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Sample records for intensive insulin therapy

  1. Intensive Insulin Therapy: Tight Blood Sugar Control

    MedlinePlus

    ... insulin therapy can help you achieve desired blood sugar control and what intensive insulin therapy requires of ... aggressive treatment approach designed to control your blood sugar levels. Intensive insulin therapy requires close monitoring of ...

  2. Intensive insulin therapy in the medical ICU.

    PubMed

    Van den Berghe, Greet; Wilmer, Alexander; Hermans, Greet; Meersseman, Wouter; Wouters, Pieter J; Milants, Ilse; Van Wijngaerden, Eric; Bobbaers, Herman; Bouillon, Roger

    2006-02-02

    Intensive insulin therapy reduces morbidity and mortality in patients in surgical intensive care units (ICUs), but its role in patients in medical ICUs is unknown. In a prospective, randomized, controlled study of adult patients admitted to our medical ICU, we studied patients who were considered to need intensive care for at least three days. On admission, patients were randomly assigned to strict normalization of blood glucose levels (80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]) with the use of insulin infusion or to conventional therapy (insulin administered when the blood glucose level exceeded 215 mg per deciliter [12 mmol per liter], with the infusion tapered when the level fell below 180 mg per deciliter [10 mmol per liter]). There was a history of diabetes in 16.9 percent of the patients. In the intention-to-treat analysis of 1200 patients, intensive insulin therapy reduced blood glucose levels but did not significantly reduce in-hospital mortality (40.0 percent in the conventional-treatment group vs. 37.3 percent in the intensive-treatment group, P=0.33). However, morbidity was significantly reduced by the prevention of newly acquired kidney injury, accelerated weaning from mechanical ventilation, and accelerated discharge from the ICU and the hospital. Although length of stay in the ICU could not be predicted on admission, among 433 patients who stayed in the ICU for less than three days, mortality was greater among those receiving intensive insulin therapy. In contrast, among 767 patients who stayed in the ICU for three or more days, in-hospital mortality in the 386 who received intensive insulin therapy was reduced from 52.5 to 43.0 percent (P=0.009) and morbidity was also reduced. Intensive insulin therapy significantly reduced morbidity but not mortality among all patients in the medical ICU. Although the risk of subsequent death and disease was reduced in patients treated for three or more days, these patients could not be identified

  3. Intensive insulin therapy in septic shock.

    PubMed

    Orford, Neil R

    2006-09-01

    The use of intensive insulin therapy (IIT) to maintain blood glucose level below 8.3 mmol/L is recommended for management of severe sepsis by the Surviving Sepsis guidelines. The recent trials reporting reduced morbidity and mortality in critically ill patients treated with IIT require careful examination, including the subsequent post-hoc analyses. An understanding of the molecular and metabolic mechanisms by which IIT may be beneficial and the evidence that it benefits patients with severe sepsis, and a review of the risks of hypoglycaemia are also necessary when deciding whether to implement IIT in severe sepsis. Patients with severe sepsis are likely to benefit from IIT based on metabolic effects and their prolonged stays in the intensive care unit. The current evidence suggests IIT should be implemented, aiming for the lowest glycaemic range that can be safely achieved while avoiding hypoglycaemia.

  4. Intensive insulin therapy in the intensive cardiac care unit.

    PubMed

    Hasin, Tal; Eldor, Roy; Hammerman, Haim

    2006-01-01

    Treatment in the intensive cardiac care unit (ICCU) enables rigorous control of vital parameters such as heart rate, blood pressure, body temperature, oxygen saturation, serum electrolyte levels, urine output and many others. The importance of controlling the metabolic status of the acute cardiac patient and specifically the level of serum glucose was recently put in focus but is still underscored. This review aims to explain the rationale for providing intensive control of serum glucose levels in the ICCU, especially using intensive insulin therapy and summarizes the available clinical evidence suggesting its effectiveness.

  5. Intensive Insulin Therapy in Severely Burned Pediatric Patients

    PubMed Central

    Jeschke, Marc G.; Kulp, Gabriela A.; Kraft, Robert; Finnerty, Celeste C.; Mlcak, Ron; Lee, Jong O.; Herndon, David N.

    2010-01-01

    Rationale: Hyperglycemia and insulin resistance have been shown to increase morbidity and mortality in severely burned patients, and glycemic control appears essential to improve clinical outcomes. However, to date no prospective randomized study exists that determines whether intensive insulin therapy is associated with improved post-burn morbidity and mortality. Objectives: To determine whether intensive insulin therapy is associated with improved post-burn morbidity. Methods: A total of 239 severely burned pediatric patients with burns over greater than 30% of their total body surface area were randomized (block randomization 1:3) to intensive insulin treatment (n = 60) or control (n = 179). Measurements and Main Results: Demographics, clinical outcomes, sepsis, glucose metabolism, organ function, and inflammatory, acute-phase, and hypermetabolic responses were determined. Demographics were similar in both groups. Intensive insulin treatment significantly decreased the incidence of infections and sepsis compared with controls (P < 0.05). Furthermore, intensive insulin therapy improved organ function as indicated by improved serum markers, DENVER2 scores, and ultrasound (P < 0.05). Intensive insulin therapy alleviated post-burn insulin resistance and the vast catabolic response of the body (P < 0.05). Intensive insulin treatment dampened inflammatory and acute-phase responses by deceasing IL-6 and acute-phase proteins compared with controls (P < 0.05). Mortality was 4% in the intensive insulin therapy group and 11% in the control group (P = 0.14). Conclusions: In this prospective randomized clinical trial, we showed that intensive insulin therapy improves post-burn morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00673309). PMID:20395554

  6. Insulin therapy in the pediatric intensive care unit

    USDA-ARS?s Scientific Manuscript database

    Hyperglycemia is a major risk factor for increased morbidity and mortality in the intensive care unit. Insulin therapy has emerged in adult intensive care units, and several pediatric studies are currently being conducted. This review discusses hyperglycemia and the effects of insulin on metabolic a...

  7. Intensive insulin therapy and pentastarch resuscitation in severe sepsis.

    PubMed

    Brunkhorst, Frank M; Engel, Christoph; Bloos, Frank; Meier-Hellmann, Andreas; Ragaller, Max; Weiler, Norbert; Moerer, Onnen; Gruendling, Matthias; Oppert, Michael; Grond, Stefan; Olthoff, Derk; Jaschinski, Ulrich; John, Stefan; Rossaint, Rolf; Welte, Tobias; Schaefer, Martin; Kern, Peter; Kuhnt, Evelyn; Kiehntopf, Michael; Hartog, Christiane; Natanson, Charles; Loeffler, Markus; Reinhart, Konrad

    2008-01-10

    The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids. In a multicenter, two-by-two factorial trial, we randomly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10% pentastarch, a low-molecular-weight hydroxyethyl starch (HES 200/0.5), or modified Ringer's lactate for fluid resuscitation. The rate of death at 28 days and the mean score for organ failure were coprimary end points. The trial was stopped early for safety reasons. Among 537 patients who could be evaluated, the mean morning blood glucose level was lower in the intensive-therapy group (112 mg per deciliter [6.2 mmol per liter]) than in the conventional-therapy group (151 mg per deciliter [8.4 mmol per liter], P<0.001). However, at 28 days, there was no significant difference between the two groups in the rate of death or the mean score for organ failure. The rate of severe hypoglycemia (glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was higher in the intensive-therapy group than in the conventional-therapy group (17.0% vs. 4.1%, P<0.001), as was the rate of serious adverse events (10.9% vs. 5.2%, P=0.01). HES therapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer's lactate. The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia. As used in this study, HES was harmful, and its toxicity increased with accumulating doses. (ClinicalTrials.gov number, NCT00135473.) 2008 Massachusetts Medical Society

  8. [Intensive insulin therapy in type 2 diabetes mellitus].

    PubMed

    Jermendy, György

    2012-09-23

    In the last couple of years, the intensive conservative insulin treatment (basal-bolus regime) became more and more popular even in patients with type 2 diabetes. Using this insulin treatment, continuous patient education, co-operation between the medical team (diabetologist, dietician and diabetes-nurses) and the patient as well as the availability of modern insulins, pens and glucometers are of great importance. Clearly, the basal-bolus treatment with human insulin has advantages over the conservative (conventional) treatment with twice daily premix insulins. Moreover, the basal-bolus treatment with insulin-analogues proved to be superior in some aspects as compared to human insulins. The intensive insulin treatment (basal-bolus regime with insulin-analogues) approaches the optimal insulin substitution and, with its use the adequate correction of each element of the glucose triad (fasting blood glucose, postprandial blood glucose, HbA1c) should be considered feasible even in patients with type 2 diabetes.

  9. Intensive insulin therapy to maintain normoglycemia after cardiac surgery.

    PubMed

    Van den Berghe, G

    2011-01-01

    Drugs used in the perioperative period could have an effect on survival as recently pointed out by an international consensus conference on the reduction in mortality in cardiac anesthesia and intensive care. Insulin infusion to achieve a strict glycemic control is the best example of how an ancillary (i.e. non-surgical) drug/technique/strategy might influence survival rates in patients undergoing cardiac surgery. The author of this "expert opinion" presents her insights into the use of insulin in this setting and suggest that based on available evidence based medicine, insulin infusion, titrated to "normoglycemia" is a complex intervention, that not only requires the simple administration of a "drug", the hormone insulin, but also needs tools and skills to accurately measure and control blood glucose to achieve normoglycemia while avoiding hypoglycemia and large glucose fluctuations.

  10. Intensive insulin therapy in severely burned pediatric patients: a prospective randomized trial.

    PubMed

    Jeschke, Marc G; Kulp, Gabriela A; Kraft, Robert; Finnerty, Celeste C; Mlcak, Ron; Lee, Jong O; Herndon, David N

    2010-08-01

    Hyperglycemia and insulin resistance have been shown to increase morbidity and mortality in severely burned patients, and glycemic control appears essential to improve clinical outcomes. However, to date no prospective randomized study exists that determines whether intensive insulin therapy is associated with improved post-burn morbidity and mortality. To determine whether intensive insulin therapy is associated with improved post-burn morbidity. A total of 239 severely burned pediatric patients with burns over greater than 30% of their total body surface area were randomized (block randomization 1:3) to intensive insulin treatment (n = 60) or control (n = 179). Demographics, clinical outcomes, sepsis, glucose metabolism, organ function, and inflammatory, acute-phase, and hypermetabolic responses were determined. Demographics were similar in both groups. Intensive insulin treatment significantly decreased the incidence of infections and sepsis compared with controls (P < 0.05). Furthermore, intensive insulin therapy improved organ function as indicated by improved serum markers, DENVER2 scores, and ultrasound (P < 0.05). Intensive insulin therapy alleviated post-burn insulin resistance and the vast catabolic response of the body (P < 0.05). Intensive insulin treatment dampened inflammatory and acute-phase responses by deceasing IL-6 and acute-phase proteins compared with controls (P < 0.05). Mortality was 4% in the intensive insulin therapy group and 11% in the control group (P = 0.14). In this prospective randomized clinical trial, we showed that intensive insulin therapy improves post-burn morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00673309).

  11. Clinical effects of intensive insulin therapy treating traumatic shock combined with multiple organ dysfunction syndrome.

    PubMed

    Du, Jundong; Liu, Hongming; Liu, Rong; Yao, Yongming; Jiao, Huabo; Zhao, Xiaodong; Yin, Huinan; Li, Zhanliang

    2011-04-01

    The therapeutic effects of intensive insulin therapy in treatment of traumatic shock combined with multiple organ dysfunction syndrome (MODS) were investigated. A total of 114 patients with traumatic shock combined with MODS were randomly divided into two groups: control group (n=56) treated with conventional therapy, and intensive insulin therapy group (n=58) treated with conventional therapy plus continuous insulin pumping to control the blood glucose level at range of 4.4-6.1 mmol/L. White blood cells (WBC) counts, prothrombin time (PT), serum creatinine (SCr), alanine aminotransferase (ALT), serum albumin and PaO(2) were measured before and at the day 1, 3, 5, 7 and 14 after treatment. The incidence of gastrointestinal dysfunction, the incidence of MODS, hospital stay and the mortality were also observed and compared. After intensive insulin therapy, the WBC counts, SCr, ALT and PT were significantly reduced (P<0.05), but the level of serum albumin was significantly increased (P<0.05) at the day 3, 5, 7 and 14. In the meantime, the PaO2 was significantly elevated at the day 3, 5 and 7 (P<0.01) after intensive insulin therapy. The incidence of gastrointestinal dysfunction, the incidence of MODS, the length of hospital stay and the mortality were markedly decreased (P<0.01). The results suggest early treatment with intensive insulin therapy is effective for traumatic shock combined with MODS and can decrease the length of hospital stay and the mortality.

  12. Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial.

    PubMed

    Annane, Djillali; Cariou, Alain; Maxime, Virginie; Azoulay, Elie; D'honneur, Gilles; Timsit, Jean François; Cohen, Yves; Wolf, Michel; Fartoukh, Muriel; Adrie, Christophe; Santré, Charles; Bollaert, Pierre Edouard; Mathonet, Armelle; Amathieu, Roland; Tabah, Alexis; Clec'h, Christophe; Mayaux, Julien; Lejeune, Julie; Chevret, Sylvie

    2010-01-27

    Corticosteroid therapy induces potentially detrimental hyperglycemia in septic shock. In addition, the benefit of adding fludrocortisone in this setting is unclear. To test the efficacy of intensive insulin therapy in patients whose septic shock was treated with hydrocortisone and to assess, as a secondary objective, the benefit of fludrocortisone. A multicenter, 2 x 2 factorial, randomized trial, involving 509 adults with septic shock who presented with multiple organ dysfunction, as defined by a Sequential Organ Failure Assessment score of 8 or more, and who had received hydrocortisone treatment was conducted from January 2006 to January 2009 in 11 intensive care units in France. Patients were randomly assigned to 1 of 4 groups: continuous intravenous insulin infusion with hydrocortisone alone, continuous intravenous insulin infusion with hydrocortisone plus fludrocortisone, conventional insulin therapy with hydrocortisone alone, or conventional insulin therapy with intravenous hydrocortisone plus fludrocortisone. Hydrocortisone was administered in a 50-mg bolus every 6 hours, and fludrocortisone was administered orally in 50-microg tablets once a day, each for 7 days. In-hospital mortality. Of the 255 patients treated with intensive insulin, 117 (45.9%), and 109 of 254 (42.9%) treated with conventional insulin therapy died (relative risk [RR], 1.07; 95% confidence interval [CI], 0.88-1.30; P = .50). Patients treated with intensive insulin experienced significantly more episodes of severe hypoglycemia (<40 mg/dL) than those in the conventional-treatment group, with a difference in mean number of episodes per patient of 0.15 (95% CI, 0.02-0.28; P = .003). At hospital discharge, 105 of 245 patients treated with fludrocortisone (42.9%) died and 121 of 264 (45.8%) in the control group died (RR, 0.94; 95% CI, 0.77-1.14; P = .50). Compared with conventional insulin therapy, intensive insulin therapy did not improve in-hospital mortality among patients who were treated

  13. Intensive insulin therapy in mixed medical/surgical intensive care units: benefit versus harm.

    PubMed

    Van den Berghe, Greet; Wilmer, Alexander; Milants, Ilse; Wouters, Pieter J; Bouckaert, Bernard; Bruyninckx, Frans; Bouillon, Roger; Schetz, Miet

    2006-11-01

    Intensive insulin therapy (IIT) improves the outcome of prolonged critically ill patients, but concerns remain regarding potential harm and the optimal blood glucose level. These questions were addressed using the pooled dataset of two randomized controlled trials. Independent of parenteral glucose load, IIT reduced mortality from 23.6 to 20.4% in the intention-to-treat group (n = 2,748; P = 0.04) and from 37.9 to 30.1% among long stayers (n = 1,389; P = 0.002), with no difference among short stayers (8.9 vs. 10.4%; n = 1,359; P = 0.4). Compared with blood glucose of 110-150 mg/dl, mortality was higher with blood glucose >150 mg/dl (odds ratio 1.38 [95% CI 1.10-1.75]; P = 0.007) and lower with <110 mg/dl (0.77 [0.61-0.96]; P = 0.02). Only patients with diabetes (n = 407) showed no survival benefit of IIT. Prevention of kidney injury and critical illness polyneuropathy required blood glucose strictly <110 mg/day, but this level carried the highest risk of hypoglycemia. Within 24 h of hypoglycemia, three patients in the conventional and one in the IIT group died (P = 0.0004) without difference in hospital mortality. No new neurological problems occurred in survivors who experienced hypoglycemia in intensive care units (ICUs). We conclude that IIT reduces mortality of all medical/surgical ICU patients, except those with a prior history of diabetes, and does not cause harm. A blood glucose target <110 mg/day was most effective but also carried the highest risk of hypoglycemia.

  14. Effects of intensive insulin therapy combined with low molecular weight heparin anticoagulant therapy on severe pancreatitis

    PubMed Central

    DU, JUN-DONG; ZHENG, XI; HUANG, ZHI-QIANG; CAI, SHOU-WANG; TAN, JING-WANG; LI, ZHAN-LIANG; YAO, YONG-MING; JIAO, HUA-BO; YIN, HUI-NAN; ZHU, ZI-MAN

    2014-01-01

    The current study explored the effects of intensive insulin therapy (IIT) combined with low molecular weight heparin (LMWH) anticoagulant therapy on severe acute pancreatitis (SAP). A total of 134 patients with SAP that received treatment between June 2008 and June 2012 were divided randomly into groups A (control; n=33), B (IIT; n=33), C (LMWH; n=34) and D (IIT + LMWH; n=34). Group A were treated routinely. Group B received continuous pumped insulin, as well as the routine treatment, to maintain the blood sugar level between 4.4 and 6.1 mmol/l. Group C received a subcutaneous injection of LMWH every 12 h in addition to the routine treatment. Group D received IIT + LMWH and the routine treatment. The white blood cell count, hemodiastase, serum albumin, arterial partial pressure of oxygen and prothrombin time were recorded prior to treatment and 1, 3, 5, 7 and 14 days after the initiation of treatment. The intestinal function recovery time, incidence rate of multiple organ failure (MOF), length of hospitalization and fatality rates were observed. IIT + LMWH noticeably increased the white blood cell count, hemodiastase level, serum albumin level and the arterial partial pressure of oxygen in the patients with SAP (P<0.05). It markedly shortened the intestinal recovery time and the length of stay and reduced the incidence rate of MOF, the surgery rate and the fatality rate (P<0.05). It did not aggravate the hemorrhagic tendency of SAP (P>0.05). IIT + LMWH had a noticeably improved clinical curative effect on SAP compared with that of the other treatments. PMID:24944612

  15. Hypocaloric Enteral Nutrition Protects Against Hypoglycemia Associated with Intensive Insulin Therapy Better Than Intravenous Dextrose

    PubMed Central

    Kauffmann, Rondi M.; Hayes, Rachel M.; Vanlaeken, Amanda H.; Norris, Patrick R.; Diaz, Jose J.; May, Addison K.; Collier, Bryan R.

    2015-01-01

    Intensive insulin therapy treats hyperglycemia but increases the risk of hypoglycemia. Typically, intravenous dextrose is given to prevent hypoglycemia; however, enteral nutrition is preferred. We hypothesized that the provision of hypocaloric enteral nutrition would protect against hypoglycemia. A retrospective analysis was performed evaluating patients treated with intensive insulin therapy comparing the use of enteral nutrition versus a dextrose-only intravenous solution. Nutrition in the 2 hours before each blood glucose test was assessed, and the association with hypoglycemia (50 mg/dL or less) evaluated. Risk of hypoglycemia as a function of nutrition type and rate was estimated by multivariable regression. A total of 26,140 blood glucose tests were collected on 1289 patients. Hypoglycemia occurred in 6.4 per cent of patients. In regression models, enteral nutrition was the strongest protective factor against hypoglycemia (P < 0.001) with the largest risk reduction (steepest portion of the curve) occurring at 60 per cent goal. Hypocaloric enteral nutrition showed a greater risk reduction than a peripheral dextrose-only intravenous solution alone. In the setting of intensive insulin therapy, the provision of enteral nutrition, even if hypocaloric, is sufficient to protect against hypoglycemia. Future prospective studies should evaluate the efficacy of enteral nutrition in reducing the risk of hypoglycemia and whether lower rates of hypoglycemia correspond to improved outcomes. PMID:25347500

  16. Hypocaloric enteral nutrition protects against hypoglycemia associated with intensive insulin therapy better than intravenous dextrose.

    PubMed

    Kauffmann, Rondi M; Hayes, Rachel M; VanLaeken, Amanda H; Norris, Patrick R; Diaz, Jose J; May, Addison K; Collier, Bryan R

    2014-11-01

    Intensive insulin therapy treats hyperglycemia but increases the risk of hypoglycemia. Typically, intravenous dextrose is given to prevent hypoglycemia; however, enteral nutrition is preferred. We hypothesized that the provision of hypocaloric enteral nutrition would protect against hypoglycemia. A retrospective analysis was performed evaluating patients treated with intensive insulin therapy comparing the use of enteral nutrition versus a dextrose-only intravenous solution. Nutrition in the 2 hours before each blood glucose test was assessed, and the association with hypoglycemia (50 mg/dL or less) evaluated. Risk of hypoglycemia as a function of nutrition type and rate was estimated by multivariable regression. A total of 26,140 blood glucose tests were collected on 1289 patients. Hypoglycemia occurred in 6.4 per cent of patients. In regression models, enteral nutrition was the strongest protective factor against hypoglycemia (P < 0.001) with the largest risk reduction (steepest portion of the curve) occurring at 60 per cent goal. Hypocaloric enteral nutrition showed a greater risk reduction than a peripheral dextrose-only intravenous solution alone. In the setting of intensive insulin therapy, the provision of enteral nutrition, even if hypocaloric, is sufficient to protect against hypoglycemia. Future prospective studies should evaluate the efficacy of enteral nutrition in reducing the risk of hypoglycemia and whether lower rates of hypoglycemia correspond to improved outcomes.

  17. Changing practice with changing research: results of two UK national surveys of intensive insulin therapy in intensive care patients.

    PubMed

    Paddle, J J; Eve, R L; Sharpe, K A

    2011-02-01

    We conducted two telephone surveys of all United Kingdom adult intensive care units in 2007/8 and 2010 to assess practice with regard to intensive insulin therapy for glycaemic control in critically ill patients, and to assess the change in practice following publications in 2008 and 2009 that challenged the evidence for this therapy. Of 243 units that had a written policy for intensive insulin therapy in 2007/8, 232 (96%) still had a policy in 2010. One hundred and six (46%) units had updated their policy in response to new evidence, whereas 126 (54%) stated that it had remained the same. Where intensive care units had changed their policy, we found a significant increase in target limits and a wider target range. Regional variations in practice were also seen. Across seven regions, the percentage of units where the glycaemic control policy had been updated since 2007/8 varied from nil to 78.9%. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

  18. [The nonlinear relationship between the resuscitation therapy and intensive insulin therapy in severe sepsis and septic shock patients].

    PubMed

    Wang, Da-ming; Zhu, Bin; Ding, Liang-cai; Liu, Ning; Zhang, Jin-song

    2010-06-01

    To study the relationship between the resuscitation therapy and intensive insulin therapy on stress-induced hyperglycemia in severe sepsis and septic shock patients, and to evaluate the value on nonlinear viewpoint in the treatment of patients with sepsis. The data of 129 hospitalized patients with severe sepsis and septic shock were analyzed and they were divided into eight groups every 6 hours in ascending order for full recovery. The resuscitation therapy time of each group was compared with insulin dosage in each unit time with nonlinear least square method. The relationship of the exponential function fit very well between the resuscitation therapy time of each group and the insulin dosage in each unit time. The exponential curve equation was y=e0.739 3-0.015 2x2 (a=0.739 3, b=0.015 2) and the curve fit very well (R2=0.976 943 6). It conforms to the nonlinear viewpoint that the resuscitation therapy time is closely correlated with recovery of dysfunction of endocrine system during the treatment for patients with severe sepsis and septic shock. Therefore, the essence of successful treatment is to concentrate on helping the body rebuild the disorganized network and the recovery of physiological harmony rather than to support and repair the damaged organs.

  19. Intensive insulin therapy for preventing postoperative infection in patients with traumatic brain injury

    PubMed Central

    Wang, Yan; Li, Jin-ping; Song, Ying-lun; Zhao, Qi-huang

    2017-01-01

    Abstract Objective: To assess the effect of intensive insulin therapy (IIT) for preventing postoperative infection in patients with traumatic brain injury (TBI). Methods: In total, 88 patients with TBI were randomly divided into 2 groups, 44 in each group. One group (group ITT) received IIT and the other group (group CIT) received conventional insulin therapy (CIT). This study was conducted between February 2013 and January 2016. Outcomes included infection rate, mortality, and neurological outcome (measured by the Glasgow Outcome Scale [GOS]). Results: A total of 81 patients completed the study. IIT showed greater efficacy than CIT, with a decreased infection rate in the IIT group compared to the CIT group (31.9% vs 52.3%, P = 0.03), and also a reduced duration of stay in intensive care unit (ICU) (IIT group, 4.5 ± 2.1 days vs CIT group, 5.7 ± 2.8 days, P = 0.02). In addition, a significant difference in scores on the GOS scale was observed between the 2 groups (P = 0.04). The mortality rates in hospital and at the 26-week follow-up were similar between the 2 groups. Conclusion: IIT leads to a reduced infection rate, shorter stays in ICU, and improved neurological outcome. PMID:28353579

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

    PubMed

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

    2014-03-04

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

  1. [The influence of intensive insulin therapy on hemodynamics in patients with septic shock].

    PubMed

    Dong, Shi-min; Qin, Yan-jun; Gao, Yu-fang

    2009-05-01

    To elucidate effects of intensive insulin therapy and target glucose control on hemodynamics and cardiac function in patients with septic shock. Twenty-seven patients of septic shock with myocardial depression were divided into routine group (14 cases, level of blood glucose was 4.1 to 6.1 mmol/L) and target group (13 cases, level of blood glucose was 6.2 to 8.3 mmol/L). Hemodynamics and cardiac function parameters were obtained via pulmonary artery catheter after 48 hours. Mean blood glucose level in target group was lower than that in routine group [(6.0+/-1.5) mmol/L vs. (8.2+/-1.9) mmol/L, P<0.05], with dosage of insulin infusion in target group increased as compared with that of routine group [(10.3+/-3.7) U/h vs. (7.5+/-3.0) U/h, P<0.05]. Furthermore, oxygenation index (PaO(2)/FiO(2)), stroke volume index (SVI), cardiac index (CI) and oxygen delivery index (DO(2)I) were increased 20.2%, 23.3%, 15.1% and 11.7%, respectively (all P<0.05). On the other hands, there was no significant difference between target and routine group in mean artery pressure, acute physiology and chronic health evaluation II (APACHEII) score, blood lactic acid (all P>0.05), although the incidence of severe hypoglycemia was higher in target group than the routine group (38.5% vs. 28.6%, P>0.05). Intensive insulin therapy and blood glucose control may improve hemodynamic status and enhance cardiac function in patients with septic shock and myocardial depression.

  2. Acute intensive insulin therapy exacerbates diabetic blood-retinal barrier breakdown via hypoxia-inducible factor-1α and VEGF

    PubMed Central

    Poulaki, Vassiliki; Qin, Wenying; Joussen, Antonia M.; Hurlbut, Peter; Wiegand, Stanley J.; Rudge, John; Yancopoulos, George D.; Adamis, Anthony P.

    2002-01-01

    Acute intensive insulin therapy is an independent risk factor for diabetic retinopathy. Here we demonstrate that acute intensive insulin therapy markedly increases VEGF mRNA and protein levels in the retinae of diabetic rats. Retinal nuclear extracts from insulin-treated rats contain higher hypoxia-inducible factor-1α (HIF-1α) levels and demonstrate increased HIF-1α–dependent binding to hypoxia-responsive elements in the VEGF promoter. Blood-retinal barrier breakdown is markedly increased with acute intensive insulin therapy but can be reversed by treating animals with a fusion protein containing a soluble form of the VEGF receptor Flt; a control fusion protein has no such protective effect. The insulin-induced retinal HIF-1α and VEGF increases and the related blood-retinal barrier breakdown are suppressed by inhibitors of p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol (PI) 3-kinase, but not inhibitors of p42/p44 MAPK or protein kinase C. Taken together, these findings indicate that acute intensive insulin therapy produces a transient worsening of diabetic blood-retinal barrier breakdown via an HIF-1α–mediated increase in retinal VEGF expression. Insulin-induced VEGF expression requires p38 MAPK and PI 3-kinase, whereas hyperglycemia-induced VEGF expression is HIF-1α–independent and requires PKC and p42/p44 MAPK. To our knowledge, these data are the first to identify a specific mechanism for the transient worsening of diabetic retinopathy, specifically blood-retinal barrier breakdown, that follows the institution of intensive insulin therapy. PMID:11901189

  3. Clinical Impact of Sample Interference on Intensive Insulin Therapy in Severely Burned Patients: A Pilot Study

    PubMed Central

    Tran, Nam K.; Godwin, Zachary R.; Bockhold, Jennifer C.; Passerini, Anthony G.; Cheng, Julian; Ingemason, Morgan

    2013-01-01

    Objective Severely burned patients benefit from intensive insulin therapy (IIT) for tight glycemic control (TGC). We evaluated the clinical impact of automatic correction of hematocrit and ascorbic acid interference for bedside glucose monitoring performance in critically ill burn patients. Methods The performance of two point-of-care glucose monitoring systems (GMS): (a) GMS1, an autocorrecting device, and (b) GMS2, a non-correcting device were compared. Sixty remnant arterial blood samples were collected in a prospective observational study to evaluate hematocrit and ascorbic acid effects on GMS1 vs. GMS2 accuracy paired against a plasma glucose reference. Next we enrolled 12 patients in a pilot randomized controlled trial (RCT). Patients were randomized 1:1 to receive IIT targeting a TGC interval of 111–151 mg/dL and guided by either GMS1 or GMS2. GMS bias, mean insulin rate, and glycemic variability were calculated. Results In the prospective study, GMS1 results were similar to plasma glucose results (mean bias: −0.75[4.0] mg/dL, n=60, P=0.214). GMS2 results significantly differed from paired plasma glucose results (mean bias: −5.66[18.7] mg/dL, n=60, P=0.048). Ascorbic acid therapy elicited significant GMS2 performance bias (29.2[27.2], P<0.001). RCT results reported lower mean bias (P<0.001), glycemic variability (P<0.05), mean insulin rate (P<0.001), and frequency of hypoglycemia (P<0.001) in the GMS1 group than the GMS2 group. Conclusions Anemia and high dose ascorbic acid therapy negatively impact GMS accuracy and TGC in burn patients. Automatic correction of confounding factors improves glycemic control. Further studies are warranted to determine outcomes associated with accurate glucose monitoring during IIT. PMID:23884048

  4. Severe hypoglycemia while on intensive insulin therapy is not an independent predictor of death after trauma.

    PubMed

    Mowery, Nathan T; Guillamondegui, Oscar D; Gunter, Oliver L; Diaz, Jose J; Collier, Bryan R; Dossett, Lesly A; Dortch, Marcus J; May, Addison K

    2010-02-01

    Fear of the adverse effects of hypoglycemia has limited the widespread application of intensive insulin therapy (goal, 80-110 mg/dL) in the trauma population. We hypothesized that severe hypoglycemia (SH; intensive insulin therapy from November 2005 to May 2008 was performed. The primary outcomes of interest were any episode of SH (<40 mg/dL) and all-cause inhospital mortality. Multivariate logistic regression was used to estimate the independent relationship between hypoglycemia and death. : Fifty-seven thousand two hundred eighty-four data entries (1,824 patients) from the euglycemia protocol were analyzed (mortality = 16.0%). Median glucose was 119 mg/dL, with 43% of values between 80 mg/dL and 110 mg/dL, 81% between 80 mg/dL and 150 mg/dL, and 0.3% <40 mg/dL. There were 126 severe hypoglycemic episodes in 111 patients (6.1% of the patients). Multivariate logistic regression revealed that SH was not independently associated with death after adjusting for other known risk factors (odds ratio, 1.244; 95% confidence interval, 0.853-1.816; p = 0.257). Hypoglycemia may be an unavoidable byproduct of tight glucose control with 6.1% of the patients experiencing a severe hypoglycemic event (<40 mg/dL). Hypoglycemia is not an independent predictor of death. Hypoglycemia is a statistical probability of time spent on protocol rather than an event leading to death. These data suggest that lower glucose ranges should be targeted in the trauma population without fear of hypoglycemia's adverse effect on mortality.

  5. [Is intensive functional insulin therapy the method of choice in newly diagnosed type-1 diabetes mellitus?].

    PubMed

    Araszkiewicz, Aleksandra; Zozulińska, Dorota; Trepińska, Magdalena; Wierusz-Wysocka, Bogna

    2004-11-01

    The aim of our study was a prospective evaluation of type 1 diabetic patients treated with intensive insulin therapy. We recruited 100 patients (62 males and 38 females) aged 24.3+/-6.2 years with newly diagnosed type 1 diabetes. The mean observation period was 5.2+/-1.5 years. Parameters of diabetes metabolic balance, occurrence of chronic complications and patients' knowledge about the disease and the methods of its treatment were evaluated. 68% of the patients controlled their glycaemia regularly before main meals and 53% of them had a diabetic diary. In the knowledge test 20% of the subjects reached < or = 11 points, 62% 11-17 points and 18% > 17 points (mean 14.4+/-3.2 points of maximal 20 to achieve). The mean result in the questionnaire of knowledge about the disease was 28.1+/-4.9 points. Fasting glycaemia was 7.2+/-3.4 mmol/l, 2h postprandial glycaemia 9.4+/-3.6 mmol/l, HbA1c 7.5+/-1.4%, the mean C-peptide level 0.9+/-0.4 ng/ml and the number of hypoglycaemic episodes was 6/individual/month. We observed a statistically significant correlation between the level of patients' knowledge and HbA1c (r=-0.31, p<0.05). Retinopathy and nephropathy were detected in 8 (9%) and 6 (6.8%) subjects respectively. The risk of microangiopathy was connected with low knowledge (RR: 5.67; 95% CI: 2.02-15.82, p<0.0002). The study confirms the crucial role of intensive insulin therapy and systematic patients' education concerning the disease in maintaining a good metabolic control and thus reducing the risk of diabetic vascular complications.

  6. Full Neurological Recovery after Extreme Hypoglycemia during Intensive Insulin Therapy: A Case Report

    PubMed Central

    Piot, Veerle M.; Verrijcken, Anton; Vanhoof, Marc; Mertens, Ilse; Soetens, Filiep

    2012-01-01

    Since 2000, there has been an ongoing debate regarding tightness of glycemic control in critically ill patients. An increased risk of hypoglycemia is observed in patients treated with an intensive insulin protocol targeting “normoglycemia,” probably accounting for a reduction of the overall benefit. Hypoglycemia is associated with neurological side effects and is found to be an independent predictor of mortality in most trials; however, long-term sequelae are rare if glucose is administered early. We describe a case of prolonged, extreme hypoglycemia in a critically ill patient treated according to an intensive insulin protocol who recovered without any neurological deficit at discharge. PMID:22920826

  7. Barriers and facilitators to the use of computer-based intensive insulin therapy.

    PubMed

    Campion, Thomas R; Waitman, Lemuel R; Lorenzi, Nancy M; May, Addison K; Gadd, Cynthia S

    2011-12-01

    Computerized clinical decision support systems (CDSSs) for intensive insulin therapy (IIT) are increasingly common. However, recent studies question IIT's safety and mortality benefit. Researchers have identified factors influencing IIT performance, but little is known about how workflow affects computer-based IIT. We used ethnographic methods to evaluate IIT CDSS with respect to other clinical information systems and care processes. We conducted direct observation of and unstructured interviews with nurses using IIT CDSS in the surgical and trauma intensive care units at an academic medical center. We observed 49h of intensive care unit workflow including 49 instances of nurses using IIT CDSS embedded in a provider order entry system. Observations focused on the interaction of people, process, and technology. By analyzing qualitative field note data through an inductive approach, we identified barriers and facilitators to IIT CDSS use. Barriers included (1) workload tradeoffs between computer system use and direct patient care, especially related to electronic nursing documentation, (2) lack of IIT CDSS protocol reminders, (3) inaccurate user interface design assumptions, and (4) potential for error in operating medical devices. Facilitators included (1) nurse trust in IIT CDSS combined with clinical judgment, (2) nurse resilience, and (3) paper serving as an intermediary between patient bedside and IIT CDSS. This analysis revealed sociotechnical interactions affecting IIT CDSS that previous studies have not addressed. These issues may influence protocol performance at other institutions. Findings have implications for IIT CDSS user interface design and alerts, and may contribute to nascent general CDSS theory. 2011 Elsevier Ireland Ltd. All rights reserved.

  8. Peers, Regulators, and Professions: The Influence of Organizations in Intensive Insulin Therapy Adoption

    PubMed Central

    Campion, Thomas R.; Gadd, Cynthia S.

