the early group tended to have longer, though not statistically significant, OS and DFS times than those in the delayed group. In 67 patients without postoperative complications, patients in the early group had longer OS (42.8 vs. 20.5 months, p = 0.002) and DFS (19.6 vs. 9.1 months, p = 0.005) than those in the delayed group. By multivariate analysis, incompletion of treatment (hazard ratio [HR]: 4.039, 95% confidence interval [CI]: 2.334–6.992), delayed treatment initiation (HR: 1.822, 95% CI: 1.081–3.070), and positive angiolymphatic invasion (HR: 2.116, 95% CI: 1.160–3.862) were significantly associated with shorter OS. Conclusions Adjuvant treatment should be delivered earlier and completed for better outcomes in resected PDAC patients, especially without postoperative complications. PMID:28301556

  3. Immediate newborn care practices delay thermoregulation and breastfeeding initiation

    PubMed Central

    Sobel, Howard L; Silvestre, Maria Asuncion A; Mantaring, Jacinto Blas V; Oliveros, Yolanda E; Nyunt-U, Soe

    2011-01-01

    Aim A deadly nosocomial outbreak in a Philippine hospital drew nationwide attention to neonatal sepsis. Together with specific infection control measures, interventions that protect newborns against infection-related mortality include drying, skin-to-skin contact, delayed cord clamping, breastfeeding initiation and delayed bathing. This evaluation characterized hospital care in the first hours of life with the intent to drive policy change, strategic planning and hospital reform. Methods Trained physicians observed 481 consecutive deliveries in 51 hospitals using a standardized tool to record practices and timing of immediate newborn care procedures. Results Drying, weighing, eye care and vitamin K injections were performed in more than 90% of newborns. Only 9.6% were allowed skin-to-skin contact. Interventions were inappropriately sequenced, e.g. immediate cord clamping (median 12 sec), delayed drying (96.5%) and early bathing (90.0%). While 68.2% were put to the breast, they were separated two minutes later. Unnecessary suctioning was performed in 94.9%. Doctors trained in neonatal resuscitation were 2.5 (1.1–5.7) times more likely to unnecessarily suction vigorous newborns. Two per cent died and 5.7% developed sepsis/pneumonia. Conclusions This minute-by-minute observational assessment revealed that performance and timing of immediate newborn care interventions are below WHO standards and deprive newborns of basic protections against infection and death. PMID:21375583

  4. The Initiation of Smooth Pursuit is Delayed in Anisometropic Amblyopia

    PubMed Central

    Raashid, Rana Arham; Liu, Ivy Ziqian; Blakeman, Alan; Goltz, Herbert C.; Wong, Agnes M. F.

    2016-01-01

    Purpose Several behavioral studies have shown that the reaction times of visually guided movements are slower in people with amblyopia, particularly during amblyopic eye viewing. Here, we tested the hypothesis that the initiation of smooth pursuit eye movements, which are responsible for accurately keeping moving objects on the fovea, is delayed in people with anisometropic amblyopia. Methods Eleven participants with anisometropic amblyopia and 14 visually normal observers were asked to track a step-ramp target moving at ±15°/s horizontally as quickly and as accurately as possible. The experiment was conducted under three viewing conditions: amblyopic/nondominant eye, binocular, and fellow/dominant eye viewing. Outcome measures were smooth pursuit latency, open-loop gain, steady state gain, and catch-up saccade frequency. Results Participants with anisometropic amblyopia initiated smooth pursuit significantly slower during amblyopic eye viewing (206 ± 20 ms) than visually normal observers viewing with their nondominant eye (183 ± 17 ms, P = 0.002). However, mean pursuit latency in the anisometropic amblyopia group during binocular and monocular fellow eye viewing was comparable to the visually normal group. Mean open-loop gain, steady state gain, and catch-up saccade frequency were similar between the two groups, but participants with anisometropic amblyopia exhibited more variable steady state gain (P = 0.045). Conclusions This study provides evidence of temporally delayed smooth pursuit initiation in anisometropic amblyopia. After initiation, the smooth pursuit velocity profile in anisometropic amblyopia participants is similar to visually normal controls. This finding differs from what has been observed previously in participants with strabismic amblyopia who exhibit reduced smooth pursuit velocity gains with more catch-up saccades. PMID:27070109

  5. The Initiation of Smooth Pursuit is Delayed in Anisometropic Amblyopia.

    PubMed

    Raashid, Rana Arham; Liu, Ivy Ziqian; Blakeman, Alan; Goltz, Herbert C; Wong, Agnes M F

    2016-04-01

    Several behavioral studies have shown that the reaction times of visually guided movements are slower in people with amblyopia, particularly during amblyopic eye viewing. Here, we tested the hypothesis that the initiation of smooth pursuit eye movements, which are responsible for accurately keeping moving objects on the fovea, is delayed in people with anisometropic amblyopia. Eleven participants with anisometropic amblyopia and 14 visually normal observers were asked to track a step-ramp target moving at ±15°/s horizontally as quickly and as accurately as possible. The experiment was conducted under three viewing conditions: amblyopic/nondominant eye, binocular, and fellow/dominant eye viewing. Outcome measures were smooth pursuit latency, open-loop gain, steady state gain, and catch-up saccade frequency. Participants with anisometropic amblyopia initiated smooth pursuit significantly slower during amblyopic eye viewing (206 ± 20 ms) than visually normal observers viewing with their nondominant eye (183 ± 17 ms, P = 0.002). However, mean pursuit latency in the anisometropic amblyopia group during binocular and monocular fellow eye viewing was comparable to the visually normal group. Mean open-loop gain, steady state gain, and catch-up saccade frequency were similar between the two groups, but participants with anisometropic amblyopia exhibited more variable steady state gain (P = 0.045). This study provides evidence of temporally delayed smooth pursuit initiation in anisometropic amblyopia. After initiation, the smooth pursuit velocity profile in anisometropic amblyopia participants is similar to visually normal controls. This finding differs from what has been observed previously in participants with strabismic amblyopia who exhibit reduced smooth pursuit velocity gains with more catch-up saccades.

  6. Time to and factors associated with insulin initiation in patients with type 2 diabetes mellitus.

    PubMed

    Machado-Alba, Jorge Enrique; Machado-Duque, Manuel Enrique; Moreno-Gutierrez, Paula Andrea

    2015-03-01

    Determine the time between the start of oral antidiabetic therapy (OAD) and the initiation of insulin therapy and to establish factors associated with insulin prescription among patients with type 2 diabetes mellitus (T2DM) in Colombia. Cohort, retrospective, population-based study. We identify patients with T2DM who started OAD therapy between 1 January 2007 and 31 December 2008, and a 5-year follow-up was performed. Kaplan-Meier survival analysis for time to start insulin therapy was generated and factors associated with insulin initiation were determined using logistic regression. A total of 1042 patients (52.4% women), mean age 63.4 years at the start of pharmacological treatment. After 5 years, 272 patients (26.1%) initiated insulin therapy. Using combination therapy of metformin and glibenclamide was associated with greater risk of insulin initiation (OR: 1.64, 95% CI: 1.12-2.40, p=0.010), while being a male over 45 years of age (OR: 0.59, 95% CI: 0.37-0.96, p=0.034) and initiating OAD therapy with metformin (OR: 0.30, 95% CI: 0.20-0.46, p<0.001) reduced the risk of insulin use. After 5 years of OAD treatment, 26.1% of people with T2DM started insulin therapy. Age, sex and type of initial OAD affected the probability of switching to insulin in these patients in Colombia. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Barriers that practitioners face when initiating insulin therapy in general practice settings and how they can be overcome

    PubMed Central

    Bin rsheed, Abdulaziz; Chenoweth, Ian

    2017-01-01

    AIM To explore primary care physicians’ perspectives on possible barriers to the use of insulin. METHODS This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eight electronic databases were searched (between January 1, 1994 and August 31, 2014) for relevant studies. A search for grey literature and a review of the references in the retrieved studies were also conducted. Studies that focused on healthcare providers’ perspectives on possible barriers to insulin initiation with type 2 diabetic patients were included, as well as articles suggesting solutions for these barriers. Review articles and studies that only considered patients’ perspectives were excluded. RESULTS A total of 19 studies met the inclusion criteria and were therefore included in this study: 10 of these studies used qualitative methods, 8 used quantitative methods and 1 used mixed methods. Studies included a range of different health care settings. The findings are reported under four broad categories: The perceptions of primary care physicians about the barriers to initiate insulin therapy for type 2 diabetes patients, how primary care physicians assess patients prior to initiating insulin, professional roles and possible solutions to overcome these barriers. The barriers described were many and covered doctor, patient, system and technological aspects. Interventions that focused on doctor training and support, or IT-based decision support were few, and did not result in significant improvement. CONCLUSION Primary care physicians’ known delay in insulin initiation is multifactorial. Published reports of attempts to find solutions for these barriers were limited in number. PMID:28138362

  8. Initiation of insulin therapy in elderly patients taking oral antidiabetes drugs

    PubMed Central

    Pérez, Norma; Moisan, Jocelyne; Sirois, Caroline; Poirier, Paul; Grégoire, Jean-Pierre

    2009-01-01

    Background We sought to estimate the rate of initiation of insulin therapy among elderly patients using oral anti-diabetes drugs and to identify the factors associated with this initiation. Methods We conducted a population-based cohort study involving people aged 66 or more years who were newly dispensed an oral antidiabetes drug. Individuals who had received acarbose or a thiazolidinedione were excluded. The rate of insulin initiation was calculated by use of the Kaplan–Meier method. Factors associated with insulin initiation were identified by multivariable Cox regression analyses. Results In this cohort of 69 674 new users of oral antidiabetes drugs, insulin was initiated at rate of 9.7 cases per 1000 patient-years. Patients who had initially received an insulin secretagogue (rather than metformin), who were prescribed an oral antidiabetes drug by an endocrinologist or an internist, who received higher initial doses of an oral antidiabetes drug, who received oral corticosteroids, used glucometer strips, or were admitted to hospital in the year before initiation of oral antidiabetes therapy, or who received 16 or more medications were more likely than those without these characteristics to have insulin therapy initiated. In contrast, patients who received thiazides or who used up to 12 medications (v. none) were less likely to have insulin therapy initiated. Interpretation Several factors related to drugs and health services are associated with the initiation of insulin therapy in elderly patients receiving oral antidiabetes drugs. It is unclear whether these factors predict secondary failure of oral antidiabetes drugs or instead reflect better management of type 2 diabetes. PMID:19546456

  9. Bridging waitlist delays with Interim Buprenorphine Treatment: Initial feasibility

    PubMed Central

    Sigmon, Stacey C.; Meyer, Andrew; Hruska, Bryce; Ochalek, Taylor; Rose, Gail; Badger, Gary J.; Brooklyn, John R.; Heil, Sarah H.; Higgins, Stephen T.; Moore, Brent A.; Schwartz, Robert P.

    2015-01-01

    Despite the effectiveness of agonist maintenance for opioid dependence, individuals can remain on waitlists for months, during which they are at significant risk for morbidity and mortality. Interim dosing, consisting of daily medication without counseling, can reduce these risks. In this pilot study, we examined the initial feasibility of a novel technology-assisted interim buprenorphine treatment for waitlisted opioid-dependent adults. Following buprenorphine induction during Week 1, participants (n=10) visited the clinic at Weeks 2, 4, 6, 8, 10 and 12 to ingest their medication under staff observation, provide a urine specimen and receive their remaining doses via a computerized Med-O-Wheel Secure device. They also received daily monitoring via an Interactive Voice Response (IVR) platform, as well as random call-backs for urinalysis and medication adherence checks. The primary outcome was percent of participants negative for illicit opioids at each 2-week visit, with secondary outcomes of past-month drug use, adherence and acceptability. Participants achieved high levels of illicit opioid abstinence, with 90% abstinent at the Week 2 and 4 visits and 60% at Week 12. Significant reductions were observed in self-reported past-month illicit opioid use (p<.001), opioid withdrawal (p<.001), opioid craving (p<.001) and ASI Drug composite score (p=.008). Finally, adherence with buprenorphine administration (99%), daily IVR calls (97%) and random call-backs (82%) was high. Interim buprenorphine treatment shows promise for reducing patient and societal risks during delays to conventional treatment. A larger-scale, randomized clinical trial is underway to more rigorously examine the efficacy of this treatment approach. PMID:26256469

  10. Bridging waitlist delays with interim buprenorphine treatment: initial feasibility.

    PubMed

    Sigmon, Stacey C; C Meyer, Andrew; Hruska, Bryce; Ochalek, Taylor; Rose, Gail; Badger, Gary J; Brooklyn, John R; Heil, Sarah H; Higgins, Stephen T; Moore, Brent A; Schwartz, Robert P

    2015-12-01

    Despite the effectiveness of agonist maintenance for opioid dependence, individuals can remain on waitlists for months, during which they are at significant risk for morbidity and mortality. Interim dosing, consisting of daily medication without counseling, can reduce these risks. In this pilot study, we examined the initial feasibility of a novel technology-assisted interim buprenorphine treatment for waitlisted opioid-dependent adults. Following buprenorphine induction during Week 1, participants (n=10) visited the clinic at Weeks 2, 4, 6, 8, 10 and 12 to ingest their medication under staff observation, provide a urine specimen and receive their remaining doses via a computerized Med-O-Wheel Secure device. They also received daily monitoring via an Interactive Voice Response (IVR) platform, as well as random call-backs for urinalysis and medication adherence checks. The primary outcome was percent of participants negative for illicit opioids at each 2-week visit, with secondary outcomes of past-month drug use, adherence and acceptability. Participants achieved high levels of illicit opioid abstinence, with 90% abstinent at the Week 2 and 4 visits and 60% at Week 12. Significant reductions were observed in self-reported past-month illicit opioid use (p<.001), opioid withdrawal (p<.001), opioid craving (p<.001) and ASI Drug composite score (p=.008). Finally, adherence with buprenorphine administration (99%), daily IVR calls (97%) and random call-backs (82%) was high. Interim buprenorphine treatment shows promise for reducing patient and societal risks during delays to conventional treatment. A larger-scale, randomized clinical trial is underway to more rigorously examine the efficacy of this treatment approach.

  11. The hybrid delay task: Can capuchin monkeys (Cebus apella) sustain a delay after an initial choice to do so?

    PubMed Central

    Paglieri, Fabio; Focaroli, Valentina; Bramlett, Jessica; Tierno, Valeria; McIntyre, Joseph M.; Addessi, Elsa; Evans, Theodore A.; Beran, Michael J.

    2013-01-01

    Choosing to wait for a better outcome (delay choice) and sustaining the delay prior to that outcome (delay maintenance) are both prerequisites for successful self control in intertemporal choices. However, most existing experimental methods test these skills in isolation from each other, and no significant correlation has been observed in performance across these tasks. In this study we introduce a new paradigm, the hybrid delay task, which combines an initial delay choice with a subsequent delay maintenance stage. This allows testing how often choosing to wait is paired with the actual ability to do so. We tested 18 capuchin monkeys (Cebus apella) from two laboratories in various conditions, and we found that subjects frequently chose the delayed reward but then failed to wait for it, due to poor delay maintenance. However, performance improved with experience and different behavioral responses for error correction were evident. These findings have far reaching implications: if such a high error rate was observed also in other species (possibly including Homo sapiens), this may indicate that delay choice tasks that make use of salient, prepotent stimuli do not reliably assess generalized self control, insofar as choosing to wait does not entail always being able to do so. PMID:23274585

  12. Impact of patient attitudes and beliefs to insulin therapy upon initiation, and their attitudinal changes after initiation: the DAWN Japan study.

    PubMed

    Odawara, Masato; Ishii, Hitoshi; Tajima, Naoko; Iwamoto, Yasuhiko

    2016-01-01

    Objective As a part of the Diabetes Attitudes, Wishes and Needs (DAWN) Japan study, a multi-center, questionnaire-based survey conducted between 2004 and 2005, this analysis aimed to (1) explore patients' attitudes and beliefs contributing to their decision to start insulin therapy, and (2) assess the changes in their attitudes and beliefs after actual initiation. Methods Insulin-naive patients with type 2 diabetes who were recommended to start insulin therapy (n = 149) were invited to answer a 21-item questionnaire consisting of five clusters assessing their attitudes and beliefs toward insulin therapy. The questionnaire was administered twice: first upon insulin recommendation, and then 1 month after insulin initiation for those who started and 4 months after for those who did not. Results Of 130 patients included in the analysis, 74 patients (56.9%) started insulin therapy. 'Negative image of injections' and 'Positive image toward insulin therapy' were significantly associated with patient decision to start insulin therapy (odds ratios [95% CI]: 0.49 [0.32-0.76] and 2.58 [1.51-4.42], respectively). After insulin initiation, 'Negative image of injections', 'Positive image toward insulin therapy', 'Feelings of guilt regarding diabetes self-management', and 'Negative image toward insulin therapy' decreased significantly (P < 0.001 for all). 'Social/interpersonal effects' did not change after insulin initiation. Conclusions This study demonstrated that patients who started insulin therapy were less likely to have negative images of injections and more likely to have positive images toward insulin therapy. Starting insulin therapy did not deteriorate the patient's overall impression of therapy. The key limitation is the relatively small sample size (n = 130). The results suggest that education about the benefits of insulin therapy may help patients who are not ready to initiate insulin overcome their barrier to early insulin initiation and practical

  13. Adipocyte-Specific Deficiency of NADPH Oxidase 4 Delays the Onset of Insulin Resistance and Attenuates Adipose Tissue Inflammation in Obesity.

    PubMed

    Den Hartigh, Laura J; Omer, Mohamed; Goodspeed, Leela; Wang, Shari; Wietecha, Tomasz; O'Brien, Kevin D; Han, Chang Yeop

    2017-03-01

    Obesity is associated with insulin resistance and adipose tissue inflammation. Reactive oxygen species (ROS) increase in adipose tissue during the development of obesity. We previously showed that in response to excess nutrients like glucose and palmitate, adipocytes generated ROS via NADPH oxidase (NOX) 4, the major adipocyte isoform, instead of using mitochondrial oxidation. However, the role of NOX4-derived ROS in the development of whole body insulin resistance, adipocyte inflammation, and recruitment of macrophages to adipose tissue during the development of obesity is unknown. In this study, control C57BL/6 mice and mice in which NOX4 has been deleted specifically in adipocytes were fed a high-fat, high-sucrose diet. During the development of obesity in control mice, adipocyte NOX4 and pentose phosphate pathway activity were transiently increased. Primary adipocytes differentiated from mice with adipocytes deficient in NOX4 showed resistance against high glucose or palmitate-induced adipocyte inflammation. Mice with adipocytes deficient in NOX4 showed a delayed onset of insulin resistance during the development of obesity, with an initial reduction in adipose tissue inflammation that normalized with prolonged high-fat, high-sucrose feeding. These findings imply that NOX4-derived ROS may play a role in the onset of insulin resistance and adipose tissue inflammation. As such, therapeutics targeting NOX4-mediated ROS production could be effective in preventing obesity-associated conditions, such as insulin resistance. © 2016 American Heart Association, Inc.

  14. 4S-Hydroxylation of Insulin at ProB28 Accelerates Hexamer Dissociation and Delays Fibrillation.

    PubMed

    Lieblich, Seth A; Fang, Katharine Y; Cahn, Jackson K B; Rawson, Jeffrey; LeBon, Jeanne; Ku, H Teresa; Tirrell, David A

    2017-06-28

    Daily injections of insulin provide lifesaving benefits to millions of diabetics. But currently available prandial insulins are suboptimal: The onset of action is delayed by slow dissociation of the insulin hexamer in the subcutaneous space, and insulin forms amyloid fibrils upon storage in solution. Here we show, through the use of noncanonical amino acid mutagenesis, that replacement of the proline residue at position 28 of the insulin B-chain (ProB28) by (4S)-hydroxyproline (Hzp) yields an active form of insulin that dissociates more rapidly, and fibrillates more slowly, than the wild-type protein. Crystal structures of dimeric and hexameric insulin preparations suggest that a hydrogen bond between the hydroxyl group of Hzp and a backbone amide carbonyl positioned across the dimer interface may be responsible for the altered behavior. The effects of hydroxylation are stereospecific; replacement of ProB28 by (4R)-hydroxyproline (Hyp) causes little change in the rates of fibrillation and hexamer disassociation. These results demonstrate a new approach that fuses the concepts of medicinal chemistry and protein design, and paves the way to further engineering of insulin and other therapeutic proteins.

  15. The Initial Assessment of Daily Insulin Dose in Chinese Newly Diagnosed Type 2 Diabetes

    PubMed Central

    Zhou, Huan; Xu, Hua; Chen, Xie; Teng, Xiangyu; Liu, Qianjing; Liu, Wei

    2016-01-01

    Background. It has been well accepted that insulin therapy is the ideal treatment for newly diagnosed diabetic patients. However, there was no study about assessment of the initial insulin dosage in new onset Chinese patients with type 2 diabetes. Research Design and Methods. 65 newly diagnosed patients with type 2 diabetes (39 males/26 females; HbA1c ≥ 11.80 ± 0.22%) were investigated. All patients had random hyperglycaemia (at 21.8 ± 3.9 mmol/L) on the first day of admission and received insulin infusion intravenously (5 U/per hour). When the blood glucose level dropped to around 10 mmol/L, patients were then transferred to continuous subcutaneous insulin infusion (CSII). The reduction of blood glucose levels in response to per unit of insulin (RBG/RI) was recorded. The target glucose level was achieved in about 3 days. The total daily insulin dose (TDD) and basal insulin dose (TBD) were calculated. Results. TDD was 45.97 ± 1.28 units and TBD was 19.00 ± 0.54 units. TBD was about 40% of the total daily insulin requirement. There was a negative correlation between the ratio of RBG/RI and TDD. Conclusions. TDD was correlated with blood glucose reduction in response to intravenous insulin infusion in Chinese new onset patients with type 2 diabetes. PMID:26697503

  16. Insulin

    MedlinePlus

    ... Information by Audience For Women Women's Health Topics Insulin Share Tweet Linkedin Pin it More sharing options ... medicines. You can do it. Back to Top Insulin Safety Tips Never drink insulin. Do not share ...

  17. Clinician Perspectives on Delaying Initiation of Antiretroviral Therapy for Clinically Eligible HIV-Infected Patients

    PubMed Central

    Valverde, Eduardo E.; Raiford, Jerris L.; Weiser, John; White, Becky L.; Skarbinski, Jacek

    2015-01-01

    Objectives: Guidelines for antiretroviral therapy (ART) initiation have evolved, but consistently note that adherence problems should be considered and addressed. Little is known regarding the reasons providers delay ART initiation in clinically eligible patients. Methods: In 2009, we surveyed a probability sample of HIV care providers in 582 outpatient facilities in the United States and Puerto Rico with an open-ended question about nonclinical reasons for delaying ART initiation in otherwise clinically eligible patients. Results: Very few providers (2%) reported never delaying ART. Reasons for delaying ART were concerns about patient adherence (68%), patient acceptance (60%), and structural barriers (33%). Provider and practice characteristics were associated with reasons for delaying ART. Conclusion: Reasons for delaying ART were consistent with clinical guidelines and were both patient level and structural. Providers may benefit from training and access to referrals for ancillary services to enhance their ability to monitor and address these issues with their patients. PMID:25394912

  18. Predictors of Insulin Initiation in Metformin and Sulfonylurea Users in Primary Care Practices

    PubMed Central

    Dippel, Franz-Werner; Rathmann, Wolfgang

    2014-01-01

    The aims were to investigate predictors of insulin initiation in new users of metformin or sulfonylureas in primary care practices, in particular, its association with decreased renal function. Data from 9103 new metformin and 1120 sulfonylurea users with normal baseline glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 from 1072 practices were retrospectively analyzed (Disease Analyzer Germany: 01/2003-06/2012). Cox regression models and propensity score matching was used to adjust for confounders (age, sex, practice characteristics, comorbidity). Insulin treatment was started in 394 (4.3%) metformin and in 162 (14.5%) sulfonylurea users within 6 years (P < .001). Kaplan-Meier curves (propensity score matched patients) showed that the metformin group was at a lower risk of insulin initiation compared to sulfonylurea users throughout the study period. A substantial eGFR decline (category: 15-<30 ml/min/1.73 m2) was significantly associated with a higher likelihood to have insulin initiated (adjusted hazard ratio [HR]: 2.39; 95% CI: 1.09-5.23) in metformin but not in sulfonylurea (HR: 0.45; 95% CI: 0.16-1.30) users. New users of sulfonylurea monotherapy in primary care practices in Germany were about 3-fold more likely to start insulin therapy than those with metformin. Kidney function decline was associated with earlier insulin initiation in metformin but not in sulfonylurea users. PMID:24876433

  19. Myocardial delayed-enhancement CT: initial experience in children and young adults.

    PubMed

    Goo, Hyun Woo

    2017-05-23

    Clinical utility of myocardial delayed enhancement CT has not been reported in children and young adults. To describe initial experience of myocardial delayed enhancement CT regarding image quality, radiation dose and identification of myocardial lesions in children and young adults. Between August 2013 and November 2016, 29 consecutive children and young adults (median age 16 months) with suspected coronary artery or myocardial abnormality underwent arterial- and delayed-phase cardiac CT at our institution. We measured CT densities in normal myocardium, left ventricular cavity, and arterial and delayed hypo-enhancing and delayed hyperenhancing myocardial lesions. We then compared the extent of delayed hyperenhancing lesions with delayed-enhancement MRI or thallium single-photon emission CT. Normal myocardium and left ventricular cavity showed significantly higher CT numbers on arterial-phase CT than on delayed-phase CT (t-test, P<0.0001). Contrast-to-noise ratios of the arterial and delayed hypo-enhancing and delayed hyperenhancing lesions on CT were 26.7, 17.6 and 18.7, respectively. Delayed-phase CT findings were equivalent to those of delayed-enhancement MRI in all cases (7/7) and to those of thallium single-photon emission CT in 70% (7/10). Myocardial delayed-enhancement CT can be added to evaluate myocardial lesions in select children and young adults with suspected coronary artery or myocardial abnormality.

  20. Effects on a Later Recall by Delaying Initial Recall

    ERIC Educational Resources Information Center

    Modigliani, Vito

    1976-01-01

    Attempts to define the relationships between four measures of recall in a two-recall task, namely (a) initial short-term recall (STR), (b) unconditional final free recall (FFR), (c) final free recall conditionalized on an initial successful recall (FFR/STR), and (d) final free recall conditionalized on an unsuccessful recall (FFR/STR). (Author/RK)

  1. Clinical Evidence for the Earlier Initiation of Insulin Therapy in Type 2 Diabetes

    PubMed Central

    2013-01-01

    Abstract The natural history of type 2 diabetes mellitus (T2DM) is a relentless progression of β-cell failure and dysregulation of β-cell function with increasing metabolic derangement. Insulin remains the only glucose-lowering therapy that is efficacious throughout this continuum. However, the timing of introduction and the choice of insulin therapy remain contentious because of the heterogeneity of T2DM and the well-recognized behavioral and therapeutic challenges associated with this mode of therapy. Nevertheless, the early initiation of basal insulin has been shown to improve glycemic control and affect long-term outcomes in people with T2DM and is a treatment strategy supported by international guidelines as part of an individualized approach to chronic disease management. The rationale for early initiation of insulin is based on evidence demonstrating multifaceted benefits, including overcoming the glucotoxic effects of hyperglycemia, thereby facilitating “β-cell rest,” and preserving β-cell mass and function, while also improving insulin sensitivity. Independent of its effects on glycemic control, insulin possesses anti-inflammatory and antioxidant properties that may help protect against endothelial dysfunction and damage resulting in vascular disease. Insulin therapy and the achievement of good glycemic control earlier in T2DM provide long-term protection to end organs via “metabolic memory” regardless of subsequent treatments and degree of glycemic control. This is evidenced from long-term observations continuing from trials such as the United Kingdom Prospective Diabetes Study. As such, early initiation of insulin therapy may not only help to avoid the effects of prolonged glycemic burden, but may also positively alter the course of disease progression. PMID:23786228

  2. Treatment delay among tuberculosis patients in Tanzania: Data from the FIDELIS Initiative

    PubMed Central

    2011-01-01

    Background Several FIDELIS projects (Fund for Innovative DOTS Expansion through Local Initiatives to Stop TB) in Tanzania were conducted by the National Tuberculosis and Leprosy Programme (NTLP) during the years 2004-2008 to strengthen diagnostic and treatment services. These projects collected information on treatment delay and some of it was available for research purposes. With this database our objective was to assess the duration and determinants of treatment delay among new smear positive pulmonary tuberculosis (TB) patients in FIDELIS projects, and to compare delay according to provider visited prior to diagnosis. Methods Treatment delay among new smear positive TB patients was recorded for each patient at treatment initiation and this information was available and fairly complete in 6 out of 57 districts with FIDELIS projects enrolling patients between 2004 and 2007; other districts had discarded their forms at the time of analysis. It was analysed as a cross sectional study. Results We included 1161 cases, 10% of all patients recruited in the FIDELIS projects in Tanzania. Median delay was 12 weeks. The median duration of cough, weight loss and haemoptysis was 12, 8 and 3 weeks, respectively. Compared to Hai district Handeni had patients with longer delays and Mbozi had patients with shorter delays. Urban and rural patients reported similar delays. Patients aged 15-24 years and patients of 65 years or older had longer delays. Patients reporting contact with traditional healers before diagnosis had a median delay of 15 weeks compared to 12 weeks among those who did not. Patients with dyspnoea and with diarrhoea had longer delays. Conclusion In this patient sample in Tanzania half of the new smear positive pulmonary tuberculosis patients had a treatment delay longer than 12 weeks. Delay was similar in men and women and among urban and rural patients, but longer in the young and older age groups. Patients using traditional healers had a 25% longer median delay

  3. Investigation of stability in a two-delay model of the ultradian oscillations in glucose-insulin regulation

    NASA Astrophysics Data System (ADS)

    Huard, B.; Easton, J. F.; Angelova, M.

    2015-09-01

    In this paper, a two-delay model for the ultradian oscillatory behaviour of the glucose-insulin regulation system is studied. Hill functions are introduced to model nonlinear physiological interactions within this system and ranges on parameters reproducing biological oscillations are determined on the basis of analytical and numerical considerations. Local and global stability are investigated and delay-dependent conditions are obtained through the construction of Lyapunov-Krasovskii functionals. The effect of Hill parameters on these conditions, as well as the boundary of the stability region in the delay domain, are established for the first time. Numerical simulations demonstrate that the model with Hill functions represents well the oscillatory behaviour of the system with the advantage of incorporating new meaningful parameters. The influence of the time delays on the period of oscillations and the sensitivity of the latter to model parameters, in particular glucose infusion, are investigated. The model can contribute to the better understanding and treatment of diabetes.

  4. The evaluation of clinical and cost outcomes associated with earlier initiation of insulin in patients with type 2 diabetes mellitus.

    PubMed

    Smolen, Harry J; Murphy, Daniel R; Gahn, James C; Yu, Xueting; Curtis, Bradley H

    2014-09-01

    The treatment for patients with type 2 diabetes mellitus (T2DM) follows a stepwise progression. As a treatment loses its effectiveness, it is typically replaced with a more complex and frequently more costly treatment. Eventually this progression leads to the use of basal insulin typically with concomitant treatments (e.g., metformin, a GLP-1 RA [glucagon-like peptide-1 receptor agonist], a TZD [thiazolidinedione] or a DPP-4i [dipeptidyl peptidase 4 inhibitor]) and, ultimately, to basal-bolus insulin in some forms. As the cost of oral antidiabetics (OADs) and noninsulin injectables have approached, and in some cases exceeded, the cost of insulin, we reexamined the placement of insulin in T2DM treatment progression. Our hypothesis was that earlier use of insulin produces clinical and cost benefits due to its superior efficacy and treatment scalability at an acceptable cost when considered over a 5-year period. To (a) estimate clinical and payer cost outcomes of initiating insulin treatment for patients with T2DM earlier in their treatment progression and (b) estimate clinical and payer cost outcomes resulting from delays in escalating treatment for T2DM when indicated by patient hemoglobin A1c levels. We developed a Monte Carlo microsimulation model to estimate patients reaching target A1c, diabetes-related complications, mortality, and associated costs under various treatment strategies for newly diagnosed patients with T2DM. Treatment efficacies were modeled from results of randomized clinical trials, including the time and rate of A1c drift. A typical treatment progression was selected based on the American Diabetes Association and the European Association for the Study of Diabetes guidelines as the standard of care (SOC). Two treatment approaches were evaluated: two-stage insulin (basal plus antidiabetics followed by biphasic plus metformin) and single-stage insulin (biphasic plus metformin). For each approach, we analyzed multiple strategies. For each analysis

  5. Delayed luminescence of luminol initiated by a membrane-bound peroxidase.

    PubMed

    Ikariyama, Y; Suzuki, S; Aizawa, M

    1981-09-01

    The luminescense of the luminol-H2O2 system was initiated by either free or membrane-bound horseradish peroxideae (HRP). The instantaneous luminescene decayed rapidly and was followed by the delayed luminescence in the presence of excess luminol. The delayed luminescence was characterized by a chain reaction, in which luminescence intensity increased exponentially. Membrane-bound HRP demonstrated that the delayed luminescence took place even in the absence of HRP if the instantaneous luminescence was initiated by HRP. A mechanism for the nonenzymatic luminescence is proposed and discussed.

  6. Electronic delay ignition module for single bridgewire Apollo standard initiator

    NASA Technical Reports Server (NTRS)

    Ward, R. D.

    1975-01-01

    An engineering model and a qualification model of the EDIM were constructed and tested to Scout flight qualification criteria. The qualification model incorporated design improvements resulting from the engineering model tests. Compatibility with single bridgewire Apollo standard initiator (SBASI) was proven by test firing forty-five (45) SBASI's with worst case voltage and temperature conditions. The EDIM was successfully qualified for Scout flight application with no failures during testing of the qualification unit. Included is a method of implementing the EDIM into Scout vehicle hardware and the ground support equipment necessary to check out the system.

  7. Treatment persistence after initiating basal insulin in type 2 diabetes patients: A primary care database analysis.

    PubMed

    Pscherer, Stefan; Chou, Engels; Dippel, Franz-Werner; Rathmann, Wolfgang; Kostev, Karel

    2015-10-01

    To compare persistence and its predictors in type 2 diabetes patients in primary care, initiating either basal supported oral therapy (BOT) or intensified conventional therapy (ICT) with glargine, detemir, or NPH insulin. In the BOT cohort, 1398 glargine (mean age: 68 years), 292 detemir (66 years), and 874 NPH (65 years) users from 918 practices were retrospectively analyzed (Disease Analyzer, Germany: 2008-2012). The ICT group incorporated 866 glargine (64 years), 512 detemir (60 years), and 1794 NPH (64 years) new users. Persistence was defined as proportion of patients remaining on the initial basal insulin (glargine, detemir and NPH insulin) over 2 years. Persistence was evaluated by Kaplan-Meier curves (log-rank tests) and Cox regression adjusting for age, sex, diabetes duration, antidiabetic co-therapy, comorbidities, specialist care, and private health insurance. In BOT, two-year persistence was 65%, 53%, and 59% in glargine, detemir, and NPH users, respectively (p<0.001). In ICT, persistence was higher without differences between groups: 84%, 85%, 86% in glargine, detemir, and NPH, respectively (p=0.536). In BOT, detemir and NPH users were more likely to discontinue basal insulin compared with glargine (detemir vs. glargine: adjusted Hazard Ratio; 95% CI: 1.56; 1.31-1.87; NPH vs. glargine: 1.22; 1.07-1.38). Heart failure (1.39; 1.16-1.67) was another predictor of non-persistence, whereas higher age (per year: 0.99; 0.98-0.99), metformin (0.61; 0.54-0.69), and sulfonylurea co-medication (0.86; 0.77-0.97) were associated with lower discontinuation. In BOT, treatment persistence among type 2 diabetes patients initiating basal insulin is influenced by type of insulin, antidiabetic co-medication, and patient characteristics. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  8. Insulin resistance and delayed clearance of peptide hormones in cirrhotic rat liver

    SciTech Connect

    Shankar, T.P.; Drake, S.; Solomon, S.S.

    1987-06-01

    Clearance of porcine insulin, glucagon, and human growth hormone was measured in intact perfused cirrhotic and normal rat livers. Binding and degradation of /sup 125/I-insulin by hepatocytes isolated from cirrhotic and normal livers were also studied. The half-lives (t/sub 1/2/) of immunoreactive insulin and glucagon were 14.0 +/- 3.1 and 9.6 +/- 2.1 min in normal livers and 26.0 +/- 6.1 and 25.0 +/- 7.1 min in cirrhotic livers. Insulin binding and degradation by hepatocytes from control and cirrhotic livers showed no significant differences. Intraportal insulin infusion in perfusion studies suppressed glucagon-stimulated increases in glucose output from control livers but failed to suppress glucose production by cirrhotic livers, suggesting the presence of hepatic insulin resistance in cirrhosis. Impaired clearance of insulin and glucagon by the intact cirrhotic liver and normal binding and degradation of insulin by isolated hepatocytes suggest that factors such as intrahepatic fibrosis and shunting and postbinding defects may be responsible for the impaired hormone clearance and hepatic insulin resistance.

  9. Optimizing insulin initiation in primary care: the Diabetes CoStars patient support program

    PubMed Central

    Lutzko, Olga K; Schifferle, Helen; Ariola, Marita; Rich, Antonia; Kon, Khen Meng

    2016-01-01

    Purpose The purpose of this study was to evaluate the optimization of fasting blood glucose (FBG) levels in patients with type 2 diabetes mellitus newly initiated on insulin glargine who were enrolled in the Australian Diabetes CoStars Patient Support Program (PSP). Patients and methods A retrospective analysis of data from 514 patients with type 2 diabetes mellitus who completed the 12-week Diabetes CoStars PSP was performed. All patients were initiated on insulin glargine in primary care and enrolled by their general practitioner, who selected a predefined titration plan and support from a local Credentialled Diabetes Educator. The data collected included initial and final insulin dose, self-reported FBG, and glycated hemoglobin (A1c) levels. Results The insulin dose increased in 81% of patients. Mean FBG was reduced from 208.8 mg/dL (11.6 mmol/L) to 136.8 mg/dL (7.6 mmol/L) after 12 weeks. Initial and final A1c values were available for 99 patients; mean A1c was reduced from 9.5% (80 mmol/mol) to 8.1% (65 mmol/mol). The reductions in mean FBG and A1c were similar irrespective of titration plan. Overall, 27.2% of patients achieved FBG levels within the titration plan target range of 72–108 mg/dL (4–6 mmol/L) and an additional 43.4% of patients achieved FBG within the range recommended by current Australian guidelines (110–144 mg/dL [6.1–8.0 mmol/L]). Overall, 23.3% of patients achieved the A1c target of ≤7%. Conclusion These data demonstrate that the majority of patients enrolled in the Diabetes CoStars PSP achieved acceptable FBG levels 12 weeks after starting insulin therapy irrespective of titration plan. PMID:27799841

  10. The Haiti Breast Cancer Initiative: Initial Findings and Analysis of Barriers-to-Care Delaying Patient Presentation

    PubMed Central

    Sharma, Ketan; Costas, Ainhoa; Damuse, Ruth; Hamiltong-Pierre, Jean; Pyda, Jordan; Ong, Cecilia T.; Shulman, Lawrence N.; Meara, John G.

    2013-01-01

    Background. In Haiti, breast cancer patients present at such advanced stages that even modern therapies offer modest survival benefit. Identifying the personal, sociocultural, and economic barriers-to-care delaying patient presentation is crucial to controlling disease. Methods. Patients presenting to the Hôpital Bon Sauveur in Cange were prospectively accrued. Delay was defined as 12 weeks or longer from initial sign/symptom discovery to presentation, as durations greater than this cutoff correlate with reduced survival. A matched case-control analysis with multivariate logistic regression was used to identify factors predicting delay. Results. Of N = 123 patients accrued, 90 (73%) reported symptom-presentation duration and formed the basis of this study: 52 patients presented within 12 weeks of symptoms, while 38 patients waited longer than 12 weeks. On logistic regression, lower education status (OR = 5.6, P = 0.03), failure to initially recognize mass as important (OR = 13.0, P < 0.01), and fear of treatment cost (OR = 8.3, P = 0.03) were shown to independently predict delayed patient presentation. Conclusion. To reduce stage at presentation, future interventions must educate patients on the recognition of initial breast cancer signs and symptoms and address cost concerns by providing care free of charge and/or advertising that existing care is already free. PMID:23840209

  11. A qualitative study on healthcare professionals’ perceived barriers to insulin initiation in a multi-ethnic population

    PubMed Central

    2012-01-01

    Background Nationwide surveys have shown that the prevalence of diabetes rates in Malaysia have almost doubled in the past ten years; yet diabetes control remains poor and insulin therapy is underutilized. This study aimed to explore healthcare professionals’ views on barriers to starting insulin therapy in people with type 2 diabetes. Methods Healthcare professionals consisting of general practitioners (n = 11), family medicine specialists (n = 10), medical officers (n = 8), government policy makers (n = 4), diabetes educators (n = 3) and endocrinologists (n = 2) were interviewed. A semi-structured topic guide was used to guide the interviews by trained facilitators. The interviews were transcribed verbatim and analysed using a thematic analysis approach. Results Insulin initiation was found to be affected by patient, healthcare professional and system factors. Patients’ barriers include culture-specific barriers such as the religious purity of insulin, preferred use of complementary medication and perceived lethality of insulin therapy. Healthcare professionals’ barriers include negative attitudes towards insulin therapy and the ‘legacy effect’ of old insulin guidelines; whilst system barriers highlight the lack of resources, language and communication challenges. Conclusions Tackling the issue of insulin initiation should not only happen during clinical consultations. It requires health education to emphasise the progressive nature of diabetes and the eventuality of insulin therapy at early stage of the illness. Healthcare professionals should be trained how to initiate insulin and communicate effectively with patients from various cultural and religious backgrounds. PMID:22469132

  12. Low-melting elemental metal or fusible alloy encapsulated polymerization initiator for delayed initiation

    DOEpatents

    Hermes, Robert E.

    2015-12-22

    An encapsulated composition for polymerization includes an initiator composition for initiating a polymerization reaction, and a capsule prepared from an elemental metal or fusible alloy having a melting temperature from about 20.degree. C. to about 200.degree. C. A fluid for polymerization includes the encapsulated composition and a monomer. When the capsule melts or breaks open, the initiator is released.

  13. Low-melting elemental metal or fusible alloy encapsulated polymerization initiator for delayed initiation

    DOEpatents

    Hermes, Robert E.

    2017-08-15

    An encapsulated composition for polymerization includes an initiator composition for initiating a polymerization reaction, and a capsule prepared from an elemental metal or fusible alloy having a melting temperature from about 20.degree. C. to about 200.degree. C. A fluid for polymerization includes the encapsulated composition and a monomer. When the capsule melts or breaks open, the initiator is released.

  14. [INITIATING AND INTENSIFYING INSULIN THERAPY IN GENERAL PRACTICE: INSUSTAR, AN OBSERVATIONAL BELGIAN PROSPECTIVE STUDY IN TYPE 2 DIABETES].

    PubMed

    Scheen, A J; Mathieu, C; Nobels, F

    2015-09-01

    Initiating or intensifying insulin therapy is often considered as a challenge in general practice. The observational prospective Belgian study InsuStar was performed in 2011-2013 among 150 representative general practitioners, who were invited to initiate or intensify insulin therapy when necessary in 523 patients with type 2 diabetes (mean age: 65.5 years; mean HbAk: 8.8%). The initiation of insulin therapy (glargine in > 50%) was justified by insufficient glycaemic control (96%) and its intensification (replacement of insulin NPH or premixed insulins by insulin glargine, eventually with the addition of a short-acting insulin analogue) aimed at improving glucose control (58%), avoiding hypoglycaemia (17%) or both (17%). After a follow up of 6:1 months, HbAlc level decreased from 8.79% to 7.52% (-1.27%; 95% confidence interval: -1.43, -1.11; p<0.001). Overall 27.6% of patients reached an HbAl, < 7% versus 5.9% at inclusion (p<0.001), with rather few hypoglycaemia and a high physi- cian confidence level regarding insulin therapy. These results should encourage general practitioners to initiate insulin therapy at an earlier stage and to intensify it when necessary in patients with insufficiently controlled type 2 diabetes.

  15. Clinical and economic outcomes among patients with diabetes mellitus initiating insulin glargine pen versus vial.

    PubMed

    Grabner, Michael; Chu, James; Raparla, Swetha; Quimbo, Ralph; Zhou, Steve; Conoshenti, Joseph

    2013-05-01

    Insulin pens may help patients reach glycated hemoglobin (HbA1c) target levels, but a substantial proportion of patients continue to use insulin vials/syringes. The objective of the current study was to evaluate real-world clinical and economic outcomes of patients with type 2 diabetes mellitus (T2DM) initiating insulin glargine via pen delivery (pen) or vial/syringe (vial) within a large managed-care population in the United States. This retrospective administrative claims study used data on adult, insulin-naïve patients with T2DM treated with ≥ 1 oral antidiabetic or glucagon-like peptide-1 receptor agonist at baseline. The index date was the earliest pen or vial prescription date. Propensity score matching (1:1) of patients in the pen and vial cohorts was used when comparing 1-year outcomes, including treatment persistence and adherence, HbA1c levels, hypoglycemia rates, and all-cause and diabetes-related health care costs (computed as paid amounts on claims). Patients in the matched cohorts (n = 733 per cohort) were well balanced with regard to demographics (mean age 52 years; 43% women), clinical measures (mean HbA1c level, 9.4%; mean Quan-Modified Charlson Comorbidity Index score, 0.9), and health care utilization at baseline. Following initiation of insulin glargine, pen patients were more persistent (60.6% vs 50.1%; P < 0.001) and adherent (medication possession ratio, 0.73 vs 0.57; P < 0.001), with lower HbA1c levels during follow-up (mean adjusted change, -1.05 vs -0.73; P < 0.001), compared with vial patients. Hypoglycemic events occurred at similar rates across pen and vial cohorts (3.8% vs 5.2%, respectively; P = 0.21). Study drug costs were higher among pen users ($1164 vs $762, respectively; P < 0.001), but this did not translate into higher total all-cause or diabetes-related costs. For patients with diabetes newly initiating insulin glargine, using an insulin pen device was associated with increased therapy persistence and adherence, and lower

  16. Gaze-Assisted User Intention Prediction for Initial Delay Reduction in Web Video Access.

    PubMed

    Lee, Seungyup; Yoo, Juwan; Han, Gunhee

    2015-06-19

    Despite the remarkable improvement of hardware and network technology, the inevitable delay from a user's command action to a system response is still one of the most crucial influence factors in user experiences (UXs). Especially for a web video service, an initial delay from click action to video start has significant influences on the quality of experience (QoE). The initial delay of a system can be minimized by preparing execution based on predicted user's intention prior to actual command action. The introduction of the sequential and concurrent flow of resources in human cognition and behavior can significantly improve the accuracy and preparation time for intention prediction. This paper introduces a threaded interaction model and applies it to user intention prediction for initial delay reduction in web video access. The proposed technique consists of a candidate selection module, a decision module and a preparation module that prefetches and preloads the web video data before a user's click action. The candidate selection module selects candidates in the web page using proximity calculation around a cursor. Meanwhile, the decision module computes the possibility of actual click action based on the cursor-gaze relationship. The preparation activates the prefetching for the selected candidates when the click possibility exceeds a certain limit in the decision module. Experimental results show a 92% hit-ratio, 0.5-s initial delay on average and 1.5-s worst initial delay, which is much less than a user's tolerable limit in web video access, demonstrating significant improvement of accuracy and advance time in intention prediction by introducing the proposed threaded interaction model.

  17. Gaze-Assisted User Intention Prediction for Initial Delay Reduction in Web Video Access

    PubMed Central

    Lee, Seungyup; Yoo, Juwan; Han, Gunhee

    2015-01-01

    Despite the remarkable improvement of hardware and network technology, the inevitable delay from a user's command action to a system response is still one of the most crucial influence factors in user experiences (UXs). Especially for a web video service, an initial delay from click action to video start has significant influences on the quality of experience (QoE). The initial delay of a system can be minimized by preparing execution based on predicted user's intention prior to actual command action. The introduction of the sequential and concurrent flow of resources in human cognition and behavior can significantly improve the accuracy and preparation time for intention prediction. This paper introduces a threaded interaction model and applies it to user intention prediction for initial delay reduction in web video access. The proposed technique consists of a candidate selection module, a decision module and a preparation module that prefetches and preloads the web video data before a user's click action. The candidate selection module selects candidates in the web page using proximity calculation around a cursor. Meanwhile, the decision module computes the possibility of actual click action based on the cursor-gaze relationship. The preparation activates the prefetching for the selected candidates when the click possibility exceeds a certain limit in the decision module. Experimental results show a 92% hit-ratio, 0.5-s initial delay on average and 1.5-s worst initial delay, which is much less than a user's tolerable limit in web video access, demonstrating significant improvement of accuracy and advance time in intention prediction by introducing the proposed threaded interaction model. PMID:26102494

  18. 15 CFR 4.10 - Appeals from initial determinations or untimely delays.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Appeals from initial determinations or untimely delays. 4.10 Section 4.10 Commerce and Foreign Trade Office of the Secretary of Commerce... under this subpart (as described in § 4.7(b)), the requester may file a written appeal or an...

  19. Universal Intervention Effects on Substance Use among Young Adults Mediated by Delayed Adolescent Substance Initiation

    ERIC Educational Resources Information Center

    Spoth, Richard; Trudeau, Linda; Guyll, Max; Shin, Chungyeol; Redmond, Cleve

    2009-01-01

    In this article, the authors examine whether delayed substance initiation during adolescence, achieved through universal family-focused interventions conducted in middle school, can reduce problematic substance use during young adulthood. Sixth-grade students enrolled in 33 rural midwestern schools and their families were randomly assigned to 3…

  20. Initiation of insulin glargine in children and adolescents with type 1 diabetes.

    PubMed

    Tan, Chin Yao; Wilson, Darrell M; Buckingham, Bruce

    2004-06-01

    Glargine (Lantus) is a recently approved, long-acting insulin analog that is increasingly being used in children with diabetes. The aim of this retrospective chart review was to summarize our experience in starting glargine in children and adolescents with diabetes. SUBJECTS AND STUDY METHODS: We reviewed the medical records of 71 children with type 1 diabetes (29 boys and 42 girls) who initiated glargine therapy to improve glycemic control between 1 June 2001 and 30 June 2002. Data were collected for 6 months before and 6 months after adding glargine. Subjects' mean age [+/-standard deviation (SD)] at diagnosis of diabetes was 7.5 +/- 4.1 yr. Mean age at initiation of glargine therapy was 11.5 +/- 4.9 yr. The total daily long-acting insulin dose decreased by about 20% after initiating glargine therapy. There were no significant differences in hemoglobin A1c (HbA1c) and blood glucose control prior to and after initiating glargine therapy (HbA1c at baseline 8.9 +/- 1.6% and HbA1c after 6 months of glargine therapy was 8.9 +/- 1.5%). Overall, blood glucose concentrations did not differ significantly throughout the study. Patients who switched to glargine because of nocturnal hypoglycemia had a 65% decrease in nocturnal blood glucose reading less than 50 mg/dL. There were three seizures in the first week after initiating glargine therapy. This retrospective study suggests that glargine is at least as effective as other long-acting insulins but that care must be taken during the conversion process to avoid hypoglycemia.

  1. Selective frame dropping based on hypothetical reference decoder buffer model for initial buffering delay reduction

    NASA Astrophysics Data System (ADS)

    Deshpande, Sachin

    2008-02-01

    We propose a method for selective frame dropping based on hypothetical reference decoder buffer model for initial buffering delay reduction. The client side buffering consists of two logical buffers: a de-jitter buffer and a pre-decoder buffer. To playback an encoded bit-stream without underflow the client must do a minimum initial buffering. This minimum initial buffering is a property of the bit-stream. The minimum initial buffering relates to the pre-decoder buffer. In addition the client can do additional initial buffering to handle network jitter and other bandwidth variations. Our proposed approach relates to reducing the minimum initial buffering delay for an already encoded bit-stream. We propose a method for selectively dropping frames to reduce the amount of initial buffering the client needs to do to avoid underflow during the streaming. Our proposed method is especially applicable to pre-stored content. The method is also particularly useful for variable bit-rate (VBR) encoded media. The method can be used by a streaming server. Alternatively the method can be implemented by a trans-rater/ transcoder. In a preferred embodiment our method can be applied in advance on a pre-stored bit-stream to decide which frames to drop to reduce the required minimum initial buffering.

  2. Sulfate Anion Delays the Self-Assembly of Human Insulin by Modifying the Aggregation Pathway

    PubMed Central

    Owczarz, Marta; Arosio, Paolo

    2014-01-01

    The understanding of the molecular mechanisms underlying protein self-assembly and of their dependence on solvent composition has implications in a large number of biological and biotechnological systems. In this work, we characterize the aggregation process of human insulin at acidic pH in the presence of sulfate ions using a combination of Thioflavin T fluorescence, dynamic light scattering, size exclusion chromatography, Fourier transform infrared spectroscopy, and transmission electron microscopy. It is found that the increase of sulfate concentration inhibits the conversion of insulin molecules into aggregates by modifying the aggregation pathway. At low sulfate concentrations (0–5 mM) insulin forms amyloid fibrils following the nucleated polymerization mechanism commonly observed under acidic conditions in the presence of monovalent anions. When the sulfate concentration is increased above 5 mM, the sulfate anion induces the salting-out of ∼18–20% of insulin molecules into reversible amorphous aggregates, which retain a large content of α-helix structures. During time these aggregates undergo structure rearrangements into β-sheet structures, which are able to recruit monomers and bind to the Thioflavin T dye. The alternative aggregation mechanism observed at large sulfate concentrations is characterized by a larger activation energy and leads to more polymorphic structures with respect to the self-assembly in the presence of chloride ions. The system shown in this work represents a case where amorphous aggregates on pathway to the formation of structures with amyloid features could be detected and analyzed. PMID:24988354

  3. Insulin

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The manipulation of organic materials--cells, tissues, and even living organisms--offers many exciting possibilities for the future from organic computers to improved aquaculture. Commercial researchers are using the microgravity environment to produce large near perfect protein crystals Research on insulin has yielded crystals that far surpass the quality of insulin crystals grown on the ground. Using these crystals industry partners are working to develop new and improved treatments for diabetes. Other researchers are exploring the possibility of producing antibiotics using plant cell cultures which could lead to both orbital production and the improvement of ground-based antibiotic production.

  4. Acute dietary fat intake initiates alterations in energy metabolism and insulin resistance

    PubMed Central

    Hernández, Elisa Álvarez; Kahl, Sabine; Seelig, Anett; Begovatz, Paul; Kupriyanova, Yuliya; Nowotny, Bettina; Nowotny, Peter; Herder, Christian; Carvalho, Filipa; Neschen, Susanne; Jones, John G.; de Angelis, Martin Hrabě

    2017-01-01

    BACKGROUND. Dietary intake of saturated fat is a likely contributor to nonalcoholic fatty liver disease (NAFLD) and insulin resistance, but the mechanisms that initiate these abnormalities in humans remain unclear. We examined the effects of a single oral saturated fat load on insulin sensitivity, hepatic glucose metabolism, and lipid metabolism in humans. Similarly, initiating mechanisms were examined after an equivalent challenge in mice. METHODS. Fourteen lean, healthy individuals randomly received either palm oil (PO) or vehicle (VCL). Hepatic metabolism was analyzed using in vivo 13C/31P/1H and ex vivo 2H magnetic resonance spectroscopy before and during hyperinsulinemic-euglycemic clamps with isotope dilution. Mice underwent identical clamp procedures and hepatic transcriptome analyses. RESULTS. PO administration decreased whole-body, hepatic, and adipose tissue insulin sensitivity by 25%, 15%, and 34%, respectively. Hepatic triglyceride and ATP content rose by 35% and 16%, respectively. Hepatic gluconeogenesis increased by 70%, and net glycogenolysis declined by 20%. Mouse transcriptomics revealed that PO differentially regulates predicted upstream regulators and pathways, including LPS, members of the TLR and PPAR families, NF-κB, and TNF-related weak inducer of apoptosis (TWEAK). CONCLUSION. Saturated fat ingestion rapidly increases hepatic lipid storage, energy metabolism, and insulin resistance. This is accompanied by regulation of hepatic gene expression and signaling that may contribute to development of NAFLD. REGISTRATION. ClinicalTrials.gov NCT01736202. FUNDING. Germany: Ministry of Innovation, Science, and Research North Rhine–Westfalia, German Federal Ministry of Health, Federal Ministry of Education and Research, German Center for Diabetes Research, German Research Foundation, and German Diabetes Association. Portugal: Portuguese Foundation for Science and Technology, FEDER – European Regional Development Fund, Portuguese Foundation for

  5. Extremely rapid increase in fatty acid transport and intramyocellular lipid accumulation but markedly delayed insulin resistance after high fat feeding in rats.

    PubMed

    Bonen, Arend; Jain, Swati S; Snook, Laelie A; Han, Xiao-Xia; Yoshida, Yuko; Buddo, Kathryn H; Lally, James S; Pask, Elizabeth D; Paglialunga, Sabina; Beaudoin, Marie-Soleil; Glatz, Jan F C; Luiken, Joost J F P; Harasim, Ewa; Wright, David C; Chabowski, Adrian; Holloway, Graham P

    2015-10-01

    transport. The 16-19 day delay in the onset of insulin resistance suggests that additional mechanisms besides intramyocellular lipids contribute to this pathology.

  6. Apoptosis induced by an anti-epidermal growth factor receptor monoclonal antibody in a human colorectal carcinoma cell line and its delay by insulin.

    PubMed Central

    Wu, X; Fan, Z; Masui, H; Rosen, N; Mendelsohn, J

    1995-01-01

    Both EGF and insulin, or IGF, stimulate the growth of many cell types by activating receptors that contain tyrosine kinase activities. A monoclonal antibody (mAb 225) against the EGF receptor produced in this laboratory has been shown to competitively inhibit EGF binding and block activation of receptor tyrosine kinase. Here we report that a human colorectal carcinoma cell line, DiFi, which expresses high levels of EGF receptors on plasma membranes, can be induced to undergo G1 cell cycle arrest and programmed cell death (apoptosis) when cultured with mAb 225 at concentrations that saturate EGF receptors. Addition of IGF-1 or high concentrations of insulin can delay apoptosis induced by mAb 225, while the G1 arrest cannot be reversed by either IGF-1 or insulin. Insulin/IGF-1 cannot activate EGF receptor tyrosine kinase that has been inhibited by mAb 225. Moreover, an mAb against the IGF-1 receptor, which has little direct effect on DiFi cell growth, can block the capacity of insulin/IGF-1 to delay apoptosis induced by mAb 225, suggesting that the insulin/IGF-1-mediated delay of apoptosis is acting through the IGF-1 receptor. In contrast, insulin/IGF-1 cannot delay the apoptosis caused by the DNA damaging agent, cisplatin. The results indicate that EGF receptor activation is required both for cell cycle progression and for prevention of apoptosis in DiFi cells, and that a signal transduction pathway shared by receptors for insulin/IGF-1 and EGF may be involved in regulating apoptosis triggered by blockade of the EGF receptor. Images PMID:7706497

  7. Engaging GPs in insulin therapy initiation: a qualitative study evaluating a support program in the Belgian context

    PubMed Central

    2014-01-01

    Background A program supporting the initiation of insulin therapy in primary care was introduced in Belgium, as part of a larger quality improvement project on diabetes care. This paper reports on a study exploring factors influencing the engagement of general practitioners (GPs) in insulin therapy initiation (research question 1) and exploring factors relevant for future program development (research question 2). Methods We have used semi-structured interviews to answer the first research question: two focus group interviews with GPs who had at least one patient in the insulin initiation program and 20 one-to-one interviews with GPs who were not regular users of the overall support program in the region. To explore factors relevant for future program development, the data from the GPs were triangulated with data obtained from individual interviews with patients (n = 10), the diabetes nurse educator (DNE) and the specialist involved in the program, and data extracted from meeting reports evaluating the insulin initiation support program. Results We found differences between GPs engaged and those not engaged in insulin initiation in attitude, subjective norm and perceived behavioural control regarding insulin initiation. In general the support program was evaluated in a positive way by users of the program. Some aspects need further consideration: job boundaries between the DNE and GPs, job boundaries between GPs and specialists, protocol adherence and limited case load. Conclusion The study shows that the transition of insulin initiation from secondary care to the primary care setting is a challenge. Although a support program addressing known barriers to insulin initiation was provided, a substantial number of GPs were reluctant to engage in this aspect of care. Important issues for future program development are: an interdisciplinary approach to job clarification, a dynamic approach to the integration of expertise in primary care and feedback on protocol

  8. Appropriateness and delay to initiate therapy in ventilator-associated pneumonia.

    PubMed

    Luna, C M; Aruj, P; Niederman, M S; Garzón, J; Violi, D; Prignoni, A; Ríos, F; Baquero, S; Gando, S

    2006-01-01

    Inappropriate therapy (IT) and delayed initiation of appropriate therapy (DIAT) result in inadequate therapy in patients with ventilator-associated pneumonia (VAP). The aim of the current study was to assess the impact of DIAT in VAP. A total of 76 mechanically ventilated patients with bacteriologically confirmed VAP were prospectively evaluated in the intensive care unit of six hospitals in Buenos Aires, Argentina. Appropriate therapy was defined as coverage of all the identified pathogens by the antimicrobial therapy administered at the time of VAP clinical diagnosis. The clinical pulmonary infection score was measured during the 3 days before, at the onset and during the days which followed the onset of VAP. A total of 24 patients received adequate therapy; mortality was 29.2%. The remaining 52 patients received either IT (n = 16) or DIAT (n = 36); the mortality was 63.5% combined, and 75.0 and 58.3% for IT and DIAT, respectively (statistically significant compared with adequate therapy). Inappropriate therapy and delayed initiation of appropriate therapy increased the mortality of ventilator-associated pneumonia. Patients with inappropriate therapy and/or delayed initiation of appropriate therapy had a more gradual increase in clinical pulmonary infection score than those receiving adequate therapy, and this increase was found to occur prior to the time of the clinical diagnosis. In conclusion, these findings might provide the rationale for a trial of earlier initiation of therapy, based on clinical grounds in an effort to improve the outcome of patients with ventilator-associated pneumonia.

  9. Delay in initiating adjuvant radiotherapy following breast conservation surgery and its impact on survival

    SciTech Connect

    Hershman, Dawn L. . E-mail: dlh23@columbia.edu; Wang Xiaoyan; McBride, Russell

    2006-08-01

    Purpose: Delays in the diagnosis of breast cancer are associated with advanced stage and poor survival, but the importance of the time interval between lumpectomy and initiation of radiation therapy (RT) has not been well studied. We investigated factors that influence the time interval between lumpectomy and RT, and the association between that interval and survival. Patients and Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database on women aged 65 years and older, diagnosed with Stages I-II breast cancer, between 1991 and 1999. Among patients who did not receive chemotherapy, we studied factors associated with the time interval between lumpectomy and the initiation of RT, and the association of delay with survival, using linear regression and Cox proportional hazards modeling. Results: Among 24,833 women with who underwent lumpectomy, 13,907 (56%) underwent RT. Among those receiving RT, 97% started treatment within 3 months; older age, black race, advanced stage, more comorbidities, and being unmarried were associated with longer time intervals between surgery and RT. There was no benefit to earlier initiation of RT; however, delays >3 months were associated with higher overall mortality (hazard ratio, 1.92; 95% confidence interval, 1.64-2.24) and cancer-specific mortality (hazard ratio, 3.84; 95% confidence interval 3.01-4.91). Conclusions: Reassuringly, early initiation of RT was not associated with survival. Although delays of >3 months are uncommon, they are associated with poor survival. Whether this association is causal or due to confounding factors, such as poor health behaviors, is unknown; until it is better understood, efforts should be made to initiate RT in a timely fashion.

  10. Canagliflozin Lowers Postprandial Glucose and Insulin by Delaying Intestinal Glucose Absorption in Addition to Increasing Urinary Glucose Excretion

    PubMed Central

    Polidori, David; Sha, Sue; Mudaliar, Sunder; Ciaraldi, Theodore P.; Ghosh, Atalanta; Vaccaro, Nicole; Farrell, Kristin; Rothenberg, Paul; Henry, Robert R.

    2013-01-01

    OBJECTIVE Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption. RESEARCH DESIGN AND METHODS This two-period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual-tracer method. Placebo or canagliflozin 300 mg was given 20 min before a 600-kcal mixed-meal tolerance test. Plasma glucose, 3H-glucose, 14C-glucose, and insulin were measured frequently for 6 h to calculate rates of appearance of oral glucose (RaO) in plasma, endogenous glucose production, and glucose disposal. RESULTS Compared with placebo, canagliflozin treatment reduced postprandial plasma glucose and insulin excursions (incremental 0- to 2-h area under the curve [AUC0–2h] reductions of 35% and 43%, respectively; P < 0.001 for both), increased 0- to 6-h urinary glucose excretion (UGE0–6h, 18.2 ± 5.6 vs. <0.2 g; P < 0.001), and delayed RaO. Canagliflozin reduced AUC RaO by 31% over 0 to 1 h (geometric means, 264 vs. 381 mg/kg; P < 0.001) and by 20% over 0 to 2 h (576 vs. 723 mg/kg; P = 0.002). Over 2 to 6 h, canagliflozin increased RaO such that total AUC RaO over 0 to 6 h was <6% lower versus placebo (960 vs. 1,018 mg/kg; P = 0.003). A modest (∼10%) reduction in acetaminophen absorption was observed over the first 2 h, but this difference was not sufficient to explain the reduction in RaO. Total glucose disposal over 0 to 6 h was similar across groups. CONCLUSIONS Canagliflozin reduces postprandial plasma glucose and insulin by increasing UGE (via renal SGLT2 inhibition) and delaying RaO, likely due to intestinal SGLT1 inhibition. PMID:23412078

  11. Sulfate anion delays the self-assembly of human insulin by modifying the aggregation pathway.

    PubMed

    Owczarz, Marta; Arosio, Paolo

    2014-07-01

    The understanding of the molecular mechanisms underlying protein self-assembly and of their dependence on solvent composition has implications in a large number of biological and biotechnological systems. In this work, we characterize the aggregation process of human insulin at acidic pH in the presence of sulfate ions using a combination of Thioflavin T fluorescence, dynamic light scattering, size exclusion chromatography, Fourier transform infrared spectroscopy, and transmission electron microscopy. It is found that the increase of sulfate concentration inhibits the conversion of insulin molecules into aggregates by modifying the aggregation pathway. At low sulfate concentrations (0-5 mM) insulin forms amyloid fibrils following the nucleated polymerization mechanism commonly observed under acidic conditions in the presence of monovalent anions. When the sulfate concentration is increased above 5 mM, the sulfate anion induces the salting-out of ∼18-20% of insulin molecules into reversible amorphous aggregates, which retain a large content of α-helix structures. During time these aggregates undergo structure rearrangements into β-sheet structures, which are able to recruit monomers and bind to the Thioflavin T dye. The alternative aggregation mechanism observed at large sulfate concentrations is characterized by a larger activation energy and leads to more polymorphic structures with respect to the self-assembly in the presence of chloride ions. The system shown in this work represents a case where amorphous aggregates on pathway to the formation of structures with amyloid features could be detected and analyzed. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  12. Initiation of movement and energy expenditure in children with developmental delay: a case-control study.

    PubMed

    Chen, Chiao-Nan Joyce; Hwang, Ai-Wen; Lin, Shang-Ying; Lin, Yu-Chieh

    2014-10-01

    Lower levels of physical activity in children with developmental delay (DD) usually are attributed to higher energy costs. However, there is no evidence that children with DD spend more energy on daily physical activities, such as walking. The aim of this study was to compare energy costs during walking and movement initiation times in children with DD and children with typical development (TD) and matched for age. This was a case-control study. Children who were 3 and 5 years old and had DD (n=12) or TD (n=12) participated in the study. Measurements included ranges of motion in the lower extremities, physiological costs of walking, and movement initiation times. A task designed to evaluate the initiation of movement (the "go play with the toy" task) was used to examine the reaction times for children's goal-directed walking. The physiological costs of walking were similar in the 2 groups; however, children with DD walked at a lower speed than children with TD. Importantly, children with DD took more time to initiate goal-directed walking. The nature of the study design limited causal inference from the results. Children who were 3 to 5 years old and had DD had delays in goal-directed movement that may not have been attributable to motor impairments. The findings suggest that therapists should evaluate the movement initiation ability of 3- to 5-year-old children with DD as part of the design of an overall intervention plan. © 2014 American Physical Therapy Association.

  13. Predictors of insulin initiation in metformin and sulfonylurea users in primary care practices: the role of kidney function.

    PubMed

    Kostev, Karel; Dippel, Franz-Werner; Rathmann, Wolfgang

    2014-09-01

    The aims were to investigate predictors of insulin initiation in new users of metformin or sulfonylureas in primary care practices, in particular, its association with decreased renal function. Data from 9103 new metformin and 1120 sulfonylurea users with normal baseline glomerular filtration rate (eGFR) >90 ml/min/1.73 m(2) from 1072 practices were retrospectively analyzed (Disease Analyzer Germany: 01/2003-06/2012). Cox regression models and propensity score matching was used to adjust for confounders (age, sex, practice characteristics, comorbidity). Insulin treatment was started in 394 (4.3%) metformin and in 162 (14.5%) sulfonylurea users within 6 years (P < .001). Kaplan-Meier curves (propensity score matched patients) showed that the metformin group was at a lower risk of insulin initiation compared to sulfonylurea users throughout the study period. A substantial eGFR decline (category: 15-<30 ml/min/1.73 m(2)) was significantly associated with a higher likelihood to have insulin initiated (adjusted hazard ratio [HR]: 2.39; 95% CI: 1.09-5.23) in metformin but not in sulfonylurea (HR: 0.45; 95% CI: 0.16-1.30) users. New users of sulfonylurea monotherapy in primary care practices in Germany were about 3-fold more likely to start insulin therapy than those with metformin. Kidney function decline was associated with earlier insulin initiation in metformin but not in sulfonylurea users.

  14. Modifying temporal expectations: Changing cortical responsivity to delayed self-initiated sensations with training.

    PubMed

    Elijah, Ruth B; Le Pelley, Mike E; Whitford, Thomas J

    2016-10-01

    The perceptual system makes a specific prediction regarding the timing of impending, self-initiated sensations to facilitate the attenuation of these sensations. The current study used electroencephalography to investigate whether temporal expectations can be modified with training. Participants underwent a button-press-for-tone task and evoked responses to the tones were measured. Fifty participants were randomly assigned to receive repeated exposure (training) to either immediate tones, or tones delayed by 100ms. Pre-training, N1 amplitude to delayed tones was significantly larger compared to immediate tones. However, while training to the immediate tone maintained a significant difference in N1 amplitude between the immediate and delayed tones post-training, this difference was eliminated when trained to the delayed tone. This suggests that participants' neural expectations regarding the anticipated timing of self-generated sensations can be modified with behavioural training. This result has implications for alleviating the subnormal sensory attenuation which has been observed in patients with schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Glucose delays the insulin-induced increase in thyroid hormone-mediated signaling in adipose of prolong-fasted elephant seal pups

    PubMed Central

    Soñanez-Organis, José G.; Viscarra, Jose A.; Jaques, John T.; MacKenzie, Duncan S.; Crocker, Daniel E.; Ortiz, Rudy M.

    2016-01-01

    Prolonged food deprivation in mammals typically reduces glucose, insulin, and thyroid hormone (TH) concentrations, as well as tissue deiodinase (DI) content and activity, which, collectively, suppress metabolism. However, in elephant seal pups, prolonged fasting does not suppress TH levels; it is associated with upregulation of adipose TH-mediated cellular mechanisms and adipose-specific insulin resistance. The functional relevance of this apparent paradox and the effects of glucose and insulin on TH-mediated signaling in an insulin-resistant tissue are not well defined. To address our hypothesis that insulin increases adipose TH signaling in pups during extended fasting, we assessed the changes in TH-associated genes in response to an insulin infusion in early- and late-fasted pups. In late fasting, insulin increased DI1, DI2, and THrβ-1 mRNA expression by 566%, 44%, and 267% at 60 min postinfusion, respectively, with levels decreasing by 120 min. Additionally, we performed a glucose challenge in late-fasted pups to differentiate between insulin- and glucose-mediated effects on TH signaling. In contrast to the insulin-induced effects, glucose infusion did not increase the expressions of DI1, DI2, and THrβ-1 until 120 min, suggesting that glucose delays the onset of the insulin-induced effects. The data also suggest that fasting duration increases the sensitivity of adipose TH-mediated mechanisms to insulin, some of which may be mediated by increased glucose. These responses appear to be unique among mammals and to have evolved in elephant seals to facilitate their adaptation to tolerate an extreme physiological condition. PMID:26739649

  16. Glucose delays the insulin-induced increase in thyroid hormone-mediated signaling in adipose of prolong-fasted elephant seal pups.

    PubMed

    Martinez, Bridget; Soñanez-Organis, José G; Viscarra, Jose A; Jaques, John T; MacKenzie, Duncan S; Crocker, Daniel E; Ortiz, Rudy M

    2016-03-15

    Prolonged food deprivation in mammals typically reduces glucose, insulin, and thyroid hormone (TH) concentrations, as well as tissue deiodinase (DI) content and activity, which, collectively, suppress metabolism. However, in elephant seal pups, prolonged fasting does not suppress TH levels; it is associated with upregulation of adipose TH-mediated cellular mechanisms and adipose-specific insulin resistance. The functional relevance of this apparent paradox and the effects of glucose and insulin on TH-mediated signaling in an insulin-resistant tissue are not well defined. To address our hypothesis that insulin increases adipose TH signaling in pups during extended fasting, we assessed the changes in TH-associated genes in response to an insulin infusion in early- and late-fasted pups. In late fasting, insulin increased DI1, DI2, and THrβ-1 mRNA expression by 566%, 44%, and 267% at 60 min postinfusion, respectively, with levels decreasing by 120 min. Additionally, we performed a glucose challenge in late-fasted pups to differentiate between insulin- and glucose-mediated effects on TH signaling. In contrast to the insulin-induced effects, glucose infusion did not increase the expressions of DI1, DI2, and THrβ-1 until 120 min, suggesting that glucose delays the onset of the insulin-induced effects. The data also suggest that fasting duration increases the sensitivity of adipose TH-mediated mechanisms to insulin, some of which may be mediated by increased glucose. These responses appear to be unique among mammals and to have evolved in elephant seals to facilitate their adaptation to tolerate an extreme physiological condition. Copyright © 2016 the American Physiological Society.

  17. Initial tsunami source estimation by inversion with an intelligent selection of model parameters and time delays

    NASA Astrophysics Data System (ADS)

    Mulia, Iyan E.; Asano, Toshiyuki

    2016-01-01

    We propose a method for accurately estimating the initial tsunami source. Our technique is independent of the earthquake parameters, because we only use recorded tsunami waveforms and an auxiliary basis function, instead of a fault model. We first use the measured waveforms to roughly identify the source area using backward propagated travel times, and then infer the initial sea surface deformation through inversion analysis. A computational intelligence approach based on a genetic algorithm combined with a pattern search was used to select appropriate least squares model parameters and time delays. The proposed method significantly reduced the number of parameters and suppressed the negative effect of regularization schemes that decreased the plausibility of the model. Furthermore, the stochastic approach for deriving the time delays is a more flexible strategy for simulating actual phenomena that occur in nature. The selected parameters and time delays increased the accuracy, and the model's ability to reveal the underlying physics associated with the tsunami-generating processes. In this paper, we applied the method to the 2011 Tohoku-Oki tsunami event and examined its effectiveness by comparing the results to those using the conventional method.

  18. Impact of the initial tropospheric zenith path delay on precise point positioning convergence during active conditions

    NASA Astrophysics Data System (ADS)

    Kalita, J. Z.; Rzepecka, Z.

    2017-04-01

    Tropospheric delay is one of the key factors that influence the convergence time of the precise point positioning (PPP) method. Current models do not allow for the fixing of the zenith path delay tropospheric parameter, leaving the difference between nominal and final value to the estimation process. Here, we present an analysis of several PPP result-sets using the tropospheric parameter’s nominal value adopted from models: VMF1, GPT2w, MOPS, and ZERO-WET. The last variant assumes a zero value for the initial wet part of the zenith delay. The PPP results are subtracted from a solution based on the final tropospheric product from the International GNSS Service (IGS). Several days exhibiting the most active tropospheric conditions were selected for each of the 7 stations located in the mid-latitude Central European region. During the active days, application of the VMF1 model increases the resulting height component’s quality by about 33–36% when compared to the GPT2w and MOPS. The respective improvement in VMF1 latitude and longitude components is 27% and 15%. The average relative deterioration in the result standard deviations between active and calm tropospheric conditions reaches about 20–30% of the former. We discuss the impact of the initial tropospheric parameter’s variance and bias on positioning. In addition, we compare the results with those of other studies over the impact of active tropospheric conditions on the PPP method.

  19. Dental problems delaying the initiation of interferon therapy for HCV-infected patients

    PubMed Central

    2010-01-01

    Background There has been little discussion about the importance of oral management and interferon (IFN) therapy, although management of the side effects of therapy for chronic hepatitis C has been documented. This study determined whether dental problems delayed the initiation of IFN therapy for hepatitis C virus (HCV)-infected patients. Results We analyzed 570 HCV-infected patients who were admitted to our hospital from December 2003 to June 2010 for treatment consisting of pegylated IFN (Peg-IFN) monotherapy or Peg-IFN/ribavirin combination therapy. The group comprised 274 men and 296 women with a mean age 57.2 years. Of the 570 patients, six could not commence Peg-IFN therapy, despite their admission, because of dental problems such as periodontitis, pupitis, and pericoronitis. The ages of six whose dental problems delayed the initiation of Peg-IFN ranged from 25 to 67 years, with a mean age of 47.3 ± 15.2 years. IFN therapy was deferred for 61.3 ± 47.7 days. Among the six subjects for whom IFN treatment was delayed, only one had a salivary flow that was lower than the normal value. Conclusions Treatment of dental infections is required before IFN therapy for HCV infection can be started. To increase the depth of understanding of oral health care, it is hoped that dentists and medical specialists in all areas will hold discussions to generate cooperation. PMID:20712912

  20. Hypertension management initiative prospective cohort study: comparison between immediate and delayed intervention groups.

    PubMed

    Tobe, S W; Moy Lum-Kwong, M; Von Sychowski, S; Kandukur, K; Kiss, A; Flintoft, V

    2014-01-01

    The Heart and Stroke Foundation of Ontario's Hypertension Management Initiative (HMI) was a pragmatic implementation of clinical practice guidelines for hypertension management in primary care clinics. The HMI was a prospective delayed phase cohort study of 11 sites enrolling patients in two blocks starting 9 months apart in 2007. The intervention was an evidence-informed chronic disease management program consisting of an interprofessional educational intervention with practice tools to implement the Canadian Hypertension Education Program's clinical practice guidelines. This study compares the change in blood pressure (BP) from baseline to 9 months after the intervention between groups. In the immediate intervention group, the mean BP at baseline was 134.6/79.1 mm Hg (18.2/11.5) and in the delayed intervention group 134.2/77.1 mm Hg (18.9/11.8). The fall in BP in the immediate intervention group from baseline to 9 months after the intervention was 7.3/3.6 mm Hg (95% confidence interval (CI): 5.9-8.7/2.6-4.5) and in the delayed group 8.1/3.3 mm Hg (95% CI: 7.0-9.3/2.5-4.1) (all P<0.0001 were compared from baseline to the end of 9 months of the program in both groups). This study is the first to demonstrate that implementation of an interprofessional knowledge integration initiative for the control of hypertension can rapidly lead to lower BP levels.

  1. Insulin therapy for management of type 2 diabetes mellitus: strategies for initiation and long-term patient adherence.

    PubMed

    Barag, Steven H

    2011-07-01

    Effective glycemic control is essential to minimize the long-term complications of type 2 diabetes mellitus (T2DM). However, it is well documented that many patients spend prolonged periods outside of the optimal glycemic range. The use of insulin is important to effectively control the disease process in patients with T2DM. Even so, resistance to insulin use among patients and healthcare providers often limits initiation and intensification of insulin therapy. With the increasing prevalence of T2DM across all socioeconomic strata, an expanded viewpoint of early and sustained insulin use is crucial to enhance glycemic control in patients. To manage the effects of T2DM on cardiovascular disease in the aging population, physicians can promote insulin therapy as an affordable and effective treatment option. The author reviews beliefs and myths about the use of insulin in the management of T2DM and discusses strategies to overcome barriers to initiation of insulin therapy in the primary care setting.

  2. Delays in anaphase initiation occur in individual nuclei of the syncytial Drosophila embryo.

    PubMed Central

    Sullivan, W; Daily, D R; Fogarty, P; Yook, K J; Pimpinelli, S

    1993-01-01

    The syncytial divisions of the Drosophila melanogaster embryo lack some of the well established cell-cycle checkpoints. It has been suggested that without these checkpoints the divisions would display a reduced fidelity. To test this idea, we examined division error frequencies in individuals bearing an abnormally long and rearranged second chromosome, designated C(2)EN. Relative to a normal chromosome, this chromosome imposes additional structural demands on the mitotic apparatus in both the early syncytial embryonic divisions and the later somatic divisions. We demonstrate that the C(2)EN chromosome does not increase the error frequency of the late larva neuroblast divisions. However, in the syncytial embryonic nuclear divisions, the C(2)EN chromosome produces a 10-fold increase in division errors relative to embryos with a normal karyotype. During late anaphase of the neuroblast divisions, the sister C(2)EN chromosomes cleanly separate from one another. In contrast, during late anaphase of the syncytial divisions in C(2)EN-bearing nuclei, large amounts of chromatin often lag on the metaphase plate. Live analysis of C(2)EN-bearing embryos demonstrates that individual nuclei in the syncytial population of dividing nuclei often delay in their initiation of anaphase. These delays frequently lead to division errors. Eventually the products of the nuclei delayed in anaphase sink inward and are removed from the dividing population of syncytial nuclei. These results suggest that the Drosophila embryo may be equipped with mechanisms that monitor the fidelity of the syncytial nuclear divisions. Unlike checkpoints that rely on cell cycle delays to identify and correct division errors, these embryonic mechanisms rely on cell cycle delays to identify and discard the products of division errors. Images PMID:8257792

  3. Which oral antidiabetic drug to combine with metformin to minimize the risk of hypoglycemia when initiating basal insulin?: A randomized controlled trial of a DPP4 inhibitor versus insulin secretagogues.

    PubMed

    Gautier, J F; Monguillon, P; Verier-Mine, O; Valensi, P; Fiquet, B; Dejager, S; Charbonnel, B

    2016-06-01

    We conducted a pilot study to evaluate two therapeutic strategies at the time of insulin initiation in type 2 diabetic patients insufficiently controlled with metformin+insulin-secretagogues (IS, sulfonylureas or glinides). Patients were randomized to remain under the same dual therapy or to receive metformin+DPP4 inhibitors while starting insulin. Similar glycemic control was achieved in both groups. However less hypoglycemia was observed with DPP4 inhibitors despite higher doses of insulin.

  4. Adaptive synchronization under almost every initial data for stochastic neural networks with time-varying delays and distributed delays

    NASA Astrophysics Data System (ADS)

    Zhu, Quanxin; Cao, Jinde

    2011-04-01

    This paper is concerned with the adaptive synchronization problem for a class of stochastic delayed neural networks. Based on the LaSalle invariant principle of stochastic differential delay equations and the stochastic analysis theory as well as the adaptive feedback control technique, a linear matrix inequality approach is developed to derive some novel sufficient conditions achieving complete synchronization of unidirectionally coupled stochastic delayed neural networks. In particular, the synchronization criterion considered in this paper is the globally almost surely asymptotic stability of the error dynamical system, which has seldom been applied to investigate the synchronization problem. Moreover, the delays proposed in this paper are time-varying delays and distributed delays, which have rarely been used to study the synchronization problem for coupled stochastic delayed neural networks. Therefore, the results obtained in this paper are more general and useful than those given in the previous literature. Finally, two numerical examples and their simulations are provided to demonstrate the effectiveness of the theoretical results.

  5. Disturbed phospholipid homeostasis in endoplasmic reticulum initiates tri-o-cresyl phosphate-induced delayed neurotoxicity

    PubMed Central

    Zhu, Li; Wang, Pan; Sun, Ying-Jian; Xu, Ming-Yuan; Wu, Yi-Jun

    2016-01-01

    Tri-o-cresyl phosphate (TOCP) is a widely used organophosphorus compound, which can cause a neurodegenerative disorder, i.e., organophosphate-induced delayed neurotoxicity (OPIDN). The biochemical events in the initiation of OPIDN were not fully understood except for the essential inhibition of neuropathy target esterase (NTE). NTE, located in endoplasmic reticulum (ER), catalyzes the deacylation of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) to glycerophosphocholine (GPC). The present study aims to study the changes of ER phospholipids profile as well as levels of important intermediates of phospholipid synthesis such as diacylglycerol (DAG) and phosphatidic acid (PA) at the initiation stage of OPIDN. Hens are the most commonly used animal models of OPIDN. The spinal cord phospholipidomic profiles of hens treated by TOCP were studied by using HPLC-MS-MS. The results revealed that TOCP induced an increase of PC, LPC, and sphingomyelin (SM) levels and a decrease of GPC, phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), lysophosphatidylserine (LPS), phosphatidylglycerol (PG), and phosphatidylinositol (PI) levels., Levels of DAG and PA were also decreased. Pretreatment with phenylmethylsulfonyl fluoride (PMSF) 24 h before TOCP administration prevented OPIDN and restored the TOCP-induced changes of phospholipids except GPC. Thus, the disruption of ER phospholipid homeostasis may contribute to the initiation of organophosphate-induced delayed neurotoxicity. PMID:27883027

  6. Recovery from Multiple APAs Delays Gait Initiation in Parkinson’s Disease

    PubMed Central

    Cohen, Rajal G.; Nutt, John G.; Horak, Fay B.

    2017-01-01

    Background: Freezing of gait in Parkinson’s disease (PD) has been linked with deficits in inhibitory control, but causal mechanisms are not established. Freezing at gait initiation (start hesitation) is often accompanied by multiple anticipatory postural adjustments (APAs). If inhibition deficits contribute to freezing by interfering with ability to inhibit initial weight shifts in the wrong direction, then PD subjects should experience more episodes of multiple APAs than healthy controls (HCs) do. If inhibition deficits contribute to freezing by interfering with ability to release a previously inhibited step following multiple APAs, then step onset following multiple APAs should be delayed more in people with PD than in HCs. Methods: Older adults with PD and HC subjects rapidly initiated stepping in response to a light cue in blocks of simple (SRT) and choice (CRT) conditions. We recorded kinematics and ground reaction forces, and we administered the Stroop task to assess inhibitory control. Results: Multiple APAs were more common in CRT than SRT conditions but were equally common in HC and PD subjects. Step onsets were delayed in both conditions and further delayed in trials with multiple APAs, except for HC subjects in SRT trials. Poor Stroop performance correlated with many multiple APAs, late step onset, and rearward position of center of mass (COM) at cue presentation. Forward motion of the COM during the APA was higher in trials with multiple APAs than in trials with single APAs, especially in CRT trials and in PD subjects without self-reported freezing. Conclusion: Start hesitation is not caused by multiple APAs per se, but may be associated with difficulty recovering from multiple APAs, due to difficulty releasing a previously inhibited step. PMID:28261073

  7. A quality improvement initiative for delayed umbilical cord clamping in very low-birthweight infants.

    PubMed

    Bolstridge, Jeff; Bell, Tracy; Dean, Barbara; Mackley, Amy; Moore, Gina; Swift, Cheryl; Viscount, Dina; Paul, David A; Pearlman, Stephen A

    2016-09-13

    Due to clinical benefits, delayed cord clamping (DCC) is recommended in infants born before 37 weeks gestational age. The objective was to institute a delayed cord clamping program and to evaluate clinical outcomes one year after initiation. This study occured at Christiana Care Health System, a tertiary care facility with a 52 bed level 3 Neonatal Intensive Care Unit (NICU). A multidisciplinary team created a departmental policy, a DCC protocol and educational programs to support the development of a DCC program. A year after initiation of DCC, we evaluated two cohorts of very low birth weight (VLBW) infants (<1500 g) prior to (Cohort 1) and after initiation (Cohort 2) of DCC (n = 136 and n = 142 respectively). Chart review was conducted to evaluate demographic data and clinical outcomes. Analysis was completed with a retrospective, cohort analysis on an intention-to-treat basis. There were no differences in demographic factors between the two cohorts. We demonstrated a 73 % compliance rate with the delayed cord clamping protocol and a decrease in the percentage of VLBW infants requiring red blood cell transfusion from 53.7 to 35.9 % (p = 0.003). We also found a decreased need for respiratory support in the second cohort with no increases in the balancing measures of admission hypothermia and jaundice requiring phototherapy. During the Control Phase ongoing monitoring and education has led to a 93.7 % compliance rate. A multidisciplinary team including key leadership from the obstetric and pediatric departments allowed for the rapid and safe implementation of DCC.

  8. Increased healthcare utilization costs following initiation of insulin treatment in type 2 diabetes: A long-term follow-up in clinical practice.

    PubMed

    Kalkan, Almina; Bodegard, Johan; Sundström, Johan; Svennblad, Bodil; Östgren, Carl Johan; Nilsson, Peter Nilsson; Johansson, Gunnar; Ekman, Mattias

    2017-04-01

    To compare long-term changes in healthcare utilization and costs for type 2 diabetes patients before and after insulin initiation, as well as healthcare costs after insulin versus non-insulin anti-diabetic (NIAD) initiation. Patients newly initiated on insulin (n=2823) were identified in primary health care records from 84 Swedish primary care centers, between 1999 to 2009. First, healthcare costs per patient were evaluated for primary care, hospitalizations and secondary outpatient care, before and up to seven years after insulin initiation. Second, patients prescribed insulin in second line were matched to patients prescribed NIAD in second line, and the healthcare costs of the matched groups were compared. The total mean annual healthcare cost increased from €1656 per patient 2 years before insulin initiation to €3814 seven years after insulin initiation. The total cumulative mean healthcare cost per patient at year 5 after second-line treatment was €13,823 in the insulin group compared to €9989 in the NIAD group. Initiation of insulin in type 2 diabetes patients was followed by increased healthcare costs. The increases in costs were larger than those seen in a matched patient population initiated on NIAD treatment in second-line. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  9. Reasons for delaying or engaging in early sexual initiation among adolescents in Nigeria

    PubMed Central

    Ankomah, Augustine; Mamman-Daura, Fatima; Omoregie, Godpower; Anyanti, Jennifer

    2011-01-01

    Background Annually, over 1 million births in Nigeria are to teenage mothers. Many of these pregnancies are unwanted and these mothers are also exposed to the risk of human immunodeficiency virus (HIV) infection. Sexual abstinence is a critical preventative health strategy. Several quantitative studies in Nigeria have identified the correlates and determinants of early sex, yet few have explored in depth the underlying reasons for early sex. This paper explores both the key factors that motivate some unmarried young people to engage in early sex and reasons why some delay. Methods This qualitative study was based on data from 30 focus group discussions held with unmarried 14- to 19-year-olds in four geographically and culturally dispersed Nigerian states. Focus groups were stratified by sexual experience to capture variations among different subgroups. Results Several reasons for early premarital sex were identified. The “push” factors included situations where parents exposed young female adolescents to street trading. “Pull” factors, particularly for males, included the pervasive viewing of locally produced movies, peer pressure and, for females, transactional sex (where adolescent girls exchange sex for gifts, cash, or other favors). Also noted were overtly coercive factors, including rape. There were also myths and misconceptions that “justified” early sexual initiation. Reasons cited for delay included religious injunction against premarital sex; disease prevention (especially HIV/acquired immunodeficiency syndrome); fear of pregnancy, and linked to this, the fear of dropping out of school; and, for females, the fear of bringing shame to the family, which could lead to their inability to get a “good” husband in the future. Conclusion The differences observed between sexually active and abstinent adolescents were that the latter were more confident, had greater determination, and, most important, deployed refusal skills to delay first sex

  10. Reasons for delaying or engaging in early sexual initiation among adolescents in Nigeria.

    PubMed

    Ankomah, Augustine; Mamman-Daura, Fatima; Omoregie, Godpower; Anyanti, Jennifer

    2011-01-01

    Annually, over 1 million births in Nigeria are to teenage mothers. Many of these pregnancies are unwanted and these mothers are also exposed to the risk of human immunodeficiency virus (HIV) infection. Sexual abstinence is a critical preventative health strategy. Several quantitative studies in Nigeria have identified the correlates and determinants of early sex, yet few have explored in depth the underlying reasons for early sex. This paper explores both the key factors that motivate some unmarried young people to engage in early sex and reasons why some delay. This qualitative study was based on data from 30 focus group discussions held with unmarried 14- to 19-year-olds in four geographically and culturally dispersed Nigerian states. Focus groups were stratified by sexual experience to capture variations among different subgroups. Several reasons for early premarital sex were identified. The "push" factors included situations where parents exposed young female adolescents to street trading. "Pull" factors, particularly for males, included the pervasive viewing of locally produced movies, peer pressure and, for females, transactional sex (where adolescent girls exchange sex for gifts, cash, or other favors). Also noted were overtly coercive factors, including rape. There were also myths and misconceptions that "justified" early sexual initiation. Reasons cited for delay included religious injunction against premarital sex; disease prevention (especially HIV/acquired immunodeficiency syndrome); fear of pregnancy, and linked to this, the fear of dropping out of school; and, for females, the fear of bringing shame to the family, which could lead to their inability to get a "good" husband in the future. The differences observed between sexually active and abstinent adolescents were that the latter were more confident, had greater determination, and, most important, deployed refusal skills to delay first sex. Health promoters need to focus attention on educating

  11. Do ketoanalogues still have a role in delaying dialysis initiation in CKD predialysis patients?

    PubMed

    Aparicio, Michel; Bellizzi, Vincenzo; Chauveau, Philippe; Cupisti, Adamasco; Ecder, Tevfik; Fouque, Denis; Garneata, Liliana; Lin, Shanyan; Mitch, William; Teplan, Vladimir; Yu, Xueqing; Zakar, Gabor

    2013-01-01

    Early versus later start of dialysis is still a matter of debate. Low-protein diets have been used for many decades to delay dialysis initiation. Protein-restricted diets (0.3-0.6 g protein/kg/day) supplemented with essential amino acids and ketoanalogues (sVLPD) can be offered, in association with pharmacological treatment, to motivated stage 4-5 chronic kidney disease (CKD) patients not having severe comorbid conditions; they probably represent 30-40% of the concerned population. A satisfactory adherence to such dietary prescription is observed in approximately 50% of the patients. While the results of the studies on the effects of this diet on the rate of progression of renal failure remain inconclusive, they are highly significant when initiation of dialysis is the primary outcome. The correction of uremic symptoms allows for initiation of dialysis treatment at a level of residual renal function lower than that usually recommended. Most of the CKD-associated complications of cardiovascular and metabolic origin, which hamper both lifespan and quality of life, are positively influenced by the diet. Lastly, with regular monitoring jointly assumed by physicians and dietitians, nutritional status is well preserved as confirmed by a very low mortality rate and by the absence of detrimental effect on the long-term outcome of patients once renal replacement therapy is initiated. On account of its feasibility, efficacy and safety, sVLPD deserves a place in the management of selected patients to safely delay the time needed for dialysis. © 2013 Wiley Periodicals, Inc.

  12. Disparities in head and neck cancer: assessing delay in treatment initiation.

    PubMed

    Patel, Urjeet A; Brennan, Tara E

    2012-08-01

    Disparities in outcome for head and neck cancer (HNC) treatment are related to diverse factors including tumor stage, socioeconomic status, and treatment compliance. Latency to initiation of therapy may contribute to worse outcomes for underserved populations. The objectives of this study were to measure the interval from diagnosis of HNC to initiation of cancer treatment (DTI) and to identify factors that prolong DTI. Retrospective study. We identified 150 consecutive patients treated for squamous cell HNC at a tertiary-care public hospital between 2005 and 2007. Outcome measures used were 1) interval between cancer diagnosis and treatment initiation and 2) factors that predict prolonged DTI. We included 100 patients in the analysis. Median time to perform biopsy was 8 days; time to obtain final diagnosis was 14 days; time to complete staging scans was 18 days; time to discuss treatment plan was 23 days; time to initiation of therapy was 56 days. Median DTI was 48 days. DTI was prolonged for patients receiving primary radiotherapy compared to surgical therapy: 57 versus 30 days (P < .001). Early stage tumors had shorter DTI than late-stage tumors: 38 versus 57 days (P = .02). Presenting with outside biopsy demonstrating HNC also reduced DTI (P = .03). Obtaining a computed tomography scan in the emergency department was not found to significantly affect DTI. DTI was found to be prolonged among HNC patients in this study when compared to previously published treatment intervals. Advanced stage of tumor, primary radiotherapy, and need for biopsy prolonged DTI. Future studies should better identify causes of delay and reduce latency for patients at highest risk for delay. Copyright © 2012 The American Laryngological, Rhinological, and Otological Society, Inc.

  13. Comparison of three algorithms for initiation and titration of insulin glargine in insulin-naive patients with type 2 diabetes mellitus.

    PubMed

    Dailey, George; Aurand, Lisa; Stewart, John; Ameer, Barbara; Zhou, Rong

    2014-03-01

    Several titration algorithms can be used to adjust insulin dose and attain blood glucose targets. We compared clinical outcomes using three initiation and titration algorithms for insulin glargine in insulin-naive patients with type 2 diabetes mellitus (T2DM); focusing on those receiving both metformin and sulfonylurea (SU) at baseline. This was a pooled analysis of patient-level data from prospective, randomized, controlled 24-week trials. Patients received algorithm 1 (1 IU increase once daily, if fasting plasma glucose [FPG] > target), algorithm 2 (2 IU increase every 3 days, if FPG > target), or algorithm 3 (treat-to-target, generally 2-8 IU increase weekly based on 2-day mean FPG levels). Glycemic control, insulin dose, and hypoglycemic events were compared between algorithms. Overall, 1380 patients were included. In patients receiving metformin and SU at baseline, there were no significant differences in glycemic control between algorithms. Weight-adjusted dose was higher for algorithm 2 vs algorithms 1 and 3 (P = 0.0037 and P < 0.0001, respectively), though results were not significantly different when adjusted for reductions in HbA1c (0.36 IU/kg, 0.43 IU/kg, and 0.31 IU/kg for algorithms 1, 2, and 3, respectively). Yearly hypoglycemic event rates (confirmed blood glucose <56 mg/dL) were higher for algorithm 3 than algorithms 1 (P = 0.0003) and 2 (P < 0.0001). Three algorithms for initiation and titration of insulin glargine in patients with T2DM resulted in similar levels of glycemic control, with lower rates of hypoglycemia for patients treated using simpler algorithms 1 and 2. © 2013 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  14. Insulin-Like Growth Factor Is Associated with Changes in Body Composition with Antiretroviral Therapy Initiation.

    PubMed

    Erlandson, Kristine M; Fiorillo, Suzanne P; Cardoso, Sandra Wagner; Riviere, Cynthia; Sanchez, Jorge; Hakim, James; Kumarasamy, Nagalingeswaran; Badal-Faesen, Sharlaa; Lalloo, Umesh; Kumwenda, Johnstone; Campbell, Thomas B; Brown, Todd T

    2017-09-01

    Growth hormone (GH)/insulin-like growth factor (IGF)-1 axis abnormalities have been associated with body composition changes among HIV-infected persons with wasting or lipodystrophy. Little is known of GH/IGF-1 axis alterations with antiretroviral therapy (ART) initiation or differing ART therapies. The AIDS Clinical Trials Group Prospective Evaluation of Antiretrovirals in Resource-Limited Settings (PEARLS) study was a prospective, randomized clinical trial of ART initiation with emtricitabine/tenofovir + efavirenz (FTC/TDF+EFV) versus lamivudine/zidovudine + efavirenz (3TC/ZDV+EFV) in HIV-1-infected individuals from resource-diverse settings. IGF-1 was measured from baseline, week 48, and week 96 stored serum samples. Multivariate models were constructed. 415 participants were included: 170 (41%) were randomized to FTC/TDF+EFV and 245 (59%) to 3TC/ZDV+EFV. The mean age was 35 years, 60% were black, 42% women. The mean IGF-1 level did not change significantly from baseline to week 96 (-0.65 ng/ml; 95% confidence interval (CI) -5.18-3.87), p = .78 and there were no differences by treatment arm at week 96, p = .74. Lower baseline IGF-1 was associated with age, non-white race, greater waist-hip ratio (WHR), low CD4 count, and lower baseline albumin (all p < .01) but not plasma HIV-1 RNA, body mass index, or treatment arm. Greater change in IGF-1 from baseline to 96 weeks was associated with female sex, smaller WHR change, lower baseline albumin, and higher baseline HIV-1 RNA (all p < .01). ART initiation with either ZDV or TDF did not significantly impact overall IGF-1 levels. Baseline and on-treatment changes in IGF-1 with ART initiation may be related to the body composition changes that occur after ART initiation.

  15. Failure to initiate early insulin therapy – A risk factor for diabetic retinopathy in insulin users with Type 2 diabetes mellitus: Sankara Nethralaya-Diabetic Retinopathy Epidemiology and Molecular Genetics Study (SN-DREAMS, Report number 35)

    PubMed Central

    Gupta, Aditi; Delhiwala, Kushal S; Raman, Rajiv P G; Sharma, Tarun; Srinivasan, Sangeetha; Kulothungan, Vaitheeswaran

    2016-01-01

    Context: Insulin users have been reported to have a higher incidence of diabetic retinopathy (DR). Aim: The aim was to elucidate the factors associated with DR among insulin users, especially association between duration, prior to initiating insulin for Type 2 diabetes mellitus (DM) and developing DR. Materials and Methods: Retrospective cross-sectional observational study included 1414 subjects having Type 2 DM. Insulin users were defined as subjects using insulin for glycemic control, and insulin nonusers as those either not using any antidiabetic treatment or using diet control or oral medications. The duration before initiating insulin after diagnosis was calculated by subtracting the duration of insulin usage from the duration of DM. DR was clinically graded using Klein's classification. SPSS (version 9.0) was used for statistical analysis. Results: Insulin users had more incidence of DR (52.9% vs. 16.3%, P < 0.0001) and sight threatening DR (19.1% vs. 2.4%, P < 0.0001) in comparison to insulin nonusers. Among insulin users, longer duration of DM (odds ratio [OR] 1.12, 95% confidence interval [CI] 1.00–1.25, P = 0.044) and abdominal obesity (OR 1.15, 95% CI 1.02–1.29, P = 0.021) was associated with DR. The presence of DR was significantly associated with longer duration (≥5 years) prior to initiating insulin therapy, overall (38.0% vs. 62.0%, P = 0.013), and in subjects with suboptimal glycemic control (32.5% vs. 67.5%, P = 0.022). Conclusions: The presence of DR is significantly associated with longer duration of diabetes (>5 years) and sub-optimal glycemic control (glycosylated hemoglobin <7.0%). Among insulin users, abdominal obesity was found to be a significant predictor of DR; DR is associated with longer duration prior to initiating insulin therapy in Type 2 DM subjects with suboptimal glycemic control. PMID:27488152

  16. Reduced circulating insulin-like growth factor I levels delay the onset of chemically and genetically induced mammary tumors.

    PubMed

    Wu, Yiping; Cui, Karen; Miyoshi, Keiko; Hennighausen, Lothar; Green, Jeffrey E; Setser, Jennifer; LeRoith, Derek; Yakar, Shoshana

    2003-08-01

    Insulin-like growth factors (IGFs) play a crucial role in regulating cell proliferation and differentiation. The aim of this study was to examine the potential relationship between serum IGF-I levels and breast cancer risk. To do this, we studied liver-specific IGF-I gene-deleted (LID) mice, in which circulating IGF-I levels are 25% of that in control mice. Mammary tumors were induced in two ways: (a) by exposing mice to the carcinogen 7,12-dimethybenz (a)anthracene; and (b) by crossing LID mice with C3(1)/SV40 large T-antigen transgenic mice. In both models, LID mice exhibited a delayed latency period of mammary tumor development. In the 7,12-dimethybenz (a)anthracene-induced mammary tumor model, the incidence of palpable mammary tumors was significantly lower in LID mice (26% versus 56% in controls), and the onset of the tumors was delayed (74 +/- 1.2 days in LID mice versus 59.5 +/- 1.1 days in controls). Histological analysis showed extensive squamous metaplasia in late-stage mammary tumors of control mice, whereas late-stage tumors from LID mice exhibited extensive hyperplasia, but little metaplasia. In control mice, the onset of C3(1)/SV40-large T-antigen-induced mammary tumors occurred at 21.6 +/- 1.8 weeks of age, whereas in LID mice the average age of onset was 30.2 +/- 1.7 weeks. In addition, 60% of the mice in the control group developed two or more mammary tumors per mouse, whereas in the LID mice only 30% developed more than one mammary tumor per mouse. Our data demonstrate that circulating IGF-I levels play a significant role as a risk factor in the onset and development of mammary tumors in two well-established animal models of breast cancer.

  17. Determinants and consequences of insulin initiation for type 2 diabetes in France: analysis of the National Health and Wellness Survey

    PubMed Central

    Reach, Gérard; Le Pautremat, Véronique; Gupta, Shaloo

    2013-01-01

    Background The aim of the study was to identify the intrinsic patient characteristics and extrinsic environmental factors predicting prescription and use and, more specifically, early initiation (up to 5 years of disease duration) of insulin for type 2 diabetes in France. A secondary objective was to evaluate the impact of insulin therapy on mental and physical quality of life and patient adherence. Methods The data used in this study were derived from the 2008, 2010, and 2011 France National Health and Wellness Survey. This survey is an annual, cross-sectional, self-administered, Internet-based questionnaire among a nationwide representative sample of adults (aged 18 years or older). Of the total of 45,958 persons recruited in France, 1,933 respondents (deduped) were identified as diagnosed with type 2 diabetes. All unique respondents from the three waves, currently using insulin or oral bitherapy or tritherapy at the time of assessment, were included in this analysis. Results Early (versus late) initiation of insulin therapy was 9.9 times more likely to be prescribed by an endocrinologist or diabetologist than by a primary care physician (P < 0.0001). Younger age at diagnosis and current smoking habits were significant predictors of early (versus late) insulin initiation (odds ratio [OR] 1.031, 95% confidence interval [CI] 1.005–1.059, P = 0.0196, and OR 2.537, 95% CI 1.165–5.524, P = 0.0191, respectively). Patients with a yearly income ≥€50,000 were less likely to be put on insulin early (P = 0.0399). A link between insulin prescription and complications was shown only in univariate analysis. Mental quality of life was lower in patients on early (versus late) insulin, but only in patients with diabetes-related complications. Insulin users (versus oral bitherapy or tritherapy users) had 3.0 times greater odds of being adherent than uncontrolled oral bitherapy or tritherapy users (OR 2.983, 95% CI 1.37–6.495, P = 0.0059). Conclusion This study confirms

  18. Insulin initiation in primary care for patients with type 2 diabetes: 3-year follow-up study.

    PubMed

    Dale, Jeremy; Martin, Steven; Gadsby, Roger

    2010-07-01

    To evaluate the 3-year impact of initiating basal insulin on glycaemic control (HbA1c) and weight gain in patients with poorly controlled type 2 diabetes registered with UK general practices that volunteered to participate in an insulin initiation training programme. Audit utilising data collected from practice record systems, which included data at baseline, 3, 6 months and subsequent six-monthly intervals post-insulin initiation for up to 10 patients per participating practice. Of 115 eligible practices, 55 (47.8%) contributed data on a total of 516 patients. The mean improvement in HbA1c levels in the first 6 months was 1.4% (range -3.8% to 8.2%, median=1.40%). Thereafter, there was no overall change in HbA1c levels, although the change for individual patients ranged from -4.90% to +7.50%. At 36 months, 141 (41%) patients for whom data were provided had achieved the pre-2006/2007 UK Quality and Outcomes Framework (QOF) target of 7.4% or less, including 98 (29%) who had achieved an HbA1c of 7% or less. Patients who achieved target had a lower HbA1c at baseline (mean 9.1% compared to 9.7%; p<0.001); had a lower weight at 36 months (mean 88.0kg compared to 93.5kg; p=0.05); were more likely to be on basal insulin alone (88, 47.1% compared to 46, 34.6%; p<0.05); and were slightly older (mean 64.5 years compared to 61.7 years; p<0.05). Attending an insulin initiation training programme may successfully prepare primary healthcare professionals to initiate insulin therapy as part of everyday practice for patients with poorly controlled type 2 diabetes. The impact on glycaemic control is maintained over a 3-year period. Although intensification of treatment occurred during this period, the findings suggest scope for further intensification of insulin therapy in order to improve on the glycaemic control achieved during the first 6 months post-insulin initiation.

  19. Extensive intramuscular manifestation of sarcoidosis with initially missed diagnosis and delayed therapy: a case report.

    PubMed

    Meyer, Niklaus; Sutter, Reto; Schirp, Udo; Gutzeit, Andreas

    2017-08-24

    Sarcoidosis is a multisystemic granulomatous disorder, which in nearly all cases involves the lungs and other organs. Isolated forms of sarcoidosis within the muscles, but without lung involvement, are extremely rare and can lead to delayed or even false diagnosis. A 52-year-old white, Swiss man presented with painful arm cramps and a history of symptoms over the previous 3 years. In the initial clinical investigation, our patient also showed edema in both legs without any other complaints. After performing an magnetic resonance imaging scan of his extremities and a positron emission tomography/computed tomography scan, diffuse myositis was described. The subsequent muscle biopsy provided the surprising diagnosis of muscle sarcoidosis, without involvement of the lungs or any other organ. After starting therapy with glucocorticoids, his symptoms improved immediately. Sarcoidosis is a common disorder, which in most cases affects the lungs. In this case report an isolated sarcoidosis is described without lung involvement, but with involvement of the muscles of the extremities and the trunk. Reported cases of sarcoidosis only involving skeletal muscle and without lung involvement are extremely rare. Radiologists should consider this presentation of sarcoidosis to avoid delayed diagnosis and therapy.

  20. Delays before Diagnosis and Initiation of Treatment in Patients Presenting to Mental Health Services with Bipolar Disorder.

    PubMed

    Patel, Rashmi; Shetty, Hitesh; Jackson, Richard; Broadbent, Matthew; Stewart, Robert; Boydell, Jane; McGuire, Philip; Taylor, Matthew

    2015-01-01

    Bipolar disorder is a significant cause of morbidity and mortality. Although existing treatments are effective, there is often a substantial delay before diagnosis and treatment initiation. We sought to investigate factors associated with the delay before diagnosis of bipolar disorder and the onset of treatment in secondary mental healthcare. Retrospective cohort study using anonymised electronic mental health record data from the South London and Maudsley NHS Foundation Trust (SLaM) Biomedical Research Centre (BRC) Case Register on 1364 adults diagnosed with bipolar disorder between 2007 and 2012. The following predictor variables were analysed in a multivariable Cox regression analysis: age, gender, ethnicity, compulsory admission to hospital under the UK Mental Health Act, marital status and other diagnoses prior to bipolar disorder. The outcomes were time to recorded diagnosis from first presentation to specialist mental health services (the diagnostic delay), and time to the start of appropriate therapy (treatment delay). The median diagnostic delay was 62 days (interquartile range: 17-243) and median treatment delay was 31 days (4-122). Compulsory hospital admission was associated with a significant reduction in both diagnostic delay (hazard ratio 2.58, 95% CI 2.18-3.06) and treatment delay (4.40, 3.63-5.62). Prior diagnoses of other psychiatric disorders were associated with increased diagnostic delay, particularly alcohol (0.48, 0.33-0.41) and substance misuse disorders (0.44, 0.31-0.61). Prior diagnosis of schizophrenia and psychotic depression were associated with reduced treatment delay. Some individuals experience a significant delay in diagnosis and treatment of bipolar disorder after initiation of specialist mental healthcare, particularly those who have prior diagnoses of alcohol and substance misuse disorders. These findings highlight a need for further study on strategies to better identify underlying symptoms and offer appropriate treatment sooner

  1. Voluntary Exercise Impairs Initial Delayed Spatial Alternation Performance in Estradiol Treated Ovariectomized Middle-Aged Rats

    PubMed Central

    Neese, Steven L.; Korol, Donna L.; Schantz, Susan L.

    2013-01-01

    Estrogens differentially modulate behavior in the adult female rodent. Voluntary exercise can also impact behavior, often reversing age associated decrements in memory processes. Our research group has published a series of papers reporting a deficit in the acquisition of an operant working memory task, delayed spatial alternation (DSA), following 17β-estradiol treatment to middle-aged ovariectomized (OVX) rats. The current study examined if voluntary exercise could attenuate the 17β-estradiol induced deficits on DSA performance. OVX 12-month old Long- Evans rats were implanted with a Silastic capsule containing 17β-estradiol (10% in cholesterol: low physiological range) or with a blank capsule. A subset of the 17β-estradiol and OVX untreated rats were given free access to a running wheel in their home cage. All rats were tested for 40 sessions on the DSA task. Surprisingly, we found running wheel access to impair initial acquisition of the DSA task in 17β-estradiol treated rats, an effect not seen in OVX untreated rats given running wheel access. This deficit was driven by an increase in perseverative responding on a lever no longer associated with reinforcement. We also report for the first time a 17β-estradiol induced impairment on the DSA task following a long intertrial delay (18-sec), an effect revealed following more extended testing than in our previous studies (15 additional sessions). Overall, running wheel access increased initial error rate on the DSA task in 17β-estradiol treated middle-aged OVX rats, and failed to prevent the 17β-estradiol induced deficits in performance of the operant DSA task in later testing sessions. PMID:24013039

  2. Low BMD affects initial stability and delays stem osseointegration in cementless total hip arthroplasty in women

    PubMed Central

    2012-01-01

    Background and purpose Immediate implant stability is a key factor for success in cementless total hip arthroplasty (THA). Low bone mineral density (BMD) and age-related geometric changes of the proximal femur may jeopardize initial stability and osseointegration. We compared migration of hydroxyapatite-coated femoral stems in women with or without low systemic BMD. Patients and methods 61 female patients with hip osteoarthritis were treated with cementless THA with anatomically designed hydroxyapatite-coated femoral stems and ceramic-ceramic bearing surfaces (ABG-II). Of the 39 eligible patients between the ages of 41 and 78 years, 12 had normal systemic BMD and 27 had osteopenia or osteoporosis. According to the Dorr classification, 21 had type A bone and 18 had type B. Translational and rotational migration of the stems was evaluated with radiostereometric analysis (RSA) up to 2 years after surgery. Results Patients with low systemic BMD showed higher subsidence of the femoral stem during the first 3 months after surgery than did those with normal BMD (difference = 0.6, 95% CI: 0.1–1.1; p = 0.03). Low systemic BMD (odds ratio (OR) = 0.1, CI: 0.006–1.0; p = 0.02), low local hip BMD (OR = 0.3, CI: 0.1–0.7; p = 0.005) and ageing (OR = 1.1, CI: 1.0–1.2; p = 0.02) were risk factors for delayed translational stability. Ageing and low canal flare index were risk factors for delayed rotational stabilization (OR = 3, CI: 1.1–9; p = 0.04 and OR = 1.1, CI: 1.0–1.2; p = 0.02, respectively). Harris hip score and WOMAC score were similar in patients with normal systemic BMD and low systemic BMD. Interpretation Low BMD, changes in intraosseous dimensions of the proximal femur, and ageing adversely affected initial stability and delayed osseointegration of cementless stems in women. PMID:22489886

  3. [Determinants of the cost of initiation of insulin therapy type 2 diabetic patients in France: possible approaches to optimization].

    PubMed

    Hanaire, Hélène; Attali, Claude; Lecointre, Brigitte; Fraysse, Martial; Gouet, Didier; Babel, Marie-Renée; Charbonnel, Bernard; Sarkozy, François; Gourmelen, Julie; Detournay, Bruno

    2016-12-19

    Increased costs cannot be exclusively attributed to the consequences of insulin prescription. Any initiative designed to accelerate acquisition of patient autonomy would be likely to reduce the costs observed after switching to insulin, provided this initiative is adapted to the patient’s health profile, diabetes history and available medical resources..

  4. Predictors on Delay of Initial Health-Seeking in New Pulmonary Tuberculosis Cases among Migrants Population in East China

    PubMed Central

    Li, Xinxu; Jiang, Shiwen; Li, Xue; Mei, Jian; Zhong, Qiu; Xu, Weiguo; Li, Jun; Li, Weibin; Liu, Xiaoqiu; Zhang, Hui; Wang, Lixia

    2012-01-01

    Objectives To determine the length of delay in initial health-seeking in new pulmonary tuberculosis (PTB) cases among migrant population in the eastern part of China, and factors associated with it. Methods A cross-sectional study was conducted using a structured questionnaire in six counties in Shanghai, Guangdong and Jiangsu from May to October, 2008, to estimate the extent and factors responsible for delayed initial health-seeking of the new PTB cases. The interval between self-reported onset of TB symptoms and date of first attendance at any medical institution was determined. More than the median duration was defined as delayed health-seeking. Results A total of 323 new migrant PTB patients participated in the study. Only 6.5% had medical insurance. The median and mean durations to initial health-seeking were respectively 10 and 31 days. There was no significant association between socio-demographic factors and delayed initial health-seeking. Average monthly working days >24 (AOR, 1.61; 95% CI, 1.03–2.51), and hemoptysis or bloody sputum (AOR, 0.48; 95% CI, 0.28–0.85) were significantly associated with delayed initial health-seeking. Conclusions Interventions to improve health seeking behavior among the migrant population in China must focus on strengthening their labor, medical security and health education. PMID:22384123

  5. Insulin stimulates muscle protein synthesis in neonates during endotoxemia despite repression of translation initiation

    USDA-ARS?s Scientific Manuscript database

    Skeletal muscle protein synthesis is reduced in neonatal pigs in response to endotoxemia. To examine the role of insulin in this response, neonatal pigs were infused with endotoxin (LPS, 0 and 10 µg•kg(-1)•h(-1)), whereas glucose and amino acids were maintained at fasting levels and insulin was clam...

  6. LC-MS/MS analysis of plasma polyunsaturated fatty acids in type 2 diabetic patients after insulin analog initiation therapy

    PubMed Central

    2013-01-01

    Background Eicosanoids derived from omega-6 (n6) polyunsaturated fatty acids (PUFAs) have proinflammatory functions whereas eicosanoids derived from omega-3 (n3) PUFAs have anti-inflammatory properties. This study was designed to evaluate the effect of insulin analog initiation therapy on n6 and n3 PUFAs in type 2 diabetic patients during early phase. Methods Sixteen type 2 diabetic patients with glycosylated hemoglobin (HbA1c) levels above 10% despite ongoing combination therapy with sulphonylurea and metformin were selected. Former treatment regimen was continued for the first day followed by substitution of sulphonylurea therapy with different insulin analogs (0.4 U/kg/day) plus metformin. Blood samples were obtained from all patients at 24 and 72 hours. Plasma levels of arachidonic acid (AA, C20:4n6), dihomo-gamma-linolenic acid (DGLA, C20:3n6), eicosapentaenoic acid (EPA, C20:5n3) and docosahexaenoic acid (DHA, C22:6n3) were determined by an optimized multiple reaction monitoring (MRM) method using ultra fast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Prostaglandin E2 (PGE2) was measured in serum samples by enzyme immunoassay. Results All measured PUFAs were significantly increased after treatment with insulin analogs plus metformin compared to before treatment levels. The mean AA/EPA ratio was significantly lower after treatment with insulin analogs plus metformin. A 22% decrease was observed in PGE2 levels after treatment with insulin analogs plus metformin compared to pretreatment levels (p > 0.05). Conclusion The significant decrease in AA/EPA ratio indicates that insulin analog initiation therapy has anti-inflammatory properties by favoring the increase of n3 fatty acid EPA. PMID:24195588

  7. Initiation of Basal Insulin Analog Treatment for Type 2 Diabetes and Reasons Behind Patients' Treatment Persistence Behavior: Real-World Data from Germany.

    PubMed

    Moennig, Elisabeth; Perez-Nieves, Magaly; Hadjiyianni, Irene; Cao, Dachuang; Ivanova, Jasmina; Klask, Ralf

    2017-09-11

    Background Poor treatment persistence can affect the real-world effectiveness of insulin therapy. A cross-sectional online survey in 942 patients with type 2 diabetes from 7 different countries evaluated patient experience when initiating basal insulin and the reasons behind insulin persistence patterns. Here, we report the quantitative results for the subset of patients from Germany. Methods Adults with type 2 diabetes who had initiated basal insulin during the last 3-24 months, identified from market-research panels, participated in the survey. Patients were asked if they had ≥7-day gaps in basal insulin treatment, and were then classified as "continuers" (no gap since starting insulin), "interrupters" (≥1 gap within the first 6 months after starting insulin and subsequently restarted insulin), or "discontinuers" (stopped insulin within the first 6 months after starting and had not restarted at the time of the survey). For each country, 50 participants were planned per persistence category. Enrollment ended if the target quota was reached or enrollment plateaued. Data were analyzed overall and separately for each persistence cohort. Results The 131 participants from Germany included 55 (42.0%) continuers, 50 (38.2%) interrupters and 26 (19.9%) discontinuers. The most common motivations to initiate basal insulin therapy were encouragement by physician or other healthcare provider (HCP; 54.2%) and expectation to improve glycemic control (42.0%). More than 95% of participants received training before and during insulin initiation (considered as helpful by 81.7%); most (67.2%) preferred in-person training. Continuers more frequently felt that insulin would help to manage diabetes and that their own views were considered when initiating insulin, they reported less concerns and challenges before and during insulin initiation than interrupters or discontinuers. The most common motivations to continue basal insulin were improved glycemic control (72.7%), improved

  8. Initiation of delayed hydride cracking in zirconium-niobium micro pressure tubes

    NASA Astrophysics Data System (ADS)

    Sundaramoorthy, Ravi Kumar

    Pressure tubes pick up hydrogen while they are in service within CANDU reactors. Sufficiently high hydrogen concentration can lead to hydride precipitation during reactor shutdown/repair at flaws, resulting in the potential for eventual rupture of the pressure tubes by a process called Delayed Hydride Cracking (DHC). The threshold stress intensity factor (KIH) below which the cracks will not grow by delayed hydride cracking of Zr-2.5Nb micro pressure tubes (MPTs) has been determined using a load increasing mode (LIM) method at different temperatures. MPTs have been used to allow easy study of the impact of properties like texture and grain size on DHC. Previous studies on MPTs have focused on creep and effects of stress on hydride orientation; here the use of MPTs for DHC studies is confirmed for the first time. Micro pressure tube samples were hydrided to a target hydrogen content of 100 ppm using an electrolytic method. For DHC testing, 3 mm thick half ring samples were cut out from the tubes using Electrical Discharge Machining (EDM) with a notch at the center. A sharp notch with a root radius of 15 microm was introduced by broaching to facilitate crack initiation. The direct current potential drop method was used to monitor crack growth during the DHC tests. For the temperature range tested the threshold stress intensity factors for the micro pressure tube used were found to be 6.5--10.5 MPa.m 1/2 with the value increasing with increasing temperature. The average DHC velocities obtained for the three different test temperatures 180, 230 and 250°C were 2.64, 10.87 and 8.45 x 10-8 m/s, respectively. The DHC data obtained from the MPTs are comparable to the data published in the literature for full sized CANDU pressure tubes.

  9. [Prospective observational study of insulin detemir in patients with poorly controlled type 2 diabetes mellitus initiating insulin therapy for the first time (SOLVE Study)].

    PubMed

    Orozco-Beltrán, Domingo; Artola-Menéndez, Sara

    2016-02-01

    Describe the experience in the primary care setting with insulin detemir in patients with poorly controlled type2 diabetes mellitus that need to add-on insulin to their oral antidiabetic drug therapy. Prospective observational study of 6 months of follow up, performed in 10 countries. In Spain, participating sites were only from the primary care setting. Eligible patients were those with poorly controlled type2 diabetes mellitus adding-on once-daily insulin detemir to their existing oral antidiabetic therapy in the month prior to their enrollment. The change of Hb1Ac and of weight at the end of the study and the incidence of hypoglycemia and adverse reactions, were analyzed. We report the results obtained in the Spanish cohort. Overall 17,374 patients were included, 973 in Spain [mean age 64.8 years (SE 12); duration of diabetes 9.4 years (SE 6.2); Hb1Ac 8.9% (DE 1.4)]. In the sample analyzed for efficacy (n=474) the mean change of Hb1Ac was -1.6% (95%CI: -1.75 to -1.42; P<.001), mean change of weight was -2.9 kg (95%CI: -3.72 to -2.08; P<.001). Only one episode of severe hypoglycemia was reported, which was also the only serious adverse reaction reported in the study. The incidence rate of non-severe hypoglycemia was 2.44 events/patient-year. In this cohort of patients with type 2 diabetes mellitus receiving newly initiated insulin therapy, once-daily detemir improved the glycemic control, with low incidence of hypoglycemia and a significant reduction of the weight. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  10. Clinical characteristics of patients with type 2 diabetes mellitus at the time of insulin initiation: INSTIGATE observational study in Spain

    PubMed Central

    Dilla, Tatiana; Reviriego, Jesús; Castell, Conxa; Goday, Albert

    2009-01-01

    Little information is available on the management of patients with type 2 diabetes mellitus (DM2) in regular clinical practice, prior to and at the point of initiating treatment with insulin. The INSTIGATE study provides a description of the clinical profile of the patient with DM2 who begins treatment with insulin in both primary and secondary care. A total of 224 patients who had been diagnosed with DM2, were not responding to oral treatment, and began receiving insulin were included in the INSTIGATE study in Spain. Demographic data were collected, as well as data on macro- and microvascular complications of diabetes and comorbidities, past medical history of diabetes and oral treatment administered, the clinical severity of diabetes (HbA1c concentration) and insulin treatment initiated. Mean age of the sample was 65.4 years and 56.7% were men. There were 87% of patients who had a diagnosis of at least one significant comorbidity, notably hypertension and hyperlipidemia. The patient profile for metabolic syndrome was met by 75.1% of the patients. There was a higher incidence of macrovascular complications (38.4%) than microvascular complications (16.1%). Prior to insulin initiation, the most recent mean HbA1c was 9.2%. The majority of patients had been treated in the last 12 months with sulfonylureas and/or metformin (69.6 and 57.6%). The most common treatment prior to insulinization was the co-administration of two oral antidiabetics (OADs) (37.5%). Patients with DM2 observed in the study presented with elevated mean HbA1c and body mass index levels, comorbidities and complications related to diabetes at the time of insulin initiation. Changes and adjustments in treatment from diagnosis of diabetes occur when HbA1c levels are far above those recommended by the IDF (International Diabetes Federation), a factor which could be contributing to the development of both macrovascular and microvascular complications in the patient profile described in the study. PMID

  11. Insulin Resistance and Risk of Cardiovascular Disease in Postmenopausal Women: A Cohort Study From the Women's Health Initiative.

    PubMed

    Schmiegelow, Michelle D; Hedlin, Haley; Stefanick, Marcia L; Mackey, Rachel H; Allison, Matthew; Martin, Lisa W; Robinson, Jennifer G; Hlatky, Mark A

    2015-05-01

    Insulin resistance is associated with diabetes mellitus, but it is uncertain whether it improves cardiovascular disease (CVD) risk prediction beyond traditional cardiovascular risk factors. We identified 15,288 women from the Women's Health Initiative Biomarkers studies with no history of CVD, atrial fibrillation, or diabetes mellitus at baseline (1993-1998). We assessed the prognostic value of adding fasting serum insulin, HOMA-IR (homeostasis model assessment-insulin resistance), serum-triglyceride-to-serum-high-density lipoprotein-cholesterol ratio TG/HDL-C, or impaired fasting glucose (serum glucose ≥110 mg/dL) to traditional risk factors in separate Cox multivariable analyses and assessed risk discrimination and reclassification. The study end point was major CVD events (nonfatal and fatal coronary heart disease and ischemic stroke) within 10 years, which occurred in 894 (5.8%) women. Insulin resistance was associated with CVD risk after adjusting for age and race/ethnicity with hazard ratios (95% confidence interval [CI]) per doubling in insulin of 1.21 (CI, 1.12-1.31), in HOMA-IR of 1.19 (CI, 1.11-1.28), in TG/HDL-C of 1.35 (CI, 1.26-1.45), and for impaired fasting glucose of 1.31 (CI, 1.05-1.64). Although insulin, HOMA-IR, and TG/HDL-C remained associated with increased CVD risk after adjusting for most CVD risk factors, none remained significant after adjusting for HDL-C: hazard ratios for insulin, 1.06 (CI, 0.98-1.16); for HOMA-IR, 1.06 (CI, 0.98-1.15); for TG/HDL-C, 1.11 (CI, 0.99-1.25); and for glucose, 1.20 (CI, 0.96-1.50). Insulin resistance measures did not improve CVD risk discrimination and reclassification. Measures of insulin resistance were no longer associated with CVD risk after adjustment for high-density lipoprotein-cholesterol and did not provide independent prognostic information in postmenopausal women without diabetes mellitus. URL: http://www.clinicaltrial.gov. Unique identifier: NCT00000611. © 2015 American Heart Association, Inc.

  12. A real-world study of patients with type 2 diabetes initiating basal insulins via disposable pens.

    PubMed

    Xie, Lin; Wei, Wenhui; Pan, Chunshen; Du, Juan; Baser, Onur

    2011-11-01

    Real-world data comparing outcomes of type 2 diabetes mellitus (T2DM) patients initiating different insulin regimens can help with treatment decisions and patient management. Clinical and economic outcomes following initiation with insulin glargine disposable pen (GLA-P) or insulin detemir disposable pen (DET-P) in T2DM patients were compared over 1-year follow-up. This retrospective cohort analysis was conducted on data in a US national managed care claims database (July 2006 to September 2010) from patients initiating insulin treatment with GLA-P or DET-P. Treatment persistence, adherence, glycated hemoglobin (A1C), hypoglycemic events, and healthcare costs during follow-up were compared. In all, 1682 patients were identified; 1016 (60.4%) started using GLA-P, 666 (39.6%) started using DET-P. After 1:1 propensity score matching, each cohort comprised 640 patients. Patients initiating GLA-P were significantly more likely to persist and adhere to treatment, and used a lower daily consumption dose. Over the last quarter of follow-up, fewer GLA-P users switched to DET-P compared with those switching from DET-P to GLA-P. GLA-P was associated with lower A1C levels and higher reduction of A1C levels from baseline, with no significant difference in the number of patients having hypoglycemic events. Patients in both cohorts had similar total and diabetes-related healthcare costs, but healthcare costs were lower in the GLA-P cohort for each 1% reduction in A1C from baseline. This real-world study demonstrates that patients initiating GLA-P were more likely to persist with and adhere to treatment, with better glycemic control and similar overall hypoglycemia rate at no increase in healthcare cost.

  13. Comparison Between Individually and Group-Based Insulin Pump Initiation by Time-Driven Activity-Based Costing.

    PubMed

    Ridderstråle, Martin

    2017-07-01

    Depending on available resources, competencies, and pedagogic preference, initiation of insulin pump therapy can be performed on either an individual or a group basis. Here we compared the two models with respect to resources used. Time-driven activity-based costing (TDABC) was used to compare initiating insulin pump treatment in groups (GT) to individual treatment (IT). Activities and cost drivers were identified, timed, or estimated at location. Medical quality and patient satisfaction were assumed to be noninferior and were not measured. GT was about 30% less time-consuming and 17% less cost driving per patient and activity compared to IT. As a batch driver (16 patients in one group) GT produced an upward jigsaw-shaped accumulative cost curve compared to the incremental increase incurred by IT. Taking the alternate cost for those not attending into account, and realizing the cost of opportunity gained, suggested that GT was cost neutral already when 5 of 16 patients attended, and that a second group could be initiated at no additional cost as the attendance rate reached 15:1. We found TDABC to be effective in comparing treatment alternatives, improving cost control and decision making. Everything else being equal, if the setup is available, our data suggest that initiating insulin pump treatment in groups is far more cost effective than on an individual basis and that TDABC may be used to find the balance point.

  14. Delayed Presentation of Ureteropelvic Junction Obstruction and Loss of Renal Function After Initially Mild (SFU Grade 1-2) Hydronephrosis.

    PubMed

    Bowen, Diana K; Yerkes, Elizabeth B; Lindgren, Bruce W; Gong, Edward M; Faasse, Mark A

    2015-07-01

    We report 4 pediatric cases of ureteropelvic junction obstruction involving delayed progression of initially mild postnatal hydronephrosis. All 4 children became symptomatic; however, 3 already had a substantial decrement of ipsilateral kidney function by the time of diagnosis. Two of these 3 patients had previous renal scintigraphy demonstrating normal differential function. We caution that counseling regarding hydronephrosis should emphasize the importance of prompt re-evaluation for any symptoms potentially referable to delayed presentation of ureteropelvic junction obstruction, irrespective of initial hydronephrosis grade. Future studies are needed to determine the optimal follow-up regimen for conservative management of hydronephrosis.

  15. New developments in insulin therapy for type 2 diabetes.

    PubMed

    Sorli, Christopher

    2014-10-01

    Insulin has classically been considered a treatment of last resort for individuals with type 2 diabetes, delayed until all other efforts by the patient and healthcare provider have failed. Recent treatment guidelines recommend the use of insulin, in particular basal insulin, as part of a treatment regimen earlier in the disease process. Many patients are reticent about initiating insulin, so therapies that allow insulin treatment to be more tailored to individual needs are likely to result in greater acceptance and patient adherence with therapy. To meet this need, a range of insulin products are in development that aim to increase absorption rate or prolong the duration of action, reduce peak variability and weight gain associated with insulin treatment, and offer alternative delivery methods. This review describes insulin products in clinical development, new combination therapies, and new devices for insulin delivery.

  16. Can community retail pharmacist and diabetes expert support facilitate insulin initiation by family physicians? Results of the AIM@GP randomized controlled trial.

    PubMed

    Harris, Stewart B; Gerstein, Hertzel C; Yale, Jean-François; Berard, Lori; Stewart, John; Webster-Bogaert, Susan; Tompkins, Jordan W

    2013-02-21

    Limited evidence exists on the effectiveness of external diabetes support provided by diabetes specialists and community retail pharmacists to facilitate insulin-prescribing in family practice. A stratified, parallel group, randomized control study was conducted in 15 sites across Canada. Family physicians received insulin initiation/titration education, a physician-specific 'report card' on the characteristics of their type 2 diabetes (T2DM) population, and a registry of insulin-eligible patients at a workshop. Intervention physicians in addition received: (1) diabetes specialist/educator consultation support (active diabetes specialist/educator consultation support for 2 months [the educator initiated contact every 2 weeks] and passive consultation support for 10 months [family physician initiated as needed]); and (2) community retail pharmacist support (option to refer patients to the pharmacist(s) for a 1-hour insulin-initiation session). The primary outcome was the insulin prescribing rate (IPR) per physician defined as the number of insulin starts of insulin-eligible patients during the 12-month strategy. Consenting, eligible physicians (n = 151) participated with 15 specialist sites and 107 community pharmacists providing the intervention. Most physicians were male (74%), and had an average of 81 patients with T2DM. Few (9%) routinely initiated patients on insulin. Physicians were randomly allocated to usual care (n = 78) or the intervention (n = 73). Intervention physicians had a mean (SE) IPR of 2.28 (0.27) compared to 2.29 (0.25) for control physicians, with an estimated adjusted RR (95% CI) of 0.99 (0.80 to 1.24), p = 0.96. An insulin support program utilizing diabetes experts and community retail pharmacists to enhance insulin prescribing in family practice was not successful. Too few physicians are appropriately intensifying diabetes management through insulin initiation, and aggressive therapeutic treatment is lacking.

  17. The effects of peer-play level on initiations and responses of preschool children with delayed play skills.

    PubMed

    Tanta, Kari J; Deitz, Jean C; White, Owen; Billingsley, Felix

    2005-01-01

    The potential impact of peer-play opportunities on the overall development of young children has been well-documented in the social development, occupational therapy, and special education literature. However, the effect of peer characteristics on the manifestation and facilitation of specific types of play roles and behaviors has received little attention. This topic is of key importance to occupational therapists who are striving to develop interventions that enhance the development of social participation and play in preschool children. The purpose of this study was to examine the differences in initiation and response exhibited by preschool-aged children with social-play delays when participating in free-play dyads with peers of differing developmental levels. A single-subject alternating treatments design was replicated across five preschool-aged children with developmental play delays. Each child was paired with one peer who had lower developmental play skills and one peer who had higher developmental play skills. The arranged dyads were given the opportunity to play together in a specially designed playroom at their school. Their interactions were videotaped and later coded. All five children generally showed more initiation and response to initiation during play with higher-level peers, although one participant showed less differentiation for initiation than the other four children. An occupational therapist working with a preschool child with play delays and wanting to facilitate the child's initiation and response in play situations should consider pairing the child with play delays with a child who has higher play skills.

  18. Insulin allergy.

    PubMed

    Ghazavi, Mohammad K; Johnston, Graham A

    2011-01-01

    Insulin reactions occur rarely but are of tremendous clinical importance. The first was reported in 1922 as a callus reaction at the injection site of insufficiently purified bovine insulin. Porcine insulin was subsequently found to be less allergenic than bovine insulin. Increasingly pure insulins have decreased the risk of adverse reactions, and the production of recombinant insulin with the same amino sequence as human insulin saw a large decrease in adverse reactions. Currently, the prevalence of allergic reactions to insulin products appears to be approximately 2%, and less than one-third of these events have been considered related to the insulin itself. Other reactions occur due to the preservatives added to insulin, including zinc, protamine, and meta-cresol. Allergic reactions can be type I or immunoglobulin E-mediated, type III or Arthus, and type IV or delayed-type hypersensitivity reactions. Type I reactions are the most common and can, rarely, cause anaphylaxis. In contrast, type IV reactions can occur after a delay of several days. Investigations include skin prick testing, patch testing, intradermal testing, and occasionally, skin biopsy.

  19. Heterotypic endosomal fusion as an initial trigger for insulin-induced glucose transporter 4 (GLUT4) translocation in skeletal muscle.