    2011-01-01

    Following the landmark Leuven study in 2001, health care organizations implemented intensive insulin therapy (IIT) as the standard of care for critically ill patients. However, a recent meta-analysis showed no mortality benefit and an increased safety risk for patients treated with IIT. IIT affects labor and capital decisions related to nurses, physicians, pharmacists, managers, laboratory personnel, and informatics staff. The expenditure of labor and capital to provide IIT without corresponding outcome improvements suggests the adoption of IIT produces inefficiency in hospitals. In sociology and organizational studies, the tendency for organizations to become more similar without necessarily becoming more efficient is called institutional isomorphism. Institutional isomorphism examines the pressure organizations encounter from peers, regulators, and professions through mimetic, coercive, and normative mechanisms, respectively. To enhance their prospects of survival, organizations establish and maintain legitimacy by adopting socially acceptable approaches to work endorsed by successful peer organizations, regulatory agencies, and professional societies. In this paper, the authors describe how organizational influence—through the Leuven study, the Joint Commission, and professional organizations—played a role in the widespread adoption of IIT. Divergence from institutionalized forms may explain variation in IIT studies following Leuven. Healthcare researchers, practitioners, and managers should consider organizational influence when implementing large scale clinical activities. PMID:19369854

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

    PubMed

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

    2015-09-01

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

  10. 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? ...

  11. Validity of bedside blood glucose measurement in critically ill patients with intensive insulin therapy

    PubMed Central

    Mahmoodpoor, Ata; Hamishehkar, Hadi; Shadvar, Kamran; Sanaie, Sarvin; Iranpour, Afshin; Fattahi, Vahid

    2016-01-01

    Background and Aims: There have been variable results on the practice of tight glycemic control, and studies have demonstrated that point-of-care (POC) glucometers have variable accuracy. Glucometers must be accurate, and many variables can affect blood glucose levels. The purpose of this study was to determine the difference between blood glucose concentrations obtained from POC glucometers and laboratory results in critically ill patients with intensive insulin therapy. Materials and Methods: This was a descriptive study which enrolled 300 critically ill patients. Four samples of arterial blood were collected and analyzed at the bedside with the POC glucometer and also in the central laboratory to obtain the blood glucose level. To define the effect of various factors on this relation, we noted the levels of hemoglobin (Hb), PaO2, body temperature, bilirubin, history of drug usage, and sepsis. Results: There were not any significant differences between blood sugar levels using laboratory and glucometer methods of measurements. There was a good and significant correlation between glucose levels between two methods (r = 0.81, P < 0.001). Among evaluated factors (body temperature, bilirubin level, blood pressure, Hb level, PaO2, sepsis, and drugs) which added one by one in model, just drugs decreased the correlation more than others (r = 0.78). Conclusions: The results of POC glucometer differ from laboratory glucose concentrations, especially in critically ill patients with unstable hemodynamic status while receiving several drugs. This may raise the concern about using POC devices for tight glycemic control in critically ill patients. These results should be interpreted with caution because of the large variation of accuracy among different glucometer devices. PMID:27994380

  12. Influence of and Optimal Insulin Therapy for a Low–Glycemic Index Meal in Children With Type 1 Diabetes Receiving Intensive Insulin Therapy

    PubMed Central

    Ryan, Rochelle L.; King, Bruce R.; Anderson, Donald G.; Attia, John R.; Collins, Clare E.; Smart, Carmel E.

    2008-01-01

    OBJECTIVE—The purpose of this study was to quantify the effects of glycemic index on postprandial glucose excursion (PPGE) in children with type 1 diabetes receiving multiple daily injections and to determine optimal insulin therapy for a low–glycemic index meal. RESEARCH DESIGN AND METHODS—Twenty subjects consumed test breakfasts with equal macronutrient contents on 4 consecutive days; high–and low–glycemic index meals (glycemic index 84 vs. 48) were consumed with preprandial ultra-short-acting insulin, and the low–glycemic index meal was also consumed with preprandial regular insulin and postprandial ultra-short-acting insulin. Each child's insulin dose was standardized. Continuous glucose monitoring was used. RESULTS—The PPGE was significantly lower for the low–glycemic index meal compared with the high–glycemic index meal at 30–180 min (P < 0.02) when preprandial ultra-short-acting insulin was administered. The maximum difference occurred at 60 min (4.2 mmol/l, P < 0.0001). Regular insulin produced a 1.1 mmol/l higher PPGE at 30 min compared with ultra-short-acting insulin (P = 0.015) when the low–glycemic index meal was consumed. Postprandial ultra-short-acting insulin produced a higher PPGE at 30 and 60 min compared with preprandial administration when the low–glycemic index meal was consumed. The maximum difference was 2.5 mmol/l at 60 min (P < 0.0001). CONCLUSIONS—Low–glycemic index meals produce a lower PPGE than high–glycemic index meals. Preprandial ultra-short-acting insulin is the optimal therapy for a low–glycemic index meal. PMID:18458138

  13. High-intensity Exercise in Men with Type 1 Diabetes and Mode of Insulin Therapy.

    PubMed

    Gawrecki, Andrzej; Naskret, Dariusz; Niedzwiecki, Pawel; Duda-Sobczak, Anna; Araszkiewicz, Aleksandra; Zozulinska-Ziolkiewicz, Dorota

    2017-04-01

    The purpose of this study was to evaluate the impact of high intensity exercise on glucose levels and risk of metabolic decompensation in males with type 1 diabetes (T1D), depending on the method of insulin administration. The study comprised 29 males (aged 25.3±5.1 years; duration of diabetes 10.3±3.2 years) treated with continuous subcutaneous insulin infusion (CSII) or multiple daily insulin injections (MDI). Treadmill exercise test was performed twice in each patient until subjective exhaustion as maximum according to the Borg scale. All the patients achieved ≥85% of the maximal heart rate. Distance during the test was 4 500±1 400 m and 4 473±1 559 m in the MDI and CSII groups, respectively, which was achieved in 31±8 min. During the test and in the 6 h after, no clinically significant episodes of hypoglycemia occurred. Mean glucose levels did not exceed 10 mmol/L in most patients. The risk of the composite endpoint (hypoglycemia<3.8 mmol/L, hyperglycemia≥16.6 mmol/L, ketones≥0.6 mmol/L, and lactate>2.2 mmol/L) was higher in patients treated with MDI than CSII (OR3.75, 95%CI:1.22-11.52, p=0.02). In conclusion, planned high intensity physical effort in men with well-controlled T1D is metabolically safe. CSII shows greater metabolic advantage over MDI during and after high intensity exercise in men with T1D. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Effect of intensive insulin therapy on first-phase insulin secretion in newly diagnosed type 2 diabetic patients with a family history of the disease

    PubMed Central

    LI, QING; WANG, LUAN; XIAO, LIN; WANG, ZHONGCHAO; WANG, FANG; YU, XIAOLONG; YAN, SHENGLI; WANG, YANGANG

    2015-01-01

    Intensive insulin treatment is known to improve β-cell function in the majority of patients with newly diagnosed type 2 diabetes mellitus (T2DM), and family history (FH) is known to be an important independent risk factor for T2DM. Thus, the aim of the present study was to investigate the difference in first-phase insulin secretion and the effect of intensive insulin therapy on the improvement of β-cell function between T2DM patients with and without a FH of diabetes. Patients with newly diagnosed T2DM and healthy controls were divided into groups according to their FH of diabetes. Improvement in β-cell function was evaluated with an arginine stimulation test after two weeks of continuous subcutaneous insulin infusion (CSII). Compared with the control group, the level of fasting insulin and the homeostasis model assessment of insulin resistance (HOMA2-IR) were higher in the DM group, while the homeostasis model assessment of β-cell insulin secretion (HOMA2-%β) and the first-phase peak ratio were lower (P<0.05). In addition, the first-phase peak ratio in the FH- control group was higher compared with that in the FH+ control group (P=0.023). Following CSII, all the patients achieved excellent blood glucose control in 6.2±3.6 days, without severe adverse effects. In the DM groups, the fasting insulin level and HOMA2-IR were lower, while the HOMA2-%β and first-phase peak ratio were higher, when compared with the values prior to treatment, particularly in the FH- DM group. The HOMA2-%β in the FH+ DM group was lower compared with the FH- DM group (P=0.027). Therefore, T2DM patients with and without a FH of the disease were shown to have a good response to CSII in the improvement of insulin resistance and β-cell function; however, the improvements were less significant in patients with a FH compared with patients without a FH of diabetes. PMID:25574243

  15. Retinol and alpha-tocopherol in serum of type 1 diabetic patients with intensive insulin therapy: a long term follow-up study.

    PubMed

    Granado, F; Olmedilla, B; Botella, F; Simal, A; Blanco, I

    2003-02-01

    We evaluated the effect of intensive insulin therapy and glycemic control in patients with type 1 diabetes on biochemical markers of vitamin A and E. Fifty-seven patients with type 1 diabetes were enrolled in a follow-up study for 3 to 33 mo. At entrance, all patients were on conventional insulin therapy or recently had been diagnosed with the disease. Intensive insulin therapy (multiple daily glycemia records and at least three insulin doses daily) was established, and every 3 to 6 mo patients were screened for clinical, biochemical, and hematologic indexes. Biochemical markers of vitamin A and E nutrition status were measured at each visit by a quality-controlled high-performance liquid chromatography. At entrance, serum retinol concentrations, but not the ratio of alpha-tocopherol to cholesterol, showed a negative correlation with increasing values of HbA1c and insulin dose, neither of which was significant in multiple regression models. With intensive insulin therapy, a trend to normalize parameters of glycemic control (HbA1c and fructosamine) was observed within subjects and on a group level. However, no significant changes were observed in serum retinol or alpha-tocopherol:cholesterol ratio according to the metabolic control of the disease. Patients with type 1 diabetes under intensive insulin therapy tend to normalize the clinical parameters of glycemic control, although this improvement does not significantly affect biochemical markers of vitamin A and E status.

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

    PubMed

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

    2016-05-01

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

  17. Featured Article: Oxidative stress status and liver tissue defenses in diabetic rats during intensive subcutaneous insulin therapy.

    PubMed

    Dal, Stéphanie; Jeandidier, Nathalie; Seyfritz, Elodie; Bietiger, William; Péronet, Claude; Moreau, François; Pinget, Michel; Maillard, Elisa; Sigrist, Séverine

    2016-01-01

    Long-term insulin delivery can reduce blood glucose variability in diabetic patients. In this study, its impact on oxidative stress status, inflammation, and liver injury was investigated. Diabetes was induced in Wistar rats with a single dose of streptozotocin (100 mg/kg). Untreated rats and rats administered Insuplant® (2 UI/200 g/day) through a subcutaneous osmotic pump for one or four weeks were compared with non-diabetic controls. Body weight, fructosamine level, total cholesterol, Insulin Growth Factor-1 (IGF-1) level, lipid peroxidation, and total antioxidant capacity were measured. Hepatic injury was determined through the measurement of glycogen content, reactive oxygen species (ROS) production, and macrophage infiltration. Liver oxidative stress status was evaluated through the measurement of superoxide dismutase (SOD), catalase (CAT), and nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) expression, and p38 mitogen-activated protein kinase (p38MAPK) activation. Induction of diabetes led to increased plasma oxidative stress and inflammation. Moreover, ROS production and macrophage infiltration increased in addition to SOD, CAT, and NADPH oxidase expression. Intensive insulin therapy improved metabolic control in diabetic animals as seen by a restoration of hepatic glycogen, plasma IGF-1 levels, and a decrease in plasma oxidative stress. However, insulin treatment did not result in a decrease in acute inflammation in diabetic rats as seen by continued ROS production and macrophage infiltration in the liver, and a decrease of p38MAPK activation. These results suggest that the onset of diabetes induces liver oxidative stress and inflammation, and that subcutaneous insulin administration cannot completely reverse these changes. Targeting oxidative stress and/or inflammation in diabetic patients could be an interesting strategy to improve therapeutic options.

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

    PubMed

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

    2010-07-01

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

  19. Effects of intensive insulin therapy alone and in combination with pioglitazone on body weight, composition, distribution and liver fat content in patients with type 2 diabetes.

    PubMed

    Shah, P K; Mudaliar, S; Chang, A R; Aroda, V; Andre, M; Burke, P; Henry, R R

    2011-06-01

    To evaluate the effects of intensive insulin therapy alone and with added pioglitazone on body weight, fat distribution, lean body mass (LBM) and liver fat in type 2 diabetic patients. Twenty-five insulin-treated, obese patients with type 2 diabetes were randomized to addition of pioglitazone 45 mg (n = 12) or placebo (n = 13) and treated intensively for 12-16 weeks. Dual-energy X-ray absorptiometry/abdominal computed tomography scans were performed before/after treatment. LBM, visceral/subcutaneous adipose tissue (VAT/SAT) and liver/spleen (L/S) attenuation ratios were measured pre-/posttreatment (a ratio <1 represents fatty liver). Intensive insulin alone and insulin + pioglitazone significantly improved glycaemic control (7.8 ± 0.3 to 7.2 ± 0.3% and 7.6 ± 0.3 to 7.1 ± 0.4%, respectively). Body weight gain was greater with insulin + pioglitazone (4.9 ± 4.5 kg) versus insulin therapy alone (1.7 ± 0.7 kg). SAT increased significantly with pioglitazone + insulin therapy (393.9 ± 48.5 to 443.2 ± 56.7 cm(2) , p < 0.01) compared to a non-significant increase with insulin therapy alone (412.9 ± 42.5 to 420.8 ± 43.8 cm(2) ). VAT decreased non-significantly in both groups (240.3 ± 41.7 to 223.8 ± 38.1 cm(2) with insulin + pioglitazone and 266.6 ± 27.4 to 250.5 ± 22.2 cm(2) with insulin therapy). LBM increased significantly by 1.92 ± 0.74 kg with insulin + pioglitazone treatment. The L/S attenuation ratio in the placebo + insulin group decreased from 1.08 ± 0.1 to 1.04 ± 0.1 (p = ns) and increased from 1.00 ± 0.1 to 1.08 ± 0.05 (p = 0.06) in the pioglitazone + insulin group. Intensification of insulin therapy in type 2 diabetic patients causes modest weight gain and no change in body fat distribution, LBM or liver fat. In contrast, the addition of pioglitazone, at equivalent glycaemia, increases weight gain, fat mass and SAT; increases LBM and tends to decrease liver fat. These changes in fat distribution may contribute to the beneficial effects of

  20. A critical appraisal of Vlasselaers D, Milants I, Desmet L, et al: intensive insulin therapy for patients in paediatric intensive care: a prospective, randomised controlled study. Lancet 2009; 373:547-556.

    PubMed

    Ulate, Kalia P

    2011-07-01

    To review findings and discuss implications of strict glycemic control in children. Critical appraisal of a randomized controlled trial. This is the largest prospective randomized controlled trial to date, comparing intensive insulin therapy (glycemic targets: 50.4-79.2 mg/dL [2.8-4.4 mmol/L] and 70.2-99 mg/dL [3.9-5.5 mmol/L] [for infants and children, respectively]) and conventional insulin therapy (target: 180-215 mg/dl [10-11.9 mmol/L]) among critically ill children. Groups were similar at enrollment and had comparable forms of nutrition and glucose infusion rates. Steroid use and vasoactive-inotrope scores were not compared. Intensive insulin therapy reduced pediatric intensive care unit length of stay (primary outcome measure) and attenuated C-reactive protein concentrations >5 days. The effect of intensive insulin therapy on secondary outcome measures was precise in regards to significant reductions in secondary infection occurrence (absolute risk reduction = 7.6% [95% confidence interval: 0.6-14.4], number needed to treat = 14 [95% confidence interval: 7-179]) and need for vasoactive support beyond 2 days (absolute risk reduction = 10.4% [95% confidence interval: 3-17], number needed to treat = 10 [95% confidence interval: 6-30]). Mortality decreased with intensive insulin therapy (p = .038); however, this finding was imprecise (absolute risk reduction = 3.1% [95% confidence interval: 0.2-5.4], number needed to treat = 33 [95% confidence interval: 18.6-597.3]). The incidence of hypoglycemia was significantly higher with intensive insulin therapy (absolute risk increase = 23.5% [95% confidence interval: 20-25%], number needed to harm = 4 [95% confidence interval: 4-5]). Long-term effects on outcomes were not evaluated, and the authors recognize the need for such follow-up studies. This study demonstrated efficacy of intensive insulin therapy at the same institution where the original adult intensive insulin therapy trial was conducted, but it may not

  1. Use of intensive insulin therapy for the management of glycemic control in hospitalized patients: a clinical practice guideline from the American College of Physicians.

    PubMed

    Qaseem, Amir; Humphrey, Linda L; Chou, Roger; Snow, Vincenza; Shekelle, Paul

    2011-02-15

    The American College of Physicians (ACP) developed this guideline to present the evidence for the link between the use of intensive insulin therapy to achieve different glycemic targets and health outcomes in hospitalized patients with or without diabetes mellitus. Published literature on this topic was identified by using MEDLINE and the Cochrane Library. Additional articles were obtained from systematic reviews and the reference lists of pertinent studies, reviews, and editorials, as well as by consulting experts; unpublished studies on ClinicalTrials.gov were also identified. The literature search included studies published from 1950 through March 2009. Searches were limited to English-language publications. The primary outcomes of interest were short-term mortality and hypoglycemia. This guideline grades the evidence and recommendations by using the ACP clinical practice guidelines grading system. RECOMMENDATION 1: ACP recommends not using intensive insulin therapy to strictly control blood glucose in non-surgical intensive care unit (SICU)/medical intensive care unit (MICU) patients with or without diabetes mellitus (Grade: strong recommendation, moderate-quality evidence). RECOMMENDATION 2: ACP recommends not using intensive insulin therapy to normalize blood glucose in SICU/MICU patients with or without diabetes mellitus (Grade: strong recommendation, high-quality evidence). RECOMMENDATION 3: ACP recommends a target blood glucose level of 7.8 to 11.1 mmol/L (140 to 200 mg/dL) if insulin therapy is used in SICU/MICU patients (Grade: weak recommendation, moderate-quality evidence).

  2. Long-term, intermittent, insulin-induced hypoglycemia produces marked obesity without hyperphagia or insulin resistance: A model for weight gain with intensive insulin therapy

    PubMed Central

    Teske, Jennifer A.; Kotz, Catherine M.; Dunn-Meynell, Ambrose; Levin, Barry E.; McCrimmon, Rory J.; Sherwin, Robert S.

    2013-01-01

    A major side effect of insulin treatment of diabetes is weight gain, which limits patient compliance and may pose additional health risks. Although the mechanisms responsible for this weight gain are poorly understood, it has been suggested that there may be a link to the incidence of recurrent episodes of hypoglycemia. Here we present a rodent model of marked weight gain associated with weekly insulin-induced hypoglycemic episodes in the absence of diabetes. Insulin treatment caused a significant increase in both body weight and fat mass, accompanied by reduced motor activity, lowered thermogenesis in response to a cold challenge, and reduced brown fat uncoupling protein mRNA. However, there was no effect of insulin treatment on total food intake nor on hypothalamic neuropeptide Y or proopiomelanocortin mRNA expression, and insulin-treated animals did not become insulin-resistant. Our results suggest that repeated iatrogenic hypoglycemia leads to weight gain, and that such weight gain is associated with a multifaceted deficit in metabolic regulation rather than to a chronic increase in caloric intake. PMID:23169787

  3. Long-term, intermittent, insulin-induced hypoglycemia produces marked obesity without hyperphagia or insulin resistance: a model for weight gain with intensive insulin therapy.

    PubMed

    McNay, Ewan C; Teske, Jennifer A; Kotz, Catherine M; Dunn-Meynell, Ambrose; Levin, Barry E; McCrimmon, Rory J; Sherwin, Robert S

    2013-01-15

    A major side effect of insulin treatment of diabetes is weight gain, which limits patient compliance and may pose additional health risks. Although the mechanisms responsible for this weight gain are poorly understood, it has been suggested that there may be a link to the incidence of recurrent episodes of hypoglycemia. Here we present a rodent model of marked weight gain associated with weekly insulin-induced hypoglycemic episodes in the absence of diabetes. Insulin treatment caused a significant increase in both body weight and fat mass, accompanied by reduced motor activity, lowered thermogenesis in response to a cold challenge, and reduced brown fat uncoupling protein mRNA. However, there was no effect of insulin treatment on total food intake nor on hypothalamic neuropeptide Y or proopiomelanocortin mRNA expression, and insulin-treated animals did not become insulin-resistant. Our results suggest that repeated iatrogenic hypoglycemia leads to weight gain, and that such weight gain is associated with a multifaceted deficit in metabolic regulation rather than to a chronic increase in caloric intake.

  4. How and why do patients with Type 1 diabetes sustain their use of flexible intensive insulin therapy? A qualitative longitudinal investigation of patients' self-management practices following attendance at a Dose Adjustment for Normal Eating (DAFNE) course.

    PubMed

    Rankin, D; Cooke, D D; Clark, M; Heller, S; Elliott, J; Lawton, J

    2011-05-01

    Conventional insulin therapy requires patients with Type 1 diabetes to adhere to rigid dietary and insulin injection practices. Recent trends towards flexible intensive insulin therapy enable patients to match insulin to dietary intake and lifestyle; however, little work has examined patients' experiences of incorporating these practices into real-life contexts. This qualitative longitudinal study explored patients' experiences of using flexible intensive insulin therapy to help inform the development of effective long-term support. Semi-structured interviews were conducted with 30 adult patients with Type 1 diabetes following participation in a structured education programme on using flexible intensive insulin therapy, and 6 and 12 months post-course. Longitudinal data analysis used an inductive, thematic approach. Patients consistently reported feeling committed to and wanting to sustain flexible intensive insulin therapy. This regimen was seen as a logical and effective method of self-management, as patients experienced improved blood glucose readings and/or reported feeling better. Implementing and sustaining flexible intensive insulin therapy was enhanced when patients had stable routines, with more challenges reported by those working irregular hours and during weekends/holidays. Some patients re-crafted their lives to make this approach work for them; for instance, by creating dietary routines or adjusting dietary choices. Clinical data have shown that flexible intensive insulin therapy can lead to improvement in glycaemic control. This study, drawing on patients' perspectives, provides further endorsement for flexible intensive insulin therapy by demonstrating patients' liking of, and their motivation to sustain, this approach over time. To help patients implement and sustain flexible intensive insulin therapy, follow-up support should encourage them to identify routines to better integrate this regimen into their lives. © 2011 The Authors. Diabetic

  5. The intriguing effects of time to glycemic goal in newly diagnosed type 2 diabetes after short-term intensive insulin therapy.

    PubMed

    Cheng, Lin; Xu, Mingtong; Lin, Xiuhong; Tang, Juying; Qi, Yiqin; Wan, Yan; Pan, Xiaofang; Chen, Xiaoyun; Ren, Meng; Yan, Li

    2016-08-31

    Short-term intensive insulin therapy is effective for type 2 diabetes because it offers the potential to achieve excellent glycemic control and improve β-cell function. We observed that the time to glycemic goal (TGG) was adjustable. Original data of 138 newly diagnosed type 2 diabetic patients received intensive insulin therapy by continuous subcutaneous insulin infusion for 2-3 weeks were retrospectively collected. Subjects underwent an intravenous glucose tolerance test (IVGTT) and an oral glucose tolerance test (OGTT) pre and post treatment. The glycemic goal was achieved within 6 (4-8) days. Patients were divided into two groups by TGG above (TGG-slow) and below (TGG-fast) the median value. Patients in both groups had significantly better glycemic control. Compared with TGG-fast, TGG-slow required a few more total insulin and performed more improvement of HOMA-β and IVGTT-AUCIns, but less improvement of HOMA-IR and QUICKI. Multiple linear regression analysis revealed that TGG was always an explanatory variable for the changes (HOMA-β, IVGTT-AUCIns, HOMA-IR and QUICKI). The hypoglycemia prevalence was lower in TGG-slow (1.48% vs. 3.40%, P<0.01). Multivariate logistic regression analysis indicated that individuals in TGG-slow had a lower risk of hypoglycemia (adjusted OR, 0.700; 95% CI, 0.567-0.864; P<0.05). Multiple linear regression analysis confirmed that the ratio of the incremental insulin to glucose responses over the first 30 min during OGTT (ΔIns30/ΔG30), average insulin dose before achieving targets, initial insulin dose and LDL-c were independent predictors for TGG. It is intriguing to hypothesize that patients with fast time to glycemic goal benefit more in improving insulin sensitivity, but patients with slow time benefit more in improving β-cell function and reducing the risk of hypoglycemia.

  6. Effects of intensive insulin therapy alone and with added pioglitazone on renal salt/water balance and fluid compartment shifts in type 2 diabetes.

    PubMed

    Mudaliar, S; Chang, A R; Aroda, V R; Chao, E; Burke, P; Baxi, S; Griver, K A; O'Connor, D T; Henry, R R

    2010-02-01

    To evaluate the effects of intensive insulin therapy alone or with added pioglitazone on renal salt/water balance and body fluid compartment shifts in type 2 diabetes. A total of 25 insulin-treated, obese patients with type 2 diabetes were randomized to pioglitazone 45 mg (n = 12) or placebo (n = 13) and treated intensively for 12-16 weeks to achieve equivalent glycaemic control. We measured total body water (TBW) and extracellular/intracellular fluid by bioimpedance analysis; plasma/RBC volume with I(131)albumin; sodium handling by fractional excretion of sodium/lithium (FeNa/FeLi) and other renal/hormonal parameters. Intensification of insulin therapy and the addition of pioglitazone significantly improved glycaemia (HbA1C 7.8-7.2% and 7.6-7.1%) and increased body weight (1.7 and 4.9 kg) respectively. TBW increased 1.7 l with insulin alone (65% intracellular) and 1.6 l with added pioglitazone (75% extracellular) (p = 0.06 and 0.09 respectively). Plasma volume increased 0.2 +/- 0.1 l with insulin alone (p = 0.05) and 0.4 +/- 0.1 l with added pioglitazone (p < 0.05). Extravascular, extracellular (interstitial) fluid increased significantly and more with added pioglitazone (0.8 +/- 0.2 l, p < 0.01) than with insulin alone (0.4 +/- 0.2 l, p = ns). At steady-state, FeLi (marker of proximal-tubular sodium delivery to the distal nephron) increased significantly with added pioglitazone (12.4 +/- 1.3 to 18.0 +/- 3.2%) vs. no significant change with insulin alone (15.4 +/- 1.2 to 14.5 +/- 2.3%). There were no significant changes in the other parameters. In intensively insulin-treated obese type 2 diabetic patients, at equivalent glycaemic control, the addition of pioglitazone causes greater weight gain, but a similar increase in body water that is mainly extracellular and interstitial compared with intracellular increase with insulin therapy alone. Pioglitazone also increases the filtered load of sodium reabsorbed at the distal nephron with no net change in FeNa.

  7. Continuous subcutaneous insulin infusion vs intensive conventional insulin therapy in pregnant diabetic women: a systematic review and metaanalysis of randomized, controlled trials.

    PubMed

    Mukhopadhyay, Asima; Farrell, Tom; Fraser, Robert B; Ola, Bolarinde

    2007-11-01

    The objective of the study was to study the effects of continuous subcutaneous insulin infusion (CSII) vs multiple-dose insulin (MDI) therapy on glycemic control and pregnancy outcome in diabetic women. Randomized, controlled trials comparing CSII vs MDI in pregnant diabetic women were included after an electronic database search. Studies were rated for quality independently by 2 reviewers in accordance with the Quality of Reporting of Metaanalyses statement. Summary weighted mean difference and odds ratio were estimated for insulin dose, birthweight, gestational age, mode of delivery, hypoglycemic/ketotic episodes, worsening retinopathy, neonatal hypoglycemia, and rates of intrauterine fetal death. Six randomized clinical trials met the inclusion criteria. Pregnancy outcomes and glycemic control were not significantly different among treatment groups. Higher number of ketoacidotic episodes and diabetic retinopathy found in the CSII group did not reach statistical significance. This systematic review does not show any advantage or disadvantage of using CSII over MDI in pregnant diabetic women. Large multicenter, randomized, controlled trials addressing the quality of life/cost effectiveness are required.

  8. 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.

  9. A cluster randomised trial, cost-effectiveness analysis and psychosocial evaluation of insulin pump therapy compared with multiple injections during flexible intensive insulin therapy for type 1 diabetes: the REPOSE Trial.

    PubMed

    Heller, Simon; White, David; Lee, Ellen; Lawton, Julia; Pollard, Daniel; Waugh, Norman; Amiel, Stephanie; Barnard, Katharine; Beckwith, Anita; Brennan, Alan; Campbell, Michael; Cooper, Cindy; Dimairo, Munyaradzi; Dixon, Simon; Elliott, Jackie; Evans, Mark; Green, Fiona; Hackney, Gemma; Hammond, Peter; Hallowell, Nina; Jaap, Alan; Kennon, Brian; Kirkham, Jackie; Lindsay, Robert; Mansell, Peter; Papaioannou, Diana; Rankin, David; Royle, Pamela; Smithson, W Henry; Taylor, Carolin

    2017-04-01

    Insulin is generally administered to people with type 1 diabetes mellitus (T1DM) using multiple daily injections (MDIs), but can also be delivered using infusion pumps. In the UK, pumps are recommended for patients with the greatest need and adult use is less than in comparable countries. Previous trials have been small, of short duration and have failed to control for training in insulin adjustment. To assess the clinical effectiveness and cost-effectiveness of pump therapy compared with MDI for adults with T1DM, with both groups receiving equivalent structured training in flexible insulin therapy. Pragmatic, multicentre, open-label, parallel-group cluster randomised controlled trial, including economic and psychosocial evaluations. After participants were assigned a group training course, courses were randomly allocated in pairs to either pump or MDI. Eight secondary care diabetes centres in the UK. Adults with T1DM for > 12 months, willing to undertake intensive insulin therapy, with no preference for pump or MDI, or a clinical indication for pumps. Pump or MDI structured training in flexible insulin therapy, followed up for 2 years. MDI participants used insulin analogues. Pump participants used a Medtronic Paradigm(®) Veo(TM) (Medtronic, Watford, UK) with insulin aspart (NovoRapid, Novo Nordisk, Gatwick, UK). Primary outcome - change in glycated haemoglobin (HbA1c) at 2 years in participants whose baseline HbA1c was ≥ 7.5% (58 mmol/mol). Key secondary outcome - proportion of participants with HbA1c ≤ 7.5% at 2 years. Other outcomes at 6, 12 and 24 months - moderate and severe hypoglycaemia; insulin dose; body weight; proteinuria; diabetic ketoacidosis; quality of life (QoL); fear of hypoglycaemia; treatment satisfaction; emotional well-being; qualitative interviews with participants and staff (2 weeks), and participants (6 months); and ICERs in trial and modelled estimates of cost-effectiveness. We randomised 46 courses comprising 317 participants

  10. 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.

  11. 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

  12. Intensive or conventional insulin therapy in type 2 diabetic patients? A population-based study on metabolic control and quality of life (The JEVIN-trial).

    PubMed

    Schiel, R; Müller, U A

    1999-01-01

    Long-term micro- and macrovascular complications cause major morbidity and mortality in patients with type 2 diabetes mellitus. Up to the present it is not clear whether intensified or conventional insulin treatment is more effective to keep blood glucose concentrations close to the normal range. In the present trial 90% (n = 117) of all insulin-treated type 2 diabetic patients aged 16 to 60 years and living in the city of Jena (100,247 inhabitants), Thuringia, Germany were examined. Fourty patients (34%) were on intensive insulin therapy (ICT, > or = 2 injections of normal- and > or = 1 injection of NPH-/mixed-insulin/day, > or = 1 insulin-dose adjustments/week, > or = 2 blood-glucose self-tests/day) and 77 patients (66%) were on conventional insulin therapy (CIT). Patients with ICT had more injections/d (4.3 +/- 0.7 vs CIT 2.4 +/- 0.7, p < 0.001), more insulin-dose adjustments/week < or = 11.5 +/- 8.2 vs 2.2 +/- 5.2, p < 0.001) and more blood-glucose self-tests/week (25.2 +/- 5.7 vs 9.6 +/- 8.8, p < 0.001). Patients with ICT had higher insulin doses (0.71 +/- 0.32 vs 0.47 +/- 0.2 IU/kg body wt/d, p < 0.001), were younger (50.5 +/-6.7 vs 54.0 +/- 5.9 years, p = 0.004) and they had a non-significant tendency to a better HbAlc (8.7 +/- 2.2 vs 9.2 +/- 2.0%, p = 0.23, HPLC, Diamat, normal range 4.4-5,9%). There was a negative correlation between HbAlc and the frequency of blood-glucose self-tests/week (r = -0.23, p = 0.019) and the number of insulin-dose adjustments/week (r = -0.33, p < 0.001). There were no differences between the groups as regards body-mass index (29.7 +/-4.9 vs 28.0 +/- 4.5 kg/m2, p = 0.06), diabetes duration (12.3 +/- 6.9 vs 12.2 +/- 7.5 years, p = 0.96), duration of insulin therapy (4.2 +/-3.5 versus 4.5 +/- 4.8 years, p = 0.67), incidence of acute complications (severe hypoglycaemia, diabetic coma), prevalence of retino-, nephro- and neuropathy (assessed according to Young et al.) and education or socio-economic factors. Also, in respect of

  13. [Insulin producing cells as therapy in diabetes mellitus].

    PubMed

    Schnedl, W J; Hohmeier, H E; Newgard, C B

    1996-01-01

    Even with intensive insulin therapy it is impossible to reach physiological blood glucose levels in insulin-dependent diabetes mellitus. Because of the high costs and technical problems involved in islet cell transplantation broad applicability of this therapy seems uncertain. An alternative approach is the development of molecular-engineered insulin-producing clonal cell lines. The main interest is in rodent insulinoma cell lines and neuroendocrine AtT-20ins cells. This paper reviews the current knowledge about glucose-stimulated insulin secretion and the problems that have to be solved before these cells can be used for therapy in diabetes mellitus.

  14. Insulin therapy in children and adolescents.

    PubMed

    Tamborlane, William V; Sikes, Kristin A

    2012-03-01

    Insulin therapy is the mainstay of treatment in children and adolescents with type 1 diabetes (T1D) and is a key component in the treatment of type 2 diabetes (T2D) in this population as well. A major aim of current insulin replacement therapy is to simulate the normal pattern of insulin secretion as closely as possible. This aim can best be achieved with basal-bolus therapy using multiple daily injections (MDI) or continuous insulin infusion (CSII) pump therapy. Only a few years ago, options for insulin formulations were limited. There are now more than 10 varieties of biosynthetic human and analogue insulin.

  15. Perioperative intensive insulin therapy using an artificial endocrine pancreas with closed-loop glycemic control system: the effects of no hypoglycemia.

    PubMed

    Hanazaki, Kazuhiro; Kitagawa, Hiroyuki; Yatabe, Tomoaki; Munekage, Masaya; Dabanaka, Ken; Takezaki, Yuka; Tsukamoto, Yuuki; Asano, Takuji; Kinoshita, Yoshihiko; Namikawa, Tsutomu

    2014-06-01

    We examined whether perioperative intensive insulin therapy (IIT) using an artificial pancreas (AP) with a closed-loop glycemic control system can be used to prevent hypoglycemia in surgical patients. Between 2006 and 2012, perioperative glycemic control using an AP was performed in 427 patients undergoing general surgery. A total of 305 patients undergoing IIT using an AP in the target blood glucose range of 80 to 110 mg/dL were enrolled in the study. Data were collected prospectively and were reviewed or analyzed retrospectively. No patients had hypoglycemia. Perioperative mean blood glucose level and achievement rates in target blood glucose range of 80 to 110 mg/dL were 100.5 ± 11.9 mg/dL and 88.1% ± 16.0%, respectively. For the 3 primary operative methods, including hepatic, pancreatic, and esophageal resections, there were no significant differences in glycemic control stability between the types of surgery. Perioperative IIT using an AP with a closed-loop glycemic control system can be used to prevent hypoglycemia and maintain stable glycemic control with less variability of blood glucose concentration. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. 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

  17. 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.

  18. [Insulin pump therapy: for whom and why?].

    PubMed

    Saraheimo, Markku; Honkasalo, Mikko; Miettinen, Marko

    2013-01-01

    Insulin pump therapy utilizes continuous infusion for the basic supply of insulin. As compared with multiple daily injections, pump therapy enables a clearly more precise targeting of the insulin therapy with respect to both time and quantity. This is important for insulin-sensitive patients such as small children, adults susceptible to hypoglycemia, or diabetics, whose blood glucose level exhibits a clear-cut elevation in the small hours (the dawn phenomenon). Also a diabetic with a high HbA1c and a good motivation for treatment may significantly benefit from the pump. Insulin pump therapy requires commitment to good self-monitoring from the diabetic patient.

  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. Knowledge after five-day teaching program in intensive insulin therapy performed at the onset of type 1 diabetes influence the development of late diabetic complications.