    PubMed

    Hatakeyama, Hiroyasu; Kanzaki, Makoto

    2017-08-15

    Comprehensive imaging analyses of glucose transporter 4 (GLUT4) behaviour in mouse skeletal muscle was conducted. Quantum dot-based single molecule nanometry revealed that GLUT4 molecules in skeletal myofibres are governed by regulatory systems involving 'static retention' and 'stimulus-dependent liberation'. Vital imaging analyses and super-resolution microscopy-based morphometry demonstrated that insulin liberates the GLUT4 molecule from its static state by triggering acute heterotypic endomembrane fusion arising from the very small GLUT4-containing vesicles in skeletal myofibres. Prior exposure to exercise-mimetic stimuli potentiated this insulin-responsive endomembrane fusion event involving GLUT4-containing vesicles, suggesting that this endomembranous regulation process is a potential site related to the effects of exercise. Skeletal muscle is the major systemic glucose disposal site. Both insulin and exercise facilitate translocation of the glucose transporter glucose transporter 4 (GLUT4) via distinct signalling pathways and exercise also enhances insulin sensitivity. However, the trafficking mechanisms controlling GLUT4 mobilization in skeletal muscle remain poorly understood as a resuly of technical limitations. In the present study, which employs various imaging techniques on isolated skeletal myofibres, we show that one of the initial triggers of insulin-induced GLUT4 translocation is heterotypic endomembrane fusion arising from very small static GLUT4-containing vesicles with a subset of transferrin receptor-containing endosomes. Importantly, pretreatment with exercise-mimetic stimuli potentiated the susceptibility to insulin responsiveness, as indicated by these acute endomembranous activities. We also found that AS160 exhibited stripe-like localization close to sarcomeric α-actinin and that insulin induced a reduction of the stripe-like localization accompanying changes in its detergent solubility. The results of the present study thus provide a

  20. Adding Once-Daily Lixisenatide for Type 2 Diabetes Inadequately Controlled With Newly Initiated and Continuously Titrated Basal Insulin Glargine

    PubMed Central

    Riddle, Matthew C.; Forst, Thomas; Aronson, Ronnie; Sauque-Reyna, Leobardo; Souhami, Elisabeth; Silvestre, Louise; Ping, Lin; Rosenstock, Julio

    2013-01-01

    OBJECTIVE When oral therapy for type 2 diabetes is ineffective, adding basal insulin improves glycemic control. However, when glycated hemoglobin (HbA1c) remains elevated because of postprandial hyperglycemia, the next therapeutic step is controversial. We examined the efficacy and safety of lixisenatide in patients with HbA1c still elevated after initiation of insulin glargine. RESEARCH DESIGN AND METHODS This double-blind, parallel-group trial enrolled patients with HbA1c 7–10% despite oral therapy. Insulin glargine was added and systematically titrated during a 12-week run-in, after which candidates with fasting glucose ≤7.8 mmol/L and HbA1c 7–9% were randomized to lixisenatide 20 µg or placebo for 24 weeks while insulin titration continued. The primary end point was HbA1c change after randomization. RESULTS The randomized population (n = 446) had mean diabetes duration of 9.2 years, BMI 31.8 kg/m2, and daily glargine dosage of 44 units. HbA1c had decreased during run-in from 8.6 to 7.6%; adding lixisenatide further reduced HbA1c by 0.71 vs. 0.40% with placebo (least squares mean difference, –0.32%; 95% CI, –0.46 to –0.17; P < 0.0001). More participants attained HbA1c <7% with lixisenatide (56 vs. 39%; P < 0.0001). Lixisenatide reduced plasma glucose 2 h after a standardized breakfast (difference vs. placebo –3.2 mmol/L; P < 0.0001) and had a favorable effect on body weight (difference vs. placebo –0.89 kg; P = 0.0012). Nausea, vomiting, and symptomatic hypoglycemia <3.3 mmol/L were more common with lixisenatide. CONCLUSIONS Adding lixisenatide to insulin glargine improved overall and postprandial hyperglycemia and deserves consideration as an alternative to prandial insulin for patients not reaching HbA1c goals with recently initiated basal insulin. PMID:23564915

  1. Initial uptake and insulin releasing action of chloromercuribenzene-p-sulphonic acid (CMBS) in suspensions of pancreatic islet cells.

    PubMed

    Idahl, L A; Lernmark, A; Söderberg, M; Winblad, B

    1980-04-01

    The effects of chloromercuribenzene-p-sulphonic acid on dispersed cells prepared from beta-cell-rich ob/ob-mouse islets were studied. 1) Chloromercuribenzene-p-sulphonic acid at concentrations of 0.1 mmol/l or higher diminished cell viability which was partially counteracted by increasing concentrations of bovine serum albumin. 2) The uptake of 203Hg-chloromercuribenzene-p-sulphonic acid after incubation for 4 seconds or longer showed that most of the non-toxic concentrations of chloromercuribenzene-p-sulphonic acid was bound to the cell within 40 seconds. Maximal uptake was achieved after 3 minutes of incubation. The uptake of radioactive chloromercuribenzene-p-sulphonic acid was inhibited by bovine serum albumin. 3) The dynamics of insulin release from perifused dispersed beta-cells embedded in fibrin showed a maximal 40--50-fold stimulation by 0.03 mmol/l chloromercuribenzene-p-sulphonic acid within 10 minutes of perifusion. 4) Scanning electron microscopy of beta-cells revealed no major changes in the cell surface under conditions of maximal binding and insulin releasing effects of chloromercuribenzene-p-sulphonic acid. These data support the concept that the ability of chloromercuribenzene-p-sulphonic acid to induce insulin release is related to its initial binding to the beta-cell surface. The binding of chloromercuribenzene-p-sulphonic acid and the subsequent release of insulin seem to occur without major changes in beta-cell surface morphology.

  2. Inoculation against Forgetting: Advantages of Immediate versus Delayed Initial Testing Due to Superior Verbatim Accessibility

    ERIC Educational Resources Information Center

    Pansky, Ainat

    2012-01-01

    In this study, potential benefits of early memory testing were examined in terms of "inoculating" eyewitness memory against forgetting. As predicted by fuzzy trace theory (e.g., Reyna & Titcomb, 1997), a larger testing advantage in the delayed recall of event details was expected after immediate testing than after delayed testing…

  3. Inoculation against Forgetting: Advantages of Immediate versus Delayed Initial Testing Due to Superior Verbatim Accessibility

    ERIC Educational Resources Information Center

    Pansky, Ainat

    2012-01-01

    In this study, potential benefits of early memory testing were examined in terms of "inoculating" eyewitness memory against forgetting. As predicted by fuzzy trace theory (e.g., Reyna & Titcomb, 1997), a larger testing advantage in the delayed recall of event details was expected after immediate testing than after delayed testing…

  4. Delays before Diagnosis and Initiation of Treatment in Patients Presenting to Mental Health Services with Bipolar Disorder

    PubMed Central

    Patel, Rashmi; Shetty, Hitesh; Jackson, Richard; Broadbent, Matthew; Stewart, Robert; Boydell, Jane; McGuire, Philip; Taylor, Matthew

    2015-01-01

    Background Bipolar disorder is a significant cause of morbidity and mortality. Although existing treatments are effective, there is often a substantial delay before diagnosis and treatment initiation. We sought to investigate factors associated with the delay before diagnosis of bipolar disorder and the onset of treatment in secondary mental healthcare. Method Retrospective cohort study using anonymised electronic mental health record data from the South London and Maudsley NHS Foundation Trust (SLaM) Biomedical Research Centre (BRC) Case Register on 1364 adults diagnosed with bipolar disorder between 2007 and 2012. The following predictor variables were analysed in a multivariable Cox regression analysis: age, gender, ethnicity, compulsory admission to hospital under the UK Mental Health Act, marital status and other diagnoses prior to bipolar disorder. The outcomes were time to recorded diagnosis from first presentation to specialist mental health services (the diagnostic delay), and time to the start of appropriate therapy (treatment delay). Results The median diagnostic delay was 62 days (interquartile range: 17–243) and median treatment delay was 31 days (4–122). Compulsory hospital admission was associated with a significant reduction in both diagnostic delay (hazard ratio 2.58, 95% CI 2.18–3.06) and treatment delay (4.40, 3.63–5.62). Prior diagnoses of other psychiatric disorders were associated with increased diagnostic delay, particularly alcohol (0.48, 0.33–0.41) and substance misuse disorders (0.44, 0.31–0.61). Prior diagnosis of schizophrenia and psychotic depression were associated with reduced treatment delay. Conclusions Some individuals experience a significant delay in diagnosis and treatment of bipolar disorder after initiation of specialist mental healthcare, particularly those who have prior diagnoses of alcohol and substance misuse disorders. These findings highlight a need for further study on strategies to better identify

  5. Study of Once Daily Levemir (SOLVE™): insights into the timing of insulin initiation in people with poorly controlled type 2 diabetes in routine clinical practice.

    PubMed

    Khunti, K; Damci, T; Meneghini, L; Pan, C Y; Yale, J-F

    2012-07-01

    The aim of this analysis is to determine the timing of insulin initiation in routine clinical practice, especially in relation to glycaemic control and use of oral antidiabetic drugs (OADs). Study of Once Daily Levemir was a 24-week international observational study involving 10 countries which evaluated the safety and effectiveness of initiating once-daily insulin detemir in people with type 2 diabetes mellitus (T2DM) being treated with one or more OADs (clinical trial number NCT00825643 and NCT00740519). A total of 17 374 participants were enrolled in the study: aged 62 ± 12 years, 53% male, T2DM duration 10 ± 7 years, body mass index 29.3 ± 5.4 kg/m(2) . Pre-insulin HbA1c was 8.9 ± 1.6%. The proportion of patients with HbA1c ≥9.0% ranged from 64% (UK) to 23% (Poland). Pre-insulin OAD treatment included metformin (81%), sulphonylureas (59%), glinides (16%), thiazolidinediones (TZD) (12%), α-glucosidase inhibitors (12%) and dipeptidyl peptidase (DPP)-IV inhibitors (7%). The mean starting dose of insulin detemir for the total cohort was 0.16 ± 0.09 U/kg. Differences in OAD use and insulin doses at initiation were evident among participating countries. The largest proportional changes in OAD prescribing at insulin initiation were seen with glinides (+15%), sulphonylureas (-19%), TZD (-31%) and DPP-IV inhibitors (-28%). Despite well-documented benefits of timely glycaemic control and consensus guidelines encouraging earlier use of insulin, considerable clinical inertia exists with respect to initiating appropriate insulin therapy in people with T2DM. Considerable regional differences exist in the timing of insulin initiation and in the use of OADs. © 2012 Blackwell Publishing Ltd.

  6. Increasing Patient Acceptance and Adherence Toward Insulin.

    PubMed

    Riddle, Matthew; Peters, Anne; Funnell, Martha

    2016-10-01

    Because of the progressive nature of type 2 diabetes mellitus (T2DM), the majority of patients will need insulin to achieve and maintain glycemic control. By maintaining glycemic control, patients will avoid acute osmotic symptoms of hyperglycemia, instability in plasma glucose (PG) over time, and prevent or delay the development of diabetes complications without adversely affecting quality of life. Despite recommendations for initiating insulin therapy, both patient and health system barriers stand in the way. To develop confidence in individualizing patient therapy and maximize outcomes for patients with T2DM, healthcare practitioners (HCPs) were updated on recommendations and clinical evidence supporting when to initiate insulin therapy, strategies for overcoming provider and patient barriers for initiating insulin therapy, and the safety and efficacy of current and emerging insulin therapy and delivery technology for patients with T2DM.

  7. Challenges associated with insulin therapy in type 2 diabetes mellitus.

    PubMed

    Edelman, Steven; Pettus, Jeremy

    2014-10-01

    Despite advances in treatment for type 2 diabetes in recent decades, many patients are failing to achieve adequate glycemic control. Poor glycemic control has been shown to have a detrimental effect on patients' health and well-being, and to have significant negative financial implications for both patients and healthcare systems. Insulin therapy has been proven to significantly reduce glycated hemoglobin levels; however, both patients and physicians can be reluctant to initiate insulin therapy. Research shows that both patient and provider factors contribute to a delay in initiation of insulin therapy. This review discusses the most common barriers contributing to this delay with potential solutions to overcome them.

  8. Initial experience and evaluation of reusable insulin pen devices among patients with diabetes in emerging countries.

    PubMed

    Tschiedel, Balduino; Almeida, Oscar; Redfearn, Jennifer; Flacke, Frank

    2014-12-01

    Many individuals with type 2 diabetes in emerging countries are transitioning from vial-and-syringe insulin delivery to that of insulin pens (disposable or reusable). As with all insulin delivery methods, patient preferences and comfort are of utmost importance to optimize adherence to treatment. Patient-preferred characteristics for reusable insulin pens and barriers to appropriate injection, particularly in these regions, have not been widely reported in the clinical literature, highlighting a key information gap for clinicians considering these methods as part of a comprehensive diabetes management approach. Face-to-face interviews were conducted with people with type 1/2 diabetes, including insulin-naïve and established insulin users. After moderator demonstration, participants were evaluated on their ability to perform a six-step process to inject a 10-unit dose into a pad with the AllStar(®) (AS; Sanofi, Mumbai, India), HumaPen Ergo II(®) (HE2; Eli Lilly, Indianapolis, USA), and NovoPen 4(®) (NP4; Novo Nordisk, Bagsværd, Denmark) pens. Local pens were also tested in India, China and Brazil. A total of 503 people from India, Malaysia, Brazil, Egypt, and China participated. Participants completed the six-step process in an average, 2-3 min per pen. Participants ranked ease of overall use and ease of self-injection and dialing/reading dose as most important features for new insulin pens. When using the pens, the most difficult step was priming/safety testing, with 7-12% failing and 28-40% having difficulty; 6%, 18%, and 22% failed to hold the injection button down for the required period of time using AS, NP4, and HE2, respectively. Participants ranked AS significantly higher for nine of 12 ease-of-use features including three of the top four features considered the most important for reusable pens, while HE2 was ranked higher for two features. Local pens were ranked lowest. Priming the pen and injecting the dose imparted most difficulty for people with

  9. Delayed initial recovery and long lie after a fall among middle-aged and older people with multiple sclerosis.

    PubMed

    Bisson, Etienne J; Peterson, Elizabeth W; Finlayson, Marcia

    2015-08-01

    To determine (1) the prevalence of lying on the floor or ground for ≥10 minutes (delayed initial recovery [IR]) and for >1 hour (long lie) after a fall; and (2) the factors associated with delayed IR among people with multiple sclerosis (PwMS). A secondary analysis of data available from a national, cross-sectional descriptive study of PwMS. Information regarding postfall experiences was extracted from open-ended questions about participants' most recent fall. Community. PwMS (N=700) aged ≥55 years were recruited from the North America Committee on Multiple Sclerosis Registry; 354 of them completed the interview, and 322 provided a fall story that included information regarding postfall experiences. Not applicable. Participants' self-reports regarding time lying on the floor or ground after their most recent fall were used to determine delayed IR and long lie. A total of 89 (27.6%) of 322 fallers reported delayed IR; 15 (4.7%) of them reported a long lie. Logistic regression analysis revealed 5 factors associated with delayed IR: longer disease duration (odds ratio [OR]=1.03; 95% confidence interval [CI], 1.00-1.05), fall leading to a fracture (OR=2.73; 95% CI, 1.11-6.72), received help to get up (OR=3.94; 95% CI, 2.07-7.50), depression (OR=1.96; 95% CI, 1.10-3.49), and leg weakness (OR=2.14; 95% CI, 1.13-4.03). No significant differences were found between fallers who reported a long lie and those who reported a delayed IR. The findings suggest that while delayed IR is common, long lies are not prevalent among PwMS. The high prevalence of delayed IR highlights the importance of including fall management strategies in fall prevention programs for PwMS. Copyright © 2015 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  10. Measurement of insulin-like growth factor-1 and insulin-like growth factor binding protein-3 after delayed separation of whole blood samples.

    PubMed

    Hartog, Hermien; van der Graaf, Winette T A; Wesseling, Jelle; van der Veer, Eveline; Boezen, H Marike

    2008-05-01

    Epidemiological studies benefit from unbiased blood specimens collected with minimal cost and effort of blood collection and storage. We evaluated the stability of IGF-1 and IGFBP-3 in whole blood samples stored at room temperature to justify delays in blood processing. Total IGF-1 and IGFBP-3 levels were measured in EDTA plasma (n=12), heparin plasma (n=12) and serum (n=10) samples of healthy volunteers after blood processing delays up till 14 days. Stability of measured IGF-1 and IGFBP-3 levels was tested by paired t-test and a linear mixed effect model. Longitudinal analysis showed that IGF-1 levels were not significantly affected by blood processing delays in EDTA tubes (p=0.18) and IGFBP-3 levels were marginally stable (p=0.06). In heparin plasma and serum, however, IGF-1 increased over time of delayed processing and IGFBP-3 levels tended to decrease (p<0.01). Total IGF-1 and IGFBP-3 levels are stable in whole blood collected in EDTA tubes at room temperature up till 7 days, allowing a delay in blood processing to reduce costs in large multi-center studies.

  11. Disordered Eating Behaviors in Youth with Type 1 Diabetes: Prospective Pilot Assessment Following Initiation of Insulin Pump Therapy

    PubMed Central

    Markowitz, Jessica T.; Alleyn, Cielo A.; Phillips, Roxanne; Muir, Andrew; Young-Hyman, Deborah

    2013-01-01

    Abstract Background There is risk for disordered eating behaviors in type 1 diabetes, especially related to insulin manipulation. Implementation of insulin pump therapy may encourage either normalization of eating behaviors or a greater focus on food intake due to renewed emphasis on carbohydrate counting. There is need for prospective studies to assess disordered eating behaviors upon implementation of pump therapy using diabetes-specific measurement tools. Subjects and Methods In a multicenter pilot study, 43 youth with type 1 diabetes, 10–17 years old, were assessed prior to pump initiation and after 1 and 6 months of pump therapy. Youth completed the Diabetes-specific Eating Problems Survey-Revised (DEPS-R), a validated measure of risk for both diabetes-specific and general disordered eating behaviors. Results Youth (45% female), 13.3 years old with diabetes for 2.1 years, had a mean hemoglobin A1c of 8.3±1.3% (68±14.5 mmol/mol) at baseline. DEPS-R scores decreased over time (P=0.01). Overall rate of high risk for eating disorders was low. Overweight/obese youth endorsed more disordered eating behaviors than normal-weight participants. DEPS-R scores were correlated with z-score for body mass index at all three time points and with hemoglobin A1c after 1 and 6 months. Hemoglobin A1c did not change significantly over the 6 months and was higher in overweight/obese compared with normal-weight participants. Conclusions Initiation of insulin pump therapy was associated with diminished endorsement of disordered eating behaviors in youth with type 1 diabetes. Longer follow-up studies are needed to assess the impact of insulin pump therapy on glycemic control, weight status, and disordered eating behaviors in this vulnerable population. PMID:23550556

  12. Loss of LORELEI function in the pistil delays initiation but does not affect embryo development in Arabidopsis thaliana

    PubMed Central

    Tsukamoto, Tatsuya

    2010-01-01

    Double fertilization, uniquely observed in plants, requires successful sperm cell delivery by the pollen tube to the female gametophyte, followed by migration, recognition and fusion of the two sperm cells with two female gametic cells. The female gametophyte not only regulates these steps but also controls the subsequent initiation of seed development. Previously, we reported that loss of LORELEI, which encodes a putative glycosylphosphatidylinositol (GPI)-anchored protein, in the female reproductive tissues causes a delay in initiation of seed development. From these studies, however, it was unclear if embryos derived from fertilization of lre-5 gametophytes continued to lag behind wild-type during seed development. Additionally, it was not determined if the delay in initiation of seed development had any lingering effects during seed germination. Finally, it was not known if loss of LORELEI function affects seedling development given that LORELEI is expressed in eight-day-old seedlings. Here, we showed that despite a delay in initiation, lre-5/lre-5 embryos recover, becoming equivalent to the developing wild-type embryos beginning at 72 hours after pollination. Additionally, lre-5/lre-5 seed germination, and seedling and root development are indistinguishable from wild-type indicating that loss of LORELEI is tolerated, at least under standard growth conditions, in vegetative tissues. PMID:21051955

  13. Loss of LORELEI function in the pistil delays initiation but does not affect embryo development in Arabidopsis thaliana.

    PubMed

    Tsukamoto, Tatsuya; Palanivelu, Ravishankar

    2010-11-01

    Double fertilization, uniquely observed in plants, requires successful sperm cell delivery by the pollen tube to the female gametophyte, followed by migration, recognition and fusion of the two sperm cells with two female gametic cells. The female gametophyte not only regulates these steps but also controls the subsequent initiation of seed development. Previously, we reported that loss of LORELEI, which encodes a putative glycosylphosphatidylinositol (GPI)-anchored protein, in the female reproductive tissues causes a delay in initiation of seed development. From these studies, however, it was unclear if embryos derived from fertilization of lre-5 gametophytes continued to lag behind wild type during seed development. Additionally, it was not determined if the delay in initiation of seed development had any lingering effects during seed germination. Finally, it was not known if loss of LORELEI function affects seedling development given that LORELEI is expressed in eight-day-old seedlings. Here, we showed that despite a delay in initiation, lre-5/lre-5 embryos recover, becoming equivalent to the developing wild-type embryos beginning at 72 hours after pollination. Additionally, lre-5/lre-5 seed germination, and seedling and root development are indistinguishable from wild type indicating that loss of LORELEI is tolerated, at least under standard growth conditions, in vegetative tissues.

  14. Implementation of Surgeon-Initiated Gene Expression Profile Testing (Onco type DX) Among Patients With Early-Stage Breast Cancer to Reduce Delays in Chemotherapy Initiation.

    PubMed

    Losk, Katya; Freedman, Rachel A; Lin, Nancy U; Golshan, Mehra; Pochebit, Stephen M; Lester, Susan C; Natsuhara, Kelsey; Camuso, Kristen; King, Tari R; Bunnell, Craig A

    2017-09-01

    Delays to adjuvant chemotherapy initiation in breast cancer may adversely affect clinical outcomes and patient satisfaction. We previously identified an association between genomic testing (Onco type DX) and delayed chemotherapy initiation. We sought to reduce the interval between surgery and adjuvant chemotherapy initiation by developing standardized criteria and workflows for Onco type DX testing. Criteria for surgeon-initiated reflex Onco type DX testing, workflows for communication between surgeons and medical oncologists, and a streamlined process for receiving and processing Onco type DX requests in pathology were established by multidisciplinary consensus. Criteria for surgeon-initiated testing included patients ≤ 65 years old with T1cN0 (grade 2 or 3), T2N0 (grade 1 or 2), or T1/T2N1 (grade 1 or 2) breast cancer on final surgical pathology. Medical oncologists could elect to initiate Onco type testing for cases falling outside the criteria. We then examined 720 consecutive patients with breast cancer who underwent Onco type DX testing postoperatively between January 1, 2014 and November 28, 2016 and measured intervals between date of surgery, Onco type DX order date, result received date, and chemotherapy initiation date (if applicable) before and after intervention implementation. The introduction of standardized criteria and workflows reduced time between surgery and Onco type DX ordering, and time from surgery to receipt of result, by 7.3 days ( P < .001) and 6.3 days ( P < .001), respectively. The mean number of days between surgery and initiation of chemotherapy was also reduced by 6.4 days ( P = .004). Developing consensus on Onco type DX testing criteria and implementing streamlined workflows has led to clinically significant reductions in wait times to chemotherapy decision making and initiation.

  15. Initiating or Switching to Biphasic Insulin Aspart 30/70 Therapy in Subjects with Type 2 Diabetes Mellitus. An Observational Study

    PubMed Central

    Breum, Leif; Almdal, Thomas; Eiken, Pia; Lund, Per; Christiansen, Erik; on behalf of the Danish BIAsp Study Group

    2008-01-01

    OBJECTIVE: To investigate tolerability and glycemic control over 26 weeks in patients with type 2 diabetes (T2D) who initiated insulin with, or switched to, biphasic insulin aspart 30/70 (BIAsp 30) in routine clinical care. METHODS: This was a non-randomized, non-interventional, open-label, observational study involving patients under the care of approximately 150 insulin-prescribing physicians in Denmark. All patients enrolled were prescribed BIAsp 30 in routine care. Starting dose, dose titration and injection frequency were determined individually by each physician. Information on serious adverse drug reactions (SADR), glycemic parameters and hypoglycemic events were obtained from patients’ notes, patients’ diaries and recall, and transferred to case report forms by physicians at baseline (during 4 weeks prior to BIAsp 30 therapy) and after 12 and 26 weeks of treatment. RESULTS: 421 subjects were recruited and 392 provided safety data. The age (mean ± SD) was 62.0 ± 11.4 years, body mass index (BMI) 30.4 ± 6.4 kg/m2, duration of diabetes 9.1 ± 8.1 years and HbA1c (%) 9.4 ± 1.7. 199 subjects were prior insulin users and 193 were insulin-naïve patients. Four patients reported a SADR (3 hypoglycemia, 1 severe hypoglycemia). HbA1c was significantly reduced after 26 weeks of BIAsp 30 therapy: prior insulin users -1.2%, insulin-naïve patients -2.2% (both p < 0.001). 28% and 41% of patients, respectively, reached target HbA1c < 7%. Overall the hypoglycemia rate was lower for insulin-naïve patients than for prior insulin users: 5.0 vs. 6.6 episodes/patient-year (p < 0.05). CONCLUSION: Initiating insulin with, or switching insulin to, BIAsp 30 in routine care was safe and effective in patients with T2D. PMID:19099087

  16. Why and how to use insulin therapy earlier in the management of type 2 diabetes.

    PubMed

    Meneghini, Luigi

    2007-02-01

    Most patients with type 2 diabetes are inadequately controlled on their current therapy. Suboptimal glycemic control can have devastating consequences, such as retinopathy, nephropathy, neuropathy, and cardiovascular disease that may ultimately lead to mortality. Most patients eventually need insulin therapy, and initiating insulin earlier in the course of type 2 diabetes may lead to optimal glycemic control and prevent or delay diabetes-related complications. Although insulin therapy is the most effective method of managing hyperglycemia, it is often delayed owing to concerns about the complexity and inconvenience of treatment regimens; fear of injections, hypoglycemia or weight gain; and the time required to learn how to effectively manage insulin therapy. The development of insulin analogs, biphasic insulin analogs, and more convenient insulin delivery systems may make insulin therapy more manageable and help more patients achieve their treatment goals.

  17. Antithymocyte globulin induction allows a prolonged delay in the initiation of cyclosporine in heart transplant patients with postoperative renal dysfunction.

    PubMed

    Cantarovich, Marcelo; Giannetti, Nadia; Barkun, Jeffrey; Cecere, Renzo

    2004-09-15

    The authors evaluated the efficacy of antithymocyte globulin (ATG) induction and delayed initiation of cyclosporine (CsA) in heart transplant (HTx) patients with postoperative renal dysfunction (RD). The authors compared 15 adult HTx patients with postoperative RD (serum creatinine [SCr] > or =150 microM) to 17 controls without postoperative RD. ATG was given daily (1.5 mg/kg/day for 5 days) in controls and every 2 to 5 days in RD patients (total lymphocyte count <200/mm). All patients received corticosteroids and mycophenolate mofetil. The initiation of CsA was delayed in RD patients until SCr had decreased to less than 150 microM (day 12 +/- 8 vs. 2 +/- 1, P<0.0001). One-year patient survival and acute rejection rates were 87% and 27% in RD patients and 88% and 59% in controls, respectively (P=not significant). SCr improved in RD patients and did not differ from controls after the first month. The authors' results suggest that marked prolongation of the period of ATG induction permits a safe delay in the initiation of CsA in HTx patients with postoperative RD.

  18. Hiroshima and Nagasaki initial radiations: delayed neutron contributions and comparison of calculated and measured cobalt activations

    SciTech Connect

    Loewe, W.E.

    1985-03-01

    Calculated estimates of neutron doses received by atomic-bomb survivors at Hiroshima and Nagasaki have not included contributions from delayed neutrons emitted by fission products in the debris cloud, although the possibility of a significant contribution from this source has been suggested. In the present work, an established model accounting for gamma-ray kermas from these fission products is adapted to provide the desired neutron kerma estimates. Adaptations include use of explicit time dependence of neutron emitters, properly folded with the time-dependent phenomenology of the explosion itself, and detailed air-over-ground neutron transport with a source having an energy spectrum characteristic of these delayed neutrons. Results show that delayed neutrons are indeed negligible contributors to atomic-bomb survivor dosimetry, as well as to neutron activations at Hiroshima. About half the activation at Nagasaki, however, is due to the delayed component. Calculated activation of cobalt, a revision of previous estimates, is compared to measured values at Hiroshima and at Nagasaki. The causes of the substantial discrepancies are discussed and compared to previously reported discrepancies for sulfur activation. Additional investigation is recommended.

  19. Clinical Efficacy of Two Different Methods to Initiate Sensor-Augmented Insulin Pumps: A Randomized Controlled Trial

    PubMed Central

    Gómez, Francisco Javier; Gálvez Moreno, Maria Ángeles; Castaño, Justo P.

    2016-01-01

    Aim. To analyze clinical effect of a novel approach to initiate sensor-augmented insulin pumps in type 1 diabetes mellitus (T1DM) patients through early real-time continuous glucose monitoring (RT-CGM) initiation. Methods. A 26-week pilot study with T1DM subjects randomized (1 : 1) to start RT-CGM three weeks before continuous subcutaneous insulin infusion (CGM pre-CSII) or adding RT-CGM three weeks after continuous subcutaneous insulin infusion (CGM post-CSII). Results. Twenty-two patients were enrolled with a mean age of 36.6 yr. (range 19–59 yr.) and T1DM duration of 16.8 ± 10.6 yr. Higher adherence in CGM pre-CSII patients was confirmed at study end (84.6 ± 11.1% versus 64.0 ± 25.4%; P = 0.01). The two intervention groups had similar HbA1c reduction at study end of −0.6% (P = 0.9). Hypoglycemic event frequency reduction was observed from baseline to study end only in CGM pre-CSII group (mean difference in change, −6.3%; 95% confidence interval, −12.0 to −0.5; P = 0.04). Moreover, no severe hypoglycemia was detected among CGM pre-CSII subjects during the study follow-up (0.0 ± 0.0 events versus 0.63 ± 1.0 events; P = 0.03). CGM pre-CSII patients showed better satisfaction than CGM post-CSII patients at the end of the study (27.3 ± 9.3 versus 32.9 ± 7.2; P = 0.04). Conclusions. CGM pre-CSII is a novel approach to improve glycemic control and satisfaction in type 1 diabetes sensor-augmented pump treated patients. PMID:28004007

  20. Impact of colistin-initiation delay on mortality of ventilator-associated pneumonia caused by A. baumannii.

    PubMed

    Samrah, Shaher; Bashtawi, Yazan; Hayajneh, Wail; Almomani, Basima; Momany, Suleiman; Khader, Yousef

    2016-10-31

    There has been increased incidence and high mortality in cases with ventilator-associated pneumonia (VAP) caused by colistin-only-susceptible Acinetobacter baumannii (COS-AB). Colistin has emerged as a therapeutic option for VAP caused by multidrug-resistant Gram-negative organisms including COS-AB. A retrospective study was conducted to examine the impact of early versus late initiation of colistin on 30-day mortality of critically ill patients with VAP caused by COS-AB. Critically ill patients with VAP caused by COS-AB who received colistin were enrolled. The receiver operating characteristic (ROC) curve was used to identify the temporal breakpoint that maximized the difference in 30-day mortality. A total of 56 patients (34 men and 22 women) were included in the study. About 86% of all cases were late-onset VAP. The 30-day mortality was 46.4%. The rate was higher among patients with admission Acute Physiology and Chronic Health Evaluation II (APACHE II) score > 18 and patients with a delay of more than four days in initiating colistin treatment. The mortality rate was 26.9% among patients with treatment delay of four or fewer days and 63.3% for patients with a treatment delay of more than four days. A delay of four days or more in initiating colistin in patients with VAP caused by COS-AB significantly increases mortality. Colistin should be considered in the empirical protocols in late-onset VAP cases when COS-AB is highly suspected.

  1. Continuous Subcutaneous Insulin Infusion in Children: A Pilot Study Validating a Protocol to Avoid Hypoglycemia at Initiation.

    PubMed

    Manousaki, Despoina; Deladoëy, Johnny; Geoffroy, Louis; Olivier, Patricia

    2017-01-01

    The occurrence of hypoglycemia and hyperglycemia during the first days after transition to continuous subcutaneous insulin infusion (CSII) in patients with type 1 diabetes has not been systematically studied in children. The aim of this prospective study was to demonstrate that the protocol applied in our diabetes clinic is safe at CSII initiation in children. We assessed 22 pediatric patients with type 1 diabetes, using continuous glucose monitoring (CGM) before and after CSII initiation (±3 days). After CSII initiation, there was no difference in the rates of hypoglycemic events expressed as relative rates (RRs) per person-reading (RR = 0.85, p = 0.52, 95% CI 0.52-1.39), as well as in the number of prolonged hypoglycemic events (>1 h) per day (RR = 1.12, p = 0.56, 95% CI 0.75-1.68). We observed only a trend toward prolonged episodes of hyperglycemia after pump initiation (RR = 1.52, p = 0.06, 95% CI 0.97-2.35). Our study is the first to assess, through CGM and in a prospective way, the impact of a CSII initiation protocol on glycemic values. Our protocol provides a safe model to avoid hypoglycemia at CSII initiation in children. www.ClinicalTrials.gov, identifier NCT01840358.

  2. Delay and Probability Discounting as Candidate Markers for Dementia: An Initial Investigation

    PubMed Central

    Lindbergh, Cutter A.; Puente, Antonio N.; Gray, Joshua C.; Mackillop, James; Miller, L. Stephen

    2014-01-01

    The present study investigated delay discounting and probability discounting—behavioral economic indices of impulsivity and risk proneness, respectively—in 39 healthy older adults and 25 older adults with mild cognitive impairment (MCI). Relative to the healthy group, it was hypothesized that older adults with MCI would display greater levels of impulsivity, risk proneness, and response inconsistency. The MCI group was found to display a unique delay discounting profile characterized by increasing impulsivity with decreasing reward magnitude, such that cognitively impaired older adults were significantly more impulsive than healthy controls at the small reward magnitude. The two groups exhibited similar levels of probability discounting, though older adults with MCI were significantly less consistent in their risk preferences. The present findings shed light onto decision-making in pre-dementia disease stages and suggest that discounting performance holds potential to complement early diagnostic instruments, likely due to pathophysiological processes in relevant brain regions. PMID:25236720

  3. Acyl CoA synthetase 5 (ACSL5) ablation in mice increases energy expenditure and insulin sensitivity and delays fat absorption

    PubMed Central

    Bowman, Thomas A.; O'Keeffe, Kayleigh R.; D'Aquila, Theresa; Yan, Qing Wu; Griffin, John D.; Killion, Elizabeth A.; Salter, Deanna M.; Mashek, Douglas G.; Buhman, Kimberly K.; Greenberg, Andrew S.

    2016-01-01

    Objective The family of acyl-CoA synthetase enzymes (ACSL) activates fatty acids within cells to generate long chain fatty acyl CoA (FACoA). The differing metabolic fates of FACoAs such as incorporation into neutral lipids, phospholipids, and oxidation pathways are differentially regulated by the ACSL isoforms. In vitro studies have suggested a role for ACSL5 in triglyceride synthesis; however, we have limited understanding of the in vivo actions of this ACSL isoform. Methods To elucidate the in vivo actions of ACSL5 we generated a line of mice in which ACSL5 expression was ablated in all tissues (ACSL5−/−). Results Ablation of ACSL5 reduced ACSL activity by ∼80% in jejunal mucosa, ∼50% in liver, and ∼37% in brown adipose tissue lysates. Body composition studies revealed that ACSL5−/−, as compared to control ACSL5loxP/loxP, mice had significantly reduced fat mass and adipose fat pad weights. Indirect calorimetry studies demonstrated that ACSL5−/− had increased metabolic rates, and in the dark phase, increased respiratory quotient. In ACSL5−/− mice, fasting glucose and serum triglyceride were reduced; and insulin sensitivity was improved during an insulin tolerance test. Both hepatic mRNA (∼16-fold) and serum levels of fibroblast growth factor 21 (FGF21) (∼13-fold) were increased in ACSL5−/− as compared to ACSL5loxP/loxP. Consistent with increased FGF21 serum levels, uncoupling protein-1 gene (Ucp1) and PPAR-gamma coactivator 1-alpha gene (Pgc1α) transcript levels were increased in gonadal adipose tissue. To further evaluate ACSL5 function in intestine, mice were gavaged with an olive oil bolus; and the rate of triglyceride appearance in serum was found to be delayed in ACSL5−/− mice as compared to control mice. Conclusions In summary, ACSL5−/− mice have increased hepatic and serum FGF21 levels, reduced adiposity, improved insulin sensitivity, increased energy expenditure and delayed triglyceride absorption. These studies

  4. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: results of a randomized, placebo-controlled study.

    PubMed

    Polidori, David; Sha, Sue; Mudaliar, Sunder; Ciaraldi, Theodore P; Ghosh, Atalanta; Vaccaro, Nicole; Farrell, Kristin; Rothenberg, Paul; Henry, Robert R

    2013-08-01

    Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption. This two-period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual-tracer method. Placebo or canagliflozin 300 mg was given 20 min before a 600-kcal mixed-meal tolerance test. Plasma glucose, (3)H-glucose, (14)C-glucose, and insulin were measured frequently for 6 h to calculate rates of appearance of oral glucose (RaO) in plasma, endogenous glucose production, and glucose disposal. Compared with placebo, canagliflozin treatment reduced postprandial plasma glucose and insulin excursions (incremental 0- to 2-h area under the curve [AUC0-2h] reductions of 35% and 43%, respectively; P < 0.001 for both), increased 0- to 6-h urinary glucose excretion (UGE0-6h, 18.2 ± 5.6 vs. <0.2 g; P < 0.001), and delayed RaO. Canagliflozin reduced AUC RaO by 31% over 0 to 1 h (geometric means, 264 vs. 381 mg/kg; P < 0.001) and by 20% over 0 to 2 h (576 vs. 723 mg/kg; P = 0.002). Over 2 to 6 h, canagliflozin increased RaO such that total AUC RaO over 0 to 6 h was <6% lower versus placebo (960 vs. 1,018 mg/kg; P = 0.003). A modest (∼10%) reduction in acetaminophen absorption was observed over the first 2 h, but this difference was not sufficient to explain the reduction in RaO. Total glucose disposal over 0 to 6 h was similar across groups. Canagliflozin reduces postprandial plasma glucose and insulin by increasing UGE (via renal SGLT2 inhibition) and delaying RaO, likely due to intestinal SGLT1 inhibition.

  5. Prevalence of early initiation of breastfeeding and determinants of delayed initiation of breastfeeding: secondary analysis of the WHO Global Survey.

    PubMed

    Takahashi, Kenzo; Ganchimeg, Togoobaatar; Ota, Erika; Vogel, Joshua P; Souza, João Paulo; Laopaiboon, Malinee; Castro, Cynthia Pileggi; Jayaratne, Kapila; Ortiz-Panozo, Eduardo; Lumbiganon, Pisake; Mori, Rintaro

    2017-03-21

    Early initiation of breastfeeding (EIBF) within 1 hour of birth can decrease neonatal death. However, the prevalence of EIBF is approximately 50% in many developing countries, and data remains unavailable for some countries. We conducted a secondary analysis using the WHO Global Survey on Maternal and Perinatal Health to identify factors hampering EIBF. We described the coverage of EIBF among 373 health facilities for singleton neonates for whom breastfeeding was initiated after birth. Maternal and facility characteristics of EIBF were compared to those of breastfeeding >1 hour after birth, and multiple logistic regression analysis was performed. In total, 244,569 singleton live births without severe adverse outcomes were analysed. The EIBF prevalence varied widely among countries and ranged from 17.7% to 98.4% (average, 57.6%). There was less intra-country variation for BFI <24 hours. After adjustment, EIBF was significantly lower among women with complications during pregnancy and caesarean delivery. Globally, EIBF varied considerably across countries. Maternal complications during pregnancy, caesarean delivery and absence of postnatal/neonatal care guidelines at hospitals may affect EIBF. Our findings suggest that to better promote EIBF, special support for breastfeeding promotion is needed for women with complications during pregnancy and those who deliver by caesarean section.

  6. Prevalence of early initiation of breastfeeding and determinants of delayed initiation of breastfeeding: secondary analysis of the WHO Global Survey

    PubMed Central

    Takahashi, Kenzo; Ganchimeg, Togoobaatar; Ota, Erika; Vogel, Joshua P.; Souza, João Paulo; Laopaiboon, Malinee; Castro, Cynthia Pileggi; Jayaratne, Kapila; Ortiz-Panozo, Eduardo; Lumbiganon, Pisake; Mori, Rintaro

    2017-01-01

    Early initiation of breastfeeding (EIBF) within 1 hour of birth can decrease neonatal death. However, the prevalence of EIBF is approximately 50% in many developing countries, and data remains unavailable for some countries. We conducted a secondary analysis using the WHO Global Survey on Maternal and Perinatal Health to identify factors hampering EIBF. We described the coverage of EIBF among 373 health facilities for singleton neonates for whom breastfeeding was initiated after birth. Maternal and facility characteristics of EIBF were compared to those of breastfeeding >1 hour after birth, and multiple logistic regression analysis was performed. In total, 244,569 singleton live births without severe adverse outcomes were analysed. The EIBF prevalence varied widely among countries and ranged from 17.7% to 98.4% (average, 57.6%). There was less intra-country variation for BFI <24 hours. After adjustment, EIBF was significantly lower among women with complications during pregnancy and caesarean delivery. Globally, EIBF varied considerably across countries. Maternal complications during pregnancy, caesarean delivery and absence of postnatal/neonatal care guidelines at hospitals may affect EIBF. Our findings suggest that to better promote EIBF, special support for breastfeeding promotion is needed for women with complications during pregnancy and those who deliver by caesarean section. PMID:28322265

  7. 15 CFR 4.10 - Appeals from initial determinations or untimely delays.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... be decided by the Assistant General Counsel for Administration (AGC-Admin), except that appeals for records which were initially denied by the AGC-Admin shall be decided by the General Counsel. Written appeals should be addressed to the AGC-Admin, or the General Counsel if the records were initially...

  8. 15 CFR 4.10 - Appeals from initial determinations or untimely delays.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... be decided by the Assistant General Counsel for Administration (AGC-Admin), except that appeals for records which were initially denied by the AGC-Admin shall be decided by the General Counsel. Written appeals should be addressed to the AGC-Admin, or the General Counsel if the records were initially...

  9. 15 CFR 4.10 - Appeals from initial determinations or untimely delays.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... be decided by the Assistant General Counsel for Administration (AGC-Admin), except that appeals for records which were initially denied by the AGC-Admin shall be decided by the General Counsel. Written appeals should be addressed to the AGC-Admin, or the General Counsel if the records were initially...

  10. 15 CFR 4.10 - Appeals from initial determinations or untimely delays.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... be decided by the Assistant General Counsel for Administration (AGC-Admin), except that appeals for records which were initially denied by the AGC-Admin shall be decided by the General Counsel. Written appeals should be addressed to the AGC-Admin, or the General Counsel if the records were initially...

  11. Delays in antiretroviral therapy initiation among HIV-positive individuals: results of the positive living with HIV study

    PubMed Central

    Poudel, Krishna C.; Buchanan, David R.; Poudel-Tandukar, Kalpana

    2016-01-01

    Background Lack of early initiation of antiretroviral therapy (ART) remains a major health concern due to increased risk of premature mortality and further HIV transmission. This study explored CD4+ cell count monitoring in relation to delays in ART initiation among HIV-positive individuals in the Kathmandu Valley, Nepal, where ART coverage was only 23.7% in 2011. Design We recruited a total of 87 ART-naïve, HIV-positive individuals aged 18 to 60 years through the networks of five non-government organizations working with HIV-positive individuals. We collected data on the history of ART initiation, CD4+ cell count monitoring, socio-demographic variables, perceived family support (measured with 10-item Nepali Family Support and Difficulty Scale), depression, and HIV symptom burden. Correlates of ART eligibility were examined using multivariable logistic regression analysis. Results A total of 72 of the 87 ART-naïve participants (82.8%) had monitored their CD4+ cell count in the past 6 months. Of these, 36 (50%) participants were eligible for ART initiation with CD4+ cell count <350 cells/mm3. A total of 12 participants had CD4+ cell count <200 cells/mm3. Lower level of perceived family support was associated with 6.05-fold higher odds (95% confidence interval =1.95 to 18.73) of being ART eligible with a CD4+ cell count <350 cells/mm3. Conclusions High rate of delays in ART initiation and the strong association of low perceived family support with ART eligibility in our study participants suggest that HIV service providers should consider the role and impact of family support in influencing individual decisions to initiate ART among eligible HIV-positive individuals. PMID:27369221

  12. Intensive vs. conventional insulin management initiated at diagnosis in children with diabetes: should payer source influence the choice of therapy?

    PubMed

    Beck, Joni K; Lewis, Teresa V; Logan, Kathy J; Harrison, Donald L; Gardner, Andrew W; Copeland, Kenneth C

    2009-09-01

    Intensive insulin management (IIM) in type 1 diabetes facilitates improved glycemic control and a reduction in long-term diabetes complications. We hypothesized that IIM can be started at diagnosis without deleterious effects on hemoglobin A1c (A1c), body mass index (BMI), and severe hypoglycemia regardless of payer source. Type 1 diabetes patients aged 0-18 yrs, in an academic endocrinology practice were identified for a retrospective chart review. Fifty-four patients on conventional insulin management (CIM) were compared to 51 on IIM. Insulin regimens, payer, and A1c values were compared at baseline, 12, 15, and 18 months. Secondary analyses included BMI changes and hypoglycemia frequency. Overall mean A1c values for the IIM group (8.15 +/- 1.41) were lower across all time periods compared to the CIM group (8.57 +/- 1.52). Repeated measures anova revealed a significant treatment group effect (p = 0.01) with no time effect (p = 0.87) or interaction (group by time) effect (p = 0.65). Private insurance patients had lower mean A1C values than Medicaid patients (chi(2) = 4.5186, p < 0.05), regardless of regimen. A1c values between IIM and CIM were not statistically different within the Medicaid group. BMI changes between groups were not different. Chi-square analysis for severe hypoglycemia revealed no group differences. In conclusion, IIM had improved glycemic control. Private insurance vs. Medicaid patients had lower mean A1c values regardless of treatment group. Considering Medicaid patients only, IIM was not inferior, and for those with private insurance, IIM was superior. IIM, initiated at diagnosis, is a reasonable approach for newly diagnosed children with diabetes regardless of payer source.

  13. Insulin therapy and type 2 diabetes: management of weight gain.

    PubMed

    McFarlane, Samy I

    2009-10-01

    The potential for insulin-related weight gain in patients with type 2 diabetes presents a therapeutic dilemma and frequently leads to delays in the initiation of insulin therapy. It also poses considerable challenges when treatment is intensified. Addressing insulin-related weight gain is highly relevant to the prevention of metabolic and cardiovascular consequences in this high-risk population with type 2 diabetes. In addition to lifestyle changes (eg, diet and exercise) and available medical interventions to minimize the risk of weight gain with insulin treatment, familiarity with the weight gain patterns of different insulins may help deal with this problem. The use of basal insulin analogs may offer advantages over conventional human insulin preparations in terms of more physiologic time-action profiles, reduced risk of hypoglycemia, and reduced weight gain.

  14. Delayed skeletal muscle mitochondrial ADP recovery in youth with type 1 diabetes relates to muscle insulin resistance.

    PubMed

    Cree-Green, Melanie; Newcomer, Bradley R; Brown, Mark S; Baumgartner, Amy D; Bergman, Bryan; Drew, Brendan; Regensteiner, Judith G; Pyle, Laura; Reusch, Jane E B; Nadeau, Kristen J

    2015-02-01

    Insulin resistance (IR) increases cardiovascular morbidity and is associated with mitochondrial dysfunction. IR is now recognized to be present in type 1 diabetes; however, its relationship with mitochondrial function is unknown. We determined the relationship between IR and muscle mitochondrial function in type 1 diabetes using the hyperinsulinemic-euglycemic clamp and (31)P-MRS before, during, and after near-maximal isometric calf exercise. Volunteers included 21 nonobese adolescents with type 1 diabetes and 17 nondiabetic control subjects with similar age, sex, BMI, Tanner stage, and activity levels. We found that youths with type 1 diabetes were more insulin resistant (median glucose infusion rate 10.1 vs. 18.9 mg/kglean/min; P < 0.0001) and had a longer time constant of the curve of ADP conversion to ATP (23.4 ± 5.3 vs. 18.8 ± 3.9 s, P < 0.001) and a lower rate of oxidative phosphorylation (median 0.09 vs. 0.21 mmol/L/s, P < 0.001). The ADP time constant (β = -0.36, P = 0.026) and oxidative phosphorylation (β = 0.02, P < 0.038) were related to IR but not HbA1c. Normal-weight youths with type 1 diabetes demonstrated slowed postexercise ATP resynthesis and were more insulin resistant than control subjects. The correlation between skeletal muscle mitochondrial dysfunction in type 1 diabetes and IR suggests a relationship between mitochondrial dysfunction and IR in type 1 diabetes.

  15. 37 CFR 102.10 - Appeals from initial determinations or untimely delays.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... the initial denial, if any, was in error. No opportunity for personal appearance, oral argument or... respect to the request, giving rise to a right of judicial review under 5 U.S.C. 552(a)(6)(C). If the...

  16. 37 CFR 102.10 - Appeals from initial determinations or untimely delays.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the initial denial, if any, was in error. No opportunity for personal appearance, oral argument or... respect to the request, giving rise to a right of judicial review under 5 U.S.C. 552(a)(6)(C). If the...

  17. The Effect of High-Dose Insulin Analog Initiation Therapy on Lipid Peroxidation Products and Oxidative Stress Markers in Type 2 Diabetic Patients

    PubMed Central

    Tuzcu, Hazal; Aslan, Ibrahim; Aslan, Mutay

    2013-01-01

    Effect of high-dose insulin analog initiation therapy was evaluated on lipid peroxidation and oxidative stress markers in type 2 diabetes mellitus (T2DM). Twenty-four T2DM patients with HbA1c levels above 10% despite ongoing therapy with sulphonylurea and metformin were selected. Former treatment regimen was continued for the first day followed by substitution of sulphonylurea therapy with different insulin analogs. Glycemic profiles were determined over 72 hours by Continuous Glucose Monitoring System (CGMS), and blood/urine samples were collected at 24 and 72 hours. Insulin analog plus metformin treatment significantly reduced glucose variability. Plasma and urine lipid peroxidation were markedly decreased following insulin analog plus metformin treatment. No correlation existed between glucose variability and levels of plasma and urine oxidative stress markers. Likewise, changes in mean blood glucose from baseline to end point showed no significant correlation with changes in markers of oxidative stress. On the contrary, decreased levels of oxidative stress markers following treatment with insulin analogs were significantly correlated with mean blood glucose levels. In conclusion, insulin plus metformin resulted in a significant reduction in oxidative stress markers compared with oral hypoglycemic agents alone. Data from this study suggests that insulin analogs irrespective of changes in blood glucose exert inhibitory effects on free radical formation. PMID:23577222

  18. Separable brain systems supporting cued versus self-initiated realization of delayed intentions.

    PubMed

    Gilbert, Sam J; Gollwitzer, Peter M; Cohen, Anna-Lisa; Burgess, Paul W; Oettingen, Gabriele

    2009-07-01

    In everyday life, one can link anticipated specific cues (e.g. visiting a restaurant) with desired actions (e.g., ordering a healthy meal). Alternatively, intentions such as "I intend to eat more healthily" present the option to act when one encounters the same cue. In the first case, a specific cue triggers a specific action; in the second, one must act in a more self-initiated manner. The authors compared such scenarios using functional magnetic resonance imaging. Participants were either instructed to respond in a particular manner to target events (cued condition) or told that they would score points for such responses, without being told that they were necessary (self-initiated condition). Although conditions differed only in the wording of instructions, the self-initiated condition was associated with poorer performance and greater activity in a predominantly frontoparietal network. Responses to targets in the self-initiated and cued conditions yielded greater activity in lateral and medial Brodmann area 10, respectively. The authors suggest that these results reflect differing demands for self-initiated versus externally cued behavior following different types of instruction, in line with the distinction between goal intentions and implementation intentions proposed by P. M. Gollwitzer and colleagues.

  19. Effect of insulin analog initiation therapy on LDL/HDL subfraction profile and HDL associated enzymes in type 2 diabetic patients

    PubMed Central

    2013-01-01

    Background Insulin treatment can lead to good glycemic control and result in improvement of lipid parameters in type 2 diabetic patients. This study was designed to evaluate the effect of insulin analog initiation therapy on low-density lipoprotein (LDL)/ high-density lipoprotein (HDL) sub-fractions and HDL associated enzymes in type 2 diabetic patients during early phase. Methods Twenty four type 2 diabetic patients with glycosylated hemoglobin (HbA1c) levels above 10% despite ongoing combination therapy with sulphonylurea and metformin were selected. Former treatment regimen was continued for the first day followed by substitution of sulphonylurea therapy with different insulin analogs (0.4 U/kg/day) plus metformin. Glycemic profiles were determined over 72 hours by continuous glucose monitoring system (CGMS) and blood samples were obtained from all patients at 24 and 72 hours. Plasma levels of cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-I) were determined by enzyme-linked immunosorbent assay (ELISA). Measurement of CETP and LCAT activity was performed via fluorometric analysis. Paraoxonase (PON1) enzyme activity was assessed from the rate of enzymatic hydrolysis of phenyl acetate to phenol formation. LDL and HDL subfraction analysis was done by continuous disc polyacrylamide gel electrophoresis. Results Mean blood glucose, total cholesterol (TC), triglyceride (TG) and very low-density lipoprotein cholesterol (VLDL-C) levels were significantly decreased while HDL-C levels were significantly increased after insulin treatment. Although LDL-C levels were not significantly different before and after insulin initiation therapy a significant increase in LDL-1 subgroup and a significant reduction in atherogenic LDL-3 and LDL-4 subgroups were observed. Insulin analog initiation therapy caused a significant increase in HDL-large, HDL- intermediate and a significant reduction

  20. Effect of insulin analog initiation therapy on LDL/HDL subfraction profile and HDL associated enzymes in type 2 diabetic patients.

    PubMed

    Aslan, Ibrahim; Kucuksayan, Ertan; Aslan, Mutay

    2013-04-24

    Insulin treatment can lead to good glycemic control and result in improvement of lipid parameters in type 2 diabetic patients. This study was designed to evaluate the effect of insulin analog initiation therapy on low-density lipoprotein (LDL)/ high-density lipoprotein (HDL) sub-fractions and HDL associated enzymes in type 2 diabetic patients during early phase. Twenty four type 2 diabetic patients with glycosylated hemoglobin (HbA1c) levels above 10% despite ongoing combination therapy with sulphonylurea and metformin were selected. Former treatment regimen was continued for the first day followed by substitution of sulphonylurea therapy with different insulin analogs (0.4 U/kg/day) plus metformin. Glycemic profiles were determined over 72 hours by continuous glucose monitoring system (CGMS) and blood samples were obtained from all patients at 24 and 72 hours. Plasma levels of cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-I) were determined by enzyme-linked immunosorbent assay (ELISA). Measurement of CETP and LCAT activity was performed via fluorometric analysis. Paraoxonase (PON1) enzyme activity was assessed from the rate of enzymatic hydrolysis of phenyl acetate to phenol formation. LDL and HDL subfraction analysis was done by continuous disc polyacrylamide gel electrophoresis. Mean blood glucose, total cholesterol (TC), triglyceride (TG) and very low-density lipoprotein cholesterol (VLDL-C) levels were significantly decreased while HDL-C levels were significantly increased after insulin treatment. Although LDL-C levels were not significantly different before and after insulin initiation therapy a significant increase in LDL-1 subgroup and a significant reduction in atherogenic LDL-3 and LDL-4 subgroups were observed. Insulin analog initiation therapy caused a significant increase in HDL-large, HDL- intermediate and a significant reduction in HDL-small subfractions

  1. Delayed Initiation of the Pharyngeal Swallow: Normal Variability in Adult Swallows

    ERIC Educational Resources Information Center

    Martin-Harris, Bonnie; Brodsky, Martin B.; Michel, Yvonne; Lee, Fu-Shing; Walters, Bobby

    2007-01-01

    Purpose: The purpose of this investigation was to determine bolus head timing and location relations with the onset of hyoid movement at the initiation of the pharyngeal swallow and at the onset of swallow-related apnea. Method: Bolus head timing and location and the timing of swallow-related apnea were recorded from frame-by-frame analyses of…

  2. 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 (HbA1c) 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 HbA1c of <7.0% (<53mmol/mol) per baseline HbA1c 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 HbA1c and FHG values at baseline in each HbA1c quartile regardless of whether they reached the target HbA1c. The higher the HbA1c quartile, the greater was the decrease in HbA1c, but also the smaller the percentage of patients achieving the target HbA1c. HbA1c and FHG decreased more in patients reaching the target, resulting in significantly lower values at endpoint in all baseline HbA1c quartiles with either insulin treatment. Patients not achieving the target HbA1c had slightly higher insulin doses, but lower total hypoglycaemia rates. Smaller decreases in FHG were associated with not reaching the target HbA1c, 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.

  3. Human influenza A H5N1 in Indonesia: health care service-associated delays in treatment initiation.

    PubMed

    Adisasmito, Wiku; Aisyah, Dewi Nur; Aditama, Tjandra Yoga; Kusriastuti, Rita; Trihono; Suwandono, Agus; Sampurno, Ondri Dwi; Prasenohadi; Sapada, Nurshanty A; Mamahit, M J N; Swenson, Anna; Dreyer, Nancy A; Coker, Richard

    2013-06-11

    Indonesia has had more recorded human cases of influenza A H5N1 than any other country, with one of the world's highest case fatality rates. Understanding barriers to treatment may help ensure life-saving influenza-specific treatment is provided early enough to meaningfully improve clinical outcomes. Data for this observational study of humans infected with influenza A H5N1 were obtained primarily from Ministry of Health, Provincial and District Health Office clinical records. Data included time from symptom onset to presentation for medical care, source of medical care provided, influenza virology, time to initiation of influenza-specific treatment with antiviral drugs, and survival. Data on 124 human cases of virologically confirmed avian influenza were collected between September 2005 and December 2010, representing 73% of all reported Indonesia cases. The median time from health service presentation to antiviral drug initiation was 7.0 days. Time to viral testing was highly correlated with starting antiviral treatment (p < 0.0001). We found substantial variability in the time to viral testing (p = 0.04) by type of medical care provider. Antivirals were started promptly after diagnosis (median 0 days). Delays in the delivery of appropriate care to human cases of avian influenza H5N1 in Indonesia appear related to delays in diagnosis rather than presentation to health care settings. Either cases are not suspected of being H5N1 cases until nearly one week after presenting for medical care, or viral testing and/or antiviral treatment is not available where patients are presenting for care. Health system delays have increased since 2007.

  4. [Delayed diagnosis in a case of granulomatosis with polyangiitis (Wegener's) with initial predominance of joint involvement].

    PubMed

    Macri, Anca; Ulmeanu, Ruxandra; Mihălţan, Florin; Popa, Gabriela; Stoica, Radu

    2014-01-01

    The authors present the case of a 53-year-old female, initially admitted in a rheumatology department for fever and diffuse arthritis--being diagnosed with sero-positive rheumathoid arthritis. Although the chest X-ray and CT scan of thorax showed several abnormal features (medium lobe atelectasis, pseudo-cyst in the posterior segment of the right upper lobe with satellite milliary nodules, mediastinal lymph node enlargement), the investigations performed in our pneumology department couldn't establish the etiology of radiological abnormalities. With non-steroidal antiinflamatory treatment, the patient got worse, being readmitted in our hospital after 3 months for high fever, diffuse arthralgia with functional impairment, small hemoptysis, loss of hearing and left ear ache and on chest X-ray with bilateral macronodules, some of these with cavitation. The investigations showed a slight alveolar hemorrhagic syndrome, positive cANCA antibodies, negative antiCCP antibodies--the diagnosis of Wegener's granulomatosis with lung and ENT involvement being established. Puls-therapy with Solumedrol and i.v. Cyclophosphamide was thereafter initiated with a favorable evolution. This case is special because of the initial misdiagnosis due to the atypical pulmonary manifestations and the non-specific paraclinical findings, in the context of diffuse arthritis with positive rheumatoid factor.

  5. Educational gradient in HIV diagnosis delay, mortality, antiretroviral treatment initiation and response in a country with universal health care.

    PubMed

    Sobrino-Vegas, Paz; Rodríguez-Urrego, Johana; Berenguer, Juan; Caro-Murillo, Ana María; Blanco, José Ramón; Viciana, Pompeyo; Moreno, Santiago; Bernardino, Ignacio; del Amo, Julia

    2012-01-01

    The aim of this study was to analyse associations between educational level and delayed HIV diagnosis (DD), late initiation of combined antiretroviral therapy (cART), overall and in subjects with timely HIV diagnosis, virological and immunological responses to cART, and mortality from HIV diagnosis and cART initiation. This was a multicentre cohort study of HIV-positive treatment-naive subjects in Spain between 2004-2009. Logistic and Cox regression analyses were used. Of 4,549 subjects, 44.5% had low education level (LOW), 34.4% medium education level (MED) and 21.1% high education level (HIG). In men, DD was more common in MED (OR 1.3 [95% CI 1.0, 1.7]) or LOW [OR 1.8 (95% CI 1.4, 2.3)] compared to HIG. In women, the opposite was observed; women with HIG were 40% more likely to have DD than those with LOW (OR 1.4 [95% CI 0.8, 2.5]). In individuals with timely HIV diagnoses, percentages of late cART initiators were similar (LOW 9.5%, MED 11.4% and HIG 7.0%; P=0.114). Immunological (LOW 68%, MED 76% and HIG 84%) and virological (LOW 76%, MED 83% and HIG 86%) responses to cART increased significantly with educational level; these increases remained significant in multivariate analyses. Mortality for LOW subjects was higher than for HIG, from HIV diagnosis (hazard ratio [HR] 2.3 [95% CI 1.1, 4.9]) and from cART initiation (HR 1.8 [95% CI 0.8, 3.9]). We found important differences by educational level in diagnosis delay, virological and immunological responses to cART and mortality in a country with universal health care. Women with high educational level are at higher risk of having delayed HIV diagnoses. Educational level should be taken into account when designing HIV testing and clinical management strategies.

  6. Insulin Analogs or Premixed Insulin Analogs in Combination With Oral Agents for Treatment of Type 2 Diabetes

    PubMed Central

    Levy, Philip

    2007-01-01

    Context Type 2 diabetes is a progressive disease that is reaching epidemic proportions. Whereas most patients are initially managed with oral antidiabetic agents (OADs), the majority eventually require insulin to maintain glycemic control. The availability of insulin analogs (rapid-acting, long-acting, and premixed), with more predictable time-action profiles than human insulin preparations and simple-to-use insulin delivery devices, can help ease the transition to insulin therapy, which is often delayed until glycemic control has been inadequate for several years. >Objective To review the rationale for and strategies to initiate therapy with insulin analogs earlier in the course of type 2 diabetes. Practical barriers that must be overcome to successfully initiate insulin therapy in patients with type 2 diabetes are also briefly described. Design Narrative review of clinical evidence and current diabetes treatment guidelines. Setting and Patients Outpatients with type 2 diabetes inadequately managed with OADs alone. Interventions Three of the most common approaches to initiating insulin therapy with analogs are considered, with clinical evidence and detailed dosing algorithms provided. These approaches include: (1) addition of a basal insulin analog to oral therapy to reduce and stabilize fasting plasma glucose, (2) supplementation of oral therapy with a rapid-acting mealtime insulin analog to control postprandial glucose excursions, and (3) addition of or switching to a premixed insulin analog, which can be used to control both fasting and postprandial glucose in 1 injection. Conclusions Selection of appropriate insulin analog regimens and individualization of therapy can help patients achieve recommended glycemic goals while minimizing hypoglycemia. Education about the eventual need for insulin and improvements in insulin preparations and delivery systems at the time of diagnosis can also help overcome patient barriers. PMID:17955068

  7. Experimental warming delays autumn senescence in a boreal spruce bog: Initial results from the SPRUCE experiment

    NASA Astrophysics Data System (ADS)

    Richardson, Andrew; Furze, Morgan; Aubrecht, Donald; Milliman, Thomas; Nettles, Robert; Krassovski, Misha; Hanson, Paul

    2016-04-01

    Phenology is considered one of the most robust indicators of the biological impacts of global change. In temperate and boreal regions, long-term data show that rising temperatures are advancing spring onset (e.g. budburst and flowering) and delaying autumn senescence (e.g. leaf coloration and leaf fall) in a wide range of ecosystems. While warm and cold temperatures, day length and insolation, precipitation and water availability, and other factors, have all been shown to influence plant phenology, the future response of phenology to rising temperatures and elevated CO2 still remains highly uncertain because of the challenges associated with conducting realistic manipulative experiments to simulate future environmental conditions. At the SPRUCE (Spruce and Peatland Responses Under Climatic and Environmental Change) experiment in the north-central United States, experimental temperature (0 to +9° C above ambient) and CO2 (ambient and elevated) treatments are being applied to mature, and intact, Picea mariana-Sphagnum spp. bog communities in their native habitat through the use of ten large (approximately 12 m wide, 10 m high) open-topped enclosures. We are tracking vegetation green-up and senescence in these chambers, at both the individual and whole-community level, using repeat digital photography. Within each chamber, digital camera images are recorded every 30 minutes and uploaded to the PhenoCam (http://phenocam.sr.unh.edu) project web page, where they are displayed in near-real-time. Image processing is conducted nightly to extract quantitative measures of canopy color, which we characterize using Gcc, the green chromatic coordinate. Data from a camera mounted outside the chambers (since November 2014) indicate strong seasonal variation in Gcc for both evergreen shrubs and trees. Shrub Gcc rises steeply in May and June, and declines steeply in September and October. By comparison, tree Gcc rises gradually from March through June, and declines gradually from

  8. Trans sodium crocetinate for hemorrhagic shock: effect of time delay in initiating therapy.

    PubMed

    Giassi, Lisa J; Poynter, A Kennon; Gainer, John L

    2002-12-01

    A new drug, trans sodium crocetinate (TSC), has been suggested for use in resuscitation after trauma. TSC has been shown to increase survival in a rat model of hemorrhagic shock. It also results in an increase in blood pressure and a decrease in plasma lactate levels when given immediately after hemorrhage. TSC increases whole-body oxygen consumption rates, and it is thought that its physiological effects are due to the increased oxygen availability. In fact, TSC therapy and 100% oxygen therapy show similar results when used in the same rat hemorrhage model. It has been suggested, however, that 100% oxygen therapy is effective only if begun immediately after hemorrhage. Such a window of opportunity has been said to exist for other resuscitation methods; thus, the current study is to determine if this is true for TSC. In one series of experiments, rats were bled 60% of their blood volumes and given an injection of TSC (or saline) 20 min after the hemorrhage ended. The injection was then repeated four times, spaced 10 min apart. Thirty minutes after the final injection, the animals were infused with normal saline. TSC again restored blood pressure and other parameters, but repeated dosing was necessary. In addition, this therapy prevented an increase in liver enzymes (transaminases) as measured 24 h after hemorrhage. In a second study, rats were bled 60% of their blood volumes, followed by a second bleeding (an additional 10%) done 10 min later. No subsequent fluid was infused in this group. The majority of the animals treated with TSC after the second hemorrhage survived, whereas the controls did not. These data suggest that TSC is effective when given after a delay. The dosing regimen must be different, however, presumably because of the blood acidosis that develops after hemorrhage. The results also suggest that TSC may be protective against secondary liver damage resulting from trauma.

  9. Effect of flow rate and insulin priming on the recovery of insulin from microbore infusion tubing.

    PubMed

    Fuloria, M; Friedberg, M A; DuRant, R H; Aschner, J L

    1998-12-01

    A retrospective medical record review of 13 consecutive, hyperglycemic, extremely low birth weight (ELBW) infants treated with continuous insulin infusions revealed a 14- to 24-hour delay (mean, 19 hours) in blood glucose normalization despite stepwise increases in insulin infusion rates. This in vitro study examined the effects of flow rate and insulin priming on insulin recovery from polyvinyl chloride (PVC) tubing and polyethylene (PE)-lined PVC tubing infused with a standard insulin stock solution. Stock insulin solution (0.2 U/mL) was infused through microbore PVC or PE-lined tubing at flow rates of 0.05 and 0.2 mL/h. To determine if saturation of nonspecific binding sites would alter effluent insulin concentration, we compared insulin recovery from tubing previously flushed with the stock solution and tubing primed with 5 U/mL of insulin for 20 minutes. Effluent samples, which were collected at baseline and at six time points during a 24-hour period, were immediately frozen at -20 degreesC. Insulin concentration was measured by IMx immunoassay. Data were analyzed using general linear modeling with repeated measures. At 0.05 mL/h flow rate, insulin recovery from unprimed PVC tubing at 1, 2, 4, and 8 hours was 17%, 11%, 27%, and 55%, respectively, with 100% recovery at 24 hours. From insulin-primed tubing, insulin recovery was approximately 70% at 1, 2, and 4 hours, and close to 100% at 8 hours. At a faster flow rate of 0.2 mL/h, insulin recovery at 1, 2, 4, and 8 hours was 22%, 38%, 67%, and 75% vs 42%, 85%, 91% and 95% from unprimed and insulin-primed PVC tubing, respectively. Similar results were obtained from unprimed and insulin-primed PE-lined tubing at 0.2 mL/h flow rate. Priming of microbore tubing with 5 U/mL of insulin solution for 20 minutes to block nonspecific binding sites enhances delivery of a standard insulin stock at infusion rates typically used to treat hyperglycemic ELBW infants. We conclude that priming the tubing with a higher

  10. How can insulin initiation delivery in a dual-sector health system be optimised? A qualitative study on healthcare professionals’ views

    PubMed Central

    2012-01-01

    Background The prevalence of type 2 diabetes is increasing at an alarming rate in developing countries. However, glycaemia control remains suboptimal and insulin use is low. One important barrier is the lack of an efficient and effective insulin initiation delivery approach. This study aimed to document the strategies used and proposed by healthcare professionals to improve insulin initiation in the Malaysian dual-sector (public–private) health system. Methods In depth interviews and focus group discussions were conducted in Klang Valley and Seremban, Malaysia in 2010–11. Healthcare professionals consisting of general practitioners (n = 11), medical officers (n = 8), diabetes educators (n = 3), government policy makers (n = 4), family medicine specialists (n = 10) and endocrinologists (n = 2) were interviewed. We used a topic guide to facilitate the interviews, which were audio recorded, transcribed verbatim and analysed using a thematic approach. Results Three main themes emerged from the interviews. Firstly, there was a lack of collaboration between the private and public sectors in diabetes care. The general practitioners in the private sector proposed an integrated system for them to refer patients to the public health services for insulin initiation programmes. There could be shared care between the two sectors and this would reduce the disproportionately heavy workload at the public sector. Secondly, besides the support from the government health authority, the healthcare professionals wanted greater involvement of non-government organisations, media and pharmaceutical industry in facilitating insulin initiation in both the public and private sectors. The support included: training of healthcare professionals; developing and disseminating patient education materials; service provision by diabetes education teams; organising programmes for patients’ peer group sessions; increasing awareness and demystifying insulin via public

  11. How can insulin initiation delivery in a dual-sector health system be optimised? A qualitative study on healthcare professionals' views.

    PubMed

    Lee, Ping Yein; Lee, Yew Kong; Ng, Chirk Jenn

    2012-04-30

    The prevalence of type 2 diabetes is increasing at an alarming rate in developing countries. However, glycaemia control remains suboptimal and insulin use is low. One important barrier is the lack of an efficient and effective insulin initiation delivery approach. This study aimed to document the strategies used and proposed by healthcare professionals to improve insulin initiation in the Malaysian dual-sector (public-private) health system. In depth interviews and focus group discussions were conducted in Klang Valley and Seremban, Malaysia in 2010-11. Healthcare professionals consisting of general practitioners (n = 11), medical officers (n = 8), diabetes educators (n = 3), government policy makers (n = 4), family medicine specialists (n = 10) and endocrinologists (n = 2) were interviewed. We used a topic guide to facilitate the interviews, which were audio recorded, transcribed verbatim and analysed using a thematic approach. Three main themes emerged from the interviews. Firstly, there was a lack of collaboration between the private and public sectors in diabetes care. The general practitioners in the private sector proposed an integrated system for them to refer patients to the public health services for insulin initiation programmes. There could be shared care between the two sectors and this would reduce the disproportionately heavy workload at the public sector. Secondly, besides the support from the government health authority, the healthcare professionals wanted greater involvement of non-government organisations, media and pharmaceutical industry in facilitating insulin initiation in both the public and private sectors. The support included: training of healthcare professionals; developing and disseminating patient education materials; service provision by diabetes education teams; organising programmes for patients' peer group sessions; increasing awareness and demystifying insulin via public campaigns; and subsidising glucose

  12. Clinical Predictors for Delayed or Inappropriate Initial Diagnosis of Type A Acute Aortic Dissection in the Emergency Room

    PubMed Central

    Hirata, Kazuhito; Wake, Minoru; Takahashi, Takanori; Nakazato, Jun; Yagi, Nobuhito; Miyagi, Tadayoshi; Shimotakahara, Junichi; Mototake, Hidemitsu; Tengan, Toshiho; Takara, Tsuyoshi R.; Yamaguchi, Yutaka

    2015-01-01

    Background Initial diagnosis of acute aortic dissection (AAD) in the emergency room (ER) is sometimes difficult or delayed. The aim of this study is to define clinical predictors related to inappropriate or delayed diagnosis of Stanford type A AAD. Methods We conducted a retrospective analysis of 127 consecutive patients with type A AAD who presented to the ER within 12 h of symptom onset (age: 69.0 ± 15.4 years, male/female = 49/78). An inappropriate initial diagnosis (IID) was considered if AAD was not included in the differential diagnosis or if chest computed tomography or echocardiography was not performed as initial imaging tests. Clinical variables were compared between IID and appropriate diagnosis group. The time to final diagnosis (TFD) was also evaluated. Delayed diagnosis (DD) was defined as TFD > third quartile. Clinical factors predicting DD were evaluated in comparison with early diagnosis (defined as TFD within the third quartile). In addition, TFD was compared with respect to each clinical variable using a rank sum test. Results An IID was determined for 37% of patients. Walk-in (WI) visit to the ER [odds ratio (OR) 2.6, 95% confidence interval (CI) = 1.01–6.72, P = 0.048] and coronary malperfusion (CM, OR = 6.48, 95% CI = 1.14–36.82, P = 0.035) were predictors for IID. Overall, the median TFD was 1.5 h (first/third quartiles = 0.5/4.0 h). DD (>4.5 h) was observed in 27 cases (21.3%). TFD was significantly longer in WI patients (median and first/third quartiles = 1.0 and 0.5/2.85 h for the ambulance group vs. 3.0 and 1.0/8.0 h for the WI group, respectively; P = 0.003). Multivariate analysis revealed that WI visit was the only predictor for DD (OR = 3.72, 95% CI = 1.39–9.9, P = 0.009). TFD was significantly shorter for appropriate diagnoses than for IIDs (1.0 vs. 6.0 h, respectively; P < 0.0001). Conclusions WI visit to the ER and CM were predictors for IID, and WI was the only predictor for DD in acute type A AAD in the community hospital

  13. Initial judgment task and delay of the final validity-rating task moderate the truth effect.

    PubMed

    Nadarevic, Lena; Erdfelder, Edgar

    2014-01-01

    Repeatedly seen or heard statements are typically judged to be more valid than statements one has never encountered before. This phenomenon has been referred to as the truth effect. We conducted two experiments to assess the plasticity of the truth effect under different contextual conditions. Surprisingly, we did not find a truth effect in the typical judgment design when using a ten minutes interval between statement repetitions. However, we replicated the truth effect when changing the judgment task at initial statement exposure or when using an interval of one week rather than ten minutes. Because none of the current truth effect theories can fully account for these context effects, we conclude that the cognitive processes underlying truth judgments are more complex than has hitherto been assumed. To close the theoretical gap, we propose a revised fluency attribution hypothesis as a possible explanation of our findings. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. [Insulin: initiation of pool of insulin-dependent cells, targeted transfer of triglycerides and increase of kinetic parameters of oxidation of fatty acids].

    PubMed

    Titov, V N

    2014-04-01

    The insulin, to provide with energy the biological function of locomotion, formed: a) pool of phylogenetically late insulin-dependent cells; b) highly productive vector variant of transfer of saturated and mono unsaturated fatty acids only to insulin-dependent cells; c) new variant of active absorption of substrates for acquiring energy by cells--apoE/B-100-receptor endocytosis; d) transformation of all endogenically synthesized palmitic saturated fatty acid in oleic mono saturated fatty acid and e) replacement of potentially ineffective palmitic variant of formation of energy in vivo with potentially high-performance oleic variant of metabolism of substrates for turning out of ATP. The insulin expressed synthesis of apoE glucose carrier 4 and stearyl-KoA-desaturase. These occurrences confirm that syndrome of insulin resistance primarily is the pathology of metabolism of fatty acids and only secondary the pathology metabolism of glucose. The multi-functional fatty cells of visceral areolar tissue and specialized adipocytes of subcutaneous fat depots are phylogenetically, regulatory and functionally different cells. They are formed under development of different biological functions: the first ones under realization of biological function of trophology and second ones under realization of biological function of locomotion. At the level of organism, the mechanisms of hypothalamus-fatty cells feedback are realized by peptide leptin and in case of hypothalamus-adipocytes feedback--peptide adiponectin. The potential possibilities of mitochondria in synthesis of ATP are high and are conditioned only by amount of substrate of mitochondria acetyl-KoA. This shortage can be chronic as in cases of disorder of insulin function and palmitic variant of metabolism of substrates for acquiring energy by cells. The deficiency of acetyl-KoA can be acute as is the case of diabetic coma when surplus amount of ketonic bodies follows the expressed deficiency of acetyl-KoA formed from

  15. Factors associated with relational coordination between health professionals involved in insulin initiation in the general practice setting for people with type 2 diabetes.

    PubMed

    Manski-Nankervis, Jo-Anne; Furler, John; Young, Doris; Patterson, Elizabeth; Blackberry, Irene

    2015-09-01

    To examine associations between characteristics of general practice settings and primary healthcare providers (general practitioners and practice nurses) and the degree of relational coordination for the task of insulin initiation for type 2 diabetes between primary healthcare providers and diabetes specialists. Relational coordination is a component of effective chronic disease management and can be used to measure collaboration and communication between health professionals. High levels of relational coordination may be important to support insulin initiation in general practice. Cross-sectional study. Surveys were completed by general practitioners and practice nurses participating in the Stepping Up trial. Data on demographics, practice characteristics and relational coordination were collected between October 2012-June 2014. Univariate and multivariate analyses examined factors associated with relational coordination. General practitioners (n = 174) and 115 practice nurses from 78 general practices were included in the analysis. General practice characteristics associated with relational coordination were geographical location and number of administrative staff. Female general practitioners and older practice nurses reported lower relational coordination. Practice nurses with diabetes educator qualifications and experience in insulin initiation reported higher relational coordination. An expanded role and experience of practice nurses in diabetes care increased relational coordination and has the potential to deliver more effective chronic disease management in general practice. Practice and health professional characteristics should be taken into account when designing models of care to increase insulin initiation. © 2015 John Wiley & Sons Ltd.

  16. Initial thermal heat hypoalgesia and delayed hyperalgesia in a murine model of bone cancer pain.

    PubMed

    Menéndez, Luis; Lastra, Ana; Fresno, Manuel F; Llames, Sara; Meana, Alvaro; Hidalgo, Agustín; Baamonde, Ana

    2003-04-18

    The recent development of rodent models of bone cancer pain has started to provide the basis for demonstrating the particular neurochemical and behavioral entity of cancer pain. Behaviourally, both spontaneous pain and hyperalgesia related to mechanical, but not thermal, noxious stimuli have been described in cancer-bearing animals. We have carried out a histological and behavioural study focused on the reactivity to noxious heat in C3H/HeJ mice receiving an intratibial injection of 10(5) NCTC 2472 cells. These cells, able to induce an osteosarcoma, break through bone into soft tissues 2 weeks after cell inoculation, producing a macroscopical increase of the limb size from the fourth week. Thermal reactivity is diminished during the first 2 weeks after cell implantation, this hypoalgesia being reversed by the administration of naloxone (10 mg/kg). In contrast, during the fourth and fifth weeks after NCTC 2472 cell implantation, an increased nociceptive heat reactivity, instead of hypoalgesia, was obtained. This thermal hyperalgesia was prevented by the systemic administration of morphine (15 mg/kg). Throughout the whole period studied, mice showed signs of spontaneous pain behaviour that reached its maximum 3 weeks after inoculation. In conclusion, we show that the presence of thermal heat hyperalgesia is preceded by an initial opioid-mediated hypoalgesic state, in this murine model of bone cancer pain.

  17. The Preferred Initial Time Delay Gap and Inter-Aural Cross Correlation for a Javanese Gamelan Performance Hall

    NASA Astrophysics Data System (ADS)

    Sarwono, J.; Lam, Y. W.

    2002-11-01

    This paper discusses the application of a method based on human subjective preference to the acoustic design of a Javanese gamelan performance hall. Some important distinctions between Javanese gamelan ensembles and Western classical orchestra are the tuning system, orchestral blending process, and technique of playing. The results of subjective preference test using the rank order method showed that the subjects preferred 24·25 ms for the initial time delay gap ( ITDG) and the smallest value of the inter-aural cross-correlation ( IACC). The preferred ITDG agree with the ITDG from the room response measured in a traditional pendopo in Indonesia, which is not a common concert hall but an open-sided hall. However, the preferred IACC is not in agreement with the measured ITDG in the pendopo .

  18. Medication utilization patterns among type 2 diabetes patients initiating Exenatide BID or insulin glargine: a retrospective database study

    PubMed Central

    2013-01-01

    Background Type 2 diabetes is a common and costly illness, associated with significant morbidity and mortality. Despite this, there is relatively little information on the ‘real-world’ medication utilization patterns for patients with type 2 diabetes initiating exenatide BID or glargine. The objective of this study was to evaluate the ‘real-world’ medication utilization patterns in patients with type 2 diabetes treated with exenatide BID (exenatide) versus insulin glargine (glargine). Methods Adult patients( ≥18 years of age) with type 2 diabetes who were new initiators of exenatide or glargine from October 1, 2006 through March 31, 2008 with continuous enrollment for the 12 months pre- and 18 months post-index period were selected from the MarketScan® Commercial and Medicare Databases. To control for selection bias, propensity score matching was used to complete a 1:1 match of glargine to exenatide patients. Key study outcomes (including the likelihood of overall treatment modification, discontinuation, switching, or intensification) were analyzed using survival analysis. Results A total of 9,197 exenatide- and 4,499 glargine-treated patients were selected. Propensity score matching resulted in 3,774 matched pairs with a mean age of 57 years and a mean Deyo Charlson Comorbidity Index score of 1.6; 54% of patients were males. The 18-month treatment intensification rates were 15.9% and 26.0% (p < 0.0001) and the discontinuation rates were 38.3% and 40.0% (p = 0.14) for exenatide and glargine, respectively. Alternatively, 14.9% of exenatide-treated patients switched therapies, compared to 10.0% of glargine-treated patients (p < 0.0001). Overall, glargine-treated patients were more likely to modify their treatment [hazard ratio (HR) = 1.33, p < 0.0001] with shorter mean time on treatment until modification (123 vs. 159 days, p < 0.0001). Compared to exenatide-treated patients, glargine-treated patients were more likely to

  19. Mortality associated with delays between clinic entry and ART initiation in resource-limited-settings: results of a transition-state model

    PubMed Central

    HOFFMANN, Christopher J; LEWIS, James J; DOWDY, David W; FIELDING, Katherine L; GRANT, Alison D; MARTINSON, Neil A; CHURCHYARD, Gavin J; CHAISSON, Richard E

    2013-01-01

    Objective Estimate the mortality impact of delay in antiretroviral therapy (ART) initiation from the time of entry-into-care. Design A state-transition Markov process model. This technique allows for assessing mortality before and after ART initiation associated with delays in ART initiation among a general population of ART eligible patients without conducting a randomized trial. Methods We used patient-level data from three South African cohorts to determine transition probabilities for pre-ART CD4 count changes and pre-ART and on-ART mortality. For each parameter we generated probabilities and distributions for Monte Carlo simulations with one week cycles to estimate mortality 52 weeks from clinic entry. Results We estimated an increase in mortality from 11.0% to 14.7% (relative increase of 34%) with a 10 week delay in ART for patients entering care with our pre-ART cohort CD4 distribution. When we examined low CD4 ranges, the relative increase in mortality delays remained similar; however, the absolute increase in mortality rose. For example, among patients entering with CD4 count 50–99 cells/mm3, 12 month mortality increased from 13.3% with no delay compared to 17.0% with a 10 week delay and 22.9% with a 6 month delay. Conclusions Delays in ART initiation, common in routine HIV programs, can lead to important increases in mortality. Prompt ART initiation for patients entering clinical care and eligible for ART, especially those with lower CD4 counts, could be a relatively low cost approach with a potential marked impact on mortality. PMID:23392457

  20. Hypoglycemia After Initiation of Basal Insulin in Patients with Type 2 Diabetes in the United States: Implications for Treatment Discontinuation and Healthcare Costs and Utilization.

    PubMed

    Dalal, Mehul R; Kazemi, Mahmood; Ye, Fen; Xie, Lin

    2017-08-04

    Hypoglycemia and fear of hypoglycemia may contribute to basal insulin discontinuation, poor glycemic control, and increased healthcare burden in patients with type 2 diabetes (T2D). This study aimed to determine the impact of hypoglycemia soon after basal insulin initiation on treatment discontinuation and economic outcomes in patients with T2D. Hypoglycemic events within 6 months of basal insulin initiation were identified using retrospective cohort data from patients with T2D, at least 18 years of age, initiated on basal insulin therapy in the Clinformatics™ Data Mart for Multiplan claims database from January 1, 2008, through August 31, 2012. Data were adjusted for baseline characteristics. Discontinuation was established for patients with 12-month follow-up data, while discontinuation risk was assessed in the extended analysis (6- to 24-month follow-up) by Cox regression analysis. Healthcare use and costs were determined. Of 55,608 patients, 4.5% experienced hypoglycemia within 6 months of basal insulin initiation. Patients with hypoglycemia were more likely to discontinue basal insulin within 12 months of initiation (79.0% vs. 74.2%; P < 0.001). Data, adjusted for baseline characteristics such as age, any baseline hypoglycemia, and use of oral antidiabetes drugs, showed that patients with hypoglycemia had a greater risk of discontinuation (hazard ratio 1.16; 95% confidence interval 1.03, 1.32; P = 0.0164), were more likely to have a hospitalization (41.0% vs. 24.3%; P < 0.001) or an ED visit (55.8% vs. 35.1%; P < 0.001), and had higher diabetes-related ($13,662 vs. $7506; P < 0.001) and all-cause ($30,719 vs. $19,079; P < 0.001) healthcare costs. US patients with T2D who experienced hypoglycemia within 6 months of basal insulin initiation were more likely to discontinue treatment, accompanied by a greater healthcare burden. Sanofi US, Inc.

  1. Factors influencing decision-making role preferences: A qualitative study of Malaysian patients with type 2 diabetes during insulin initiation.

    PubMed

    Lee, Yew Kong; Low, Wah Yun; Lee, Ping Yein; Ng, Chirk Jenn

    2015-05-01

    Patient decision-making role preference (DMRP) is a patient's preferred degree of control when making medical decisions. This descriptive qualitative study aimed to explore Malaysian patients' views on their DMRP. Between January 2011 and March 2012, 22 individual face-to-face in-depth interviews were conducted with patients with type 2 diabetes who were deciding about insulin initiation. The interviews were audio-recorded and analysed using a thematic approach. The age range of participants was 28-67 years old with 11 men. Ten patients preferred to make the decision themselves, six patients indicated that the clinician should make the decision and only one patient expressed a preference for a collaborative role. The following factors influenced DMRP: trust in clinicians, responsibility for diabetes care, level of knowledge and awareness, involvement of family and personal characteristics. In conclusion, the concept of shared decision-making is still alien, and a more participative communication style might help to facilitate patients' expression of DMRP. © 2014 Wiley Publishing Asia Pty Ltd.

  2. Development and implementation of mass media campaigns to delay sexual initiation among African American and White youth.

    PubMed

    Noar, Seth M; Zimmerman, Rick S; Palmgreen, Philip; Cupp, Pamela K; Floyd, Brenikki R; Mehrotra, Purnima

    2014-01-01

    Reducing new HIV/STD infections among at-risk adolescents requires developing and evaluating evidence-based health communication approaches. Research overwhelmingly supports the conclusion that early sexual initiation is associated with STDs and other negative outcomes in later years (e.g., unintended pregnancy). The authors' research group secured funding from the National Institute of Mental Health to develop, implement, and rigorously evaluate televised mass media campaigns to delay initiation of sexual intercourse among African American and White adolescents in two cities in the Southeastern United States. The focus of the present study is on the development and implementation of the campaigns, including (a) rationale and theoretical underpinnings; (b) collection, screening, and assessment of existing public service announcements; (c) development of new public service announcements; (d) study design and campaign airing plan; and (e) message exposure achieved in the campaigns. Health communication campaigns hold much promise in reaching at-risk adolescent populations with targeted, timely, and relevant risk-reduction messages.

  3. Evaluation of insulin initiation on resource utilization and direct costs of treatment over 12 months in patients with type 2 diabetes in Europe: results from INSTIGATE and TREAT observational studies.

    PubMed

    Brismar, Kerstin; Benroubi, Marianna; Nicolay, Claudia; Schmitt, Henry; Giaconia, Joseph; Reaney, Matthew

    2013-08-01

    To describe the changes in resource utilization in seven European countries (Germany, Greece, Portugal, Romania, Sweden, Spain, and Turkey) and direct costs in four European countries (Germany, Spain, Sweden, and Greece) over the first 12 months of insulin treatment in patients with type 2 diabetes mellitus (T2DM). INSTIGATE and TREAT (2005-2010) were non-interventional, prospective, observational studies in patients with T2DM and initiating insulin for the first time. A 6-month retrospective data capture was conducted at baseline (insulin initiation) followed by prospective data collections at ∼3, 6, and 12 months. Statistical analyses were descriptive; estimated costs are presented as nominal values. This study presents data for 1450 patients. Overall, in the first 6 months after insulin initiation, the use and cost of blood glucose monitoring and insulin increased, while the cost of oral diabetic medication decreased. Contributors to total direct costs differed between countries. Ranges of total mean direct costs over the 6-month period before insulin initiation were €489.10-€658.50 (Greece-Spain); 0-6 months after insulin initiation, €573.40-€1084.70 (Greece-Spain); and 6-12 months after insulin initiation, €495.80-€859.30 (Greece-Germany). Thus, the mean cost of treatment increased in all countries in the first 6 months after insulin initiation and then returned to baseline except in Germany. Overall, 15% of patients were lost to follow-up over 12 months. Costs were not pro-rated to account for variation of visits. Participating centres may not have been fully representative of all levels of care. Contributors to total cost differed between countries, potentially reflecting local clinical practice patterns and insulin regimens. In each country, mean direct total costs of T2DM care increased during the first 6 months after insulin initiation and decreased thereafter.

  4. Considerations for diabetes: treatment with insulin pen devices.

    PubMed

    Cuddihy, Robert M; Borgman, Sarah K

    2013-01-01

    Insulin is essential for the treatment of type 1 diabetes, and most patients with type 2 diabetes will eventually require insulin for glycemic control. Several barriers contribute to delays in initiating insulin therapy in type 2 diabetes. Furthermore, insulin-treated patients often miss doses or otherwise fail to self-administer their insulin as prescribed, placing themselves at the risk of developing complications. Insulin pens can help overcome barriers to initiating insulin therapy and can facilitate the self-management of diabetes. Compared with the vial and syringe, insulin pens are more accurate, associated with greater adherence, and preferred by patients because of their convenience and ease of use. Large database analyses suggest that insulin pens may reduce the rate of occurrence of hypoglycemic events in patients with type 2 diabetes. Despite higher costs of insulin pens vs vials and syringes, studies suggest little or no increase in total health care costs and decreases in diabetes-related costs associated with reduced health care utilization with pens. Interestingly, the use of insulin pens within the United States lags far behind the use of pens in Europe and Japan. Insulin pens may be disposable or refillable, and some pens have special features [eg, audible clicks, large-dose selector and dial, memory function, half-unit dosing, high dosing (ie, 80 U)] that offer the opportunity to individualize treatment by meeting patients' needs. This review compares available insulin pens, describes strategies to facilitate their usage, and discusses how insulin pens can improve self-management of diabetes while reducing cost.

  5. [The delay of pharyngeal phase initiation vs the course of the deglutition act in patients after partial or total tongue excision due to oral cancer].

    PubMed

    Halczy-Kowalik, Ludmiła; Wysocki, Rościsław; Posio, Violetta

    2006-01-01

    The coordination of the respiratory and alimentary function is indispensable to transport the food from the oral cavity to the stomach without aspiration risk. Disturbances during pharyngeal phase of swallowing, registered after oral tumour excision, are caused by diminishing of the tongue shape, decreasing of gustatory sensitivity and oral stereognosis. The aim of the work is to estimate the influence the oral tissue excision to the pharyngeal phase of deglution. videoradiological examination of deglutition by W.J. Dodds - for 95 patients after oral tumour excision, with swallowing disturbances. Duration of oral and pharyngeal activities, degree of realization these activities and aspiration risk were valued. Abnormal mobility of tongue, lack of palato-pharyngeal and glosso-pharyngeal closure, abnormal formation of bolus accompanied to delayed initiation of pharyngeal phase. The delay of pharyngeal phase initiation was the most important for beginning and ending of the larynx closure, oesophagus opening, pharynx emptying. This delay wasn't statistically significant for duration these activities. The retention in oral cavity and in lower throat, additional deglutitions, inter-deglutition and postdeglutition leakage correlated with delay of the pharyngeal phase initiation. 1. The delay of pharyngeal phase initation after oral tumour excision is caused by oral swallowing disturbances. 2. The delay of pharyngeal phase initiation after oral tumor excision is dependent on the range of surgery and reconstruction. 3. The delay of pharyngeal phase initiation after oral tumour excision is important for beginning and ending of the pharyngeal phase activities, it isn't important for their duration. 4. The deficit of oral sensory stimuli causes desynchronization of the pharyngeal phase activities and diminishes the swallowing efficiency. 5. Improvement of the swallowing efficiency after partial or total tongue excision is possible by oral phase elongation, by monitoring of the

  6. The Leu7Pro polymorphism of preproNPY is associated with decreased insulin secretion, delayed ghrelin suppression, and increased cardiovascular responsiveness to norepinephrine during oral glucose tolerance test.

    PubMed

    Jaakkola, Ulriikka; Kuusela, Tom; Jartti, Tuomas; Pesonen, Ullamari; Koulu, Markku; Vahlberg, Tero; Kallio, Jaana

    2005-06-01

    Neuropeptide Y (NPY) plays a role in angiogenesis, cardiovascular regulation, and hormone secretion. The leucine7 to proline7 (Leu7Pro) polymorphism of preproNPY is associated with vascular diseases and has an impact on hormone levels in healthy subjects. The current study investigated the role of the Leu7Pro polymorphism in metabolic and cardiovascular autonomic regulation. A 5-h oral glucose tolerance test was performed on 27 healthy volunteers representing two preproNPY genotypes (Leu7/Pro7 and Leu7/Leu7) matched for age, sex, body mass index and physical activity. Simultaneously we performed cardiovascular autonomic function tests and plasma measurements of sympathetic transmitters, glucose, insulin, and ghrelin. The subjects with Leu7/Pro7 genotype had decreased plasma NPY, norepinephrine (NE), and insulin concentrations and insulin to glucose ratios. The suppression of ghrelin concentrations after glucose ingestion was delayed in these subjects. They also had increased heart rate variability indices and baroreflex sensitivity. However, they displayed significant negative association of NE concentration with variability of low-frequency R-R-intervals and with baroreflex sensitivity. The Leu7Pro polymorphism of preproNPY is related to decreased level of basal sympathetic activity, decreased insulin secretion, and delayed ghrelin suppression during oral glucose tolerance test. The increased responsiveness of autonomic functions to NE associated with the polymorphism may be connected to increased cardiovascular vulnerability.

  7. Delayed Initiation but Not Gradual Advancement of Enteral Formula Feeding Reduces the Incidence of Necrotizing Enterocolitis (NEC) in Preterm Pigs

    PubMed Central

    Ghoneim, Nada; Bauchart-Thevret, Caroline; Oosterloo, Berthe; Stoll, Barbara; Kulkarni, Madhulika; de Pipaon, Miguel Saenz; Zamora, Irving J.; Olutoye, Oluyinka O.; Berg, Brian; Wittke, Anja; Burrin, Douglas G.

    2014-01-01

    Enteral formula feeding is a risk factor for necrotizing enterocolitis (NEC) in premature infants, yet studies are conflicting regarding the safest timing for introduction and advancement of feeds. Our aim was to test the effects of early vs. late initiation and abrupt vs. gradual advancement of enteral feeding of an intact vs. hydrolyzed protein formula on NEC incidence and severity in preterm pigs. In Experiment 1, preterm pigs received total parenteral nutrition (TPN) at birth with abrupt initiation of enteral formula feeds (50% full intake) on d of life (DOL) 2 (EA) or 5 (LA) while PN continued. Pigs were also fed formula containing either intact or hydrolyzed protein. In Experiment 2, preterm pigs received TPN at birth with enteral, hydrolyzed-protein formula feeds introduced on DOL 2 either abruptly (EA; 50% full feeds) or gradually (EG; 10–50% full feeds over 5 d) while PN continued. NEC incidence and severity were assessed based on macroscopic and histological scoring. In Experiment 1, NEC incidence (41% vs. 70%, P<0.05) and severity were reduced in LA vs. EA groups and LA was associated with a higher survival rate, daily weight gain and jejunum villus height. Piglets fed hydrolyzed vs. intact protein formula had lower stomach content weights and similar NEC incidence. In Experiment 2, NEC incidence and severity were not different between pigs the EG vs. EA group. Proinflammatory gene expression (IL-1β, IL-6 and S100A9) in the ileum was lower in both LA and EG vs. EA groups. In conclusion, delayed initiation but not gradual advancement of enteral feeding is protective against NEC in preterm pigs. Feeding hydrolyzed vs. intact protein formula improved gastric transit without affecting the NEC incidence. PMID:25238061

  8. Systemic delays in the initiation of antiretroviral therapy during pregnancy do not improve outcomes of HIV-positive mothers: a cohort study

    PubMed Central

    2012-01-01

    Background Antiretroviral therapy (ART) initiation in eligible HIV-infected pregnant women is an important intervention to promote maternal and child health. Increasing the duration of ART received before delivery plays a major role in preventing vertical HIV transmission, but pregnant women across Africa experience significant delays in starting ART, partly due the perceived need to deliver ART counseling and patient education before ART initiation. We examined whether delaying ART to provide pre-ART counseling was associated with improved outcomes among HIV-infected women in Cape Town, South Africa. Methods We undertook a retrospective cohort study of 490 HIV-infected pregnant women referred to initiate treatment at an urban ART clinic. At this clinic all patients including pregnant women are screened by a clinician and then undergo three sessions of counseling and patient education prior to starting treatment, commonly introducing delays of 2–4 weeks before ART initiation. Data on viral suppression and retention in care after ART initiation were taken from routine clinic records. Results A total of 382 women initiated ART before delivery (78%); ART initiation before delivery was associated with earlier gestational age at presentation to the ART service (p < 0.001). The median delay between screening and ART initiation was 21 days (IQR, 14–29 days). Overall, 84.7%, 79.6% and 75.0% of women who were pregnant at the time of ART initiation were retained in care at 4, 8 and 12 months after ART initiation, respectively. Among those retained, 91% were virally suppressed at each follow-up visit. However the delay from screening to ART initiation was not associated with retention in care and/or viral suppression throughout the first year on ART in unadjusted or adjusted analyses. Conclusions A substantial proportion of eligible pregnant women referred for ART do not begin treatment before delivery in this setting. Among women who do initiate ART, delaying

  9. Importance of transcapillary insulin transport on insulin action in vivo

    SciTech Connect

    Yang, Y.J.

    1989-01-01

    The relationship between transcapillary insulin transport and insulin action was examined in normal conscious dogs. Plasma and thoracic duct lymph insulin, and insulin action were simultaneously measured during euglycemic clamps and intravenous glucose tolerance tests. During the clamps, while {sup 14}C-inulin reached an equilibrium, steady-state (ss) plasma insulin was higher than lymph and the ratio of 3:2 was maintained during basal, activation and deactivation phases: 18 {+-} 2 vs. 12 {+-} 1, 51 {+-} 2 vs. 32 {+-} 1, and 18 {+-} 3 vs. 13 {+-} 1 {mu}U/ml. In addition, it took longer for lymph insulin to reach ss than plasma insulin during activation and deactivation: 11 {+-} 2 vs. 31 {+-} 5 and 8 {+-} 2 vs. 32 {+-} 6 min. During IVGTT, plasma insulin peaked within 5 {+-} 2 min; lymph insulin rose slowly to a lower peak. The significant gradient and delay between plasma and lymph insulin concentrations suggest a restricted transcapillary insulin transport.

  10. Delayed bone regeneration and low bone mass in a rat model of insulin-resistant type 2 diabetes mellitus is due to impaired osteoblast function.

    PubMed

    Hamann, Christine; Goettsch, Claudia; Mettelsiefen, Jan; Henkenjohann, Veit; Rauner, Martina; Hempel, Ute; Bernhardt, Ricardo; Fratzl-Zelman, Nadja; Roschger, Paul; Rammelt, Stefan; Günther, Klaus-Peter; Hofbauer, Lorenz C

    2011-12-01

    Patients with diabetes mellitus have an impaired bone metabolism; however, the underlying mechanisms are poorly understood. Here, we analyzed the impact of type 2 diabetes mellitus on bone physiology and regeneration using Zucker diabetic fatty (ZDF) rats, an established rat model of insulin-resistant type 2 diabetes mellitus. ZDF rats develop diabetes with vascular complications when fed a Western diet. In 21-wk-old diabetic rats, bone mineral density (BMD) was 22.5% (total) and 54.6% (trabecular) lower at the distal femur and 17.2% (total) and 20.4% (trabecular) lower at the lumbar spine, respectively, compared with nondiabetic animals. BMD distribution measured by backscattered electron imaging postmortem was not different between diabetic and nondiabetic rats, but evaluation of histomorphometric indexes revealed lower mineralized bone volume/tissue volume, trabecular thickness, and trabecular number. Osteoblast differentiation of diabetic rats was impaired based on lower alkaline phosphatase activity (-20%) and mineralized matrix formation (-55%). In addition, the expression of the osteoblast-specific genes bone morphogenetic protein-2, RUNX2, osteocalcin, and osteopontin was reduced by 40-80%. Osteoclast biology was not affected based on tartrate-resistant acidic phosphatase staining, pit formation assay, and gene profiling. To validate the implications of these molecular and cellular findings in a clinically relevant model, a subcritical bone defect of 3 mm was created at the left femur after stabilization with a four-hole plate, and bone regeneration was monitored by X-ray and microcomputed tomography analyses over 12 wk. While nondiabetic rats filled the defects by 57%, diabetic rats showed delayed bone regeneration with only 21% defect filling. In conclusion, we identified suppressed osteoblastogenesis as a cause and mechanism for low bone mass and impaired bone regeneration in a rat model of type 2 diabetes mellitus.

  11. Delay in initiation of treatment after diagnosis of pulmonary tuberculosis in primary health care setting: eight year cohort analysis from district Faridabad, Haryana, North India.

    PubMed

    Kant, Shashi; Singh, Arvind K; Parmeshwaran, Giridara G; Haldar, Partha; Malhotra, Sumit; Kaur, Ravneet

    2017-01-01

    Delay in initiation of tuberculosis (TB) treatment may have a tremendous impact on disease transmission, development of drug resistance, poor outcome and overall survival of TB patients. The delay can occur at various levels. Delay in initiation of treatment after diagnosis is mostly due to health system failure and has immense programmatic implications. It has not been studied extensively in the Indian setting. The authors did a cohort analysis of all TB patients initiated on treatment from two primary health centres (PHCs) at Ballabgarh Health and Demographic Surveillance System between January 2007 and December 2014. Diagnosis and treatment of TB in the study area was done as per the protocol envisaged in the national program. Information related to demography, details of diagnosis and treatment of TB and outcome of treatment were extracted from the TB register. Delay in initiation of treatment after diagnosis was considered if the gap between diagnosis and treatment was greater than 7 days. Bivariate and multivariate analyses were done to find the association of various factors with delay in initiation of treatment after diagnosis. Out of 885 patients, 662 patients started treatment for pulmonary TB. Mean time interval between diagnosis and initiation of treatment was 8.95 days. Only 57.7% of pulmonary TB patients were started on treatment within 7 days of diagnosis, and an additional 24.5% were started on treatment 8-14 days after diagnosis. Patients on retreatment regimens and those residing in villages without a PHC were more likely to have delayed initiation of treatment (odds ratio (OR)=1.82 (1.3-2.7, p=0.001) and OR=1.62 (1.1-2.5, p=0.01) respectively). Delay in initiation of treatment was also associated with unfavourable treatment outcome such as default, failure or death. There is a need to have healthcare changes related to TB care to enable initiation of treatment as early as possible. Pretreatment counselling especially for retreatment

  12. Insulin secretagogues for prevention or delay of type 2 diabetes mellitus and its associated complications in persons at increased risk for the development of type 2 diabetes mellitus.

    PubMed

    Hemmingsen, Bianca; Sonne, David Peick; Metzendorf, Maria-Inti; Richter, Bernd

    2016-10-17

    The projected rise in the incidence of type 2 diabetes mellitus (T2DM) could develop into a substantial health problem worldwide. Whether insulin secretagogues (sulphonylureas and meglitinide analogues) are able to prevent or delay T2DM and its associated complications in people at risk for the development of T2DM is unknown. To assess the effects of insulin secretagogues on the prevention or delay of T2DM and its associated complications in people with impaired glucose tolerance, impaired fasting blood glucose, moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and the reference lists of systematic reviews, articles and health technology assessment reports. We asked investigators of the included trials for information about additional trials. The date of the last search of all databases was April 2016. We included randomised controlled trials (RCTs) with a duration of 12 weeks or more comparing insulin secretagogues with any pharmacological glucose-lowering intervention, behaviour-changing intervention, placebo or no intervention in people with impaired fasting glucose, impaired glucose tolerance, moderately elevated HbA1c or combinations of these. Two review authors read all abstracts and full-text articles/records, assessed quality and extracted outcome data independently. One review author extracted data which were checked by a second review author. We resolved discrepancies by consensus or the involvement of a third review author. For meta-analyses we used a random-effects model with investigation of risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We carried out trial sequential analyses (TSAs) for all outcomes that could be meta

  13. Clinical utility of insulin and insulin analogs.

    PubMed

    Sanlioglu, Ahter D; Altunbas, Hasan Ali; Balci, Mustafa Kemal; Griffith, Thomas S; Sanlioglu, Salih

    2013-01-01

    Diabetes is a pandemic disease characterized by autoimmune, genetic and metabolic abnormalities. While insulin deficiency manifested as hyperglycemia is a common sequel of both Type-1 and Type-2 diabetes (T1DM and T2DM), it does not result from a single genetic defect--rather insulin deficiency results from the functional loss of pancreatic β cells due to multifactorial mechanisms. Since pancreatic β cells of patients with T1DM are destroyed by autoimmune reaction, these patients require daily insulin injections. Insulin resistance followed by β cell dysfunction and β cell loss is the characteristics of T2DM. Therefore, most patients with T2DM will require insulin treatment due to eventual loss of insulin secretion. Despite the evidence of early insulin treatment lowering macrovascular (coronary artery disease, peripheral arterial disease and stroke) and microvascular (diabetic nephropathy, neuropathy and retinopathy) complications of T2DM, controversy exists among physicians on how to initiate and intensify insulin therapy. The slow acting nature of regular human insulin makes its use ineffective in counteracting postprandial hyperglycemia. Instead, recombinant insulin analogs have been generated with a variable degree of specificity and action. Due to the metabolic variability among individuals, optimum blood glucose management is a formidable task to accomplish despite the presence of novel insulin analogs. In this article, we present a recent update on insulin analog structure and function with an overview of the evidence on the various insulin regimens clinically used to treat diabetes.

  14. Clinical utility of insulin and insulin analogs

    PubMed Central

    Sanlioglu, Ahter D.; Altunbas, Hasan Ali; Balci, Mustafa Kemal; Griffith, Thomas S.; Sanlioglu, Salih

    2013-01-01

    Diabetes is a pandemic disease characterized by autoimmune, genetic and metabolic abnormalities. While insulin deficiency manifested as hyperglycemia is a common sequel of both Type-1 and Type-2 diabetes (T1DM and T2DM), it does not result from a single genetic defect—rather insulin deficiency results from the functional loss of pancreatic β cells due to multifactorial mechanisms. Since pancreatic β cells of patients with T1DM are destroyed by autoimmune reaction, these patients require daily insulin injections. Insulin resistance followed by β cell dysfunction and β cell loss is the characteristics of T2DM. Therefore, most patients with T2DM will require insulin treatment due to eventual loss of insulin secretion. Despite the evidence of early insulin treatment lowering macrovascular (coronary artery disease, peripheral arterial disease and stroke) and microvascular (diabetic nephropathy, neuropathy and retinopathy) complications of T2DM, controversy exists among physicians on how to initiate and intensify insulin therapy. The slow acting nature of regular human insulin makes its use ineffective in counteracting postprandial hyperglycemia. Instead, recombinant insulin analogs have been generated with a variable degree of specificity and action. Due to the metabolic variability among individuals, optimum blood glucose management is a formidable task to accomplish despite the presence of novel insulin analogs. In this article, we present a recent update on insulin analog structure and function with an overview of the evidence on the various insulin regimens clinically used to treat diabetes. PMID:23584214

  15. Initial Accuracy of HIV Rapid Test Kits Stored in Suboptimal Conditions and Validity of Delayed Reading of Oral Fluid Tests.

    PubMed

    Choko, Augustine T; Taegtmeyer, Miriam; MacPherson, Peter; Cocker, Derek; Khundi, McEwen; Thindwa, Deus; Sambakunsi, Rodrick S; Kumwenda, Moses K; Chiumya, Kondwani; Malema, Owen; Makombe, Simon D; Webb, Emily L; Corbett, Elizabeth L

    2016-01-01

    To evaluate the effect of storing commonly used rapid diagnostic tests above manufacturer-recommended temperature (at 37°C), and the accuracy of delayed reading of oral fluid kits with relevance to HIV self-testing programmes. A quality assurance study of OraQuick (OraSure), Determine HIV 1/2™ (Alere) and Uni-Gold™ (Recombigen®). Consecutive adults (≥18y) attending Ndirande Health Centre in urban Blantyre, Malawi in January to April 2012 underwent HIV testing with two of each of the three rapid diagnostic test kits stored for 28 days at either 18°C (optimally-stored) or at 37°C (pre-incubated). Used OraQuick test kits were stored in a laboratory for delayed day 1 and subsequent monthly re-reading was undertaken for one year. Of 378 individuals who underwent parallel testing, 5 (1.3%) were dropped from the final analysis due to discordant or missing reference standard results (optimally-stored Determine and Uni-Gold). Compared to the diagnostic reference standard, OraQuick had a sensitivity of 97.2% (95% CI: 93.6-99.6). There were 7 false negative results among all test kits stored at 37°C and three false negatives among optimally stored kits. Excellent agreement between pre-incubated tests and optimally-stored tests with Kappa values of 1.00 for Determine and Uni-Gold; and 0.97 (95% CI: 0.95; 1.00) for OraQuick were observed. There was high visual stability on re-reading of OraQuick, with only 1/375 pre-incubated and 1/371 optimally-stored OraQuick kits changing from the initial result over 12 months. Erroneous results observed during HIV testing in low income settings are likely to be due to factors other than suboptimal storage conditions. Re-reading returned OraQuick kits may offer a convenient and accurate quality assurance approach, including in HIV self-testing programmes.

  16. Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial

    PubMed Central

    Grinsztejn, Beatriz; Hosseinipour, Mina C; Ribaudo, Heather J; Swindells, Susan; Eron, Joseph; Chen, Ying Q; Wang, Lei; Ou, San-San; Anderson, Maija; McCauley, Marybeth; Gamble, Theresa; Kumarasamy, Nagalingeshwaran; Hakim, James G; Kumwenda, Johnstone; Pilotto, Jose H S; Godbole, Sheela V; Chariyalertsak, Suwat; de Melo, Marineide Gonçalves; Mayer, Kenneth H; Eshleman, Susan H; Piwowar-Manning, Estelle; Makhema, Joseph; Mills, Lisa A; Panchia, Ravindre; Sanne, Ian; Gallant, Joel; Hoffman, Irving; Taha, Taha E; Nielsen-Saines, Karin; Celentano, David; Essex, Max; Havlir, Diane; Cohen, Myron S

    2014-01-01

    Summary Background Use of antiretroviral treatment for HIV-1 infection has decreased AIDS-related morbidity and mortality and prevents sexual transmission of HIV-1. However, the best time to initiate antiretroviral treatment to reduce progression of HIV-1 infection or non-AIDS clinical events is unknown. We reported previously that early antiretroviral treatment reduced HIV-1 transmission by 96%. We aimed to compare the effects of early and delayed initiation of antiretroviral treatment on clinical outcomes. Methods The HPTN 052 trial is a randomised controlled trial done at 13 sites in nine countries. We enrolled HIV-1-serodiscordant couples to the study and randomly allocated them to either early or delayed antiretroviral treatment by use of permuted block randomisation, stratified by site. Random assignment was unblinded. The HIV-1-infected member of every couple initiated antiretroviral treatment either on entry into the study (early treatment group) or after a decline in CD4 count or with onset of an AIDS-related illness (delayed treatment group). Primary events were AIDS clinical events (WHO stage 4 HIV-1 disease, tuberculosis, and severe bacterial infections) and the following serious medical conditions unrelated to AIDS: serious cardiovascular or vascular disease, serious liver disease, end-stage renal disease, new-onset diabetes mellitus, and non-AIDS malignant disease. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00074581. Findings 1763 people with HIV-1 infection and a serodiscordant partner were enrolled in the study; 886 were assigned early antiretroviral treatment and 877 to the delayed treatment group (two individuals were excluded from this group after randomisation). Median CD4 counts at randomisation were 442 (IQR 373–522) cells per μL in patients assigned to the early treatment group and 428 (357–522) cells per μL in those allocated delayed antiretroviral treatment. In the delayed group

  17. Initial bone preparation followed by a 2-week delay before implant placement enhances the clinical and radiographic outcome: a randomized controlled trial.

    PubMed

    Bansal, J; Suresh, D K; Bansal, A

    2014-10-01

    Initial bone preparation followed by a 2-week delay before implant placement enhances the biological activity at the osteotomy site, which may improve the treatment outcome. The aim of this study was to compare the clinical and radiographic outcomes of initial bone preparation and a 2-week delay in implant placement with the conventional method. Subjects were outpatients selected from a department of periodontology and oral implantology. The implant sites were randomly allocated to a test group and a control group (n=7 each). Test sites were treated with initial bone preparation followed by implant placement after a 2-week delay; control sites were treated with the conventional protocol. All sites were assessed over 12 months for the keratinized mucosa index, probing depth, implant mobility, and radiographic peri-implant crestal bone levels. A total of 14 implants were placed in 12 subjects (five males and seven females, mean age 31.5 years, range 18-45 years). The results showed a statistically significant reduction in peri-implant probing depth and crestal bone levels in the test group (P<0.01). This randomized controlled trial demonstrated better clinical and radiographic outcomes for initial bone preparation followed by a 2-week delay in implant placement; this may be an alternative to the conventional protocol. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  18. The dynamic relationship between current and previous severe hypoglycemic events: a lagged dependent variable analysis among patients with type 2 diabetes who have initiated basal insulin.

    PubMed

    Ganz, Michael L; Li, Qian; Wintfeld, Neil S; Lee, Yuan-Chi; Sorli, Christopher; Huang, Joanna C

    2015-01-01

    Past studies have found episodes of severe hypoglycemia (SH) to be serially dependent. Those studies, however, only considered the impact of a single (index) event on future risk; few have analyzed SH risk as it evolves over time in the presence (or absence) of continuing events. The objective of this study was to determine the dynamic risks of SH events conditional on preceding SH events among patients with type 2 diabetes (T2D) who have initiated basal insulin. We used an electronic health records database from the United States that included encounter and laboratory data and clinical notes on T2D patients who initiated basal insulin therapy between 2008 and 2011 and to identify SH events. We used a repeated-measures lagged dependent variable logistic regression model to estimate the impact of SH in one quarter on the risk of SH in the next quarter. We identified 7235 patients with T2D who initiated basal insulin. Patients who experienced ≥1 SH event during any quarter were more likely to have ≥1 SH event during the subsequent quarter than those who did not (predicted probabilities of 7.4% and 1.0%, respectively; p < 0.01). This effect was stronger than the impact of history of SH before starting basal insulin (predicted probabilities of 1.0% and 3.2%, respectively; p < 0.01) or of a history of SH during the titration period (predicted probabilities of 1.1% and 2.8%, respectively; p < 0.01). The risk of experiencing a SH event is highly dependent on a patient's immediate history of SH events and therefore the value of preventing one SH event may be substantial. These results can inform patient care by providing clinicians with dynamic data on a patient's risk of SH, which in turn can facilitate appropriate adjustment of the risk-benefit ratio for individualized patient care. These results should, however, be interpreted in light of the key limitations of our study: not all SH events may have been captured or coded in the database, data on filled

  19. Individualizing insulin therapy in the management of type 2 diabetes.

    PubMed

    Moghissi, Etie; King, Allen B

    2014-10-01

    It is recognized that reducing hyperglycemia early on in disease progression has long-term benefits for patients with diabetes. Insulin therapy has greater potential to reduce hyperglycemia than other therapies; however, there is often a significant delay in insulin initiation and intensification. Insulin replacement therapy in type 2 diabetes should no longer be viewed as the treatment of last resort. With the development of modern insulin analogs, the field has evolved. Large clinical trials have improved our understanding of the potential benefits and risks associated with intensive glycemic control in different patient populations and highlighted the need for individualization of glycemic targets and treatment strategies. Current treatment guidelines recognize the important role of insulin therapy both early on and throughout the progression of type 2 diabetes.

  20. Delays in hiring Air Traffic Collegiate Training Initiative (AT-CTI) graduates and the impact on their training success rate

    NASA Astrophysics Data System (ADS)

    Jorgenson, Terra A.

    This research project identified three distinct groups of individuals the Federal Aviation Administration (FAA) utilizes when filling the employee ranks of Air Traffic Controllers (ATC). After a nationwide strike, President Reagan fired the entire ATC workforce in 1981 (Pavel, 2012). Since then the FAA has worked very diligently in filling the vacant positions. Now three decades later the impending retirements and attrition of those hired earlier is estimated at nearly 14,000 controllers over the next 10 years (FAA CWP, 2012). In response to this shortage it would be advantageous for the FAA to minimize the time lapsed in the selection, hiring and training processes. If the hiring process time was decreased, it would save the FAA money in terms of a reduction in the initial cost of training Air Traffic Controllers (GAO, 2012; IRP, 2011). Traditionally the FAA hires from three distinct groups of people. The first is those with prior ATC experience which was usually obtained through the military. Second the general public with no experience and third the Air Traffic Collegiate Training Initiative (AT-CTI) candidates. The AT-CTI program is a valued partner with the FAA that helps educate the next generation of Air Traffic Controllers; however in the past the program has had difficulty producing the total number of replacement controllers needed. Due to the delay some CTI graduates may choose other career paths rather than wait and be hired to go to the FAA Academy which will further reduce the number of candidates for the FAA to hire. To date, no public research has been done pertaining to the time delay in the hiring process of AT-CTI candidates and the impact on training success at the FAA Academy and at the CTI's first FAA facility. This study used a survey tool to gather information on how long AT-CTI graduates wait to be hired to attend the FAA Academy. Information was gathered on the factors that may affect the time lapse between graduation and the time they

  1. Baseline and 1-year interim follow-up assessment of Japanese patients initiating insulin therapy who were enrolled in the cardiovascular risk evaluation in people with type 2 diabetes on insulin therapy study: an international, multicenter, observational study.

    PubMed

    Kawamori, Ryuzo; Node, Koichi; Hanafusa, Toshiaki; Atsumi, Yoshihito; Naito, Yusuke; Oka, Yoshitomo

    2013-09-08

    21.8% of patients over 6 to 12 months. Our results suggest that insulin treatment is an effective and safe therapeutic option in Japanese patients with T2DM, and earlier insulin initiation might be associated with better glycemic control.

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

    PubMed

    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.

  3. Predictors of Initiating Rapid-Acting Insulin Analog Using Vial/Syringe, Prefilled Pen, and Reusable Pen Devices in Patients with Type 2 Diabetes

    PubMed Central

    Lee, Lauren J.; Anderson, Julie; Foster, Shonda A.; Corrigan, Sheila M.; Smith, David M.; Curkendall, Suellen

    2010-01-01

    Background Limited data are available on the predictors of insulin delivery device choice. This study assessed the patient- and health-care-system-related factors that predict the initiation of one rapid-acting insulin analog (RAIA) delivery system over another. Methods A retrospective analysis using a claims database (January 1, 2007, through March 31, 2009) was conducted. Patients were required to be diagnosed with type 2 diabetes mellitus, and have ≥12 months of continuous eligibility prior to their first prescription of a RAIA on or after January 1, 2008. The three cohorts in the study were vial/syringe (n = 6820), prefilled pen (n = 5840), and reusable pen (n = 2052). Multiple factors were examined using stepwise logistic regression. Results Factors that increased the likelihood of initiating RAIA using prefilled pen versus vial/syringe included endocrinologist visit [odds ratio (OR) = 3.13, 95% confidence interval (CI) = 2.56, 3.82], prior basal insulin use with pen (OR = 4.85, 95% CI = 4.21, 5.59), and use of ≥1 oral antihyperglycemic agents (OR = 1.32, 95% CI = 1.20, 1.45). Factors that decreased the likelihood included inpatient admission (OR = 0.76, 95% CI = 0.70, 0.83), nursing home visit (OR = 0.22, 95% CI = 0.18, 0.27), and obesity (OR = 0.67, 95% CI = 0.53, 0.83). There were fewer differences between prefilled and reusable pen initiators. Factors that increased the likelihood of initiating with prefilled versus reusable pen included endocrinologist visit (OR = 1.87, CI = 1.50, 2.34) and inpatient admission (OR = 1.46, 95% CI = 1.30, 1.64). Conclusion Significant differences in predictors were observed between prefilled pen and vial/syringe initiators. The differences were fewer between prefilled and reusable pen initiators. These differences should be taken into consideration when evaluating outcomes associated with specific insulin delivery systems. PMID:20513319

  4. Initiation of insulin glargine therapy in type 2 diabetes subjects suboptimally controlled on oral antidiabetic agents: results from the AT.LANTUS trial.

    PubMed

    Davies, M; Lavalle-González, F; Storms, F; Gomis, R

    2008-05-01

    For many patients with type 2 diabetes, oral antidiabetic agents (OADs) do not provide optimal glycaemic control, necessitating insulin therapy. Fear of hypoglycaemia is a major barrier to initiating insulin therapy. The AT.LANTUS study investigated optimal methods to initiate and maintain insulin glargine (LANTUS, glargine, Sanofi-aventis, Paris, France) therapy using two treatment algorithms. This subgroup analysis investigated the initiation of once-daily glargine therapy in patients suboptimally controlled on multiple OADs. This study was a 24-week, multinational (59 countries), multicenter (611), randomized study. Algorithm 1 was a clinic-driven titration and algorithm 2 was a patient-driven titration. Titration was based on target fasting blood glucose < or =100 mg/dl (< or =5.5 mmol/l). Algorithms were compared for incidence of severe hypoglycaemia [requiring assistance and blood glucose <50 mg/dl (<2.8 mmol/l)] and baseline to end-point change in haemoglobin A(1c) (HbA(1c)). Of the 4961 patients enrolled in the study, 865 were included in this subgroup analysis: 340 received glargine plus 1 OAD and 525 received glargine plus >1 OAD. Incidence of severe hypoglycaemia was <1%. HbA(1c) decreased significantly between baseline and end-point for patients receiving glargine plus 1 OAD (-1.4%, p < 0.001; algorithm 1 -1.3% vs. algorithm 2 -1.5%; p = 0.03) and glargine plus >1 OAD (-1.7%, p < 0.001; algorithm 1 -1.5% vs. algorithm 2 -1.8%; p = 0.001). This study shows that initiation of once-daily glargine with OADs results in significant reduction of HbA(1c) with a low risk of hypoglycaemia. The greater reduction in HbA(1c) was seen in patients randomized to the patient-driven algorithm (algorithm 2) on 1 or >1 OAD.

  5. Inhaled technosphere regular insulin powder.

    PubMed

    Anderson, Zachary L; Clements, Jennifer N

    2015-11-01

    The lungs are an effective way to deliver insulin for patients with diabetes, but an initial inhaled insulin product was withdrawn from the market because of high cost and inconsistent dosing. This article describes a recently approved inhaled insulin that appears to control blood glucose as well as rapid-acting injectable insulin.

  6. Comparison of propranolol, metoprolol, and acebutolol on insulin-induced hypoglycaemia.

    PubMed Central

    Newman, R J

    1976-01-01

    Metoprolol and acebutolol, two supposedly cardio-selective beta-adrenergic recptor blocking agents, were tested in healthy volunteers against propranolol, a non-selective drug, for their effect on blood glucose levels during insulin-induced hypoglycaemia. There was not significant difference between propranolol and metoprolol, which both potentiated the initial hypoglycaemic action of the insulin and delayed the return to normoglycaemia. Acebutolol, even though potentiating the initial hypoglycaemia, did not possess a significant delaying effect. A similar trial should be undertaken in diabetics to determine with certainty the safety of such drugs in diabetes mellitus. PMID:8187

  7. Insulin therapy in type 2 diabetes.

    PubMed

    Mudaliar, S; Edelman, S V

    2001-12-01

    Type 2 diabetes is a common disorder often accompanied by numerous metabolic abnormalities leading to a high risk of cardiovascular morbidity and mortality. Results from the UKPDS have confirmed that intensive glucose control delays the onset and retards the progression of microvascular disease and possibly of macrovascular disease in patients with type 2 diabetes. In the early stages of the disease, insulin resistance plays a major role in the development of hyperglycemia and other metabolic abnormalities, and patients with type 2 diabetes often benefit from measures to improve insulin sensitivity such as weight loss, dietary changes, and exercise. Later, the use of oral insulin secretagogues and insulin sensitizers as monotherapy and in combination helps maintain glycemia for varying periods of time. Ultimately, because of the progressive nature of the disease and the progressive decline in pancreatic beta-cell function, insulin therapy is almost always obligatory to achieve optimal glycemic goals. Not all patients are candidates for aggressive insulin management; therefore, the goals of therapy should be modified, especially in elderly individuals and those with co-morbid conditions. Candidates for intensive management should be motivated, compliant, and educable, without other major medical conditions and physical limitations that would preclude accurate and reliable HGM and insulin administration. In selected patients, combination therapy with insulin and oral antidiabetic medications can be an effective method for normalizing glycemia without the need for rigorous multiple-injection regimens. The patients for whom combination therapy is most commonly successful are those who do not achieve adequate glycemic control using daytime oral agents but who still show some evidence of responsiveness to the medications. Bedtime intermediate-acting or predinner premixed intermediate- and rapid-acting insulin is administered and progressively increased until the FPG

  8. Insulin use in NIDDM.

    PubMed

    Genuth, S

    1990-12-01

    The effects of insulin treatment on the pathophysiology of non-insulin-dependent diabetes mellitus (NIDDM) are reviewed herein. Short-term studies indicate variable and partial reduction in excessive hepatic glucose output, decrease in insulin resistance, and enhancement of beta-cell function. These beneficial actions may be due to a decrease in secondary glucose toxicity rather than a direct attack on the primary abnormality. Insulin should be used as initial treatment of new-onset NIDDM in the presence of ketosis, significant diabetes-induced weight loss (despite residual obesity), and severe hyperglycemic symptoms. In diet-failure patients, prospective randomized studies comparing insulin to sulfonylurea treatment show approximately equal glycemic outcomes or a slight advantage to insulin. A key goal of insulin therapy is to normalize the fasting plasma glucose level. In contrast to the conventional use of morning injections of intermediate- and long-acting insulin, preliminary studies suggest potential advantages of administering the same insulins only at bedtime. Obese patients may require several hundred units of insulin daily and still not achieve satisfactory control. In some, addition of a sulfonylurea to insulin may reduce hyperglycemia, the insulin dose, or both. However, long-term benefits from such combination therapy remain to be demonstrated conclusively. Established adverse effects of insulin treatment in NIDDM are hypoglycemia, particularly in the elderly, and weight gain. Self-monitoring of blood glucose can identify patients in whom excessive weight gain is caused by subtle hypoglycemia. Whether insulin causes weight gain by direct effects on appetite or energy utilization remains controversial. A potential adverse effect of insulin has been suggested by epidemiological studies showing associations between hyperinsulinemia or insulin resistance and increased risk for coronary artery disease, stroke, and hypertension. Although potential mechanisms

  9. Insulin and Insulin Resistance

    PubMed Central

    2005-01-01

    As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, structure, synthesis, secretion, actions and interactions followed by a discussion of insulin resistance and its associated clinical manifestations. Specific areas of focus include the actions of insulin and manifestations of insulin resistance in specific organs and tissues, physiological, environmental and pharmacological influences on insulin action and insulin resistance as well as clinical syndromes associated with insulin resistance. Clinical and functional measures of insulin resistance are also covered. Despite our incomplete understanding of the complex biological mechanisms of insulin action and insulin resistance, we need to consider the dramatic social changes of the past century with respect to physical activity, diet, work, socialisation and sleep patterns. Rapid globalisation, urbanisation and industrialisation have spawned epidemics of obesity, diabetes and their attendant co-morbidities, as physical inactivity and dietary imbalance unmask latent predisposing genetic traits. PMID:16278749

  10. Relationship Between Subjective Preference and the Alpha-Brain Wave in Relation to the Initial Time Delay Gap with Vocal Music

    NASA Astrophysics Data System (ADS)

    MOURI, K.; AKIYAMA, K.; ANDO, Y.

    2000-04-01

    Previously, it was reported that the most preferred initial time delay gap [Δt1]pand subsequent reverberation time are described by the minimum value of the effective duration (τe)minof the running autocorrelation function (ACF) of music signals (2 T=2·0 s) (Y. ANDO et al. 1989 Journal of Acoustical Society of America86, 644-649). This paper shows whether this result is supported or not by use of the electro-physiological method. Experiments were performed for sound fields changing the initial time delay gapΔt1 of a single reflection with vocal music as a source signal, which has large changes in runningτe . The results at the time interval when (τe)minof the music is observed reveal that the scale value of subjective preference is closely related to the value of τeof the alpha wave obtained from the left heimsphere.

  11. Factors and Costs Associated With Delay in Treatment Initiation and Prolonged Length of Stay With Inpatient EPOCH Chemotherapy in Patients With Hematologic Malignancies.

    PubMed

    Accordino, Melissa K; Wright, Jason D; Vasan, Sowmya; Neugut, Alfred I; Hillyer, Grace C; Hershman, Dawn L

    2017-03-16

    Reducing delays related to inpatient chemotherapy may reduce healthcare costs. Using a national database, we identified patients with lymphoma/leukemia with ≥1 etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone (EPOCH) chemotherapy claim and evaluated chemotherapy initiation delay (ID), >1 day from admission. Standard tests/procedures prior to initiation were evaluated. Among 4453 inpatient cycles, 19.7% had ID, odds ratio 2.28 (95% confidence interval: 1.83-2.85) with cycle 1 compared to cycle 2, and mean costs were higher in patients with ID than without ID (p < .0001). Prior to cycle 1, patients were more likely to undergo routine diagnostic procedures compared to subsequent cycles. Efforts to perform routine procedures prior to admission may reduce hospital length of stay and costs.

  12. Impact of patient and treatment characteristics on glycemic control and hypoglycemia in patients with type 2 diabetes initiated to insulin glargine or NPH

    PubMed Central

    Porcellati, Francesca; Lin, Jay; Lucidi, Paola; Bolli, Geremia B.; Fanelli, Carmine G.

    2017-01-01

    Abstract Background: The goal of this post hoc analysis was to determine key patient and treatment-related factors impacting glycosylated hemoglobin (A1C) and hypoglycemia in patients with uncontrolled type 2 diabetes who were initiated to basal insulin (neutral protamine Hagedorn [NPH] or glargine). Methods: Using individual patient-level data pooled from 6 treat-to-target trials, 2600 patients with type 2 diabetes on oral antidiabetic agents initiated to insulin glargine or NPH and treated for 24 to 36 weeks were analyzed. Results: Both treatments led to significant reduction in A1C levels compared with baseline, with no differences between treatment groups (mean ± standard deviation; glargine: −1.32 ± 1.2% vs NPH: −1.26 ± 1.2%; P = 0.15), with greater reduction in the BMI ≥30 kg/m2 group than in the BMI <30 kg/m2 group. Glargine reduced A1C significantly more than NPH in the BMI <30 kg/m2 group (−1.30 ± 1.18% vs −1.14 ± 1.22, respectively; P = 0.008), but not in the BMI ≥ 30 kg/m2 group (−1.37 ± 1.19 vs −1.48 ± 1.22, respectively; P = 0.18). Similar proportions of patients achieved A1C target of <7% (glargine 30.6%, NPH 29.1%; P = 0.39). Incidence of severe and severe nocturnal hypoglycemia was significantly lower in glargine versus NPH-treated patients (2.0% vs 3.9%; P = 0.04, and 0.7% vs 2.1%; P = 0.002, respectively), and occurred primarily in the BMI <30 kg/m2 group. Conclusions: Initiation of basal insulin is highly effective in lowering A1C after oral antidiabetic agent failure. Glargine decreases A1C more than NPH in nonobese patients, and reduces the risk for severe and severe nocturnal hypoglycemia versus NPH both in obese and nonobese patients, but more so in nonobese patients. Thus, it is the nonobese patients who may benefit more from initiation of basal insulin as glargine than NPH. PMID:28151905

  13. Insulin-stimulated kinase from rat fat cells that phosphorylates initiation factor 4E-binding protein 1 on the rapamycin-insensitive site (serine-111).

    PubMed

    Heesom, K J; Avison, M B; Diggle, T A; Denton, R M

    1998-11-15

    The effects of insulin and rapamycin on the phosphorylation of the translation regulator, initiation factor 4E-binding protein 1 (4E-BP1) have been studied in rat fat cells by following changes in the incorporation of 32P from [32P]Pi under steady-state conditions. Both unbound 4E-BP1 and 4E-BP1 bound to eukaryotic initiation factor 4E (eIF4E) were isolated from the cells and then digested with trypsin and other proteases; the radiolabelled phosphopeptides were then separated by two-dimensional thin- layer analysis and HPLC. The results provide confirmation of the conclusion of Fadden, Haystead and Lawrence [J. Biol. Chem. (1997) 272, 10240-10247] that insulin increases the phosphorylation of four sites that fit a Ser/Thr-Pro motif (Thr-36, Thr-45, Ser-64 and Thr-69) and that taken together these phosphorylations result in the dissociation of 4E-BP1 from eIF4E. The effects of insulin on the phosphorylation of these sites, and hence dissociation from eIF4E, are blocked by rapamycin. However, the present study also provides evidence that insulin increases the phosphorylation of 4E-BP1 bound to eIF4E on a further site (Ser-111) and that this is by a rapamycin-insensitive mechanism. Extraction of rat epididymal fat cells followed by chromatography on Mono-S and Superose 12 columns resulted in the separation of both an insulin-stimulated eIF4E kinase and an apparently novel kinase that is highly specific for Ser-111 of 4E-BP1. The 4E-BP1 kinase was activated more than 10-fold by incubation of the cells with insulin and was markedly more active towards 4E-BP1 bound to eIF4E than towards unbound 4E-BP1. The effects of insulin were blocked by wortmannin, but not by rapamycin. A 14-mer peptide based on the sequence surrounding Ser-111 of 4E-BP1 was also a substrate for the kinase, but peptide substrates for other known protein kinases were not. The kinase is quite distinct from casein kinase 2, which also phosphorylates Ser-111 of 4E-BP1. The possible importance of these

  14. Scientific and regulatory reasons for delay and denial of FDA approval of initial applications for new drugs, 2000-2012.

    PubMed

    Sacks, Leonard V; Shamsuddin, Hala H; Yasinskaya, Yuliya I; Bouri, Khaled; Lanthier, Michael L; Sherman, Rachel E

    Some new drug applications fail because of inadequate drug performance and others are not approved because the information submitted to the US Food and Drug Administration (FDA) is unsatisfactory to make that determination. Resubmission of failed applications is costly, delaying marketing approval and the availability of new drugs to patients. To identify the reasons that FDA marketing approval for new drugs was delayed or denied. A retrospective review of FDA documents and extraction of data were performed. We examined all drug applications first submitted to the FDA between 2000 and 2012 for new molecular entities (NMEs), which are active ingredients never before marketed in the United States in any form. Using FDA correspondence and reviews, we investigated the reasons NMEs failed to obtain FDA approval. Reasons for delayed FDA approval or nonapproval of NME applications. Of the 302 identified NME applications, 151 (50%) were approved when first submitted and 222 (73.5%) were ultimately approved. Seventy-one applications required 1 or more resubmissions before approval, with a median delay to approval of 435 days following the first unsuccessful submission. Of the unsuccessful first-time applications, 24 (15.9%) included uncertainties related to dose selection, 20 (13.2%) choice of study end points that failed to adequately reflect a clinically meaningful effect, 20 (13.2%) inconsistent results when different end points were tested, 17 (11.3%) inconsistent results when different trials or study sites were compared, and 20 (13.2%) poor efficacy when compared with the standard of care. The frequency of safety deficiencies was similar among never-approved drugs compared with those with delayed approval (43 of 80 never approved [53.8%] vs 37 of 71 eventually approved [52.1%]; difference, 1.7% [95% CI, -14.86% to 18.05%]; P = .87). However, efficacy deficiencies were significantly more frequent among the never-approved drugs than among those with delayed approvals

  15. Adding Recognition Discriminability Index to the Delayed Recall Is Useful to Predict Conversion from Mild Cognitive Impairment to Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative.

    PubMed

    Russo, María J; Campos, Jorge; Vázquez, Silvia; Sevlever, Gustavo; Allegri, Ricardo F

    2017-01-01

    Background: Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to Alzheimer's disease (AD). We investigated whether recognition memory tasks in combination with delayed recall measure of episodic memory and CSF biomarkers can predict MCI to AD conversion at 24-month follow-up. Methods: A total of 397 amnestic-MCI subjects from Alzheimer's disease Neuroimaging Initiative were included. Logistic regression modeling was done to assess the predictive value of all RAVLT measures, risk factors such as age, sex, education, APOE genotype, and CSF biomarkers for progression to AD. Estimating adjusted odds ratios was used to determine which variables would produce an optimal predictive model, and whether adding tests of interaction between the RAVLT Delayed Recall and recognition measures (traditional score and d-prime) would improve prediction of the conversion from a-MCI to AD. Results: 112 (28.2%) subjects developed dementia and 285 (71.8%) subjects did not. Of the all included variables, CSF Aβ1-42 levels, RAVLT Delayed Recall, and the combination of RAVLT Delayed Recall and d-prime were predictive of progression to AD (χ(2) = 38.23, df = 14, p < 0.001). Conclusions: The combination of RAVLT Delayed Recall and d-prime measures may be predictor of conversion from MCI to AD in the ADNI cohort, especially in combination with amyloid biomarkers. A predictive model to help identify individuals at-risk for dementia should include not only traditional episodic memory measures (delayed recall or recognition), but also additional variables (d-prime) that allow the homogenization of the assessment procedures in the diagnosis of MCI.