    PubMed

    Araszkiewicz, Aleksandra; Zozulinska-Ziolkiewicz, Dorota; Trepinska, Magdalena; Wierusz-Wysocka, Bogna

    2008-07-01

    We evaluated the influence of baseline diabetic knowledge on clinical course of type 1 diabetes treated with intensive functional insulin therapy (IFIT) from the onset of the disease. 86 subjects with newly diagnosed type 1 diabetes, aged 23.4+/-5.1 attended a five-day structured training program in IFIT at baseline, followed by a test consisting of 20 questions. Patients were divided into subgroups according to test results: group A>16, group B 12-16 and group C<12 scores. At follow-up (7.1+/-1.5 years) metabolic control and development of microangiopathy were assessed. Patients with low knowledge at baseline had higher HbA1c levels than subjects with higher knowledge (group C: 9.2+/-1.9 vs. group A: 7.7+/-1.5%, p<0.05 and vs. group B: 7.8+/-1.6%, p<0.05), higher BMI (group C: 23.9+/-3.2 vs. group A: 21.8+/-3.1 kg/m(2), p<0.05) and lower HDL-cholesterol level (group C: 1.8+/-0.5 vs. group A: 2.0+/-0.3 mmol/l, p<0.05). Patients with retinopathy and albuminuria at follow-up had lower level of diabetic knowledge at baseline (respectively: 12.5+/-3.6 vs. 14.2+/-3.3 scores, p<0.05; and 12.6+/-2.9 vs. 14.1+/-3.5 scores, p<0.05). The development of microangiopathy was associated with lower diabetic knowledge (RR=3.71; 95%CI: 1.15-12.01, p=0.02 for retinopathy and RR=4.33; 95%CI: 0.98-19.10, p=0.04 for microalbuminuria). The higher diabetic knowledge at baseline the better metabolic control and lower risk of microangiopathy in the future.

  1. Insulin therapy--role beyond glucose control.

    PubMed

    Pandit, Kaushik; Mukhopadhyay, Pradip

    2004-10-01

    Larger studies had shown improved patient outcome and lower probability of coronary artery disease in insulin treated groups. The classical lipid abnormalities associated with type 2 diabetes are low HDL-cholesterol concentration and high triglyceride concentration. Insulin usage leads to a decrease in triglyceride concentration, primarily by its effect on the enzyme adipose tissue lipoprotein lipase. Insulin suppresses the enzyme, thereby controlling lipolysis in uncontrolled diabetes. Insulins therapy also improves the endothelial dysfunction especially in people with evident macrovascular complications. Though insulin is noted to increase adrenergic tone and may cause elevation of blood pressure, still patients with insulinoma do not have high blood pressure. Some studies suggest weight gain with insulin therapy, others contradict it. One study suggests that insulin does not affect treatment satisfaction. Insulin is known to improve the glycaemic scenario and also the insulin secretory pattern by reducing the glucotoxicity.

  2. Insulin therapy in children and adolescents with type 1 diabetes.

    PubMed

    Malik, Faisal S; Taplin, Craig E

    2014-04-01

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

  3. 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.

  4. Intensity modulated proton therapy

    PubMed Central

    Grassberger, C

    2015-01-01

    Intensity modulated proton therapy (IMPT) implies the electromagnetic spatial control of well-circumscribed “pencil beams” of protons of variable energy and intensity. Proton pencil beams take advantage of the charged-particle Bragg peak—the characteristic peak of dose at the end of range—combined with the modulation of pencil beam variables to create target-local modulations in dose that achieves the dose objectives. IMPT improves on X-ray intensity modulated beams (intensity modulated radiotherapy or volumetric modulated arc therapy) with dose modulation along the beam axis as well as lateral, in-field, dose modulation. The clinical practice of IMPT further improves the healthy tissue vs target dose differential in comparison with X-rays and thus allows increased target dose with dose reduction elsewhere. In addition, heavy-charged-particle beams allow for the modulation of biological effects, which is of active interest in combination with dose “painting” within a target. The clinical utilization of IMPT is actively pursued but technical, physical and clinical questions remain. Technical questions pertain to control processes for manipulating pencil beams from the creation of the proton beam to delivery within the patient within the accuracy requirement. Physical questions pertain to the interplay between the proton penetration and variations between planned and actual patient anatomical representation and the intrinsic uncertainty in tissue stopping powers (the measure of energy loss per unit distance). Clinical questions remain concerning the impact and management of the technical and physical questions within the context of the daily treatment delivery, the clinical benefit of IMPT and the biological response differential compared with X-rays against which clinical benefit will be judged. It is expected that IMPT will replace other modes of proton field delivery. Proton radiotherapy, since its first practice 50 years ago, always required the

  5. Intensive insulin treatment induces insulin resistance in diabetic rats by impairing glucose metabolism-related mechanisms in muscle and liver.

    PubMed

    Okamoto, Maristela Mitiko; Anhê, Gabriel Forato; Sabino-Silva, Robinson; Marques, Milano Felipe dos Santos Ferreira; Freitas, Helayne Soares; Mori, Rosana Cristina Tieko; Melo, Karla Fabiana S; Machado, Ubiratan Fabres

    2011-10-01

    Insulin replacement is the only effective therapy to manage hyperglycemia in type 1 diabetes mellitus (T1DM). Nevertheless, intensive insulin therapy has inadvertently led to insulin resistance. This study investigates mechanisms involved in the insulin resistance induced by hyperinsulinization. Wistar rats were rendered diabetic by alloxan injection, and 2 weeks later received saline or different doses of neutral protamine Hagedorn insulin (1.5, 3, 6, and 9 U/day) over 7 days. Insulinopenic-untreated rats and 6U- and 9U-treated rats developed insulin resistance, whereas 3U-treated rats revealed the highest grade of insulin sensitivity, but did not achieve good glycemic control as 6U- and 9U-treated rats did. This insulin sensitivity profile was in agreement with glucose transporter 4 expression and translocation in skeletal muscle, and insulin signaling, phosphoenolpyruvate carboxykinase/glucose-6-phosphatase expression and glycogen storage in the liver. Under the expectation that insulin resistance develops in hyperinsulinized diabetic patients, we believe insulin sensitizer approaches should be considered in treating T1DM.

  6. 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.

  7. Glycaemic control with continuous subcutaneous insulin infusion compared with intensive insulin injections in patients with type 1 diabetes: meta-analysis of randomised controlled trials

    PubMed Central

    Pickup, John; Mattock, Martin; Kerry, Sally

    2002-01-01

    injection regimensWhat this study addsThough glycaemic control was better during continuous subcutaneous insulin infusion than optimised insulin injection therapy, the difference was relatively smallContinuous subcutaneous insulin infusion is an effective form of intensive insulin therapy that should lower the risk of microvascular complicationsInsulin pump therapy is unnecessary for most people with type 1 diabetes and should be reserved for those with special problems with optimised insulin injections PMID:11909787

  8. 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

  9. Effects of Prior Intensive Insulin Therapy on Cardiac Autonomic Nervous System Function in Type 1 Diabetes: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC)

    PubMed Central

    Pop-Busui, Rodica; Low, Phillip A.; Waberski, Barbara H.; Martin, Catherine L.; Albers, James W.; Feldman, Eva L.; Sommer, Catherine; Cleary, Patricia; Lachin, John M.; Herman, William H.

    2009-01-01

    Background The Epidemiology of Diabetes Interventions and Complications (EDIC) study, a prospective observational follow-up of the Diabetes Control and Complications Trial (DCCT) cohort, reported persistent benefit of prior intensive therapy on retinopathy and nephropathy in type 1 diabetes. We evaluated the effects of prior intensive insulin therapy on the prevalence and incidence of cardiac autonomic neuropathy (CAN) in former DCCT intensive (INT) and conventional (CONV) therapy subjects13-to-14 (13/14) years after DCCT closeout. Methods and Results DCCT autonomic measures (R-R variation with paced breathing, Valsalva ratio, postural blood pressure changes, and autonomic symptoms) were repeated in 1,226 EDIC subjects in EDIC year 13/14. Logistic regression models were used to calculate the odds of incident CAN by DCCT treatment group after adjusting for DCCT baseline covariates, duration in the DCCT, and quantitative autonomic measures at DCCT closeout. In EDIC year 13/14, the prevalence of CAN using the DCCT composite definition was significantly lower in former INT group vs. former CONV group (28.9 vs. 35.2%; P = 0.018). Adjusted R-R variation was significantly greater in former DCCT INT vs. former CONV group (29.9 vs.25.9, P < 0.001). Prior DCCT intensive therapy reduced the risks of incident CAN by 31% [odds ratio(95% CI) 0.69 (0.51–0.93)] and of incident abnormal R-R variation by 30% [odds ratio(95%CI) 0.70 (0.51–0.96)] in EDIC year 13/14. Conclusions Although CAN prevalence increased in both groups, the incidence was significantly lower in former INT group compared to former CONV group. The benefits of former intensive therapy extend to measures of CAN up to 14 years after DCCT closeout. PMID:19470886

  10. Qualitative assessment of user experiences of a novel smart phone application designed to support flexible intensive insulin therapy in type 1 diabetes.

    PubMed

    Knight, Brigid A; McIntyre, H David; Hickman, Ingrid J; Noud, Marina

    2016-09-15

    Modern flexible multiple daily injection (MDI) therapy requires people with diabetes to manage complex mathematical calculations to determine insulin doses on a day to day basis. Automated bolus calculators assist with these calculations, add additional functionality to protect against hypoglycaemia and enhance the record keeping process, however uptake and use depends on the devices meeting the needs of the user. We aimed to obtain user feedback on the usability of a mobile phone bolus calculator application in adults with T1DM to inform future development of mobile phone diabetes support applications. Adults with T1DM who had previously received education in flexible MDI therapy were invited to participate. Eligible respondents attended app education and one month later participated in a focus group to provide feedback on the features of the app in relation to usability for patient-based flexible MDI and future app development. Seven adults participated in the app training and follow up interview. App features that support dose adjustment to reduce hypoglycaemia risk and features that enable greater efficiency in dose calculation, record keeping and report generation were highly valued. Adults who are self managing flexible MDI found the Rapidcalc mobile phone app to be a useful self-management tool and additional features to further improve usability, such as connectivity with BG meter and food databases, shortcut options to economise data entry and web based storage of data, were identified. Further work is needed to ascertain specific features and benefit for those with lower health literacy.

  11. Therapy: Intensive glucose control in the ICU: is sugar nice?

    PubMed

    Sacks, David B

    2009-09-01

    intensive insulin therapy is extensively used to lower blood glucose concentrations in critically ill patients hospitalized within the intensive care unit. The discovery by the nice-SUgAr study investigators that tight glucose control in this setting might actually increase mortality has generated considerable discussion about the wisdom of this approach.

  12. Intensity-Modulated Radiation Therapy (IMRT)

    MedlinePlus

    ... Resources Professions Site Index A-Z Intensity-Modulated Radiation Therapy (IMRT) Intensity-modulated radiotherapy (IMRT) uses linear ... and after this procedure? What is Intensity-Modulated Radiation Therapy and how is it used? Intensity-modulated ...

  13. Acceptance of insulin therapy: a long shot? Psychological insulin resistance in primary care.

    PubMed

    Woudenberg, Y J C; Lucas, C; Latour, C; Scholte op Reimer, W J M

    2012-06-01

    To explore which factors are associated with psychological insulin resistance in insulin-naive patients with Type 2 diabetes in primary care. A sample of 101 insulin-naive patients with Type 2 diabetes completed self-administered questionnaires including demographic and clinical characteristics, the Insulin Treatment Appraisal Scale and the Center for Epidemiological Studies Depression scale. Psychological insulin resistance was denoted by negative appraisal of insulin (Insulin Treatment Appraisal Scale). Thirty-nine per cent of the sample were unwilling to accept insulin therapy. Unwilling participants perceived taking insulin more often as a failure to control their diabetes with tablets or lifestyle compared with willing participants (59 vs. 33%), unwilling participants were more reluctant to accept the responsibilities of everyday management of insulin therapy (49 vs. 24%). Multiple linear regression analysis revealed that depression and objection to lifelong insulin therapy were independently associated with psychological insulin resistance. In this study in primary care, depression and objection to lifelong insulin therapy are associated with psychological insulin resistance. Analysis of the objection to the indefiniteness of insulin therapy showed a sense of limitation of daily life and loss of independence that should not be underestimated. Insulin should be offered as a means to improve health as this might facilitate the acceptance of insulin therapy. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

  14. [Current concept of insulin therapy intensification, and the role of human regular insulin and rapid-acting insulin analogs in insulin treatment].

    PubMed

    Hamaguchi, Tomoya; Sadahiro, Katsuhiko; Satoh, Tomomi

    2015-03-01

    The evolution of insulin therapy from animal insulin to recombinant human regular insulin has improved diabetes treatment. Generating of rapid-acting insulin analogs, mimicking physiologic insulin action enables us to provide better control of post-prandial glucose level and lower incidence of hypoglycemia compared with human regular insulin. These rapid-acting insulin analogs show lower susceptibility of insulin precipitation and catheter occlusions, and are suitable for insulin pump therapy of continuous subcutaneous insulin infusion. Insulin lispro and insulin aspart are also applicable for diabetic patients with pregnancy, requiring excellent glycemic control. In some studies, stepwise addition of prandial insulin, as well as full basal-bolus regimen can improve glycemic control with less hypoglycemia. Treatment intensification with rapid-acting insulin analogs may offer a proper method to reach glycemic goals.

  15. Intensity-modulated radiation therapy.

    PubMed

    Goffman, Thomas E; Glatstein, Eli

    2002-07-01

    Intensity-modulated radiation therapy (IMRT) is an increasingly popular technical means of tightly focusing the radiation dose around a cancer. As with stereotactic radiotherapy, IMRT uses multiple fields and angles to converge on the target. The potential for total dose escalation and for escalation of daily fraction size to the gross cancer is exciting. The excitement, however, has greatly overshadowed a range of radiobiological and clinical concerns.

  16. 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.

  17. Insulin kinetics and the Neonatal Intensive Care Insulin-Nutrition-Glucose (NICING) model.

    PubMed

    Dickson, J L; Pretty, C G; Alsweiler, J; Lynn, A; Chase, J G

    2017-02-01

    Models of human glucose-insulin physiology have been developed for a range of uses, with similarly different levels of complexity and accuracy. STAR (Stochastic Targeted) is a model-based approach to glycaemic control. Elevated blood glucose concentrations (hyperglycaemia) are a common complication of stress and prematurity in very premature infants, and have been associated with worsened outcomes and higher mortality. This research identifies and validates the model parameters for model-based glycaemic control in neonatal intensive care. C-peptide, plasma insulin, and BG from a cohort of 41 extremely pre-term (median age 27.2 [26.2-28.7] weeks) and very low birth weight infants (median birth weight 839 [735-1000] g) are used alongside C-peptide kinetic models to identify model parameters associated with insulin kinetics in the NICING (Neonatal Intensive Care Insulin-Nutrition-Glucose) model. A literature analysis is used to determine models of kidney clearance and body fluid compartment volumes. The full, final NICING model is validated by fitting the model to a cohort of 160 glucose, insulin, and nutrition data records from extremely premature infants from two different NICUs (neonatal intensive care units). Six model parameters related to insulin kinetics were identified. The resulting NICING model is more physiologically descriptive than prior model iterations, including clearance pathways of insulin via the liver and kidney, rather than a lumped parameter. In addition, insulin diffusion between plasma and interstitial spaces is evaluated, with differences in distribution volume taken into consideration for each of these spaces. The NICING model was shown to fit clinical data well, with a low model fit error similar to that of previous model iterations. Insulin kinetic parameters have been identified, and the NICING model is presented for glycaemic control neonatal intensive care. The resulting NICING model is more complex and physiologically relevant, with no

  18. 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.

  19. Microdialysis based monitoring of subcutaneous interstitial and venous blood glucose in Type 1 diabetic subjects by mid-infrared spectrometry for intensive insulin therapy

    NASA Astrophysics Data System (ADS)

    Heise, H. Michael; Kondepati, Venkata Radhakrishna; Damm, Uwe; Licht, Michael; Feichtner, Franz; Mader, Julia Katharina; Ellmerer, Martin

    2008-02-01

    Implementing strict glycemic control can reduce the risk of serious complications in both diabetic and critically ill patients. For this purpose, many different blood glucose monitoring techniques and insulin infusion strategies have been tested towards the realization of an artificial pancreas under closed loop control. In contrast to competing subcutaneously implanted electrochemical biosensors, microdialysis based systems for sampling body fluids from either the interstitial adipose tissue compartment or from venous blood have been developed, which allow an ex-vivo glucose monitoring by mid-infrared spectrometry. For the first option, a commercially available, subcutaneously inserted CMA 60 microdialysis catheter has been used routinely. The vascular body interface includes a double-lumen venous catheter in combination with whole blood dilution using a heparin solution. The diluted whole blood is transported to a flow-through dialysis cell, where the harvesting of analytes across the microdialysis membrane takes place at high recovery rates. The dialysate is continuously transported to the IR-sensor. Ex-vivo measurements were conducted on type-1 diabetic subjects lasting up to 28 hours. Experiments have shown excellent agreement between the sensor readout and the reference blood glucose concentration values. The simultaneous assessment of dialysis recovery rates renders a reliable quantification of whole blood concentrations of glucose and metabolites (urea, lactate etc) after taking blood dilution into account. Our results from transmission spectrometry indicate, that the developed bed-side device enables reliable long-term glucose monitoring with reagent- and calibration-free operation.

  20. A randomized controlled trial of liraglutide versus insulin detemir plus sitagliptin: Effective switch from intensive insulin therapy to the once-daily injection in patients with well-controlled type 2 diabetes.

    PubMed

    Inoue, Yuichiro; Nakamura, Akinobu; Kondo, Yoshinobu; Hamano, Kumiko; Satoh, Shinobu; Terauchi, Yasuo

    2015-07-01

    This study aimed to compare the efficacy and safety of liraglutide versus insulin detemir plus sitagliptin in Japanese patients with type 2 diabetes treated with a basal-bolus insulin regimen. In this multicenter, open-label trial, 90 patients whose diabetes had been controlled well or moderately (glycated hemoglobin [HbA1c ] ≤ 7.3%) with basal-bolus insulin regimen were randomly assigned to a liraglutide group or a detemir group and were followed up for 24 weeks. The primary end point was HbA1c change from baseline to 24 weeks. Of the 90 enrolled patients, 82 completed this trial. At 24 weeks, the mean changes in HbA1c from baseline were 0.1% ± 0.9% versus 0.3% ± 0.8% in the liraglutide versus detemir groups, respectively (P = .46). The "overall" satisfaction score for the Diabetes Treatment Satisfaction Questionnaire changed from 25.2 ± 7.4 to 29.9 ± 5.3 (P < .001) and from 26.4 ± 6.1 to 28.3 ± 6.4 (P = .12) in the liraglutide and detemir groups, respectively. Although the mean change difference in HbA1c between both groups was not significant, switching from a basal-bolus insulin regimen to liraglutide once daily improved patient satisfaction levels without loss of glycemic control.

  1. Evaluating older patients with diabetes for insulin pump therapy.

    PubMed

    Stephens, Elizabeth A; Heffner, John

    2010-06-01

    The increasing prevalence of diabetes among elderly patients underscores the importance of matching the most effective therapy for diabetes self-management with patients' cognitive and motor skills, as these diminish with advancing age. Although many geriatric patients state interest in insulin pump therapy for tight glycemic control, few studies have examined the effectiveness, safety, and feasibility of insulin pumps compared to traditional injected insulin therapy in older age groups. It is important, therefore, for physicians to recognize the indications and the age-related barriers to insulin pump therapy in geriatric patients. Indications include glucose variability, hypoglycemia, and poor glycemic control with traditional insulin regimens. Common barriers include poor vision, dexterity, and cognitive status. Successful implementation of insulin pump therapy for older patients requires an experienced diabetes management team that can assess patient needs and tailor therapy in the context of age-related disabilities.

  2. 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.

  3. [Insulin pump therapy in children, adolescents and adults].

    PubMed

    Stadler, Marietta; Zlamal-Fortunat, Sandra; Schütz-Fuhrmann, Ingrid; Rami-Merhar, Birgit; Fröhlich-Reiterer, Elke; Hofer, Sabine; Mader, Julia; Resl, Michael; Kautzky-Willer, Alexandra; Weitgasser, Raimund; Prager, Rudolf; Bischof, Martin

    2016-04-01

    This position statement is based on the current evidence available on the safety and benefits of continuous subcutaneous insulin pump therapy (CSII) in diabetes with an emphasis on the effects of CSII on glycemic control, hypoglycaemia rates, occurrence of ketoacidosis, quality of life and the use of insulin pump therapy in pregnancy. The current article represents the recommendations of the Austrian Diabetes Association for the clinical praxis of insulin pump treatment in children, adolescents and adults.

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

    PubMed Central

    2014-01-01

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

  5. [Continuous insulin therapy versus multiple insulin injections in the management of type 1 diabetes: a longitutinal study].

    PubMed

    Ribeiro, Maria Estela Bellini; Del Roio Liberatore Junior, Raphael; Custodio, Rodrigo; Martinelli Junior, Carlos Eduardo

    2016-01-01

    To compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes melito. 40 patients with type 1 diabetes melito (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). Although mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15-40 patients have severe hypoglycemic events versus 5-40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. This is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  6. Continuous insulin therapy versus multiple insulin injections in the management of type 1 diabetes: a longitutinal study

    PubMed Central

    Ribeiro, Maria Estela Bellini; Liberatore, Raphael Del Roio; Custodio, Rodrigo; Martinelli, Carlos Eduardo

    2016-01-01

    Abstract Objective: To compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes mellitus. Methods: 40 patients with type 1 diabetes mellitus (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). Results: Although mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15–40 patients have severe hypoglycemic events versus 5–40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. Conclusions: This is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy. PMID:26826879

  7. [Insulin therapy by insulin pump: continuous or conventional self-blood glucose monitoring? ].

    PubMed

    Renard, E

    2003-04-01

    Use of portable pumps is increasing to achieve intensive insulin treatment. Beside unpredictable insulin absorption and insufficient reactivity to changes of insulin flow rate due to the subcutaneous route, this therapy is however limited by the lack of information on blood glucose level provided by self-blood glucose monitoring. Thus, patient interpretation only leads to speculative adaptation of pump flow rate. The lack of alert toward the risk of hypoglycemia or hyperglycemic ketogenic deviations can lead to the occurrence of deleterious metabolic distorsions, among which severe hypoglycemia stands in first rank. Starting experiences of continuous recording of interstitial glucose level by portable systems using glucose-oxidase allow on short time durations the identification of daily periods of poor metabolic control. Retrospective availability of information gives the possibility of more adequate treatment adaptations than conventional capillary blood glucose monitoring, but does not allow immediate prevention of metabolic events. Only devices providing real time or near-real time information to the patient can fulfill this function. However, the absence of tight parallelism between variations of interstitial and blood glucose levels may lead to erroneous decisions. A true continuous real time information on blood glucose level on long-term seems only expectable from implantable glucose sensors. Still under investigation, these systems should be able to insure vigilance toward the risk of hypo- and hyperglycemia on weekly or monthly periods. Initially used as complementary to capillary self-monitoring, their reliability should allow their use as substitutes for conventional monitoring, except for measurements aimed at signal calibration. Pump control by the sensor signal is conceivable if it corresponds to a direct, continuous, real time measurement of blood glucose, and subject to a simultaneous improvement of insulin infusion modes.

  8. Glycaemic control with modified intensive insulin injections (MII) using insulin pens and premixed insulin in children with type-1 diabetes: a randomized controlled trial.

    PubMed

    Soliman, Ashraf T; Omar, Magdi; Rizk, Mostafa M; El Awwa, Ahmad; AlGhobashy, Fatma M

    2006-08-01

    The objective of this study was to compare glycemic control and insulin dosage in children with type 1 diabetes treated by a modified intensified insulin therapy MII using insulin pens (and premixed and regular insulin) with those on conventional insulin therapy. This was a longitudinal, randomized controlled trial for 6 months or more. From a cohort of 125 children with previously diagnosed type-1 diabetes (more than a year after diagnosis) two groups were randomly selected Group AI (n=20) and Group B (n=20). Group AI children and 10 children with recently diagnosed type 1 diabetes (Group AII) were allocated to MII using regular insulin and premixed insulin (30/70 and 40/60 and 50/50). Group B patients continued their conventional insulin therapy for the whole period of the trial. The main outcome measures were glycemic control measured by mean blood glucose concentration and percentage of glycated haemoglobin and total daily insulin dose. Mean blood glucose concentrations before the three main meals, and at midnight, (148, 147, 179 and 127 mg/dl, respectively) were lower in children receiving intensified MII compared with those receiving conventional insulin therapy (192, 174, 194 and 179 mg/dl, respectively) (standardized mean difference 34+/-15 mg/dl), equivalent to a difference of 1.9+/-0.8 mmol/l. This improved control during MII was achieved with no change in the average daily insulin dose in group-AI. In group-AII insulin dose decreased significantly during their first 6 moths of treatment (honeymooning). Glycemic control is better during MII using insulin pens and premixed and regular insulin compared with conventional insulin therapy, without any significant change in insulin dose needed to achieve this level of control. The difference in glycemic control between the two methods is significant and could reduce the risk of micro-vascular complications.

  9. 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.

  10. 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.

  11. Local insulin therapy affects fracture healing in a rat model.

    PubMed

    Park, Andrew G; Paglia, David N; Al-Zube, Loay; Hreha, Jeremy; Vaidya, Swaroopa; Breitbart, Eric; Benevenia, Joseph; O'Connor, J Patrick; Lin, Sheldon S

    2013-05-01

    A significant number of lower extremity fractures result in mal-union necessitating effective treatments to restore ambulation. Prior research in diabetic animal fracture models demonstrated improved healing following local insulin application to the fracture site and indicated that local insulin therapy can aid bone regeneration, at least within an insulin-dependent diabetic animal model. This study tested whether local insulin therapy could accelerate femur fracture repair in normal, non-diabetic rats. High (20 units) and low (10 units) doses of insulin were delivered in a calcium sulfate carrier which provided sustained release of the exogenous insulin for 7 days after fracture. Histomorphometry, radiographic scoring, and torsional mechanical testing were used to measure fracture healing. The fracture calluses from rats treated with high-dose insulin had significantly more cartilage than untreated rats after 7 and 14 days of healing. After 4 weeks of healing, femurs from rats treated with low-dose insulin had significantly higher radiographic scores and mechanical strength (p < 0.05), compared to the no treatment control groups. The results of this study suggest that locally delivered insulin is a potential therapeutic agent for treating bone fractures. Further studies are necessary, such as large animal proof of concepts, prior to the clinical use of insulin for bone fracture treatment.

  12. [Cardiovascular effects of insulin therapy: from pharmacology to clinical trials].

    PubMed

    Mannucci, Edoardo

    2016-03-01

    Insulin has direct effects on vascular walls which, depending on experimental models, can be either predominantly antiatherogenic or proatherogenic. In observational studies, insulin therapy is usually associated with an increase in the incidence of major cardiovascular events. However, this result is probably determined by the effect of confounders. In clinical trials performed in the acute phase of coronary syndromes, the benefits observed with insulin therapy are probably due to the improvement of glycemic control, rather than to direct effects of insulin on the cardiovascular system. In long-term trials for primary or secondary prevention such as UKPDS and ORIGIN insulin has no relevant effects on major cardiovascular events beyond those determined by the improvement of metabolic control. On the other hand, severe hypoglycemia, which is a possible side effect of insulin therapy, is associated with a worse prognosis of cardiovascular disease. The availability of new long-acting insulin analogs, which reduce the incidence of hypoglycemia for similar levels of glycemic control, makes insulin therapy easier and potentially safer for the cardiovascular system.

  13. [Insulin infusion in intensive care: randomized controlled trial].

    PubMed

    Miranda, Milena Penteado Ferraro; Crespo, Jeiel Carlos Lamonica; Secoli, Silvia Regina

    2013-06-01

    This randomized controlled trial compared the use of an intensive and conventional insulin protocol on clinical outcomes in patients with severe sepsis and septic shock, in the first 72 hours. It was conducted at a university hospital in the city of São Paulo. Patients (n=46) were allocated into two groups: intensive glycemic (blood glucose between 80-110mg/dl) and conventional (180-220mg/dl). The Student's t-test and chi-square test were used for data analysis. A statistically significant (p<0.001) difference was observed in mean glycemia, but there was no difference in the variables of mean minimum arterial pressure (p=0.06) or maximum (p=0.11), serum creatinine (p=0,33) or in mortality (p=0.11). Although there was no difference between the groups regarding mortality, hemodynamic instability in the conventional group was longer and the only deaths occurred in it.

  14. Availability of insulin pump therapy in clinical practice.

    PubMed

    Carlsson, B-M; Andersson, P Nord; Alnervik, J; Carstensen, J; Lind, M

    2012-08-01

    To examine the availability of insulin pump therapy in patients with Type 1 diabetes. Patients using insulin pumps among a cohort of 7224 patients with Type 1 diabetes were studied. In logistic regression, used to evaluate variables not changing over time among the total cohort, use of insulin pumps varied by outpatient clinic (P<0.001) and sex (P<0.001). Cox regression analysis in 5854 patients with detailed patient data prior to use of an insulin pump showed higher HbA(1c) (P<0.0001), lower creatinine (P=0.002), high and low insulin doses (P<0.0001), younger age (P<0.0001) and female sex (P<0.0001) to be associated with use of an insulin pump. Women were 1.5-fold more likely to start using an insulin pump (hazard ratio 1.52, 95% confidence interval 1.29-1.79) and patients in the 20- to 30-years age range were more than twice as likely to begin use of an insulin pump than patients aged 40-50 years (hazard ratio 8.63, 95% confidence interval 5.91-12.59 and hazard ratio 3.98, 95% confidence interval 2.80-5.64, respectively). A 10-μmol/l higher level of creatinine was associated with a hazard ratio of 0.56 (95% confidence interval 0.39-0.81) of starting use of an insulin pump. At 10 hospital outpatient clinics in Sweden, use of insulin pumps therapy varied by clinic. A higher proportion of women began using insulin pumps. Younger patients and patients with fewer complications were also more likely to start using an insulin pump. Further research is needed to confirm these findings in other geographical regions and to understand whether the availability of insulin pumps today is optimized. © 2011 The Author. Diabetic Medicine © 2011 Diabetes UK.

  15. Optimizing insulin therapy in pregnant women with type 1 diabetes mellitus.

    PubMed

    Gottlieb, Peter A; Frias, Juan P; Peters, Kelly A; Chillara, Bhavani; Garg, Satish K

    2002-01-01

    Pregnancy complicated by type 1 diabetes mellitus is associated with an increased risk of complications in the mother and infant. Normal or near normal glycemic control prior to and during pregnancy reduces many of these risks to levels observed in the general population. This degree of glycemic control is generally achievable only with intensive insulin therapy: multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) via an insulin pump. These therapeutic regimens have been found to result in comparable glycemic control, although CSII provides increased flexibility in terms of patient lifestyle, and may reduce the incidence of hypoglycemia. Frequent home blood glucose monitoring is imperative during pregnancy in order to optimize glycemic control and reduce the risk of hypoglycemia. Furthermore, insulin requirements change significantly over the course of pregnancy. The new short-acting insulin analogs, insulin lispro and insulin aspart, have pharmacodynamic properties which make them ideal for use during pregnancy. Although the number of published studies evaluating the use of insulin lispro during pregnancy is limited, the majority support its safety. No studies of insulin aspart in pregnancy have been published in full. In addition to optimization of glycemic control, frequent assessment for development and/or progression of microvascular complications is necessary during pregnancy.

  16. Insulin gene therapy for type 1 diabetes mellitus.

    PubMed

    Handorf, Andrew M; Sollinger, Hans W; Alam, Tausif

    2015-04-01

    Type 1 diabetes mellitus is an autoimmune disease resulting from the destruction of pancreatic β cells. Current treatments for patients with type 1 diabetes mellitus include daily insulin injections or whole pancreas transplant, each of which are associated with profound drawbacks. Insulin gene therapy, which has shown great efficacy in correcting hyperglycemia in animal models, holds great promise as an alternative strategy to treat type 1 diabetes mellitus in humans. Insulin gene therapy refers to the targeted expression of insulin in non-β cells, with hepatocytes emerging as the primary therapeutic target. In this review, we present an overview of the current state of insulin gene therapy to treat type 1 diabetes mellitus, including the need for an alternative therapy, important features dictating the success of the therapy, and current obstacles preventing the translation of this treatment option to a clinical setting. In so doing, we hope to shed light on insulin gene therapy as a viable option to treat type 1 diabetes mellitus.

  17. Leptin therapy in insulin-deficient type I diabetes

    PubMed Central

    Wang, May-yun; Chen, Lijun; Clark, Gregory O.; Lee, Young; Stevens, Robert D.; Ilkayeva, Olga R.; Wenner, Brett R.; Bain, James R.; Charron, Maureen J.; Newgard, Christopher B.; Unger, Roger H.

    2010-01-01

    In nonobese diabetic mice with uncontrolled type 1 diabetes, leptin therapy alone or combined with low-dose insulin reverses the catabolic state through suppression of hyperglucagonemia. Additionally, it mimics the anabolic actions of insulin monotherapy and normalizes hemoglobin A1c with far less glucose variability. We show that leptin therapy, like insulin, normalizes the levels of a wide array of hepatic intermediary metabolites in multiple chemical classes, including acylcarnitines, organic acids (tricarboxylic acid cycle intermediates), amino acids, and acyl CoAs. In contrast to insulin monotherapy, however, leptin lowers both lipogenic and cholesterologenic transcription factors and enzymes and reduces plasma and tissue lipids. The results imply that leptin administration may have multiple short- and long-term advantages over insulin monotherapy for type 1 diabetes. PMID:20194735

  18. Engineering Synthetically Modified Insulin for Glucose-Responsive Diabetes Therapy.

    PubMed

    Webber, Matthew J; Anderson, Daniel G; Langer, Robert

    Though a suite of different insulin variants have been used clinically to provide greater control over pharmacokinetics, no clinically used insulin can tune its potency and/or bioavailability in a glucose-dependent manner. In order to improve therapy for diabetic patients, a vision has been the development of autonomous closed-loop approaches. Toward this goal, insulin has been synthetically modified with glucose-sensing groups or groups that can compete with free glucose for binding to glucose-binding proteins and evaluated in pre-clinical models. Specifically, it was demonstrated that site-specific modification of insulin with phenylboronic acid can result in glucose-responsive activity, leading to faster recovery in diabetic mice following a glucose challenge but with less observed hypoglycemia in healthy mice. This strategy, along with several others being pursued, holds promise to improve the fidelity in glycemic control with routine insulin therapy.

  19. Engineering Synthetically Modified Insulin for Glucose-Responsive Diabetes Therapy

    PubMed Central

    Webber, Matthew J.; Anderson, Daniel G.; Langer, Robert

    2016-01-01

    Summary Though a suite of different insulin variants have been used clinically to provide greater control over pharmacokinetics, no clinically used insulin can tune its potency and/or bioavailability in a glucose-dependent manner. In order to improve therapy for diabetic patients, a vision has been the development of autonomous closed-loop approaches. Toward this goal, insulin has been synthetically modified with glucose-sensing groups or groups that can compete with free glucose for binding to glucose-binding proteins and evaluated in pre-clinical models. Specifically, it was demonstrated that site-specific modification of insulin with phenylboronic acid can result in glucose-responsive activity, leading to faster recovery in diabetic mice following a glucose challenge but with less observed hypoglycemia in healthy mice. This strategy, along with several others being pursued, holds promise to improve the fidelity in glycemic control with routine insulin therapy. PMID:27570535

  20. [Insulin dose analysis during pregnancy in type 1 diabetic patients treated with insulin pump therapy].

    PubMed

    Qiu, L L; Weng, J P; Zheng, X Y; Luo, S H; Yang, D Z; Xu, W; Cai, M Y; Xu, F; Yan, J H; Yao, B

    2017-02-28

    Objective: To analyze the insulin dose of type 1 diabetic patients who treated with insulin pump therapy during pregnancy in order to explore the features of these patients' insulin requirement during gestation. Methods: A total of 12 well-controlled type 1 diabetic women patients who were treated with insulin pump therapy before and during gestation without any adverse pregnancy outcomes from June 2011 to December 2014 were selected from Guangdong Type 1 Diabetes Translational Medicine Study and included in the study. Demographic data, hemoglobin A1c (HbA1c) before pregnancy and before delivery, insulin dose, hypoglycemia episodes and pregnancy outcomes were collected to analyze the insulin dose of preconception, the 1(st,) the 2(nd) and the 3(rd) trimester to analyze the requirement of insulin before and throughout pregnancy. Results: Subjects were (26.9±2.6) years old, with a diabetes duration of (6.6±4.4) years. HbA1c were (5.8±0.5)% before conception. The preconception total daily insulin dose, basal rate, bolus and bolus proportion were (0.60±0.18)U/kg, (0.28±0.10)U/kg, (0.32±0.13)U/kg and (54.8±12.9)%, respectively. Both of the insulin dose indexes mentioned above changed significantly in different trimesters compared with that in preconception (P value was <0.001, 0.034, <0.001 and <0.001, respectively). The total daily insulin dose, bolus and bolus proportion kept increasing during pregnancy. In the 1(st,) the 2(nd) and the 3(rd) trimester, the total daily insulin dose rose by 0.2%, 45.4% and 72.7%, respectively, the bolus rose by 8.0%, 72.2% and 106.8%, respectively, and the bolus proportion rose by 8.0%, 16.8% and 19.0%, respectively. While the basal rate decreased by 9.0% in the 1(st) trimester and rose by 14.1% and 32.9% in the 2(nd) and 3(rd) trimester, respectively. Conclusions: In well-controlled pregnant women with type 1 diabetes mellitus, insulin requirement increased throughout pregnancy. Most of the increased insulin requirement was

  1. 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

  2. Neutron Measurements for Intensity Modulated Radiation Therapy

    SciTech Connect

    Ipe, Nisy E.