  16. Adding Recognition Discriminability Index to the Delayed Recall Is Useful to Predict Conversion from Mild Cognitive Impairment to Alzheimer's Disease in the Alzheimer's Disease Neuroimaging Initiative

    PubMed Central

    Russo, María J.; Campos, Jorge; Vázquez, Silvia; Sevlever, Gustavo; Allegri, Ricardo F.; Weiner, Michael W.

    2017-01-01

    Background: Ongoing research is focusing on the identification of those individuals with mild cognitive impairment (MCI) who are most likely to convert to Alzheimer's disease (AD). We investigated whether recognition memory tasks in combination with delayed recall measure of episodic memory and CSF biomarkers can predict MCI to AD conversion at 24-month follow-up. Methods: A total of 397 amnestic-MCI subjects from Alzheimer's disease Neuroimaging Initiative were included. Logistic regression modeling was done to assess the predictive value of all RAVLT measures, risk factors such as age, sex, education, APOE genotype, and CSF biomarkers for progression to AD. Estimating adjusted odds ratios was used to determine which variables would produce an optimal predictive model, and whether adding tests of interaction between the RAVLT Delayed Recall and recognition measures (traditional score and d-prime) would improve prediction of the conversion from a-MCI to AD. Results: 112 (28.2%) subjects developed dementia and 285 (71.8%) subjects did not. Of the all included variables, CSF Aβ1-42 levels, RAVLT Delayed Recall, and the combination of RAVLT Delayed Recall and d-prime were predictive of progression to AD (χ2 = 38.23, df = 14, p < 0.001). Conclusions: The combination of RAVLT Delayed Recall and d-prime measures may be predictor of conversion from MCI to AD in the ADNI cohort, especially in combination with amyloid biomarkers. A predictive model to help identify individuals at-risk for dementia should include not only traditional episodic memory measures (delayed recall or recognition), but also additional variables (d-prime) that allow the homogenization of the assessment procedures in the diagnosis of MCI. PMID:28344552

  17. Insulin Basics

    MedlinePlus

    ... Text Size: A A A Listen En Español Insulin Basics There are different types of insulin depending ... you may be experiencing a reaction. Types of Insulin Rapid-acting insulin , begins to work about 15 ...

  18. Insulin Secretagogues

    MedlinePlus

    ... Your Body in Balance › Insulin Secretagogues Fact Sheet Insulin Secretagogues March, 2012 Download PDFs English Espanol Editors ... medicines can help you stay healthy. What are insulin secretagogues? Insulin secretagogues (pronounced seh-KREET-ah-gogs) ...

  19. Overcoming clinical inertia in insulin initiation in primary care for patients with type 2 diabetes: 24-month follow-up of the Stepping Up cluster randomised controlled trial.

    PubMed

    Manski-Nankervis, Jo-Anne; Furler, John; O'Neal, David; Ginnivan, Louise; Thuraisingam, Sharmala; Blackberry, Irene

    2017-10-01

    To examine the two-year impact of Stepping Up, a general practice based model of care intervention for insulin initiation and titration in Australia. 266 participants from 74 general practices participated in the Stepping Up cluster randomised controlled trial between 2012-2014. Control practices received training in the model of care on completion of the 12-month trial. Patients were followed for 24 months. Participant baseline characteristics, insulin and non-insulin medication use were summarised for each study group. Linear mixed-effects models with random intercepts were used to estimate differences in mean outcome (HbA1c and weight) between the study groups using restricted maximum likelihood estimation. At baseline 61% of patients were male, mean (SD) age 62 (10) years, diabetes duration 9 (5, 13) years and mean (95% CI) HbA1c was 8.9 (8.8-9.1)% (74 (73-76)mmol/mol) for both groups. There was a significant between group difference at 6 months which was sustained at 24 months; Mean (95% CI) HbA1c at 24 months in the intervention group was 7.6 (7.5-7.8)% (60 (58-62)mmol/mol) and 8.0 (7.7-8.4)% (64 (61-68)mmol/mol) in the control group. At 24 months 97 (71.3%) of the intervention group and 26 (31.0%) of the control group were prescribed insulin; there was no significant difference in weight. Use of non-insulin anti-hyperglycaemic agents was similar in both groups with the exception of dipeptidyl peptidase-4 inhibitors which were prescribed more frequently in the control group (30(36%) vs 21(16%)). Stepping Up was associated with improved glycaemic control compared to usual care for 24 months, suggesting that the model facilitated more timely treatment intensification. Ongoing RN-CDE support may be needed to facilitate ongoing treatment intensification. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  20. Cigarette Demand and Delayed Reward Discounting in Nicotine Dependent Individuals with Schizophrenia and Controls: An Initial Study

    PubMed Central

    MacKillop, James; Tidey, Jennifer W.

    2012-01-01

    Rationale The high prevalence of smoking and low cessation rates among individuals with schizophrenia and similar conditions are not well understood. Behavioral economics has been extensively applied to studying addictive behavior and may contribute to understanding smoking in this subpopulation. Objectives This study compared smokers with schizophrenia or schizoaffective disorder (SS) and control smokers (CS) on indices of cigarette demand and delayed reward discounting, a behavioral economic index of impulsivity. Materials and methods The SS (n = 25) and CS (n = 24) groups participated in two sessions approximately one week apart. During the first session, delay discounting was assessed using the Monetary Choice Questionnaire. During the second session, participants smoked their usual brand ad libitum through a smoking topography assessment device, after which cigarette demand was assessed using a cigarette purchase task. Primary comparisons were of the hyperbolic discounting function, k, and indices of cigarette demand. Results Compared to the CS group, the SS group exhibited significantly higher intensity of demand, and significantly greater consumption and expenditure across the inelastic portion of the demand curve, but no differences were evident on the other demand indices. No differences were evident for delay discounting. The SS group also exhibited heavier smoking topography and two indices of smoking topography were significantly correlated with demand. Conclusions These results provide further evidence of higher incentive value of cigarettes among SS individuals, but not greater impulsivity, as measured by discounting. Considerations include potentially important methodological factors and the role of satiation/withdrawal. PMID:21327760

  1. Current role of short-term intensive insulin strategies in newly diagnosed type 2 diabetes.

    PubMed

    Xu, Wen; Weng, Jianping

    2013-09-01

    Type 2 diabetes mellitus (T2DM) is a progressive disease characterized by worsening insulin resistance and a decline in β-cell function. Achieving good glycemic control becomes more challenging as β-cell function continues to deteriorate throughout the disease process. The traditional management paradigm emphasizes a stepwise approach, and insulin has generally been reserved as a final armament. However, mounting evidence indicates that short-term intensive insulin therapy used in the early stages of type 2 diabetes could improve β-cell function, resulting in better glucose control and more extended glycemic remission than oral antidiabetic agents. Improvements in insulin sensitivity and lipid profile were also seen after the early initiation of short-term intensive insulin therapy. Thus, administering short-term intensive insulin therapy to patients with newly diagnosed T2DM has the potential to delay the natural process of this disease, and should be considered when clinicians initiate treatment. Although the early use of insulin is advocated by some guidelines, the optimal time to initiate insulin therapy is not clearly defined or easily recognized, and a pragmatic approach is lacking. Herein we summarize the current understanding of early intensive insulin therapy in patients with newly diagnosed T2DM, focusing on its clinical benefit and problems, as well as possible biological mechanisms of action, and discuss our perspective.

  2. Psychological insulin resistance: patient beliefs and implications for diabetes management.

    PubMed

    Brod, Meryl; Kongsø, Jens Harald; Lessard, Suzanne; Christensen, Torsten L

    2009-02-01

    To define and understand patient psychological insulin resistance (PIR) and its impact on diabetes management. Systematic literature review of peer-refereed journals using the MEDLINE database, including all articles in English from 1985 to 2007. The population included patients with type 1 and type 2 diabetes, insulin naïve, and those currently using insulin. A total of 116 articles were reviewed. PIR is impacted by patients' beliefs and knowledge about diabetes and insulin, negative self-perceptions and attitudinal barriers, the fear of side effects and complications from insulin use, as well as lifestyle adaptations, restrictions required by insulin use, and social stigma. These etiological influences, both independently and in combination, constitute a patient's PIR and may result in the reluctance of patients to both initiate and intensify treatment, leading to delayed treatment initiation and compromised glucose control. PIR is complex and multifaceted. It plays an important, although often ignored, role in diabetes management. Assisting health care professionals in better understanding PIR from the patient's perspective should result in improved treatment outcomes. By tailoring treatments to patients' PIR, clinicians may be better able to help their patients begin insulin treatment sooner and improve compliance, thus facilitating target glycemic control.

  3. Ewing sarcoma/primitive neuroectodermal tumor of the chest wall: impact of initial versus delayed resection on tumor margins, survival, and use of radiation therapy.

    PubMed

    Shamberger, Robert C; LaQuaglia, Michael P; Gebhardt, Mark C; Neff, James R; Tarbell, Nancy J; Marcus, Karen C; Sailer, Scott L; Womer, Richard B; Miser, James S; Dickman, Paul S; Perlman, Elizabeth J; Devidas, Meenakshi; Linda, Stephen B; Krailo, Mark D; Grier, Holcombe E; Granowetter, Linda

    2003-10-01

    To establish outcome and optimal timing of local control for patients with nonmetastatic Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET) of the chest wall. Patients < or =30 years of age with ES/PNET of the chest wall were entered in 2 consecutive protocols. Therapy included multiagent chemotherapy; local control was achieved by resection, radiotherapy, or both. We compared completeness of resection and disease-free survival in patients undergoing initial surgical resection versus those treated with neoadjuvant chemotherapy followed by resection, radiotherapy, or both. Patients with a positive surgical margin received radiotherapy. Ninety-eight (11.3%) of 869 patients had primary tumors of the chest wall. Median follow-up was 3.47 years and 5-year event-free survival was 56% for the chest wall lesions. Ten of 20 (50%) initial resections resulted in negative margins compared with 41 of 53 (77%) negative margins with delayed resections after chemotherapy (P = 0.043). Event-free survival did not differ by timing of surgery (P = 0.69) or type of local control (P = 0.17). Initial chemotherapy decreased the percentage of patients needing radiation therapy. Seventeen of 24 patients (70.8%) with initial surgery received radiotherapy compared with 34 of 71 patients (47.9%) who started with chemotherapy (P = 0.061). If a delayed operation was performed, excluding those patients who received only radiotherapy for local control, only 25 of 62 patients needed radiotherapy (40.3%; P = 0.016). The likelihood of complete tumor resection with a negative microscopic margin and consequent avoidance of external beam radiation and its potential complications is increased with neoadjuvant chemotherapy and delayed resection of chest wall ES/PNET.

  4. Routine delayed voiding cystourethography after initial successful endoscopic treatment with Dextranomer/Hialuronic Acid Copolimer (Dx/HA) of vesicoureteral reflux (VUR). Is it necessary?

    PubMed

    García-Aparicio, L; Blázquez-Gómez, E; Vila Santandreu, A; Camacho Diaz, J A; Vila-Cots, J; Ramos Cebrian, M; de Haro, I; Martin, O; Tarrado, X

    2016-12-01

    Some guidelines recommend an early voiding cystourethrography (VCUG) after endoscopic treatment of vesicoureteral reflux (VUR), but there's no consensus if it's necessary a long-term follow-up in these patients. The aim of our study is analyze if it's necessary a delayed VCUG after initial successful treatment with Dx/HA. We have reviewed all medical charts of patients that underwent Dx/HA treatment from 2006 to 2010. We have selected patients with initial successful treatment and more than 3 years of radiological and clinical follow-up. We have analyzed late clinical and radiological outcomes. One hundred and sixty children with 228 refluxing ureters underwent Dx/HA endoscopic treatment with a mean follow-up of 52.13 months. Early VCUG was performed in 215 ureters with an initial successful rate of 84.1%. The group of study was 94/215 ureters with more than 3 years of follow-up with a delayed VCUG. VUR was still resolved in 79,8% of the ureters. Clinical success rate was 91.7%. The incidence of febrile urinary tract infection in those patients with cured VUR and those with a relapsed VUR was 8 and 15%, respectively; but there were no significant differences. We have not found any variable related with relapsed VUR except those ureters that initially received 2 injections (P<.05). If our objective in the treatment of VUR is to reduce the incidence of febrile urinary tract infection it is not necessary to perform a delayed VCUG even though the long-term radiological outcomes is worse than clinical outcome. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Initiation of human regular U-500 insulin use is associated with improved glycemic control: a real-world US cohort study.

    PubMed

    Eby, Elizabeth L; Curtis, Bradley H; Gelwicks, Steven C; Hood, Robert C; Idris, Iskandar; Peters, Anne L; Bergenstal, Richard M; Jackson, Jeffrey A

    2015-01-01

    Describe the characteristics of patients initiating human regular U-500 insulin (U-500R) and their subsequent glycemic control in a real-world setting. US Humedica electronic health record system data (July 2007-September 2011) were used to identify patients with diabetes aged ≥18 years with ≥1 records for U-500R prescriptions, 6 months of preindex data, 12 months following first use of U-500R, and at least one glycated hemoglobin (HbA1c) value in both preindex and postindex periods. Paired t tests were used to measure the change in HbA1c from preindex to postindex periods (last or most recent values) and hypoglycemia. Among patients initiating U-500R (N=445), 96.9% had type 2 diabetes with mean age 57 years and mean body mass index 40.4 kg/m(2). Postindex prescriptions were written for U-500R alone (47.0%, group A) and concomitant U-500R/U-100 insulins (53.0%, group B). Concomitant oral antihyperglycemic agents (AHAs) and non-insulin injectable AHAs were used by 43.4% and 14.6% of patients, respectively. Following initiation of U-500R, mean HbA1c improved 0.68% in all patients (p<0.0001 compared with baseline), but the decrease in HbA1c did not differ significantly between groups (A: 0.78%; B: 0.60%). Overall, hypoglycemic events, largely captured in the outpatient setting, increased in incidence from 6.7% to 11.9% (p≤0.0001) and from 0.23 to 0.39 events/patient/year, an increase of 0.16 (p=0.003), from preindex to postindex. This real-world outcomes analysis demonstrates that U-500R initiation is associated with a clinically meaningful improvement in glycemic control over the subsequent 12-month period with modest increase in incidence and rate of hypoglycemia.

  6. Tracking delays in report availability caused by incorrect exam status with Web-based issue tracking: a quality initiative.

    PubMed

    Awan, Omer Abdulrehman; van Wagenberg, Frans; Daly, Mark; Safdar, Nabile; Nagy, Paul

    2011-04-01

    Many radiology information systems (RIS) cannot accept a final report from a dictation reporting system before the exam has been completed in the RIS by a technologist. A radiologist can still render a report in a reporting system once images are available, but the RIS and ancillary systems may not get the results because of the study's uncompleted status. This delay in completing the study caused an alarming number of delayed reports and was undetected by conventional RIS reporting techniques. We developed a Web-based reporting tool to monitor uncompleted exams and automatically page section supervisors when a report was being delayed by its incomplete status in the RIS. Institutional Review Board exemption was obtained. At four imaging centers, a Python script was developed to poll the dictation system every 10 min for exams in five different modalities that were signed by the radiologist but could not be sent to the RIS. This script logged the exams into an existing Web-based tracking tool using PHP and a MySQL database. The script also text-paged the modality supervisor. The script logged the time at which the report was finally sent, and statistics were aggregated onto a separate Web-based reporting tool. Over a 1-year period, the average number of uncompleted exams per month and time to problem resolution decreased at every imaging center and in almost every imaging modality. Automated feedback provides a vital link in improving technologist performance and patient care without assigning a human resource to manage report queues.

  7. Initial design and physical characterization of a polymeric device for osmosis-driven delayed burst delivery of vaccines.

    PubMed

    Melchels, Ferry P W; Fehr, Ingo; Reitz, Annika S; Dunker, Urip; Beagley, Kenneth W; Dargaville, Tim R; Hutmacher, Dietmar W

    2015-09-01

    Achieving the combination of delayed and immediate release of a vaccine from a delivery device without applying external triggers remains elusive in implementing single administration vaccination strategies. Here a means of vaccine delivery is presented, which exploits osmosis to trigger delayed burst release of an active compound. Poly(ε-caprolactone) capsules of 2 mm diameter were prepared by dip-coating, and their burst pressure and release characteristics were evaluated. Burst pressures (in bar) increased with wall thickness (t in mm) following Pburst  = 131(.) t + 3(.) 4 (R(2)  = 0.93). Upon immersion in PBS, glucose solution-filled capsules burst after 8.7 ± 2.9 days. Copolymers of hydrophobic ε -caprolactone and hydrophilic polyethylene glycol were synthesized and their physico-chemical properties were assessed. With increasing hydrophilic content, the copolymer capsules showed increased water uptake rates and maximum weight increase, while the burst release was earlier: 5.6 ± 2.0 days and 1.9 ± 0.2 days for 5 and 10 wt% polyethylene glycol, respectively. The presented approach enables the reproducible preparation of capsules with high versatility in materials and properties, while these vaccine delivery vehicles can be prepared separately from, and independently of the active compound. © 2015 Wiley Periodicals, Inc.

  8. Estimating the state of a geophysical system with sparse observations: time delay methods to achieve accurate initial states for prediction

    NASA Astrophysics Data System (ADS)

    An, Zhe; Rey, Daniel; Ye, Jingxin; Abarbanel, Henry D. I.

    2017-01-01

    The problem of forecasting the behavior of a complex dynamical system through analysis of observational time-series data becomes difficult when the system expresses chaotic behavior and the measurements are sparse, in both space and/or time. Despite the fact that this situation is quite typical across many fields, including numerical weather prediction, the issue of whether the available observations are "sufficient" for generating successful forecasts is still not well understood. An analysis by Whartenby et al. (2013) found that in the context of the nonlinear shallow water equations on a β plane, standard nudging techniques require observing approximately 70 % of the full set of state variables. Here we examine the same system using a method introduced by Rey et al. (2014a), which generalizes standard nudging methods to utilize time delayed measurements. We show that in certain circumstances, it provides a sizable reduction in the number of observations required to construct accurate estimates and high-quality predictions. In particular, we find that this estimate of 70 % can be reduced to about 33 % using time delays, and even further if Lagrangian drifter locations are also used as measurements.

  9. Supporting insulin initiation in type 2 diabetes in primary care: results of the Stepping Up pragmatic cluster randomised controlled clinical trial.

    PubMed

    Furler, John; O'Neal, David; Speight, Jane; Manski-Nankervis, Jo-Anne; Gorelik, Alexandra; Holmes-Truscott, Elizabeth; Ginnivan, Louise; Young, Doris; Best, James; Patterson, Elizabeth; Liew, Danny; Segal, Leonie; May, Carl; Blackberry, Irene

    2017-03-08

    Objective To compare the effectiveness of a novel model of care ("Stepping Up") with usual primary care in normalising insulin initiation for type 2 diabetes, leading to improved glycated haemoglobin (HbA1c) levels.Design Cluster randomised controlled trial.Setting Primary care practices in Victoria, Australia, with a practice nurse and at least one consenting eligible patient (HbA1c ≥7.5% with maximal oral treatment).Participants 266 patients with type 2 diabetes and 74 practices (mean cluster size 4 (range 1-8) patients), followed up for 12 months.Intervention The Stepping Up model of care intervention involved theory based change in practice systems and reorientation of the roles of health professionals in the primary care diabetes team. The core components were an enhanced role for the practice nurse in leading insulin initiation and mentoring by a registered nurse with diabetes educator credentials.Main outcome measures The primary endpoint was change in HbA1c. Secondary endpoints included the proportion of participants who transitioned to insulin, proportion who achieved target HbA1c, and a change in depressive symptoms (patient health questionnaire, PHQ-9), diabetes specific distress (problem areas in diabetes scale, PAID), and generic health status (assessment of quality of life instrument, AQoL-8D).Results HbA1c improved in both arms, with a clinically significant between arm difference (mean difference -0.6%, 95% confidence interval -0.9% to -0.3%), favouring the intervention. At 12 months, in intervention practices, 105/151 (70%) of participants had started insulin, compared with 25/115 (22%) in control practices (odds ratio 8.3, 95% confidence interval 4.5 to 15.4, P<0.001). Target HbA1c (≤7% (53 mmol/mol)) was achieved by 54 (36%) intervention participants and 22 (19%) control participants (odds ratio 2.2, 1.2 to 4.3, P=0.02). Depressive symptoms did not worsen at 12 months (PHQ-9: -1.1 (3.5) v -0.1 (2.9), P=0.05). A statistically

  10. A randomized trial of basiliximab with three different patterns of cyclosporin A initiation in renal transplant from expanded criteria donors and at high risk of delayed graft function.

    PubMed

    Andrés, Amado; Marcén, Roberto; Valdés, Francisco; Plumed, Jaime Sánchez; Solà, Ricard; Errasti, Pedro; Lauzurica, Ricardo; Pallardó, Luis; Bustamante, Jesús; Amenábar, Juan José; Plaza, Juan José; Gómez, Ernesto; Grinyó, Josep Maria; Rengel, Manuel; Puig, Josep Maria; Sanz, Aurelio; Asensio, Concepción; Andrés, Inés

    2009-01-01

    This study assays therapy with basiliximab and different patterns of cyclosporin A (CsA) initiation in renal transplant (RT) recipients from expanded criteria donors (ECD) and at high risk of delayed graft function (DGF). A multicentre six-month open-label randomized trial with three parallel groups treated with basiliximab plus steroids, mycophenolate mofetil and different patterns of CsA initiation: early within 24 h post-RT at 3 mg/kg/d (Group 1; n = 38), and at 5 mg/kg/d (Group 2; n = 40), or delayed after 7-10 d at 5 mg/kg/d (Group 3; n = 36). There were no differences among groups in six months GFR (43.1 +/- 12, 48.0 +/- 14 and 47.2 +/- 17 mL/min, respectively), DGF (Group 1: 31%, Group 2: 37%, Group 3: 42%), nor biopsy-proven acute rejection, although clinically treated and biopsy-proven acute rejection was significantly higher in Group 3 (25%) vs. Group 1 (5.3%, p < 0.05). At six months no differences were observed in death-censored graft survival or patient survival. Induction therapy with basiliximab and three CsA-ME initiation patterns in RT recipients from ECD and at high risk of DGF presented good renal function and graft survival at six months. Late onset group did not achieve improvement in DGF rate and showed a higher incidence of clinically treated and biopsy-proven acute rejection.

  11. Elevation of the plasma level of insulin-like growth factor-I with reproductive maturation prior to initiation of spawning migration of chum salmon.

    PubMed

    Onuma, Takeshi A; Makino, Keita; Ban, Masatoshi; Ando, Hironori; Fukuwaka, Masa-aki; Azumaya, Tomonori; Swanson, Penny; Urano, Akihisa

    2009-04-01

    When, where, and how oceanic chum salmon initiate spawning migration is unknown although gonadal development and elevation of the activity of the pituitary-gonadal axis (PG-axis) are essential. Insulin-like growth factor-I (IGF-I) is a somatotropic signal that interacts with the PG-axis for gametogenesis. We thus examined the plasma level of IGF-I in immature and maturing chum salmon in the Bering Sea and the Gulf of Alaska. The maturing adults which had maturing gonads left the Bering Sea for the natal river by the end of summer, because almost all fish were immature in September. The plasma level of IGF-I and corresponding body size in the maturing adults were two- to threefold that of immature fish. The plasma IGF-I level correlated positively with the pituitary contents of follicle-stimulating hormone and the plasma levels of 11-ketotestosterone and estradiol-17beta. Therefore, the plasma level of IGF-I increased with elevation of the PG-axis activity prior to the initiation of spawning migration from the Bering Sea. Circulatory IGF-I from visceral organs may inform the status of body growth to the PG-axis for gonadal development that is inseparable from decision of chum salmon whether to initiate homing behavior from the Bering Sea or not to initiate spawning migration by the coming spawning season.

  12. Early Versus Delayed Initiation of Concurrent Palliative Oncology Care: Patient Outcomes in the ENABLE III Randomized Controlled Trial

    PubMed Central

    Bakitas, Marie A.; Tosteson, Tor D.; Li, Zhigang; Lyons, Kathleen D.; Hull, Jay G.; Li, Zhongze; Dionne-Odom, J. Nicholas; Frost, Jennifer; Dragnev, Konstantin H.; Hegel, Mark T.; Azuero, Andres; Ahles, Tim A.

    2015-01-01

    Purpose Randomized controlled trials have supported integrated oncology and palliative care (PC); however, optimal timing has not been evaluated. We investigated the effect of early versus delayed PC on quality of life (QOL), symptom impact, mood, 1-year survival, and resource use. Patients and Methods Between October 2010 and March 2013, 207 patients with advanced cancer at a National Cancer Institute cancer center, a Veterans Affairs Medical Center, and community outreach clinics were randomly assigned to receive an in-person PC consultation, structured PC telehealth nurse coaching sessions (once per week for six sessions), and monthly follow-up either early after enrollment or 3 months later. Outcomes were QOL, symptom impact, mood, 1-year survival, and resource use (hospital/intensive care unit days, emergency room visits, chemotherapy in last 14 days, and death location). Results Overall patient-reported outcomes were not statistically significant after enrollment (QOL, P = .34; symptom impact, P = .09; mood, P = .33) or before death (QOL, P = .73; symptom impact, P = .30; mood, P = .82). Kaplan-Meier 1-year survival rates were 63% in the early group and 48% in the delayed group (difference, 15%; P = .038). Relative rates of early to delayed decedents' resource use were similar for hospital days (0.73; 95% CI, 0.41 to 1.27; P = .26), intensive care unit days (0.68; 95% CI, 0.23 to 2.02; P = .49), emergency room visits (0.73; 95% CI, 0.45 to 1.19; P = .21), chemotherapy in last 14 days (1.57; 95% CI, 0.37 to 6.7; P = .27), and home death (27 [54%] v 28 [47%]; P = .60). Conclusion Early-entry participants' patient-reported outcomes and resource use were not statistically different; however, their survival 1-year after enrollment was improved compared with those who began 3 months later. Understanding the complex mechanisms whereby PC may improve survival remains an important research priority. PMID:25800768

  13. Early Versus Delayed Initiation of Concurrent Palliative Oncology Care: Patient Outcomes in the ENABLE III Randomized Controlled Trial.

    PubMed

    Bakitas, Marie A; Tosteson, Tor D; Li, Zhigang; Lyons, Kathleen D; Hull, Jay G; Li, Zhongze; Dionne-Odom, J Nicholas; Frost, Jennifer; Dragnev, Konstantin H; Hegel, Mark T; Azuero, Andres; Ahles, Tim A

    2015-05-01

    Randomized controlled trials have supported integrated oncology and palliative care (PC); however, optimal timing has not been evaluated. We investigated the effect of early versus delayed PC on quality of life (QOL), symptom impact, mood, 1-year survival, and resource use. Between October 2010 and March 2013, 207 patients with advanced cancer at a National Cancer Institute cancer center, a Veterans Affairs Medical Center, and community outreach clinics were randomly assigned to receive an in-person PC consultation, structured PC telehealth nurse coaching sessions (once per week for six sessions), and monthly follow-up either early after enrollment or 3 months later. Outcomes were QOL, symptom impact, mood, 1-year survival, and resource use (hospital/intensive care unit days, emergency room visits, chemotherapy in last 14 days, and death location). Overall patient-reported outcomes were not statistically significant after enrollment (QOL, P = .34; symptom impact, P = .09; mood, P = .33) or before death (QOL, P = .73; symptom impact, P = .30; mood, P = .82). Kaplan-Meier 1-year survival rates were 63% in the early group and 48% in the delayed group (difference, 15%; P = .038). Relative rates of early to delayed decedents' resource use were similar for hospital days (0.73; 95% CI, 0.41 to 1.27; P = .26), intensive care unit days (0.68; 95% CI, 0.23 to 2.02; P = .49), emergency room visits (0.73; 95% CI, 0.45 to 1.19; P = .21), chemotherapy in last 14 days (1.57; 95% CI, 0.37 to 6.7; P = .27), and home death (27 [54%] v 28 [47%]; P = .60). Early-entry participants' patient-reported outcomes and resource use were not statistically different; however, their survival 1-year after enrollment was improved compared with those who began 3 months later. Understanding the complex mechanisms whereby PC may improve survival remains an important research priority. © 2015 by American Society of Clinical Oncology.

  14. The Mechanisms of Crack Initiation and Crack Propagation in Metal-Induced Embrittlement of Metals. Part I. Delayed Failure in the Embrittlement of 4140 Steel by Indium.

    DTIC Science & Technology

    1980-12-12

    differ. To confirm the presence of this gap , a series of tests was run at several other stress levels at the two temperatures 154°C (just below the...times across the gap at the melting point persists unchanged, within a substantial scatter, for all stress levels at which delayed failure takes place...initiation time at the melting point of indium is larger by a factor of 6.5 in SMIE than in LMIE. This time gap at the melting point persists at about the

  15. Utilization of a Cloud-Based Diabetes Management Program for Insulin Initiation and Titration Enables Collaborative Decision Making Between Healthcare Providers and Patients.

    PubMed

    Hsu, William C; Lau, Ka Hei Karen; Huang, Ruyi; Ghiloni, Suzanne; Le, Hung; Gilroy, Scott; Abrahamson, Martin; Moore, John

    2016-02-01

    Overseeing proper insulin initiation and titration remains a challenging task in diabetes care. Recent advances in mobile technology have enabled new models of collaborative care between patients and healthcare providers (HCPs). We hypothesized that the adoption of such technology could help individuals starting basal insulin achieve better glycemic control compared with standard clinical practice. This was a 12 ± 2-week randomized controlled study with 40 individuals with type 2 diabetes who were starting basal insulin due to poor glycemic control. The control group (n = 20) received standard face-to-face care and phone follow-up as needed in a tertiary center, whereas the intervention group (n = 20) received care through the cloud-based diabetes management program where regular communications about glycemic control and insulin doses were conducted via patient self-tracking tools, shared decision-making interfaces, secure text messages, and virtual visits (audio, video, and shared screen control) instead of office visits. By intention-to-treat analysis, the intervention group achieved a greater hemoglobin A1c decline compared with the control group (3.2 ± 1.5% vs. 2.0% ± 2.0%; P = 0.048). The Diabetes Treatment Satisfaction Questionnaire showed a significant improvement in the intervention group compared with the control group (an increase of 10.1 ± 11.7 vs. 2.1 ± 6.5 points; P = 0.01). HCPs spent less time with patients in the intervention group compared with those in the control group (65.9 min per subject vs. 81.6 min per subject). However, the intervention group required additional training time to use the mobile device. Mobile health technology could be an effective tool in sharing data, enhancing communication, and improving glycemic control while enabling collaborative decision making in diabetes care.

  16. Associations of serum insulin-like growth factor-I and insulin-like growth factor-binding protein 3 levels with biomarker-calibrated protein, dairy product and milk intake in the Women's Health Initiative.

    PubMed

    Beasley, Jeannette M; Gunter, Marc J; LaCroix, Andrea Z; Prentice, Ross L; Neuhouser, Marian L; Tinker, Lesley F; Vitolins, Mara Z; Strickler, Howard D

    2014-03-14

    It is well established that protein-energy malnutrition decreases serum insulin-like growth factor (IGF)-I levels, and supplementation of 30 g of whey protein daily has been shown to increase serum IGF-I levels by 8 % after 2 years in a clinical trial. Cohort studies provide the opportunity to assess associations between dietary protein intake and IGF axis protein levels under more typical eating conditions. In the present study, we assessed the associations of circulating IGF axis protein levels (ELISA, Diagnostic Systems Laboratories) with total biomarker-calibrated protein intake, as well as with dairy product and milk intake, among postmenopausal women enrolled in the Women's Health Initiative (n 747). Analyses were carried out using multivariate linear regression models that adjusted for age, BMI, race/ethnicity, education, biomarker-calibrated energy intake, alcohol intake, smoking, physical activity and hormone therapy use. There was a positive association between milk intake and free IGF-I levels. A three-serving increase in milk intake per d (approximately 30 g of protein) was associated with an estimated average 18·6 % higher increase in free IGF-I levels (95 % CI 0·9, 39·3 %). However, total IGF-I and insulin-like growth factor-binding protein 3 (IGFBP-3) levels were not associated with milk consumption and nor were there associations between biomarker-calibrated protein intake, biomarker-calibrated energy intake, and free IGF-I, total IGF-I or IGFBP-3 levels. The findings of the present study carried out in postmenopausal women are consistent with clinical trial data suggesting a specific relationship between milk consumption and serum IGF-I levels, although in the present study this association was only statistically significant for free, but not total, IGF-I or IGFBP-3 levels.

  17. Delayed Temporal Lobe Hemorrhage After Initiation of Acyclovir in an Immunocompetent Patient with Herpes Simplex Virus-2 Encephalitis: A Case Report

    PubMed Central

    Ryan, Joshua E; Tai, Alex; Armonda, Rocco A

    2017-01-01

    Herpes simplex virus (HSV) is the most common cause of non-epidemic, sporadic, acute focal encephalitis in the United States. Inflammation of the vasculature makes them friable and susceptible to hemorrhage. Massive hemorrhage, though rare, can present in a delayed fashion after initiation of acyclovir and often requires surgical intervention. We report a unique case of delayed temporal lobe hemorrhage after initiation of acyclovir in an immunocompetent patient, specifically for its presentation, virology, and surgical management. A 40-year-old left-handed Caucasian female with chronic headaches, along with a 20-pack-year smoking history, presented to an outside facility with one week of diffuse, generalized headache, fever, nausea, and vomiting. Initial cranial imaging was negative for hemorrhage. Cerebrospinal fluid (CSF) studies showed a lymphocytic pleocytosis with elevated protein, along with polymerase chain reaction (PCR) positive staining for HSV, establishing the diagnosis of HSV-2 encephalitis, which is less common in adults. Acyclovir was initiated and one week later while still hospitalized, the patient developed acute altered mental status with cranial imaging showing a large right temporal lobe hemorrhage with significant midline shift. She was transferred to our facility for surgical intervention. Computed tomography angiography (CTA) was negative for any underlying vascular lesion. She was taken to the operating room for a decompressive unilateral (right) hemicraniectomy and temporal lobectomy. She had no postoperative complications and completed a three-week course of acyclovir. She was discharged to acute rehab with plans to return at a later date for cranioplasty. Intracerebral hemorrhage is an uncommon, although possible sequela, of herpes encephalitis. Despite initiation of early antiviral therapy, close monitoring is warranted, given the pathophysiology of the vasculature. Any decline in the neurological exam and/or increasing symptomatology

  18. Critical quench dynamics of random quantum spin chains: ultra-slow relaxation from initial order and delayed ordering from initial disorder

    NASA Astrophysics Data System (ADS)

    Roósz, Gergö; Lin, Yu-Cheng; Iglói, Ferenc

    2017-02-01

    By means of free fermionic techniques combined with multiple precision arithmetic we study the time evolution of the average magnetization, \\overline{m}(t), of the random transverse-field Ising chain after global quenches. We observe different relaxation behaviors for quenches starting from different initial states to the critical point. Starting from a fully ordered initial state, the relaxation is logarithmically slow described by \\overline{m}(t)∼ {{ln}}at, and in a finite sample of length L the average magnetization saturates at a size-dependent plateau {\\overline{m}}p(L)∼ {L}-b; here the two exponents satisfy the relation b/a=\\psi =1/2. Starting from a fully disordered initial state, the magnetization stays at zero for a period of time until t={t}{{d}} with {ln}{t}{{d}}∼ {L}\\psi and then starts to increase until it saturates to an asymptotic value {\\overline{m}}p(L)∼ {L}-b^{\\prime }, with b\\prime ≈ 1.5. For both quenching protocols, finite-size scaling is satisfied in terms of the scaled variable {ln}t/{L}\\psi . Furthermore, the distribution of long-time limiting values of the magnetization shows that the typical and the average values scale differently and the average is governed by rare events. The non-equilibrium dynamical behavior of the magnetization is explained through semi-classical theory.

  19. "Saving Sex for Later": Developing a Parent-Child Communication Intervention to Delay Sexual Initiation among Young Adolescents

    ERIC Educational Resources Information Center

    O'Donnell, Lydia; Wilson-Simmons, Renee; Dash, Kim; Jeanbaptiste, Varzi; Myint-U, Athi; Moss, Jesse; Stueve, Ann

    2007-01-01

    Young adolescents in communities with high rates of early sexual initiation are at risk of multiple negative health outcomes. Although sex education programs for this age group are often controversial, surveys document that many mothers and fathers would appreciate guidance about how to discuss sexuality with their children. This paper presents an…

  20. Delayed initiation but not gradual advancement of enteral formula feeding reduces the incidence of necrotizing enterocolitis (NEC) in preterm pigs

    USDA-ARS?s Scientific Manuscript database

    Enteral formula feeding is a risk factor for necrotizing enterocolitis (NEC) in premature infants, yet studies are conflicting regarding the safest timing for introduction and advancement of feeds. Our aim was to test the effects of early vs. late initiation and abrupt vs. gradual advancement of ent...

  1. Evaluation of a Randomized Intervention to Delay Sexual Initiation among Fifth-Graders Followed through the Sixth Grade

    ERIC Educational Resources Information Center

    Koo, Helen P.; Rose, Allison; El-Khorazaty, M. Nabil; Yao, Qing; Jenkins, Renee R.; Anderson, Karen M.; Davis, Maurice; Walker, Leslie R.

    2011-01-01

    US adolescents initiate sex at increasingly younger ages, yet few pregnancy prevention interventions for children as young as 10-12 years old have been evaluated. Sixteen Washington, DC schools were randomly assigned to intervention versus control conditions. Beginning in 2001/02 with fifth-grade students and continuing during the sixth grade,…

  2. Evaluation of a Randomized Intervention to Delay Sexual Initiation among Fifth-Graders Followed through the Sixth Grade

    ERIC Educational Resources Information Center

    Koo, Helen P.; Rose, Allison; El-Khorazaty, M. Nabil; Yao, Qing; Jenkins, Renee R.; Anderson, Karen M.; Davis, Maurice; Walker, Leslie R.

    2011-01-01

    US adolescents initiate sex at increasingly younger ages, yet few pregnancy prevention interventions for children as young as 10-12 years old have been evaluated. Sixteen Washington, DC schools were randomly assigned to intervention versus control conditions. Beginning in 2001/02 with fifth-grade students and continuing during the sixth grade,…

  3. "Saving Sex for Later": Developing a Parent-Child Communication Intervention to Delay Sexual Initiation among Young Adolescents

    ERIC Educational Resources Information Center

    O'Donnell, Lydia; Wilson-Simmons, Renee; Dash, Kim; Jeanbaptiste, Varzi; Myint-U, Athi; Moss, Jesse; Stueve, Ann

    2007-01-01

    Young adolescents in communities with high rates of early sexual initiation are at risk of multiple negative health outcomes. Although sex education programs for this age group are often controversial, surveys document that many mothers and fathers would appreciate guidance about how to discuss sexuality with their children. This paper presents an…

  4. Surgical castration efficiently delays the time of starting a systemic chemotherapy in castration-resistant prostate cancer patients refractory to initial androgen-deprivation therapy

    PubMed Central

    Kang, Minyong; Lee, Sangchul; Oh, Jong Jin; Hong, Sung Kyu; Lee, Sang Eun; Byun, Seok-Soo

    2015-01-01

    Background The aim of this study was to investigate the effects of surgical castration, particularly delaying the time to entrance of systemic chemotherapy, in castration-resistant prostate cancer (CRPC) patients who were refractory to initial combination androgen deprivation therapy. Materials and methods We analyzed the clinical data of 14 CRPC patients diagnosed at Seoul National University Bundang Hospital (SNUBH) from November 2008 through May 2015. After exclusion of three patients, we finally analyzed the baseline characteristics of 11 CRPC patients. We also assessed the delaying time of docetaxel administration, which was defined as response duration, after surgical castration. Results After bilateral orchiectomy, the treatment response rate was 45.4% and the median duration of response was 9 months (range 4–48 mo). Responders had less aggressive biopsy Gleason scores compared to nonresponders. Notably, responders showed the reducing pattern of serum prostate specific antigen levels, while nonresponders demonstrated increasing tendency after surgical castration. Moreover, responders also presented with a reduction pattern of serum testosterone levels, whereas nonresponders showed an increasing pattern of testosterone levels after bilateral orchiectomy. Conclusions In summary, despite the limited number of cases for convincing evidence, our results shed light again on the clinical benefits of surgical castration prior to the systemic chemotherapy in some CRPC patients after initial hormone therapy. PMID:26779458

  5. Insulin Test

    MedlinePlus

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Insulin Share this page: Was this page helpful? Also known as: Fasting Insulin Formal name: Insulin, serum Related tests: C-peptide , ...

  6. What to Expect from the Virtual Seismologist: Delay Times and Uncertainties of Initial Earthquake Alerts in California

    NASA Astrophysics Data System (ADS)

    Behr, Y.; Cua, G. B.; Clinton, J. F.; Racine, R.; Meier, M.; Cauzzi, C.

    2013-12-01

    The Virtual Seismologist (VS) method is a Bayesian approach to regional network-based earthquake early warning (EEW) originally formulated by Cua and Heaton (2007). Implementation of VS into real-time EEW codes has been an on-going effort of the Swiss Seismological Service at ETH Zürich since 2006, with support from ETH Zürich, various European projects, and the United States Geological Survey (USGS). VS is one of three EEW algorithms that form the basis of the California Integrated Seismic Network (CISN) ShakeAlert system, a USGS-funded prototype end-to-end EEW system that could potentially be implemented in California. In Europe, VS is currently operating as a real-time test system in Switzerland, western Greece and Istanbul. As part of the on-going EU project REAKT (Strategies and Tools for Real-Time Earthquake Risk Reduction), VS installations in southern Italy, Romania, and Iceland are planned or underway. The possible use cases for an EEW system will be determined by the speed and reliability of earthquake source parameter estimates. A thorough understanding of both is therefore essential to evaluate the usefulness of VS. For California, we present state-wide theoretical alert times for hypothetical earthquakes by analyzing time delays introduced by the different components in the VS EEW system. Taking advantage of the fully probabilistic formulation of the VS algorithm we further present an improved way to describe the uncertainties of every magnitude estimate by evaluating the width and shape of the probability density function that describes the relationship between waveform envelope amplitudes and magnitude. We evaluate these new uncertainty values for past seismicity in California through off-line playbacks and compare them to the previously defined static definitions of uncertainty based on real-time detections. Our results indicate where VS alerts are most useful in California and also suggest where most effective improvements to the VS EEW system

  7. Correction of diabetic pattern of insulin release from islets of the spiny mouse (Acomys cahirinus) by glucose priming in vitro.

    PubMed

    Nesher, R; Abramovitch, E; Cerasi, E

    1985-04-01

    Insulin release kinetics were studied in perifused islets of Langerhans, isolated from mildly hyperglycaemic and from normoglycaemic spiny mice (Acomys cahirinus), a rodent predisposed to develop spontaneously non-ketotic diabetes. In both groups, insulin response to glucose (16.7 mmol/l) was delayed in comparison with that of rat islets, the release kinetics being analogous to that of human Type 2 (non-insulin-dependent) diabetes. Thirty min priming of the isolated Acomys islets with glucose (16.7 mmol/l) resulted in potentiation of the insulin release to a second stimulation. The degree of potentiation decreased exponentially with the time interval between stimulations, showing a t1/2 of 18 min. Induction of potentiation by glucose was time-dependent, giving a maximal effect after 20 min of priming. In addition to overall amplification of the insulin response, priming with glucose accelerated markedly the initial release rates, correcting the dynamics of the response. We conclude that: (1) decreased and delayed insulin secretion is found in Acomys cahirinus before the development of hyperglycaemia; (2) induction of time-dependent potentiation in the islet by priming with glucose corrects the diabetic-type dynamics of insulin release; (3) therefore the deficient insulin release of Acomys is of a functional nature, the mechanism of potentiation bypassing the defect; (4) since insulin release in Acomys resembles that in prediabetic and diabetic man, similar conclusions might apply to the islet dysfunction in Type 2 diabetes.

  8. Control of phenylalanine hydroxylase synthesis in tissue culture by serum and insulin.

    PubMed

    Tourian, A

    1976-01-01

    Stationary-phase, minimal deviation hepatoma H4-II-E-C3 cell cultures that are serum-deprived respond with a biphasic time course of phenylalanine hydroxylase induction when dialyzed fetal calf serum or insulin is added. These two agents induce phenylalanine hydroxylase additively, during both the initial 3-hour and the delayed 24-hour phases. The initial phase of induction by insulin is inhibited by cycloheximide but not by actinomycin D. The delayed induction by both dialyzed fetal calf serum and insulin is inhibited by 10(-6) M cycloheximide and 0.20 mug/ml actinomycin D. H4-II-E-C3 cells in culture do not synthesize the factor(s) in serum that induce phenylalanine hydroxylase.

  9. Depressive symptoms prior to and following insulin initiation in patients with type 2 diabetes mellitus: Prevalence, risk factors and effect on physician resource utilisation.

    PubMed

    Dzida, Grzegorz; Karnieli, Eddy; Svendsen, Anne Louise; Sølje, Kristine Steensen; Hermanns, Norbert

    2015-10-01

    To study the frequency and intensity of depressive symptoms and associations with physician resource utilisation following insulin initiation in patients with type 2 diabetes mellitus. SOLVE was a 24-week observational study. In this sub-analysis of data from Poland, depressive symptoms were evaluated using the Patient Health Questionnaire (PHQ)-9. PHQ-9 was completed by 942 of 1169 patients (80.6%) at baseline, and 751 (64.2%) at both baseline and final (24-week) visit. PHQ-9 scores indicated depressive symptoms in 45.6% (n=430) at baseline, and 27.2% (n=223) at final visit. Mean PHQ-9 change was -2.38 [95% CI -2.73, -2.02], p<0.001. Depressive symptoms at baseline (OR 6.32, p<0.001), microvascular disease (OR 2.45, p=0.016), number of physician contacts (OR 1.16, p=0.009), and change in HbA1c (OR 0.60, p=0.025) were independently associated with moderate/severe depressive symptoms at final visit. Patients with more severe depressive symptoms spent more time training to self-inject (p=0.0016), self-adjust (p=0.0023) and manage other aspects of insulin delivery (p<0.0001). Patients with persistent depressive symptoms had more telephone contacts and dose changes at final visit than those without (both p<0.05). Depressive symptoms are common with type 2 diabetes and associated with increased healthcare utilisation, reinforcing the need for holistic interdisciplinary management approaches. Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  10. SPECTRAL ENERGY DISTRIBUTION OF z {approx}> 1 TYPE Ia SUPERNOVA HOSTS IN GOODS: CONSTRAINTS ON EVOLUTIONARY DELAY AND THE INITIAL MASS FUNCTION

    SciTech Connect

    Thomson, M. G.; Chary, R. R.

    2011-04-10

    We identify a sample of 22 host galaxies of Type Ia Supernovae (SNe Ia) at redshifts 0.95 < z < 1.8 discovered in the Hubble Space Telescope (HST) observations of the Great Observatories Origins Deep Survey (GOODS) fields. We measure the photometry of the hosts in Spitzer Space Telescope and ground-based imaging of the GOODS fields to provide flux densities from the U band to 24 {mu}m. We fit the broadband photometry of each host with simple stellar population models to estimate the age of the stellar population giving rise to the SN Ia explosions. We break the well-known age-extinction degeneracy in such analyses using the Spitzer 24 {mu}m data to place upper limits on the thermally reprocessed, far-infrared emission from dust. The ages of these stellar populations give us an estimate of the delay times between the first epoch of star formation in the galaxies and the explosion of the SNe Ia. We find a bi-modal distribution of delay times ranging from 0.06 to 4.75 Gyr although at the 95% confidence interval, the delay time distribution is consistent with a single power law as well. We also constrain the first epoch of low-mass star formation using these results, showing that stars of mass {approx}<8 M{sub sun} were formed within 3 Gyr after the big bang and possibly by z {approx} 6. This argues against a truncated stellar initial mass function in high-redshift galaxies.

  11. Treatment of sulfonylurea and insulin overdose.

    PubMed

    Klein-Schwartz, Wendy; Stassinos, Gina L; Isbister, Geoffrey K

    2016-03-01

    The most common toxicity associated with sulfonylureas and insulin is hypoglycaemia. The article reviews existing evidence to better guide hypoglycaemia management. Sulfonylureas and insulin have narrow therapeutic indices. Small doses can cause hypoglycaemia, which may be delayed and persistent. All children and adults with intentional overdoses need to be referred for medical assessment and treatment. Unintentional supratherapeutic ingestions can be initially managed at home but if symptomatic or if there is persistent hypoglycaemia require medical referral. Patients often require intensive care and prolonged observation periods. Blood glucose concentrations should be assessed frequently. Asymptomatic children with unintentional sulfonylurea ingestions should be observed for 12 h, except if this would lead to discharge at night when they should be kept until the morning. Prophylactic intravenous dextrose is not recommended. The goal of therapy is to restore and maintain euglycaemia for the duration of the drug's toxic effect. Enteral feeding is recommended in patients who are alert and able to tolerate oral intake. Once insulin or sulfonylurea-induced hypoglycaemia has developed, it should be initially treated with an intravenous dextrose bolus. Following this the mainstay of therapy for insulin-induced hypoglycaemia is intravenous dextrose infusion to maintain the blood glucose concentration between 5.5 and 11 mmol l(-1) . After sulfonylurea-induced hypoglycaemia is initially corrected with intravenous dextrose, the main treatment is octreotide which is administered to prevent insulin secretion and maintain euglycaemia. The observation period varies depending on drug, product formulation and dose. A general guideline is to observe for 12 h after discontinuation of intravenous dextrose and, if applicable, octreotide.

  12. Treatment effect expressed as the novel Delay of Event measure is associated with high willingness to initiate preventive treatment - A randomized survey experiment comparing effect measures.

    PubMed

    Berglund, Erik; Westerling, Ragnar; Sundström, Johan; Lytsy, Per

    2016-12-01

    This study aimed to investigate patients' willingness to initiate a preventive treatment and compared two established effect measures to the newly developed Delay of Events (DoE) measure that expresses treatment effect as a gain in event-free time. In this cross-sectional, randomized survey experiment in the general Swedish population,1079 respondents (response rate 60.9%) were asked to consider a preventive cardiovascular treatment. Respondents were randomly allocated to one of three effect descriptions: DoE, relative risk reduction (RRR), or absolute risk reduction (ARR). Univariate and multivariate analyses were performed investigating willingness to initiate treatment, views on treatment benefit, motivation and importance to adhere and willingness to pay for treatment. Eighty-one percent were willing to take the medication when the effect was described as DoE, 83.0% when it was described as RRR and 62.8% when it was described as ARR. DoE and RRR was further associated with positive views on treatment benefit, motivation, importance to adhere and WTP. Presenting treatment effect as DoE or RRR was associated with a high willingness to initiate treatment. An approach based on the novel time-based measure DoE may be of value in clinical communication and shared decision making. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  13. Overexpression of eIF5 or its protein mimic 5MP perturbs eIF2 function and induces ATF4 translation through delayed re-initiation

    PubMed Central

    Kozel, Caitlin; Thompson, Brytteny; Hustak, Samantha; Moore, Chelsea; Nakashima, Akio; Singh, Chingakham Ranjit; Reid, Megan; Cox, Christian; Papadopoulos, Evangelos; Luna, Rafael E.; Anderson, Abbey; Tagami, Hideaki; Hiraishi, Hiroyuki; Slone, Emily Archer; Yoshino, Ken-ichi; Asano, Masayo; Gillaspie, Sarah; Nietfeld, Jerome; Perchellet, Jean-Pierre; Rothenburg, Stefan; Masai, Hisao; Wagner, Gerhard; Beeser, Alexander; Kikkawa, Ushio; Fleming, Sherry D.; Asano, Katsura

    2016-01-01

    ATF4 is a pro-oncogenic transcription factor whose translation is activated by eIF2 phosphorylation through delayed re-initiation involving two uORFs in the mRNA leader. However, in yeast, the effect of eIF2 phosphorylation can be mimicked by eIF5 overexpression, which turns eIF5 into translational inhibitor, thereby promoting translation of GCN4, the yeast ATF4 equivalent. Furthermore, regulatory protein termed eIF5-mimic protein (5MP) can bind eIF2 and inhibit general translation. Here, we show that 5MP1 overexpression in human cells leads to strong formation of 5MP1:eIF2 complex, nearly comparable to that of eIF5:eIF2 complex produced by eIF5 overexpression. Overexpression of eIF5, 5MP1 and 5MP2, the second human paralog, promotes ATF4 expression in certain types of human cells including fibrosarcoma. 5MP overexpression also induces ATF4 expression in Drosophila. The knockdown of 5MP1 in fibrosarcoma attenuates ATF4 expression and its tumor formation on nude mice. Since 5MP2 is overproduced in salivary mucoepidermoid carcinoma, we propose that overexpression of eIF5 and 5MP induces translation of ATF4 and potentially other genes with uORFs in their mRNA leaders through delayed re-initiation, thereby enhancing the survival of normal and cancer cells under stress conditions. PMID:27325740

  14. Downhole delay assembly for blasting with series delay

    DOEpatents

    Ricketts, Thomas E.

    1982-01-01

    A downhole delay assembly is provided which can be placed into a blasthole for initiation of explosive in the blasthole. The downhole delay assembly includes at least two detonating time delay devices in series in order to effect a time delay of longer than about 200 milliseconds in a round of explosions. The downhole delay assembly provides a protective housing to prevent detonation of explosive in the blasthole in response to the detonation of the first detonating time delay device. There is further provided a connection between the first and second time delay devices. The connection is responsive to the detonation of the first detonating time delay device and initiates the second detonating time delay device. A plurality of such downhole delay assemblies are placed downhole in unfragmented formation and are initiated simultaneously for providing a round of explosive expansions. The explosive expansions can be used to form an in situ oil shale retort containing a fragmented permeable mass of formation particles.

  15. Unique combination of hyperintense vessel sign on initial FLAIR and delayed vasoconstriction on MRA in reversible cerebral vasoconstriction syndrome: a case report.

    PubMed

    Kameda, Tomoaki; Namekawa, Michito; Shimazaki, Haruo; Minakata, Daisuke; Matsuura, Tohru; Nakano, Imaharu

    2014-11-01

    Reversible cerebral vasoconstriction syndrome is characterized by thunderclap headache and reversible cerebral vasoconstriction on angiographic findings. It can be difficult to diagnose when initial angiography is normal. A 30-year-old woman was admitted because of sudden-onset thunderclap headache and seizure on postpartum day 7. Brain MRI on fluid-attenuated inversion recovery (FLAIR) showed hyperintense vessel sign (HVS), which usually means slow flow due to severe proximal arterial stenosis. However, magnetic resonance angiography (MRA) indicated that proximal arteries was normal. After nicardipine treatment, her symptoms improved dramatically. Follow-up FLAIR on day 7 showed complete resolution of HVS, while a series of MRAs revealed reversible multifocal segmental vasoconstriction. HVS on initial FLAIR is useful for an early diagnosis of reversible cerebral vasoconstriction syndrome. As the delayed vasoconstriction on MRA can be observed, reversible cerebral vasoconstriction syndrome may progress from distal small to proximal larger arteries. © International Headache Society 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  16. Immunologic insulin resistance.

    PubMed

    Davidson, J K; DeBra, D W

    1978-03-01

    The efficacy of sulfated beef insulin for plasma glucose control in 35 patients with immunologic insulin resistance was studied. Patients were on a mean dose of 550 U./day (range 200--2,000) of U-500 regular beef insulin. Mean maximum 125I-insulin-binding capacity was 191 mU./ml. serum (range 13--1,080). Mean in vivo half-life (T 1/2) of 125I-regular beef insulin was 614 minutes (range 114--1,300), as against a mean T 1/2 of 13.9 minutes (range 11.8--16.5) in normal controls. Treatment was successful in 34 patients and unsuccessful in one with lipoatrophic diabetes. The mean initial dose of sulfated insulin was 89 U./day (range 15--400) and at three months was 66 U./day (range 20--400). Twenty-eight patients who responded and survived have been on sulfated insulin for a mean of 39 months (range 2-66) and are on a mean dose of 25 U./day (range 0--100). The mean maximum binding capacity fell to 9 mU./ml. (range 0--34) during therapy (p less than 0.01). Mean 125I-insulin T 1/2 fell from 614 to 249 minutes after sulfated insulin therapy (p less than 0.001). A comparative study of 15 patients on consecutive days showed a 35 sulfated insulin T 1/2 of 60 minutes (range 15--94) and a mean 125I-regular insulin T 1/2 of 246 minutes (range 62--560, p less than 0.001). These results indicate that sulfated insulin is less antigenic than regular beef insulin and combines less avidly with human antibodies to regular beef insulin. The response to sulfated insulin therapy was significantly better than the response reported by other investigators to pork insulin or to steroid therapy in similar patients.

  17. Insulin signaling and insulin resistance.

    PubMed

    Beale, Elmus G

    2013-01-01

    Insulin resistance or its sequelae may be the common etiology of maladies associated with metabolic syndrome (eg, hypertension, type 2 diabetes, atherosclerosis, heart attack, stroke, and kidney failure). It is thus important to understand those factors that affect insulin sensitivity. This review stems from the surprising discovery that interference with angiotensin signaling improves insulin sensitivity, and it provides a general overview of insulin action and factors that control insulin sensitivity.

  18. Impact of insulin sensitivity, beta-cell function and glycaemic control on initiation of second-line glucose-lowering treatment in newly diagnosed type 2 diabetes.

    PubMed

    Rathmann, Wolfgang; Strassburger, Klaus; Bongaerts, Brenda; Bobrov, Pavel; Kuss, Oliver; Müssig, Karsten; Markgraf, Daniel F; Szendroedi, Julia; Herder, Christian; Roden, Michael

    2017-06-01

    The aim of this study was to investigate whether insulin sensitivity, beta-cell function or glycaemic control at diagnosis predict initiation of second-line treatment in newly diagnosed type 2 diabetes. Type 2 diabetes patients (n = 138) undergoing initial metformin monotherapy (age [mean ± SD], 52 ± 10 years; 67% males; BMI, 32 ± 6 kg/m(2) ) from the prospective German Diabetes Study cohort (n = 398) were included. Patients remained under care of their general practitioners, yet underwent detailed metabolic characterization after diabetes diagnosis for study purposes (hyperinsulinemic-euglycemic clamp, M value; i.v. glucose tolerance test, incremental C-peptide area under the curve0-60 minutes, CP iAUC). The associations of baseline M value, CP iAUC, fasting glucose and HbA1c with time to second-line therapy were assessed using parametric survival analysis, accounting for interval-censoring. Second-line treatment was initiated in 26% of newly diagnosed type 2 diabetes patients within the first 3.3 years after diagnosis, using mostly DPP-4 inhibitors or GLP-1 receptor agonists (64%). In age-, sex- and BMI-adjusted survival models, higher baseline HbA1c and fasting glucose values were associated with earlier treatment intensification. Lower baseline M value and C-peptide secretion (CP iAUC) were also related to an earlier initiation of second-line treatment. In the best multivariable model, baseline HbA1c ≥ 7% (hazard ratio, HR; 95% CI: 3.18; 1.35-7.50) and fasting glucose ≥140 mg/dL (HR, 2.45; 95% CI, 1.04-5.78) were associated with shorter time to second-line therapy, adjusting for age, sex and BMI. Baseline hyperglycaemia is a strong predictor of requirement of early intensification of glucose-lowering therapy in newly diagnosed type 2 diabetes. © 2017 John Wiley & Sons Ltd.

  19. Practical Focus on American Diabetes Association/European Association for the Study of Diabetes Consensus Algorithm in Patients with Type 2 Diabetes Mellitus: Timely Insulin Initiation and Titration (Iran-AFECT)

    PubMed Central

    Yousefzadeh, Gholamreza; Banazadeh, Zahra; Ghareh, Sahar

    2017-01-01

    Background The aim of this study was to evaluate the safety and effectiveness of insulin glargine in a large population from a variety of clinical care in Iranian people with type 2 diabetes mellitus (T2DM) and to measure the percentage of patients achieving glycosylated hemoglobin (HbA1c) <7% by the end of 24 weeks of treatment in routine clinical practice. Methods This study was a 24 week, observational study of patients with T2DM, for whom the physician had decided to initiate or to switch to insulin glargine. The safety and efficacy of glargine were assessed at baseline and at week 24. Results Seven hundred and twenty-five people with T2DM (63% female) including both insulin naïve and prior insulin users were recruited in this study. The mean age of the participants was 54.2±11.2 years, and the mean HbA1c level was 8.88%±0.93% at baseline. By the end of the study, 27% of the entire participants reached to HbA1c target of less than 7% and 52% had HbA1c ≤7.5%. No serious adverse event was reported in this study. Furthermore, overall hypoglycemia did not increase in prior insulin users and the entire cohort. In addition, body weight did not change in participants while lipid profile improved significantly. Conclusion Treatment with insulin glargine could improve glycemic control without increasing the risk of hypoglycemic events in people with T2DM. In addition, a significant clinical improvement was observed in lipid profile. PMID:28236383

  20. BeAM value: an indicator of the need to initiate and intensify prandial therapy in patients with type 2 diabetes mellitus receiving basal insulin

    PubMed Central

    Zisman, Ariel; Morales, Francienid; Stewart, John; Stuhr, Andreas; Vlajnic, Aleksandra; Zhou, Rong

    2016-01-01

    Introduction In patients with type 2 diabetes mellitus (T2DM) with uncontrolled glycemia despite ongoing upward titration of basal insulin, targeting postprandial hyperglycemia may be required. Nevertheless, the point at which basal insulin is fully optimized and postprandial glucose (PPG) should be targeted with additional treatment remains unclear. We report here on the BeAM value (difference between bedtime and morning blood glucose values) as an indicator of the need to target PPG. Methods This study had 3 stages: exploratory, main, and proof-of-concept analyses. For the exploratory and main analyses, data were pooled from phase 3 trials in adults with T2DM adding basal insulin to oral antidiabetic drugs (OADs). The main analysis included only patients who did not reach A1C ≤7.0% (53 mmol/mol) at week 24. The proof-of-concept analysis used pooled data from phase 3 trials in adults with T2DM adding insulin glargine and a single insulin glulisine injection to OADs. Results In patients undergoing basal insulin titration, BeAM value increased over 24 weeks (27.8–61.7 mg/dL, n=1188; 32.6–71.2 mg/dL, n=553; exploratory and main analyses, respectively). There were significant correlations between week 24 BeAM value and postprandial contribution to hyperglycemia (Pearson's correlation coefficient (r)=0.375, p<0.001; r=0.396, p<0.001; exploratory and main analyses, respectively). When PPG was targeted (proof-of-concept analysis), the BeAM value reduced from 77.0 to 40.4 mg/dL (n=299). Conclusions The BeAM value described in this study is a simple, easy-to-calculate value that may identify patients with T2DM using basal insulin that need targeting of postprandial control rather than advancing basal insulin dose. PMID:27110368

  1. Initial segment Kv2.2 channels mediate a slow delayed rectifier and maintain high frequency action potential firing in medial nucleus of the trapezoid body neurons.

    PubMed

    Johnston, Jamie; Griffin, Sarah J; Baker, Claire; Skrzypiec, Anna; Chernova, Tatanya; Forsythe, Ian D

    2008-07-15

    The medial nucleus of the trapezoid body (MNTB) is specialized for high frequency firing by expression of Kv3 channels, which minimize action potential (AP) duration, and Kv1 channels, which suppress multiple AP firing, during each calyceal giant EPSC. However, the outward K(+) current in MNTB neurons is dominated by another unidentified delayed rectifier. It has slow kinetics and a peak conductance of approximately 37 nS; it is half-activated at -9.2 +/- 2.1 mV and half-inactivated at -35.9 +/- 1.5 mV. It is blocked by several non-specific potassium channel antagonists including quinine (100 microm) and high concentrations of extracellular tetraethylammonium (TEA; IC(50) = 11.8 mM), but no specific antagonists were found. These characteristics are similar to recombinant Kv2-mediated currents. Quantitative RT-PCR showed that Kv2.2 mRNA was much more prevalent than Kv2.1 in the MNTB. A Kv2.2 antibody showed specific staining and Western blots confirmed that it recognized a protein approximately 110 kDa which was absent in brainstem tissue from a Kv2.2 knockout mouse. Confocal imaging showed that Kv2.2 was highly expressed in axon initial segments of MNTB neurons. In the absence of a specific antagonist, Hodgkin-Huxley modelling of voltage-gated conductances showed that Kv2.2 has a minor role during single APs (due to its slow activation) but assists recovery of voltage-gated sodium channels (Nav) from inactivation by hyperpolarizing interspike potentials during repetitive AP firing. Current-clamp recordings during high frequency firing and characterization of Nav inactivation confirmed this hypothesis. We conclude that Kv2.2-containing channels have a distinctive initial segment location and crucial function in maintaining AP amplitude by regulating the interspike potential during high frequency firing.

  2. Induction of the 5S RNP-Mdm2-p53 ribosomal stress pathway delays the initiation but fails to eradicate established murine acute myeloid leukemia.

    PubMed

    Jaako, P; Ugale, A; Wahlestedt, M; Velasco-Hernandez, T; Cammenga, J; Lindström, M S; Bryder, D

    2017-01-01

    Mutations resulting in constitutive activation of signaling pathways that regulate ribosome biogenesis are among the most common genetic events in acute myeloid leukemia (AML). However, whether ribosome biogenesis presents as a therapeutic target to treat AML remains unexplored. Perturbations in ribosome biogenesis trigger the 5S ribonucleoprotein particle (RNP)-Mdm2-p53 ribosomal stress pathway, and induction of this pathway has been shown to have therapeutic efficacy in Myc-driven lymphoma. In the current study we address the physiological and therapeutic role of the 5S RNP-Mdm2-p53 pathway in AML. By utilizing mice that have defective ribosome biogenesis due to downregulation of ribosomal protein S19 (Rps19), we demonstrate that induction of the 5S RNP-Mdm2-p53 pathway significantly delays the initiation of AML. However, even a severe Rps19 deficiency that normally results in acute bone marrow failure has no consistent efficacy on already established disease. Finally, by using mice that harbor a mutation in the Mdm2 gene disrupting its binding to 5S RNP, we show that loss of the 5S RNP-Mdm2-p53 pathway is dispensable for development of AML. Our study suggests that induction of the 5S RNP-Mdm2-p53 ribosomal stress pathway holds limited potential as a single-agent therapy in the treatment of AML.

  3. Insulin treatment of type 2 diabetes: considerations when converting from human insulin to insulin analogs.

    PubMed

    Griffin, Stacy

    2013-03-01

    Type 2 diabetes mellitus is a highly prevalent disease characterized by insulin resistance, hyperglycemia, and diminished pancreatic β-cell function. Conventional insulin products used to manage this disease include regular human insulin and intermediate-acting human insulin. However, due to several limitations imposed by human insulins, such as onset and duration of action that do not coincide with physiologic needs and increased risk of hypoglycemia, insulin analogs were developed. Because they more closely mimic the physiologic action of endogenous insulin, insulin analogs are associated with more effective glucose control, a lower risk of hypoglycemia, greater convenience, and, in some instances, less weight gain. Switching from human insulin to insulin analogs is easily accomplished. Several studies have demonstrated a high rate of success with patient-initiated, self-adjusted dosing algorithms compared to investigator/clinician-initiated dose adjustments. These studies and several other published guidelines on insulin analogs provide patients and clinicians with information pertaining to better treatment options and can help increase overall patient satisfaction.

  4. Chromium and insulin resistance.

    PubMed

    Anderson, Richard A

    2003-12-01

    Insulin resistance leads to the inability of insulin to control the utilization and storage of glucose. It is associated initially with elevated levels of circulating insulin followed by glucose intolerance which may progress to type 2 diabetes, hyperlipidaemia, hypertension, obesity and cardiovascular diseases. While the causes of these diseases are multifactorial, one nutrient that is associated with all of these abnormalities is Cr. In the presence of Cr, in a biologically active form, much lower levels of insulin are required. Modern diets, which are often high in refined carbohydrates, are not only low in Cr, but lead to enhanced Cr losses. In response to the consumption of refined carbohydrates, there is a rapid rise in blood sugar leading to elevations in insulin that cause a mobilization of Cr. Once mobilized, Cr is not reabsorbed but lost via the urine leading to decreased Cr stores. Several studies involving both human subjects and experimental animals have reported improvements in insulin sensitivity, blood glucose, insulin, lipids, haemoglobin A1c, lean body mass and related variables in response to improved Cr nutrition. However, not all studies have reported beneficial effects associated with improved Cr nutrition. Well-controlled human studies are needed to document an unequivocal effect of Cr on insulin sensitivity in human subjects. Studies need to involve a significant number of subjects with insulin resistance, glucose intolerance or early stages of diabetes, who have not been taking supplements containing Cr for at least 4 months, and involve at least 400 to 600 microg supplemental Cr daily or more. Studies should be at least 4 months to document sustained effects of supplemental Cr on insulin resistance and related variables. Cr is a nutrient and not a therapeutic agent and therefore will only be of benefit to those whose problems are due to suboptimal intake of Cr.

  5. Pulsatile Portal Vein Insulin Delivery Enhances Hepatic Insulin Action and Signaling

    PubMed Central

    Matveyenko, Aleksey V.; Liuwantara, David; Gurlo, Tatyana; Kirakossian, David; Dalla Man, Chiara; Cobelli, Claudio; White, Morris F.; Copps, Kyle D.; Volpi, Elena; Fujita, Satoshi; Butler, Peter C.

    2012-01-01

    Insulin is secreted as discrete insulin secretory bursts at ∼5-min intervals into the hepatic portal vein, these pulses being attenuated early in the development of type 1 and type 2 diabetes mellitus (T2DM). Intraportal insulin infusions (pulsatile, constant, or reproducing that in T2DM) indicated that the pattern of pulsatile insulin secretion delivered via the portal vein is important for hepatic insulin action and, therefore, presumably for hepatic insulin signaling. To test this, we examined hepatic insulin signaling in rat livers exposed to the same three patterns of portal vein insulin delivery by use of sequential liver biopsies in anesthetized rats. Intraportal delivery of insulin in a constant versus pulsatile pattern led to delayed and impaired activation of hepatic insulin receptor substrate (IRS)-1 and IRS-2 signaling, impaired activation of downstream insulin signaling effector molecules AKT and Foxo1, and decreased expression of glucokinase (Gck). We further established that hepatic Gck expression is decreased in the HIP rat model of T2DM, a defect that correlated with a progressive defect of pulsatile insulin secretion. We conclude that the physiological pulsatile pattern of insulin delivery is important in hepatic insulin signaling and glycemic control. Hepatic insulin resistance in diabetes is likely in part due to impaired pulsatile insulin secretion. PMID:22688333

  6. Delayed ejaculation

    MedlinePlus

    Ejaculatory incompetence; Sex - delayed ejaculation; Retarded ejaculation; Anejaculation; Infertility - delayed ejaculation ... include: Religious background that makes the person view sex as sinful Lack of attraction for a partner ...

  7. [Insulin signaling and insulin resistance].

    PubMed

    Ferré, Pascal

    2007-01-01

    Insulin controls carbohydrate and lipid metabolism. Among other things, it stimulates glucose storage as glycogen and lipid storage as triglycerides. Insulin acts through a membrane receptor which is a tyrosine kinase. When activated by insulin binding, the tyrosine kinase will recruit and phosphorylate intracellular substrates called IRS (insulin receptor substrate). Phosphorylated IRS will be used as docking sites for proteins which will transmit the insulin signal through several systems (e.g. PI3-kinase). The insulin resistance which is concomitant with type 2 diabetes and obesity is linked to an increased intracellular availability of fatty acids which are precursors of lipid mediators inducing a decreased efficiency of insulin signal transmission. Therapies aimed at improving insulin sensitivity could then target proteins involved in the regulation of intacellular fatty acid availibility.

  8. Insulin therapy refusal among type II diabetes mellitus patients in Kubang Pasu district, Kedah, Malaysia

    PubMed Central

    Tan, Wei Leong; Asahar, Siti Fairus; Harun, Noor Liani

    2015-01-01

    INTRODUCTION Diabetes mellitus is a rising non-communicable disease in Malaysia. Insulin therapy refusal is a challenge for healthcare providers, as it results in delayed insulin initiation. This study was conducted to determine the prevalence of insulin therapy refusal and its associated factors. METHODS This cross-sectional study was conducted at seven public health clinics in Kubang Pasu district of Kedah, Malaysia, from March to October 2012. A newly developed and validated questionnaire was used and participants were selected via systematic random sampling. Only patients diagnosed with type II diabetes mellitus (T2DM) and under the public health clinic care in Kubang Pasu were included in the study. Multiple logistic regression was used to study the association between insulin therapy refusal and its associated factors. RESULTS There were 461 respondents and the response rate was 100%. Among these 461 patients with T2DM, 74.2% refused insulin therapy. The most common reason given for refusal was a lack of confidence in insulin injection (85.4%). Multiple logistic regression revealed that respondents who had secondary education were 55.0% less likely to refuse insulin therapy than those who had primary education or no formal education (adjusted odds ratio [OR] 0.45, 95% confidence interval [CI] 0.25–0.82, p = 0.009). There was also a significant inverse association between glycated haemoglobin (HbA1c) level and insulin therapy refusal (adjusted OR 0.87, 95% CI 0.76–1.00, p = 0.047). CONCLUSION Insulin therapy refusal is common in Kubang Pasu. Educational status and HbA1c level should be taken into consideration when counselling patients on insulin therapy initiation. PMID:25532511

  9. Insulin Delivery System

    NASA Technical Reports Server (NTRS)

    1988-01-01

    When Programmable Implantable Medication System (PIMS) is implanted in human body, it delivers precise programmed amounts of insulin over long periods of time. Mini-Med Technologies has been refining the Technologies since initial development at APL. The size of a hockey puck, and encased in titanium shell, PIMS holds about 2 1/2 teaspoons of insulin at a programmed basal rate. If a change in measured blood sugar level dictates a different dose, the patient can vary the amount of insulin delivered by holding a small radio transceiver over the implanted system and dialing in a specific program held in the PIMS computer memory. Insulin refills are accomplished approximately 4 times a year by hypodermic needle.

  10. Biosimilar insulins.

    PubMed

    Heinemann, Lutz

    2012-08-01

    Until now most insulin used in developed countries is manufactured and distributed by a small number of multinational companies. Other pharmaceutical companies - many of these are located in countries such as India or China - are also able to manufacture insulin with modern biotechnological methods. Additionally, the patents for many insulin formulations have expired or are going to expire soon. This enables such companies to produce insulins and to apply for market approval of these as biosimilar insulins (BIs) in highly regulated markets such as the EU or the US. To understand the complexity of BIs' approval and usage, scientific and regulatory aspects have to be discussed. Differences in the manufacturing process (none of the insulin-manufacturing procedures are identical) result in the fact that all insulin that might become BIs differ from the originator insulin to some extent. The question is, have such differences in the structure of the insulin molecule and or the purity and so on clinically relevant consequences for the biological effects induced or not. The guidelines already in place in the EU for market approval require that the manufacturer demonstrates that his insulin has a safety and efficacy profile that is similar to that of the 'original' insulin formulation. Recently guidelines for biosimilars were issued in the US; however, these do not cover insulin. Although a challenging approval process for insulins to become BI might be regarded as a hurdle to keep companies out of certain markets, it is fair to say that the potential safety and efficacy issues surrounding BI are substantial and relevant, and do warrant a careful and evidence-driven approval process. Nevertheless, it is very likely that in the next years, BIs will come to the market also in highly regulated markets.

  11. Validity and reliability of the Chinese version of the Insulin Treatment Appraisal Scale among primary care patients in Hong Kong.

    PubMed

    Lee, K P

    2016-08-01

    Patients with diabetes mellitus often delay insulin initiation and titration due to psychological factors. This phenomenon is known as 'psychological insulin resistance'. Tools that identify psychological insulin resistance are valuable for detecting its causes and can lead to appropriate counselling. The Insulin Treatment Appraisal Scale was initially developed for western populations and has been translated and validated to measure psychological insulin resistance in Taiwan (Chinese version of the Insulin Treatment Appraisal Scale, C-ITAS). The current study examined the prevalence of psychological insulin resistance and the validity of the C-ITAS in a local population. This cross-sectional study involved 360 patients with diabetes mellitus from a government-funded general out-patient clinic who completed the C-ITAS questionnaire. The total C-ITAS score was compared for patients with psychological insulin resistance and those without, and the internal consistency and test-retest reliability of the C-ITAS were calculated. An exploratory factor analysis was used to identify factors within the C-ITAS. The prevalence of psychological insulin resistance was 44.9%. The internal consistency of the scale was high (Cronbach's alpha=0.78). The test-retest reliability was positive with all C-ITAS questions (0.294-0.725). The mean C-ITAS score was significantly higher among patients with psychological insulin resistance than those without (42.42 vs 35.78; P<0.001). The exploratory factor analysis, however, failed to identify the two clear factors identified in the original validation study. The C-ITAS appears to be a feasible and potentially useful tool for identifying psychological insulin resistance, but additional validation or translation is required before it can be widely used clinically.

  12. Intracellular insulin-receptor dissociation and segregation in a rat fibroblast cell line transfected with a human insulin receptor gene

    SciTech Connect

    Levy, J.R.; Olefsky, J.M.

    1988-05-05

    The cellular processing of insulin and insulin receptors was studied using a rat fibroblast cell line that had been transfected with a normal human insulin receptor gene, expressing approximately 500 times the normal number of native fibroblasts insulin receptors. These cells bind and internalize insulin normally. Biochemically assays based on the selective precipitation by polyethylene glycol of intact insulin-receptor complexes but not of free intracellular insulin were developed to study the time course of intracellular insulin-receptor dissociation. Fibroblasts were incubated with radiolabeled insulin at 4/sup 0/C, and internalization of insulin-receptor complexes was initiated by warming the cells to 37/sup 0/C. Within 2 min, 90% of the internalized radioactivity was composed of intact insulin-receptor complexes. The dissociation of insulin from internalized insulin-receptor complexes was markedly inhibited by monensin and chloroquine. Furthermore, chloroquine markedly increased the number of cross-linkable intracellular insulin-receptor complexes, as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiography. These findings suggest that acidification of intracellular vesicles is responsible for insulin-receptor dissociation. Physical segregation of dissociated intracellular insulin from its receptor was monitored. The results are consistent with the view that segregation of insulin and receptor occurs 5-10 min after initiation of dissociation. These studies demonstrate the intracellular itinerary of insulin-receptor complexes, including internalization, dissociation of insulin from the internalized receptor within an acidified compartment, segregation of insulin from the receptor, and subsequent ligand degradation.

  13. Obviating much of the need for insulin therapy in type 2 diabetes mellitus: A re-assessment of insulin therapy's safety profile.

    PubMed

    Schwartz, Stanley S; Jellinger, Paul S; Herman, Mary E

    2016-08-01

    reduce reliance on insulin through delayed initiation, minimized dose, and, drug switching to safer agents, and, potentially, reframes processes of care.

  14. Consensus on Insulin Dose and Titration Algorithms in Ambulatory Care of Type 2 Diabetes in India.

    PubMed

    Kovil, Rajiv; Chawla, Manoj; Rajput, Rajesh; Singh, A K; Sinha, Binayak; Ghosal, Samit; Ballani, Piya; Gupta, Sunil; Tanna, Snehal; Bandukwala, S M; Shah, Tejas; Negalur, Vijay; Bhoraskar, Anil; Aravind, S R; Zargar, Abdul H; Kesavadev, Jothydev; Das, Ashok Kumar

    2017-02-01

    Insulin is the oldest of the currently available treatment options in Type 2 diabetes mellitus (T2DM) and is considered as the most effective glucose lowering agent. Despite this, decision on starting insulin therapy is often delayed in India as well as worldwide due to various barriers at both patient and physician levels. Appropriate insulin dosing and titration is also critical to the successful achievement of tight glycaemic control. To provide simple and easily implementable guidelines to primary care physicians on appropriate insulin dosing and titration of various insulin regimens for both initiation and intensification. Each insulin regimen (once daily [OD] basal, OD, twice daily and thrice daily premixed, basal-plus and basal-bolus) was presented and evaluated for dosing and titration based on established guidelines, data from approved pack inserts, and published scientific literature. These evaluations were then factored into the national context based on the expert committee representatives patient-physician experience in their clinical practice and common therapeutic practices followed in India. Recommendations for dosing and titration of basal, basal-plus, premixed and basal-bolus insulins were developed. The key recommendations are that insulin doses can be adjusted once or twice weekly; adjustment can be based on lowest/mean of three recent self-monitoring of plasma glucose pre-meal/fasting plasma glucose (FPG) values. The titration should be based on FPG or pre-meal value of 80-130 mg/dL and the dose should be reduced by 10-20% for patients reporting hypoglycaemia(<70mg/dL). The consensus based recommendations mentioned in this paper will be a useful reference tool for health care practitioners, to initiate, optimise and intensify insulin therapy and to successfully achieve optimal glucose control.

  15. The importance of early insulin secretion and its impact on glycaemic regulation.

    PubMed

    Garber, A J

    2000-09-01

    Type 2 diabetes is characterised by a progressive deterioration of the prandial insulin response, in a situation of continuing insulin resistance. Early phase insulin release is attenuated and delayed and there is a consequent failure to suppress glucagon secretion and curtail hepatic glucose production and gluconeogenesis. Postprandial plasma glucose concentration rises to pathological levels and fails to return to normal before the patient consumes their next meal, creating a problem of continuous daytime hyperglycaemia. Although late insulin secretion is preserved it does not rectify the hyperglycaemia. The pathology of excessive prandial glucose excursions and continual daytime hyperglycaemia can be normalised, at least in part, if early-phase insulin availability is restored through pharmacologic intervention. Initially, the feasibility of this approach was demonstrated experimentally with the use of carefully controlled insulin infusions or insulin analogue injections. More recently, the availability of the rapid or early augmentor of insulin secretion--repaglinide--provides a means for restoring prandial glucose regulation with oral therapy. Placebo-controlled and oral hypoglycaemic agent (OHA) comparative studies of repaglinide have established its antidiabetic efficacy and flexible mealtime/dosing studies have confirmed the importance of the prandial approach to treatment. Prandial glucose regulation with repaglinide has also been demonstrated to provide synergies when used as combination therapy with insulin sensitising agents. As a strategy, prandial glucose regulation has a number of theoretical advantages over the use of fixed doses of conventional insulin secretagogues, and these have been borne out in clinical trials. As well as offering a more flexible approach to treatment, prandial repaglinide is associated with a reduced risk of severe hypoglycaemia.

  16. Viva Delay.

    PubMed

    Yahaghi, Hossein; Sorooshian, Shahryar; Yahaghi, Javad

    2016-06-28

    The time delay between submission of a thesis and Viva Voce is intolerable for students. This letter tries to draw the readers' attention to the effect of choosing the right examiner, in order to reduce the Viva Voce delay.

  17. Continuous Subcutaneous Insulin Infusion in Neonates and Infants Below 1 Year: Analysis of Initial Bolus and Basal Rate Based on the Experiences from the German Working Group for Pediatric Pump Treatment.

    PubMed

    Kapellen, Thomas M; Heidtmann, Bettina; Lilienthal, Eggert; Rami-Merhar, Birgit; Engler-Schmidt, Charlotte; Holl, Reinhard W

    2015-12-01

    Diabetes mellitus is rare in young infants and neonates. Continuous subcutaneous insulin infusion (CSII) is used most frequently for insulin treatment in this age group. However, the individual doctor's experience is scarce because of the low prevalence of diabetes in this age. For this study patients treated with CSII with an age below 1 year were selected from the German/Austrian DPV (Diabetes-Patienten-Verlaufsdokumentation) database, and basal rate and bolus calculation were described. For all patients less than 1 year of age, basal rate and mealtime boluses were compared among infants with type 1 diabetes mellitus (T1DM), infants with neonatal diabetes mellitus (NDM), and infants with antibody status unknown diabetes mellitus (AUDM). Fifty-eight patients with T1DM, 67 neonates with NDM, and 43 infants with early diabetes development after 6 months and negative β-cell antibodies (AUDM) could be analyzed. T1DM patients at onset required a median total insulin amount of 0.83 IU/kg of body weight, whereas NDM patients required 0.74 IU/kg of body weight (P = 0.63). Basal insulin requirement however, was different between the two groups (0.56 IU/kg of body weight in NDM vs. 0.43 IU/kg in T1DM) (P = 0.036). The percentage basal profile of NDM and T1DM patients was quite similar to children at the age of 1-5 years. The proportion of prandial insulin at onset was significantly different (32% in NDM vs. 53% in T1DM) (P < 0.00001). AUDM patients showed almost similar data to T1DM patients. The pattern of mealtime bolus insulin was not different among the groups. The presented data can be used as an initial guide value to start CSII treatment in neonates and infants. To be on the safe side we recommend the lower quartile for the dosage as the starting value in nonketotic patients.

  18. Renal and segmental pancreatic grafting with draining of exocrine secretion and initial continuous intravenous cyclosporin A in a patient with insulin-dependent diabetes and renal failure

    PubMed Central

    Calne, R Y; White, D J G; Rolles, K; Duffy, T J; Kass, T

    1982-01-01

    A patient with renal failure and insulin-dependent diabetes received renal and segmental pancreatic allografts from the same donor, with exocrine drainage of the pancreas being directed into the bowel. An attempt was made to maintain the serum concentrations of cyclosporin A between 300 and 1000 μg/l to avoid serious nephrotoxicity and rejection. Considerable difficulty was experienced in controlling the serum concentrations even with continuous intravenous infusion. When the concentrations were maintained between 300 and 1000 μg/l function in both allografts was satisfactory. At seven months the patient required no insulin and had good renal function. He was not receiving corticosteroids. ImagesFIG 1 PMID:6809184

  19. Immediate versus delayed initiation of the levonorgestrel-releasing intrauterine system following medical termination of pregnancy - 1 year continuation rates: a randomised controlled trial.

    PubMed

    Korjamo, R; Mentula, M; Heikinheimo, O

    2017-06-26

    To assess the 1-year continuation rates and new pregnancies following immediate versus delayed insertion of the levonorgestrel-releasing intrauterine system (LNG-IUS) after medical termination of pregnancy (MTOP) up to 20 weeks of gestation. A randomised controlled trial. Helsinki University Hospital, Finland, January 2013 to December 2014. A total of 267 women requesting MTOP and planning LNG-IUS for post-MTOP contraception. Insertion of LNG-IUS occurred immediately (0-3 days) or after a delay (2-4 weeks) following MTOP. Follow-up visits were at 3 months and 1 year after MTOP. LNG-IUS use at 1 year after MTOP. Women were randomised to immediate (n = 134) or delayed (n = 133) insertion of the LNG-IUS, and 133 and 131 were analysed; 127 (95.5%) women received immediate insertion and 111 (84.7%) women had delayed insertion of the LNG-IUS (risk ratio [RR] 1.13, 95% CI 1.04-1.22). The verified numbers of women continuing the LNG-IUS use at 1 year were 83 (62.4%) and 52 (39.7%) (RR 1.57, 95% CI 1.23-2.02). The numbers of new pregnancies were 6 (4.5%) and 16 (12.2%) (RR 0.37, 95% CI 0.15-0.91), and numbers of subsequent TOPs were 4 (3.0%) and 5 (3.8%) (RR 0.79, 95% CI 0.22-2.87). Immediate insertion of the LNG-IUS following MTOP resulted in higher 1-year continuation rates compared with delayed insertion. In addition, those receiving immediate insertion demonstrated a decreased new pregnancy rate, but no difference in the numbers of another TOP. Immediate LNG-IUS insertion after MTOP results in a higher 1-year continuation compared with delayed insertion. © 2017 Royal College of Obstetricians and Gynaecologists.

  20. Socio-economic factors and use of maternal health services are associated with delayed initiation and non-exclusive breastfeeding in Indonesia: secondary analysis of Indonesia Demographic and Health Surveys 2002/2003 and 2007.

    PubMed

    Titaley, Christiana R; Loh, Philips C; Prasetyo, Sabarinah; Ariawan, Iwan; Shankar, Anuraj H

    2014-01-01

    This analysis aims to examine factors associated with delayed initiation and non-exclusive breastfeeding in Indonesia. Data were derived from the 2002/2003 and 2007 Indonesia Demographic and Health Survey. Information from 12,191 singleton live-born infants aged 0-23 months was used to examine factors associated with delayed initiation of breastfeeding. Furthermore, information from 3,187 singleton live-born infants aged 0-5 months was used to identify factors associated with non-exclusive breastfeeding. Associations between potential predictors and study outcomes were examined using logistic regression. Our study found that infants from high household wealth-index had significantly increased odds of both delayed initiation and non-exclusive breastfeeding. Other factors associated with an increased odds of delayed initiation of breastfeeding included infants from Sumatera region (OR=1.64, 95% CI: 1.38-1.95), Caesarean-section deliveries (OR=1.84, 95% CI: 1.39-2.44) and deliveries in government-owned (OR=1.38, 95% CI: 1.08-1.76) and non-health facility (OR=1.20, 95% CI: 1.00-1.43). Other factors associated with an increased odds for non-exclusive breastfeeding included parents who were in the workforce (OR=1.37, 95% CI: 1.06-1.78) and mothers with obstetric complication at childbirth (OR=1.35, 95% CI: 1.05-1.74). However, the odds reduced for infants from Eastern Indonesia (OR=0.64, 95% CI: 0.49-0.85). Poor breastfeeding practices are associated with environmental, socio-economic, pregnancy-birthing characteristics and maternal health services factors. Efforts to promote breastfeeding practices should be conducted comprehensively to target population at risk for poor breastfeeding practices.

  1. Impaired insulin signaling in endothelial cells reduces insulin-induced glucose uptake by skeletal muscle.

    PubMed

    Kubota, Tetsuya; Kubota, Naoto; Kumagai, Hiroki; Yamaguchi, Shinichi; Kozono, Hideki; Takahashi, Takehiro; Inoue, Mariko; Itoh, Shinsuke; Takamoto, Iseki; Sasako, Takayoshi; Kumagai, Katsuyoshi; Kawai, Tomoko; Hashimoto, Shinji; Kobayashi, Tsuneo; Sato, Maki; Tokuyama, Kumpei; Nishimura, Satoshi; Tsunoda, Masaki; Ide, Tomohiro; Murakami, Koji; Yamazaki, Tomomi; Ezaki, Osamu; Kawamura, Koichi; Masuda, Hirotake; Moroi, Masao; Sugi, Kaoru; Oike, Yuichi; Shimokawa, Hiroaki; Yanagihara, Nobuyuki; Tsutsui, Masato; Terauchi, Yasuo; Tobe, Kazuyuki; Nagai, Ryozo; Kamata, Katsuo; Inoue, Kenji; Kodama, Tatsuhiko; Ueki, Kohjiro; Kadowaki, Takashi

    2011-03-02

    In obese patients with type 2 diabetes, insulin delivery to and insulin-dependent glucose uptake by skeletal muscle are delayed and impaired. The mechanisms underlying the delay and impairment are unclear. We demonstrate that impaired insulin signaling in endothelial cells, due to reduced Irs2 expression and insulin-induced eNOS phosphorylation, causes attenuation of insulin-induced capillary recruitment and insulin delivery, which in turn reduces glucose uptake by skeletal muscle. Moreover, restoration of insulin-induced eNOS phosphorylation in endothelial cells completely reverses the reduction in capillary recruitment and insulin delivery in tissue-specific knockout mice lacking Irs2 in endothelial cells and fed a high-fat diet. As a result, glucose uptake by skeletal muscle is restored in these mice. Taken together, our results show that insulin signaling in endothelial cells plays a pivotal role in the regulation of glucose uptake by skeletal muscle. Furthermore, improving endothelial insulin signaling may serve as a therapeutic strategy for ameliorating skeletal muscle insulin resistance. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Management of the hospitalized diabetes patient with an insulin pump.

    PubMed

    McCrea, Deborah

    2013-03-01

    More than 375,000 Americans manage their diabetes with an insulin pump, and this number continues to increase. Many of these patients will want to remain on their insulin pump while hospitalized, so the nurse needs to know about how to care for the hospitalized patient wearing an insulin pump. This article discusses the benefits of intensive insulin therapy, how the insulin pump works, initial insulin-pump dosing, candidate selection, advantages and disadvantages of using an insulin pump, troubleshooting the pump, nursing care of the hospitalized patient wearing an insulin pump, and development of hospital protocols for the care of such patients. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Human insulin versus porcine insulin in rhesus monkeys with diabetes mellitus.

    PubMed

    Jin, Xi; Zeng, Li; Zhang, Shuang; He, Sirong; Ren, Yan; Chen, Younan; Wei, Lingling; Wang, Li; Li, Hongxia; Cheng, Jingqiu; Lu, Yanrong

    2013-02-01

    Monkeys with insulin-dependent diabetes are important preclinical animal models for islet transplantation. Exogenous insulin should be administered to achieve good glycemic control and minimize the long-term vascular complications associated with diabetes until the graft function recovered completely. However, the effect of multiple daily injections of porcine or human insulin and the long-term effects of porcine insulin have not been studied in diabetic rhesus monkeys. Diabetic rhesus monkeys, using a 6-month self-control insulin comparison experiment, were used to detect the incidence of adverse events and long-term diabetes complication events after long-term administration of porcine insulin. In this study, we found that a 20% higher dose of porcine insulin results in similar glycemic control as the human insulin regimen, and adverse events were seldom reported when porcine insulin was administered. Moreover, long-term injection with porcine insulin could delay the rate and severity of diabetes-related complications. Porcine insulin as a competent candidate for regular insulin therapy to maintain blood glucose levels in insulin-dependent diabetic monkeys during preclinical studies of islet transplantation. © 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  4. Insulin Resistance and Mitochondrial Dysfunction.

    PubMed

    Gonzalez-Franquesa, Alba; Patti, Mary-Elizabeth

    2017-01-01

    Insulin resistance precedes and predicts the onset of type 2 diabetes (T2D) in susceptible humans, underscoring its important role in the complex pathogenesis of this disease. Insulin resistance contributes to multiple tissue defects characteristic of T2D, including reduced insulin-stimulated glucose uptake in insulin-sensitive tissues, increased hepatic glucose production, increased lipolysis in adipose tissue, and altered insulin secretion. Studies of individuals with insulin resistance, both with established T2D and high-risk individuals, have consistently demonstrated a diverse array of defects in mitochondrial function (i.e., bioenergetics, biogenesis and dynamics). However, it remains uncertain whether mitochondrial dysfunction is primary (critical initiating defect) or secondary to the subtle derangements in glucose metabolism, insulin resistance, and defective insulin secretion present early in the course of disease development. In this chapter, we will present the evidence linking mitochondrial dysfunction and insulin resistance, and review the potential for mitochondrial targets as a therapeutic approach for T2D.

  5. Removal of Bovine Insulin From Cow's Milk Formula and Early Initiation of Beta-Cell Autoimmunity in the FINDIA Pilot Study.

    PubMed

    Vaarala, Outi; Ilonen, Jorma; Ruohtula, Terhi; Pesola, Jouni; Virtanen, Suvi M; Härkönen, Taina; Koski, Matti; Kallioinen, Harri; Tossavainen, Olli; Poussa, Tuija; Järvenpää, Anna-Liisa; Komulainen, Jorma; Lounamaa, Raisa; Akerblom, Hans K; Knip, Mikael

    2012-07-01

    OBJECTIVE To test whether weaning to a bovine insulin-free cow's milk formula (CMF) reduces type 1 diabetes mellitus-associated autoantibodies in children at genetic risk. DESIGN Randomized, double-blind pilot trial (Finnish Dietary Intervention Trial for the Prevention of Type 1 Diabetes [FINDIA]). SETTING Three pediatric hospitals in Finland from May 15, 2002, to November 22, 2005. PARTICIPANTS A total of 1113 infants with HLA-conferred susceptibility to type 1 diabetes were randomly assigned to receive study infant formulas; 908 children provided at least 1 follow-up blood sample (last follow-up, June 2009). INTERVENTION The CMF (n = 389), whey-based hydrolyzed formula (WHF) (n = 350), or whey-based FINDIA formula essentially free of bovine insulin (n = 365) during the first 6 months of life whenever breast milk was not available. MAIN OUTCOME MEASURES Primary outcome was beta-cell autoimmunity monitored at ages 3, 6, and 12 months and then annually until age 3 years. Autoantibodies to insulin, the 65-kDa isoform of glutamic acid decarboxylase, and the tyrosine phosphatase-related IA-2 molecule were screened, and islet cell autoantibodies and autoantibodies to zinc transporter 8 were analyzed in infants whose primary screening test results were positive. RESULTS In the intention-to-treat analysis, 6.3% of children in the CMF group, 4.9% of those in the WHF group, and 2.6% of children in the FINDIA group were positive for at least 1 autoantibody by age 3 years. The odds ratios were 0.75 (95% CI, 0.37-1.54) in the WHF group and 0.39 (0.17-0.91) in the FINDIA group when compared with the CMF group. In the treatment-received analysis, the corresponding odds ratios were 0.81 (95% CI, 0.37-1.76) and 0.23 (0.08-0.69). CONCLUSION In comparison with ordinary CMF, weaning to an insulin-free CMF reduced the cumulative incidence of autoantibodies by age 3 years in children at genetic risk of type 1 diabetes mellitus. TRIAL REGISTRATION clinicaltrials.gov Identifier

  6. Insulin pens: the modern delivery devices.

    PubMed

    Baruah, Manash P

    2011-04-01

    Strict glycemic control helps in reducing complications and mortality in patients with diabetes. Insulin remains the mainstay in treatment of diabetes. One of the most important barriers to insulin therapy is the use of conventional insulin delivery system, which remains time-consuming, cumbersome, inconvenient and painful. Insulin dosing via syringe is associated with a high risk of dosage errors. The modern pen devices have various advantages over the conventional insulin delivery methods. The user-friendliness and comfort of injection makes the initiation of insulin easier. The ease of use of insulin pens and the flexibility of incorporating insulin injections into a busy lifestyle may improve diabetes control with much less effort, while maintaining the quality of life for the diabetic patients. Reusable and prefilled pens are available.

  7. [Delayed puberty].

    PubMed

    Edouard, T; Tauber, M

    2010-02-01

    Delayed puberty is defined in girls by the absence of breast development beyond 13 years old and in boys by the absence of testicular enlargement (< 4 ml) beyond 14 years old. Simple investigations lead to the diagnosis of central or peripheral hypogonadism and constitutional delay of puberty. In girls, delayed puberty is rare and often organic, and then Turner syndrome should be systematically suspected. In boys, delayed puberty is often constitutional and functional. Treatment is etiologic when possible, hormonal replacement therapy (oestrogen in girls and testosterone in boys) and psychological management.

  8. Anti-insulin antibody test

    MedlinePlus

    Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... You appear to have an allergic response to insulin Insulin no longer seems to control your diabetes

  9. Evidence that the dephosphorylation of Ser(535) in the epsilon-subunit of eukaryotic initiation factor (eIF) 2B is insufficient for the activation of eIF2B by insulin.

    PubMed Central

    Wang, Xuemin; Janmaat, Maarten; Beugnet, Anne; Paulin, Fiona E M; Proud, Christopher G

    2002-01-01

    Eukaryotic initiation factor (eIF) 2B is a guanine-nucleotide exchange factor that plays a key role in the regulation of protein synthesis. It is activated by insulin, serum and other agents that stimulate general protein synthesis. The largest (epsilon) subunit of eIF2B is a substrate for glycogen synthase kinase (GSK)-3 in vitro, and phosphorylation by GSK3 inhibits the activity of eIF2B. The site of phosphorylation has previously been identified as Ser(535). GSK3 is inactivated by phosphorylation in response to insulin or serum. In Chinese-hamster ovary cells, insulin and serum bring about the dephosphorylation of Ser(535) in vivo, concomitantly with the phosphorylation of GSK3, and these effects are mediated through signalling via phosphoinositide 3-kinase. We have made use of inhibitors of GSK3 to determine whether GSK3 is responsible for phosphorylation of Ser(535) in vivo and to explore the role of phosphorylation of Ser(535) in the regulation of eIF2B. Treatment of cells with LiCl or with either of two recently developed GSK3 inhibitors, SB-415286 and SB-216763, brought about the dephosphorylation of Ser(535), which strongly indicates that this site is indeed a target for GSK3 in vivo. However, these compounds did not elicit significant activation of eIF2B, indicating, consistent with conclusions from one of our previous studies, that additional inputs are required for the activation of eIF2B. Our results also show that each of the inhibitors used affects overall protein synthesis and have additional effects on translation factors or signalling pathways apparently unrelated to their effects on GSK3, indicating that caution must be exercised when interpreting data obtained using these compounds. PMID:12133000

  10. 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

  11. PRECISION TIME-DELAY CIRCUIT

    DOEpatents

    Creveling, R.

    1959-03-17

    A tine-delay circuit which produces a delay time in d. The circuit a capacitor, an te back resistance, connected serially with the anode of the diode going to ground. At the start of the time delay a negative stepfunction is applied to the series circuit and initiates a half-cycle transient oscillatory voltage terminated by a transient oscillatory voltage of substantially higher frequency. The output of the delay circuit is taken at the junction of the inductor and diode where a sudden voltage rise appears after the initiation of the higher frequency transient oscillations.

  12. Estimating the state of a geophysical system with sparse observations: time delay methods to achieve accurate initial states for prediction

    DOE PAGES

    An, Zhe; Rey, Daniel; Ye, Jingxin; ...

    2017-01-16

    The problem of forecasting the behavior of a complex dynamical system through analysis of observational time-series data becomes difficult when the system expresses chaotic behavior and the measurements are sparse, in both space and/or time. Despite the fact that this situation is quite typical across many fields, including numerical weather prediction, the issue of whether the available observations are "sufficient" for generating successful forecasts is still not well understood. An analysis by Whartenby et al. (2013) found that in the context of the nonlinear shallow water equations on a β plane, standard nudging techniques require observing approximately 70 % of themore » full set of state variables. Here we examine the same system using a method introduced by Rey et al. (2014a), which generalizes standard nudging methods to utilize time delayed measurements. Here, we show that in certain circumstances, it provides a sizable reduction in the number of observations required to construct accurate estimates and high-quality predictions. In particular, we find that this estimate of 70 % can be reduced to about 33 % using time delays, and even further if Lagrangian drifter locations are also used as measurements.« less

  13. Diabetes and Insulin

    MedlinePlus

    ... in the abdomen just behind the stomach, produces insulin. Insulin is a hormone that takes glucose from the ... occurs when the pancreas does not produce enough insulin or when the body doesn’t use insulin ...

  14. Prediction of Weather Related Center Delays

    NASA Technical Reports Server (NTRS)

    Deepak, Kulkarni; Banavar, Sridhar

    2008-01-01

    This paper presents results of an initial study of relations between national delay, center level delays and weather. The results presented in the paper indicate: (a) the methodology used for estimating the delay at the national level can be extended to estimate delays caused by a center and delays experienced by a center, (b)delays caused by a center can be predicted using that center's Weather Impacted Traffic Index (WITI) whereas delays experienced by a center are best predicted using WITI of that center and that of a few prominent centers (c) there is differential impact of weather of different centers on center delays.

  15. Insulin Therapy

    MedlinePlus

    ... results yourself or insert the strip into a machine called an electronic glucose meter. The results will tell you whether or not your blood sugar is in a healthy range. Your doctor will give you additional information about monitoring your blood sugar.When should I take insulin? ...

  16. The Use of Video Modeling with the Picture Exchange Communication System to Increase Independent Communicative Initiations in Preschoolers with Autism and Developmental Delays

    ERIC Educational Resources Information Center

    Cihak, David F.; Smith, Catherine C.; Cornett, Ashlee; Coleman, Mari Beth

    2012-01-01

    The use of video modeling (VM) procedures in conjunction with the picture exchange communication system (PECS) to increase independent communicative initiations in preschool-age students was evaluated in this study. The four participants were 3-year-old children with limited communication skills prior to the intervention. Two of the students had…

  17. Insulin and the prevention of insulin-dependent diabetes mellitus.

    PubMed

    Coutant, R; Carel, J C; Timsit, J; Boitard, C; Bougnères, P

    1997-09-01

    Insulin deficiency due to autoimmune destruction of pancreatic beta cells (insulin is an autoantigen) is responsible for insulin-dependent diabetes mellitus. Since 1923, substitutive administration of insulin has been used to treat the disease. Surprisingly, initial usage of insulin is associated with partial resumption of insulin secretion in most patients. This phenomenon is intensified by aggressive insulin therapy. When observed at a late phase of destruction, it has been interpreted as an immunomodulatory effect of insulin which is presumed to act either by masking the target of effector cells in the autoimmune reaction (beta cells at rest because of glycaemic normalisation would expose fewer antigens) or by direct action on autoreactive T lymphocytes (which are rich in insulin receptors). There could also be a direct beneficial effect on anti-apoptotic or pro-regenerative beta cells. Efficient prevention of diabetes has been achieved by administration of parenteral insulin to non-obese diabetic (NOD) mice. Certain sequences of the B chain appear to be responsible for this effect, which seems to be immunomediated. Some preliminary data from the groups of G. Eisenbarth and N. MacLaren have suggested that this effect could be obtained in man by administering small doses of subcutaneous insulin to prediabetic patients. Two trials have been under way since 1994: DPT1 (a non-randomised trial concerning children and adults at high risk) in the United States, and EPP-SCIT (a randomised trial concerning children at very high risk) in Europe. Another approach has also been attempted in diabetes as well as other diseases with an organ-specific autoimmune reaction (SEP, PR) i.e. oral administration of an antigen present at the reaction site. A positive effect has been shown by the group of H. Weiner in the NOD mouse in which islet infiltration was reduced and diabetes prevented by "oral tolerisation" with insulin. Oral insulin is easy to use in therapeutic studies and is

  18. PIK3R1 Mutations Cause Syndromic Insulin Resistance with Lipoatrophy

    PubMed Central

    Thauvin-Robinet, Christel; Auclair, Martine; Duplomb, Laurence; Caron-Debarle, Martine; Avila, Magali; St-Onge, Judith; Le Merrer, Martine; Le Luyer, Bernard; Héron, Delphine; Mathieu-Dramard, Michèle; Bitoun, Pierre; Petit, Jean-Michel; Odent, Sylvie; Amiel, Jeanne; Picot, Damien; Carmignac, Virginie; Thevenon, Julien; Callier, Patrick; Laville, Martine; Reznik, Yves; Fagour, Cédric; Nunes, Marie-Laure; Capeau, Jacqueline; Lascols, Olivier; Huet, Frédéric; Faivre, Laurence; Vigouroux, Corinne; Rivière, Jean-Baptiste

    2013-01-01

    Short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay (SHORT) syndrome is a developmental disorder with an unknown genetic cause and hallmarks that include insulin resistance and lack of subcutaneous fat. We ascertained two unrelated individuals with SHORT syndrome, hypothesized that the observed phenotype was most likely due to de novo mutations in the same gene, and performed whole-exome sequencing in the two probands and their unaffected parents. We then confirmed our initial observations in four other subjects with SHORT syndrome from three families, as well as 14 unrelated subjects presenting with syndromic insulin resistance and/or generalized lipoatrophy associated with dysmorphic features and growth retardation. Overall, we identified in nine affected individuals from eight families de novo or inherited PIK3R1 mutations, including a mutational hotspot (c.1945C>T [p.Arg649Trp]) present in four families. PIK3R1 encodes the p85α, p55α, and p50α regulatory subunits of class IA phosphatidylinositol 3 kinases (PI3Ks), which are known to play a key role in insulin signaling. Functional data from fibroblasts derived from individuals with PIK3R1 mutations showed severe insulin resistance for both proximal and distal PI3K-dependent signaling. Our findings extend the genetic causes of severe insulin-resistance syndromes and provide important information with respect to the function of PIK3R1 in normal development and its role in human diseases, including growth delay, Rieger anomaly and other ocular affections, insulin resistance, diabetes, paucity of fat, and ovarian cysts. PMID:23810378

  19. Cellular Players and Role of Selectin Ligands in Leukocyte Recruitment in a T-Cell-Initiated Delayed-Type Hypersensitivity Reaction

    PubMed Central

    Doebis, Cornelia; Siegmund, Kerstin; Loddenkemper, Christoph; Lowe, John B.; Issekutz, Andrew C.; Hamann, Alf; Huehn, Jochen; Syrbe, Uta

    2008-01-01

    Delayed-type hypersensitivity (DTH) reactions are characterized by a strong cellular infiltrate, including neutrophils, macrophages, and T lymphocytes. In all these cell types, both E- and P-selectin-dependent adhesion pathways play a significant role in recruitment into the inflamed skin. Accordingly, inhibition of selectin-mediated interactions (eg, by antibodies) results in impairment of acute DTH reactions. However, whether inhibition of a specific cell type is responsible for the anti-inflammatory effect or whether all leukocytes are affected remains unclear. To address this question, we used fucosyltransferase-VII knockout mice that lack functional selectin ligands as either donors or recipients in a DTH model elicited by Th1 cell and antigen transfer. We found that selectin-mediated adhesion is required by Th1 effector cells to enter the DTH reaction site and, additionally, to elicit the DTH reaction. On the other hand, elimination of selectin binding in the recipient’s neutrophils and macrophages by use of fucosyltransferase-deficient mice receiving wild-type Th1 effector cells resulted in a strongly reduced infiltration of neutrophils and macrophages but unimpaired footpad swelling. These findings demonstrate a major role for both E- and P-selectin in the recruitment of different leukocyte cell types. However, only the presence of selectin ligands on T cells was critical for the inflammatory reaction. These findings reveal T cells as the predominant targets for selectin blockade that aim to suppress skin inflammation. PMID:18755847

  20. INSULIN-INDUCED GLOMERULOSCLEROSIS IN THE RABBIT

    PubMed Central

    Mohos, Steven C.; Hennigar, Gordon R.; Fogelman, John A.

    1963-01-01

    An attempt has been made to induce intercapillary glomerulosclerosis in rabbits by immunization with insulin incorporated in Freund's adjuvant and followed by repeated challenges with subcutaneously given insulin. It was observed that lesions resembling human diabetic glomerulosclerosis with occasional nodule-like formation could be produced and that the challenge insulin injections produced proteinuria. The presence of a delayed type of hypersensitivity seemed necessary for the lesions to occur as did the dissemination of the immunizing material to the kidneys. The experiment also disclosed that intravenously given DIS-tagged insulin localizes in a subtly different kind of glomerular lesion with different staining properties. The significance of these findings and the possible role of insulin treatment in the pathogenesis of human diabetic glomerulosclerosis is discussed. PMID:14087614

  1. Insulin management of type 2 diabetes mellitus.

    PubMed

    Petznick, Allison

    2011-07-15

    Insulin therapy is recommended for patients with type 2 diabetes mellitus and an initial A1C level greater than 9 percent, or if diabetes is uncontrolled despite optimal oral glycemic therapy. Insulin therapy may be initiated as augmentation, starting at 0.3 unit per kg, or as replacement, starting at 0.6 to 1.0 unit per kg. When using replacement therapy, 50 percent of the total daily insulin dose is given as basal, and 50 percent as bolus, divided up before breakfast, lunch, and dinner. Augmentation therapy can include basal or bolus insulin. Replacement therapy includes basal-bolus insulin and correction or premixed insulin. Glucose control, adverse effects, cost, adherence, and quality of life need to be considered when choosing therapy. Metformin should be continued if possible because it is proven to reduce all-cause mortality and cardiovascular events in overweight patients with diabetes. In a study comparing premixed, bolus, and basal insulin, hypoglycemia was more common with premixed and bolus insulin, and weight gain was more common with bolus insulin. Titration of insulin over time is critical to improving glycemic control and preventing diabetes-related complications.

  2. Insulin effects on honeybee appetitive behaviour.

    PubMed

    Mengoni Goñalons, Carolina; Guiraud, Marie; de Brito Sanchez, María Gabriela; Farina, Walter M

    2016-10-01

    Worker honeybees (Apis mellifera) carry out multiple tasks throughout their adult lifespan. It has been suggested that the insulin/insulin-like signalling pathway participates in regulating behavioural maturation in eusocial insects. Insulin signalling increases as the honeybee worker transitions from nurse to food processor to forager. As behavioural shifts require differential usage of sensory modalities, our aim was to assess insulin effects on olfactory and gustatory responsiveness as well as on olfactory learning in preforaging honeybee workers of different ages. Adults were reared in the laboratory or in the hive. Immediately after being injected with insulin or vehicle (control), and focusing on the proboscis extension response, bees were tested for their spontaneous response to odours, sucrose responsiveness and ability to discriminate odours through olfactory conditioning. Bees injected with insulin have higher spontaneous odour responses. Sucrose responsiveness and odour discrimination are differentially affected by treatment according to age: whereas insulin increases gustatory responsiveness and diminishes learning abilities of younger workers, it has the opposite effect on older bees. In summary, insulin can improve chemosensory responsiveness in young workers, but also worsens their learning abilities to discriminate odours. The insulin signalling pathway is responsive in young workers, although they are not yet initiating outdoor activities. Our results show strong age-dependent effects of insulin on appetitive behaviour, which uncover differences in insulin signalling regulation throughout the honeybee worker's adulthood. © 2016. Published by The Company of Biologists Ltd.

  3. Delayed puberty.

    PubMed

    Traggiai, Cristina; Stanhope, Richard

    2002-03-01

    Puberty is the acquisition of secondary sexual characteristics associated with a growth spurt and resulting in the attainment of reproductive function. Delayed puberty is diagnosed when there is no breast development by 13.4 years of age in a girl and no testicular enlargement by 14.0 years in a boy. The aetiologies are: (i) pubertal delay, either with constitutional delay of growth and puberty or secondary to chronic illness, and (ii) pubertal failure, with hypogonadotrophic (defect in the hypothalamo-pituitary region) or hypergonadotrophic (secondary to gonadal failure) hypogonadism, or both (secondary to radio/chemotherapy). The investigation includes: history, auxological data and pubertal development examination. Boys usually require treatment and, if they do not respond, investigation. In girls it is appropriate to measure the thyroid function and karyotype first and, if necessary, to offer treatment. If they present with dysmorphic features, or positive familial history, an assessment is required before treatment.

  4. Diabetes reduces basal retinal insulin receptor signaling: reversal with systemic and local insulin.

    PubMed

    Reiter, Chad E N; Wu, Xiaohua; Sandirasegarane, Lakshman; Nakamura, Makoto; Gilbert, Kirk A; Singh, Ravi S J; Fort, Patrice E; Antonetti, David A; Gardner, Thomas W

    2006-04-01

    Diabetic retinopathy is characterized by early onset of neuronal cell death. We previously showed that insulin mediates a prosurvival pathway in retinal neurons and that normal retina expresses a highly active basal insulin receptor/Akt signaling pathway that is stable throughout feeding and fasting. Using the streptozotocin-induced diabetic rat model, we tested the hypothesis that diabetes diminishes basal retinal insulin receptor signaling concomitantly with increased diabetes-induced retinal apoptosis. The expression, phosphorylation status, and/or kinase activity of the insulin receptor and downstream signaling proteins were investigated in retinas of age-matched control, diabetic, and insulin-treated diabetic rats. Four weeks of diabetes reduced basal insulin receptor kinase, insulin receptor substrate (IRS)-1/2-associated phosphatidylinositol 3-kinase, and Akt kinase activity without altering insulin receptor or IRS-1/2 expression or tyrosine phosphorylation. After 12 weeks of diabetes, constitutive insulin receptor autophosphorylation and IRS-2 expression were reduced, without changes in p42/p44 mitogen-activated protein kinase or IRS-1. Sustained systemic insulin treatment of diabetic rats prevented loss of insulin receptor and Akt kinase activity, and acute intravitreal insulin administration restored insulin receptor kinase activity. Insulin treatment restored insulin receptor-beta autophosphorylation in rat retinas maintained ex vivo, demonstrating functional receptors and suggesting loss of ligand as a cause for reduced retinal insulin receptor/Akt pathway activity. These results demonstrate that diabetes progressively impairs the constitutive retinal insulin receptor signaling pathway through Akt and suggests that loss of this survival pathway may contribute to the initial stages of diabetic retinopathy.

  5. Does milk intake promote prostate cancer initiation or progression via effects on insulin-like growth factors (IGFs)? A systematic review and meta-analysis.

    PubMed

    Harrison, Sean; Lennon, Rosie; Holly, Jeff; Higgins, Julian P T; Gardner, Mike; Perks, Claire; Gaunt, Tom; Tan, Vanessa; Borwick, Cath; Emmet, Pauline; Jeffreys, Mona; Northstone, Kate; Rinaldi, Sabina; Thomas, Stephen; Turner, Suzanne D; Pease, Anna; Vilenchick, Vicky; Martin, Richard M; Lewis, Sarah J

    2017-06-01

    To establish whether the association between milk intake and prostate cancer operates via the insulin-like growth factor (IGF) pathway (including IGF-I, IGF-II, IGFBP-1, IGFBP-2, and IGFBP-3). Systematic review, collating data from all relevant studies examining associations of milk with IGF, and those examining associations of IGF with prostate cancer risk and progression. Data were extracted from experimental and observational studies conducted in either humans or animals, and analyzed using meta-analysis where possible, with summary data presented otherwise. One hundred and seventy-two studies met the inclusion criteria: 31 examining the milk-IGF relationship; 132 examining the IGF-prostate cancer relationship in humans; and 10 animal studies examining the IGF-prostate cancer relationship. There was moderate evidence that circulating IGF-I and IGFBP-3 increase with milk (and dairy protein) intake (an estimated standardized effect size of 0.10 SD increase in IGF-I and 0.05 SD in IGFBP-3 per 1 SD increase in milk intake). There was moderate evidence that prostate cancer risk increased with IGF-I (Random effects meta-analysis OR per SD increase in IGF-I 1.09; 95% CI 1.03, 1.16; n = 51 studies) and decreased with IGFBP-3 (OR 0.90; 0.83, 0.98; n = 39 studies), but not with other growth factors. The IGFBP-3 -202A/C single nucleotide polymorphism was positively associated with prostate cancer (pooled OR for A/C vs. AA = 1.22; 95% CI 0.84, 1.79; OR for C/C vs. AA = 1.51; 1.03, 2.21, n = 8 studies). No strong associations were observed for IGF-II, IGFBP-1 or IGFBP-2 with either milk intake or prostate cancer risk. There was little consistency within the data extracted from the small number of animal studies. There was additional evidence to suggest that the suppression of IGF-II can reduce tumor size, and contradictory evidence with regards to the effect of IGFBP-3 suppression on tumor progression. IGF-I is a potential mechanism underlying the

  6. The insulin receptor concept and its relation to the treatment of diabetes.

    PubMed

    Ward, G M

    1987-02-01

    The initial step in insulin action is binding to specific receptors. Two covalent receptor modifications possibly involved in producing pharmacodynamic effects as a result of insulin receptor binding are autophosphorylation and disulphide insulin binding. Insulin receptor numbers are 'down regulated' by insulin, but this effect may be minimised by pulsatile insulin secretion. Insulin receptor affinity is modulated rapidly by fasting, exercise and dietary composition. In non-insulin-dependent diabetes coupling of receptor binding to bioeffects is impaired. Binding is also reduced in those subjects with hyperinsulinaemia and non-insulin-dependent diabetes. Insulin-dependent diabetics have reduced insulin sensitivity, which is only partially reversed by conventional insulin therapy. 'Post-binding defects' in some diabetics could be related to defective covalent receptor modifications resulting from genetic receptor defects. High carbohydrate diets improve diabetes control through effects on the binding and coupling defects. In addition to stimulating insulin secretion, oral hypoglycaemics stimulate post-binding insulin action in vivo and in vitro. Insulin therapy in diabetes also tends to reverse post-binding defects. Pulsatile insulin delivery is more effective in lowering blood sugar than continuous administration, and produces less 'down regulation' of receptors. Combined insulin and sulphonylurea drugs reduce insulin requirements only in insulin-dependent diabetics with some endogenous insulin secretion, whereas metformin reduces insulin requirement in C-peptide negative insulin-dependent diabetes mellitus.

  7. Whittling Down the Wait Time: Exploring Models to Minimize the Delay from Initial Concern to Diagnosis and Treatment of Autism Spectrum Disorder.

    PubMed

    Gordon-Lipkin, Eliza; Foster, Jessica; Peacock, Georgina

    2016-10-01

    The process from initial concerns to diagnosis of autism spectrum disorder (ASD) can be a long and complicated process. The traditional model for evaluation and diagnosis of ASD often consists of long wait-lists and evaluations that result in a 2-year difference between the earliest signs of ASD and mean age of diagnosis. Multiple factors contribute to this diagnostic bottleneck, including time-consuming evaluations, cost of care, lack of providers, and lack of comfort of primary care providers to diagnose autism. This article explores innovative clinical models that have been implemented to address this as well as future directions and opportunities. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Antagonistic effects of a covalently dimerized insulin derivative on insulin receptors in 3T3-L1 adipocytes

    SciTech Connect

    Weiland, M.; Joost, H.G. ); Brandenburg, C.; Brandenburg, D. )

    1990-02-01

    In the present study the authors describe the antagonistic effects of the covalently dimerized insulin derivative B29,B29{prime}-suberoyl-insulin on insulin receptors in 3T3-L1 mouse cells. In differentiated 3T3-L1 adipocytes, the derivative fully inhibits binding of {sup 125}I-labeled insulin to its receptor with about the same affinity as unlabeled insulin. In contrast, the dimerized derivative only partially (approximately 20%) mimics insulin's effects on glucose transport and DNA synthesis in the absence of insulin. In the presence of insulin, the agent competitively inhibits insulin-stimulated DNA synthesis (({sup 3}H)thymidine incorporation into total DNA), glucose transport activity (2-deoxyglucose uptake rate), and insulin receptor tyrosine kinase activity. In rat adipocytes, in contrast, the dimerized derivative stimulates glucose transport (initial 3-O-methylglucose as well as 2-deoxyglucose uptake rates) to the same extent as insulin does, and it fails to inhibit the effect of insulin. The data indicate that the dimerized insulin derivative B29,B29{prime}-suberoyl-insulin is an insulin receptor antagonist (partial agonist) which retains a moderate intrinsic activity. The effects of this agent reveal a striking difference in insulin receptor-mediated stimulation of glucose transport between 3T3-L1 fatty fibroblasts and the mature rat adipocyte.

  9. (68)Ga-PSMA Ligand PET/CT-based Radiotherapy for Lymph Node Relapse of Prostate Cancer After Primary Therapy Delays Initiation of Systemic Therapy.

    PubMed

    Henkenberens, Christoph; VON Klot, Christoph A; Ross, Tobias L; Bengel, Frank M; Wester, Hans-Jürgen; Katja, Hüper; Christiansen, Hans; Derlin, Thorsten

    2017-03-01

    To evaluate (68)Ga-PSMA ligand positron-emission tomography-computed tomography (PET/CT)-based radiotherapy for lymph node metastases of prostate cancer after primary therapy. Twenty-three patients received radiotherapy for PSMA ligand-positive lymph node metastases. The median follow-up time was 12.4 (range=6.0-28.5) months. The median pre-treatment prostate-specific antigen (PSA) decreased from 2.75 (range=0.52-8.92) ng/ml to a nadir of 1.37 (range=0.11-8.00) ng/ml (p=0.001) following radiotherapy. Except for one patient (4.4%), PSA level decreased in 22 patients (95.6%). The biochemical failure-free survival and time to initiation of systemic therapy at the median follow-up were 95.6% and 100%, respectively. Three patients (12.9%) presented with recurrent disease outside the initial radiation field. No grade III acute toxicities or late grade II toxicities were observed. (68)Ga-PSMA ligand PET/CT-based radiotherapy is a promising local treatment option for isolated lymph node metastases of prostate cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. Delayed puberty.

    PubMed

    Fenichel, Patrick

    2012-01-01

    Since puberty is a long ongoing developmental process with significant individual and population differences in timing, the definition of delayed puberty for a given individual needs to rest on simple, though arbitrary criteria based on epidemiological data. Although several genes involved in the hypothalamic-pituitary-gonadal maturation cascade have been characterized recently from familial or sporadic cases of primitive isolated hypogonadotropic hypogonadism, many genes regulating puberty onset remain undetermined. In case of delayed puberty and/or primary amenorrhea, a complete clinical examination including a detailed past history will evaluate the development of secondary sex characteristics, verify the association with a growth delay and look for specific indicative features pertaining to the etiological diagnosis. This clinical check-up completed if necessary with biological, ultrasonographic, radiological and genetic investigations will try to determine which girls will have a permanent sexual infantilism of gonadal, hypophyseal or hypothalamic origin, which girls will undergo spontaneous but delayed puberty and which girls have primary amenorrhea with developed secondary sex characteristics. Therapeutic attitude will have to integrate etiological factors, statural prognosis, bone mass preservation and psychological factors.

  11. Hepatitis B virus inhibits insulin receptor signaling and impairs liver regeneration via intracellular retention of the insulin receptor.

    PubMed

    Barthel, Sebastian Robert; Medvedev, Regina; Heinrich, Thekla; Büchner, Sarah Manon; Kettern, Nadja; Hildt, Eberhard

    2016-11-01

    Hepatitis B virus (HBV) causes severe liver disease but the underlying mechanisms are incompletely understood. During chronic HBV infection, the liver is recurrently injured by immune cells in the quest for viral elimination. To compensate tissue injury, liver regeneration represents a vital process which requires proliferative insulin receptor signaling. This study aims to investigate the impact of HBV on liver regeneration and hepatic insulin receptor signaling. After carbon tetrachloride-induced liver injury, liver regeneration is delayed in HBV transgenic mice. These mice show diminished hepatocyte proliferation and increased expression of fibrosis markers. This is in accordance with a reduced activation of the insulin receptor although HBV induces expression of the insulin receptor via activation of NF-E2-related factor 2. This leads to increased intracellular amounts of insulin receptor in HBV expressing hepatocytes. However, intracellular retention of the receptor simultaneously reduces the amount of functional insulin receptors on the cell surface and thereby attenuates insulin binding in vitro and in vivo. Intracellular retention of the insulin receptor is caused by elevated amounts of α-taxilin, a free syntaxin binding protein, in HBV expressing hepatocytes preventing proper targeting of the insulin receptor to the cell surface. Consequently, functional analyses of insulin responsiveness revealed that HBV expressing hepatocytes are less sensitive to insulin stimulation leading to delayed liver regeneration. This study describes a novel pathomechanism that uncouples HBV expressing hepatocytes from proliferative signals and thereby impedes compensatory liver regeneration after liver injury.

  12. Delay in cART initiation results in persistent immune dysregulation and poor recovery of T-cell phenotype despite a decade of successful HIV suppression.

    PubMed

    Ndumbi, Patricia; Falutz, Julian; Pant Pai, Nitika; Tsoukas, Christos M

    2014-01-01

    Successful combination antiretroviral therapy (cART) increases levels of CD4+ T-cells, however this increase may not accurately reflect long-term immune recovery since T-cell dysregulation and loss of T-cell homeostasis often persist. We therefore assessed the impact of a decade of effective cART on immune regulation, T-cell homeostasis, and overall T-cell phenotype. We conducted a retrospective study of 288 HIV+ cART-naïve patients initiating therapy. We identified 86 individuals who received cART for at least a decade, of which 44 consistently maintained undetectable plasma HIV-RNA levels throughout therapy. At baseline, participants were classified into three groups according to pre-treatment CD4+ T-cell counts: Group I (CD4<200 cells/mm3); Group II (CD4: 200-350 cells/mm3); Group III (CD4>350 cells/mm3). Outcomes of interest were: (1) CD4+ T-cell count restoration (CD4>532 cells/mm3); (2) normalization of CD4:CD8 T-cell ratio (1.2-3.3); (3) maintenance of CD3+ T-cell homeostasis (CD3: 65%-85% of peripheral lymphocytes); (4) normalization of the complete T-cell phenotype (TCP). Despite a decade of sustained successful cART, complete T-cell phenotype normalization only occurred in 16% of patients, most of whom had initiated therapy at high CD4+ T-cell counts (>350 cells/mm3). The TCP parameter that was the least restored among patients was the CD4:CD8 T-cell ratio. Failure to normalize the complete T-cell phenotype was most apparent in patients who initiated cART with a CD4+ T-cell count <200 cells/mm3. The impact of this impaired T-cell phenotype on life-long immune function and potential comorbidities remains to be elucidated.

  13. Delay in cART Initiation Results in Persistent Immune Dysregulation and Poor Recovery of T-Cell Phenotype Despite a Decade of Successful HIV Suppression

    PubMed Central

    Ndumbi, Patricia; Falutz, Julian; Pant Pai, Nitika; Tsoukas, Christos M.

    2014-01-01

    Background Successful combination antiretroviral therapy (cART) increases levels of CD4+ T-cells, however this increase may not accurately reflect long-term immune recovery since T-cell dysregulation and loss of T-cell homeostasis often persist. We therefore assessed the impact of a decade of effective cART on immune regulation, T-cell homeostasis, and overall T-cell phenotype. Methods We conducted a retrospective study of 288 HIV+ cART-naïve patients initiating therapy. We identified 86 individuals who received cART for at least a decade, of which 44 consistently maintained undetectable plasma HIV-RNA levels throughout therapy. At baseline, participants were classified into three groups according to pre-treatment CD4+ T-cell counts: Group I (CD4<200 cells/mm3); Group II (CD4: 200–350 cells/mm3); Group III (CD4>350 cells/mm3). Outcomes of interest were: (1) CD4+ T-cell count restoration (CD4>532 cells/mm3); (2) normalization of CD4:CD8 T-cell ratio (1.2–3.3); (3) maintenance of CD3+ T-cell homeostasis (CD3: 65%–85% of peripheral lymphocytes); (4) normalization of the complete T-cell phenotype (TCP). Results Despite a decade of sustained successful cART, complete T-cell phenotype normalization only occurred in 16% of patients, most of whom had initiated therapy at high CD4+ T-cell counts (>350 cells/mm3). The TCP parameter that was the least restored among patients was the CD4:CD8 T-cell ratio. Conclusions Failure to normalize the complete T-cell phenotype was most apparent in patients who initiated cART with a CD4+ T-cell count <200 cells/mm3. The impact of this impaired T-cell phenotype on life-long immune function and potential comorbidities remains to be elucidated. PMID:24710051

  14. Delaying the initiation of progesterone supplementation until the day of fertilization does not compromise cycle outcome in patients receiving donated oocytes: a randomized study.

    PubMed

    Escribá, María-José; Bellver, José; Bosch, Ernesto; Sánchez, María; Pellicer, Antonio; Remohí, José

    2006-07-01

    To determine whether the initiation of P supplementation as artificial luteal phase support (day -1, day 0, or day +1 of egg donation) in extensive programs of ovum donation influences cycle cancellation, pregnancy outcome, and implantation rate in day 3 embryo transfers. Prospective randomized trial. Oocyte donation program at the Instituto Valenciano de Infertilidad, Valencia, Spain. Three hundred recipients with normal ovarian function, absence of uterine anomalies, and undergoing their first egg donation were recruited between September 2003 and September 2004. A computer-based randomization divided the recipients into three groups when hCG was administered to their matched donors. The first group (group A) started P supplementation the day before oocyte retrieval; the second group (group B) started P supplementation on the day of the oocyte retrieval; and the third group (group C) started P supplementation 1 day after the egg retrieval once fertilization was confirmed. Implantation, pregnancy, and ongoing pregnancy rates were the primary outcome measures considered. The secondary outcome measure was the cancellation rate, especially due to fertilization failure. Global cancellation rate and cancellation rate due to fertilization failure were significantly higher in group A (12.4% and 8.2%, respectively) than in group C (3.3% and 0%, respectively). Reproductive outcome was similar in all the groups except for a higher biochemical pregnancy rate in group A (12.9%) than in groups B (6.6%) and C (2.3%). Initiation of P on day +1 of embryo development decreases cancellation rates of day 3 embryo transfers in extensive programs of ovum donation without any deleterious effect on pregnancy outcome or implantation rate.

  15. Internalization and localization of basal insulin peglispro in cells.

    PubMed

    Moyers, Julie S; Volk, Catherine B; Cao, Julia X C; Zhang, Chen; Ding, Liyun; Kiselyov, Vladislav V; Michael, M Dodson

    2017-10-15

    Basal insulin peglispro (BIL) is a novel, PEGylated insulin lispro that has a large hydrodynamic size compared with insulin lispro. It has a prolonged duration of action, which is related to a delay in insulin absorption and a reduction in clearance. Given the different physical properties of BIL compared with native insulin and insulin lispro, it is important to assess the cellular internalization characteristics of the molecule. Using immunofluorescent confocal imaging, we compared the cellular internalization and localization patterns of BIL, biosynthetic human insulin, and insulin lispro. We assessed the effects of BIL on internalization of the insulin receptor (IR) and studied cellular clearance of BIL. Co-localization studies using antibodies to either insulin or PEG, and the early endosomal marker EEA1 showed that the overall internalization and subcellular localization pattern of BIL was similar to that of human insulin and insulin lispro; all were rapidly internalized and co-localized with EEA1. During ligand washout for 4 h, concomitant loss of insulin, PEG methoxy group, and PEG backbone immunostaining was observed for BIL, similar to the loss of insulin immunostaining observed for insulin lispro and human insulin. Co-localization studies using an antibody to the lysosomal marker LAMP1 did not reveal evidence of lysosomal localization for insulin lispro, human insulin, BIL, or PEG using either insulin or PEG immunostaining reagents. BIL and human insulin both induced rapid phosphorylation and internalization of human IR. Our findings show that treatment of cells with BIL stimulates internalization and localization of IR to early endosomes. Both the insulin and PEG moieties of BIL undergo a dynamic cellular process of rapid internalization and transport to early endosomes followed by loss of cellular immunostaining in a manner similar to that of insulin lispro and human insulin. The rate of clearance for the insulin lispro portion of BIL was slower than

  16. Derivation and computation of discrete-delay and continuous-delay SDEs in mathematical biology.

    PubMed

    Allen, Edward J

    2014-06-01

    Stochastic versions of several discrete-delay and continuous-delay differential equations, useful in mathematical biology, are derived from basic principles carefully taking into account the demographic, environmental, or physiological randomness in the dynamic processes. In particular, stochastic delay differential equation (SDDE) models are derived and studied for Nicholson's blowflies equation, Hutchinson's equation, an SIS epidemic model with delay, bacteria/phage dynamics, and glucose/insulin levels. Computational methods for approximating the SDDE models are described. Comparisons between computational solutions of the SDDEs and independently formulated Monte Carlo calculations support the accuracy of the derivations and of the computational methods.

  17. [Hypoglycemia in patients treated with an external insulin pump].

    PubMed

    Laurent, Jean-Christophe; Waeber, Gerard; Ruiz, Juan; Carron, Pierre-Nicolas

    2011-01-19

    Hypoglycemia is a potentially serious complication of insulin therapy. Some insulin-dependent diabetic patients can benefit from continuous subcutaneous insulin infusion therapy (an "insulin pump"), which in most case improves glycemia control and decreases the occurrence of hypoglycemic episodes. However, such events may occur, particularly during initial treatment phases or pregnancy. Severe hypoglycemia is mainly managed by stopping the insulin pump and insuring an adequate carbohydrate intake. Patients with insulin pumps and their entourage should receive specific instruction in the adjustment of pump flow in the presence of dysglycemia-inducing circumstances (illness, physical exertion), as well as in anticipation of high-risk situations, such as motor-vehicle driving.

  18. Delayed traumatic diaphragmatic hernia

    PubMed Central

    Lu, Jing; Wang, Bo; Che, Xiangming; Li, Xuqi; Qiu, Guanglin; He, Shicai; Fan, Lin

    2016-01-01

    Abstract Background: Traumatic diaphragmatic hernias (TDHs) are sometimes difficult to identify at an early stage and can consequently result in diagnostic delays with life-threatening outcomes. It is the aim of this case study to highlight the difficulties encountered with the earlier detection of traumatic diaphragmatic hernias. Methods: Clinical data of patients who received treatment for delayed traumatic diaphragmatic hernias in registers of the First Affiliated Hospital of Xi’an Jiaotong University from 1998 to 2014 were analyzed retrospectively. Results: Six patients were included in this study. Left hemidiaphragm was affected in all of them. Most of the patients had a history of traffic accident and 1 a stab-penetrating injury. The interval from injury to developing symptoms ranged from 2 to 11 years (median 5 years). The hernial contents included the stomach, omentum, small intestine, and colon. Diaphragmatic injury was missed in all of them during the initial managements. All patients received operations once the diagnosis of delayed TDH was confirmed, and no postoperative mortality was detected. Conclusions: Delayed TDHs are not common, but can lead to serious consequences once occurred. Early detection of diaphragmatic injuries is crucial. Surgeons should maintain a high suspicion for injuries of the diaphragm in cases with abdominal or lower chest traumas, especially in the initial surgical explorations. We emphasize the need for radiographical follow-up to detect diaphragmatic injuries at an earlier stage. PMID:27512848

  19. Insulin Human Inhalation

    MedlinePlus

    Insulin inhalation is used in combination with a long-acting insulin to treat type 1 diabetes (condition in which the body does not produce insulin and therefore cannot control the amount of sugar ...

  20. Giving an insulin injection

    MedlinePlus

    ... want. Put the needle into and through the rubber top of the insulin bottle. Push the plunger ... longer-acting insulin. Put the needle into the rubber top of that insulin bottle. Push the plunger ...

  1. Insulin accelerates global and mitochondrial protein synthesis rates in neonatal muscle during sepsis

    USDA-ARS?s Scientific Manuscript database

    In neonatal pigs, sepsis decreases protein synthesis in skeletal muscle by decreasing translation initiation. However, insulin stimulates muscle protein synthesis despite persistent repression of translation initiation signaling. To determine whether the insulin-induced increase in global rates of m...

  2. Delayed puberty.

    PubMed

    Reiter, Edward O; Lee, Peter A

    2002-02-01

    Normal puberty is a time of life and a process of development that results in full adult maturity of growth, sexual development, and psychosocial achievement. Delayed puberty describes the clinical condition in which the pubertal events start late (usually > +2.5 SD later than the mean) or are attenuated in progression. The differential diagnosis includes syndromes of low gonadotropin production, usually constitutional delay of growth and maturation associated with chronic disease, but also an array of gene-mediated disorders, and syndromes of primary gonadal dysfunction with hypergonadotropic hypogonadism, including Turner and Klinefelter syndromes, and a group of acquired and genetic abnormalities. Diagnostic assessment and varied therapeutic modalities are discussed. The issues of androgen or estrogen therapy are important to assess, and growth hormone treatment remains a difficult dilemma.

  3. High temperature induces cyp26b1 mRNA expression and delays meiotic initiation of germ cells by increasing cortisol levels during gonadal sex differentiation in Japanese flounder.

    PubMed

    Yamaguchi, Toshiya; Kitano, Takeshi

    2012-03-09

    The Japanese flounder (Paralichthys olivaceus) is a teleost fish with an XX/XY sex determination system. XX flounder can be induced to develop into phenotypic females or males, by rearing them at 18°C or 27°C, respectively, during the sex differentiation period. Therefore, the flounder provides an excellent model to study the molecular mechanisms underlying temperature-dependent sex determination. We previously showed that cortisol, the major glucocorticoid produced by the interrenal cells in teleosts, causes female-to-male sex reversal by directly suppressing mRNA expression of ovary-type aromatase (cyp19a1), a steroidogenic enzyme responsible for the conversion of androgens to estrogens in the gonads. Furthermore, an inhibitor of cortisol synthesis prevented masculinization of XX flounder at 27°C, suggesting that masculinization by high temperature is due to the suppression of cyp19a1 mRNA expression by elevated cortisol levels during gonadal sex differentiation in the flounder. In the present study, we found that exposure to high temperature during gonadal sex differentiation upregulates the mRNA expression of retinoid-degrading enzyme (cyp26b1) concomitantly with masculinization of XX gonads and delays meiotic initiation of germ cells. We also found that cortisol induces cyp26b1 mRNA expression and suppresses specific meiotic marker synaptonemal complex protein 3 (sycp3) mRNA expression in gonads during the sexual differentiation. In conclusion, these results suggest that exposure to high temperature induces cyp26b1 mRNA expression and delays meiotic initiation of germ cells by elevating cortisol levels during gonadal sex differentiation in Japanese flounder.