    2000-04-21

    The beam-on time for intensity modulated radiation therapy (IMRT) is increased significantly compared with conventional radiotherapy treatments. Further, the presence of beam modulation devices may potentially affect neutron production. Therefore, neutron measurements were performed for 15 MV photon beams on a Varian Clinac accelerator to determine the impact of IMRT on neutron dose equivalent to the patient.

  3. 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.

  4. Guidelines for Application of Continuous Subcutaneous Insulin Infusion (Insulin Pump) Therapy in the Perioperative Period

    PubMed Central

    Boyle, Mary E; Seifert, Karen M; Beer, Karen A; Apsey, Heidi A; Nassar, Adrienne A; Littman, Stephanie D; Magallanez, Janice M; Schlinkert, Richard T; Stearns, Joshua D; Hovan, Michael J; Cook, Curtiss B

    2012-01-01

    Case reports indicate that diabetes patients receiving outpatient insulin pump therapy have been allowed to continue treatment during surgical procedures. Although allowed during surgery, there is actually little information in the medical literature on how to manage patients receiving insulin pump therapy during a planned surgical procedure. A multidisciplinary work group reviewed current information regarding the use of insulin pumps in the perioperative period. Although the work group identified safety issues specific to surgical scenarios, it believed that with the use of standardized guidelines and a checklist, continuation of insulin pump therapy during the perioperative period is feasible. A sample set of protocols have been developed and are summarized. A policy outlining clear procedures should be established at the institutional level to guide physicians and other staff if the devices are to be employed during the perioperative period. Additional clinical experience with the technology in surgical scenarios is needed, and consensus should be developed for insulin pump use in the perioperative phases of care. PMID:22401338

  5. The fluctuation of blood glucose, insulin and glucagon concentrations before and after insulin therapy in type 1 diabetes

    NASA Astrophysics Data System (ADS)

    Arif, Idam; Nasir, Zulfa

    2015-09-01

    A dynamical-systems model of plasma glucose, insulin and glucagon concentrations has been developed to investigate the effects of insulin therapy on blood glucose, insulin and glucagon regulations in type 1 diabetic patients. Simulation results show that the normal regulation of blood glucose concentration depends on insulin and glucagon concentrations. On type 1 diabetic case, the role of insulin on regulating blood glucose is not optimal because of the destruction of β cells in pancreas. These β cells destructions cause hyperglycemic episode affecting the whole body metabolism. To get over this, type 1 diabetic patients need insulin therapy to control the blood glucose level. This research has been done by using rapid acting insulin (lispro), long-acting insulin (glargine) and the combination between them to know the effects of insulin therapy on blood glucose, insulin and glucagon concentrations. Simulation results show that these different types of insulin have different effects on blood glucose concentration. Insulin therapy using lispro shows better blood glucose control after consumption of meals. Glargin gives better blood glucose control between meals and during sleep. Combination between lispro and glargine shows better glycemic control for whole day blood glucose level.

  6. 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

  7. Problems of intensive therapy in childhood cancer

    SciTech Connect

    Skelton, J.; Pizzo, P.A.

    1986-07-15

    Tremendous progress has been made in the treatment of childhood cancers. Certain hematologic malignancies have an impressive cure rate with the current intensive antineoplastic treatment regimens. There is optimism that the treatment of children who have advanced stage solid tumors with intensive, multimodality therapy may improve their chances for long-term survival. These treatment programs, though potentially curative, are highly toxic, with severe myelosuppression and damage to other organ systems. An awareness of these potential toxicities, an understanding of how to prevent or minimize certain problems, and the ability to treat those complications which do arise are all essential to the successful management of childhood cancer. 206 references.

  8. [Intensive therapy in complicated forms of purulent gestational pyelonephritis].

    PubMed

    Dovlatian, A A

    2008-01-01

    The experience with 65 cases of purulent gestational pyelonephritis (PGP) is reviewed. The efficacy of PGP intensive therapy depends on early surgical elimination of the source of bacteriemia and sepsis. Choice of the surgical technique should be based both on extension of destructive changes in the kidney and severity of the complications. In some cases it is necessary to perform nephrostomy with sanation of the pyonecrotic foci in the kidney, in the other--it is necessary to perform urgent nephrectomy. Three basic components of pre- and postoperative intensive care should be considered: antibacterial treatment, infusion-transfusion therapy and efferent detoxication. Etiotropic therapy is conducted with three antibiotics injected intravenously and intramuscularly to provide effective concentrations of the drugs in the blood, urine and affected organs. PGP medication is based on inhibitor-defended penicillines and cephalosporines of the third-forth generation. Combined use of these antibiotics is effective in 95% cases. If the condition is life-threatening, carbapenems, fluoroguinolones, aminoglycosides and metronidasol can be applied. Detoxication is provided by 24-h infusion of crystalloids, concentrated glucose solutions (10-20%) with insulin, transfusion of fresh frozen plasm, albumin, protein. Plasmapheresis accelerates recovery, diminished nephrectomy rate by 14% and obstetric complications 1.8 fold, enables physiological term of delivery (37-39 weeks) in significant reduction of postnatal complications. Lethal outcomes were absent.

  9. [Non-insulin-dependent diabetics with secondary failure: insulin therapy at bedtime combined with glibenclamide].

    PubMed

    Maiz, A; Arteaga, A; Klaassen, J; Velasco, N; Borkosky, M; Jiménez, M; Acosta, A M

    1993-10-01

    Secondary failure and the requirement is common in patients with non-insulin dependent diabetes mellitus. The combination of sulfonylureas with NPH insulin at bedtime has been proposed to avoid high doses of insulin. We treated 18 patients (2 men, age range 47-76 yr) non respondent to diet and glibenclamide, combining NPH insulin in an average dose of 0.3 +/- 0.03 U/kg BW at bedtime for 6 months. Fasting serum glucose improved from 256 +/- 11 to 132 +/- 6 mg/dl and HbA1C from 13.6 +/- 0.4 to 9.9 +/- 0.2%. Four patients achieved a good control (defined as a HbA1C < 9), 9 a fair control (HbA1C 9.1-10) and 5 persisted with a bad control (HbA1C > 10). Well controlled patients were younger, had a shorter duration of diabetes and had a non significantly higher body mass index. Fasting serum insulin and C peptide levels achieved after glucagon injection were not predictors of the metabolic response to combined therapy. Tolerance to treatment was good, without changes in blood pressure or serum lipids and with a low incidence of hypoglycemia. There was a mean increase of 3.6 kg in body weight. After 6 months of therapy, maximum achieved C peptide values after glucagon increased from 3.3 +/- 0.3 to 4.5 +/- 0.4 ng/ml. It is concluded that combined glibenclamide and NPH insulin at bedtime is useful to treat secondary failure in non-insulin dependent diabetic patients, but their response in variable and non dependent on their beta insular secretion.

  10. Optimizing insulin pump therapy: a quality improvement project.

    PubMed

    Meade, Lisa T; Rushton, Wanda E

    2013-01-01

    The purpose of the study was to assess insulin pump use and provide ongoing education. A quality improvement project using a pump assessment questionnaire was implemented at an endocrinology office in the southeastern United States. The questionnaire was designed to evaluate all aspects of insulin pump therapy, including pump operations, infusion set failure, management of acute complications, and usage of advanced device features. Eighty-nine patients (80% with type 1 diabetes and 20% with type 2 diabetes) completed the questionnaire at the endocrinology practice. A certified diabetes educator reviewed the questions with each patient, identifying deficiencies and training opportunities. The most common areas of deficiency identified after implementation of the assessment form included the following: expired or no basal insulin prescription in the event of pump failure or removal, no mupirocin (Bactroban®, GlaxoSmithKline, Research Triangle Park, North Carolina) prescription for suspected site infections, lack of insulin syringe if pump stopped working, failure to check urine ketones, no antiemetic prescription for sick day intervention, using manual bolus instead of bolus calculator, and lack of in-date glucagon kit. Use of a pump assessment questionnaire allows for focused discussion concerning patient behaviors related to pump operations, troubleshooting, and self-management. Incorporating use of a pump assessment questionnaire into routine practice may result in improved patient education and avoidance of adverse events specific to insulin pump therapy.

  11. Myostatin inhibition therapy for insulin-deficient type 1 diabetes

    PubMed Central

    Coleman, Samantha K.; Rebalka, Irena A.; D’Souza, Donna M.; Deodhare, Namita; Desjardins, Eric M.; Hawke, Thomas J.

    2016-01-01

    While Type 1 Diabetes Mellitus (T1DM) is characterized by hypoinsulinemia and hyperglycemia, persons with T1DM also develop insulin resistance. Recent studies have demonstrated that insulin resistance in T1DM is a primary mediator of the micro and macrovascular complications that invariably develop in this chronic disease. Myostatin acts to attenuate muscle growth and has been demonstrated to be elevated in streptozotocin-induced diabetic models. We hypothesized that a reduction in mRNA expression of myostatin within a genetic T1DM mouse model would improve skeletal muscle health, resulting in a larger, more insulin sensitive muscle mass. To that end, Akita diabetic mice were crossed with MyostatinLn/Ln mice to ultimately generate a novel mouse line. Our data support the hypothesis that decreased skeletal muscle expression of myostatin mRNA prevented the loss of muscle mass observed in T1DM. Furthermore, reductions in myostatin mRNA increased Glut1 and Glut4 protein expression and glucose uptake in response to an insulin tolerance test (ITT). These positive changes lead to significant reductions in resting blood glucose levels as well as pronounced reductions in associated diabetic symptoms, even in the absence of exogenous insulin. Taken together, this study provides a foundation for considering myostatin inhibition as an adjuvant therapy in T1DM as a means to improve insulin sensitivity and blood glucose management. PMID:27581061

  12. Evaluation of current trends and recent development in insulin therapy for management of diabetes mellitus.

    PubMed

    Nawaz, Muhammad Sarfraz; Shah, Kifayat Ullah; Khan, Tahir Mehmood; Rehman, Asim Ur; Rashid, Haroon Ur; Mahmood, Sajid; Khan, Shahzeb; Farrukh, Muhammad Junaid

    2017-07-08

    Diabetes mellitus is a major health problem in developing countries. There are various insulin therapies to manage diabetes mellitus. This systematic review evaluates various insulin therapies for management of diabetes mellitus worldwide. This review also focuses on recent developments being explored for better management of diabetes mellitus. We reviewed a number of published articles from 2002 to 2016 to find out the appropriate management of diabetes mellitus. The paramount parameters of the selected studies include the insulin type & its dose, type of diabetes, duration and comparison of different insulin protocols. In addition, various newly developed approaches for insulin delivery with potential output have also been evaluated. A great variability was observed in managing diabetes mellitus through insulin therapy and the important controlling factors found for this therapy include; dose titration, duration of insulin use, type of insulin used and combination therapy of different insulin. A range of research articles on current trends and recent advances in insulin has been summarized, which led us to the conclusion that multiple daily insulin injections or continuous subcutaneous insulin infusion (insulin pump) is the best method to manage diabetes mellitus. In future perspectives, development of the oral and inhalant insulin would be a tremendous breakthrough in Insulin therapy. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  13. Metabolic control and educational status in children with type 1 diabetes: effects of a summer camp and intensive insulin treatment.

    PubMed

    Karagüzel, G; Bircan, I; Erişir, S; Bundak, R

    2005-12-01

    Our aim was to evaluate prospectively, in our diabetic patients, the impacts of a summer camp and intensive insulin treatment (IIT) on both metabolic control and disease-related educational level. Twenty-five patients participated in a 7-day-long summer camp. Before the camp, all patients were on therapy with short-acting human insulin (SAI) and intermediate-acting insulin (IAI) twice daily. On arrival, their insulin therapy regimen was changed by IIT including either SAI or rapid-acting insulin analogue (RAI) three times before meals supplemented by IAI at bedtime. Following the camp, all participants were given IIT with RAI plus IAI. Frequency of hypoglycaemia, insulin dose, body mass index (BMI) and glycohaemoglobin (HbA1c) levels were assessed at pre-camp and post-camp controls. To evaluate the effectiveness of camp-assisted education, all participants were regularly tested. We observed significant elevations in total daily dose of insulin and BMI at months 3 and 6 when compared with the pre-camp values but, by month 12, they were not significantly different from precamp values. The mean HbA(1c) level decreased significantly at months 6 and 12. Severe hypoglycaemic episodes and ketoacidosis were not detected during the camp and the following year. Significant improvements in knowledge about diabetes and self-management were determined at the end of the camp, after 6 and 12 months. Camp-assisted IIT with RAI improved metabolic control of diabetic children. Additionally, camp-assisted education has a positive effect on disease-related educational level and self-management.

  14. Virtual micro-intensity modulated radiation therapy.

    PubMed

    Siochi, R A

    2000-11-01

    Virtual micro-intensity modulated radiation therapy (VMIMRT) combines a 10 x 5 mm2 intensity map with a 5 x 10 mm2 intensity map, delivered at orthogonal collimator settings. The superposition of these component maps (CM) yields a 5 x 5 mm2 virtual micro-intensity map (VMIM) that can be delivered with a 1 cm leaf width MLC. A pair of CMs with optimal delivery efficiency and quality must be chosen, since a given VMIM can be delivered using several different pairs. This is possible since, for each group of four VMIM cells that can be covered by an MLC leaf in either collimator orientation, the minimum intensity can be delivered from either collimator setting. By varying the proportions of the minimum values that go into each CM, one can simultaneously minimize the number of potential junction effects and the number of segments required to deliver the VMIM. The minimization is achieved by reducing high leaf direction gradients in the CMs. Several pseudoclinical and random VMIMs were studied to determine the applicability of this new technique. A nine level boost map was also studied to investigate dosimetric and spatial resolution issues. Finally, clinical issues for this technique are discussed.

  15. [Pharmaceutical and insulin therapy of diabetes mellitus type 2. Update].

    PubMed

    Siegel, E

    2015-05-01

    The prevalence of diabetes mellitus type 2 in the adult population is > 7 %. Despite new therapy options and modern insulins, the therapy remains a challenge. Especially in patients with obesity or high insulin resistance it is often difficult to achieve the necessary target values. In most cases the disease is initially asymptomatic so that the aim is the early recognition and avoidance of complications. This article provides an update on the approach options of modern therapy forms in diabetes management. The foundations of every treatment program are lifestyle interventions, including diabetes schooling. When these fail a pharmaceutical therapy must be initiated which among others is oriented to hemoglobin A1c (HbA1c). The HbA1c target value should take patient-specific circumstances into consideration and should be determined together with the patient. If no contraindications or intolerances are present, metformin is the medication of choice. Apart from metformin, the available data which can be used for guidance are limited. A combination therapy with one or two other oral or injectable medications is suitable to keep the side effects as low as possible. The advantages of other substances in individual cases could be a lower risk of hypoglycemia, reduced weight increase, oral administration and compatibility with renal insufficiency. Ultimately, insulin therapy will be necessary for many patients, either as monotherapy or in combination with other substances. Therapy decisions should be made together with the patient, taking personal preferences into consideration and should include age, body weight, comorbidities, occupational situation and compliance. The Reorganization of the Pharmaceutical Market Act represents a momentarily perceived clear barrier. In the interests of an individualized therapy and personalized disease management, a target-aimed flexibility in diabetes management should be possible in the future.

  16. UK service level audit of insulin pump therapy in paediatrics.

    PubMed

    Ghatak, A; Paul, P; Hawcutt, D B; White, H D; Furlong, N J; Saunders, S; Morrison, G; Langridge, P; Weston, P J

    2015-12-01

    To conduct an audit of insulin pump therapy in the UK after the issue of guidelines for the use of continuous subcutaneous insulin infusion by NICE in 2008 (Technology Appraisal 151). All centres in the UK, providing pump services to children and young people were invited to participate in an online audit. Audit metrics were aligned to NICE Technology Appraisal 151 and an electronic data collection tool was used. Of the 176 UK centres identified as providing pump services, 166 (94.3%) participated in the study. A total of 5094 children and young people were identified as using continuous subcutaneous insulin infusion (19% of all paediatric patients with Type 1 diabetes), with a median (range) of 16.9 (0.67-69.4)% per centre. Units had a median of 0.58 consultant sessions, 0.43 full-time equivalent diabetic specialist nurses, and 0.1 full-time equivalent dieticians delivering the pump service. The majority of this time was not formally funded. Families could access 24-h clinical and technical support (83% units), although the delivery varied between consultant, diabetic specialist nurse and company representatives. Only 53% of units ran, or accessed, structured education programmes for continuous subcutaneous insulin infusion use. Most units (86%) allowed continuous subcutaneous insulin infusion use for paediatric inpatients, but only 56% had written guidelines for this scenario. Nine percent of units had encountered funding refusal for a patient fulfilling NICE (Technology Appraisal 151) criteria. The number of children and young people on continuous subcutaneous insulin infusion therapy is consistent with numbers estimated by NICE. There is a worrying lack of funded healthcare professional time. The audit also identified gaps in the provision of structured education and absence of written inpatient guidelines. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

  17. Fan-beam intensity modulated proton therapy

    SciTech Connect

    Hill, Patrick; Westerly, David; Mackie, Thomas

    2013-11-15

    Purpose: This paper presents a concept for a proton therapy system capable of delivering intensity modulated proton therapy using a fan beam of protons. This system would allow present and future gantry-based facilities to deliver state-of-the-art proton therapy with the greater normal tissue sparing made possible by intensity modulation techniques.Methods: A method for producing a divergent fan beam of protons using a pair of electromagnetic quadrupoles is described and particle transport through the quadrupole doublet is simulated using a commercially available software package. To manipulate the fan beam of protons, a modulation device is developed. This modulator inserts or retracts acrylic leaves of varying thickness from subsections of the fan beam. Each subsection, or beam channel, creates what effectively becomes a beam spot within the fan area. Each channel is able to provide 0–255 mm of range shift for its associated beam spot, or stop the beam and act as an intensity modulator. Results of particle transport simulations through the quadrupole system are incorporated into the MCNPX Monte Carlo transport code along with a model of the range and intensity modulation device. Several design parameters were investigated and optimized, culminating in the ability to create topotherapy treatment plans using distal-edge tracking on both phantom and patient datasets.Results: Beam transport calculations show that a pair of electromagnetic quadrupoles can be used to create a divergent fan beam of 200 MeV protons over a distance of 2.1 m. The quadrupole lengths were 30 and 48 cm, respectively, with transverse field gradients less than 20 T/m, which is within the range of water-cooled magnets for the quadrupole radii used. MCNPX simulations of topotherapy treatment plans suggest that, when using the distal edge tracking delivery method, many delivery angles are more important than insisting on narrow beam channel widths in order to obtain conformal target coverage

  18. Fan-beam intensity modulated proton therapy

    PubMed Central

    Hill, Patrick; Westerly, David; Mackie, Thomas

    2013-01-01

    Purpose: This paper presents a concept for a proton therapy system capable of delivering intensity modulated proton therapy using a fan beam of protons. This system would allow present and future gantry-based facilities to deliver state-of-the-art proton therapy with the greater normal tissue sparing made possible by intensity modulation techniques. Methods: A method for producing a divergent fan beam of protons using a pair of electromagnetic quadrupoles is described and particle transport through the quadrupole doublet is simulated using a commercially available software package. To manipulate the fan beam of protons, a modulation device is developed. This modulator inserts or retracts acrylic leaves of varying thickness from subsections of the fan beam. Each subsection, or beam channel, creates what effectively becomes a beam spot within the fan area. Each channel is able to provide 0–255 mm of range shift for its associated beam spot, or stop the beam and act as an intensity modulator. Results of particle transport simulations through the quadrupole system are incorporated into the MCNPX Monte Carlo transport code along with a model of the range and intensity modulation device. Several design parameters were investigated and optimized, culminating in the ability to create topotherapy treatment plans using distal-edge tracking on both phantom and patient datasets. Results: Beam transport calculations show that a pair of electromagnetic quadrupoles can be used to create a divergent fan beam of 200 MeV protons over a distance of 2.1 m. The quadrupole lengths were 30 and 48 cm, respectively, with transverse field gradients less than 20 T/m, which is within the range of water-cooled magnets for the quadrupole radii used. MCNPX simulations of topotherapy treatment plans suggest that, when using the distal edge tracking delivery method, many delivery angles are more important than insisting on narrow beam channel widths in order to obtain conformal target coverage

  19. 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.

  20. Nanoparticle based insulin delivery system: the next generation efficient therapy for Type 1 diabetes.

    PubMed

    Sharma, Garima; Sharma, Ashish Ranjan; Nam, Ju-Suk; Doss, George Priya C; Lee, Sang-Soo; Chakraborty, Chiranjib

    2015-10-24

    Diabetic cases have increased rapidly in recent years throughout the world. Currently, for type-1 diabetes mellitus (T1DM), multiple daily insulin (MDI) injections is the most popular treatment throughout the world. At this juncture, researchers are trying to develop different insulin delivery systems, especially through oral and pulmonary route using nanocarrier based delivery system. This next generation efficient therapy for T1DM may help to improve the quality of life of diabetic patients who routinely employ insulin by the subcutaneous route. In this paper, we have depicted various next generation nanocarrier based insulin delivery systems such as chitosan-insulin nanoparticles, PLGA-insulin nanoparticles, dextran-insulin nanoparticles, polyalkylcyanoacrylated-insulin nanoparticles and solid lipid-insulin nanoparticles. Modulation of these insulin nanocarriers may lead to successful oral or pulmonary insulin nanoformulations in future clinical settings. Therefore, applications and limitations of these nanoparticles in delivering insulin to the targeted site have been thoroughly discussed.

  1. Insulin therapy induces changes in the inflammatory response in a murine 2-hit model.

    PubMed

    Barkhausen, Tanja; Probst, Christian; Hildebrand, Frank; Pape, Hans-Christoph; Krettek, Christian; van Griensven, Martijn

    2009-08-01

    Post-traumatic complications commonly seen on intensive care units include sepsis and associated disorders, which are accompanied by alterations in inflammatory cytokine expression patterns and in activation of neutrophils. Hyperglycaemia, often occurring after trauma and sepsis, is a further risk factor for morbidity and mortality among critically ill people. Clinical investigations have suggested that strict glycaemic control by insulin titration reduces overall mortality. This study aimed to further elucidate the pathophysiological and immunomodulative actions of insulin. Femoral fracture was induced in a murine model, followed by 1h of haemorrhage. Two days after the first hit, sepsis was induced by caecal ligation and puncture (CLP). In control animals, laparotomy only was performed. Insulin in two different concentrations (10IU or 20IU) or vehicle was administered daily. Insulin therapy was associated with improvement of clinical parameters, slightly improved survival rates and, in lungs and liver, fewer infiltrating neutrophils and reduced IL-6 and IL-10 mRNA expression. These results suggested that, in this animal model, insulin had a direct anti-inflammatory effect that was independent of modulation of blood glucose levels.

  2. Insulin pump therapy in patients with diabetes undergoing surgery.

    PubMed

    Nassar, Adrienne A; Boyle, Mary E; Seifert, Karen M; Beer, Karen A; Apsey, Heidi A; Schlinkert, Richard T; Stearns, Joshua D; Cook, Curtiss B

    2012-01-01

    To assess perioperative management of patients with diabetes mellitus who were being treated with insulin pump therapy. We reviewed records for documentation of insulin pump status and glucose monitoring during preoperative, intraoperative, and postanesthesia care unit (PACU) phases of surgery. Thirty-five patients (21 men) with insulin pumps underwent surgical procedures between January 1, 2006, and December 31, 2010. Mean age was 56 years, mean diabetes duration was 31 years, and mean duration of insulin pump therapy was 7 years. All patients were white, and 29 had type 1 diabetes mellitus. Of the 50 surgical procedures performed during the study period, 16 were orthopedic, 9 were general surgical, 7 were urologic, and 7 were kidney transplant operations; the remaining 11 procedures were in other surgical specialties. The mean (± standard deviation) time in the preoperative area was 118 ± 75 minutes, mean intraoperative time was 177 ± 102 minutes, and mean PACU time was 170 ± 78 minutes. Of the 50 procedures, status of pump use was documented in 32 cases in the preoperative area, 14 cases intraoperatively, and 30 cases in the PACU. Glucose values were recorded in 47 cases preoperatively, 30 cases intraoperatively, and 48 cases in the PACU. Results showed inconsistent documentation of pump use and glucose monitoring throughout the perioperative period, even for patients with prolonged anesthesia and recovery times. It was often unclear whether the pump was in place and operational during the intraoperative period. Guidelines should be developed for management of insulin pump-treated patients who are to undergo surgery.

  3. 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.

  4. Alternative routes of administration as an approach to improve insulin therapy: update on dermal, oral, nasal and pulmonary insulin delivery.

    PubMed

    Heinemann, L; Pfützner, A; Heise, T

    2001-09-01

    For the past 75 years subcutaneous injections have been the only route of delivery of insulin therapy to diabetic patients. During this time, numerous attempts have been made to explore alternative routes for systemic insulin administration. However, thus far, no feasible other way of non-invasive insulin delivery has been developed. Dermal insulin application does not result in a reproducible and sufficient transfer of insulin across the highly efficient skin barrier. The dream of an "insulin tablet" has also not become a reality, the main problem being digestion and a lack of a specific peptide carrier system in the gut. Nasal insulin application was considered for a number of years as a potential method, because of the rapid absorption of insulin across the nasal mucosa. However, relative bioavailability was low and required use of absorption enhancers and more importantly, the metabolic effect lasted too short to be of clinical usefulness. To date the most promising alternative route of insulin administration, is the pulmonary delivery of insulin by inhalation which will likely lead to a practically usable system within the next few years. For maximal rate of absorption insulin must be applied deep into the lung, i.e., into the alveoli. A considerable number of inhalers (in combination with appropriate insulin formulations), which are ask to generate insulin particles with an appropriate size for pulmonary delivery, are currently in the clinical phase of development. The pharmaco dynamic effects of insulin formulations administered via the lung are comparable to, or even faster than, those of s.c. injected regular insulin or rapid-acting insulin analogues. The relative biopotency of inhaled insulin in most cases is approximately 10%, i.e., the dose of insulin administered must be 10-fold higher than with s.c. application. The published results of clinical trials thus far, indicate that metabolic control is comparable to that of s.c. insulin therapy. As of to

  5. [New therapies for diabetes: beyond injectable insulin and oral antidiabetics].

    PubMed

    Alfonso, John Edwin Feliciano; Ariza, Iván Darío Sierra

    2008-01-01

    New medicines for the therapy of the type 1 and type 2 diabetes have been incorporated in the list of traditional drugs: oral agents and injectable insulin. These treatment alternatives have a new mechanism of action that takes advantage of the antidiabetic properties of certain peptides such as amylin and glucagon like peptide-1 (GLP-1), whose levels are wanting or insufficient in diabetes. This is attained through amylin and GLP-1 analogues, although it can also be achieved by inhibiting the enzyme that degrades the latter. Furthermore, a new system to administer insulin in a noninvasive way through inhalation has become available in the market. This paper summarizes the most important and updated findings on the action mechanism, efficacy, adverse effects and indications of these innovative drugs.

  6. Comparative effectiveness and costs of insulin pump therapy for diabetes.

    PubMed

    Ackermann, Ronald T; Wallia, Amisha; Kang, Raymond; Cooper, Andrew; Prospect, Theodore A; Sandy, Lewis G; Vojta, Deneen

    2017-06-01

    Continuous subcutaneous insulin infusion (CSII), or "insulin pump" therapy, is an alternative to multiple daily insulin injections (MDII) for management of diabetes. This study evaluates patterns of healthcare utilization, costs, and blood glucose control for patients with diabetes who initiate CSII. Pre-post with propensity-matched comparison design involving commercially insured US adults (aged 18-64 years) with insulin-requiring diabetes who transitioned from MDII to CSII between July 1, 2009, and June 30, 2012 ("CSII initiators"; n = 2539), or who continued using MDI (n = 2539). Medical claims and laboratory results files obtained from a large US-wide health payer were used to construct direct medical expenditures, hospital use, healthcare encounters for hypoglycemia, and mean concentration of glycated hemoglobin (A1C). We fit difference-in-differences regression models to compare healthcare expenditures for 3 years following the switch to CSII. Stratified analyses were performed for prespecified patient subgroups. Over 3 years, mean per-person total healthcare expenditures were $1714 (95% confidence interval [CI], $1184-$2244) higher per quarter for CSII initiators compared with matched MDII patients (total mean 3-year difference of $20,565). Compared with matched controls, mean A1C concentrations became lower for CSII initiators by 0.46% in year 2 (P = .0003) and by 0.32% in year 3 (P = .047). CSII initiators also had a higher rate of hypoglycemia encounters in year 1 (P = .002). For adults with insulin-requiring diabetes, transitioning from MDII to CSII was associated with modest improvements in A1C but more hypoglycemia encounters and increased healthcare expenditures, without significant improvement in other potentially offsetting areas of healthcare consumption.

  7. Film Dosimetry for Intensity Modulated Radiation Therapy

    NASA Astrophysics Data System (ADS)

    Benites-Rengifo, J.; Martínez-Dávalos, A.; Celis, M.; Lárraga, J.

    2004-09-01

    Intensity Modulated Radiation Therapy (IMRT) is an oncology treatment technique that employs non-uniform beam intensities to deliver highly conformal radiation to the targets while minimizing doses to normal tissues and critical organs. A key element for a successful clinical implementation of IMRT is establishing a dosimetric verification process that can ensure that delivered doses are consistent with calculated ones for each patient. To this end we are developing a fast quality control procedure, based on film dosimetry techniques, to be applied to the 6 MV Novalis linear accelerator for IMRT of the Instituto Nacional de Neurología y Neurocirugía (INNN) in Mexico City. The procedure includes measurements of individual fluence maps for a limited number of fields and dose distributions in 3D using extended dose-range radiographic film. However, the film response to radiation might depend on depth, energy and field size, and therefore compromise the accuracy of measurements. In this work we present a study of the dependence of Kodak EDR2 film's response on the depth, field size and energy, compared with those of Kodak XV2 film. The first aim is to devise a fast and accurate method to determine the calibration curve of film (optical density vs. doses) commonly called a sensitometric curve. This was accomplished by using three types of irradiation techniques: Step-and-shoot, dynamic and static fields.

  8. [Palliative therapy concepts in intensive care medicine].

    PubMed

    Schuster, M; Ferner, M; Bodenstein, M; Laufenberg-Feldmann, R

    2017-04-01

    Involvement of palliative care is so far not common practice for critically ill patients on surgical intensive care units (ICUs) in Germany. The objectives of palliative care concepts are improvement of patient quality of life by relief of disease-related symptoms using an interdisciplinary approach and support of patients and their relatives considering their current physical, psychological, social and spiritual needs. The need for palliative care can be identified via defined screening criteria. Integration of palliative care can either be realized using a consultative model which focusses on involvement of palliative care consultants or an integrative model which embeds palliative care principles into the routine daily practice by the ICU team. Early integration of palliative care in terms of advance care planning (ACP) can lead to an increase in goals of care discussions and quality of life as well as a decrease of mortality and length of stay on the ICU. Moreover, stress reactions of relatives and ICU staff can be reduced and higher satisfaction with therapy can be achieved. The core of goal of care discussions is professional and well-structured communication between patients, relatives and staff. Consideration of palliative care principles by model-based integration into ICU practice can improve complex intensive care courses of disease in a productive but dignified way without neglecting curative attempts.

  9. Intensity of Therapy Services: What Are the Considerations?

    ERIC Educational Resources Information Center

    Palisano, Robert J.; Murr, Susan

    2009-01-01

    Research on intensity of therapy services is limited and perspectives often vary considerably among families, therapists, administrators, policy makers, and health insurers. In this commentary, the authors share their perspectives on intensity of physical therapy and/or occupational therapy services for children with developmental conditions. Five…

  10. Intensity of Therapy Services: What Are the Considerations?

    ERIC Educational Resources Information Center

    Palisano, Robert J.; Murr, Susan

    2009-01-01

    Research on intensity of therapy services is limited and perspectives often vary considerably among families, therapists, administrators, policy makers, and health insurers. In this commentary, the authors share their perspectives on intensity of physical therapy and/or occupational therapy services for children with developmental conditions. Five…

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2017-02-09

    Similar to muscles, the intestine is also insulin resistant in obese subjects and subjects with impaired glucose tolerance. Exercise training improves muscle insulin sensitivity, but its effects on intestinal metabolism are not known. We studied the effects of high intensity interval training (HIIT) and moderate intensity continuous training (MICT) on intestinal glucose and free fatty acid uptake from circulation in humans. Twenty-eight healthy middle-aged sedentary men were randomized for two weeks of HIIT or MICT. Intestinal insulin-stimulated glucose uptake and fasting free fatty acid uptake from circulation were measured using positron emission tomography and [(18)F]FDG and [(18)F]FTHA. In addition, effects of HIIT and MICT on intestinal Glut2 and CD36 protein expression were studied in rats. Training improved aerobic capacity (p=0.001) and whole-body insulin sensitivity (p=0.04), but not differently between HIIT and MICT. Insulin-stimulated glucose uptake increased only after the MICT in the colon [HIIT=0%; MICT=37%] (p=0.02 for time*training) and tended to increase in the jejunum [HIIT=-4%; MICT=13%] (p=0.08 for time*training). Fasting free fatty acid uptake decreased in the duodenum in both groups [HIIT=-6%; MICT=-48%] (p=0.001 time) and tended to decrease in the colon in the MICT group [HIIT=0%; MICT=-38%] (p=0.08 for time*training). In rats, both training groups had higher Glut2 and CD36 expression compared to control animals. This study shows that already two weeks of MICT enhances insulin-stimulated glucose uptake while both training modes reduce fasting free fatty acid uptake in the intestine in healthy middle-aged men, providing an additional mechanism by which exercise training can improve whole body metabolism.

  13. Diabetes therapy--focus on Asia: second-line therapy debate: insulin/secretagogues.

    PubMed

    Eldor, Roy; Raz, Itamar

    2012-12-01

    The following review is based on the second part of a debate entitled 'Diabetes therapy--focus on Asia: 2nd line therapy: GLP1/DPP4 inhibitors versus Secretagogue/insulin therapy', which was held during the '1st Asia Pacific Congress on Controversies to Consensus in Diabetes, Obesity and Hypertension (CODHy)', in Shanghai, China, 2011. As such we reviewed only insulin and secretagogue therapy despite the existence of other therapeutic options. The article aims to shed light on the circumstances most adequate for use of these as second-line agents, despite possible drawbacks. It is important to emphasize that regardless of it being a review of published evidence, it primarily represents the professional opinion of the writers.

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

    PubMed Central

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

    2017-01-01

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

  15. Low intensity laser therapy: the clinical approach

    NASA Astrophysics Data System (ADS)

    Kahn, Fred

    2006-02-01

    Recently, there has been significant improvement in the process of research and application of Low Intensity Laser Therapy (LILT). Despite this positive direction, a wide discrepancy between the research component and clinical understanding of the technology remains. In our efforts to achieve better clinical results and more fully comprehend the mechanisms of interaction between light and cells, further studies are required. The clinical results presented in this paper are extrapolated from a wide range of musculoskeletal problems including degenerative osteoarthritis, repetitive motion injuries, sports injuries, etc. The paper includes three separate clinical studies comprising 151, 286 and 576 consecutive patient discharges at our clinic. Each patient studied received a specific course of treatment that was designed for that individual and was modified on a continuing basis as the healing process advanced. On each visit, clinical status correlation with the duration, dosage and other parameters was carried out. The essentials of the treatment consisted of a three stage approach. This involved a photon stream emanating from a number of specified gallium-aluminum-arsenide diodes; stage one, red light array, stage two consisting of an array of infrared diodes and stage three consisting of the application of an infrared laser diode probe. On average, each of these groups required less than 10 treatments per patient and resulted in a significant improvement / cure rate greater than 90% in all conditions treated. This report clearly demonstrates the benefits of LILT, indicating that it should be more widely adapted in all medical therapeutic settings.

  16. Glycemic profile and effectiveness and safety of insulin therapy in septic patients: is the blood glucose level sufficient?

    PubMed

    Szrama, Jakub; Smuszkiewicz, Piotr; Trojanowska, Iwona

    2009-10-01

    Hyperglycemia in sepsis is managed by intensive insulin therapy, which can cause hypoglycemia. The aim of the study was to evaluate the glycemic profile as well as safety and effectiveness of a nurse-controlled insulin therapy protocol in patients with severe sepsis and septic shock. The study included 16 septic patients who died (nonsurvivors) and 61 septic patients who survived. Glycemia was measured every 4 h, and the dose of insulin infusion was adjusted to maintain glycemia of 4.4 mmol/l to 8.3 mmol/l. We analyzed glycemia levels and daily variations, insulin dose, episodes of hypo- and hyperglycemia. Nonsurvivors and survivors had similar mean glycemia levels (7.38 vs. 7.08 mmol/l; p = 0.20) and insulin requirements (median [Me] = 26.9 vs. 23.9 units/d; p = 0.22; Me = 1.7 vs. 1.4 units/h; p = 0.25). Daily glycemia variation (Me = 4.81 vs. 3.03 mmol/l; p <0.001), episodes of hypoglycemia (18.8% vs. 3.3%; p = 0.02), spontaneous severe hypoglycemia (12.5% vs. 0%; p = 0.006) and hyperglycemia (75.0% vs. 45.9%; p = 0.04) were higher and more frequent in nonsurvivors. Three of 5393 blood samples (0.05%) met severe insulin-induced hypoglycemia criteria, and 74.4% of samples met the recommended range of 4.4-8.3 mmol/l. Patients who died experienced more episodes of hyperglycemia, spontaneous hypoglycemia and greater variation in the daily glycemia level. Daily glycemia variation is more reliable than a mean glycemic level in evaluating glucose homeostasis in septic patients. Few episodes of severe insulin-induced hypoglycemia occurred while using the nurse-controlled insulin therapy protocol.