  4. Ciprofloxacin prophylaxis delays initiation of broad-spectrum antibiotic therapy and reduces the overall use of antimicrobial agents during induction therapy for acute leukaemia: A single-centre study.

    PubMed

    Hallböök, Helene; Lidström, Anna-Karin; Pauksens, Karlis

    2016-01-01

    Due to an outbreak of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, the routine use of fluoroquinolone prophylaxis was questioned. As a result, this study was conducted with the aim to evaluate the impact of ciprofloxacin-prophylaxis on the use of broad-spectrum antibioctics and anti-mycotics. A cohort of 139 consecutive patients with acute leukaemia treated with remission-inducing induction chemotherapy between 2004-2012 at the Department of Haematology in Uppsala University Hospital was analysed. Fifty-three patients (38%) received broad-spectrum antibiotics at the initiation of chemotherapy and were not eligible for prophylaxis. Of the remaining patients, the initiation of broad-spectrum antibiotics was delayed by 3 days in those receiving ciprofloxacin prophylaxis (n = 47) compared with those receiving no prophylaxis (n = 39). The median duration of systemic antibiotic treatment was 6 days shorter in patients receiving ciprofloxacin prophylaxis (12 vs 18 days; p = 0.0005) and the cumulative (total) median days on systemic antibiotic treatment was shortened by 8 days (15 vs 23 days, p = 0.0008). Piperacillin/tazobactam (p = 0.02), carbapenems (p = 0.05) and empiric broad-spectrum antifungals (p < 0.01) were used significantly less often when ciprofloxacin prophylaxis was given. Ciprofloxacin prophylaxis delayed empiric therapy by 3 days and reduced overall antibiotic use in this study. These benefits must be evaluated vs the risks of development of resistant bacterial strains, making fluoroquinolone prophylaxis an open question for debate.

  5. 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

  6. Misadventures in insulin therapy: are you at risk?

    PubMed

    Grissinger, Matthew; Lease, Michael

    2003-02-01

    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.

  7. Massive insulin overdose managed by monitoring daily insulin levels.

    PubMed

    Mork, Tyler A; Killeen, Colin T; Patel, Neel K; Dohnal, James M; Karydes, Harry C; Leikin, Jerrold B

    2011-09-01

    We present a case of a significant insulin overdose that was managed by monitoring daily plasma insulin levels. A 39-year-old male with poorly controlled diabetes mellitus presented to the Emergency Department via emergency medical services after an attempted suicide by insulin overdose. In the attempted suicide, he injected 800 U of insulin lispro and 3800 U of insulin glargine subcutaneously over several parts of his abdomen. The patient was conscious upon arrival to the emergency department. His vital parameters were within normal range. The abdominal examination, in particular, was nonfocal and showed no evidence of hematomas. He was awake, alert, conversant, tearful, and without any focal deficits. An infusion of 10% dextrose was begun at 100 mL/h with hourly blood glucose (BG) checks. The patient was transferred to the intensive care unit where his BG began to decrease and fluctuate between 50 and 80 mg/dL, and the rate of 10% dextrose was increased to 200 mL/h where it was maintained for the next 48 hours. The initial plasma insulin level was found to be 3712.6 uU/mL (reference range 2.6-31.1 uU/mL). At 10 hours, this had decreased to 1582.1 uU/ml. On five occasions, supplemental dextrose was needed when the BG was <70 mg/dL. Thirty-four hours after admission, the plasma insulin level was 724.8 uU/mL. Fifty-eight hours after admission, the plasma insulin level was 321.2 uU/mL, and the 10% dextrose infusion was changed to 5% dextrose solution at 200 mL/h. The plasma insulin levels continued to fall daily to 112.7 uU/mL at 80 hours and to 30.4 uU/mL at 108 hours. He was transferred to an inpatient psychiatric facility 109 hours after initial presentation. Monitoring daily plasma insulin levels and adjusting treatment on a day-to-day basis in terms of basal glucose infusions provides fewer opportunities for episodic hypoglycemia. Furthermore, it was easier to predict daily glucose requirements and eventual medical clearance based on the plasma levels. (C) 2011

  8. Contingency Tracking during Unsignaled Delayed Reinforcement

    ERIC Educational Resources Information Center

    Keely, Josue; Feola, Tyler; Lattal, Kennon A.

    2007-01-01

    Three experiments were conducted with rats in which responses on one lever (labeled the functional lever) produced reinforcers after an unsignaled delay period that reset with each response during the delay. Responses on a second, nonfunctional, lever did not initiate delays, but, in the first and third experiments, such responses during the last…

  9. Contingency Tracking during Unsignaled Delayed Reinforcement

    ERIC Educational Resources Information Center

    Keely, Josue; Feola, Tyler; Lattal, Kennon A.

    2007-01-01

    Three experiments were conducted with rats in which responses on one lever (labeled the functional lever) produced reinforcers after an unsignaled delay period that reset with each response during the delay. Responses on a second, nonfunctional, lever did not initiate delays, but, in the first and third experiments, such responses during the last…

  10. Chromium–Insulin Reduces Insulin Clearance and Enhances Insulin Signaling by Suppressing Hepatic Insulin-Degrading Enzyme and Proteasome Protein Expression in KKAy Mice

    PubMed Central

    Wang, Zhong Q.; Yu, Yongmei; Zhang, Xian H.; Komorowski, James

    2014-01-01

    JDS–chromium–insulin (CRI)-003 is a novel form of insulin that has been directly conjugated with chromium (Cr) instead of zinc. Our hypothesis was that CRI enhances insulin’s effects by altering insulin-degrading enzyme (IDE) and proteasome enzymes. To test this hypothesis, we measured hepatic IDE content and proteasome parameters in a diabetic animal model. Male KKAy mice were randomly divided into three groups (n = 8/group); Sham (saline), human regular insulin (Reg-In), and chromium conjugated human insulin (CRI), respectively. Interventions were initiated at doses of 2 U insulin/kg body weight daily for 8-weeks. Plasma glucose and insulin were measured. Hepatic IDE, proteasome, and insulin signaling proteins were determined by western blotting. Insulin tolerance tests at week 7 showed that both insulin treatments significantly reduced glucose concentrations and increased insulin levels compared with the Sham group, CRI significantly reduced glucose at 4 and 6 h relative to Reg-In (P < 0.05), suggesting the effects of CRI on reducing glucose last longer than Reg-In. CRI treatment significantly increased hepatic IRS-1 and Akt1 and reduced IDE, 20S as well as 19S protein abundance (P < 0.01, P < 0.05, and P < 0.001, respectively), but Reg-In only significantly increased Akt1 (P < 0.05). Similar results were also observed in Reg-In- and CRI-treated HepG2 cells. This study, for the first time, demonstrates that CRI reduces plasma insulin clearance by inhibition of hepatic IDE protein expression and enhances insulin signaling as well as prevents degradation of IRS-1 and IRS-2 by suppressing ubiquitin-proteasome pathway in diabetic mice. PMID:25071716

  11. Fluidity of insulin action.

    PubMed

    Elmendorf, Jeffrey S

    2004-06-01

    Unlike the intensive research in pursuit of understanding the molecular mechanisms of insulin signaling and resistance to its biological action associated most significantly with obesity and type 2 diabetes, the influence of the plasma membrane on insulin sensitivity has been intermittently studied over the years-mainly because it was thought that mediators of insulin action, such as the insulin receptor and the insulin-responsive glucose transporter GLUT4, localize more or less uniformly in the lipids that form cell membranes. Recent insights into membrane physiology suggest that the plasma membrane impacts the function of membrane proteins mediating insulin action. Furthermore, membrane disturbances may be the basis of insulin resistance. Relevant insulin signal transduction data in terms of plasma membrane and insulin resistance are the focus of this review. The discussion visits the cell membrane hypothesis of insulin resistance that suggests insulin action could be related to changes in cell membrane properties.

  12. [Physiopathology of non-insulin-dependent diabetes: current data and therapeutic consequences].

    PubMed

    Broussolle, C; Orgiazzi, J; Noël, G

    1990-01-01

    Non insulin-dependent diabetes mellitus results from the combination in varying proportions of low plasma insulin levels (insulinopenia), peripheral resistance to insulin and increased hepatic glucose production. Abnormalities of insulin secretion can be demonstrated without and after stimulation. Insulin resistance mainly occurs in skeletal muscle and is primarily due to a "postreceptor" defect. A pancreatic peptide, amylin, may participate in insulin resistance. Hepatic glucose production correlates with high fasting plasma glucose concentrations. Whatever its initial mechanism, hyperglycaemia maintains low insulin secretion and insulin resistance by its toxicity. In the light of these data, the effects of weight loss in obese non insulin-dependent diabetics have become clearer. The action of biguanides on insulin sensitivity is confirmed. Sulphonylureas have a pancreatic and an extrapancreatic action. The normoglycaemia obtained by intermittent insulin therapy can break the vicious circle of glucose toxicity. The use of prolonged insulin therapy is discussed. Finally, new compounds with an original mode of action offer hopes for the future.

  13. Recombinant DNA derived monomeric insulin analogue: comparison with soluble human insulin in normal subjects.

    PubMed Central

    Vora, J. P.; Owens, D. R.; Dolben, J.; Atiea, J. A.; Dean, J. D.; Kang, S.; Burch, A.; Brange, J.

    1988-01-01

    OBJECTIVE--To compare the rate of absorption from subcutaneous tissue and the resulting hypoglycaemic effect of iodine-125 labelled soluble human insulin and a monomeric insulin analogue derived by recombinant DNA technology. DESIGN--Single blind randomised comparison of equimolar doses of 125I labelled soluble human insulin and insulin analogue. SETTING--Study in normal people at a diabetes research unit and a university department of medical physics. SUBJECTS--Seven healthy male volunteers aged 20-39 not receiving any other drugs. INTERVENTIONS--After an overnight fast and a basal period of one hour two doses (0.05 and 0.1 U/kg) of 125I labelled soluble human insulin and insulin analogue were injected subcutaneously into the anterior abdominal wall on four separate days. END POINT--To find a fast acting insulin for meal related requirements in insulin dependent diabetics. MEASUREMENTS and main results--Residual radioactivity at the injection site was measured continuously for the first two hours after injection of the 125I labelled preparations and thereafter for five minutes simultaneously with blood sampling. Frequent venous blood samples were obtained over six hours for determination of plasma immunoreactive insulin, insulin analogue, glucose, and glucagon values. Time to 50% of initial radioactivity at the injection site for the insulin analogue compared with soluble insulin was 61 v 135 minutes (p less than 0.05) with 0.05 U/kg and 67 v 145 minutes (p less than 0.001) with 0.1 U/kg. Concentrations in plasma increased faster after the insulin analogue compared with soluble insulin, resulting in higher plasma concentrations between 10 and 150 minutes (0.001 less than p less than 0.05) after 0.05 U/kg and between 40 and 360 minutes (0.001 less than p less than 0.05) after 0.1 U/kg. The hypoglycaemic response to insulin analogue was a plasma glucose nadir at 60 minutes with both doses compared with 90 and 120 minutes with soluble insulin at 0.5 and 0.1 U

  14. Delaying obsolescence.

    PubMed

    Lawlor, Rob

    2015-04-01

    This paper argues that those who emphasise that designers and engineers need to plan for obsolescence are too conservative. Rather, in addition to planning for obsolescence, designers and engineers should also think carefully about what they could do in order delay obsolescence. They should so this by thinking about the design itself, thinking of ways in which products could be useful and appealing for longer before becoming obsolete, as well thinking about the wider context in terms of the marketing of products, and also the social and legal. The paper also considers objections that these suggestions are unrealistically idealistic, failing to recognise the economic realities. I respond to these objections appealing to research in advertising, psychology, cognitive linguistics, philosophy, history, and economics, as well as drawing on the Statement of Ethical Principles developed by the Royal Academy of Engineering and the Engineering Council.

  15. INTERACTION OF INSULIN WITH THE CELL MEMBRANE: THE PRIMARY ACTION OF INSULIN

    PubMed Central

    Cuatrecasas, Pedro

    1969-01-01

    Insulin can be covalently attached to a large polymers of Sepharose through the α-amino group of the N-terminal residue of the B chain, or through the ε-amino group of its lysyl residue. Such derivatives effectively increase the utilization of glucose, and suppress the hormone-stimulated lipolysis, of isolated fat cells. The effects occur with concentrations of insulin-Sepharose that are nearly as low as those of native insulin, and the maximal responses are the same. The results indicate that interaction of insulin with superficial membrane structures alone may suffice to initiate transport as well as other metabolic alterations. PMID:5257136

  16. Insulin Secretion Improves in Cystic Fibrosis Following Ivacaftor Correction of CFTR: A Small Pilot Study

    PubMed Central

    Bellin, Melena D.; Laguna, Theresa; Leschyshyn, Janice; Regelmann, Warren; Dunitz, Jordan; Billings, JoAnne; Moran, Antoinette

    2013-01-01

    Objective To determine whether the cystic fibrosis transmembrane conductance regulator (CFTR) is involved in human insulin secretion by assessing the metabolic impact of the new CFTR corrector, ivacaftor. Methods This open-label pilot study was conducted in CF patients with the G551D mutation given new prescriptions for ivacaftor. At baseline and 4 weeks after daily ivacaftor therapy, intravenous (IVGTT) and oral glucose (OGTT) tolerance tests were performed. Results Five patients age 6–52 were studied. After 1 month on ivacaftor, the insulin response to oral glucose improved by 66–178% in all subjects except one with long-standing diabetes. OGTT glucose levels were not lower in the two individuals with diabetes or the two with normal glucose tolerance (NGT), but the glucose tolerance category in the subject with impaired glucose tolerance (IGT) improved to NGT after treatment. In response to intravenous glucose, the only patient whose acute insulin secretion did not improve had newly diagnosed, untreated CFRD. The others improved by 51–346%. Acute insulin secretion was partially restored in two subjects with no measurable acute insulin response at baseline, including the one with IGT and the one with long-standing diabetes. Conclusions This small pilot study suggests there is a direct role of CFTR in human insulin secretion. Larger, long-term longitudinal studies are necessary to determine whether early initiation of CFTR correction, particularly in young children with CF who have not yet lost considerable beta-cell mass, will delay or prevent development of diabetes in this high risk population. PMID:23952705

  17. Basin stability in delayed dynamics

    PubMed Central

    Leng, Siyang; Lin, Wei; Kurths, Jürgen

    2016-01-01

    Basin stability (BS) is a universal concept for complex systems studies, which focuses on the volume of the basin of attraction instead of the traditional linearization-based approach. It has a lot of applications in real-world systems especially in dynamical systems with a phenomenon of multi-stability, which is even more ubiquitous in delayed dynamics such as the firing neurons, the climatological processes, and the power grids. Due to the infinite dimensional property of the space for the initial values, how to properly define the basin’s volume for delayed dynamics remains a fundamental problem. We propose here a technique which projects the infinite dimensional initial state space to a finite-dimensional Euclidean space by expanding the initial function along with different orthogonal or nonorthogonal basis. A generalized concept of basin’s volume in delayed dynamics and a highly practicable calculating algorithm with a cross-validation procedure are provided to numerically estimate the basin of attraction in delayed dynamics. We show potential applicabilities of this approach by applying it to study several representative systems of biological or/and physical significance, including the delayed Hopfield neuronal model with multistability and delayed complex networks with synchronization dynamics. PMID:26907568

  18. Importance of insulin immunoassays in the diagnosis of factitious hypoglycemia.

    PubMed

    Nalbantoğlu Elmas, Özlem; Demir, Korcan; Soylu, Nusret; Çelik, Nilüfer; Özkan, Behzat

    2014-12-01

    We report two cases emphasizing the importance of insulin assays for evaluation of hypoglycemia in diabetic patients. Case 1 was a 96/12-year-old female patient with type 1 diabetes mellitus and case 2 was a 1010/12-year-old male patient with DIDMOAD. Both patients were on a basal-bolus insulin regimen. Both were admitted because of persistent hypoglycemia. Analyses of serum samples obtained at the time of hypoglycemia initially showed low insulin and C-peptide levels. Recurrent episodes of unexplained hypoglycemia necessitated measurement of insulin levels by using different insulin assays, which revealed hyperinsulinemic hypoglycemia with low C-peptide levels, findings which confirmed a diagnosis of factitious hypoglycemia. Surreptitious administration of insulin should not be excluded in diabetic patients with hypoglycemia without taking into account the rate of cross-reactivity of insulin analogues with the insulin assay used.

  19. Blueberries’ Impact on Insulin Resistance and Glucose Intolerance

    PubMed Central

    Stull, April J.

    2016-01-01

    Blueberries are a rich source of polyphenols, which include anthocyanin bioactive compounds. Epidemiological evidence indicates that incorporating blueberries into the diet may lower the risk of developing type 2 diabetes (T2DM). These findings are supported by pre-clinical and clinical studies that have shown improvements in insulin resistance (i.e., increased insulin sensitivity) after obese and insulin-resistant rodents or humans consumed blueberries. Insulin resistance was assessed by homeostatic model assessment-estimated insulin resistance (HOMA-IR), insulin tolerance tests, and hyperinsulinemic-euglycemic clamps. Additionally, the improvements in glucose tolerance after blueberry consumption were assessed by glucose tolerance tests. However, firm conclusions regarding the anti-diabetic effect of blueberries cannot be drawn due to the small number of existing clinical studies. Although the current evidence is promising, more long-term, randomized, and placebo-controlled trials are needed to establish the role of blueberries in preventing or delaying T2DM. PMID:27916833

  20. Severe hypoglycemia rates and associated costs among type 2 diabetics starting basal insulin therapy in the United States.

    PubMed

    Ganz, Michael L; Wintfeld, Neil S; Li, Qian; Lee, Yuan-Chi; Gatt, Elyse; Huang, Joanna C

    2014-10-01

    To derive current real-world data on the rates and costs of severe hypoglycemia (SH) for people with type 2 diabetes mellitus (T2D) who have initiated basal insulin therapy and to examine differences in SH rates and costs stratified by history of prior SH events. We used a nation-wide electronic health records database that included encounter and laboratory data, as well as clinical notes, to estimate the rates and costs of SH events among adults with T2D who initiated basal insulin between 2008 and 2011. Unadjusted and regression-adjusted rates and quarterly costs were calculated for all patients as well as stratified by history of a SH event before starting basal insulin and history of a SH event during the basal insulin titration period. We identified 7235 incident cases of basal insulin use among patients with T2D who did not use insulin during the previous 12 months. Regression-adjusted incidence and total event rates were 10.36 and 11.21 per 100 patient-years, respectively. A history of SH events during the pre-index baseline and post-index titration periods were statistically significantly associated with both the incidence and total event rates (p < 0.01). Regression-adjusted total healthcare and diabetes-related costs were statistically significantly (p < 0.01) higher in those quarters when a SH event occurred than in those quarters without any SH events ($3591 vs. $487 and $3311 vs. $406, respectively). A history of previous SH or SH events during the titration period were not statistically significantly associated with costs. These results suggest that the real-world burden of SH is high among people with T2D who start using basal insulin and that history of previous SH events, both before starting insulin and during the insulin titration period, influences future SH. These results can also provide insights into interventions that can prevent or delay SH. These results should, however, be interpreted in light of the key limitations of our study

  1. Can primary care team-based transition to insulin improve outcomes in adults with type 2 diabetes: the stepping up to insulin cluster randomized controlled trial protocol

    PubMed Central

    2014-01-01

    Background Type 2 diabetes (T2D) brings significant human and healthcare costs. Its progressive nature means achieving normoglycaemia is increasingly difficult, yet critical to avoiding long term vascular complications. Nearly one-half of people with T2D have glycaemic levels out of target. Insulin is effective in achieving glycaemic targets, yet initiation of insulin is often delayed, particularly in primary care. Given limited access to specialist resources and the size of the diabetes epidemic, primary care is where insulin initiation must become part of routine practice. This would also support integrated holistic care for people with diabetes. Our Stepping Up Program is based on a general practitioner (GP) and practice nurse (PN) model of care supported appropriately by endocrinologists and credentialed diabetes educator-registered nurses. Pilot work suggests the model facilitates integration of the technical work of insulin initiation within ongoing generalist care. Methods This protocol is for a cluster randomized controlled trial to examine the effectiveness of the Stepping Up Program to enhance the role of the GP-PN team in initiating insulin and improving glycaemic outcomes for people with T2D. 224 patients between the ages of 18 and 80 years with T2D, on two or more oral hypoglycaemic agents and with an HbA1c ≥7.5% in the last six months will be recruited from 74 general practices. The unit of randomization is the practice. Primary outcome is change in glycated haemoglobin HbA1c (measured as a continuous variable). We hypothesize that the intervention arm will achieve an absolute HbA1c mean difference of 0.5% lower than control group at 12 months follow up. Secondary outcomes include the number of participants who successfully transfer to insulin and the proportion who achieve HbA1c measurement of <7.0%. We will also collect data on patient psychosocial outcomes and healthcare utilization and costs. Discussion The study is a pragmatic translational

  2. Can primary care team-based transition to insulin improve outcomes in adults with type 2 diabetes: the stepping up to insulin cluster randomized controlled trial protocol.

    PubMed

    Furler, John S; Young, Doris; Best, James; Patterson, Elizabeth; O'Neal, David; Liew, Danny; Speight, Jane; Segal, Leonie; May, Carl; Manski-Nankervis, Jo-Anne; Holmes-Truscott, Elizabeth; Ginnivan, Louise; Blackberry, Irene D

    2014-02-14

    Type 2 diabetes (T2D) brings significant human and healthcare costs. Its progressive nature means achieving normoglycaemia is increasingly difficult, yet critical to avoiding long term vascular complications. Nearly one-half of people with T2D have glycaemic levels out of target. Insulin is effective in achieving glycaemic targets, yet initiation of insulin is often delayed, particularly in primary care. Given limited access to specialist resources and the size of the diabetes epidemic, primary care is where insulin initiation must become part of routine practice. This would also support integrated holistic care for people with diabetes. Our Stepping Up Program is based on a general practitioner (GP) and practice nurse (PN) model of care supported appropriately by endocrinologists and credentialed diabetes educator-registered nurses. Pilot work suggests the model facilitates integration of the technical work of insulin initiation within ongoing generalist care. This protocol is for a cluster randomized controlled trial to examine the effectiveness of the Stepping Up Program to enhance the role of the GP-PN team in initiating insulin and improving glycaemic outcomes for people with T2D. 224 patients between the ages of 18 and 80 years with T2D, on two or more oral hypoglycaemic agents and with an HbA1c ≥7.5% in the last six months will be recruited from 74 general practices. The unit of randomization is the practice.Primary outcome is change in glycated haemoglobin HbA1c (measured as a continuous variable). We hypothesize that the intervention arm will achieve an absolute HbA1c mean difference of 0.5% lower than control group at 12 months follow up. Secondary outcomes include the number of participants who successfully transfer to insulin and the proportion who achieve HbA1c measurement of <7.0%. We will also collect data on patient psychosocial outcomes and healthcare utilization and costs. The study is a pragmatic translational study with important potential

  3. Insulin delivery route for the artificial pancreas: subcutaneous, intraperitoneal, or intravenous? Pros and cons.

    PubMed

    Renard, Eric

    2008-07-01

    Insulin delivery is a crucial component of a closed-loop system aiming at the development of an artificial pancreas. The intravenous route, which has been used in the bedside artificial pancreas model for 30 years, has clear advantages in terms of pharmacokinetics and pharmacodynamics, but cannot be used in any ambulatory system so far. Subcutaneous (SC) insulin infusion benefits from the broad expansion of insulin pump therapy that promoted the availability of constantly improving technology and fast-acting insulin analog use. However, persistent delays of insulin absorption and action, variability and shortterm stability of insulin infusion from SC-inserted catheters generate effectiveness and safety issues in view of an ambulatory, automated, glucose-controlled, artificial beta cell. Intraperitoneal insulin delivery, although still marginally used in diabetes care, may offer an interesting alternative because of its more-physiological plasma insulin profiles and sustained stability and reliability of insulin delivery.

  4. Use of a two-stage insulin infusion study to assess the relationship between insulin suppression of lipolysis and insulin-mediated glucose uptake in overweight/obese, nondiabetic women.

    PubMed

    McLaughlin, Tracey; Yee, Gail; Glassford, Alec; Lamendola, Cindy; Reaven, Gerald

    2011-12-01

    Differences in insulin regulation of free fatty acids (FFAs) are not readily apparent at the same insulin concentrations used to differentiate relative insulin-mediated glucose disposal. Resistance to insulin-mediated glucose disposal and higher daylong FFA concentrations occur more commonly in obese individuals. However, the relationship between the ability of insulin to suppress FFA release from adipose tissue and stimulate glucose disposal in muscle has not been clearly defined in this population. The current study was initiated to test the hypothesis that these 2 facets of insulin action are related, with greater defects in insulin-mediated glucose disposal associated with less effective insulin inhibition of FFA release from adipose tissue. Subjects included 56 healthy nondiabetic overweight/moderately obese women classified as insulin resistant or insulin sensitive based on whole-body glucose disposal. All underwent a modified 240-minute 2-stage insulin infusion with basal (∼15 µU/mL) and physiologically elevated (∼80 µU/mL) steady-state insulin concentrations. Plasma glucose, insulin, FFA, and glycerol were measured throughout. Whereas plasma glucose differed most during physiological hyperinsulinemia in insulin-resistant vs insulin-sensitive subjects, plasma FFA/glycerol differed most during basal insulin concentrations. The FFA concentrations during the basal insulin steady state correlated highly (r = 0.85, P < .001) with glucose concentrations during the hyperinsulinemic steady state. Overweight/moderately obese women exhibit dramatic differences in the ability of insulin to suppress plasma FFA, which correlate highly with differences in insulin-mediated glucose disposal. Variability in insulin regulation of FFA is most apparent at basal insulin concentrations, whereas differences in glucose disposal are most apparent during physiologic hyperinsulinemia. Both can be quantified using a simple 2-stage insulin infusion study, with first-stage FFA

  5. Hamlet's delay.

    PubMed

    Dendy, E B

    2001-01-01

    This paper raises a question about Freud's understanding of Hamlet and offers a fresh psychoanalytic perspective on the play, emphasizing the psychological use made of Hamlet by the audience. It suggests Hamlet and Claudius both serve as sacrificial objects, scapegoats, for the audience, embodying, through a mechanism of both identification and disidentification, the fulfillment, punishment, and renunciation of the audience's forbidden (i.e. Oedipal) wishes. The play is thus seen to represent unconsciously a rite of sacrifice in which both Claudius and Hamlet, both the father and the son, are led, albeit circuitously, to the slaughter. The need for delay on the part of Hamlet is thus seen to arise not merely from Hamlet's psychology, whatever the audience may project onto it, but ultimately from the function (both sadistic and defensive) that the sacrificial spectacle, the play as a whole, serves for the audience. The paper also speculates somewhat on the role of tragic heroes and heroines in general, and points to the unconscious collusion that permits author and audience to make use of them. Finally, in an addendum, the paper discusses the work of René Girard, a nonpsychoanalytic thinker whose ideas nonetheless are somewhat similar to those presented here.

  6. Host insulin stimulates Echinococcus multilocularis insulin signalling pathways and larval development

    PubMed Central

    2014-01-01

    Background The metacestode of the tapeworm Echinococcus multilocularis is the causative agent of alveolar echinococcosis, a lethal zoonosis. Infections are initiated through establishment of parasite larvae within the intermediate host’s liver, where high concentrations of insulin are present, followed by tumour-like growth of the metacestode in host organs. The molecular mechanisms determining the organ tropism of E. multilocularis or the influences of host hormones on parasite proliferation are poorly understood. Results Using in vitro cultivation systems for parasite larvae we show that physiological concentrations (10 nM) of human insulin significantly stimulate the formation of metacestode larvae from parasite stem cells and promote asexual growth of the metacestode. Addition of human insulin to parasite larvae led to increased glucose uptake and enhanced phosphorylation of Echinococcus insulin signalling components, including an insulin receptor-like kinase, EmIR1, for which we demonstrate predominant expression in the parasite’s glycogen storage cells. We also characterized a second insulin receptor family member, EmIR2, and demonstrated interaction of its ligand binding domain with human insulin in the yeast two-hybrid system. Addition of an insulin receptor inhibitor resulted in metacestode killing, prevented metacestode development from parasite stem cells, and impaired the activation of insulin signalling pathways through host insulin. Conclusions Our data indicate that host insulin acts as a stimulant for parasite development within the host liver and that E. multilocularis senses the host hormone through an evolutionarily conserved insulin signalling pathway. Hormonal host-parasite cross-communication, facilitated by the relatively close phylogenetic relationship between E. multilocularis and its mammalian hosts, thus appears to be important in the pathology of alveolar echinococcosis. This contributes to a closer understanding of organ tropism and

  7. Insulin Degludec/Liraglutide: A Review in Type 2 Diabetes.

    PubMed

    Greig, Sarah L; Scott, Lesley J

    2015-09-01

    Insulin degludec/liraglutide (Xultophy(®)), a fixed-ratio combination of an ultra-long-acting insulin analogue and a glucagon-like protein-1 (GLP-1) receptor agonist, is available in the EU for the management of inadequately controlled type 2 diabetes. Once-daily subcutaneous insulin degludec/liraglutide as add-on therapy to oral antidiabetics was effective and generally well tolerated in adults with inadequately controlled type 2 diabetes in several well designed 26-week phase III trials. In insulin-naive patients, add-on insulin degludec/liraglutide provided significantly greater improvements in glycated haemoglobin (HbA1c) levels than add-on insulin degludec, liraglutide or placebo, or unchanged GLP-1 receptor agonists (i.e. liraglutide or exenatide). In the extension of one of these trials, the efficacy of add-on insulin degludec/liraglutide was maintained for a total of 52 weeks. In insulin-experienced patients, add-on insulin degludec/liraglutide was significantly more effective with regard to improvements in HbA1c levels than add-on insulin degludec (at equivalent doses) or ongoing insulin glargine therapy. Add-on insulin degludec/liraglutide was associated with a lower incidence of confirmed hypoglycaemia than add-on insulin degludec in insulin-naive patients or ongoing insulin glargine in insulin-experienced patients, and a lower initial rate of nausea than add-on liraglutide. Thus, once-daily subcutaneous insulin degludec/liraglutide is a useful add-on therapy option for adult patients with inadequately controlled type 2 diabetes.

  8. Generalised insulin oedema after intensification of treatment with insulin analogues.

    PubMed

    Adamo, Luigi; Thoelke, Mark

    2013-02-20

    We report a case of generalised insulin oedema after intensification of treatment with genetically modified insulin. This is the first case of generalised oedema in response to treatment with insulin analogues in a patient not insulin naive.

  9. Human insulin genome sequence map, biochemical structure of insulin for recombinant DNA insulin.

    PubMed

    Chakraborty, Chiranjib; Mungantiwar, Ashish A

    2003-08-01

    Insulin is a essential molecule for type I diabetes that is marketed by very few companies. It is the first molecule, which was made by recombinant technology; but the commercialization process is very difficult. Knowledge about biochemical structure of insulin and human insulin genome sequence map is pivotal to large scale manufacturing of recombinant DNA Insulin. This paper reviews human insulin genome sequence map, the amino acid sequence of porcine insulin, crystal structure of porcine insulin, insulin monomer, aggregation surfaces of insulin, conformational variation in the insulin monomer, insulin X-ray structures for recombinant DNA technology in the synthesis of human insulin in Escherichia coli.

  10. UAVs and Control Delays

    DTIC Science & Technology

    2005-09-01

    Transport Delay itI tl2 s2+(tl +t2tI2)s+ 1 Delay Figure 17 A Matlab Simulink model used to compare a simple delayed system , in this case an integrator...23 3 Control of tim e-delay system s...discuss the various sources of delays, leading to an assessment of typical delays to be expected in a few example systems . Sources of delay that will

  11. Cognitively impaired elderly exhibit insulin resistance and no memory improvement with infused insulin.

    PubMed

    Morris, Jill K; Vidoni, Eric D; Mahnken, Jonathan D; Montgomery, Robert N; Johnson, David K; Thyfault, John P; Burns, Jeffrey M

    2016-03-01

    Insulin resistance is a risk factor for Alzheimer's disease (AD), although its role in AD etiology is unclear. We assessed insulin resistance using fasting and insulin-stimulated measures in 51 elderly subjects with no dementia (ND; n = 37) and with cognitive impairment (CI; n = 14). CI subjects exhibited either mild CI or AD. Fasting insulin resistance was measured using the homeostatic model assessment of insulin resistance (HOMA-IR). Insulin-stimulated glucose disposal was assessed using the hyperinsulinemic-euglycemic clamp to calculate glucose disposal rate into lean mass, the primary site of insulin-stimulated glucose disposal. Because insulin crosses the blood-brain barrier, we also assessed whether insulin infusion would improve verbal episodic memory compared to baseline. Different but equivalent versions of cognitive tests were administered in counterbalanced order in the basal and insulin-stimulated state. Groups did not differ in age or body mass index. Cognitively impaired subjects exhibited greater insulin resistance as measured at fasting (HOMA-IR; ND: 1.09 [1.1] vs. CI: 2.01 [2.3], p = 0.028) and during the hyperinsulinemic clamp (glucose disposal rate into lean mass; ND: 9.9 (4.5) vs. AD 7.2 (3.2), p = 0.040). Cognitively impaired subjects also exhibited higher fasting insulin compared to ND subjects, (CI: 8.7 [7.8] vs. ND: 4.2 [3.8] μU/mL; p = 0.023) and higher fasting amylin (CI: 24.1 [39.1] vs. 8.37 [14.2]; p = 0.050) with no difference in fasting glucose. Insulin infusion elicited a detrimental effect on one test of verbal episodic memory (Free and Cued Selective Reminding Test) in both groups (p < 0.0001) and no change in performance on an additional task (delayed logical memory). In this study, although insulin resistance was observed in cognitively impaired subjects compared to ND controls, insulin infusion did not improve memory. Furthermore, a significant correlation between HOMA-IR and glucose disposal rate was present only in ND

  12. Delayed coking process

    SciTech Connect

    Shigley, J.K.; Roussel, K.M.; Harris, S.D.

    1991-07-02

    This patent describes improvement in a delayed premium coking process in which an aromatic mineral oil feedstock is heated to elevated temperature and introduced continuously to a coking drum under delayed coking conditions wherein the heated feedstock soaks in its contained heat to convert the feedstock to cracked vapors and premium coke at lower than normal coking temperatures in the range of about 780{degrees} F. to about 895{degrees} F. and in which the introduction of feedstock to the coking drum is discontinued after the coking drum is filled to a desired level. The improvement comprises: introducing additional aromatic mineral oil capable of forming coke admixed with a non-coking material to the coking drum under delayed coking conditions for a sufficient period of time to convert unconverted liquid material to coke wherein the concentration of aromatic mineral oil in the admixture is from 5 to 90 percent, and thereafter subjecting the contents of the coke drum to a heat soak at a temperature greater than the initial coking temperature whereby a premium coke having improved CTE and reduced fluff is obtained.

  13. Rationale for, Initiation and Titration of the Basal Insulin/GLP-1RA Fixed-Ratio Combination Products, IDegLira and IGlarLixi, for the Management of Type 2 Diabetes.

    PubMed

    Valentine, Virginia; Goldman, Jennifer; Shubrook, Jay H

    2017-08-01

    Type 2 diabetes (T2D) is a progressive disease affecting glucose regulation and a major cause of morbidity and mortality globally. Many patients are not escalated up the treatment ladder appropriately despite failing to achieve glycemic control, with barriers such as fear of hypoglycemia, weight gain, and treatment burden recognized as factors. Exogenous basal insulin is titrated to address control of fasting plasma glucose and may preserve residual β-cell function, thus promoting a greater endogenous prandial insulin response. Native glucagon-like peptide-1 (GLP-1) is a peptide hormone secreted by the gut in response to nutrient ingestion; it increases insulin secretion, inhibits glucagon secretion, and prolongs gastric emptying, thereby lowering overall food intake. As its glucose-lowering action is glucose dependent, a GLP-1 receptor agonist (GLP-1RA) achieves these benefits with a lower risk of hypoglycemia compared with other diabetes therapies. Two products, an insulin degludec/liraglutide combination (IDegLira) and an insulin glargine/lixisenatide combination (IGlarLixi), were approved for use in adults with T2D by the US Food and Drug Administration in 2016. The efficacy and safety of these two basal insulin/GLP-1RA combination products were studied in the DUAL program (NCTs 01336023, 01392573, 01676116, 01618162, 01952145, and 02298192) and the LixiLan program (NCTs 02058160 and 02058147). Compared with basal insulin, insulin/GLP-1RA fixed-ratio combinations are superior at reducing HbA1c with weight neutrality or weight loss rather than weight gain, as well as reduced hypoglycemia rates, and reduced insulin-dose requirement with IDegLira. A combination of different medications may often be required to achieve glycemic control, and fixed-ratio combination products allow such therapies to be given in simple regimens. Clinical trial data for these products highlight the great potential of these agents, not merely their efficacy and safety but also their

  14. Rhus coriaria ameliorates insulin resistance in non-insulin-dependent diabetes mellitus (NIDDM) rats.

    PubMed

    Anwer, Tarique; Sharma, Manju; Khan, Gyas; Iqbal, Muzaffar; Ali, Mohammad Sajid; Alam, Mohammad Sarfaraz; Safhi, Mohammed Mohsen; Gupta, Nakul

    2013-01-01

    We have investigated the effect of methanolic extract of Rhus coriaria (RC) on hyperinsulinemia, glucose intolerance and insulin sensitivity in non-insulin-dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by single intraperitoneal injection of streptozotocin (STZ, 100 mg/kg) to 2 days old rat pups. RC (200 mg/kg and 400 mg/kg) was administered orally once a day for 5 weeks after the animals were confirmed diabetic (i.e, 90 days after STZ injection). A group of citrate control rats were also maintained which has received citrate buffer on the 2nd day of their birth. There was a significant increase in blood glucose, glycosylated hemoglobin (HbA1c) and serum insulin levels were observed in NIDDM control rats. Treatment with RC reduced the elevated levels of blood glucose, HbA1c and insulin in the NIDDM rats. An oral glucose tolerance test (OGTT) was also performed in the same groups, in which we found a significant improvement in glucose tolerance in the rats treated with RC. The insulin sensitivity was assessed for both peripheral insulin resistance and hepatic insulin resistance. RC treatment significantly improved insulin sensitivity index (K(ITT)) which was significantly decreased in NIDDM control rats. There was significant rise in homeostasis model assessment of insulin resistance (HOMA-R) in NIDDM control rats whereas RC treatment significantly prevented the rise in HOMA-R in NIDDM treated rats. Our data suggest that methanolic extract of RC significantly delayed the onset of hyperinsulinemia and glucose intolerance and improved insulin sensitivity in NIDDM rats.

  15. New concept for long-acting insulin: spontaneous conversion of an inactive modified insulin to the active hormone in circulation: 9-fluorenylmethoxycarbonyl derivative of insulin.

    PubMed

    Gershonov, E; Shechter, Y; Fridkin, M

    1999-07-01

    new concept for prolonging the half-life of insulin in the circulatory system, in which receptor-mediated endocytosis and degradation is delayed and accompanied by a time-dependent generation of basal insulin.

  16. Insulin C-peptide

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003701.htm Insulin C-peptide test To use the sharing features ... a product that is created when the hormone insulin is produced and released into the body. The ...

  17. Insulin pump (image)

    MedlinePlus

    The catheter at the end of the insulin pump is inserted through a needle into the abdominal ... with diabetes. Dosage instructions are entered into the pump's small computer and the appropriate amount of insulin ...

  18. Suicide by Insulin?

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_165701.html Suicide by Insulin? Self-harm and suicidal behavior may ... higher rates of depression, the researchers explained. And suicide or suicide attempts using insulin or other diabetes ...

  19. High-mix insulins

    PubMed Central

    Kalra, Sanjay; Farooqi, Mohammad Hamed; El-Houni, Ali E.

    2015-01-01

    Premix insulins are commonly used insulin preparations, which are available in varying ratios of different molecules. These drugs contain one short- or rapid-acting, and one intermediate- or long-acting insulin. High-mix insulins are mixtures of insulins that contain 50% or more than 50% of short-acting insulin. This review describes the clinical pharmacology of high-mix insulins, including data from randomized controlled trials. It suggests various ways, in which high-mix insulin can be used, including once daily, twice daily, thrice daily, hetero-mix, and reverse regimes. The authors provide a rational framework to help diabetes care professionals, identify indications for pragmatic high-mix use. PMID:26425485

  20. Insulin Receptor Signaling in Cones*

    PubMed Central

    Rajala, Ammaji; Dighe, Radhika; Agbaga, Martin-Paul; Anderson, Robert E.; Rajala, Raju V.S.

    2013-01-01

    In humans, age-related macular degeneration and diabetic retinopathy are the most common disorders affecting cones. In retinitis pigmentosa (RP), cone cell death precedes rod cell death. Systemic administration of insulin delays the death of cones in RP mouse models lacking rods. To date there are no studies on the insulin receptor signaling in cones; however, mRNA levels of IR signaling proteins are significantly higher in cone-dominant neural retina leucine zipper (Nrl) knock-out mouse retinas compared with wild type rod-dominant retinas. We previously reported that conditional deletion of the p85α subunit of phosphoinositide 3-kinase (PI3K) in cones resulted in age-related cone degeneration, and the phenotype was not rescued by healthy rods, raising the question of why cones are not protected by the rod-derived cone survival factors. Interestingly, systemic administration of insulin has been shown to delay the death of cones in mouse models of RP lacking rods. These observations led to the hypothesis that cones may have their own endogenous neuroprotective pathway, or rod-derived cone survival factors may be signaled through cone PI3K. To test this hypothesis we generated p85α−/−/Nrl−/− double knock-out mice and also rhodopsin mutant mice lacking p85α and examined the effect of the p85α subunit of PI3K on cone survival. We found that the rate of cone degeneration is significantly faster in both of these models compared with respective mice with competent p85α. These studies suggest that cones may have their own endogenous PI3K-mediated neuroprotective pathway in addition to the cone viability survival signals derived from rods. PMID:23673657

  1. Degradative processing of internalized insulin in isolated adipocytes

    SciTech Connect

    Marshall, S.

    1985-11-05

    Based on the distribution of SVI-insulin between the cell surface and the cell interior, it was found that insulin rapidly binds (t 1/2 = 0.4 min) to surface receptors at 37 degrees C, and after an initial lag period of about 1 min, accumulates intracellularly until steady state is reached (t 1/2 = 3.5 min). At this time about 40% of the total cell-associated SVI-insulin resides in the cell interior reflecting a dynamic equilibrium between the rate of insulin endocytosis and the rate at which internalized insulin is processed and extruded from cells. Since this percentage decreased to 15% at 16 degrees C, it appears that internalization is more temperative-sensitive than the intracellular processing of insulin. When SVI-insulin was preloaded into the cell interior, it was found that internalized insulin was rapidly released to the medium at 37 degrees C (t 1/2 = 6.5 min) and consisted of both degraded products and intact insulin (as assessed by trichloroacetic acid precipitability and column chromatography). Since 75% of internalized insulin was ultimately degraded, and 25% was released intact, this indicates that degradation is the predominant pathway. To determine when incoming insulin enters a degradative compartment, cells were continually exposed to SVI-insulin and the composition of insulin in the cell interior over time was assessed. After 2 min all endocytosed insulin was intact, between 2-3 min degradation products began accumulating intracellularly, and by 15 min equilibrium was reached with 20% of internalized insulin consisting of degraded products. Degraded insulin was then released from the cell interior within 4-5 min after endocytotic uptake, since this was the earliest time chloroquine was found to inhibit the release of degradation products.

  2. All about Insulin Resistance

    MedlinePlus

    Toolkit No. 2 All About Insulin Resistance Insulin resistance is a condition that raises your risk for type 2 diabetes and heart disease. ... Diabetes Association, Inc. 1/15 Toolkit No. 2: All About Insulin Resistance continued J Order the smallest ...

  3. Delayed childbearing.

    PubMed

    Francis, H H

    1985-06-01

    In many Western nations, including England and Wales, Sweden, and the US, there is a current trend towards delayed childbearing because of women's pursuit of a career, later marriage, a longer interval between marriage and the 1st birth, and the increasing number of divorcees having children in a 2nd marriage. Wives of men in social classes I and II in England and Wales are, on average, having their 1st child at 27.9 years, 1.6 years later than in 1973, and in social classes IV and V, 1.0 years later than in 1973, at a mean age of 23.7 years. Consequently, the total period fertility rate for British women aged 30-34 years, 35-39 years, and 40 and over increased by 4%, 2%, and 4%, respectively, between 1982-83, in contrast to reductions of 2% and 3%, respectively, in the 15-19 year and 20-24 year age groups, with the 25-29-year-olds remaining static. The average maternal mortality for all parties in England and Wales during 1976-78 was 106/million for adolescents, 70.4/million for 20-24 year-olds, and 1162/million for those aged 40 years and older. The specific obstetric and allied conditions which increase with age are the hypertensive diseases of pregnancy, hemorrhage, pulmonary embolism, abortion, cardiac disease, caesarean section, ruptured uterus, and amniotic fluid embolism. The Swedish Medical Birth Registry of all live births and perinatal deaths since 1973 has shown that the risk of late fetal death is significantly greater in women aged 30-39 years than in those of the same parity and gravidity aged 20-24 years. The risk of giving birth to low birth weight babies preterm and at term and of premature labor are similarly increased. The early neonatal death rate also was increased for primigravidas and nulliparas in the 30-39 year age group but not in parous women. This is, in part, due to the rise in incidence of fetal abnormalities with advancing maternal age because of chromosomal and nonchromosomal anomalies. These also appear to be the cause of the

  4. Study Design for the IMMEDIATE (Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care) Trial: A Double-blind Randomized Controlled Trial of Intravenous Glucose, Insulin, and Potassium (GIK) for Acute Coronary Syndromes in Emergency Medical Services

    PubMed Central

    Selker, Harry P.; Beshansky, Joni R.; Griffith, John L.; D’Agostino, Ralph B.; Massaro, Joseph M.; Udelson, James E.; Rashba, Eric J.; Ruthazer, Robin; Sheehan, Patricia R.; Desvigne-Nickens, Patrice; Rosenberg, Yves D.; Atkins, James M.; Sayah, Assaad J.; Aufderheide, Tom P.; Rackley, Charles E.; Opie, Lionel H.; Lambrew, Costas T.; Cobb, Leonard A.; MacLeod, Bruce A.; Ingwall, Joanne S.; Zalenski, Robert J.; Apstein, Carl S.

    2014-01-01

    Background Experimental studies suggest that metabolic myocardial support by intravenous (IV) glucose, insulin, and potassium (GIK) reduces ischemia-induced arrhythmias, cardiac arrest, mortality, progression from unstable angina pectoris (UAP) to acute myocardial infarction (AMI), and MI size. However, trials of hospital administration of IV GIK to patients with ST elevation MI (STEMI) have generally not shown favorable effects, possibly due to the GIK intervention taking place many hours after ischemic symptom onset. A trial of GIK used in the very first hours of ischemia has been needed, consistent with the timing of benefit seen in experimental studies. Objective The Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care (IMMEDIATE) Trial tested whether, if given very early, GIK could have the impact seen in experimental studies. Accordingly, distinct from prior trials, IMMEDIATE tested the impact of GIK 1) in patients with acute coronary syndromes (ACS), rather than only AMI or STEMI, and 2) administered in prehospital emergency medical service (EMS) settings, rather than later, in hospitals, following emergency department evaluation. Design IMMEDIATE was an EMS-based randomized placebo-controlled clinical effectiveness trial conducted in 13 cities across the US which enrolled 911 participants. Eligible were patients age 30 or older for whom a paramedic performed a 12-lead electrocardiogram (ECG)to evaluate chest pain or other symptoms suggestive of ACS for whom electrocardiograph-based ACI-TIPI (acute cardiac ischemia time-insensitive predictive instrument) indicated a > 75% probability of ACS, and/or the TPI (thrombolytic predictive instrument) indicated presence of a STEMI, or if local criteria for STEMI notification of receiving hospitals were met. Prehospital IV GIK or placebo was started immediately. Pre-specified were the primary endpoint of progression of ACS to infarction, and as major secondary endpoints

  5. One-year outcomes of out-of-hospital administration of intravenous glucose, insulin, and potassium (GIK) in patients with suspected acute coronary syndromes (from the IMMEDIATE [Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency Care] Trial).

    PubMed

    Selker, Harry P; Udelson, James E; Massaro, Joseph M; Ruthazer, Robin; D'Agostino, Ralph B; Griffith, John L; Sheehan, Patricia R; Desvigne-Nickens, Patrice; Rosenberg, Yves; Tian, Xin; Vickery, Ellen M; Atkins, James M; Aufderheide, Tom P; Sayah, Assaad J; Pirrallo, Ronald G; Levy, Michael K; Richards, Michael E; Braude, Darren A; Doyle, Delanor D; Frascone, Ralph J; Kosiak, Donald J; Leaming, James M; Van Gelder, Carin M; Walter, Gert-Paul; Wayne, Marvin A; Woolard, Robert H; Beshansky, Joni R

    2014-05-15

    The Immediate Myocardial Metabolic Enhancement During Initial Assessment and Treatment in Emergency care Trial of very early intravenous glucose-insulin-potassium (GIK) for acute coronary syndromes (ACS) in out-of-hospital emergency medical service (EMS) settings showed 80% reduction in infarct size at 30 days, suggesting potential longer-term benefits. Here we report 1-year outcomes. Prespecified 1-year end points of this randomized, placebo-controlled, double-blind, effectiveness trial included all-cause mortality and composites including cardiac arrest, mortality, or hospitalization for heart failure (HF). Of 871 participants randomized to GIK versus placebo, death occurred within 1 year in 11.6% versus 13.5%, respectively (unadjusted hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.57 to 1.23, p = 0.36). The composite of cardiac arrest or 1-year mortality was 12.8% versus 17.0% (HR 0.71, 95% CI 0.50 to 1.02, p = 0.06). The composite of hospitalization for HF or mortality within 1 year was 17.2% versus 17.2% (HR 0.98, 95% CI 0.70 to 1.37, p = 0.92). The composite of mortality, cardiac arrest, or HF hospitalization within 1 year was 18.1% versus 20.4% (HR 0.85, 95% CI 0.62 to 1.16, p = 0.30). In patients presenting with suspected ST elevation myocardial infarction, HRs for 1-year mortality and the 3 composites were, respectively, 0.65 (95% CI 0.33 to 1.27, p = 0.21), 0.52 (95% CI 0.30 to 0.92, p = 0.03), 0.63 (95% CI 0.35 to 1.16, p = 0.14), and 0.51 (95% CI 0.30 to 0.87, p = 0.01). In patients with suspected acute coronary syndromes, serious end points generally were lower with GIK than placebo, but the differences were not statistically significant. However, in those with ST elevation myocardial infarction, the composites of cardiac arrest or 1-year mortality, and of cardiac arrest, mortality, or HF hospitalization within 1 year, were significantly reduced.

  6. Human blood-brain barrier insulin receptor.

    PubMed

    Pardridge, W M; Eisenberg, J; Yang, J

    1985-06-01

    A new model system for characterizing the human brain capillary, which makes up the blood-brain barrier (BBB) in vivo, is described in these studies and is applied initially to the investigation of the human BBB insulin receptor. Autopsy brains were obtained from the pathologist between 22-36 h postmortem and were used to isolate human brain microvessels which appeared intact on both light and phase microscopy. The microvessels were positive for human factor 8 and for a BBB-specific enzyme marker, gamma-glutamyl transpeptidase. The microvessels avidly bound insulin with a high-affinity dissociation constant, KD = 1.2 +/- 0.5 nM. The human brain microvessels internalized insulin based on acid-wash assay, and 75% of insulin was internalized at 37 degrees C. The microvessels transported insulin to the medium at 37 degrees C with a t1/2 = approximately 70 min. Little of the 125I-insulin was metabolized by the microvessels under these conditions based on the elution profile of the medium extract over a Sephadex G-50 column. Plasma membranes were obtained from the human brain microvessels and these membranes were enriched in membrane markers such as gamma-glutamyl transpeptidase or alkaline phosphatase. The plasma membranes bound 125I-insulin with and ED50 = 10 ng/ml, which was identical to the 50% binding point in intact microvessels. The human BBB plasma membranes were solubilized in Triton X-100 and were adsorbed to a wheat germ agglutinin Sepharose affinity column, indicating the BBB insulin receptor is a glycoprotein. Affinity cross-linking of insulin to the plasma membranes revealed a 127K protein that specifically binds insulin.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. Insulin adherence behaviours and barriers in the multinational Global Attitudes of Patients and Physicians in Insulin Therapy study.

    PubMed

    Peyrot, M; Barnett, A H; Meneghini, L F; Schumm-Draeger, P-M

    2012-05-01

    To examine patient and physician beliefs regarding insulin therapy and the degree to which patients adhere to their insulin regimens. Internet survey of 1250 physicians (600 specialists, 650 primary care physicians) who treat patients with diabetes and telephone survey of 1530 insulin-treated patients (180 with Type 1 diabetes, 1350 with Type 2 diabetes) in China, France, Japan, Germany, Spain, Turkey, the UK or the USA. One third (33.2%) of patients reported insulin omission/non-adherence at least 1 day in the last month, with an average of 3.3 days. Three quarters (72.5%) of physicians report that their typical patient does not take their insulin as prescribed, with a mean of 4.3 days per month of basal insulin omission/non-adherence and 5.7 days per month of prandial insulin omission/non-adherence. Patients and providers indicated the same five most common reasons for insulin omission/non-adherence: too busy; travelling; skipped meals; stress/emotional problems; public embarrassment. Physicians reported low patient success at initiating insulin in a timely fashion and adjusting insulin doses. Most physicians report that many insulin-treated patients do not have adequate glucose control (87.6%) and that they would treat more aggressively if not for concern about hypoglycaemia (75.5%). Although a majority of patients (and physicians) regard insulin treatment as restrictive, more patients see insulin treatment as having positive than negative impacts on their lives. Glucose control is inadequate among insulin-treated patients, in part attributable to insulin omission/non-adherence and lack of dose adjustment. There is a need for insulin regimens that are less restrictive and burdensome with lower risk of hypoglycaemia. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  8. Increased Clearance and Degradation of [3H]Insulin in Streptozotocin Diabetic Rats

    PubMed Central

    Philippe, Jacques; Halban, Philippe A.; Gjinovci, Asllan; Duckworth, William C.; Estreicher, Jurek; Renold, Albert E.

    1981-01-01

    The role of the insulin-receptor compartment in the pharmacokinetics of intravenously injected insulin in rats was studied. Since streptozotocin-diabetes in rats results in increased insulin binding to tissues in vitro, insulin pharmacokinetics in streptozotocin-diabetic rats were compared to controls, using semisynthetic [3H]insulin as the tracer. The initial distribution volume for [3H]insulin was elevated by 60% in diabetic rats. By contrast, no difference in initial distribution volume for [14C]inulin was observed, and the absolute values were lower than those found for [3H]insulin. The metabolic clearance rate of [3H]insulin was elevated by 44% in diabetic rats. That these differences were the result of increased binding of insulin to a specific receptor compartment in diabetic rats was shown by three additional experiments. The first involved receptor saturation by injection of 10 U native insulin 2 min before the tracer injection, resulting in identical [3H]insulin disappearance rates in the two groups of rats. The second consisted of displacing [3H]insulin from receptors by injecting 10 U unlabeled insulin 6 min after the tracer injection. Displacement of intact [3H]insulin from receptors and subsequent reappearance in the circulation occurred in both control and diabetic animals; however, such displacement was 25% greater in the diabetic rats. Finally, treatment of diabetic rats with insulin for 8 d normalized [3H]insulin clearance even though the tracer was injected at a time when the animals were again hyperglycemic and hypoinsulinemic. This suggests that down-regulation of insulin receptors had occurred during insulin therapy. These results confirm that a specific compartment for insulin exists (the insulin-receptor compartment) and that this compartment plays an important role in insulin clearance. PMID:6451633

  9. Effect of glucagon-like peptide 1(7-36) amide on glucose effectiveness and insulin action in people with type 2 diabetes.

    PubMed

    Vella, A; Shah, P; Basu, R; Basu, A; Holst, J J; Rizza, R A

    2000-04-01

    Although it is well established that glucagon-like peptide 1(7-36) amide (GLP-1) is a potent stimulator of insulin secretion, its effects on insulin action and glucose effectiveness are less clear. To determine whether GLP-1 increases insulin action and glucose effectiveness, subjects with type 2 diabetes were studied on two occasions. Insulin was infused during the night on both occasions to ensure that baseline glucose concentrations were comparable. On the morning of study, either GLP-1 (1.2 pmol x kg(-1) x min(-1)) or saline were infused along with somatostatin and replacement amounts of glucagon. Glucose also was infused in a pattern mimicking that typically observed after a carbohydrate meal. Insulin concentrations were either kept constant at basal levels (n = 6) or varied so as to create a prandial insulin profile (n = 6). The increase in glucose concentration was virtually identical on the GLP-1 and saline study days during both the basal (1.21 +/- 0.15 vs. 1.32 +/- 0.19 mol/l per 6 h) and prandial (0.56 +/- 0.14 vs. 0.56 +/- 0.10 mol/l per 6 h) insulin infusions. During both the basal and prandial insulin infusions, glucose disappearance promptly increased after initiation of the glucose infusion to rates that did not differ on the GLP-1 and saline study days. Suppression of endogenous glucose production also was comparable on the GLP-1 and saline study days during both the basal (-2.7 +/- 0.3 vs. -3.1 +/- 0.2 micromol/kg) and prandial (-3.1 +/- 0.4 vs. -3.0 +/- 0.6 pmol/kg) insulin infusions. We conclude that when insulin and glucagon concentrations are matched, GLP-1 has negligible effects on either insulin action or glucose effectiveness in people with type 2 diabetes. These data strongly support the concept that GLP-1 improves glycemic control in people with type 2 diabetes by increasing insulin secretion, by inhibiting glucagon secretion, and by delaying gastric emptying rather than by altering extrapancreatic glucose metabolism.

  10. Insulin oedema in a child with newly diagnosed diabetes mellitus.

    PubMed

    Aravamudhan, Avinash; Gardner, Chris; Smith, Claire; Senniappan, Senthil

    2014-05-01

    Insulin oedema is a rare complication of insulin therapy for diabetes mellitus. It has been reported in type 1 diabetes mellitus, in poorly controlled type 2 diabetes mellitus following either the initiation or intensification of insulin therapy and in underweight patients on large doses of insulin. There are only a few case reports since it was first described in 1928, showing that it is an uncommon and probably an under-reported complication. The majority of those reports have been in the adult population. The generalised oedema tends to develop shortly after initiation or intensification of insulin therapy and resolves spontaneously within few weeks. We present one of the youngest patients reported in the literature, a 9-year-old boy who developed insulin oedema within few days of presenting with diabetic ketoacidosis. The case highlights the importance of recognising this generally transient and self-resolving complication and differentiating it from other serious causes of oedema.

  11. Insulin and IGF1 Receptors Are Essential for XX and XY Gonadal Differentiation and Adrenal Development in Mice

    PubMed Central

    Romero, Yannick; Conne, Béatrice; Truong, Vy; Papaioannou, Marilena D.; Schaad, Olivier; Docquier, Mylène; Herrera, Pedro Luis; Wilhelm, Dagmar; Nef, Serge

    2013-01-01

    Mouse sex determination provides an attractive model to study how regulatory genetic networks and signaling pathways control cell specification and cell fate decisions. This study characterizes in detail the essential role played by the insulin receptor (INSR) and the IGF type I receptor (IGF1R) in adrenogenital development and primary sex determination. Constitutive ablation of insulin/IGF signaling pathway led to reduced proliferation rate of somatic progenitor cells in both XX and XY gonads prior to sex determination together with the downregulation of hundreds of genes associated with the adrenal, testicular, and ovarian genetic programs. These findings indicate that prior to sex determination somatic progenitors in Insr;Igf1r mutant gonads are not lineage primed and thus incapable of upregulating/repressing the male and female genetic programs required for cell fate restriction. In consequence, embryos lacking functional insulin/IGF signaling exhibit (i) complete agenesis of the adrenal cortex, (ii) embryonic XY gonadal sex reversal, with a delay of Sry upregulation and the subsequent failure of the testicular genetic program, and (iii) a delay in ovarian differentiation so that Insr;Igf1r mutant gonads, irrespective of genetic sex, remained in an extended undifferentiated state, before the ovarian differentiation program ultimately is initiated at around E16.5. PMID:23300479

  12. Oral Insulin Reloaded

    PubMed Central

    Heinemann, Lutz; Plum-Mörschel, Leona

    2014-01-01

    Optimal coverage of insulin needs is the paramount aim of insulin replacement therapy in patients with diabetes mellitus. To apply insulin without breaking the skin barrier by a needle and/or to allow a more physiological provision of insulin are the main reasons triggering the continuous search for alternative routes of insulin administration. Despite numerous attempts over the past 9 decades to develop an insulin pill, no insulin for oral dosing is commercially available. By way of a structured approach, we aim to provide a systematic update on the most recent developments toward an orally available insulin formulation with a clear focus on data from clinical-experimental and clinical studies. Thirteen companies that claim to be working on oral insulin formulations were identified. However, only 6 of these companies published new clinical trial results within the past 5 years. Interestingly, these clinical data reports make up a mere 4% of the considerably high total number of publications on the development of oral insulin formulations within this time period. While this picture clearly reflects the rising research interest in orally bioavailable insulin formulations, it also highlights the fact that the lion’s share of research efforts is still allocated to the preclinical stages. PMID:24876606

  13. Inhaled human insulin.

    PubMed

    Strack, Thomas R

    2006-04-01

    The benefit of subcutaneous insulin therapy in patients with diabetes is frequently limited due to difficulty in convincing patients of the importance of multiple daily insulin injections to cope effectively with meal-associated glycemic changes. Thus, the aim of achieving tight glycemic control, which is critical for reducing the risk of long-term diabetes-related complications, frequently remains elusive. The successful development of an inhalable insulin as a noninvasive alternative promises to change the management of diabetes. The first product to become available to patients is inhaled human insulin, a dry-powder formulation packaged into discrete blisters containing 1 or 3 mg of dry-powder human insulin and administered via a unique pulmonary inhaler device. It has recently been approved in both the United States and the European Union for the control of hyperglycemia in adult patients with type 1 or type 2 diabetes. The pharmacokinetic profile of inhaled human insulin closely mimics the natural pattern of insulin secretion, and resembles that of rapid-acting subcutaneous analogs. Similarly to rapid-acting subcutaneous analogs, inhaled human insulin has a more rapid onset of glucose-lowering activity compared to subcutaneous regular insulin, allowing it to be administered shortly before meals. It has a duration of glucose-lowering activity comparable to subcutaneous regular insulin and longer than rapid-acting insulin analogs. Inhaled human insulin effectively controls postprandial glucose concentrations in patients with type 1 or type 2 diabetes without increasing the risk of hypoglycemia, and even improves fasting glucose levels compared to subcutaneous insulin. Inhaled human insulin has an overall favorable safety profile. There are small reductions in lung function (1-1.5% of total lung forced expiratory volume in the first second [FEV1] capacity) after onset of treatment that are reversible in most patients if treatment is discontinued. Inhaled human

  14. Acceleration of insulin pharmacodynamic profile by a novel insulin infusion site warming device.

    PubMed

    Cengiz, Eda; Weinzimer, Stuart A; Sherr, Jennifer L; Tichy, Eileen; Martin, Melody; Carria, Lori; Steffen, Amy; Tamborlane, William V

    2013-05-01

    Subcutaneously injected rapid-acting insulin analogs do not replicate physiologic insulin action due to delays in their onset and peak action resulting in postprandial glucose excursions. The InsuPatch (IP) is a novel insulin infusion site warming device developed to accelerate insulin action by increasing blood flow to the area of insulin absorption. Thirteen adolescents with type 1 diabetes (T1D, mean age 14 ± 4 yr) were enrolled in this study to investigate the effect of the IP on the pharmacodynamics and pharmacokinetics of a 0.2 unit/kg bolus dose of aspart insulin using the euglycemic clamp technique. Each subject underwent two euglycemic clamp procedures on separate occasions: one with IP and one without IP activation in random order. When the insulin bolus was given with IP activation as compared to without IP activation, time to reach maximum insulin action (T(GIRmax)) and to reach 50% maximum action (T(50%GIRmax)) were 35 and 18 min earlier (125 ± 8 min vs. 90 ± 6 min, p = 0.002 and 58 ± 5 min. vs. 40 ± 3 min, p = 0.01, respectively), and the area under curve, AUC(GIR 0-90 min), reflecting early glucodynamic action, was significantly greater (p = 0.001). IP activation also accelerated the rise in plasma insulin levels after the bolus (p = 0.03) and resulted in a higher peak (p = 0.04) and greater overall increase (p = 0.02) in plasma insulin levels. Our results show that insulin infusion site warming with IP activation accelerates the time action profile of aspart insulin which may be of benefit to current open-loop and future closed-loop insulin delivery in patients with T1D. © 2012 John Wiley & Sons A/S.

  15. A primer on concentrated insulins: what an internist should know.

    PubMed

    Barnosky, Adrienne; Shah, Lisa; Meah, Farah; Emanuele, Nicholas; Emanuele, Mary Ann; Mazhari, Alaleh

    2016-05-01

    The common insulin concentration in most preparations of insulin is 100 units per mL or U-100. Human regular U-500 insulin was the first concentrated insulin introduced and it has been available in the United States since the 1950s. Humulin R is the only human regular U-500 available on the market. Human regular U-500 is five times more concentrated than U-100 and because of its pharmacodynamic properties, works as both a basal and a bolus insulin. Human regular U500 allows for delivery of a larger insulin dose with a smaller volume leading to better absorption compared to U-100 and has traditionally been used in patients with moderate to severe insulin resistance. More recently other forms of concentrated insulin have become available and the newer concentrated insulin preparations can be used in diabetic patients with or without insulin resistance. Our intent is to provide primary care physicians with a review of the pharmacology and current literature on concentrated insulins as well as recommendations for patient selection, dose initiation, and dose adjustment.

  16. Insulin and Lispro Insulin: What is Common and Different in their Behavior?

    PubMed

    Selivanova, Olga M; Suvorina, Mariya Yu; Surin, Alexey K; Dovidchenko, Nikita V; Galzitskaya, Oxana V

    2017-01-01

    There are different insulin analogues with various pharmacokinetic characteristics, such as, rapid-acting, long-acting, or intermediate-acting analogues. Since insulin tends to form amyloid aggregates, it is of particular interest to measure characteristic times of formation of amyloid aggregates and compare those to action times for insulin and its analogues. For the study we have chosen one of the insulin analogues - insulin Lispro, which is a fast acting insulin analog. It is usually thought of amyloid aggregation as a nucleation-dependent process. We have estimated the size of the primary nucleus to be one monomer and the size of the secondary nucleus to be around zero in both insulin and Lispro insulin aggregation processes. The main structural element of insulin and Lispro insulin amyloid fibrils is a rounded ring oligomer of about 6-7 nm in diameter, about 2-3 nm in height and about 2 nm in diameter of the hole. Fibrils of several μm in length are produced due to interaction of such oligomers. The packing of ring oligomers in fibrils differs because of the difference in their orderliness. Though the initial stages of fibril formation (monomer, oligomer) are similar, the further process depends on the unique sequence of each peptide. Namely the sequence affects the final morphology of mature amyloids. These observations allow us to conclude that formation of fibrils by short peptides occurs via and by means of oligomer ring structures. Such an important issue as the nature of polymorphism of insulin amyloid fibrils has been settled by us. The role of early oligomeric aggregates in such processes as nucleation and aggregation of amyloid fibrils has been examined.

  17. Glycemic control in hospitalized patients not in intensive care: beyond sliding-scale insulin.

    PubMed

    Nau, Konrad C; Lorenzetti, Rosemarie C; Cucuzzella, Mark; Devine, Timothy; Kline, Jonathan

    2010-05-01

    Glycemic control in hospitalized patients who are not in intensive care remains unsatisfactory. Despite persistent expert recommendations urging its abandonment, the use of sliding-scale insulin remains pervasive in U.S. hospitals. Evidence for the effectiveness of sliding-scale insulin is lacking after more than 40 years of use. New physiologic subcutaneous insulin protocols use basal, nutritional, and correctional insulin. The initial total daily dose of subcutaneous insulin is calculated using a factor of 0.3 to 0.6 units per kg body weight, with one half given as long-acting insulin (the basal insulin dose), and the other one half divided daily over three meals as short-acting insulin doses (nutritional insulin doses). A correctional insulin dose provides a final insulin adjustment based on the preprandial glucose value. This correctional dose resembles a sliding scale, but is only a small fine-tuning of therapy, as opposed to traditional sliding-scale insulin alone. Insulin sensitivity, nutritional intake, and total daily dosing review can alter the physiologic insulin-dosing schedule. Prospective trials have demonstrated reductions in hyperglycemic measurements, hypoglycemia, and adjusted hospital length of stay when physiologic subcutaneous insulin protocols are used. Transitions in care require special considerations and attention to glycemic control medications. Changing the sliding-scale insulin culture requires a multidisciplinary effort to improve patient safety and outcomes.

  18. Insulin production hampered by intermittent hypoxia via impaired zinc homeostasis.

    PubMed

    Pae, Eung-Kwon; Kim, Gyuyoup

    2014-01-01

    Without zinc, pancreatic beta cells cannot either assemble insulin molecules or precipitate insulin crystals; thus, a lack of zinc concentration in the beta cells would result in a decreased insulin production. ZIP8 is one of the zinc uptake transporters involved in zinc influx into the cytosol of beta cells. Thus, if ZIP8 is down-regulated, a decreased insulin production would result. We assumed that intermittent hypoxic exposure to the beta cells may result in a decreased production of insulin due to a lack of zinc. To test this hypothesis we harvested pancreatic islets from the rats conditioned under intermittent hypoxia (IH) (fluctuating between 20.5% and 10% every 4 min for 1 h) and compared the results with those from control animals and islets. We also compared their insulin and glucose homeostasis using glucose tolerance tests (GTT) after 3 weeks. GTT results show a significant delay (P<0.05) in recovery of the blood glucose level in IH treated pups. ZIP8 expression in the beta cell membrane was down-regulated. The zinc concentration in the cell as well as insulin production was significantly decreased in the islets harvested from IH animals. However, mRNA for insulin and C-peptide/insulin protein levels in the total cell lysates remained the same as those of controls. When we treated the beta cells using siRNA mediated ZIP8, we observed the commensurate results from the IH-treated islets. We conclude that a transient IH exposure could knockdown ZIP8 transporters at mRNA as well as protein levels in the beta cells, which would decrease the level of blood insulin. However, the transcriptional activity of insulin remains the same. We conclude that the precipitation process of insulin crystal may be disturbed by a lack of zinc in the cytosol that is modulated by mainly ZIP8 after IH exposure.

  19. Biosimilar Insulins: Basic Considerations.

    PubMed

    Heinemann, Lutz; Hompesch, Marcus

    2014-01-01

    Until now most of the insulin used in developed countries has been manufactured and distributed by a small number of multinational companies. Beyond the established insulin manufacturers, a number of new players have developed insulin manufacturing capacities based on modern biotechnological methods. Because the patents for many of the approved insulin formulations have expired or are going to expire soon, these not yet established companies are increasingly interested in seeking market approval for their insulin products as biosimilar insulins (BI) in highly regulated markets like the EU and the United States. Differences in the manufacturing process (none of the insulin manufacturing procedures are 100% identical) can lead to insulins that to some extent may differ from the originator insulin. The key questions are if subtle differences in the structure of the insulins, purity, and so on are clinically relevant and may result in different biological effects. The aim of this article is to introduce and discuss basic aspects that may be of relevance with regard to BI. © 2014 Diabetes Technology Society.

  20. Basal insulin: beyond glycemia.

    PubMed

    Niswender, Kevin D

    2011-07-01

    Insulin is a pleiotropic hormone with numerous effects at the cellular, tissue, and organismal levels. Clinicians are familiar with physiological effects of insulin on carbohydrate metabolism, including stimulation of glucose uptake in skeletal muscle and the suppression of glucose production from the liver. Other metabolic effects of insulin include inhibiting the release of free fatty acids from adipose tissue and stimulating the incorporation of amino acids into proteins. Indeed, every organ in the body, including the brain, is a target for insulin action. Insulin resistance, typically defined with respect to glucose metabolism, is a condition in which normal levels of insulin do not trigger the signal for glucose disposition. The effects of insulin resistance and impaired insulin signaling have profound pathophysiologic effects, such as hyperglycemia-induced tissue damage, hypertension, dyslipidemia, metabolic syndrome, and cardiovascular and renal disease. An integrated view of insulin action in all of these tissues may yield improved therapeutic insight and possibly even illuminate new therapeutic opportunities. With the increase in the number of patients diagnosed with prediabetes and diabetes, an updated understanding of the disease and the pharmacologic armamentarium used to treat it is needed to improve outcomes. To help expand the clinical care provider's perspective, this article will provide a provocative discussion about the pathophysiology of diabetes, the role of insulin and insulin resistance, and the clinical efficacy potential of insulin. Understanding the cellular and molecular mechanisms underlying the effects of insulin and how these translate into clinical consequences beyond glycemia will assist primary care physicians in the care of their patients with diabetes and metabolic syndrome.

  1. An unusual cause of delayed puberty: Berardinelli- Seip syndrome.

    PubMed

    Upreti, Vimal; Dhull, Pawan; Patnaik, Saroj Kumar; Kumar, K V S Hari

    2012-01-01

    Berardinelli- Seip syndrome is an autosomal recessive disorder characterized by generalized lipoatrophy, extreme insulin resistance with dyslipidemia in childhood and development of diabetes in adolescence. Menstrual irregularities are commonly seen as a result of secondary polycystic ovarian syndrome. Delayed puberty as a manifestation of these abnormalities in girls has rarely been described earlier. We report one such case patient who had delayed puberty and portal hypertension as unique features amongst the characteristic phenotypes of this syndrome.

  2. Computation of signal delays in RC networks

    NASA Technical Reports Server (NTRS)

    Hidalgo, Juan Carlos; Narendran, Paliath; Chaiken, Seth

    1993-01-01

    A model for signal delay computation in RC networks is presented. The strength of the paradigm is its generality and simplicity. The definition of delay is applicable to RC meshes with potential resistive attenuating paths to ground. The algorithms can also be applied to undriven circuits (static charge sharing) and circuits with initial charge. To compute the delays, each node in the network is explored locally to derive a system of sparse linear equations. The solutions of the system are delay values based on the Elmore time constant at each point in the circuit.

  3. Biosimilar Insulin and Costs

    PubMed Central

    Heinemann, Lutz

    2015-01-01

    The costs for insulin treatment are high, and the steady increase in the number of patients with diabetes on insulin presents a true challenge to health care systems. Therefore, all measures to lower these costs are welcomed by patients, physicians, and health care providers. The market introduction of biosimilar insulins presents an option to lower treatment costs as biosimilars are usually offered at a lower price than the originator product. However, the assumption that a drastic reduction in insulin prices will take place, as was observed with many generic drugs, is most probably not realistic. As the first biosimilar insulin has now been approved in the EU, this commentary discusses a number of aspects that are relevant when it comes to the potential cost reduction we will see with the use of biosimilar insulins. PMID:26350722

  4. Adipokines and insulin action

    PubMed Central

    Knights, Alexander J; Funnell, Alister PW; Pearson, Richard CM; Crossley, Merlin; Bell-Anderson, Kim S

    2014-01-01

    Obesity is a major public health concern and a strong risk factor for insulin resistance, type 2 diabetes mellitus (T2DM), and cardiovascular disease. The last two decades have seen a reconsideration of the role of white adipose tissue (WAT) in whole body metabolism and insulin action. Adipose tissue-derived cytokines and hormones, or adipokines, are likely mediators of metabolic function and dysfunction. While several adipokines have been associated with obese and insulin-resistant phenotypes, a select group has been linked with insulin sensitivity, namely leptin, adiponectin, and more recently, adipolin. What is known about these insulin-sensitizing molecules and their effects in healthy and insulin resistant states is the subject of this review. There remains a significant amount of research to do to fully elucidate the mechanisms of action of these adipokines for development of therapeutics in metabolic disease. PMID:24719781

  5. [Transdermal delivery of insulin].

    PubMed

    Sevast'ianov, V I; Salomatina, L A; Kuznetsova, E G; Iakovleva, N V; Shumakov, V I

    2003-01-01

    A possibility is studied of the transdermal delivery of insulin by using a mixture of synthetic analogues of phosphoglycerides (SAP), as a potential activator of hormone diffusion, through the skin. Experimentally in vitro, it was proven that the diffusion of insulin through the skin of two types of transdermal therapeutic form (TTF)--matrix-type and matrix-hydrogel-type--is possible only in presence of activator SAP-M-99. The detected optimal composition of insulin matrix TTF with the area of 40 sq cm enabled a trandermal hormone diffusion speed of 0.26 UNITS/h, which is compatible with the secretion of insulin by the pancreas of an adult (0.25-1.5 UNITS/h). A change-over for the matrix-hydrogel system of insulin delivery based on a 40 sq cm collagenous sponge enabled to increase the insulin diffusion up to 0.54 UNITS/h.

  6. Evidence-based clinical use of insulin premixtures

    PubMed Central

    2013-01-01

    Brazil is expected to have 19.6 million patients with diabetes by the year 2030. A key concept in the treatment of type 2 diabetes mellitus (T2DM) is establishing individualized glycemic goals based on each patient’s clinical characteristics, which impact the choice of antihyperglycemic therapy. Targets for glycemic control, including fasting blood glucose, postprandial blood glucose, and glycated hemoglobin (A1C), are often not reached solely with antihyperglycemic therapy, and insulin therapy is often required. Basal insulin is considered an initial strategy; however, premixed insulins are convenient and are equally or more effective, especially for patients who require both basal and prandial control but desire a more simplified strategy involving fewer daily injections than a basal-bolus regimen. Most physicians are reluctant to transition patients to insulin treatment due to inappropriate assumptions and insufficient information. We conducted a nonsystematic review in PubMed and identified the most relevant and recently published articles that compared the use of premixed insulin versus basal insulin analogues used alone or in combination with rapid-acting insulin analogues before meals in patients with T2DM. These studies suggest that premixed insulin analogues are equally or more effective in reducing A1C compared to basal insulin analogues alone in spite of the small increase in the risk of nonsevere hypoglycemic events and nonclinically significant weight gain. Premixed insulin analogues can be used in insulin-naïve patients, in patients already on basal insulin therapy, and those using basal-bolus therapy who are noncompliant with blood glucose self-monitoring and titration of multiple insulin doses. We additionally provide practical aspects related to titration for the specific premixed insulin analogue formulations commercially available in Brazil. PMID:24011173

  7. Tea enhances insulin activity.

    PubMed

    Anderson, Richard A; Polansky, Marilyn M

    2002-11-20

    The most widely known health benefits of tea relate to the polyphenols as the principal active ingredients in protection against oxidative damage and in antibacterial, antiviral, anticarcinogenic, and antimutagenic activities, but polyphenols in tea may also increase insulin activity. The objective of this study was to determine the insulin-enhancing properties of tea and its components. Tea, as normally consumed, was shown to increase insulin activity >15-fold in vitro in an epididymal fat cell assay. Black, green, and oolong teas but not herbal teas, which are not teas in the traditional sense because they do not contain leaves of Camellia senensis, were all shown to increase insulin activity. High-performance liquid chromatography fractionation of tea extracts utilizing a Waters SymmetryPrep C18 column showed that the majority of the insulin-potentiating activity for green and oolong teas was due to epigallocatechin gallate. For black tea, the activity was present in several regions of the chromatogram corresponding to, in addition to epigallocatechin gallate, tannins, theaflavins, and other undefined compounds. Several known compounds found in tea were shown to enhance insulin with the greatest activity due to epigallocatechin gallate followed by epicatechin gallate, tannins, and theaflavins. Caffeine, catechin, and epicatechin displayed insignificant insulin-enhancing activities. Addition of lemon to the tea did not affect the insulin-potentiating activity. Addition of 5 g of 2% milk per cup decreased the insulin-potentiating activity one-third, and addition of 50 g of milk per cup decreased the insulin-potentiating activity approximately 90%. Nondairy creamers and soy milk also decreased the insulin-enhancing activity. These data demonstrate that tea contains in vitro insulin-enhancing activity and the predominant active ingredient is epigallocatechin gallate.

  8. Insulin resistance and atherosclerosis

    PubMed Central

    Semenkovich, Clay F.

    2006-01-01

    Considerable evidence supports the association between insulin resistance and vascular disease, and this has led to wide acceptance of the clustering of hyperlipidemia, glucose intolerance, hypertension, and obesity as a clinical entity, the metabolic syndrome. While insulin resistance, by promoting dyslipidemia and other metabolic abnormalities, is part of the proatherogenic milieu, it is possible that insulin resistance itself in the vascular wall does not promote atherosclerosis. Recent findings suggest that insulin resistance and atherosclerosis could represent independent and ultimately maladaptive responses to the disruption of cellular homeostasis caused by the excess delivery of fuel. PMID:16823479

  9. Insulin, cognition, and dementia

    PubMed Central

    Cholerton, Brenna; Baker, Laura D.; Craft, Suzanne

    2015-01-01

    Cognitive disorders of aging represent a serious threat to the social and economic welfare of current society. It is now widely recognized that pathology related to such conditions, particularly Alzheimer’s disease, likely begins years or decades prior to the onset of clinical dementia symptoms. This revelation has led researchers to consider candidate mechanisms precipitating the cascade of neuropathological events that eventually lead to clinical Alzheimer’s disease. Insulin, a hormone with potent effects in the brain, has recently received a great deal of attention for its potential beneficial and protective role in cognitive function. Insulin resistance, which refers to the reduced sensitivity of target tissues to the favorable effects of insulin, is related to multiple chronic conditions known to impact cognition and increase dementia risk. With insulin resistance-associated conditions reaching epidemic proportions, the prevalence of Alzheimer’s disease and other cognitive disorders will continue to rise exponentially. Fortunately, these chronic insulin-related conditions are amenable to pharmacological intervention. As a result, novel therapeutic strategies that focus on increasing insulin sensitivity in the brain may be an important target for protecting or treating cognitive decline. The following review will highlight our current understanding of the role of insulin in brain, potential mechanisms underlying the link between insulin resistance and dementia, and current experimental therapeutic strategies aimed at improving cognitive function via modifying the brain’s insulin sensitivity. PMID:24070815

  10. Insulin depot formation in subcutaneoue tissue.

    PubMed

    Jockel, James P Leuenberger; Roebrock, Philipp; Shergold, Oliver A

    2013-01-01

    The size and geometry of an insulin depot that is formed during subcutaneous administration by an insulin pump is evaluated. A novel method is used to visualize accurately the depot formation for small volumes of insulin (of the order of 10-100 µl) at a given point in time. Conventional visualization methods such as magnetic resonance imaging are unable to provide such accurate measurements because of their coarse imaging resolution and long measurement time. The described method consists of subcutaneously infusing dyed insulin into porcine tissue and subsequently shock freezing it with liquid nitrogen. The frozen sample is then sliced into thin layers using a cryomicrotome. A digital image of each layer is taken and then processed with proprietary software, which identifies the dyed areas on each layer and reconstructs a three-dimensional model of the insulin depot with a planar resolution of 30 × 30 µm(2) and a depth resolution of 100 µm. Since this process is not viable for living organisms, porcine tissue was used immediately following slaughter of the animal. To date, it is most often assumed that the insulin depot takes the shape of a sphere around the tip of the cannula (e.g., 50 µl insulin equates to a spherical radius of 2.3 mm). However, in practice, such a depot form is never observed. Instead, the insulin depot initially spreads laterally (i.e., parallel) to the skin surface and in the collagen matrix that binds the adipose cells together. The depot outreach increases with larger infused volumes, e.g., maximum outreach measured at 5.0/5.7/7.1 mm (quartiles, n = 17) for 50 µl of infused insulin. Beyond a given infused volume (approximately 100 µl), the insulin also starts to spread perpendicular to the skin surface. It is concluded that formation of the insulin depot depends on the opening of channels at the boundaries between adipose cells. Hence the insulin follows a path of least resistance and depot formation is determined by the local

  11. Insight into Insulin Secretion from Transcriptome and Genetic Analysis of Insulin-Producing Cells of Drosophila

    PubMed Central

    Cao, Jian; Ni, Julie; Ma, Wenxiu; Shiu, Vanessa; Milla, Luis A.; Park, Sangbin; Spletter, Maria L.; Tang, Sheng; Zhang, Jun; Wei, Xing; Kim, Seung K.; Scott, Matthew P.

    2014-01-01

    Insulin-producing cells (IPCs) in the Drosophila brain produce and release insulin-like peptides (ILPs) to the hemolymph. ILPs are crucial for growth and regulation of metabolic activity in flies, functions analogous to those of mammalian insulin and insulin-like growth factors (IGFs). To identify components functioning in IPCs to control ILP production, we employed genomic and candidate gene approaches. We used laser microdissection and messenger RNA sequencing to characterize the transcriptome of larval IPCs. IPCs highly express many genes homologous to genes active in insulin-producing β-cells of the mammalian pancreas. The genes in common encode ILPs and proteins that control insulin metabolism, storage, secretion, β-cell proliferation, and some not previously linked to insulin production or β-cell function. Among these novelties is unc-104, a kinesin 3 family gene, which is more highly expressed in IPCs compared to most other neurons. Knockdown of unc-104 in IPCs impaired ILP secretion and reduced peripheral insulin signaling. Unc-104 appears to transport ILPs along axons. As a complementary approach, we tested dominant-negative Rab genes to find Rab proteins required in IPCs for ILP production or secretion. Rab1 was identified as crucial for ILP trafficking in IPCs. Inhibition of Rab1 in IPCs increased circulating sugar levels, delayed development, and lowered weight and body size. Immunofluorescence labeling of Rab1 showed its tight association with ILP2 in the Golgi of IPCs. Unc-104 and Rab1 join other proteins required for ILP transport in IPCs. PMID:24558258

  12. RESPONSE ACQUISITION BY HUMANS WITH DELAYED REINFORCEMENT

    PubMed Central

    Okouchi, Hiroto

    2009-01-01

    The present experiment examined whether a response class was acquired by humans with delayed reinforcement. Eight white circles were presented on a computer touch screen. If the undergraduates touched two of the eight circles in a specified sequence (i.e., touching first the upper-left circle then the bottom-left circle), then the touches initiated an unsignaled resetting delay culminating in point delivery. Participants experienced one of three different delays (0 s, 10 s, or 30 s). Rates of the target two-response sequence were higher with delayed reinforcement than with no reinforcement. Terminal rates of the target sequence decreased and postreinforcement pauses increased as a function of delay duration. Other undergraduates exposed to yoked schedules of response-independent point deliveries failed to acquire the sequence. The results demonstrate that a response class was acquired with delayed reinforcement, extending the generality of this phenomenon found with nonhuman animals to humans. PMID:19949494

  13. Delay banking for air traffic management

    NASA Technical Reports Server (NTRS)

    Green, Steven M. (Inventor)

    2007-01-01

    A method and associated system for time delay banking for aircraft arrival time, aircraft departure time and/or en route flight position. The delay credit value for a given flight may decrease with passage of time and may be transferred to or traded with other flights having the same or a different user (airline owner or operator). The delay credit value for a given aircraft flight depends upon an initial delay credit value, which is determined by a central system and depends upon one or more other flight characteristics. Optionally, the delay credit value decreases with passage of time. Optionally, a transaction cost is assessed against a delay credit value that is used on behalf of another flight with the same user or is traded with a different user.

  14. Toll-like receptor 2 deficiency improves insulin sensitivity and hepatic insulin signalling in the mouse.

    PubMed

    Kuo, L-H; Tsai, P-J; Jiang, M-J; Chuang, Y-L; Yu, L; Lai, K-T A; Tsai, Y-S

    2011-01-01

    Substantial evidence suggests a link between elevated inflammation and development of insulin resistance. Toll-like receptor 2 (TLR2) recognises a large number of lipid-containing molecules and transduces inflammatory signalling in a variety of cell types, including insulin-responsive cells. Considering the contribution of the fatty acid composition in TLR2-depedent signalling, we hypothesised that the inflammatory signals transduced by TLR2 contribute to insulin resistance. Mice deficient in TLR2 were used to investigate the in vivo roles of TLR2 in initiating and maintaining inflammation-associated insulin resistance and energy homeostasis. We first recapitulated the observation with elevated expression of TLR2 and inflammatory cytokines in white adipose tissue and liver of ob/ob mice. Aged or high-fat-fed TLR2-deficient mice were protected from obesity and adipocyte hypertrophy compared with wild-type mice. Moreover, mice lacking TLR2 exhibited improved glucose tolerance and insulin sensitivity regardless of feeding them regular chow or a high-fat diet. This is accompanied by reductions in expression of inflammatory cytokines and activation of extracellular signal-regulated kinase (ERK) in a liver-specific manner. The attenuated hepatic inflammatory cytokine expression and related signalling are correlated with increased insulin action specifically in the liver in TLR2-deficient mice, reflected by increased insulin-stimulated protein kinase B (Akt) phosphorylation and IRS1 tyrosine phosphorylation and increased insulin-suppressed hepatocyte glucose production. The absence of TLR2 attenuates local inflammatory cytokine expression and related signalling and increases insulin action specifically in the liver. Thus, our work has identified TLR2 as a key mediator of hepatic inflammation-related signalling and insulin resistance.

  15. Early identification of motor delay

    PubMed Central

    Harris, Susan R.

    2016-01-01

    Objective To describe the Harris Infant Neuromotor Test (HINT), an infant neuromotor test using Canadian norms published in 2010 that could be used to screen for motor delay during the first year of life. Quality of evidence Extensive research has been published on the intrarater, interrater, and test-retest reliability and the content, concurrent, predictive, and known-groups validity of the HINT, as well as on the sensitivity, specificity, and positive and negative predictive values of parental concerns, as assessed by the HINT. Most evidence is level II. Main message Diagnosing motor delays during the first year of life is important because these often indicate more generalized developmental delays or specific disabilities, such as cerebral palsy. Parental concerns about their children’s motor development are strongly predictive of subsequent diagnoses involving motor delay. Conclusion Only through early identification of developmental motor delays, initially with screening tools such as the HINT, is it possible to provide referrals for early intervention that could benefit both the infant and the family. PMID:27521388

  16. ERAD-icating mutant insulin promotes functional insulin secretion.

    PubMed

    Moore, Daniel J

    2017-01-18

    Overexpression of a chaperone protein liberates functional insulin from a misfolded mutant partner to improve insulin secretion. Copyright © 2017, American Association for the Advancement of Science.

  17. Insulin access to skeletal muscle is impaired during the early stages of diet-induced obesity.

    PubMed

    Broussard, Josiane L; Castro, Ana V B; Iyer, Malini; Paszkiewicz, Rebecca L; Bediako, Isaac Asare; Szczepaniak, Lidia S; Szczepaniak, Edward W; Bergman, Richard N; Kolka, Cathryn M

    2016-09-01

    Insulin must move from the blood to the interstitium to initiate signaling, yet access to the interstitium may be impaired in cases of insulin resistance, such as obesity. This study investigated whether consuming a short- and long-term high-fat diet (HFD) impairs insulin access to skeletal muscle, the major site of insulin-mediated glucose uptake. Male mongrel dogs were divided into three groups consisting of control diet (n = 16), short-term (n = 8), and long-term HFD (n = 8). Insulin sensitivity was measured with intravenous glucose tolerance tests. A hyperinsulinemic euglycemic clamp was performed in each animal at the conclusion of the study. During the clamp, lymph fluid was measured as a representation of the interstitial space to assess insulin access to muscle. Short- and long-term HFD induced obesity and reduced insulin sensitivity. Lymph insulin concentrations were approximately 50% of plasma insulin concentrations under control conditions. Long-term HFD caused fasting plasma hyperinsulinemia; however, interstitial insulin concentrations were not increased, suggesting impaired insulin access to muscle. A HFD rapidly induces insulin resistance at the muscle and impairs insulin access under basal insulin concentrations. Hyperinsulinemia induced by a long-term HFD may be a compensatory mechanism necessary to maintain healthy insulin levels in muscle interstitium. © 2016 The Obesity Society.

  18. Human insulin microcrystals with lactose carriers for pulmonary delivery.

    PubMed

    Lim, Se-Hwan; Park, Hye Won; Shin, Chang-Hoon; Kwon, Jai-Hyun; Kim, Chan-Wha

    2009-12-01

    Dry powder formulations for pulmonary delivery are attractive because many issues of solubility and stability can be minimized. Human insulin microcrystals with lactose carriers were produced for pulmonary delivery. The average particle diameter was 2.3 microm, with a narrow, monodispersed size distribution. The percentages of high molecular weight proteins (%HMWPs), other insulin-related compounds (%OIRCs), and A-21 desamido insulin (%D(es)) were very low throughout the microcrystal preparation process. Administration of the microcrystal powder by intratracheal insufflation significantly reduced the blood glucose levels of Sprague-Dawley rats. The percent minimum reductions of the blood glucose concentration (%MRBG) produced by the insulin microcrystal powder and by an insulin solution reached 40.4% and 33.4% of the initial glucose levels respectively, and their bioavailability relative to subcutaneous injection (F) was 15% and 10% respectively. These results confirm that the insulin microcrystal powder prepared is suitable for pulmonary delivery in an effective dosage form.

  19. Protein Crystal Bovine Insulin

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The comparison of protein crystal, Bovine Insulin space-grown (left) and earth-grown (right). Facilitates the incorporation of glucose into cells. In diabetics, there is either a decrease in or complete lack of insulin, thereby leading to several harmful complications. Principal Investigator is Larry DeLucas.

  20. [Hypersensitivity reactions to insulin].

    PubMed

    Becerril-Ángeles, Martín; Moctezuma-Trejo, Cristina; Espinosa-Larrañaga, Francisco

    2012-01-01

    Hypersensitivity reactions to insulin are infrequent, yet of clinical importance. The mechanisms of hypersensitivity involved can be of three types: I, III and IV. To describe the pathophysiology of hypersensitivity to insulin, its clinical features and diagnostic and therapeutic approach, that help identify the cases of allergy to insulin and begin a treatment, or if necessary, to refer patients to a specialists or appropriate medical attention. An electronic search of papers related to insulin hypersensitivity was performed in PubMed and the articles selected were those considered the most relevant for this review. Thirty eight papers about pathophysiology, mechanisms of injury and the different types of insulin involved in hypersensitivity reactions were included. Likewise, information for the diagnosis of insulin hypersensitivity and some options of treatment for first contact physicians or the referral of patients to specialists in endocrinology and allergy were included. Insulin hypersensitivity has a low prevalence and diverse clinical manifestations. The different types of insulin suitable allow the majority of cases of hypersensitivity to continue the treatment in a efficient and flexible manner.

  1. Protein Crystal Bovine Insulin

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The comparison of protein crystal, Bovine Insulin space-grown (left) and earth-grown (right). Facilitates the incorporation of glucose into cells. In diabetics, there is either a decrease in or complete lack of insulin, thereby leading to several harmful complications. Principal Investigator is Larry DeLucas.

  2. Therapeutics of Diabetes Mellitus: Focus on Insulin Analogues and Insulin Pumps

    PubMed Central

    Valla, Vasiliki

    2010-01-01

    Aim. 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. Results. 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. Conclusions. 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. PMID:20589066

  3. Comparison of the post-meal glucose response to different insulin bolus waveforms in insulin pump- and pre-meal pramlintide-treated type 1 diabetes patients.

    PubMed

    King, Allen B

    2010-02-01

    Both pramlintide and insulin pump waveforms separately provide improved post-meal glucose control. However, when used together there may be a mismatch in actions leading to hypoglycemia. We studied the three currently available waveforms and a "modified combination wave" (MC) in pramlintide-treated patients. The MC was a "square" (SQ) wave combined with a "standard" (ST) bolus that was delayed 1 h into the mealtime. Using the CGMS Gold (Medtronics, Northridge, CA) we measured the glucose response 0-4 h after the beginning of a meal and 15 min after the initiation of the insulin bolus wave and pramlintide (60 microg), bolus. Pump-treated type 1 diabetes subjects were randomized to one bolus waveform for one full day of three meals and then crossed over to the other bolus waveforms. In the first study nine subjects were randomized to the ST, SQ, or "combination" (C) wave consisting of a ST wave at the beginning of a SQ wave. In the second study nine subjects were randomized to SQ or MC. With ST and C waves glucose fell approximately 40 mg/dL 0-2 h post-meal and then returned to baseline by the fourth hour. Initially isoglycemic, the SQ wave increased approximately 20 mg/dL in the late meal period. The MC demonstrated minimal (approximately 10 mg/dL) change during the entire post-meal period. For currently available insulin pump bolus waves, SQ and MC may be least likely to cause hypoglycemia in pramlintide-treated patients.

  4. Determinants of weight change in patients on basal insulin treatment: an analysis of the DIVE registry

    PubMed Central

    Bramlage, Peter; Bluhmki, Tobias; Fleischmann, Holger; Kaltheuner, Matthias; Beyersmann, Jan; Holl, Reinhard W; Danne, Thomas

    2017-01-01

    Objective We aimed to describe patterns of weight change in insulin-naive patients with type 2 diabetes mellitus (T2DM) starting basal insulin (BI) treatment. Research design and methods Diabetes Versorgungs-Evaluation (DIVE) is an observational, multicenter, prospective registry in patients with T2DM. Patients were divided into those initiating BI therapy for the first time (with optional oral antidiabetic drugs (OADs)) and those initiating OADs only (OADo). Results 521 patients were included in the analysis, 113 in the BI arm and 408 in the OADo arm. Relative to baseline, the BI group gained an average of 0.98±7.1 kg at 1 year, compared with a loss of 1.52±11.8 kg in the OADo group (p<0.001). This difference remained statistically significant when expressed as a proportional change from baseline (+0.014±0.08 vs −0.015±0.12, respectively (p<0.001)). Baseline weight (regression coefficient (RC) 0.89; 95% CI 0.81 to 0.97; p<0.001) and diabetes duration (RC 2.52; 95% CI 0.53 to 4.52; p=0.01) were the only factors identified as significant predictors of weight gain between baseline and 1 year follow-up in BI patients. Conclusions Though BI therapy leads to modest weight gain over the subsequent year, this may be limited by BI initiation at an early stage of the disease. As such, delaying the start of insulin therapy based on fears of weight gain appears counter-productive, and should be reconsidered. PMID:28176957

  5. Delayed puberty in girls

    MedlinePlus

    ... hormones. These changes normally begin to appear in girls between ages 8 to 14 years old. With delayed puberty, these changes either don't occur, or if they do, they don't progress normally. Delayed puberty is more common in boys than in girls. Causes In most cases of delayed puberty, growth ...

  6. The Effects of Delay of Feedback on a Delayed Concept Formation Transfer Task.

    ERIC Educational Resources Information Center

    Schroth, Marvin L.

    1992-01-01

    Delay and completeness of verbal information feedback were investigated within a transfer of learning paradigm involving concept formation. An experiment with 192 undergraduates indicates that, although delay of feedback (up to 30 seconds) slows speed of learning on the initial task, it has positive effects on the transfer task. (SLD)

  7. Implementing a pharmacist consultation model for multimodal insulin therapy.

    PubMed

    Hodges, Angela; Hall, James; Castellanos, Esther; Laue, Edward; Ellis, Tammy; Oelschlaeger, LaDonna

    2017-05-01

    The implementation of pharmacist-managed insulin dosing for selected hospitalized patients under a multimodal insulin protocol (MMIP) is described. Hyperglycemia has been linked to increased thrombosis, decreased wound healing, and decreased immune response. Current recommendations support the use of multimodal (basal-bolus) insulin therapy in noncritically ill inpatients. As part of a systemwide quality-improvement initiative to improve glycemic management, the pharmacy department of a community hospital initiated a service to provide protocol-directed insulin dosing for selected patients under a pharmacist consultation model. An MMIP targeting patients with 2 blood glucose (BG) readings of >180 mg/dL within a 12-hour period was developed and approved. Pharmacist consultations, including patient assessment, entry of initial insulin orders, and ongoing insulin dosage adjustments, are performed pursuant to electronic notifications and computerized prescriber order entry. Noncritically ill patients who meet the criteria for protocol-guided insulin dosing are managed according to an approved weight-based MMIP for calculating and adjusting nutritional and basal insulin doses. Prior to the initiation of MMIP-guided insulin dosing, pharmacists were trained on the use of the protocol and passed a competency assessment. In the 90-day period after protocol implementation, 158 hyperglycemic patients received pharmacist-managed insulin dosing. The goal of achieving a mean BG concentration of ≤180 mg/dL by day 3 of hyperglycemia management under a pharmacist-managed MMIP was attained in the second and third months after protocol implementation. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  8. Reassessment of insulin dosing guidelines in continuous subcutaneous insulin infusion treated type 1 diabetes.

    PubMed

    King, Allen Bennett

    2014-06-01

    It is a daunting task to initiate or evaluate continuous subcutaneous insulin infusion, pump, dosing in a patient with type 1 diabetes. Choosing a low dose may lead to hyperglycemia or, too high, hypoglycemia. Mathematical dosing guidelines were used with the first human insulin injection in 1922. Since that time, they have been enlarged and modified. The current widely published guidelines were developed from retrospective evaluations of pump-downloads in patients without specified diet conditions or timed glucose testing. When diet is controlled and glucose testing is timed to evaluate post-meal excursions and during sleep, recent prospective studies found that these current dosing recommendations for basal insulin were too high and for bolus insulin too low. Further, simple mathematical interrelationships were published that kept the right proportions between the bolus dosing factors and the basal dose.

  9. Tagging insulin in microgravity

    NASA Technical Reports Server (NTRS)

    Dobeck, Michael; Nelson, Ronald S.

    1992-01-01

    Knowing the exact subcellular sites of action of insulin in the body has the potential to give basic science investigators a basis from which a cause and cure for this disease can be approached. The goal of this project is to create a test reagent that can be used to visualize these subcellular sites. The unique microgravity environment of the Shuttle will allow the creation of a reagent that has the possibility of elucidating the subcellular sites of action of insulin. Several techniques have been used in an attempt to isolate the sites of action of items such as insulin. One of these is autoradiography in which the test item is obtained from animals fed radioactive materials. What is clearly needed is to visualize individual insulin molecules at their sites of action. The insulin tagging process to be used on G-399 involves the conjugation of insulin molecules with ferritin molecules to create a reagent that will be used back on Earth in an attempt to elucidate the sites of action of insulin.

  10. Etiopathogenesis of Insulin Autoimmunity

    PubMed Central

    Kanatsuna, Norio; Papadopoulos, George K.; Moustakas, Antonis K.; Lenmark, Åke

    2012-01-01

    Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (pro)insulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and -DQ8 is reviewed and illustrated by molecular modeling. The importance of the cellular immune reaction involving cytotoxic CD8-positive T cells to kill beta cells through Class I MHC is discussed along with speculations of the possible role of B lymphocytes in presenting the proinsulin autoantigen over and over again through insulin-carrying insulin autoantibodies. In contrast to autoantibodies against other islet autoantigens such as GAD65, IA-2, and ZnT8 transporters, it has not been possible yet to standardize the insulin autoantibody test. As islet autoantibodies predict type 1 diabetes, it is imperative to clarify the mechanisms of insulin autoimmunity. PMID:22567309

  11. Drosophila insulin degrading enzyme and rat skeletal muscle insulin protease cleave insulin at similar sites

    SciTech Connect

    Duckworth, W.C.; Garcia, J.V.; Liepnieks, J.J.; Hamel, F.G.; Hermodson, M.A.; Frank, B.H.; Rosner, M.R. )

    1989-03-21

    Insulin degradation is an integral part of the cellular action of insulin. Recent evidence suggests that the enzyme insulin protease is involved in the degradation of insulin in mammalian tissues. Drosophila, which has insulin-like hormones and insulin receptor homologues, also expresses an insulin degrading enzyme with properties that are very similar to those of mammalian insulin protease. In the present study, the insulin cleavage products generated by the Drosophila insulin degrading enzyme were identified and compared with the products generated by the mammalian insulin protease. Both purified enzymes were incubated with porcine insulin specifically labeled with {sup 125}I on either the A19 or B26 position, and the degradation products were analyzed by HPLC before and after sulfitolysis. Isolation and sequencing of the cleavage products indicated that both enzymes cleave the A chain of intact insulin at identical sites between residues A13 and A14 and A14 and A15. These results demonstrate that all the insulin cleavage sites generated by the Drosopohila insulin degrading enzyme are shared in common with the mammalian insulin protease. These data support the hypothesis that there is evolutionary conservation of the insulin degrading enzyme and further suggest that this enzyme plays an important role in cellular function.

  12. Algorithms for intravenous insulin delivery.

    PubMed

    Braithwaite, Susan S; Clement, Stephen

    2008-08-01

    establish freedom from hypoglycemia, eliminate the need for administration of concentrated dextrose during euglycemia, control variability within the treatment course of individual patients, achieve adaptability to differing blood glucose targets, and minimize variability of glycemic control between treatment courses of different patients or patient populations. Areas for future work include the reduction of nursing burden, the development of a theory that will account for lag time of interstitial monitoring and pharmacodynamic delay of insulin action, and management strategies for the narrow euglycemic range. It is hoped that hypoglycemia and variability of control will become negligible problems, and that fear of hypoglycemia no longer will deflect investigators and caregivers from providing optimal glycemic management.

  13. Infliximab and insulin resistance.

    PubMed

    Ursini, Francesco; Naty, Saverio; Grembiale, Rosa Daniela

    2010-06-01

    Insulin resistance is the most important pathophysiologic feature of obesity, type 2 diabetes mellitus and prediabetic states. TNF-alpha, a proinflammatory cytokine, plays a pivotal role in the pathogenesis of inflammation-associated insulin resistance during the course of rheumatic diseases. Therapies aimed at neutralizing TNF-alpha, such as the monoclonal antibody infliximab, represent a novel approach for the treatment of rheumatic diseases and allow to obtain significant results in terms of control of the inflammatory process. In this article we reviewed the scientific evidence published in the literature about a potential role of TNF-alpha blockade in improving insulin resistance in non-diabetic rheumatic patients.

  14. Insulin adherence and persistence among Chinese patients with type 2 diabetes: a retrospective database analysis

    PubMed Central

    He, Xiaoning; Chen, Liming; Wang, Ke; Wu, Haiya; Wu, Jing

    2017-01-01

    Objective To assess adherence and persistence to insulin therapy and identify its associated factors among Chinese insulin-naïve patients with type 2 diabetes (T2D). Methods Tianjin Urban Employee Basic Medical Insurance claims database was used (2008–2011). Adult patients with T2D who initiated insulin therapy during January 2009 through December 2010 and were continuously enrolled for 12 months pre-(baseline) and 12 months post-initiation (follow-up) were included. Patients who had a ≥80% medication possession ratio were deemed adherent, while patients who had no gaps of ≥90 days in insulin therapy were deemed persistent. Associated factors of insulin adherence and persistence were detected by univariate and multivariate analyses. Results A total of 24,192 patients were included; the patients had a mean age of 58.9 years, with 49.5% being female. About 51.9% of the patients had human insulin as initiation therapy, while 39.1% were initiated with insulin analog and 9.0% with animal-derived insulin. Premixed insulin (77.3%) was prescribed most often in comparison with basal (11.8%) and prandial (10.9%) insulin. Only 30.9% of patients were adherent, and the mean (standard deviation) medication possession ratio was 0.499 (0.361). About 53.0% of patients persisted insulin therapy during follow-up, and the mean time to nonpersistence was 230.3 (145.5) days. Patients initiated with analog were more likely to be adherent (adjusted odds ratio: 1.07, P=0.036) and persistent (adjusted hazard ratio: 0.88, P<0.001) compared with those initiated with human insulin. Patients initiation with basal insulin had lower adherence relative to premixed (adjusted odds ratio: 0.79, P<0.001). Patients comorbid with hypertension or dyslipidemia, initiated with prandial insulin, and with baseline severe hypoglycemic events were more likely to be nonadherent/nonpersistent. Conclusion The insulin adherence and persistence among Chinese patients with T2D are generally poor. Initiation

  15. Insulin action and insulin resistance in vascular endothelium.

    PubMed

    Muniyappa, Ranganath; Quon, Michael J

    2007-07-01

    Vasodilator actions of insulin are mediated by phosphatidylinositol 3-kinase dependent insulin signaling pathways in endothelium, which stimulate production of nitric oxide. Insulin-stimulated nitric oxide mediates capillary recruitment, vasodilation, increased blood flow, and subsequent augmentation of glucose disposal in skeletal muscle. Distinct mitogen-activated protein kinase dependent insulin signaling pathways regulate secretion of the vasoconstrictor endothelin-1 from endothelium. These vascular actions of insulin contribute to the coupling of metabolic and hemodynamic homeostasis that occurs under healthy conditions. Insulin resistance is characterized by pathway-specific impairment in phosphatidylinositol 3-kinase dependent signaling in both metabolic and vascular insulin target tissues. Here we discuss consequences of pathway-specific insulin resistance in endothelium and therapeutic interventions targeting this selective impairment. Shared causal factors such as glucotoxicity, lipotoxicity, and inflammation selectively impair phosphatidylinositol 3-kinase dependent insulin signaling pathways, creating reciprocal relationships between insulin resistance and endothelial dysfunction. Diet, exercise, cardiovascular drugs, and insulin sensitizers simultaneously modulate phosphatidylinositol 3-kinase and mitogen-activated protein kinase dependent pathways, improving metabolic and vascular actions of insulin. Pathway-specific impairment in insulin action contributes to reciprocal relationships between endothelial dysfunction and insulin resistance, fostering clustering of metabolic and cardiovascular diseases in insulin-resistant states. Therapeutic interventions that target this selective impairment often simultaneously improve both metabolic and vascular function.

  16. Delay in diagnosis: the experience in Denmark

    PubMed Central

    Olesen, F; Hansen, R P; Vedsted, P

    2009-01-01

    Background: Denmark has poorer 5-year survival rates than many other Western European countries, and cancer patients tend to have more advanced stages at diagnosis than those in other Scandinavian countries. Part of this may be due to delay in diagnosis. The aim of this paper is to give an overview of the initiatives currently underway to reduce delays. Methods: Description of Danish actions to reduce delay. Results: Results of surveys of patient-, doctor- and system-related delays are presented and so are the political initiatives to ensure that cancer is seen as an acute disease. Conclusion: In future, fast-track diagnosis and treatment will be provided for suspected cancers and access to general diagnostic investigations will be improved. A large national experiment with cancer seen as an acute disease is currently being implemented, and as yet the results are unknown. PMID:19956163

  17. Characteristics of basal insulin requirements by age and gender in Type-1 diabetes patients using insulin pump therapy.

    PubMed

    Scheiner, Gary; Boyer, Bret A

    2005-07-01

    Establishment of appropriate basal insulin levels is an essential component of intensive insulin therapy. While the existence of a "dawn phenomenon" is widely recognized, the present study sought to establish whether diurnal basal insulin patterns exist in Type-1 diabetes, and whether these patterns vary by age and gender. Participant data was drawn from 322 Type-1 insulin pump users treated at a private diabetes education practice in suburban Philadelphia. All participants completed a battery of fasting tests designed to match basal insulin levels to endogenous glucose production and insulin sensitivity. Analysis of resultant basal patterns revealed significant differences between juvenile (age < or =20) and adult (age >20) basal insulin patterns. The younger group exhibited a more pronounced and sustained night-time peak; the older group exhibiting a briefer and less pronounced early-morning peak. Lower overall basal insulin requirements were found in the youngest (age < or =10) and oldest (age >60) groups. No noteworthy gender differences were found. Results can serve as a guide for clinicians when initiating and fine-tuning patients who utilize basal/bolus insulin therapy.

  18. Real-world insulin treatment persistence among patients with type 2 diabetes.

    PubMed

    Wei, Wenhui; Pan, Chunshen; Xie, Lin; Baser, Onur

    2014-01-01

    To evaluate real-world treatment persistence among patients with type 2 diabetes mellitus (T2DM) initiating treatment with insulin. Patient-level data were pooled from 3 previously published observational retrospective studies evaluating patients with T2DM who were previously on oral antidiabetic drugs (OADs) and initiated with a basal analog insulin (insulin glargine or insulin detemir). Treatment persistence was defined as remaining on the study drug during the 1-year follow-up period without discontinuation or switching after study drug initiation. Analyses were conducted to identify baseline factors associated with persistence with insulin therapy and to estimate the association between insulin treatment persistence and patients' clinical and economic outcomes during the follow-up period. A total of 4,804 patients with T2DM (insulin glargine: n = 4,172, insulin detemir: n = 632) were included. The average insulin persistence rate over the 1-year follow-up period was 65.0%. A significantly higher persistence rate was associated with older age, initiation with insulin glargine using either disposable pens or vial-and-syringe, and with baseline exenatide or sitagliptin use. Higher insulin treatment persistence was also associated with lower hemoglobin A1c (A1C) at follow-up, a greater reduction in A1C from baseline, and lower health care utilization. In real-world settings, treatment persistence among patients with T2DM initiating basal insulin is influenced by the type of insulin and patient factors. Greater insulin treatment persistence is linked to improved clinical outcomes and reduced health care utilization.

  19. Insulin Lispro Injection

    MedlinePlus

    ... a solution (liquid) and a suspension (liquid with particles that will settle on standing) to inject subcutaneously ( ... if it is colored, cloudy, or contains solid particles. If you are using insulin lispro suspension, the ...

  20. Insulin and insulin signaling play a critical role in fat induction of insulin resistance in mouse

    PubMed Central

    Ning, Jie; Hong, Tao; Yang, Xuefeng; Mei, Shuang; Liu, Zhenqi; Liu, Hui-Yu

    2011-01-01

    The primary player that induces insulin resistance has not been established. Here, we studied whether or not fat can cause insulin resistance in the presence of insulin deficiency. Our results showed that high-fat diet (HFD) induced insulin resistance in C57BL/6 (B6) mice. The HFD-induced insulin resistance was prevented largely by the streptozotocin (STZ)-induced moderate insulin deficiency. The STZ-induced insulin deficiency prevented the HFD-induced ectopic fat accumulation and oxidative stress in liver and gastrocnemius. The STZ-induced insulin deficiency prevented the HFD- or insulin-induced increase in hepatic expression of long-chain acyl-CoA synthetases (ACSL), which are necessary for fatty acid activation. HFD increased mitochondrial contents of long-chain acyl-CoAs, whereas it decreased mitochondrial ADP/ATP ratio, and these HFD-induced changes were prevented by the STZ-induced insulin deficiency. In cultured hepatocytes, we observed that expressions of ACSL1 and -5 were stimulated by insulin signaling. Results in cultured cells also showed that blunting insulin signaling by the PI3K inhibitor LY-294002 prevented fat accumulation, oxidative stress, and insulin resistance induced by the prolonged exposure to either insulin or oleate plus sera that normally contain insulin. Finally, knockdown of the insulin receptor prevented the oxidative stress and insulin resistance induced by the prolonged exposure to insulin or oleate plus sera. Together, our results show that insulin and insulin signaling are required for fat induction of insulin resistance in mice and cultured mouse hepatocytes. PMID:21586696

  1. MSW Variable Time-Delay Techniques.

    DTIC Science & Technology

    1982-07-01

    Phase Measurements Delay Dispersion Angle YIG Epitaxy Microwaves Films 20. ABSTRACT (Coninv. an r..eves side it nocesomr and identUify by Nocak ne...Work performed during the first year of a program to investigate magneto- static wave device techniques for phased arrays and microwave signal...device techniques for phased antenna arrays and microwave signal processing. At the start of this " program, initial experiments on variable delay(1

  2. Mechanisms for greater insulin-stimulated glucose uptake in normal and insulin-resistant skeletal muscle after acute exercise.

    PubMed

    Cartee, Gregory D

    2015-12-15

    Enhanced skeletal muscle and whole body insulin sensitivity can persist for up to 24-48 h after one exercise session. This review focuses on potential mechanisms for greater postexercise and insulin-stimulated glucose uptake (ISGU) by muscle in individuals with normal or reduced insulin sensitivity. A model is proposed for the processes underlying this improvement; i.e., triggers initiate events that activate subsequent memory elements, which store information that is relayed to mediators, which translate memory into action by controlling an end effector that directly executes increased insulin-stimulated glucose transport. Several candidates are potential triggers or memory elements, but none have been conclusively verified. Regarding potential mediators in both normal and insulin-resistant individuals, elevated postexercise ISGU with a physiological insulin dose coincides with greater Akt substrate of 160 kDa (AS160) phosphorylation without improved proximal insulin signaling at steps from insulin receptor binding to Akt activity. Causality remains to be established between greater AS160 phosphorylation and improved ISGU. The end effector for normal individuals is increased GLUT4 translocation, but this remains untested for insulin-resistant individuals postexercise. Following exercise, insulin-resistant individuals can attain ISGU values similar to nonexercising healthy controls, but after a comparable exercise protocol performed by both groups, ISGU for the insulin-resistant group has been consistently reported to be below postexercise values for the healthy group. Further research is required to fully understand the mechanisms underlying the improved postexercise ISGU in individuals with normal or subnormal insulin sensitivity and to explain the disparity between these groups after similar exercise.

  3. Mechanisms for greater insulin-stimulated glucose uptake in normal and insulin-resistant skeletal muscle after acute exercise

    PubMed Central

    2015-01-01

    Enhanced skeletal muscle and whole body insulin sensitivity can persist for up to 24–48 h after one exercise session. This review focuses on potential mechanisms for greater postexercise and insulin-stimulated glucose uptake (ISGU) by muscle in individuals with normal or reduced insulin sensitivity. A model is proposed for the processes underlying this improvement; i.e., triggers initiate events that activate subsequent memory elements, which store information that is relayed to mediators, which translate memory into action by controlling an end effector that directly executes increased insulin-stimulated glucose transport. Several candidates are potential triggers or memory elements, but none have been conclusively verified. Regarding potential mediators in both normal and insulin-resistant individuals, elevated postexercise ISGU with a physiological insulin dose coincides with greater Akt substrate of 160 kDa (AS160) phosphorylation without improved proximal insulin signaling at steps from insulin receptor binding to Akt activity. Causality remains to be established between greater AS160 phosphorylation and improved ISGU. The end effector for normal individuals is increased GLUT4 translocation, but this remains untested for insulin-resistant individuals postexercise. Following exercise, insulin-resistant individuals can attain ISGU values similar to nonexercising healthy controls, but after a comparable exercise protocol performed by both groups, ISGU for the insulin-resistant group has been consistently reported to be below postexercise values for the healthy group. Further research is required to fully understand the mechanisms underlying the improved postexercise ISGU in individuals with normal or subnormal insulin sensitivity and to explain the disparity between these groups after similar exercise. PMID:26487009

  4. Insulin use and persistence in patients with type 2 diabetes adding mealtime insulin to a basal regimen: a retrospective database analysis

    PubMed Central

    2011-01-01

    Background The objective of this study was to characterize insulin use and examine factors associated with persistence to mealtime insulin among patients with type 2 diabetes (T2D) on stable basal insulin therapy initiating mealtime insulin therapy. Methods Insulin use among patients with T2D initiating mealtime insulin was investigated using Thomson Reuters MarketScan® research databases from July 2001 through September 2006. The first mealtime insulin claim preceded by 6 months with 2 claims for basal insulin was used as the index event. A total of 21 months of continuous health plan enrollment was required. Patients were required to have a second mealtime insulin claim during the 12-month follow-up period. Persistence measure 1 defined non-persistence as the presence of a 90-day gap in mealtime insulin claims, effective the date of the last claim prior to the gap. Persistence measure 2 required 1 claim per quarter to be persistent. Risk factors for non-persistence were assessed using logistic regression. Results Patients initiating mealtime insulin (n = 4752; 51% male, mean age = 60.3 years) primarily used vial/syringe (87%) and insulin analogs (60%). Patients filled a median of 2, 3, and 4 mealtime insulin claims at 3, 6, and 12 months, respectively, with a median time of 76 days between refills. According to measure 1, persistence to mealtime insulin was 40.7%, 30.2%, and 19.1% at 3, 6, and 12 months, respectively. Results for measure 2 were considerably higher: 74.3%, 55.3%, and 42.2% of patients were persistent at 3, 6, and 12 months, respectively. Initiating mealtime insulin with human insulin was a risk factor for non-persistence by both measures (OR < 0.80, p < 0.01). Additional predictors of non-persistence at 12 months included elderly age, increased insulin copayment, mental health comorbidity, and polypharmacy (p < 0.05 for all). Conclusions Mealtime insulin use and persistence were both considerably lower than expected, and were significantly lower

  5. CGI delay compensation

    NASA Technical Reports Server (NTRS)

    Mcfarland, Richard E.

    1986-01-01

    Computer-generated graphics in real-time helicopter simulation produces objectionable scene-presentation time delays. In the flight simulation laboratory at Ames Research Center, it has been determined that these delays have an adverse influence on pilot performance during aggressive tasks such as nap-of-the-earth (NOE) maneuvers. Using contemporary equipment, computer-generated image (CGI) time delays are an unavoidable consequence of the operations required for scene generation. However, providing that magnitide distortions at higher frequencies are tolerable, delay compensation is possible over a restricted frequency range. This range, assumed to have an upper limit of perhaps 10 or 15 rad/sec, conforms approximately to the bandwidth associated with helicopter handling qualities research. A compensation algorithm is introduced here and evaluated in terms of tradeoffs in frequency responses. The algorithm has a discrete basis and accommodates both a large, constant transport delay interval and a periodic delay interval, as associated with asynchronous operations.

  6. Looking at the carcinogenicity of human insulin analogues via the intrinsic disorder prism.

    PubMed

    Redwan, Elrashdy M; Linjawi, Moustafa H; Uversky, Vladimir N

    2016-03-17

    Therapeutic insulin, in its native and biosynthetic forms as well as several currently available insulin analogues, continues to be the protein of most interest to researchers. From the time of its discovery to the development of modern insulin analogues, this important therapeutic protein has passed through several stages and product generations. Beside the well-known link between diabetes and cancer risk, the currently used therapeutic insulin analogues raised serious concerns due to their potential roles in cancer initiation and/or progression. It is possible that structural variations in some of the insulin analogues are responsible for the appearance of new oncogenic species with high binding affinity to the insulin-like growth factor 1 (IGF1) receptor. The question we are trying to answer in this work is: are there any specific features of the distribution of intrinsic disorder propensity within the amino acid sequences of insulin analogues that may provide an explanation for the carcinogenicity of the altered insulin protein?

  7. Environmentally Benign Pyrotechnic Delays

    DTIC Science & Technology

    2012-06-01

    jay.poret@us.army.mil † School of Mechanical Engineering, Purdue University, West Lafayette, Indiana, USA ABSTRACT Pyrotechnic delays are used in...benign formulations are described. The delay time of the new system is easily tunable. These compositions will consistently function in aluminum ...tunable. These compositions will consistently function in aluminum housings which is generally difficult for delay compositions due to extreme thermal

  8. Moving toward the ideal insulin for insulin pumps.

    PubMed

    Cengiz, Eda; Bode, Bruce; Van Name, Michelle; Tamborlane, William V

    2016-01-01

    Advances in insulin formulations have been important for diabetes management and achieving optimal glycemic control. Rapid-acting insulin analogs provide a faster time-action profile than regular insulin and are approved for use in pumps. However, the need remains for therapy to deliver a more physiologic insulin profile. New insulin formulations and delivery methods are in development, with the aim of accelerating insulin absorption to accomplish ultra-fast-acting insulin time-action profiles. Furthermore, the integration of continuous glucose monitoring with insulin pump therapy enables on-going adjustment of insulin delivery to optimize glycemic control throughout the day and night. These technological and pharmacological advances are likely to facilitate the development of closed-loop pump systems (i.e., artificial pancreas), and improve glycemic control and quality of life for patients with diabetes.

  9. Response acquisition with delayed reinforcement.

    PubMed

    Lattal, K A; Gleeson, S

    1990-01-01

    Discrete responses of experimentally naive, food-deprived White Carneaux pigeons (key pecks) or Sprague-Dawley rats (bar or omnidirectional lever presses) initiated unsignaled delay periods that terminated with food delivery. Each subject first was trained to eat from the food source, but no attempt was made to shape or to otherwise train the response. In both species, the response developed and was maintained. Control procedures excluded the simple passage of time, response elicitation or induction by food presentation, type of operandum, food delivery device location, and adventitious immediate reinforcement of responding as the basis for the effects. Results revealed that neither training nor immediate reinforcement is necessary to establish new behavior. The conditions that give rise to both the first and second response are discussed, and the results are related to other studies of the delay of reinforcement and to explanations of behavior based on contingency or correlation and contiguity.

  10. Delayed puberty and amenorrhea.

    PubMed

    Hoffman, Barbara; Bradshaw, Karen D

    2003-11-01

    The ability to diagnose and manage disorders that cause delayed puberty requires a thorough understanding of the physical and hormonal events of puberty. Wide variation exists within normal pubertal maturation, but most adolescent girls in the United States have begun to mature by the age of 13. Delayed puberty, a rare condition in girls, occurs in only approximately 2.5% of the population. Constitutional delay, genetic defects, or hypothalamic-pituitary disorders are common causes. Amenorrhea, often found as a symptom of delayed puberty, may be due to congenital genital tract anomalies, ovarian failure, or chronic anovulation with estrogen presence or with estrogen absence.

  11. Delayed Orgasm and Anorgasmia

    PubMed Central

    Jenkins, Lawrence C.; Mulhall, John P.

    2016-01-01

    Delayed orgasm/anorgasmia defined as the persistent or recurrent difficulty, delay in, or absence of attaining orgasm after sufficient sexual stimulation, which causes personal distress. Delayed orgasm and anorgasmia are associated with significant sexual dissatisfaction. A focused medical history can shed light on the potential etiologies; which include: medications, penile sensation loss, endocrinopathies, penile hyperstimulation and psychological etiologies, amongst others. Unfortunately, there are no excellent pharmacotherapies for delayed orgasm/anorgasmia, and treatment revolves largely around addressing potential causative factors and psychotherapy. PMID:26439762

  12. Delayed orgasm and anorgasmia.

    PubMed

    Jenkins, Lawrence C; Mulhall, John P

    2015-11-01

    Delayed orgasm/anorgasmia defined as the persistent or recurrent difficulty, delay in, or absence of attaining orgasm after sufficient sexual stimulation, which causes personal distress. Delayed orgasm and anorgasmia are associated with significant sexual dissatisfaction. A focused medical history can shed light on the potential etiologies, which include medications, penile sensation loss, endocrinopathies, penile hyperstimulation, and psychological etiologies. Unfortunately, there are no excellent pharmacotherapies for delayed orgasm/anorgasmia, and treatment revolves largely around addressing potential causative factors and psychotherapy. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  13. Delayed emergence after anesthesia.

    PubMed

    Tzabazis, Alexander; Miller, Christopher; Dobrow, Marc F; Zheng, Karl; Brock-Utne, John G

    2015-06-01

    In most instances, delayed emergence from anesthesia is attributed to residual anesthetic or analgesic medications. However, delayed emergence can be secondary to unusual causes and present diagnostic dilemmas. Data from clinical studies is scarce and most available published material is comprised of case reports. In this review, we summarize and discuss less common and difficult to diagnose reasons for delayed emergence and present cases from our own experience or reference published case reports/case series. The goal is to draw attention to less common reasons for delayed emergence, identify patient populations that are potentially at risk and to help anesthesiologists identifying a possible cause why their patient is slow to wake up.

  14. VARIABLE TIME DELAY MEANS

    DOEpatents

    Clemensen, R.E.

    1959-11-01

    An electrically variable time delay line is described which may be readily controlled simuitaneously with variable impedance matching means coupied thereto such that reflections are prevented. Broadly, the delay line includes a signal winding about a magnetic core whose permeability is electrically variable. Inasmuch as the inductance of the line varies directly with the permeability, the time delay and characteristic impedance of the line both vary as the square root of the permeability. Consequently, impedance matching means may be varied similariy and simultaneously w:th the electrically variable permeability to match the line impedance over the entire range of time delay whereby reflections are prevented.

  15. AZD5363 Inhibits Inflammatory Synergy between Interleukin-17 and Insulin/Insulin-Like Growth Factor 1.

    PubMed

    Chen, Chong; Zhang, Qiuyang; Liu, Sen; Lambrechts, Mark; Qu, Yine; You, Zongbing

    2014-01-01

    In the United States, one-third of population is affected by obesity and almost 29 million people are suffering from type 2 diabetes. Obese people have elevated serum levels of insulin, insulin-like growth factor 1 (IGF1), and interleukin-17 (IL-17). Insulin and IGF1 are known to enhance IL-17-induced expression of inflammatory cytokines and chemokines, which may contribute to the chronic inflammatory status observed in obese people. We have previously demonstrated that insulin/IGF1 signaling pathway crosstalks with IL-17-activated nuclear factor-κB pathway through inhibiting glycogen synthase kinase 3β (GSK3β) activity. However, it is unclear whether GSK3α also plays a role and whether this crosstalk can be manipulated by AZD5363, a novel pan-Akt inhibitor that has been shown to increase glycogen synthase kinase 3 activity through reducing phosphorylation of GSK3α and GSK3β. In this study, we investigated IL-17-induced expression of C-X-C motif ligand 1 (Cxcl1), C-C motif ligand 20 (Ccl20), and interleukin-6 (Il-6) in wild-type, GSK3α(-/-), and GSK3β(-/-) mouse embryonic fibroblast cells as well as in mouse prostate tissues by real-time quantitative PCR. We examined the proteins involved in the signaling pathways by Western blot analysis. We found that insulin and IGF1 enhanced IL-17-induced expression of Cxcl1, Ccl20, and Il-6, which was associated with increased phosphorylation of GSK3α and GSK3β in the presence of insulin and IGF1. AZD5363 inhibited the synergy between IL-17 and insulin/IGF1 through reducing phosphorylation of GSK3α and GSK3β by inhibiting Akt function. These findings imply that the cooperative crosstalk of IL-17 and insulin/IGF1 in initiating inflammatory responses may be alleviated by AZD5363.

  16. Administration technique and storage of disposable insulin pens reported by patients with diabetes.

    PubMed

    Mitchell, Virginia D; Porter, Kyle; Beatty, Stuart J

    2012-01-01

    The purpose of the study was to evaluate insulin injection technique and storage of insulin pens as reported by patients with diabetes and to compare correct pen use to initial education on injection technique, hemoglobin A1C, duration of insulin therapy, and duration of insulin pen. Cross-sectional questionnaire orally administered to patients at a university-affiliated primary care practice. Subjects were patients with diabetes who were 18 years or older and prescribed a disposable insulin pen for at least 4 weeks. A correct usage score was calculated for each patient based on manufacturer recommendations for disposable insulin pen use. Associations were made between the correct usage score and certainty in technique, initial education, years of insulin therapy, duration of pen use, and hemoglobin A1C. Sixty-seven patients completed the questionnaire, reporting total use of 94 insulin pens. The 3 components most often neglected by patients were priming pen needle, holding for specific count time before withdrawal of pen needle from skin, and storing an in-use pen. For three-fourths of the insulin pens being used, users did not follow the manufacturer's instructions for proper administration and storage of insulin pens. Correct usage scores were significantly higher if initial education on insulin pens was performed by a pharmacist or nurse. The majority of patients may be ignoring or unaware of key components for consistent insulin dosing using disposable insulin pens; therefore, initial education and reeducation on correct use of disposable insulin pens by health care professionals are needed.

  17. Mouse models of insulin resistance.

    PubMed

    Hribal, Marta Letizia; Oriente, Francesco; Accili, Domenico

    2002-05-01

    The hallmarks of type 2 diabetes are impaired insulin action in peripheral tissues and decreased pancreatic beta-cell function. Classically, the two defects have been viewed as separate entities, with insulin resistance arising primarily from impaired insulin-dependent glucose uptake in skeletal muscle, and beta-cell dysfunction arising from impaired coupling of glucose sensing to insulin secretion. Targeted mutagenesis and transgenesis involving components of the insulin action pathway have changed our understanding of these phenomena. It appears that the role of insulin signaling in the pathogenesis of type 2 diabetes has been overestimated in classic insulin target tissues, such as skeletal muscle, whereas it has been overlooked in liver, pancreatic beta-cells, and brain, which had been thought not to be primary insulin targets. We review recent progress and try to reconcile areas of apparent controversy surrounding insulin signaling in skeletal muscle and pancreatic beta-cells.

  18. Insulin pump therapy in pregnancy.

    PubMed

    Kesavadev, Jothydev

    2016-09-01

    Control of blood glucose during pregnancy is difficult because of wide variations, ongoing hormonal changes and mood swings. The need for multiple injections, pain at the injection site, regular monitoring and skillful handling of the syringes/pen further makes insulin therapy inconvenient. Insulin pump is gaining popularity in pregnancy because it mimics the insulin delivery of a healthy human pancreas. Multiple guidelines have also recommended the use of insulin pump in pregnancy to maintain the glycaemic control. The pump can release small doses of insulin continuously (basal), or a bolus dose close to mealtime to control the spike in blood glucose after a meal and the newer devices can shut down insulin delivery before the occurrence of hypoglycaemia. Pump insulin of choice is rapid acting analogue insulin. This review underscores the role of insulin pump in pregnancy, their usage, advantages and disadvantages in the light of existing literature and clinic experience.

  19. Insulin algorithms in the self-management of insulin-dependent diabetes: the interactive 'Apple Juice' program.

    PubMed

    Williams, A G

    1996-01-01

    The 'Apple Juice' program is an interactive diabetes self-management program which runs on a lap-top Macintosh Powerbook 100 computer. The dose-by-dose insulin advisory program was initially designed for children with insulin-dependent (type 1) diabetes mellitus. It utilizes several different insulin algorithms, measurement formulae, and compensation factors for meals, activity, medication and the dawn phenomenon. It was developed to assist the individual with diabetes and/or care providers, in determining specific insulin dosage recommendations throughout a 24 h period. Information technology functions include, but are not limited to automated record keeping, data recall, event reminders, data trend/pattern analyses and education. This paper highlights issues, observations and recommendations surrounding the use of the current version of the software, along with a detailed description of the insulin algorithms and measurement formulae applied successfully with the author's daughter over a six year period.

  20. II - Insulin processing in mitochondria.

    PubMed

    Camberos, María Del Carmen; Pérez, Adriana A; Passicot, Gisel A; Martucci, Lucía C; Wanderley, María I; Udrisar, Daniel P; Cresto, Juan C

    2016-10-01

    Our objective was to know how insulin is processing in mitochondria; if IDE is the only participant in mitochondrial insulin degradation and the role of insulin degradation on IDE accumulation in mitoplasts. Mitochondria and its fractions were isolated as described by Greenwalt. IDE was purified and detected in immunoblot with specific antibodies. High insulin degradation was obtained through addition to rat's diet of 25 g/rat of apple and 10 g/rat of hard-boiled eggs, 3 days a week. Mitochondrial insulin degradation was assayed with 5 % TCA, insulin antibody or Sephadex G50 chromatography. Degradation was also assayed 60 min at 37 °C in mitochondrial fractions (IMS and Mx) with diet or not and without IDE. Degradation in fractions precipitated with ammonium sulfates (60-80 %) were studied after mitochondrial insulin incubation (1 ng. insulin during 15 min, at 30 °C) or with addition of 2.5 mM ATP. Supplementary diet increased insulin degradation. High insulin did not increase mitoplasts accumulation and did not decrease mitochondrial degradation. High insulin and inhibition of degradation evidence insulin competition for a putative transport system. Mitochondrial incubation with insulin increased IDE in matrix as observed in immunoblot. ATP decreased degradation in Mx and increased it in IMS. Chromatography of IMS demonstrated an ATP-dependent protease that degraded insulin, similar to described by Sitte et al. Mitochondria participate in insulin degradation and the diet increased it. High insulin did not accomplish mitochondrial decrease of degradation or its accumulation in mitoplasts. Mitochondrial incubation with insulin increased IDE in matrix. ATP suggested being a regulator of mitochondrial insulin degradation.

  1. Angiotensin II induces differential insulin action in rat skeletal muscle.

    PubMed

    Surapongchai, Juthamard; Prasannarong, Mujalin; Bupha-Intr, Tepmanas; Saengsirisuwan, Vitoon

    2017-03-01

    Angiotensin II (ANGII) is reportedly involved in the development of skeletal muscle insulin resistance. The present investigation evaluated the effects of two ANGII doses on the phenotypic characteristics of insulin resistance syndrome and insulin action and signaling in rat skeletal muscle. Male Sprague-Dawley rats were infused with either saline (SHAM) or ANGII at a commonly used pressor dose (100 ng/kg/min; ANGII-100) or a higher pressor dose (500 ng/kg/min; ANGII-500) via osmotic minipumps for 14 days. We demonstrated that ANGII-100-infused rats exhibited the phenotypic features of non-obese insulin resistance syndrome, including hypertension, impaired glucose tolerance and insulin resistance of glucose uptake in the soleus muscle, whereas ANGII-500-treated rats exhibited diabetes-like symptoms, such as post-prandial hyperglycemia, impaired insulin secretion and hypertriglyceridemia. At the cellular level, insulin-stimulated glucose uptake in the soleus muscle of the ANGII-100 group was 33% lower (P < 0.05) than that in the SHAM group and was associated with increased insulin-stimulated IRS-1 Ser(307) and decreased Akt Ser(473) and AS160 Thr(642) phosphorylation and GLUT-4 expression. However, ANGII-500 infusion did not induce skeletal muscle insulin resistance or impair insulin signaling elements as initially anticipated. Moreover, we found that insulin-stimulated glucose uptake in the ANGII-500 group was accompanied by the enhanced expression of ACE2 and MasR proteins, which are the key elements in the non-classical pathway of the renin-angiotensin system. Collectively, this study demonstrates for the first time that chronic infusion with these two pressor doses of ANGII induced differential metabolic responses at both the systemic and skeletal muscle levels. © 2017 Society for Endocrinology.

  2. The Metabolism of Proinsulin and Insulin by the Liver

    PubMed Central

    Rubenstein, A. H.; Pottenger, L. A.; Mako, M.; Getz, G. S.; Steiner, D. F.

    1972-01-01

    The removal of bovine proinsulin by the isolated perfused rat liver has been studied and the results compared with the removal of insulin. At high concentrations of insulin (> 180 ng/ml) the removal process was saturated and the t½ varied between 35 and 56 min. With low initial insulin levels the disappearance followed first-order kinetics, the mean regression coefficient being — 0.022, t½ 13.8 min, and the hepatic extraction 4.0 ml/min. The results with proinsulin were in striking contrast to these findings. At both high and low concentrations the hepatic removal of proinsulin was considerably slower, averaging 10-15 times less than that of insulin. Specific immunoassay techniques and gel filtration of samples taken from perfusions to which both labeled and unlabeled proinsulin had been added did not show conversion to either insulin or the C-peptide. Bovine and rat 131I-labeled proinsulins were degraded more slowly than bovine insulin-131I by bovine and rat liver homogenates. Both proinsulin and insulin inhibited the degradation of insulin-131I, equimolar quantities of proinsulin being 2-5 times less effective than insulin. These results indicate sign