  17. The role of insulin pump therapy for type 2 diabetes mellitus.

    PubMed

    Landau, Zohar; Raz, Itamar; Wainstein, Julio; Bar-Dayan, Yosefa; Cahn, Avivit

    2017-01-01

    Many patients with type 2 diabetes fail to achieve adequate glucose control despite escalation of treatment and combinations of multiple therapies including insulin. Patients with long-standing type 2 diabetes often suffer from the combination of severe insulin deficiency in addition to insulin resistance, thereby requiring high doses of insulin delivered in multiple injections to attain adequate glycemic control. Insulin-pump therapy was first introduced in the 1970s as an approach to mimic physiological insulin delivery and attain normal glucose in patients with type 1 diabetes. The recent years have seen an increase in the use of this technology for patients with type 2 diabetes. This article summarizes the clinical studies evaluating insulin pump use in patients with type 2 diabetes and discusses the benefits and shortcomings of pump therapy in this population. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Management of insulin pump therapy in children with type 1 diabetes.

    PubMed

    Abdullah, Nadeem; Pesterfield, Claire; Elleri, Daniela; Dunger, David B

    2014-12-01

    Insulin pump therapy is a current treatment option for children and adolescents with type 1 diabetes. Insulin pumps can provide a greater flexibility in insulin administration and meal planning, as compared with multiple insulin injections, and they may be particularly suitable for the paediatric age group. Many young people with diabetes have integrated insulin pumps into their daily practice. The use of insulin pumps can also be supplemented by the information retrieved from continuous glucose monitoring in the sensor-augmented pump therapy, which may improve glycaemic control. In this review, we describe the principles of pump therapy and summarise features of commercially available insulin pumps, with focus on practical management and the advantages and disadvantages of this technology. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  19. An experimental study of pulsed micro-flows pertinent to continuous subcutaneous insulin infusion therapy

    NASA Astrophysics Data System (ADS)

    Wang, Bin; Demuren, Ayodeji; Gyuricsko, Eric; Hu, Hui

    2011-07-01

    An experimental study was conducted to investigate the unsteady micro-flow driven by an insulin pump commonly used in continuous subcutaneous insulin infusion (CSII) therapy. A microscopic particle image velocimetry (PIV) system was used to characterize the transient behavior of the micro-flow upon the pulsed excitation of the insulin pump in order to elucidate the underlying physics for a better understanding of the microphysical process associated with the insulin delivery in CSII therapy. The effects of air bubbles entrained inside the micro-sized CSII tubing system on the insulin delivery process were also assessed based on the micro-PIV measurements. While most solutions to insulin occlusion-related problems are currently based on clinical trials, the findings derived from the present study can be used to provide a better guidance for the troubleshooting of insulin occlusion in CSII therapy.

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

    PubMed Central

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

    2014-01-01

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

  1. Evaluation of perception of insulin therapy among Chinese patients with type 2 diabetes mellitus.

    PubMed

    Chen, C-C; Chang, M-P; Hsieh, M-H; Huang, C-Y; Liao, L-N; Li, T-C

    2011-11-01

    To evaluate whether perception of insulin therapy differs between patients with type 2 diabetes treated with insulin and those treated with oral hypoglycaemic agents (OHAs), and to examine whether gender, education level, injection duration and mode of injection were associated with the patients' perception of insulin therapy. The validated Chinese version of the Insulin Treatment Appraisal Scale (ITAS) was used to evaluate the perception of insulin therapy among 100 insulin-treated patients and 100 OHA-treated patients. The higher the total score, the more negative is the appraisal. The OHA-treated group had a higher mean total score (20 items), a higher mean total score for 16 negative items and a lower mean total score for four positive items than the insulin-treated group. The proportion of participants who rated the negative items as "agree" or "strongly agree" was significantly higher in the OHA-treated group than in the insulin-treated group. In addition, the proportion of participants who rated the four positive items as "agree" or "strongly agree" was lower in the OHA-treated group than in the insulin-treated group. Gender, education level, duration of insulin injection and mode of injection did not have a significant impact on perception of insulin therapy. Chinese type 2 diabetic patients taking OHAs had more negative beliefs and attitudes towards insulin therapy than patients being treated with insulin. This difference was not associated with either gender or education level. Furthermore, neither injection duration nor type of device was related to perception of insulin therapy. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

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

    PubMed

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

    2015-01-01

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

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

    PubMed

    Scheen, A J

    2006-09-01

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

  4. 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

    Current processes of care for diabetes mellitus (DM) were shaped during the era when insulin therapy was considered inexorable to the management of advanced stage type 2 (T2DM), though this no longer appears to be categorically true. There are also dashed hopes that insulin therapy can prevent or stall diabetes. While exogenous insulin remains a life-sparing tool for fully insulin-dependent DM, insulin therapy-induced hyperinsulinemia now appears to contribute to serious safety issues beyond hypoglycemia and weight gain. Iatrogenic and compensatory hyperinsulinemia are metabolic disruptors of β-cells, liver, muscle, kidney, brain, heart and vasculature, inflammation, and lipid homeostasis, among other systems. This may compromise β-cells, exacerbate insulin resistance (IR), and increase risk of cardiovascular (CV) disease. Striking associations between exogenous insulin and risks of CV events, cancer, and all-cause mortality in clinical trial and real-world cohorts caution that insulin may pose more harm than previously evidenced. At our disposal are numerous alternate tools that, alone or in combination, efficaciously manage hyperglycemia and glucolipotoxicity, and do so without inducing hypoglycemia, weight gain, or hyperinsulinemia. Moreover, these new tools support true precision therapy, as modern day drug classes can be aligned with the various mediating pathways of hyperglycemia at work in any given patient. Some also appear to promote β-cell survival, with intriguing data being presented for newer agents, such as incretins. As such, we encourage preferential use of non-insulin antidiabetic agents to injected insulin for the management of non-insulin-dependent patients with T2DM, including in advanced stage T2DM. The goal of this article is to augment existing literature to 1) correct misconceptions on the rationale and necessity for insulin therapy in T2DM, 2) discuss emerging negative safety data with insulin therapy, and, 3) offer a practical means to

  5. Attitudes of patients and physicians to insulin therapy in Japan: an analysis of the Global Attitude of Patients and Physicians in Insulin Therapy study.

    PubMed

    Harashima, Shin-Ichi; Nishimura, Akiko; Inagaki, Nobuya

    2017-01-01

    The barriers to insulin therapy perceived by Japanese patients with diabetes and their physicians are unclear. We performed sub-analyses of the Global Attitude of Patients and Physicians in Insulin Therapy (GAPP™) study, which included 100 Japanese physicians (of 1250 participating physicians) and 150 Japanese patients (of 1530 patients) who participated in Internet surveys (physicians) or computer-assisted telephone surveys (patients) across eight countries in 2010. We compared the results of Japanese participants with those obtained for the other seven countries. Overall, 44% of the Japanese patients reported omission or non-adherence to insulin, a greater value than that reported in other countries. Japanese physicians reported that non-adherence to insulin was driven by their patients' lifestyles. A greater proportion of patients had a history of hypoglycemia in Japan than in other countries. Most of the physicians (94%) and patients (84%) in Japan reported that the currently available insulin treatment regimens do not fit the diverse lifestyles of patients. Many Japanese patients receiving insulin therapy omit or do not adhere to insulin, possibly because of fear of hypoglycemia, or for lifestyle reasons. Insulin regimens that reduce the risk of hypoglycemia without interfering with patients' lifestyles are needed.

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

    PubMed

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

    2015-12-01

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

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

    PubMed Central

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

    2015-01-01

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

  8. Insulin Therapy Increases Cardiovascular Risk: Time for a Sea of Change in Type 2 Diabetes Treatment.

    PubMed

    Herman, Mary E; O'Keefe, James H; Bell, David S H; Schwartz, Stanley S

    2017-09-25

    Insulin therapy increased cardiovascular (CV) risk and mortality among type 2 diabetes (T2D) patients in several recently reported clinical outcomes trials. To assess whether this association is causative or coincidental, PubMed searches were used to query the effects of insulin therapy for T2D on CV health and longevity from large-scale outcomes trials, meta-analyses, and patient registry studies, as well as basic research on insulin's direct and pleiotropic actions. Although several old studies provided conflicting results, the majority of large observational studies show strong dose-dependent associations for injected insulin with increased CV risk and worsened mortality. Insulin clearly causes weight gain, recurrent hypoglycemia, and, other potential adverse effects, including iatrogenic hyperinsulinemia. This over-insulinization with use of injected insulin predisposes to inflammation, atherosclerosis, hypertension, dyslipidemia, heart failure (HF), and arrhythmias. These associations support the findings of large-scale evaluations that strongly suggest that insulin therapy has a poorer short- and long-term safety profile than that found to many other anti-T2D therapies. The potential adverse effects of insulin therapy should be weighed against proven CV benefits noted for select other therapies for T2D as reported in recent large randomized controlled trials. Copyright © 2017. Published by Elsevier Inc.

  9. A Survey of Insulin-Dependent Diabetes—Part I: Therapies and Devices

    PubMed Central

    Takahashi, Daisuke; Xiao, Yang; Hu, Fei; Lewis, Michael

    2008-01-01

    This paper surveys diabetes therapies from telemedicine viewpoint. In type 1 diabetes therapies, the exogenous insulin replacement is generally considered as a primary treatment. However, the complete replacement of exogenous insulin is still a challenging issue because of its complexity of modeling the dynamics, which is typically modeled nonlinearly. On the other hand, thanks to the progress of medical devices, currently the diabetes therapies are being automated. These medical devices include automated insulin pumps and blood glucose sensors. Insulin pumps are designed to create artificial insulin perfusion while they largely rely on the blood glucose profile measurements and these measurements are achieved by one or more blood glucose sensors. The blood glucose measurements are also important for the insulin-dependent diabetes therapies. An insulin pump along with sensors establishes a good feedback system providing the appropriate amount of the exogenous insulin on demand. Controlling the amount of exogenous insulin to suppress the blood glucose levels requires complicated computations. This paper mostly explains both type 1 and 2 diabetes and their mechanisms accompanied by descriptions of diabetes therapy and medical devices currently utilized in the therapy. PMID:18437199

  10. 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 ...

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2015-01-01

    Objectives To analyze the effects of a long-term intensive lifestyle intervention including high-intensity interval training (HIIT) and Mediterranean diet (MedD) counseling on glycemic control parameters, insulin resistance and β-cell function in obese subjects. Methods The glycemic control parameters (fasting plasma glucose, glycated hemoglobin), insulin resistance, and β-cell function of 72 obese subjects (54 women; mean age = 53 ± 9 years) were assessed at baseline and upon completion of a 9-month intensive lifestyle intervention program conducted at the cardiovascular prevention and rehabilitation center of the Montreal Heart Institute, from 2009 to 2012. The program included 2–3 weekly supervised exercise training sessions (HIIT and resistance exercise), combined to MedD counseling. Results Fasting plasma glucose (FPG) (mmol/L) (before: 5.5 ± 0.9; after: 5.2 ± 0.6; P < 0.0001), fasting insulin (pmol/L) (before: 98 ± 57; after: 82 ± 43; P = 0.003), and insulin resistance, as assessed by the HOMA-IR score (before: 3.6 ± 2.5; after: 2.8 ± 1.6; P = 0.0008) significantly improved, but not HbA1c (%) (before: 5.72 ± 0.55; after: 5.69 ± 0.39; P = 0.448), nor β-cell function (HOMA-β, %) (before: 149 ± 78; after: 144 ± 75; P = 0.58). Conclusion Following a 9-month intensive lifestyle intervention combining HIIT and MedD counseling, obese subjects experienced significant improvements of FPG and insulin resistance. This is the first study to expose the effects of a long-term program combining HIIT and MedD on glycemic control parameters among obese subjects. PMID:26844086

  13. Diabetes Patients' Experiences With the Implementation of Insulin Therapy and Their Perceptions of Computer-Assisted Self-Management Systems for Insulin Therapy

    PubMed Central

    Gude, Wouter T; Holleman, Frits; Hoekstra, Joost BL; Peek, Niels

    2014-01-01

    Background Computer-assisted decision support is an emerging modality to assist patients with type 2 diabetes mellitus (T2DM) in insulin self-titration (ie, self-adjusting insulin dose according to daily blood glucose levels). Computer-assisted insulin self-titration systems mainly focus on helping patients overcome barriers related to the cognitive components of insulin titration. Yet other (eg, psychological or physical) barriers could still impede effective use of such systems. Objective Our primary aim was to identify experiences with and barriers to self-monitoring of blood glucose, insulin injection, and insulin titration among patients with T2DM. Our research team developed a computer-assisted insulin self-titration system, called PANDIT. The secondary aim of this study was to evaluate patients’ perceptions of computer-assisted insulin self-titration. We included patients who used PANDIT in a 4-week pilot study as well as patients who had never used such a system. Methods In-depth, semi-structured interviews were conducted individually with patients on insulin therapy who were randomly recruited from a university hospital and surrounding general practices in the Netherlands. The interviews were transcribed verbatim and analyzed qualitatively. To classify the textual remarks, we created a codebook during the analysis, in a bottom-up and iterative fashion. To support examination of the final coded data, we used three theories from the field of health psychology and the integrated model of user satisfaction and technology acceptance by Wixom and Todd. Results When starting insulin therapy, some patients feared a lifelong commitment to insulin therapy and disease progression. Also, many barriers arose when implementing insulin therapy (eg, some patients were embarrassed to inject insulin in public). Furthermore, patients had difficulties increasing the insulin dose because they fear hypoglycemia, they associate higher insulin doses with disease progression

  14. New forms of insulin and insulin therapies for the treatment of type 2 diabetes.

    PubMed

    Cahn, Avivit; Miccoli, Roberto; Dardano, Angela; Del Prato, Stefano

    2015-08-01

    Insulin is a common treatment option for many patients with type 2 diabetes, and is generally used late in the natural history of the disease. Its injectable delivery mode, propensity for weight gain and hypoglycaemia, and the paucity of trials assessing the risk-to-safety ratio of early insulin use are major shortcomings associated with its use in patients with type 2 diabetes. Development of new insulins-such as insulin analogues, including long-acting and short-acting insulins-now provide alternative treatment options to human insulin. These novel insulin formulations and innovative insulin delivery methods, such as oral or inhaled insulin, have been developed with the aim to reduce insulin-associated hypoglycaemia, lower intraindividual pharmacokinetic and pharmacodynamic variability, and improve imitation of physiological insulin release. Availability of newer glucose-lowering drugs (such as glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose co-transporter-2 inhibitors) also offers the opportunity for combination treatment; the results of the first trials in this area of research suggest that such treatment might lead to use of reduced insulin doses, less weight gain, and fewer hypoglycaemic episodes than insulin treatment alone. These and future developments will hopefully offer better opportunities for individualisation of insulin treatment for patients with type 2 diabetes.

  15. Robust optimization of intensity modulated proton therapy

    SciTech Connect

    Liu Wei; Zhang Xiaodong; Li Yupeng; Mohan, Radhe

    2012-02-15

    Purpose: Intensity modulated proton therapy (IMPT) is highly sensitive to range uncertainties and uncertainties caused by setup variation. The conventional inverse treatment planning of IMPT optimized based on the planning target volume (PTV) is not often sufficient to ensure robustness of treatment plans. In this paper, a method that takes the uncertainties into account during plan optimization is used to mitigate the influence of uncertainties in IMPT. Methods: The authors use the so-called ''worst-case robust optimization'' to render IMPT plans robust in the face of uncertainties. For each iteration, nine different dose distributions are computed--one each for {+-} setup uncertainties along anteroposterior (A-P), lateral (R-L) and superior-inferior (S-I) directions, for {+-} range uncertainty, and the nominal dose distribution. The worst-case dose distribution is obtained by assigning the lowest dose among the nine doses to each voxel in the clinical target volume (CTV) and the highest dose to each voxel outside the CTV. Conceptually, the use of worst-case dose distribution is similar to the dose distribution achieved based on the use of PTV in traditional planning. The objective function value for a given iteration is computed using this worst-case dose distribution. The objective function used has been extended to further constrain the target dose inhomogeneity. Results: The worst-case robust optimization method is applied to a lung case, a skull base case, and a prostate case. Compared with IMPT plans optimized using conventional methods based on the PTV, our method yields plans that are considerably less sensitive to range and setup uncertainties. An interesting finding of the work presented here is that, in addition to reducing sensitivity to uncertainties, robust optimization also leads to improved optimality of treatment plans compared to the PTV-based optimization. This is reflected in reduction in plan scores and in the lower normal tissue doses for the

  16. Intensive Care Unit Insulin Delivery Algorithms: Why So Many? How to Choose?

    PubMed Central

    Steil, Garry M.; Deiss, Dorothee; Shih, Judy; Buckingham, Bruce; Weinzimer, Stuart; Agus, Michael S.D.

    2009-01-01

    Objective Studies showing improved outcomes with tight glycemic control in the intensive care unit (ICU) have resulted in a substantial number of new insulin delivery algorithms being proposed. The present study highlights mechanisms used in the better-known approaches, examines what might be critical differences among them, and uses systems theory to characterize the conditions under which each can be expected to perform best. Methods Algorithm dose (ΔI/ΔG) and step (response to a persistent elevation in glucose) response curves were calculated for written instruction algorithms, developed at the Providence Heart and Vascular Institute (Portland [P] protocol), the University of Washington (UW), and Yale University (Y), together with similar curves for the Glucommander (GM) and proportional integral derivative (PID) computer algorithms. From the simulated curves, different mechanisms used to adjust insulin delivery were identified. Results All algorithms increased insulin delivery in response to persistent hyperglycemia, but the mechanism used altered the algorithm's sensitivity to glucose, or gain, in the GM, UW, and Y protocols, while leaving it unchanged for the P protocol and PID algorithm. Conclusions The increase in insulin delivery in response to persistent hyperglycemia observed with all the algorithms can be expected to bring subjects who respond to insulin to targeted glucose ranges. However, because the PID and P protocols did not alter the insulin delivery response curves, these algorithms can be expected to take longer to achieve target glucose levels in individuals who are insulin resistant and/or are exposed to increased carbohydrate loads (e.g., glucose infusions). By contrast, the GM, UW, and Y algorithms can be expected to adapt to the insulin resistance such that the time to achieve target levels is unchanged if the time for insulin to act does not change. If the insulin resistance is accompanied by a longer time for insulin to act, the UW, Y

  17. Exercise at anaerobic threshold intensity and insulin secretion by isolated pancreatic islets of rats

    PubMed Central

    de Oliveira, Camila Aparecida Machado; Paiva, Mauricio Ferreira; Mota, Clécia Alencar Soares; Ribeiro, Carla; de Almeida Leme, José Alexandre Curiacos; Luciano, Eliete

    2010-01-01

    To evaluate the effect of acute exercise and exercise training at the anaerobic threshold (AT) intensity on aerobic conditioning and insulin secretion by pancreatic islets, adult male Wistar rats were submitted to the lactate minimum test (LMT) for AT determination. Half of the animals were submitted to swimming exercise training (trained), 1 h/day, 5 days/week during 8 weeks, with an overload equivalent to the AT. The other half was kept sedentary. At the end of the experimental period, the rats were submitted to an oral glucose tolerance test and to another LMT. Then, the animals were sacrificed at rest or immediately after 20 minutes of swimming exercise at the AT intensity for pancreatic islets isolation. At the end of the experiment mean workload (% bw) at AT was higher and blood lactate concentration (mmol/L) was lower in the trained than in the control group. Rats trained at the AT intensity showed no alteration in the areas under blood glucose and insulin during OGTT test. Islet insulin content of trained rats was higher than in the sedentary rats while islet glucose uptake did not differ among the groups. The static insulin secretion in response to the high glucose concentration (16.7 mM) of the sedentary group at rest was lower than the sedentary group submitted to the acute exercise and the inverse was observed in relation to the trained groups. Physical training at the AT intensity improved the aerobic condition and altered insulin secretory pattern by pancreatic islets. PMID:21099318

  18. Glucose turnover after replacement of usual therapy by insulin in insulin-naive type 2 diabetes subjects.

    PubMed

    Thabit, H; Kumareswaran, K; Haidar, A; Leelarathna, L; Caldwell, K; Elleri, D; Allen, J M; Nodale, M; Wilinska, M E; Jackson, N C; Umpleby, A M; Evans, M L; Hovorka, R

    2014-06-01

    Discontinuation of anti-hyperglycemic oral agents and initiation of insulin is recommended in certain clinical situations for inpatients with type 2 diabetes (T2D). The effects on glucose turnover when these agents are acutely withdrawn are poorly understood and may be of importance when insulin therapy is initiated. Our objective was to investigate alterations in glucose turnover after acute withdrawal of noninsulin therapy. This was a randomized crossover study at a clinical research facility. Participants included 12 insulin-naive subjects with T2D. Subjects attended two 24-hour visits. Standard therapy was discontinued and replaced by closed-loop insulin delivery during the intervention visit. Usual anti-hyperglycemic therapy was continued during the control visit. Systemic glucose appearance (Ra) and glucose disposal (Rd) were measured using a tracer dilution technique with iv [6,6-(2)H2]glucose. Plasma glucose profiles during both visits were comparable (P = .48). Glucose Ra increased during the day (21.4 [19.5, 23.5] vs 18.6 [17.0, 21.6) μmol/kg/min, P = .019) and decreased overnight (9.7 [8.5, 11.4] vs 11.6 [10.3, 12.9] μmol/kg/min, P = .004) when the usual therapy was discontinued and replaced with insulin. Increased daytime glucose Rd (21.2 [19.4, 23.9] vs 18.8 [18.3, 21.7] μmol/kg/min, P = .002) and decreased overnight Rd (10.4 [9.1, 12.0] vs 11.8 [10.7, 13.7] μmol/kg/min, P = .005) were observed when the usual therapy was discontinued, whereas daytime peripheral insulin sensitivity was reduced (47.8 [24.8, 66.1] vs 62.5 [34.8, 75.8] nmol/kg/min per pmol/L, P = .034). In T2D, acute discontinuation of anti-hyperglycemic therapy and replacement with insulin increases postprandial Ra and reduces peripheral insulin sensitivity. Insulin dose initiation may need to compensate for these alterations.

  19. Insulin Knockout Mice Have Extended Survival but Volatile Blood Glucose Levels on Leptin Therapy.

    PubMed

    Neumann, Ursula H; Denroche, Heather C; Mojibian, Majid; Covey, Scott D; Kieffer, Timothy J

    2016-03-01

    Leptin can reverse hyperglycemia in rodent models of type 1 diabetes. However, these models have used chemical or immune mediated β-cell destruction where insulin depletion is incomplete. Thus it is unknown which actions of leptin are entirely insulin independent, versus those which require insulin. To directly assess this we maximized blockage of insulin action using an insulin receptor antagonist in combination with streptozotocin-diabetic mice; leptin treatment was still able to reduce blood glucose. Next, we leptin-treated adult insulin knockout (InsKO) mice. Remarkably, leptin-treated InsKO mice were viable for up to 3 weeks without insulin therapy. Leptin treatment reduced plasma corticosterone, glucagon, β-hydroxybutyrate, triglycerides, cholesterol, fatty acids and glycerol. However, leptin-treated InsKO mice exhibited overt fed hyperglycemia and severe fasting hypoglycemia. Therefore, leptin can normalize many metabolic parameters in the complete absence of insulin, but blood glucose levels are volatile and the length of survival finite.

  20. Intensive diabetes therapy and ocular surgery in type 1 diabetes.

    PubMed

    Aiello, Lloyd Paul; Sun, Wanjie; Das, Arup; Gangaputra, Sapna; Kiss, Szilard; Klein, Ronald; Cleary, Patricia A; Lachin, John M; Nathan, David M

    2015-04-30

    The Diabetes Control and Complications Trial (DCCT) showed a beneficial effect of 6.5 years of intensive glycemic control on retinopathy in patients with type 1 diabetes. Between 1983 and 1989, a total of 1441 patients with type 1 diabetes in the DCCT were randomly assigned to receive either intensive diabetes therapy or conventional therapy aimed at preventing hyperglycemic symptoms. They were treated and followed until 1993. Subsequently, 1375 of these patients were followed in the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. The self-reported history of ocular surgical procedures was obtained annually. We evaluated the effect of intensive therapy as compared with conventional therapy on the incidence and cost of ocular surgery during these two studies. Over a median follow-up of 23 years, 130 ocular operations were performed in 63 of 711 patients assigned to intensive therapy (8.9%) and 189 ocular operations in 98 of 730 patients assigned to conventional therapy (13.4%) (P<0.001). After adjustment for DCCT baseline factors, intensive therapy was associated with a reduction in the risk of any diabetes-related ocular surgery by 48% (95% confidence interval [CI], 29 to 63; P<0.001) and a reduction in the risk of all such ocular procedures by 37% (95% CI, 12 to 55; P=0.01). Forty-two patients who received intensive therapy and 61 who received conventional therapy underwent cataract extraction (adjusted risk reduction with intensive therapy, 48%; 95% CI, 23 to 65; P=0.002); 29 patients who received intensive therapy and 50 who received conventional therapy underwent vitrectomy, retinal-detachment surgery, or both (adjusted risk reduction, 45%; 95% CI, 12 to 66; P=0.01). The costs of surgery were 32% lower in the intensive-therapy group. The beneficial effects of intensive therapy were fully attenuated after adjustment for mean glycated hemoglobin levels over the entire follow-up. Intensive therapy in patients with type 1

  1. Insulin sensitivity and counter-regulatory hormones in hypothyroidism and during thyroid hormone replacement therapy.

    PubMed

    Stanická, Sona; Vondra, Karel; Pelikánová, Terezie; Vlcek, Petr; Hill, Martin; Zamrazil, Václav

    2005-01-01

    We examined insulin sensitivity and secretion, together with the levels of selected glucoregulatory hormones, in 15 female patients with severe hypothyroidism (H) and during subsequent thyroid hormone replacement therapy (HRT) using the euglycaemic hyperinsulinaemic clamp technique. Insulin action, as evaluated by glucose disposal, the insulin sensitivity index, and fasting post-hepatic insulin delivery rate were established. The basal levels of insulin, C-peptide and counter-regulatory hormones were measured in basal condition. In H, glucose disposal (p<0.01), the insulin sensitivity index (p<0.01) and post-hepatic insulin delivery rate (p<0.05) were significantly lower than during HRT. No significant changes in the levels of fasting insulin and C-peptide were observed. The levels of counter-regulatory hormones in patients with H were significantly higher than during HRT (glucagon, p<0.05; epinephrine, p<0.01; cortisol, p<0.05; growth hormone, p<0.05). In H, an inverse correlation between insulin sensitivity and insulin secretion was observed (p<0.05). Cortisol was the most important factor affecting the variability of insulin sensitivity values, regardless of thyroid function (p=0.0012). In conclusion, H altered both insulin sensitivity and the levels of selected counter-regulatory hormones. The situation was restored by HRT, as manifested not only by normalisation of insulin sensitivity, secretion and levels of glucoregulatory hormones, but also by improvement of their relationships.

  2. 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

  3. Long-term Effectiveness of Intensive Therapy in Chronic Stroke.

    PubMed

    Wu, Xiaotian; Guarino, Peter; Lo, Albert C; Peduzzi, Peter; Wininger, Michael

    2016-07-01

    Background While recent clinical trials involving robot-assisted therapy have failed to show clinically significant improvement versus conventional therapy, it is possible that a broader strategy of intensive therapy-to include robot-assisted rehabilitation-may yield clinically meaningful outcomes. Objective To test the immediate and sustained effects of intensive therapy (robot-assisted therapy plus intensive conventional therapy) on outcomes in a chronic stroke population. Methods A multivariate mixed-effects model adjusted for important covariates was established to measure the effect of intensive therapy versus usual care. A total of 127 chronic stroke patients from 4 Veterans Affairs medical centers were randomized to either robot-assisted therapy (n = 49), intensive comparison therapy (n = 50), or usual care (n = 28), in the VA-ROBOTICS randomized clinical trial. Patients were at least 6 months poststroke, of moderate-to-severe upper limb impairment. The primary outcome measure was the Fugl-Meyer Assessment at 12 and 36 weeks. Results There was significant benefit of intensive therapy over usual care on the Fugl-Meyer Assessment at 12 weeks with a mean difference of 4.0 points (95% CI = 1.3-6.7); P = .005; however, by 36 weeks, the benefit was attenuated (mean difference 3.4; 95% CI = -0.02 to 6.9; P = .05). Subgroup analyses showed significant interactions between treatment and age, treatment and time since stroke. Conclusions Motor benefits from intensive therapy compared with usual care were observed at 12 and 36 weeks posttherapy; however, this difference was attenuated at 36 weeks. Subgroups analysis showed that younger age, and a shorter time since stroke were associated with greater immediate and long-term improvement of motor function. © The Author(s) 2015.

  4. Psychological resistance to insulin therapy in adults with type 2 diabetes: mixed-method systematic review.

    PubMed

    Wang, Huey-Fen; Yeh, Mei Chang

    2012-04-01

    This paper is a report of a review that aimed to describe the phenomenon of psychological resistance to insulin therapy from the perspective of adults with type 2 diabetes mellitus. Although the benefits of insulin for people with diabetes who are poorly controlled by oral agents have been established, delay in transition to insulin treatment is common. An understanding of the barriers to insulin from the client's viewpoint provides information to facilitate appropriate and effective care. Searches were carried out between 1999 and 2009 using computerized databases, three in English language and one in Chinese. Review design was a mixed-method systematic review, and data abstraction and synthesis were undertaken by thematic synthesis. Reviewed articles were restricted to adults with type 2 diabetes and published in English or Chinese. Sixteen articles were included. For adults with type 2 diabetes, psychological resistance to insulin therapy could be explained by five themes. Three themes were categorized as cognitive appraisal, including 'people do not see the necessity for insulin and actively seek ways to control blood sugars without insulin', 'people have a holistic view of the consequences of insulin' and 'people see insulin therapy as less feasible'. Two themes were categorized as emotional reactions: 'people see insulin as a source of fear/anxiety', and 'the necessity to start insulin therapy has a very negative connotation for them and is associated with dysfunctional emotions'. Psychological resistance to insulin therapy can result from a range of personal viewpoints involving cognitive appraisal and/or emotional reactions. © 2011 Blackwell Publishing Ltd.

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

    PubMed

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

    2013-12-01

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

  6. Patients' with type 2 diabetes willingness to pay for insulin therapy and clinical outcomes

    PubMed Central

    Feher, Michael D; Brazier, John; Schaper, Nicolaas; Vega-Hernandez, Gabriela; Bøgelund, Mette

    2016-01-01

    Objectives This study assessed patient preferences, using willingness to pay as a method to measure different treatment characteristics or attributes associated with injectable insulin therapy in patients with type 2 diabetes. Research design and methods Adults with type 2 diabetes in 12 countries, diagnosed >6 months prior and receiving insulin for >3 months, were recruited through a representative online panel. Data were collected via online questionnaire and analyzed using a standard choice model for discrete choice experiment. Results A total of 3758 patients from North America (n=646), South America (n=1537), and Europe (n=1575) completed the study. Mean glycated hemoglobin (HbA1c) levels in North America, South America, and Europe were 63 mmol/mol (7.9%), 75 mmol/mol (9.0%), and 64 mmol/mol (8.0%), respectively. In the three regions, monthly willingness to pay was US$116, US$74, and US$92, respectively, for a 1%-point decrease in HbA1c; US$99, US$80, and US$104 for one less major hypoglycemic event per year; and US$64, US$37 and US$60 for a 3 kg weight decrease. To avoid preinjection preparation of insulin, the respective values were US$47, US$18, and US$37, and US$25, US$25, and US$24 for one less injection per day. Among respondents on basal-only insulin who had previously tried a more intensive regimen, reasons for switching back included difficulty in handling multiple injections and risk of hypoglycemic events. Conclusions Reducing HbA1c, frequency of major hypoglycemic events and weight decrease were the highest valued outcomes in each region. The administrative burden of injections was also considered important. PMID:27158518

  7. Important determinants of diabetes control in insulin pump therapy in patients with type 1 diabetes mellitus.

    PubMed

    Deeb, Asma; Abu-Awad, Samar; Abood, Salima; El-Abiary, Mohamed; Al-Jubeh, Jamal; Yousef, Hana; AbdelRahman, Laila; Al Hajeri, Ahlam; Mustafa, Huda

    2015-03-01

    Insulin pumps are equipped with advanced functions. Intensive training and adherence are required for optimum use of the technology. We aimed to assess the association of various key elements in insulin pump functions on blood glucose control. Patients on insulin pump therapy were enrolled. Insulin pumps were downloaded (CareLink(®) Pro 3 software; Medtronic Minimed, Northridge, CA), and data were collected over an 8-12-week period. Glycemic control of patients was classified as controlled (hemoglobin A1c [HbA1c] level of 7.5% or less in adults and 8% or less in children) and uncontrolled based on HbA1c level at enrollment. Variables studied were use of sensors and duration, frequency of blood glucose monitoring, Bolus Wizard (Medtronic Minimed) use, frequency of correction boluses, and frequency of cannula changing. Seventy-two patients were enrolled (50 children). Median age was 12 years for children and 27.5 years for adults. Respective median numbers of blood glucose checks were 4.4 and 3.2 for controlled and uncontrolled children (P<0.021) and 3.1 and 2.8 for controlled and uncontrolled adults, respectively. Respective frequency of Bolus Wizard use per day showed a median of 6 and 4.15 for controlled and uncontrolled children (P<0.001) and 3.8 and 3.5 for controlled and uncontrolled adults. Controlled children wore sensors for longer (5 vs. 2.9 days/week) and did more corrections (3.9 vs. 2.5). There was no difference in the frequency of changing the infusion cannula in children's or adults' groups. We conclude that the frequency of blood glucose monitoring and Bolus Wizard use have a favorable association with glycemic control. These observations were more significant in the children's groups. Our data shows that patients with better control tend to bolus more for correction and wear sensors longer.

  8. Treating the whole patient for optimal management of type 2 diabetes: considerations for insulin therapy.

    PubMed

    Campos, Carlos

    2007-08-01

    Primary care physicians are responsible for providing healthcare to most patients with type 2 diabetes. In this role, it is critical that physicians utilize a whole-patient treatment approach that includes lifestyle modifications and pharmacotherapy aimed to achieve glycemic control, in addition to the management of any comorbid conditions or risk factors for cardiovascular complications of diabetes. Due to the progressive nature of the disease, most patients with type 2 diabetes will eventually require insulin to achieve and maintain glycemic control, because of both increased insulin resistance and diminished secretory capacity of the pancreatic beta cells. Thus, physicians need to be knowledgeable about and comfortable with the use of insulin, as well as with educating patients and discussing any potential barriers to insulin therapy. The use of a stepwise approach--beginning with basal insulin therapy and adding prandial insulin if necessary--is simple, effective, and appropriate for use in many patients.

  9. Lipoprotein metabolism in patients with type 1 diabetes under intensive insulin treatment

    PubMed Central

    2013-01-01

    Background Type 1 diabetes (T1DM) is frequently accompanied by dyslipidemia related with insulin-dependent steps of the intravascular lipoprotein metabolism. T1DM dyslipidemia may predispose to precocious cardiovascular disease and the lipid status in T1DM under intensive insulin treatment has not been sufficiently explored. The aim was to investigate the plasma lipids and the metabolism of LDL and HDL in insulin-treated T1DM patients with high glycemic levels. Methods Sixteen male patients with T1DM (26 ± 7 yrs) with glycated hemoglobin >7%, and 15 control subjects (28 ± 6 yrs) were injected with a lipid nanoemulsion (LDE) resembling LDL and labeled with 14C-cholesteryl ester and 3H-free-cholesterol for determination of fractional clearance rates (FCR, in h-1) and cholesterol esterification kinetics. Transfer of labeled lipids from LDE to HDL was assayed in vitro. Results LDL-cholesterol (83 ± 15 vs 100 ± 29 mg/dl, p=0.08) tended to be lower in T1DM than in controls; HDL-cholesterol and triglycerides were equal. LDE marker 14C-cholesteryl ester was removed faster from plasma in T1DM patients than in controls (FCR=0.059 ± 0.022 vs 0.039 ± 0.022h-1, p=0.019), which may account for their lower LDL-cholesterol levels. Cholesterol esterification kinetics and transfer of non-esterified and esterified cholesterol, phospholipids and triglycerides from LDE to HDL were also equal. Conclusion T1DM patients under intensive insulin treatment but with poor glycemic control had lower LDL-cholesterol with higher LDE plasma clearance, indicating that LDL plasma removal was even more efficient than in controls. Furthermore, HDL-cholesterol and triglycerides, cholesterol esterification and transfer of lipids to HDL, an important step in reverse cholesterol transport, were all normal. Coexistence of high glycemia levels with normal intravascular lipid metabolism may be related to differences in exogenous insulin bioavailabity and different insulin mechanisms of action on

  10. Insulin requirement profiles in Japanese hospitalized subjects with type 2 diabetes treated with basal-bolus insulin therapy.

    PubMed

    Shimoda, Seiya; Okubo, Mina; Koga, Kotaro; Sekigami, Taiji; Kawashima, Junji; Kukidome, Daisuke; Igata, Motoyuki; Ishii, Norio; Shimakawa, Akiko; Matsumura, Takeshi; Motoshima, Hiroyuki; Furukawa, Noboru; Nishida, Kenro; Araki, Eiichi

    2015-01-01

    To assess the total daily inulin dose (TDD) and contribution of basal insulin to TDD and to identify the predictive factors for insulin requirement profiles in subjects with type 2 diabetes, we retrospectively examined insulin requirement profiles of 275 hospitalized subjects treated with basal-bolus insulin therapy (BBT) (mean age, 60.1 ± 12.9 years; HbA1c, 10.2 ± 4.5%). Target plasma glucose level was set between 80 and 129 mg/dL before breakfast and between 80 and 179 mg/dL at 2-hour after each meal without causing hypoglycemia. We also analyzed the relationship between the insulin requirement profiles (TDD and basal/total daily insulin ratio [B/TD ratio]) and insulin-associated clinical parameters. The mean TDD was 0.463 ± 0.190 unit/kg/day (range, 0.16-1.13 unit/kg/day). The mean B/TD ratio was 0.300 ± 0.099 (range, 0.091-0.667). A positive correlation of TDD with B/TD ratio was revealed by linear regression analysis (r=0.129, p=0.03). Stepwise multiple regression analysis identified post-breakfast glucose levels before titrating insulin as an independent determinant of the insulin requirement profile [Std β (standard regression coefficient) = 0.228, p<0.01 for TDD, Std β = -0.189, p<0.01 for B/TD ratio]. The TDD was <0.6 unit/kg/day and the B/TD ratio was <0.4 in the majority (70.2%) of subjects in the present study. These findings may have relevance in improving glycemic control and decreasing the risk of hypoglycemia and weight gain in subjects with type 2 diabetes treated with BBT.

  11. Evolution of insulin resistance in coronary artery disease patients on four different pharmacological therapies

    PubMed Central

    Piedrola, G.; Novo, E.; Serrano-Gotarredo..., J.; de Teresa, M. L.; Garcia-Robles, R.

    1999-01-01

    The objective of the study was to examine the evolution of insulin sensitivity in a group of patients with stable coronary artery disease receiving one of four different pharmacological therapies. Insulin sensitivity was evaluated using an insulin suppression test in 40 newly diagnosed patients with coronary artery disease and no previous history of metabolic disorders, who were not taking any medication which might affect insulin sensitivity. The insulin suppression test consisted of a constant infusion of glucose, insulin and somatostatin for 150 min; insulin resistance was estimated by determining the steady-state plasma glucose concentrations during the last 60 minutes of the test. The insulin sensitivity index was calculated by the formula: insulin sensitivity index = (glucose infusion rate/steady state plasma glucose concentrations) × 103. A second insulin suppression test was performed after 6 months' therapy with either isosorbide mononitrate, atenolol, diltiazem or captopril in 30 of the 40 patients.
  There were no differences between any of the groups before therapy was initiated. After 6 months, patients treated with captopril and, to a lesser extent, those treated with diltiazem showed statistically significantly decreased steady state plasma glucose concentrations and increased insulin sensitivity index compared to basal values. No statistically significant differences were found in the other two groups. We conclude that captopril and, to a lesser extent, diltiazem improve insulin sensitivity in patients with stable coronary artery disease.


Keywords: insulin resistance; coronary artery disease; captopril; diltiazem PMID:10396583

  12. Switching from multiple daily injections to CSII pump therapy: insulin expenditures in type 2 diabetes.

    PubMed

    David, Guy; Gill, Max; Gunnarsson, Candace; Shafiroff, Jeff; Edelman, Steven

    2014-11-01

    To identify variations in expenditures and utilization of insulin and other antidiabetes medications by comparing patients with type 2 diabetes mellitus using continuous subcutaneous insulin infusion (CSII) pump therapy versus multiple daily injection (MDI) therapy. Truven Health Analytics MarketScan Commercial Claims and Encounters Database and Medicare Supplemental Database for 2006 to 2010 were used in a difference-in-differences approach that took advantage of variation in the timing of the switch from MDI therapy to CSII pump therapy. Continuous users of MDI therapy throughout the study period were compared with those who switched to the CSII pump therapy during this period. Specifications included: coefficient estimates from cross-sectional ordinary least squares (OLS) regressions with: 1) no additional controls, 2) controls for patient demographics and comorbidities, and 3) patient fixed effects. Propensity score matching at baseline mitigated concerns regarding patient selection bias. While insulin expenditures rose during the study period, switching to CSII pump therapy led to sizable reductions in insulin expenditures. This reduction in insulin expenditures due to switching varied between $657 (standard error [SE] $126; P<.01) and $1011 (SE $250.60; P<.01) per year. This study demonstrated a significant reduction in insulin expenditures among MDI patients who switched to CSII pump therapy at various times throughout the study period.

  13. Do Perceptions of Insulin Pump Usability Impact Attitudes Toward Insulin Pump Therapy? A Pilot Study of Individuals With Type 1 and Insulin-Treated Type 2 Diabetes

    PubMed Central

    Gilgen, Emily

    2014-01-01

    Background: We assessed the impact of perceived insulin pump usability on attitudes toward insulin pump therapy in diabetic individuals currently treated with multiple daily insulin injections (MDI). Method: This comparative, single-arm study recruited 28 adults with type 1 (n = 16) and insulin-treated type 2 diabetes (n = 12) to evaluate 2 current insulin pumps: Medtronic Revel 723 (Pump 1), Asante Snap Insulin Pump (Pump 2). Participants were randomized 1:1 to 1 of 2 assessment sequences: Pump 1 followed by Pump 2; and Pump 2 followed by Pump 1. Structured observational protocols were utilized to assess participants’ ability and time required to learn/perform common tasks associated with pump setup/use. Participants used a modified version of the System Usability Scale (SUS) and investigator-developed questionnaires to rate pump usability and task difficulty; pre-post questionnaires assessed changes in attitudes toward insulin pump therapy. Results: All participants completed the study. SUS scores showed Pump 2 to be more usable than Pump 1 on all usability attributes. Participants rated Pump 2 more positively than Pump 1, overall mean SUS scores of 5.7 versus 4.1 respectively, F(1, 52) = 32.7, P < .001, and SUS scores were higher if participants used the Pump 2 last, 5.3 versus 4.4 for Pump 1 last, F(1, 52) = 10.8, P < .01. Pump 2 was preferred for all tasks: manual bolus (86%), bolus calculation (71%), managing basal rates (93%), interpreting alarms (96%), transferring settings (100%), changing insulin and infusion sets (93%), all P < .05. Conclusions: Perceptions of pump usability can directly impact acceptance and use of features that may benefit those who wear them. Simpler pump devices that decrease perceptions of complexity may encourage broader use of this technology. PMID:25269659

  14. Do perceptions of insulin pump usability impact attitudes toward insulin pump therapy? A pilot study of individuals with type 1 and insulin-treated type 2 diabetes.

    PubMed

    Chamberlain, James J; Gilgen, Emily

    2015-01-01

    We assessed the impact of perceived insulin pump usability on attitudes toward insulin pump therapy in diabetic individuals currently treated with multiple daily insulin injections (MDI). This comparative, single-arm study recruited 28 adults with type 1 (n = 16) and insulin-treated type 2 diabetes (n = 12) to evaluate 2 current insulin pumps: Medtronic Revel 723 (Pump 1), Asante Snap Insulin Pump (Pump 2). Participants were randomized 1:1 to 1 of 2 assessment sequences: Pump 1 followed by Pump 2; and Pump 2 followed by Pump 1. Structured observational protocols were utilized to assess participants' ability and time required to learn/perform common tasks associated with pump setup/use. Participants used a modified version of the System Usability Scale (SUS) and investigator-developed questionnaires to rate pump usability and task difficulty; pre-post questionnaires assessed changes in attitudes toward insulin pump therapy. All participants completed the study. SUS scores showed Pump 2 to be more usable than Pump 1 on all usability attributes. Participants rated Pump 2 more positively than Pump 1, overall mean SUS scores of 5.7 versus 4.1 respectively, F(1, 52) = 32.7, P < .001, and SUS scores were higher if participants used the Pump 2 last, 5.3 versus 4.4 for Pump 1 last, F(1, 52) = 10.8, P < .01. Pump 2 was preferred for all tasks: manual bolus (86%), bolus calculation (71%), managing basal rates (93%), interpreting alarms (96%), transferring settings (100%), changing insulin and infusion sets (93%), all P < .05. Perceptions of pump usability can directly impact acceptance and use of features that may benefit those who wear them. Simpler pump devices that decrease perceptions of complexity may encourage broader use of this technology.

  15. Lactation Intensity and Postpartum Maternal Glucose Tolerance and Insulin Resistance in Women With Recent GDM

    PubMed Central

    Gunderson, Erica P.; Hedderson, Monique M.; Chiang, Vicky; Crites, Yvonne; Walton, David; Azevedo, Robert A.; Fox, Gary; Elmasian, Cathie; Young, Stephen; Salvador, Nora; Lum, Michael; Quesenberry, Charles P.; Lo, Joan C.; Sternfeld, Barbara; Ferrara, Assiamira; Selby, Joseph V.

    2012-01-01

    OBJECTIVE To examine the association between breastfeeding intensity in relation to maternal blood glucose and insulin and glucose intolerance based on the postpartum 2-h 75-g oral glucose tolerance test (OGTT) results at 6–9 weeks after a pregnancy with gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS We selected 522 participants enrolled into the Study of Women, Infant Feeding, and Type 2 Diabetes (SWIFT), a prospective observational cohort study of Kaiser Permanente Northern California members diagnosed with GDM using the 3-h 100-g OGTT by the Carpenter and Coustan criteria. Women were classified as normal, prediabetes, or diabetes according to American Diabetes Association criteria based on the postpartum 2-h 75-g OGTT results. RESULTS Compared with exclusive or mostly formula feeding (>17 oz formula per 24 h), exclusive breastfeeding and mostly breastfeeding (≤6 oz formula per 24 h) groups, respectively, had lower adjusted mean (95% CI) group differences in fasting plasma glucose (mg/dL) of −4.3 (−7.4 to −1.3) and −5.0 (−8.5 to −1.4), in fasting insulin (μU/mL) of −6.3 (−10.1 to −2.4) and −7.5 (−11.9 to −3.0), and in 2-h insulin of −21.4 (−41.0 to −1.7) and −36.5 (−59.3 to −13.7) (all P < 0.05). Exclusive or mostly breastfeeding groups had lower prevalence of diabetes or prediabetes (P = 0.02). CONCLUSIONS Higher intensity of lactation was associated with improved fasting glucose and lower insulin levels at 6–9 weeks’ postpartum. Lactation may have favorable effects on glucose metabolism and insulin sensitivity that may reduce diabetes risk after GDM pregnancy. PMID:22011407

  16. Occupational Therapy in the Intensive Care Unit: A Systematic Review.

    PubMed

    Weinreich, Mark; Herman, Jennifer; Dickason, Stephanie; Mayo, Helen

    2017-07-01

    This paper is a synthesis of the available literature on occupational therapy interventions performed in the adult intensive care unit (ICU). The databases of Ovid MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov and CINAHL databases were systematically searched from inception through August 2016 for studies of adults who received occupational therapy interventions in the ICU. Of 1,938 citations reviewed, 10 studies met inclusion criteria. Only one study explicitly discussed occupational therapy interventions performed and only one study specifically tested the efficacy of occupational therapy. Future research is needed to clarify the specific interventions and role of occupational therapy in the ICU and the efficacy of these interventions.

  17. Physical Therapy Intervention in the Neonatal Intensive Care Unit

    ERIC Educational Resources Information Center

    Byrne, Eilish; Garber, June

    2013-01-01

    This article presents the elements of the Intervention section of the Infant Care Path for Physical Therapy in the Neonatal Intensive Care Unit (NICU). The types of physical therapy interventions presented in this path are evidence-based and the suggested timing of these interventions is primarily based on practice knowledge from expert…

  18. [Intensive therapy for patients with Guillian-Barré syndrome].

    PubMed

    Buus, Lone; Tønnesen, Else K

    2014-10-13

    Guillain-Barré syndrome is the leading cause of acute flaccid paralysis in the industrialized world. Approximately 25% of the patients suffering from Guillain-Barré syndrome develop respiratory failure requiring mechanical ventilation and intensive therapy. We seek answers to when it is optimal to start respiratory supportive therapy and review various complications associated with Guillain-Barré syndrome.

  19. Physical Therapy Intervention in the Neonatal Intensive Care Unit

    ERIC Educational Resources Information Center

    Byrne, Eilish; Garber, June

    2013-01-01

    This article presents the elements of the Intervention section of the Infant Care Path for Physical Therapy in the Neonatal Intensive Care Unit (NICU). The types of physical therapy interventions presented in this path are evidence-based and the suggested timing of these interventions is primarily based on practice knowledge from expert…

  20. Intense Pulsed Light Therapy for Skin Rejuvenation.

    PubMed

    DiBernardo, Barry E; Pozner, Jason N

    2016-07-01

    Intense pulsed light (IPL), also known as pulsed light and broad band light, is a nonlaser light source used to treat a variety of vascular and pigmented lesions, photo damage, active acne, and unwanted hair. Current IPL systems are much improved from older-generation devices with better calibration, integrated cooling, and improved tuning. These devices are extremely popular because of their versatility and are often the first devices recommended and purchased in many offices. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Stuttering: An Account of Intensive Demonstration Therapy. Publication N. 8.

    ERIC Educational Resources Information Center

    Starkweather, C. Woodruff

    Presented is a summary of a 5 week program of intensive demonstration therapy conducted with three adult severe stutterers by three master clinicians aided by seven consultants and 15 participating fellows. A main purpose of the institute is said to have been the improvement of student clinicians through demonstration of intensive therapy…

  2. Chronic insulin therapy reduces adipose tissue macrophage content in LDL-receptor-deficient mice.

    PubMed

    Yoon, J; Subramanian, S; Ding, Y; Wang, S; Goodspeed, L; Sullivan, B; Kim, J; O'Brien, K D; Chait, A

    2011-05-01

    Insulin has anti-inflammatory effects in short-term experiments. However, the effects of chronic insulin administration on inflammation are unknown. We hypothesised that chronic insulin administration would beneficially alter adipose tissue inflammation and several circulating inflammatory markers. We administered two forms of long-acting insulin, insulin glargine (A21Gly,B31Arg,B32Arg human insulin) and insulin detemir (B29Lys[ε-tetradecanoyl],desB30 human insulin), to LDL-receptor-deficient mice. After 8 weeks on a diet that causes obesity, hyperglycaemia, adipose tissue macrophage accumulation and atherosclerosis, the mice received subcutaneous glargine, detemir or NaCl (control) for 12 weeks. Serum amyloid A (SAA) and serum amyloid P (SAP), metabolic variables, adipose tissue macrophages and aortic atherosclerosis were evaluated. Weight gain was equivalent in all groups. The glycated haemoglobin level fell equivalently in both insulin-treated groups. Plasma cholesterol and triacylglycerol levels, and hepatic triacylglycerol level significantly improved in the glargine compared with the detemir or control groups. Levels of mRNA expression for monocyte chemotactic protein-1 and F4/80, a macrophage marker, in adipose tissue were decreased only in the glargine group (p < 0.05). Visceral adipose tissue macrophage content decreased in both insulin groups (p < 0.05), whereas atherosclerosis decreased only in the glargine group. Circulating SAA and SAP did not decrease in either insulin-treated group, but IL-6 levels fell in the glargine-treated mice. While chronic insulin administration did not decrease SAA and SAP, administration of glargine but not detemir insulin improved dyslipidaemia, IL-6 levels and atherosclerosis, and both insulins reduced macrophage accumulation in visceral adipose tissue. Thus, chronic insulin therapy has beneficial tissue effects independent of circulating inflammatory markers in this murine model of diet-induced obesity and

  3. Insulin resistance in postmenopausal women: concurrent effects of hormone replacement therapy and coffee.

    PubMed

    Catalano, D; Trovato, G M; Spadaro, D; Martines, G F; Garufi, G; Tonzuso, A; Grasso, D; Sciacchitano, S G

    2008-10-01

    In postmenopausal women, an increase in insulin resistance is associated with an increased risk of diabetes, cardiovascular disease and breast cancer. Hormone replacement therapy (HRT) can reduce insulin resistance and coffee use is reported to decrease the incidence of diabetes. The aim of our study was to assess possible concurrent effects of HRT and espresso coffee intake on insulin resistance and on interdependent nutritional and clinical features. A total of 478 healthy postmenopausal, non-diabetic women (aged 54.5 +/- 4.2 years) were studied: 360 had been on HRT for at least 2 years and 118 were not treated. Insulin resistance was assessed by a conventional homeostasis model (HOMA-IR). Insulin resistance is directly related to body mass index (p < 0.0001), and not with age and blood pressure; hypertensive menopausal women have a slightly higher body mass index but the same degree of insulin resistance as normotensive women. Women on HRT show lower insulin resistance, but not lower prevalence of arterial hypertension. Coffee use is associated with a decrease in insulin resistance in non-obese women receiving HRT, but not in other subsets. The combination of coffee consumption and HRT could lower insulin resistance in postmenopausal women. In overweight women, greater insulin sensitivity is associated with intake of espresso coffee and not with HRT; in normal weight women, only HRT is associated with lower insulin resistance.

  4. Combination therapy with GLP-1 receptor agonists and basal insulin: a systematic review of the literature

    PubMed Central

    Balena, R; Hensley, I E; Miller, S; Barnett, A H

    2013-01-01

    Treatment algorithms for type 2 diabetes call for intensification of therapy over time as the disease progresses and glycaemic control worsens. If diet, exercise and oral antihyperglycaemic medications (OAMs) fail to maintain glycaemic control then basal insulin is added and ultimately prandial insulin may be required. However, such an intensification strategy carries risk of increased hypoglycaemia and weight gain, both of which are associated with worse long-term outcomes. An alternative strategy is to intensify therapy by the addition of a short-acting glucagon-like peptide-1 receptor agonist (GLP-1 RA) rather than prandial insulin. Short-acting GLP-1 RAs such as exenatide twice daily are particularly effective at reducing postprandial glucose while basal insulin has a greater effect on fasting glucose, providing a physiological rationale for this complementary approach. This review analyzes the latest randomized controlled clinical trials of insulin/GLP-1 RA combination therapy and examines results from ‘real-world’ use of the combinations as reported through observational and clinical practice studies. The most common finding across all types of studies was that combination therapy improved glycaemic control without weight gain or an increased risk of hypoglycaemia. Many studies reported weight loss and a reduction in insulin use when a GLP-1 RA was added to existing insulin therapy. Overall, the relative degree of benefit to glycaemic control and weight was influenced by the insulin titration employed in conjunction with the GLP-1 RA. The greatest glycaemic benefits were observed in studies with structured titration of insulin to glycaemic targets while the greatest weight benefits were observed in studies with a protocol-specified focus on insulin sparing. The adverse event profile of GLP-1 RAs in the reviewed trials was similar to that reported with GLP-1 RAs as monotherapy or in combination with OAMs with gastrointestinal events being the most commonly

  5. Treatment intensification using long-acting insulin -predictors of future basal insulin supported oral therapy in the DIVE registry.

    PubMed

    Danne, Thomas; Bluhmki, Tobias; Seufert, Jochen; Kaltheuner, Matthias; Rathmann, Wolfgang; Beyersmann, Jan; Bramlage, Peter

    2015-10-07

    In patients with type-2 diabetes receiving oral antidiabetic drugs (OADs), the addition of insulin is frequently required to achieve sufficient control over blood glucose levels. It is, however, difficult to predict if, when and in which patients insulin therapy will be needed. We aimed to identify patient related variables associated with the addition of basal insulin to oral therapy resulting in a basal supported oral therapy (BOT). DIVE (DIabetes Versorgungs-Evaluation) is a prospective, observational, multi-centre diabetes registry established in Germany in 2011. For the present explorative analysis, 31,008 patients with type-2 diabetes prescribed at least one OAD were included. Patients who had previously received insulin and those over 90 years old were excluded. The event of interest was defined as the initiation of BOT during the observational period. Cause-specific Cox proportional hazards models based on a competing risk framework were applied for risk quantification. Multivariable adjusted hazard ratios demonstrated that longer diabetes duration, higher BMI, poorer glycaemic control, documentation of any micro- or macrovascular comorbidity, the presence of concomitant non-antidiabetic pharmacotherapies, and greater numbers of prescribed OADs increased the likelihood of BOT initiation. On the other hand BOT initiation was less likely in patients with older age and female gender. Analysing the likelihood of OAD termination without initiation of BOT provided supportive evidence for the variables predictive of BOT initiation. Analysis of the DIVE registry has resulted in the identification of a number of factors that may be predictive for the initiation of BOT for type-2 diabetes patients initially prescribed one or more OADs. Poor glycaemic control, the presence of vascular comorbidities and concomitant medications, and a greater number of OADs were all detected to increase the risk of a switch to BOT. Female gender and younger age showed protective

  6. Linagliptin as add-on therapy to insulin for patients with type 2 diabetes.

    PubMed

    von Websky, Karoline; Reichetzeder, Christoph; Hocher, Berthold

    2013-01-01

    Type 2 diabetes mellitus (T2DM) is a highly prevalent, progressive disease that often is poorly controlled. The combination of an incretin-based therapy and insulin is a promising approach to optimize the management of glycemic control without hypoglycemia and weight gain. Linagliptin, a recently approved oral dipeptidyl peptidase-4 inhibitor, has a unique pharmacological profile. The convenient, once-daily dosing does not need adjustment in patients with hepatic and/or renal impairment. In clinical studies linagliptin shows an important reduction of blood glucose with an overall safety profile similar to that of placebo. So far, the combination of linagliptin and insulin has been tested in three major clinical studies in different populations. It has been shown that linagliptin is an effective and safe add-on therapy to insulin in patients with T2DM. The efficacy and safety of this combination was also shown in vulnerable, elderly T2DM patients and in patients with T2DM and renal impairment. Favorable effects regarding the counteraction of hypoglycemia make linagliptin especially interesting as an add-on therapy to insulin. This review aims to present the existing clinical studies on the efficacy and safety of linagliptin as add-on therapy to insulin in patients with T2DM in the context of current literature. Additionally, the possible advantages of linagliptin as an add-on therapy to insulin in relation to cardiovascular safety, patient-centered therapy and the prevention of hypoglycemia, are discussed.

  7. Dipeptidyl peptidase-4 inhibitors as add-on therapy to insulin: rationale and evidences.

    PubMed

    Singh, Awadhesh Kumar; Singh, Ritu

    2016-01-08

    Type 2 diabetes mellitus being a progressive disease will eventually require insulin therapy. While insulin therapy is the ultimate option, many patients still fall short of target glycemic goals. This could, perhaps be due to the fear, unwillingness and practical barriers to insulin intensification. Hypoglycemia, oedema and weight gain is another limitation. Newer therapies with dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose co-transporter-2 (SGLT-2) inhibitors are exciting options as both classes do not cause hypoglycemia and are either weight neutral or cause weight loss. DPP-4 inhibitors are an appealing option as an add-on therapy to insulin especially in elderly and patients with renal impairment. Moreover, glucose-dependent insulinotropic polypeptide (GIP) mediated augmentation of glucagon by DPP-4 inhibitors could also protect against hypoglycemia. These collective properties make these class a potential add-on candidate to insulin therapy. This article will review the efficacy and safety of DPP-4 inhibitors as an add-on to insulin therapy.

  8. Novel hormonal delivery method using the ink-jet technology: application to pulmonary insulin therapies.

    PubMed

    Nemoto, Masami; Hiki, Yoshito; Shimada, Kousuke; Nakai, Nozomu; Fujimoto, Kei; Inoue, Sachiko; Sakurada, Naoko; Kaneko, Hideki; Sugita, Masaru; Okabe, Masataka; Sasaki, Takashi

    2011-05-01

    A device developed based on ink-jet printer technology can precisely control the size and volume of droplets ejected. Here, we evaluated the application of this technology to the pulmonary administration of insulin mist as a therapeutic measure for diabetes. Insulin ejected from the ink-jet device was initially characterized by high-performance liquid chromatography (HPLC) and mass spectrometry. Its effects on D-glucose uptake rate by L6 cells were then investigated. Next, different insulin solutions (with or without additives or ink-jet processing) were subcutaneously administered, and their pharmacodynamic features were evaluated. Finally, decreases in plasma glucose level in rats were examined after ventilator-assisted pulmonary administration of insulin mist. Neither the HPLC nor the mass spectrometry profile of insulin was altered by the ink-jet process. The D-glucose uptake rate by L6 cells that received the recovered aerosolized insulin solution was similar to that of cells treated with control insulin, at 107%. Neither the addition of additives nor the ink-jet process used for insulin aerosolization impaired the plasma glucose-lowering action of subcutaneously injected insulin. Similarly, the efficacy of pulmonary insulin administration was not affected by the additives or the ink-jet process. Plasma glucose levels showed a trend towards decreasing after ventilator-assisted pulmonary administration of insulin mist. Plasma insulin level increased 30 min after the inhalation. The ink-jet process did not affect the quality or biological activity of insulin, suggesting the potential use of the ink-jet device for insulin inhalation therapy for diabetes.

  9. New-generation diabetes management: glucose sensor-augmented insulin pump therapy

    PubMed Central

    Cengiz, Eda; Sherr, Jennifer L; Weinzimer, Stuart A; Tamborlane, William V

    2011-01-01

    Diabetes is one of the most common chronic disorders with an increasing incidence worldwide. Technologic advances in the field of diabetes have provided new tools for clinicians to manage this challenging disease. For example, the development of continuous subcutaneous insulin infusion systems have allowed for refinement in the delivery of insulin, while continuous glucose monitors provide patients and clinicians with a better understanding of the minute to minute glucose variability, leading to the titration of insulin delivery based on this variability when applicable. Merging of these devices has resulted in sensor-augmented insulin pump therapy, which became a major building block upon which the artificial pancreas (closed-loop systems) can be developed. This article summarizes the evolution of sensor-augmented insulin pump therapy until present day and its future applications in new-generation diabetes management. PMID:21728731

  10. A REVIEW OF LOW-INTENSITY ULTRASOUND FOR CANCER THERAPY

    PubMed Central

    WOOD, ANDREW K. W.; SEHGAL, CHANDRA M.

    2015-01-01

    The literature describing the use of low-intensity ultrasound in four major areas of cancer therapy was reviewed - sonodynamic therapy, ultrasound mediated chemotherapy, ultrasound mediated gene delivery and antivascular ultrasound therapy. Each technique consistently resulted in the death of cancer cells and the bioeffects of ultrasound were primarily attributed to thermal actions and inertial cavitation. In each therapeutic modality, theranostic contrast agents composed of microbubbles played a role in both therapy and vascular imaging. The development of these agents is important as it establishes a therapeutic-diagnostic platform which can monitor the success of anti-cancer therapy. Little attention, however, has been given to either the direct assessment of the underlying mechanisms of the observed bioeffects or to the viability of these therapies in naturally occurring cancers in larger mammals; if such investigations provided encouraging data there could be a prompt application of a therapy technique in treating cancer patients. PMID:25728459

  11. [Insulin therapy in type 2 diabetes: a review of "when" over "how" up to "why"].

    PubMed

    Laimer, Markus; Jenni, Stefan; Stettler, Christoph

    2015-02-11

    Type 2 Diabetes is characterized by its progressive character. An intensification of the therapy is necessary in most cases over the years and insulin is typically used as an add-on agent when oral antidiabetic regimes are judged to be no longer sufficient. However, insulin can also be used in the initial phase of the disease directly after diagnosis of diabetes. Intermittent worsening of glycemic control (e.g. due to infectious diseases or corticosteroids) may be additional indications for an insulin treatment at an earlier stage. Noticeably, insulin can often be stopped if the triggering event or treatment is reversible, thereby countering the widely spread fear of dependency on insulin. We recommend a rather cautious starting dose of insulin and individual adaptations thereafter. Well-informed patients can also perform such adaptations themselves.

  12. Maternal insulin therapy does not restore foetoplacental endothelial dysfunction in gestational diabetes mellitus.

    PubMed

    Subiabre, Mario; Silva, Luis; Villalobos-Labra, Roberto; Toledo, Fernando; Paublo, Mario; López, Marcia A; Salsoso, Rocío; Pardo, Fabián; Leiva, Andrea; Sobrevia, Luis

    2017-07-26

    Pregnant women diagnosed with gestational diabetes mellitus subjected to diet (GDMd) that do not reach normal glycaemia are passed to insulin therapy (GDMi). GDMd associates with increased human cationic amino acid transporter 1 (hCAT-1)-mediated transport of L-arginine and nitric oxide synthase (NOS) activity in foetoplacental vasculature, a phenomenon reversed by exogenous insulin. Whether insulin therapy results in reversal of the GDMd effect on the foetoplacental vasculature is unknown. We assayed whether insulin therapy normalizes GDMd-associated foetoplacental endothelial dysfunction. Primary cultures of human umbilical vein endothelial cells (HUVECs) from GDMi pregnancies were used to assay L-arginine transport kinetics, NOS activity, p44/42(mapk) and protein kinase B/Akt activation, and umbilical vein rings reactivity. HUVECs from GDMi or GDMd show increased hCAT-1 expression and maximal transport capacity, NOS activity, and eNOS, and p44/42(mapk), but not Akt activator phosphorylation. Dilation in response to insulin or calcitonin-gene related peptide was impaired in umbilical vein rings from GDMi and GDMd pregnancies. Incubation of HUVECs in vitro with insulin (1 nmol/L) restored hCAT-1 and eNOS expression and activity, and eNOS and p44/42(mapk) activator phosphorylation. Thus, maternal insulin therapy does not seem to reverse GDMd-associated alterations in human foetoplacental vasculature. Copyright © 2017. Published by Elsevier B.V.

  13. Insulin pump therapy in the perioperative period: a review of care after implementation of institutional guidelines.

    PubMed

    Boyle, Mary E; Seifert, Karen M; Beer, Karen A; Mackey, Patricia; Schlinkert, Richard T; Stearns, Joshua D; Cook, Curtiss B

    2012-09-01

    An institutional policy was previously established for patients with diabetes on insulin pump therapy undergoing elective surgical procedures. Electronic medical records were reviewed to assess documentation of insulin pump status and glucose monitoring during preoperative, intraoperative, and postanesthesia care unit (PACU) phases of care. Twenty patients with insulin pumps underwent 23 procedures from March 1 to December 31, 2011. Mean (standard deviation) age was 58 (13) years, mean diabetes duration was 28 (17) years, and mean duration of insulin pump therapy was 7 (6) years. Nearly all cases (86%) during the preoperative phase had the presence of the device documented--an improvement over the 64% noted in data collected before the policy. Intraoperatively, 13 cases (61%) had the presence of the pump documented, which was higher than the 28% before implementation of the policy. However, documentation of pump status was found in only 38% in the PACU and was actually less than the 60% documented previously. Over 90% of cases had glucose checked in the preoperative area and the PACU, and only 60% had it checked intraoperatively, which was nearly identical to the percentages seen before policy implementation. No adverse events occurred when insulin pump therapy was continued. Although some processes still require improvement, preliminary data suggest that the policy for perioperative management of insulin pumps has provided useful structure for care of these cases. The data thus far indicate that insulin pump therapy can be continued safely during the perioperative period. © 2012 Diabetes Technology Society.

  14. Insulin Pump Therapy in the Perioperative Period: A Review of Care after Implementation of Institutional Guidelines

    PubMed Central

    Boyle, Mary E.; Seifert, Karen M.; Beer, Karen A.; Mackey, Patricia; Schlinkert, Richard T.; Stearns, Joshua D.; Cook, Curtiss B.

    2012-01-01

    Background An institutional policy was previously established for patients with diabetes on insulin pump therapy undergoing elective surgical procedures. Method Electronic medical records were reviewed to assess documentation of insulin pump status and glucose monitoring during preoperative, intraoperative, and postanesthesia care unit (PACU) phases of care. Results Twenty patients with insulin pumps underwent 23 procedures from March 1 to December 31, 2011. Mean (standard deviation) age was 58 (13) years, mean diabetes duration was 28 (17) years, and mean duration of insulin pump therapy was 7 (6) years. Nearly all cases (86%) during the preoperative phase had the presence of the device documented—an improvement over the 64% noted in data collected before the policy. Intraoperatively, 13 cases (61%) had the presence of the pump documented, which was higher than the 28% before implementation of the policy. However, documentation of pump status was found in only 38% in the PACU and was actually less than the 60% documented previously. Over 90% of cases had glucose checked in the preoperative area and the PACU, and only 60% had it checked intraoperatively, which was nearly identical to the percentages seen before policy implementation. No adverse events occurred when insulin pump therapy was continued. Conclusions Although some processes still require improvement, preliminary data suggest that the policy for perioperative management of insulin pumps has provided useful structure for care of these cases. The data thus far indicate that insulin pump therapy can be continued safely during the perioperative period. PMID:23063026

  15. Physical therapy intervention in the neonatal intensive care unit.

    PubMed

    Byrne, Eilish; Garber, June

    2013-02-01

    This article presents the elements of the Intervention section of the Infant Care Path for Physical Therapy in the Neonatal Intensive Care Unit (NICU). The types of physical therapy interventions presented in this path are evidence-based and the suggested timing of these interventions is primarily based on practice knowledge from expert therapists, with supporting evidence cited. Physical therapy intervention in the NICU is infant-driven and focuses on providing family-centered care. In this context, interventions to facilitate a calm behavioral state and motor organization in the infant, address positioning and handling of the infant, and provide movement therapy are presented.

  16. Treatment duration (persistence) of basal insulin supported oral therapy (BOT) in Type-2 diabetic patients: comparison of insulin glargine with NPH insulin.

    PubMed

    Quinzler, Renate; Ude, Miriam; Franzmann, Alexandra; Feldt, Sandra; Schüssel, Katrin; Leuner, Kristina; Müller, Walter E; Dippel, Franz-Werner; Schulz, Martin

    2012-01-01

    To compare the persistence (treatment duration) of basal insulin supported oral therapy (BOT) using insulin glargine (GLA) or NPH insulin (NPH) in Type-2 diabetic patients. This retrospective cohort study reports results from an analysis of claims data from prescriptions for ambulatory patients within the German Statutory Health Insurance scheme. The study is based on claims data from more than 80% of German community pharmacies. Treatment duration until switching to a basal bolus treatment regimen (intensified conventional insulin therapy: ICT) was determined in insulin-naïve patients who began treatment with BOT using GLA or NPH between 01/2003 and 12/2006. A total of 97,998 patients (61,070 GLA and 36,928 NPH) were included. Within the observation period, 23.5% of GLA patients and 28.0% of NPH patients switched from BOT to ICT. The upper quartile of probability of continuation of therapy (the 75th percentile) was reached after 769 days in GLA patients and after 517 days in NPH patients. Therefore, the risk of switching to ICT was significantly higher with NPH compared to GLA: hazard ratios were 1.34 (99% CI: 1.29-1.38; unadjusted) and 1.22 (99% CI: 1.18-1.27) after adjustment for predefined covariates. Various sensitivity analyses using modified inclusion criteria and endpoint definitions were applied and these confirmed the initial results. Type-2 diabetic patients under BOT with GLA stayed significantly longer on the initial therapy before switching to ICT than patients on BOT using NPH.

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

    PubMed Central

    Singh, Awadhesh Kumar; Singh, Ritu

    2016-01-01

    The gradual decline in β-cell function is inevitable in type 2 diabetes mellitus and therefore, substantial proportions of patients require insulin subsequently, in order to achieve optimal glucose control. While weight gain, hypoglycemia, and fluid retention especially during dose intensification is a known limitation to insulin therapy, these adverse effects also reduce patient satisfaction and treatment adherence. It is also possible that the benefits of intensive control achieved by insulin therapy, perhaps get nullified by the weight gain and hypoglycemia. In addition, improvement in plasma glucose or glycated hemoglobin (HbA1c) itself is associated with weight gain. Notably, studies have already suggested that reduction in body weight by ~3–5%, may allow a significantly better glycemic control. Thus, a class of drugs, which can reduce HbA1c effectively, yet are weight neutral or preferably reduce body weight, could be the most sought out strategy as an add-on therapy to insulin. While sulfonylureas (SUs) are associated with weight gain and hypoglycemia, pioglitazone increases body weight and fluid retention. Moreover, SUs are not recommended once premix or prandial insulin is commenced. The addition of newer agents, such as glucagon-like peptide-1 receptor agonist to insulin certainly appears to be an effective tool in reducing both HbA1c and body weight as is evident across the studies; however, this approach incurs an additional injection as well as cost. Dipeptidyl peptidase-4 inhibitors (DPP-4I) and sodium-glucose co-transporter-2 inhibitors (SGLT-2I) are other exciting options, as an add-on to insulin therapy primarily because these are oral drugs and do not possess any intrinsic potential of hypoglycemia. Furthermore, these are either weight neutral or induce significant weight loss. This review article aims to comparatively analyze the safety and efficacy of DPP-4I and SGLT-2I, as an add-on therapy to insulin. PMID:26904466

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

    PubMed

    Singh, Awadhesh Kumar; Singh, Ritu

    2016-01-01

    The gradual decline in β-cell function is inevitable in type 2 diabetes mellitus and therefore, substantial proportions of patients require insulin subsequently, in order to achieve optimal glucose control. While weight gain, hypoglycemia, and fluid retention especially during dose intensification is a known limitation to insulin therapy, these adverse effects also reduce patient satisfaction and treatment adherence. It is also possible that the benefits of intensive control achieved by insulin therapy, perhaps get nullified by the weight gain and hypoglycemia. In addition, improvement in plasma glucose or glycated hemoglobin (HbA1c) itself is associated with weight gain. Notably, studies have already suggested that reduction in body weight by ~3-5%, may allow a significantly better glycemic control. Thus, a class of drugs, which can reduce HbA1c effectively, yet are weight neutral or preferably reduce body weight, could be the most sought out strategy as an add-on therapy to insulin. While sulfonylureas (SUs) are associated with weight gain and hypoglycemia, pioglitazone increases body weight and fluid retention. Moreover, SUs are not recommended once premix or prandial insulin is commenced. The addition of newer agents, such as glucagon-like peptide-1 receptor agonist to insulin certainly appears to be an effective tool in reducing both HbA1c and body weight as is evident across the studies; however, this approach incurs an additional injection as well as cost. Dipeptidyl peptidase-4 inhibitors (DPP-4I) and sodium-glucose co-transporter-2 inhibitors (SGLT-2I) are other exciting options, as an add-on to insulin therapy primarily because these are oral drugs and do not possess any intrinsic potential of hypoglycemia. Furthermore, these are either weight neutral or induce significant weight loss. This review article aims to comparatively analyze the safety and efficacy of DPP-4I and SGLT-2I, as an add-on therapy to insulin.

  19. Comparison of Combined Tofogliflozin and Glargine, Tofogliflozin Added to Insulin, and Insulin Dose-Increase Therapy in Uncontrolled Type 2 Diabetes

    PubMed Central

    Suzuki, Katsunori; Mitsuma, Yurie; Sato, Takaaki; Anraku, Takumi; Hatta, Mariko

    2016-01-01

    Background Some patients with type 2 diabetes mellitus (T2DM) on insulin have poor glycemic control and require add-on therapy to reach target glucose values. Increased insulin doses or the addition of an oral antidiabetic drug (OAD) may improve glycemic control, but many patients fail to achieve target values. The aim of this study was to compare the treatment efficacy and safety of three different therapies in such patients. Methods T2DM outpatients with poor glycemic control (HbA1c ≥ 7.0%) despite insulin therapy (including patients on OADs other than a sodium-glucose cotransporter 2 (SGLT2) inhibitor) were included. The patients had a body mass index (BMI) of ≥ 22 kg/m2 and an estimated glomerular filtration rate (eGFR) of ≥ 45 mL/min/1.73 m2, did not have depletion of endogenous insulin, and had stable glucose levels for 3 months before study entry on insulin therapy. Treatment was continued for 24 weeks with insulin dose-increase therapy, tofogliflozin add-on therapy, or a combination of insulin glargine + tofogliflozin. The primary endpoints were HbA1c, weight, and total insulin dose. Secondary endpoints included fasting plasma glucose (FPG), blood pressure, lipid profiles, and incidence of adverse events. Results At baseline, the participants’ median age was 59.0 years, mean BMI was 28.7 kg/m2, mean eGFR was 89.2 mL/min/1.73 m2, mean HbA1c was 8.7%, and mean FPG was 174.1 mg/dL. The mean duration of insulin therapy was approximately 7 years. The mean daily insulin dose was approximately 40 U in the three groups. Overall, 85% received other background OADs in addition to insulin. Over the 24-week period, HbA1c in the insulin group decreased slightly initially and then plateaued; daily total insulin dose and weight increased, and blood pressure increased slightly. In the insulin + tofogliflozin group and the glargine + tofogliflozin group, HbA1c decreased greatly initially, and this continued over the 24-week period, with HbA1c decreases of -1.0% and

  20. Intensive Cognitive Therapy for PTSD: A Feasibility Study

    PubMed Central

    Ehlers, Anke; Clark, David M.; Hackmann, Ann; Grey, Nick; Liness, Sheena; Wild, Jennifer; Manley, John; Waddington, Louise; McManus, Freda

    2010-01-01

    Background: Cognitive Behaviour Therapy (CBT) of anxiety disorders is usually delivered in weekly or biweekly sessions. There is evidence that intensive CBT can be effective in phobias and obsessive compulsive disorder. Studies of intensive CBT for posttraumatic stress disorder (PTSD) are lacking. Method: A feasibility study tested the acceptability and efficacy of an intensive version of Cognitive Therapy for PTSD (CT-PTSD) in 14 patients drawn from consecutive referrals. Patients received up to 18 hours of therapy over a period of 5 to 7 working days, followed by 1 session a week later and up to 3 follow-up sessions. Results: Intensive CT-PTSD was well tolerated and 85.7 % of patients no longer had PTSD at the end of treatment. Patients treated with intensive CT-PTSD achieved similar overall outcomes as a comparable group of patients treated with weekly CT-PTSD in an earlier study, but the intensive treatment improved PTSD symptoms over a shorter period of time and led to greater reductions in depression. Conclusions: The results suggest that intensive CT-PTSD is a feasible and promising alternative to weekly treatment that warrants further evaluation in randomized trials. PMID:20573292

  1. 'The pump was a saviour for me.' Patients' experiences of insulin pump therapy.

    PubMed

    Garmo, A; Hörnsten, Å; Leksell, J

    2013-06-01

    The present study formed part of a larger study examining the potential long-term effects of glycaemic control and treatment satisfaction in people with Type 1 diabetes mellitus who changed from multiple daily insulin injections to insulin pump therapy. Individuals (n = 46) who made the transition between May 1999 and February 2004 participated. The aim of the study was to describe experiences of the impact of insulin pump therapy in adults with Type 1 diabetes mellitus after > 5 years' use of an insulin pump. During spring 2009, 16 of the individuals were interviewed through a narrative approach on the effects of insulin pump therapy on daily life. The interviews were analysed using content analysis. The overarching theme revealed that insulin pump therapy was experienced as both a shackle and a lifeline. Six sub-themes emerged: subjected vs. empowered; dependent vs. autonomous; vulnerable vs. strengthened; routinized vs. flexible; burdened vs. relieved; and stigmatized vs. normalized. Users of insulin pump therapy have different views about and experience of having used the technical equipment over years. Both positive and negative views emerged. However, it is difficult to identify any general trends that cover all views and can predict which individuals will be able to manage pump therapy in the best way. Even so, the sub-themes and theme that emerged could be used by physicians and diabetes specialist nurses when counselling and planning educational programmes aimed at supporting self-management among people with insulin pump treatment. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

  2. Effectiveness of insulin therapy in people with Type 2 diabetes in the Hoorn Diabetes Care System.

    PubMed

    Mast, M R; Walraven, I; Hoekstra, T; Jansen, A P D; van der Heijden, A A W A; Elders, P J M; Heine, R J; Dekker, J M; Nijpels, G; Hugtenburg, J G

    2016-06-01

    To identify HbA1c trajectories after the start of insulin treatment and to identify clinically applicable predictors of the response to insulin therapy. The study population comprised 1203 people with Type 2 diabetes included in the Hoorn Diabetes Care System (n = 9849). Inclusion criteria were: age ≥ 40 years; initiation of insulin during follow-up after failure to reach HbA1c levels ≤ 53 mmol/mol (7%) with oral glucose-lowering agents; and a follow up ≥ 2 years after initiating insulin. Latent class growth modelling was used to identify trajectories of HbA1c . Subjects considered to be 'off target' had HbA1c levels ≥ 53 mmol/mol (7.0%) during one-third or more of the follow-up time, and those considered to be 'on target' had HbA1c levels ≥ 53 mmol/mol (7.0%) during less than one-third of the follow-up time. Four HbA1c trajectories were identified. Most people (88.7%) were classified as having a stable HbA1c trajectory of ~57 mmol/mol (7.4%). Only 24.4% of the people were on target in response to insulin; this was associated with lower HbA1c levels and a higher age at the start of insulin treatment. Using latent class growth modelling, four HbA1c trajectories were identified. A quarter of the people starting insulin were on target. Low HbA1c levels and advanced age at the start of insulin therapy were associated with better response to insulin therapy. Initiating insulin earlier improves the likelihood of achieving and sustaining glycaemic control. © 2016 Diabetes UK.

  3. Effect of Insulin Sensitizer Therapy on Amino Acids and their Metabolites

    PubMed Central

    Irving, B.A.; Carter, R.E.; Soop, M.; Weymiller, A.; Syed, H.; Karakelides, H.; Bhagra, S.; Short, K.R.; Tatpati, L.; Barazzoni, R.; Nair, K.S.

    2015-01-01

    Aims Prior studies have reported that elevated concentrations of several plasma amino acids (AA) in plasma, particularly branched chain (BCAA) and aromatic AA predict the onset of type 2 diabetes. We sought to test the hypothesis that circulating BCAA, aromatic AA and related AA metabolites decline in response to the use of insulin sensitizing agents in overweight/obese adults with impaired fasting glucose or untreated diabetes. Methods We performed a secondary analysis of a randomized, double-blind, placebo, controlled study conducted in twenty five overweight/obese (BMI~30 kg/m2) adults with impaired fasting glucose or untreated diabetes. Participants were randomized to three months of pioglitazone (45 mg per day) plus metformin (1000 mg twice per day, N = 12 participants) or placebo (N = 13). We measured insulin sensitivity by the euglycemic-hyperinsulinemic clamp and fasting concentrations of AA and AA metabolites using ultra-pressure liquid chromatography tandem mass spectrometry before and after the three-month intervention. Results Insulin sensitizer therapy that significantly enhanced insulin sensitivity reduced 9 out of 33 AA and AA metabolites measured compared to placebo treatment. Moreover, insulin sensitizer therapy significantly reduced three functionally clustered AA and metabolite pairs: i) phenylalanine/tyrosine, ii) citrulline/arginine, and iii) lysine/α-aminoadipic acid. Conclusions Reductions in plasma concentrations of several AA and AA metabolites in response to three months of insulin sensitizer therapy support the concept that reduced insulin sensitivity alters AA and AA metabolites. PMID:25733201

  4. Recommendations for improving adherence to type 2 diabetes mellitus therapy--focus on optimizing insulin-based therapy.

    PubMed

    Campbell, R Keith

    2012-04-01

    Despite its unsurpassed efficacy in the management of diabetes, insulin has been resisted and feared for its risk of side effects (ie, weight gain, hypoglycemia). Many patients and providers have perceived insulin as a last resort therapy given to patients with a poor prognosis, and some patients even as a form of punishment for poor self-management. Also, fear of needles is a constant concern. Fortunately, these challenges to insulin use may be overcome via patient education as well as new developments in insulin therapy. Insulin formulations have been developed that possess pharmacokinetic profiles better adapted to the physiologic needs of patients with type 2 diabetes mellitus (T2DM), including rapid- and long-acting insulin analogues, as well as premixed formulations. Appropriate use of these agents is associated with improved glycemic control, higher levels of adherence to treatment, and lower healthcare costs. A variety of pen delivery systems for insulin delivery are available that allow for easier, more discreet, and more accurately dosed insulin therapy. Patients generally prefer pen delivery systems, and they are associated with greater adherence and better glycemic control as compared with vial and syringe use. In addition to the ever-increasing variety of insulin formulations and delivery systems, educational initiatives are absolutely vital in order to overcome the limited knowledge about diabetes, self-management, and coping skills that can be seen in a large proportion of people with T2DM. Improved adherence to treatment, better outcomes, and reduced costs are contingent upon the appropriate use of, and full access to, appropriate treatment and patient education.

  5. Insulin resistance and response to antiviral therapy in chronic hepatitis C: mechanisms and management.

    PubMed

    del Campo, José A; López, Reyes Aparcero; Romero-Gómez, Manuel

    2010-01-01

    Insulin resistance has been found to be an independent factor predicting sustained response to peginterferon plus ribavirin in patients with chronic hepatitis C. Insulin resistance seems to be involved in decreased sensitivity to interferon and could block interferon intracellular signaling. Insulin resistance promotes steatosis and fibrosis progression, induces pro-inflammatory cytokine secretion and increases adipose tissue, decreasing interferon availability. Moreover, suppressor of cytokines 3 and protein tyrosine-phosphatase seems to be able to block interferon and insulin signaling, building a feed-forward loop. Insulin resistance can be treated with exercise, diet or through the use of drugs that improve insulin sensitivity, like biguanides or glitazones. A recent controlled, randomized, double-blind clinical trial (TRIC-1) examined the effect of adding metformin to standard therapy in the treatment of hepatitis C. This study demonstrated that women infected with hepatitis C virus genotype 1 and HOMA >2 treated with metformin showed a greater drop in viral load during the first 12 weeks and a doubled sustained viral response in comparison with females receiving placebo. Pioglitazone has been used in previous nonresponders and naïve patients with disappointing results in two pilot trials. The mechanisms by which the virus promotes insulin resistance seems to be genotype-dependent and could explain, at least in part, the discrepancies between insulin sensitizers. Insulin resistance is a new target in the challenging management of chronic hepatitis C.

  6. Review of insulin therapy and pen use in hospitalized patients.

    PubMed

    Davis, Estella M; Foral, Pamela A; Dull, Ryan B; Smith, April N

    2013-05-01

    Hyperglycemia is common among hospitalized patients, affecting approximately 40% of patients at the time of hospital admission, despite the fact that 1 in every 8 patients has no previous diagnosis of diabetes. Hyperglycemia has been associated with poor patient outcomes, including higher rates of morbidity and mortality across a range of conditions. This review discusses options for the effective management of hyperglycemia with a focus on the use of disposable insulin pens in the hospital. Literature, including guidelines for hospital management of hyperglycemia, and information regarding methods of insulin administration were reviewed. Appropriate glucose control via administration of insulin within hospitals has been acknowledged as an important goal and is consistent with achieving patient safety. Insulin may be administered subcutaneously using a pen or vial and syringe or infused intravenously. Levels of patient and provider satisfaction are higher with pen administration than with vial and syringe. Insulin pens have many safety and convenience features including enhanced dose accuracy and autocover/autoshield pen needles. Use of insulin pens instead of vials and syringes can provide several advantages for hospitalized patients, including greater satisfaction among them and health care providers, improved safety, and reduced costs. These advantages can continue following patient discharge.

  7. Review of Insulin Therapy and Pen Use in Hospitalized Patients

    PubMed Central

    Foral, Pamela A.; Dull, Ryan B.; Smith, April N.

    2013-01-01

    Objective: Hyperglycemia is common among hospitalized patients, affecting approximately 40% of patients at the time of hospital admission, despite the fact that 1 in every 8 patients has no previous diagnosis of diabetes. Hyperglycemia has been associated with poor patient outcomes, including higher rates of morbidity and mortality across a range of conditions. This review discusses options for the effective management of hyperglycemia with a focus on the use of disposable insulin pens in the hospital. Methods: Literature, including guidelines for hospital management of hyperglycemia, and information regarding methods of insulin administration were reviewed Results: Appropriate glucose control via administration of insulin within hospitals has been acknowledged as an important goal and is consistent with achieving patient safety. Insulin may be administered subcutaneously using a pen or vial and syringe or infused intravenously. Levels of patient and provider satisfaction are higher with pen administration than with vial and syringe. Insulin pens have many safety and convenience features including enhanced dose accuracy and autocover/autoshield pen needles. Conclusion: Use of insulin pens instead of vials and syringes can provide several advantages for hospitalized patients, including greater satisfaction among them and health care providers, improved safety, and reduced costs. These advantages can continue following patient discharge. PMID:24421496

  8. 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

  9. 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

  10. Insulin-based versus triple oral therapy for newly diagnosed type 2 diabetes: which is better?

    PubMed

    Lingvay, Ildiko; Legendre, Jaime L; Kaloyanova, Polina F; Zhang, Song; Adams-Huet, Beverley; Raskin, Philip

    2009-10-01

    Early use of insulin after diagnosis of type 2 diabetes is met with resistance because of associated weight gain, hypoglycemia, and fear of decreased compliance and quality of life (QoL). In treatment-naive patients with newly diagnosed type 2 diabetes, insulin and metformin were initiated for a 3-month lead-in period, then patients were randomly assigned to insulin and metformin (insulin group) or metformin, pioglitazone, and glyburide (oral group) for 36 months. Hypoglycemic events, compliance, A1C, weight, QoL, and treatment satisfaction were assessed. Of 29 patients randomly assigned into each group, 83% (insulin group) and 72% (oral group) completed this 3-year study. At study completion, A1C was 6.1 +/- 0.6% (insulin group) versus 6.0 +/- 0.8% (oral group). Weight increased similarly in both groups (P = 0.09) by 4.47 kg (95% CI 0.89-8.04 kg) (insulin group) and 7.15 kg (95% CI 4.18-10.13 kg) (orals group). Hypoglycemic events did not differ between groups (mild 0.51 event/person-month in the insulin group vs. 0.68 event/person-month in the orals group, P = 0.18 and severe 0.04 event/person-year in the insulin group vs. 0.09 event/person-year in the orals group, P = 0.53). Compliance, QoL, and treatment satisfaction were similar between groups, with 100% of patients randomly assigned to insulin willing to continue such treatment. When compared with a clinically equivalent treatment regimen, insulin-based therapy is effective and did not cause greater weight gain or hypoglycemia nor decrease compliance, treatment satisfaction, or QoL. Insulin is safe, well-accepted, and effective for ongoing treatment of patients with newly diagnosed type 2 diabetes.

  11. Effects of Intensive versus Non-Intensive Physical Therapy on Children with Cerebral Palsy.

    PubMed

    Rahman, M A; Zaman, M M; Rahman, M M; Moniruzzaman, M; Ahmed, B; Chhobi, F K; Rahman, N; Akter, M R

    2016-07-01

    Cerebral Palsy (CP) is one of the most common causes of all childhood disorders. There are tone, posture and movements difficulty due to non-progressive damage to the immature brain in CP. The hallmark of CP is a disability in the development of gross motor function (GMF). The influence of gross motor development on fine motor development is more important in early developmental period, specially under three years old and in children with CP. Various therapeutic interventions have been used in the management of GMF development. Among them physical therapy is the most common intervention in CP and is usually a component of mandated programs. Physical therapy means physical stimulations in the form of various therapeutic exercises, touch, massage, limbs and trunk movement, balancing and coordination training, gait and ambulation training, cognitive stimulation as well as speech, language and occupational therapy. Our study focused to see the effect by short term intensive versus non-intensive physical therapy on children GMF development by using gross motor function measure (GMFM) Score sheet, GMFM-88, version 1.0. Study provides the information that physical therapy intervention is effective in GMF development and intensive interventions are more effective in children with spastic CP than non-intensive one. Study also inform that the more early treatment the more effective result.

  12. A Pediatric Diabetic Ketoacidosis Management Protocol Incorporating a Two-Bag Intravenous Fluid System Decreases Duration of Intravenous Insulin Therapy

    PubMed Central

    Marsh, Kourtney; Norman, Susan; Brock, Michael Alan; Peng, Monica; Shenk, Jennifer; Chen, Jerome Gene

    2016-01-01

    OBJECTIVES: Diabetic ketoacidosis (DKA) is a leading cause of morbidity and mortality in children with type 1 diabetes. We implemented a standardized DKA management protocol by using a 2-bag intravenous (IV) fluid system. The purpose of the study was to examine if the protocol improved clinical outcomes and process efficiency. METHODS: This was a retrospective study of patients who did and did not undergo the protocol. Patients were included if they were 18 years of age or younger, were diagnosed with DKA, admitted to an intensive care unit or stepdown unit, and received continuous IV insulin. RESULTS: Of 119 encounters evaluated, 46 (38.7%) received treatment with the protocol and 73 (61.3%) did not. The median time to normalization of ketoacidosis was 9 hours (IQR 5–12) and 9 hours (IQR 6.5–13) for protocol and non-protocol groups, respectively (p = 0.14). The median duration of IV insulin therapy was 16.9 hours (IQR 13.7–21.5) vs. 21 hours (IQR 15.3–26) for protocol and non-protocol groups (p = 0.03). The median number of adjustments to insulin drip rate was 0 (IQR 0–1) and 2 (IQR 0–3) for protocol and non-protocol groups (p = 0.0001). There was no difference in the incidence of hypokalemia, hypoglycemia, or cerebral edema. CONCLUSIONS: The protocol did not change time to normalization of ketoacidosis but did decrease the duration of insulin therapy, number of adjustments to insulin drip rate, and number of wasted IV fluid bags without increasing the incidence of adverse events. PMID:28018153

  13. A Pediatric Diabetic Ketoacidosis Management Protocol Incorporating a Two-Bag Intravenous Fluid System Decreases Duration of Intravenous Insulin Therapy.

    PubMed

    Veverka, Megan; Marsh, Kourtney; Norman, Susan; Brock, Michael Alan; Peng, Monica; Shenk, Jennifer; Chen, Jerome Gene

    2016-01-01

    OBJECTIVES: Diabetic ketoacidosis (DKA) is a leading cause of morbidity and mortality in children with type 1 diabetes. We implemented a standardized DKA management protocol by using a 2-bag intravenous (IV) fluid system. The purpose of the study was to examine if the protocol improved clinical outcomes and process efficiency. METHODS: This was a retrospective study of patients who did and did not undergo the protocol. Patients were included if they were 18 years of age or younger, were diagnosed with DKA, admitted to an intensive care unit or stepdown unit, and received continuous IV insulin. RESULTS: Of 119 encounters evaluated, 46 (38.7%) received treatment with the protocol and 73 (61.3%) did not. The median time to normalization of ketoacidosis was 9 hours (IQR 5-12) and 9 hours (IQR 6.5-13) for protocol and non-protocol groups, respectively (p = 0.14). The median duration of IV insulin therapy was 16.9 hours (IQR 13.7-21.5) vs. 21 hours (IQR 15.3-26) for protocol and non-protocol groups (p = 0.03). The median number of adjustments to insulin drip rate was 0 (IQR 0-1) and 2 (IQR 0-3) for protocol and non-protocol groups (p = 0.0001). There was no difference in the incidence of hypokalemia, hypoglycemia, or cerebral edema. CONCLUSIONS: The protocol did not change time to normalization of ketoacidosis but did decrease the duration of insulin therapy, number of adjustments to insulin drip rate, and number of wasted IV fluid bags without increasing the incidence of adverse events.

  14. Do We Need Updated Guidelines on the Use of Insulin Pump Therapy in Type 2 Diabetes? A Review of National and International Practice Guidelines

    PubMed Central

    Cohen, Ohad; Valentine, William

    2016-01-01

    Background: Continuous subcutaneous insulin infusion (CSII) is used less for type 2 than for type 1 diabetes because of inconsistencies in evidence of effectiveness. We reviewed published guidelines on intensive insulin therapy in type 2 diabetes to assess whether updating of guidance is needed with respect to evidence used and recommendations for CSII in diabetes management. Methods: A literature review was performed to identify published national and international guidelines on type 2 diabetes management. Searches were performed using PubMed, Cochrane Library, and Embase databases, and websites of national health care agencies, reimbursement agencies, and professional associations. Searches were limited to articles published in English between 2004 and 2014 and 1666 unique hits were identified, of which 22 were reviewed following screening. Results: Only 6 of the 22 guidelines identified from North and South America, Western Europe, Greece, and Israel provided specific recommendations on intensive insulin therapy and the role of CSII, and only 1 provided information on the grade of evidence supporting recommendations. Quality appraisal based on the AGREE II tool suggested that published guidelines may have limitations in terms of search methodology and evidence grading, and findings were of mixed rigor and clarity. Only 3 guidelines described the population for whom CSII may be appropriate. Conclusions: Guidelines need to improve the evidence base, rigor, clarity, and grading of evidence associated with recommendations on intensive insulin therapy in type 2 diabetes. Future updates may benefit from considering recent evidence on the efficacy of CSII in poorly controlled patients on MDI. PMID:27621141

  15. Long-term efficacy of insulin glargine after switching from NPH insulin as intensive replacement of basal insulin in Japanese diabetes mellitus. Comparison of efficacy between type 1 and type 2 diabetes (JUN-LAN Study 1.2).

    PubMed

    Kanazawa, Yoshie; Igarashi, Yasuhiro; Komiya, Koji; Sakurai, Yuko; Shimizu, Tomoaki; Fujitani, Yoshio; Tanaka, Yasushi; Watada, Hirotaka; Kawamori, Ryuzo; Hirose, Takahisa

    2007-12-01

    To assess and compare the efficacy and safety of insulin glargine as intensive replacement of basal insulin in Japanese patients with type 1 (n = 72) and type 2 (n = 46) diabetes, we switched their intensive insulin regimen from NPH plus regular or rapid-acting insulin to glargine plus bolus insulin, which included regular and rapid-acting insulin, and recorded changes in glycemic control and frequency of hypoglycemia for 18 months. The dose titration of basal and bolus insulin was based on home self-monitored blood glucose measurements and monthly HbA(1C). Mean HbA(1C) level was improved significantly at 3 months after switching to glargine plus bolus insulin regimen and these effects continued for 18 months in both type 1 and type 2 diabetes patients (HbA(1C) level: type 1: baseline 8.9 +/- 2.6%, 18 months 7.8 +/- 1.5% (p<0.05), type 2: baseline 8.2 +/- 2.6%, 18 months 7.7 +/- 1.5%. Body weight was slightly but significantly increased at 18 months only in type 2 diabetes. Total daily bolus insulin doses were not changed but basal insulin could be increased significantly after switching regimens in both types diabetes compared with baseline. The frequency of mild to moderate hypoglycemia (self-assisted episodes, blood glucose <70 mg/dl) was marginally lower with glargine but not significantly. Self-monitored fasting blood glucose level was significantly improved after switching in type 2 diabetes. Patients with the worst HbA(1C) level at baseline exhibited more than 10% improvement in HbA(1C) level after switching both type 1 and type 2 diabetes. The HbA(1C) levels of the effectively treated patients were comparable to those of ineffectively treated ones at 6 months and the same improvement was seen at 18 months. Our results suggested that insulin glargine is more effective than NPH insulin as intensive replacement of basal insulin, particularly in those Japanese patients with difficult glycemic control with NPH insulin, equally in both type 1 and type 2 diabetes.

  16. NOCTURNAL HYPOGLYCEMIA--THE MAIN INDICATION FOR INSULIN PUMP THERAPY IN ADULTHOOD.

    PubMed

    Baretić, Maja; Kraljević, Ivana; Renar, Ivana Pavlić

    2016-03-01

    The aim was to determine which adult type 1 diabetic patient receiving multiple daily injection therapy is the most appropriate candidate for insulin pump therapy, while taking into consideration limited insulin pump affordability in Croatia. A total of 145 type 1 diabetic patients (52% diagnosed in adult age) were monitored at the Department of Endocrinology, Clinical Department of Internal Medicine, Zagreb University Hospital Center from 2009 to 2014. Twenty-one patients started insulin pump therapy in adulthood (seven men and 14 women, median age 27). Five patients had chronic complications (retinopathy in two, polyneuropathy in one, and both nephropathy and retinopathy in two patients). The median HbA1c at the initiation of pump therapy was 6.95% versus 6.5% after 1 year of pump therapy. Patients were stratified according to indications for insulin pump therapy (frequent and/or severe hypoglycemia, specific lifestyle, having not reached glycemic goals despite adherence/labile diabetes, and preconception). Patients could meet more than one criterion. Initially, the occurrence of hypoglycemia was analyzed by 6-day continuous glucose monitoring, while re-evaluation was done after collecting history data at 1 year ± 3 months. Initially, all patients had a median of 5 hypoglycemias/6 days (30% nocturnal) versus 1 hypoglycemia/6 days (without nocturnal) after 1 year. The Wilcoxon signed-rank test yielded a statistically significant difference in hypoglycemic events, nocturnal hypoglycemia and HbA1c. Patients commencing insulin pump therapy due to hypoglycemia initially had median HbA1c of 6.7% with 7 hypoglycemia/6 days (50% nocturnal). After one year, median HbA1c was 6% with 1 hypoglycemia/6 days (without nocturnal). In conclusion, the main indication for insulin pump therapy in adults is the frequency of hypoglycemia, especially nocturnal ones.

  17. Clinical implementation of intensity-modulated arc therapy.

    PubMed

    Shepard, David M; Cao, Daliang

    2011-01-01

    Intensity-modulated arc therapy (IMAT) is a rotational approach to radiation therapy delivered on a conventional linear accelerator using a conventional multileaf collimator. There are 2 key advantages of IMAT. First, the rotational nature of the delivery provides great flexibility in shaping each dose distribution. As a result, IMAT can provide dosimetric advantages relative to fixed-field intensity-modulated radiation therapy (IMRT). The second advantage is the highly efficient nature of the delivery. For centers with an active IMRT program, the clinical implementation of IMAT should be relatively straightforward. For clinical implementation of IMAT, it is important to fully characterize the accuracy of the dose model used, and the performance of the quality assurance equipment.

  18. [Perception of insulin therapy in uncontrolled patients with type 2 diabetes mellitus].

    PubMed

    Leyva Jiménez, Rafael; Hernández Zambrano, Gustavo; Ibarra Maldonado, Silvia; Ibarra Ramírez, Carlos Tomás

    2016-10-01

    To determine the perception of insulin therapy by patients with uncontrolled type2 diabetes mellitus, who have been treated with oral hypoglycaemic agents or insulin. Prospective comparative cross-sectional study. Family Medicine Unit No. 53 León, Guanajuato of Mexican Institute of Social Security. Patients between 40 and 80years old with uncontrolled type2 mellitus diabetes, treated with insulin or oral hypoglycaemic agents. Perception was assessed using the insulin treatment appraisal scale (ITAS). The rating of the survey is from 20 to 100 points, as such that when score increases the greater is the negative opinion. A sample of 459 diabetes patients were interviewed and split into 2 groups of patients according to their treatment. The OH group were patients treated with oral hypoglycaemic drugs only (56.9%), and the IN group were patients treated with insulin alone or combined with an oral hypoglycaemic (43.1%). Perception score was significantly higher in OH group (56.95±7.78 versus 49.55±8.89 points) than in the IN group (P<.001). The perception of insulin therapy was worse in patients treated with only oral hypoglycaemic agents than in patients using insulin. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  19. Insulin pump therapy in youth with type 1 diabetes: toward closed-loop systems.

    PubMed

    Tauschmann, Martin; Hovorka, Roman

    2014-06-01

    Insulin pump technology has advanced considerably over the past three decades, leading to more favorable metabolic control and less hypoglycemic events when compared with multiple daily injection therapy. The use of insulin pumps is increasing, particularly in children and adolescents with type 1 diabetes. This review outlines recent developments in insulin pump therapy from a pediatric perspective. 'Smart' pumps, sensor-augmented pump therapy and threshold-suspend feature of insulin pumps are reviewed in terms of efficacy, safety and psychosocial impact. The current status of closed-loop systems focusing on clinical outcomes is highlighted. Closed-loop insulin delivery is gradually progressing from bench to the clinical practice. Longer and larger studies in home settings are needed to expand on short- to medium-term outpatient evaluations. Predictive low glucose management and overnight closed-loop delivery may be the next applications to be implemented in daily routine. Further challenges include improvements of control algorithms, sensor accuracy, duration of insulin action, integration and size of devices and connectivity and usability. Gradual improvements and increasing sophistication of closed-loop components lie on the path toward unsupervised hands-off fully closed-loop system.

  20. Hypersensitivity reaction associated with subcutaneous glargine insulin therapy in a cat.

    PubMed

    Murphy, Lisa A; Zuendt, Greg F; Nakamura, Reid K; Gambardella, Paul

    2016-01-01

    A 14-year-old, domestic shorthair cat was treated for transient diabetes mellitus for 3 months with glargine insulin, which was discontinued when the diabetes mellitus resolved. Approximately 36 months later the diabetes mellitus recurred and glargine insulin was restarted. Within 2-3 mins of the first injection the cat collapsed, developed profuse vomiting and diarrhea, as well as facial swelling and diffuse erythema. A hypersensitivity reaction was suspected and the cat was treated with antihistamines, aggressive fluid therapy and gastrointestinal support. The cat made a full recovery and was discharged 3 days later. Six months later the cat re-presented for relapse of its diabetes mellitus and an intradermal skin challenge with 1:20 diluted insulin was performed confirming a hypersensitivity to glargine. The cat continues to be well regulated on porcine zinc insulin without any hypersensitivity reactions noted. Hypersensitivity reactions to insulin administration are rarely described in human medicine. This is the first reported case of a hypersensitivity reaction secondary to glargine insulin in a cat. Clinicians should be aware of this potential complication, particularly in animals with a previous history of insulin administration and the potential to utilize intradermal testing with insulin.

  1. Does insulin therapy for type 1 diabetes mellitus protect against Alzheimer's disease?

    PubMed

    Rdzak, Grzegorz M; Abdelghany, Osama

    2014-12-01

    Alzheimer's disease is the most common cause of dementia in the United States. A better understanding of the disease's underlying pathways may provide novel treatment and/or prevention strategies for this progressive chronic neurodegenerative disorder. In recent years, there has been a growing interest in the possible links between insulin and Alzheimer's disease. Insulin-induced hypoglycemia causes adaptive changes in the brain, including an improved ability to use alternative fuels. Insulin has been shown to facilitate reduction of intracellular amyloid plaque and downregulation of amyloid-β-derived diffusible ligand-binding sites. Insulin also promotes tau hypophosphorylation, which stabilizes microtubules and promotes tubulin polymerization. Excess exogenous insulin may also play a role in overcoming the decreased utilization and transport of glucose in patients with Alzheimer's disease. Intranasal insulin therapy may have beneficial effects on cognition and function in patients with Alzheimer's disease, as well as having only minor adverse effects, and this route of administration been the focus in clinical trials. These data support the mechanistic pathways that might link excess exogenous insulin administered to patients with type 1 diabetes mellitus to possible protection from Alzheimer's disease and provide a rationale for using insulin to prevent the disease in high-risk patients.

  2. Insulin Pump Therapy With Automated Insulin Suspension in Response to Hypoglycemia

    PubMed Central

    Choudhary, Pratik; Shin, John; Wang, Yongyin; Evans, Mark L.; Hammond, Peter J.; Kerr, David; Shaw, James A.M.; Pickup, John C.; Amiel, Stephanie A.

    2011-01-01

    OBJECTIVE To evaluate a sensor-augmented insulin pump with a low glucose suspend (LGS) feature that automatically suspends basal insulin delivery for up to 2 h in response to sensor-detected hypoglycemia. RESEARCH DESIGN AND METHODS The LGS feature of the Paradigm Veo insulin pump (Medtronic, Inc., Northridge, CA) was tested for 3 weeks in 31 adults with type 1 diabetes. RESULTS There were 166 episodes of LGS: 66% of daytime LGS episodes were terminated within 10 min, and 20 episodes lasted the maximum 2 h. LGS use was associated with reduced nocturnal duration ≤2.2 mmol/L in those in the highest quartile of nocturnal hypoglycemia at baseline (median 46.2 vs. 1.8 min/day, P = 0.02 [LGS-OFF vs. LGS-ON]). Median sensor glucose was 3.9 mmol/L after 2-h LGS and 8.2 mmol/L at 2 h after basal restart. CONCLUSIONS Use of an insulin pump with LGS was associated with reduced nocturnal hypoglycemia in those at greatest risk and was well accepted by patients. PMID:21868778

  3. Novel therapy for insulin-dependent diabetes mellitus: infusion of in vitro-generated insulin-secreting cells.

    PubMed

    Dave, S D; Vanikar, A V; Trivedi, H L; Thakkar, U G; Gopal, S C; Chandra, T

    2015-02-01

    Insulin-dependent diabetes mellitus (IDDM) is a metabolic disease usually resulting from autoimmune-mediated β-cell destruction requiring lifetime exogenous insulin replacement. Mesenchymal stem cells (MSC) hold promising therapy. We present our experience of treating IDDM with co-infusion of in vitro autologous adipose tissue-derived MSC-differentiated insulin-secreting cells (ISC) with hematopoietic stem cells (HSC). This was an Institutional Review Board approved prospective non-randomized open-labeled clinical trial after informed consent from ten patients. ISC were differentiated from autologous adipose tissue-derived MSC and were infused with bone marrow-derived HSC in portal, thymic circulation by mini-laparotomy and in subcutaneous circulation. Patients were monitored for blood sugar levels, serum C-peptide levels, glycosylated hemoglobin (Hb1Ac) and glutamic acid decarboxylase (GAD) antibodies. Insulin administration was made on sliding scale with an objective of maintaining FBS < 150 mg/dL and PPBS around 200 mg/dL. Mean 3.34 mL cell inoculums with 5.25 × 10(4) cells/μL were infused. No untoward effects were observed. Over a mean follow-up of 31.71 months, mean serum C-peptide of 0.22 ng/mL before infusion had sustained rise of 0.92 ng/mL with decreased exogenous insulin requirement from 63.9 international units (IU)/day to 38.6 IU/day. Improvement in mean Hb1Ac was observed from 10.99 to 6.72%. Mean GAD antibodies were positive in all patients with mean of 331.10 IU/mL, which decreased to mean of 123 IU/mL. Co-infusion of autologous ISC with HSC represents a viable novel therapeutic option for IDDM.

  4. High-dose insulin therapy in beta-blocker and calcium channel-blocker poisoning.

    PubMed

    Engebretsen, Kristin M; Kaczmarek, Kathleen M; Morgan, Jenifer; Holger, Joel S

    2011-04-01

    INTRODUCTION. High-dose insulin therapy, along with glucose supplementation, has emerged as an effective treatment for severe beta-blocker and calcium channel-blocker poisoning. We review the experimental data and clinical experience that suggests high-dose insulin is superior to conventional therapies for these poisonings. PRESENTATION AND GENERAL MANAGEMENT. Hypotension, bradycardia, decreased systemic vascular resistance (SVR), and cardiogenic shock are characteristic features of beta-blocker and calcium-channel blocker poisoning. Initial treatment is primarily supportive and includes saline fluid resuscitation which is essential to correct vasodilation and low cardiac filling pressures. Conventional therapies such as atropine, glucagon and calcium often fail to improve hemodynamic status in severely poisoned patients. Catecholamines can increase blood pressure and heart rate, but they also increase SVR which may result in decreases in cardiac output and perfusion of vascular beds. The increased myocardial oxygen demand that results from catecholamines and vasopressors may be deleterious in the setting of hypotension and decreased coronary perfusion. METHODS. The Medline, Embase, Toxnet, and Google Scholar databases were searched for the years 1975-2010 using the terms: high-dose insulin, hyperinsulinemia-euglycemia, beta-blocker, calcium-channel blocker, toxicology, poisoning, antidote, toxin-induced cardiovascular shock, and overdose. In addition, a manual search of the Abstracts of the North American Congress of Clinical Toxicology and the Congress of the European Association of Poisons Centres and Clinical Toxicologists published in Clinical Toxicology for the years 1996-2010 was undertaken. These searches identified 485 articles of which 72 were considered relevant. MECHANISMS OF HIGH-DOSE INSULIN BENEFIT. There are three main mechanisms of benefit: increased inotropy, increased intracellular glucose transport, and vascular dilatation. EFFICACY OF HIGH

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

    PubMed

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

    2016-01-15

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

  6. Exercise and improved insulin sensitivity in older women: evidence of the enduring benefits of higher intensity training.

    PubMed

    DiPietro, Loretta; Dziura, James; Yeckel, Catherine W; Neufer, P Darrell

    2006-01-01

    Few studies have compared the relative benefits of moderate- vs. higher intensity exercise training on improving insulin sensitivity in older people while holding exercise volume constant. Healthy older (73 +/- 10 yr) women (N = 25) who were inactive, but not obese, were randomized into one of three training programs (9-mo duration): 1) high-intensity [80% peak aerobic capacity (V(O2)peak); T(H)] aerobic training; 2) moderate-intensity (65% V(O2)peak; T(M)) aerobic training; or 3) low-intensity (stretching) placebo control (50% V(O2)peak); C(TB)). Importantly, exercise volume (300 kcal/session) was held constant for subjects in both the T(H) and the T(M) groups. V(O2)peak was determined by using a graded exercise challenge on a treadmill. Total body fat and lean mass were determined with dual-energy X-ray absorptiometry. The rate of insulin-stimulated glucose utilization as well as the suppression of lipolysis were determined approximately 72 h after the final exercise bout by using a two-step euglycemic-hyperinsulinemic clamp. We observed improved glucose utilization at the higher insulin dose with training, but these improvements were statistically significant only in the T(H) (21%; P = 0.02) compared with the T(M) (16%; P = 0.17) and C(TB) (8%; P = 0.37) groups and were observed without changes in either body composition or V(O2)peak. Likewise in the T(H) group, we detected a significant improvement in insulin-stimulated suppression (%) of adipose tissue lipolysis at the low-insulin dose (38-55%, P < 0.05). Our findings suggest that long-term higher intensity exercise training provides more enduring benefits to insulin action compared with moderate- or low-intensity exercise, likely due to greater transient effects.

  7. Consensus on Bridges for Barriers to Insulin Therapy.

    PubMed

    Kalra, Sanjay; Ghosal, Samit; Shah, Parag

    2017-03-01

    Insulin is an effective, safe and well-tolerated drug for glycaemic control. However, there are significant barriers to its use. This consensus statement aims to define these barriers and suggest bridges to overcome them. The consensus statements are based upon deliberations of a meeting held at New Delhi, India on 20 August 2016. The expert group committee reviewed various barriers to insulin use and categorized them into various categories: patient/community-related, physician-related and drug-related. The committee further proposed recommendations, based on published literature and their clinical experience, to address each of these barriers. Barriers (and bridges) can be classified as patient/community, physician/provider, and drug/device. Patient and physician barriers can further be categorized as those related to perceived inadequacy, perceived high cost, and perceived lack of benefit. Drug and device barriers can similarly be classified as those linked with perceived inadequacy, perceived high cost, and perceived lack of tolerability. Such a classification allows diabetes care providers to build appropriate bridges, which in turn facilitate timely insulin usage. Patient related barriers can be bridged by education, support and counselling. Use of modern insulin regimes and social marketing can address barriers related to perceived cost and lack of benefit. Physician related barriers can be resolved by training on various aspects of diabetes care. This will also help to break drug and device barriers, by ensuring appropriate choice of regimes, preparations and delivery devices. The consensus statements provide an easily understandable taxonomic structure of barriers to insulin use. By using a reader-friendly rubric, and by focusing on bridges (rather than barriers alone), it promotes a proactive and positive approach to diabetes management. The consensus statement should serve as a useful pedagogic and clinical tool for diabetes care professionals, and

  8. Glucose-Responsive Implantable Polymeric Microdevices for "Smart" Insulin Therapy of Diabetes

    NASA Astrophysics Data System (ADS)

    Chu, Michael Kok Loon

    Diabetes mellitus is a chronic illness manifested by improper blood glucose management, affecting over 350 million worldwide. As a result, all type 1 patients and roughly 20% of type 2 patients require exogenous insulin therapy to survive. Typically, daily multiple injections are taken to maintain normal glucose levels in response glucose spikes from meals. However, patient compliance and dosing accuracy can fluctuate with variation in meals, exercise, glucose metabolism or stress, leading to poor clinical outcomes. A 'smart', closed-loop insulin delivery system providing on-demand release kinetics responding to circulating glucose levels would be a boon for diabetes patients, replacing constant self monitoring and insulin. This thesis focuses on the development of a novel, 'smart' insulin microdevice that can provide on-demand insulin release in response to blood glucose levels. In the early stage, the feasibility of integrating a composite membrane with pH-responsive nanoparticles embedded in ethylcellulose membrane to provide pH-responsive in vitro release was examined and confirmed using a model drug, vitamin B12. In the second microdevice, glucose oxidase for generating pH signals from glucose oxidation, catalase and manganese dioxide nanoparticles, as peroxide scavengers, were used in a bioinorganic, albumin-based membrane cross-linked with a polydimethylsiloxane (PDMS) grid-microdevice system. This prototype device demonstrated insulin release in response to glucose levels in vitro and regulating plasma glucose in type 1 diabetic rats when implanted intraperitoneally. Advancement allowing for subcutaneous implantation and improved biocompatibility was achieved with surface modification of PDMS microdevices grafted with activated 20 kDa polyethylene glycol (PEG) chains, dramatically reducing immune response and local inflammation. When implanted subcutaneously in diabetic rats, glucose-responsive insulin delivery microdevices showed short and long

  9. Cost Effectiveness of IDegLira vs. Alternative Basal Insulin Intensification Therapies in Patients with Type 2 Diabetes Mellitus Uncontrolled on Basal Insulin in a UK Setting.

    PubMed

    Davies, Melanie J; Glah, Divina; Chubb, Barrie; Konidaris, Gerasimos; McEwan, Phil

    2016-09-01

    Once-daily insulin degludec/liraglutide (IDegLira) is the first basal insulin and glucagon like peptide-1 receptor agonist combined in one delivery device. Our aim was to investigate the cost effectiveness of IDegLira vs. basal insulin intensification therapies for patients with type 2 diabetes mellitus uncontrolled on basal insulin (glycosylated haemoglobin; HbA1c >7.5 %; 58 mmol/mol) in a UK setting. Baseline cohort and clinical parameters were sourced from a pooled analysis comparing IDegLira with basal insulin plus liraglutide and basal-bolus therapy, and from the DUAL™ V trial comparing IDegLira with up-titrated insulin glargine (IGlar; Lantus(®)). The CORE Diabetes Model simulated lifetime costs and outcomes with IDegLira vs. these comparators from a UK healthcare payers' perspective. All costs were expressed in 2015 GBP. Sensitivity analyses were performed to assess the impact of key parameters in the model. Treatment with IDegLira resulted in mean increases in quality-adjusted life-years (QALYs) of 0.12, 0.41 and 0.24 vs. basal insulin plus liraglutide, basal-bolus therapy and up-titrated IGlar, respectively. IDegLira was associated with lower costs of £971 and £1698 vs. basal insulin plus liraglutide and basal-bolus therapy, respectively, and increased costs of £1441 vs. up-titrated IGlar. IDegLira was dominant, i.e., both more effective and less costly vs. basal insulin plus liraglutide and basal-bolus therapy, and highly cost effective vs. up-titrated IGlar with an incremental cost-effectiveness ratio of £6090/QALY gained. Once-daily IDegLira may be considered a cost-effective treatment option for prescribers, to improve glycaemic control for type 2 diabetes patients uncontrolled on basal insulin without an increased risk of hypoglycaemia or weight gain, and without adding to their injection burden.

  10. 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

  11. High Intensity Focused Ultrasound Tumor Therapy System and Its Application

    NASA Astrophysics Data System (ADS)

    Sun, Fucheng; He, Ye; Li, Rui

    2007-05-01

    At the end of last century, a High Intensity Focused Ultrasound (HIFU) tumor therapy system was successfully developed and manufactured in China, which has been already applied to clinical therapy. This article aims to discuss the HIFU therapy system and its application. Detailed research includes the following: power amplifiers for high-power ultrasound, ultrasound transducers with large apertures, accurate 3-D mechanical drives, a software control system (both high-voltage control and low-voltage control), and the B-mode ultrasonic diagnostic equipment used for treatment monitoring. Research on the dosage of ultrasound required for tumour therapy in multiple human cases has made it possible to relate a dosage formula, presented in this paper, to other significant parameters such as the volume of thermal tumor solidification, the acoustic intensity (I), and the ultrasound emission time (tn). Moreover, the HIFU therapy system can be applied to the clinical treatment of both benign and malignant tumors in the pelvic and abdominal cavity, such as uterine fibroids, liver cancer and pancreatic carcinoma.

  12. Insulin therapy, glycemic control, and cardiovascular risk factors in young Latin Americans with type 2 diabetes mellitus.

    PubMed

    Avilés-Santa, Larissa; Salinas, Karin; Adams-Huet, Beverley; Raskin, Philip

    2006-01-01

    Type 2 diabetes has been linked to an increased risk of cardiovascular (CV) disease, but this risk has not been well documented in young patients, especially of Latin American descent. Also, the potential CV benefits of insulin therapy have not been evaluated in young patients with type 2 diabetes. The objectives of this study were to determine any gender-related difference in the presence of CV risk factors in young Latin Americans with poorly controlled type 2 diabetes and the effect of intensive insulin therapy on these CV risk factors. Fifty-seven Latin American patients with type 2 diabetes between the ages 18 and 45 years were evaluated at baseline. All women were premenopausal and had regular menstrual periods. The mean body mass index (BMI) was > 30 kg/m2 in both genders. Percent body fat, percent hemoglobin A1c, and lipoprotein profiles were similar between genders. Highly sensitive C-reactive protein (CRP) levels were elevated and similar between genders (p = .4). Leukocyte adhesion molecules (intercellular adhesion molecule 1, vascular adhesion molecule 1, E-selectin) and monocyte chemoattractant protein 1 were elevated, whereas adiponectin levels were below normal in both gender groups. Urinary albumin excretion was similar between genders and did not show any relationship with any of the variables. In women, there was a direct relationship between waist circumference and high-sensitivity CRP levels (rho = .53, p = .01). No other significant relationships were observed. Eighteen Latin American patients with type 2 diabetes completed up to 104 weeks of post-intervention with insulin monotherapy. In these patients, glycemic, lipoprotein, and anthropometric measurements were obtained every 12 weeks. Highly sensitive CRP, leukocyte adhesion molecules, and urinary albumin excretion, among other tests, were obtained every 52 weeks. At 52 and 104 weeks, body weight, BMI, waist circumference, and percent body fat increased in a parallel and significant manner

  13. Novel diabetes mellitus treatment: mature canine insulin production by canine striated muscle through gene therapy.

    PubMed

    Niessen, S J M; Fernandez-Fuente, M; Mahmoud, A; Campbell, S C; Aldibbiat, A; Huggins, C; Brown, A E; Holder, A; Piercy, R J; Catchpole, B; Shaw, J A M; Church, D B

    2012-07-01

    Muscle-targeted gene therapy using insulin genes has the potential to provide an inexpensive, low maintenance alternative or adjunctive treatment method for canine diabetes mellitus. A canine skeletal muscle cell line was established through primary culture, as well as through transdifferentiation of canine fibroblasts after infection with a myo-differentiation gene containing adenovirus vector. A novel mutant furin-cleavable canine preproinsulin gene insert (cppI4) was designed and created through de novo gene synthesis. Various cell lines, including the generated canine muscle cell line, were transfected with nonviral plasmids containing cppI4. Insulin and desmin immunostaining were used to prove insulin production by muscle cells and specific canine insulin ELISA to prove mature insulin secretion into the medium. The canine myoblast cultures proved positive on desmin immunostaining. All cells tolerated transfection with cppI4-containing plasmid, and double immunostaining for insulin and desmin proved present in the canine cells. Canine insulin ELISA assessment of medium of cppI4-transfected murine myoblasts and canine myoblast and fibroblast mixture proved presence of mature fully processed canine insulin, 24 and 48 h after transfection. The present study provides proof of principle that canine muscle cells can be induced to produce and secrete canine insulin on transfection with nonviral plasmid DNA containing a novel mutant canine preproinsulin gene that produces furin-cleavable canine preproinsulin. This technology could be developed to provide an alternative canine diabetes mellitus treatment option or to provide a constant source for background insulin, as well as C-peptide, alongside current treatment options.

  14. A cost-effectiveness analysis of sensor-augmented insulin pump therapy and automated insulin suspension versus standard pump therapy for hypoglycemic unaware patients with type 1 diabetes.

    PubMed

    Ly, Trang T; Brnabic, Alan J M; Eggleston, Andrew; Kolivos, Athena; McBride, Margaret E; Schrover, Rudolf; Jones, Timothy W

    2014-07-01

    To assess the cost-effectiveness of sensor-augmented insulin pump therapy with "Low Glucose Suspend" (LGS) functionality versus standard pump therapy with self-monitoring of blood glucose in patients with type 1 diabetes who have impaired awareness of hypoglycemia. A clinical trial-based economic evaluation was performed in which the net costs and effectiveness of the two treatment modalities were calculated and expressed as an incremental cost-effectiveness ratio (ICER). The clinical outcome of interest for the evaluation was the rate of severe hypoglycemia in each arm of the LGS study. Quality-of-life utility scores were calculated using the three-level EuroQol five-dimensional questionnaire. Resource use costs were estimated using public sources. After 6 months, the use of sensor-augmented insulin pump therapy with LGS significantly reduced the incidence of severe hypoglycemia compared with standard pump therapy (incident rate difference 1.85 [0.17-3.53]; P = 0.037). Based on a primary randomized study, the ICER per severe hypoglycemic event avoided was $18,257 for all patients and $14,944 for those aged 12 years and older. Including all major medical resource costs (e.g., hospital admissions), the ICERs were $17,602 and $14,289, respectively. Over the 6-month period, the cost per quality-adjusted life-year gained was $40,803 for patients aged 12 years and older. Based on the Australian experience evaluating new interventions across a broad range of therapeutic areas, sensor-augmented insulin pump therapy with LGS may be considered a cost-effective alternative to standard pump therapy with self-monitoring of blood glucose in hypoglycemia unaware patients with type 1 diabetes. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  15. Continuous Subcutaneous Insulin Infusion as an Effective Method of Desensitization Therapy for Diabetic Patients with Insulin Allergy: A 4-year Single-center Experience.

    PubMed

    Yuan, Tao; Zhao, Weigang; Wang, Lianglu; Dong, Yingyue; Li, Naishi

    2016-11-01

    This article summarizes our experiences in the application of continuous subcutaneous insulin infusion (CSII) as a method of rapid desensitization therapy for diabetic patients with insulin allergy that was subsequently switched to a regimen of multiple-dose injections for long-term insulin therapy. The clinical data of 11 diabetic patients with insulin allergy in Peking Union Medical College Hospital from April 1, 2008, through December 31, 2011, were retrospectively analyzed. All 11 conditions were diagnosed by case history, skin testing, determination of serum specific anti-insulin IgE, and reaction to withdrawal of insulin. Seven patients accepted the traditional injection method of desensitization, and 5 patients accepted CSII with the protocol designed for this study (1 patient accepted CSII after failure by the formal method). Six of the 7 patients who accepted the traditional method and all 5 patients who accepted CSII had successful results. All 5 patients in the CSII group switched to a regimen of multiple dosage injections. In a survey of 28 nurses, both experienced nurses and practical nurses preferred to use CSII as the method of desensitization. It is feasible and effective for diabetic patients with insulin allergy to use CSII as a method of rapid desensitization with subsequent switching to a regimen of multiple-dose injections for long-term insulin therapy. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  16. Reversal of Diabetes Through Gene Therapy of Diabetic Rats by Hepatic Insulin Expression via Lentiviral Transduction

    PubMed Central

    Elsner, Matthias; Terbish, Taivankhuu; Jörns, Anne; Naujok, Ortwin; Wedekind, Dirk; Hedrich, Hans-Jürgen; Lenzen, Sigurd

    2012-01-01

    Due to shortage of donor tissue a cure for type 1 diabetes by pancreas organ or islet transplantation is an option only for very few patients. Gene therapy is an alternative approach to cure the disease. Insulin generation in non-endocrine cells through genetic engineering is a promising therapeutic concept to achieve insulin independence in patients with diabetes. In the present study furin-cleavable human insulin was expressed in the liver of autoimmune-diabetic IDDM rats (LEW.1AR1/Ztm-iddm) and streptozotocin-diabetic rats after portal vein injection of INS-lentivirus. Within 5–7 days after the virus injection of 7 × 109 INS-lentiviral particles the blood glucose concentrations were normalized in the treated animals. This glucose lowering effect remained stable for the 1 year observation period. Human C-peptide as a marker for hepatic release of human insulin was in the range of 50–100 pmol/ml serum. Immunofluorescence staining of liver tissue was positive for insulin showing no signs of transdifferentiation into pancreatic β-cells. This study shows that the diabetic state can be efficiently reversed by insulin release from non-endocrine cells through a somatic gene therapy approach. PMID:22354377

  17. [Advantages and disadvantages of insulin therapy in elderly diabetics with asymptomatic hyperglycemia].

    PubMed

    Straumann, M; Staffelbach, O; Sonnenberg, G E; Keller, U; Berger, W

    1979-12-01

    15 elderly diabetic patients with fasting blood glucose levels above 160 mg/100 ml, without hyperglycemic symptoms and previously treated with oral antidiabetic agents, were put on insulin. The change of treatment regimen was made in the outpatient department. Frequent clinical and laboratory controls were performed and the patients were given full instructions for injection technique and diet. On the insulin regimen a prompt and lasting improvement was observed in the metabolic parameters (blood glucose levels both fasting and after food intake, Hb A1c, serum insulin, glucagon and serum lipid concentrations). The so-called "asymptomatic" patients noticed a marked improvement in their general status and performance. Three months after insulin therapy was started 13 of our 15 patients preferred the insulin treatment to oral agents. However, weight gain and a tendency to hypoglycemia were noticed in less disciplined patients. In addition, considerable time was spent on instruction of the patients. Bearing these factors in mind, insulin therapy in elderly diabetics with so-called "sysmptomatic hyperglycemia" can be regarded as worthwhile.

  18. Reversal of diabetes through gene therapy of diabetic rats by hepatic insulin expression via lentiviral transduction.

    PubMed

    Elsner, Matthias; Terbish, Taivankhuu; Jörns, Anne; Naujok, Ortwin; Wedekind, Dirk; Hedrich, Hans-Jürgen; Lenzen, Sigurd

    2012-05-01

    Due to shortage of donor tissue a cure for type 1 diabetes by pancreas organ or islet transplantation is an option only for very few patients. Gene therapy is an alternative approach to cure the disease. Insulin generation in non-endocrine cells through genetic engineering is a promising therapeutic concept to achieve insulin independence in patients with diabetes. In the present study furin-cleavable human insulin was expressed in the liver of autoimmune-diabetic IDDM rats (LEW.1AR1/Ztm-iddm) and streptozotocin-diabetic rats after portal vein injection of INS-lentivirus. Within 5-7 days after the virus injection of 7 × 10(9) INS-lentiviral particles the blood glucose concentrations were normalized in the treated animals. This glucose lowering effect remained stable for the 1 year observation period. Human C-peptide as a marker for hepatic release of human insulin was in the range of 50-100 pmol/ml serum. Immunofluorescence staining of liver tissue was positive for insulin showing no signs of transdifferentiation into pancreatic β-cells. This study shows that the diabetic state can be efficiently reversed by insulin release from non-endocrine cells through a somatic gene therapy approach.

  19. Optimizing antibiotic therapy in the intensive care unit setting

    PubMed Central

    Kollef, Marin H

    2001-01-01

    Antibiotics are one of the most common therapies administered in the intensive care unit setting. In addition to treating infections, antibiotic use contributes to the emergence of resistance among pathogenic microorganisms. Therefore, avoiding unnecessary antibiotic use and optimizing the administration of antimicrobial agents will help to improve patient outcomes while minimizing further pressures for resistance. This review will present several strategies aimed at achieving optimal use of antimicrobial agents. It is important to note that each intensive care unit should have a program in place which monitors antibiotic utilization and its effectiveness. Only in this way can the impact of interventions aimed at improving antibiotic use (e.g. antibiotic rotation, de-escalation therapy) be evaluated at the local level. PMID:11511331

  20. Clearance of Hepatitis C Virus Improves Insulin Resistance During and After Peginterferon and Ribavirin Therapy.

    PubMed

    Chien, Cheng-Hung; Lin, Chih-Lang; Hu, Ching-Chih; Chang, Jia-Jang; Chien, Rong-Nan

    2015-12-01

    Patients with chronic hepatitis C virus (HCV) infection are at a greater risk of developing insulin resistance (IR). However, little is known about when insulin sensitivity may improve during or after treatment for hepatitis C. In this study, we examined the effect of combination therapy with pegylated interferon-α and ribavirin on IR in patients with chronic HCV infection. We also analyzed factors associated with changes in insulin sensitivity. IR was estimated by homeostasis model assessment (HOMA-IR). HOMA-IR was measured before therapy, during therapy (12 and 24 weeks), and at the end of therapy (EOT; 24 or 48 weeks). We analyzed 78 HCV patients receiving combination therapy. Twenty-two patients (28.2%) exhibited pretreatment IR (HOMA-IR >2.5). In all patients, HOMA-IR was not significantly different from baseline values at 12 weeks (P = 0.823), 24 weeks (P = 0.417), or at EOT (P = 0.158). In patients with pretreatment IR, a significant decrease in HOMA-IR was observed at 12 weeks (P = 0.023), 24 weeks (P = 0.008), and at EOT (P = 0.002). Multivariate analysis using a logistic regression model showed that baseline HOMA-IR is the only factor associated with the decline in HOMA-IR during and after therapy. The eradication of HCV infection was associated with improved insulin sensitivity among patients with pretreatment IR. This significant improvement in insulin sensitivity may occur as early as 12 weeks after the initiation of antiviral therapy.

  1. Long-term interdisciplinary therapy reduces endotoxin level and insulin resistance in obese adolescents

    PubMed Central

    2012-01-01

    Aim The purpose of the present study was to assess the dietary fat intake, glucose, insulin, Homeostasis model assessment for insulin resistance HOMA-IR, and endotoxin levels and correlate them with adipokine serum concentrations in obese adolescents who had been admitted to long-term interdisciplinary weight-loss therapy. Design The present study was a longitudinal clinical intervention of interdisciplinary therapy. Adolescents (n = 18, aged 15–19 y) with a body mass index > 95th percentile were admitted and evaluated at baseline and again after 1 year of interdisciplinary therapy. We collected blood samples, and IL-6, adiponectin, and endotoxin concentrations were measured by ELISA. Food intake was measured using 3-day diet records. In addition, we assessed glucose and insulin levels as well as the homeostasis model assessment for insulin resistance (HOMA-IR). Results The most important finding from the present investigation was that the long-term interdisciplinary lifestyle therapy decreased dietary fat intake and endotoxin levels and improved HOMA-IR. We observed positive correlations between dietary fat intake and endotoxin levels, insulin levels, and the HOMA-IR. In addition, endotoxin levels showed positive correlations with IL-6 levels, insulin levels and the HOMA-IR. Interestingly, we observed a negative correlation between serum adiponectin and both dietary fat intake and endotoxin levels. Conclusions The present results indicate an association between dietary fat intake and endotoxin level, which was highly correlated with a decreased pro-inflammatory state and an improvement in HOMA-IR. In addition, this benefits effect may be associated with an increased adiponectin level, which suggests that the interdisciplinary therapy was effective in improving inflammatory pathways. PMID:22989045

  2. Insulin therapy in patients with cystic fibrosis in the pre-diabetes stage: a systematic review

    PubMed Central

    Pu, Mariana Zorrón Mei Hsia; Christensen-Adad, Flávia Corrêa; Gonçalves, Aline Cristina; Minicucci, Walter José; Ribeiro, José Dirceu; Ribeiro, Antonio Fernando

    2016-01-01

    Abstract Objective: To elucidate whether insulin is effective or not in patients with cystic fibrosis before the diabetes mellitus phase. Data source: The study was performed according to the Prisma method between August and September 2014, using the PubMed, Embase, Lilacs and SciELO databases. Prospective studies published in English, Portuguese and Spanish from 2002 to 2014, evaluating the effect of insulin on weight parameters, body mass index and pulmonary function in patients with cystic fibrosis, with a mean age of 17.37 years before the diabetes mellitus phase were included. Data synthesis: Eight articles were identified that included 180 patients undergoing insulin use. Sample size ranged from 4 to 54 patients, with a mean age ranging from 12.4 to 28 years. The type of follow-up, time of insulin use, the dose and implementation schedule were very heterogeneous between studies. Conclusions: There are theoretical reasons to believe that insulin has a beneficial effect in the studied population. The different methods and populations assessed in the studies do not allow us to state whether early insulin therapy should or should not be carried out in patients with cystic fibrosis prior to the diagnosis of diabetes. Therefore, studies with larger samples and insulin use standardization are required. PMID:26994743

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

    PubMed

    Joseph, Joshua J; Donner, Thomas W

    2015-01-01

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

  4. 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.

  5. Gene Therapy for Diabetes Mellitus in Rats by Hepatic Expression of Insulin

    NASA Astrophysics Data System (ADS)

    Kolodka, Tadeusz M.; Finegold, Milton; Moss, Larry; Woo, Savio L. C.

    1995-04-01

    Type 1 diabetes mellitus is caused by severe insulin deficiency secondary to the autoimmune destruction of pancreatic β cells. Patients need to be controlled by periodic insulin injections to prevent the development of ketoacidosis, which can be fatal. Sustained, low-level expression of the rat insulin 1 gene from the liver of severely diabetic rats was achieved by in vivo administration of a recombinant retroviral vector. Ketoacidosis was prevented and the treated animals exhibited normoglycemia during a 24-hr fast, with no evidence of hypoglycemia. Histopathological examination of the liver in the treated animals showed no apparent abnormalities. Thus, the liver is an excellent target organ for ectopic expression of the insulin gene as a potential treatment modality for type 1 diabetes mellitus by gene therapy.

  6. Lixisenatide as add-on therapy to basal insulin

    PubMed Central

    Brown, Dominique Xavier; Butler, Emma Louise; Evans, Marc

    2014-01-01

    Many patients with type 2 diabetes mellitus do not achieve target glycosylated hemoglobin A1c levels despite optimally titrated basal insulin and satisfactory fasting plasma glucose levels. Current evidence suggests that HbA1c levels are dictated by both basal glucose and postprandial glucose levels. This has led to a consensus that postprandial glucose excursions contribute to poor glycemic control in these patients. Lixisenatide is a once-daily, prandial glucagon-like peptide 1 (GLP-1) receptor agonist with a four-fold affinity for the GLP-1 receptor compared with native GLP-1. Importantly, lixisenatide causes a significant delay in gastric emptying time, an important determinant of the once-daily dosing regimen. An exendin-4 mimetic with six lysine residues removed at the C-terminal, lixisenatide has pronounced postprandial glucose-lowering effects, making it a novel incretin agent for use in combination with optimally titrated basal insulin. Lixisenatide exerts profound effects on postprandial glucose through established mechanisms of glucose-dependent insulin secretion and glucagon suppression in combination with delayed gastric emptying. This review discusses the likely place that lixisenatide will occupy in clinical practice, given its profound effects on postprandial glucose and potential to reduce glycemic variability. PMID:24363554

  7. A pilot study of factors associated with glycaemic control in adults with Type 1 diabetes mellitus on insulin pump therapy.

    PubMed

    Wen, W; Frampton, R; Wright, K; Fattore, S; Shadbolt, B; Perampalam, S

    2016-02-01

    To identify the knowledge and management factors associated with glycaemic control among adults with Type 1 diabetes mellitus treated with insulin pump therapy. A cross-sectional study of adults with Type 1 diabetes mellitus on insulin pump therapy for at least 12 months (n = 50, 18-70 years old) was undertaken between December 2013 and May 2014. A new questionnaire was developed to evaluate participants' knowledge and management related to insulin pump therapy, and were correlated with insulin pump data, HbA1c and frequency of hypoglycaemia. Participants who changed their insulin pump settings when indicated had significantly better glycaemic control than those who did not (P = 0.04). Multivariate logistic regression analysis found that better overall insulin pump therapy management was a significant predictor of better glycaemic control (odds ratio 4.45, 95% confidence interval 1.61-12.3; P = 0.004) after adjusting for potential confounders including age, gender, duration of diabetes and insulin pump therapy. However, overall insulin pump therapy knowledge was not a significant predictor of glycaemic control (P = 0.058). There was no significant association between frequency of hypoglycaemia and insulin pump therapy knowledge or management. We identified some key knowledge and management factors associated with glycaemic control in adults with Type 1 diabetes mellitus on insulin pump therapy using a newly designed questionnaire. The pilot study assessed the clinical utility of this evaluation tool, which may facilitate provision of targeted education to insulin pump therapy users to achieve optimal glycaemic control. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

  8. Optimization of insulin pump therapy based on high order run-to-run control scheme.

    PubMed

    Tuo, Jianyong; Sun, Huiling; Shen, Dong; Wang, Hui; Wang, Youqing

    2015-07-01

    Continuous subcutaneous insulin infusion (CSII) pump is widely considered a convenience and promising way for type 1 diabetes mellitus (T1DM) subjects, who need exogenous insulin infusion. In the standard insulin pump therapy, there are two modes for insulin infusion: basal and bolus insulin. The basal-bolus therapy should be individualized and optimized in order to keep one subject's blood glucose (BG) level within the normal range; however, the optimization procedure is troublesome and it perturb the patients a lot. Therefore, an automatic adjustment method is needed to reduce the burden of the patients, and run-to-run (R2R) control algorithm can be used to handle this significant task. In this study, two kinds of high order R2R control methods are presented to adjust the basal and bolus insulin simultaneously. For clarity, a second order R2R control algorithm is first derived and studied. Furthermore, considering the differences between weekdays and weekends, a seventh order R2R control algorithm is also proposed and tested. In order to simulate real situation, the proposed method has been tested with uncertainties on measurement noise, drifts, meal size, meal time and snack. The proposed method can converge even when there are ±60 min random variations in meal timing or ±50% random variations in meal size. According to the robustness analysis, one can see that the proposed high order R2R has excellent robustness and could be a promising candidate to optimize insulin pump therapy. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. 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.

  10. Superoxide production pathways in aortas of diabetic rats: beneficial effects of insulin therapy and endurance training.

    PubMed

    Malardé, L; Rebillard, A; Le Douairon-Lahaye, S; Vincent, S; Zguira, M S; Lemoine-Morel, S; Gratas-Delamarche, A; Groussard, C

    2014-04-01

    Superoxide (O 2 (·-) ) overproduction, by decreasing the nitric oxide ((·)NO) bioavailability, contributes to vascular complications in type 1 diabetes. In this disease, the vascular O 2 (·-) can be produced by the NADPH oxidase (NOX), nitric oxide synthase (NOS), and xanthine oxidase (XO). This study aimed to determine the contribution of each enzymatic pathway in hyperglycemia-induced O 2 (·-) overproduction, and the effects of an endurance training program and insulin therapy, associated or not, on the O 2 (·-) production (amount and related enzymes) in diabetic rats. Forty male Wistar rats were divided into diabetic (D), diabetic treated with insulin (D-Ins), diabetic trained (D-Tr), or diabetic insulin-treated and trained (D-Ins + Tr) groups. An additional healthy group was used as control. Insulin therapy (Glargine Lantus, Sanofi) and endurance training (treadmill run: 60 min/day, 25 m/min, 5 days/week) started 1 week after diabetes induction by streptozotocin (45 mg/kg), and lasted for 8 weeks. At the end of the protocol, the O 2 (·-) production in aorta rings was evaluated by histochemical analyses (DHE staining). Each production pathway was studied by inhibiting NOX (apocynin), NOS (L-Name), or XO (allopurinol) before DHE staining. Diabetic rats exhibited hyperglycemia-induced O 2 (·-) overproduction, resulting from NOX, NOS, and XO activation. Insulin therapy and endurance training, associated or not, decreased efficiently and similarly the O 2 (·-) overproduction. Insulin therapy reduced the hyperglycemia and decreased the three enzymatic pathways implicated in the O 2 (·-) production. Endurance training decreased directly the NOS and XO activity. While both therapeutic strategies activated different pathways, their association did not reduce the O 2 (·-) overproduction more significantly.

  11. The Experiences of School Nurses Caring for Students Receiving Continuous Subcutaneous Insulin Infusion Therapy

    ERIC Educational Resources Information Center

    Darby, Wendy

    2006-01-01

    Diabetes mellitus is the most common metabolic disorder in childhood. Today, children with diabetes are receiving new technologically advanced treatment options, such as continuous subcutaneous insulin infusion (CSII) therapy. School nurses are the primary health caregivers of children with diabetes during school hours. Therefore, it is important…

  12. The Experiences of School Nurses Caring for Students Receiving Continuous Subcutaneous Insulin Infusion Therapy

    ERIC Educational Resources Information Center

    Darby, Wendy

    2006-01-01

    Diabetes mellitus is the most common metabolic disorder in childhood. Today, children with diabetes are receiving new technologically advanced treatment options, such as continuous subcutaneous insulin infusion (CSII) therapy. School nurses are the primary health caregivers of children with diabetes during school hours. Therefore, it is important…

  13. Arc binary intensity modulated radiation therapy (AB IMRT)

    NASA Astrophysics Data System (ADS)

    Yang, Jun

    The state of the art Intensity Modulate Radiation Therapy (IMRT) has been one of the most significant breakthroughs in the cancer treatment in the past 30 years. There are two types of IMRT systems. The first system is the binary-based tomotherapy, represented by the Peacock (Nomos Corp) and Tomo unit (TomoTherapy Inc.), adopting specific binary collimator leafs to deliver intensity modulated radiation fields in a serial or helical fashion. The other uses the conventional dynamic multileaf collimator (MLC) to deliver intensity modulated fields through a number of gantry positions. The proposed Arc Binary IMRT attempts to deliver Tomo-like IMRT with conventional dynamic MLC and combines the advantages of the two types of IMRT techniques: (1) maximizing the number of pencil beams for better dose optimization, (2) enabling conventional linear accelerator with dynamic MLC to deliver Tomo-like IMRT. In order to deliver IMRT with conventional dynamic MLC in a binary fashion, the slice-by-slice treatment with limited slice thickness has been proposed in the thesis to accommodate the limited MLC traveling speed. Instead of moving the patient to subsequent treatment slices, the proposed method offsets MLC to carry out the whole treatment, slice by slice sequentially, thus avoid patient position error. By denoting one arc pencil beam set as a gene, genetic algorithm (GA) is used as the searching engine for the dose optimization process. The selection of GA parameters is a crucial step and has been studied in depth so that the optimization process will converge with reasonable speed. Several hypothetical and clinical cases have been tested with the proposed IMRT method. The comparison of the dose distribution with other commercially available IMRT systems demonstrates the clear advantage of the new method. The proposed Arc Binary Intensity Modulated Radiation Therapy is not only theoretically sound but practically feasible. The implementation of this method would expand the

  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. Finding the right route for insulin delivery - an overview of implantable pump therapy.

    PubMed

    Bally, Lia; Thabit, Hood; Hovorka, Roman

    2017-09-01

    Implantable pump therapy adopting the intraperitoneal route of insulin delivery has been available for the past three decades. The key rationale for implantable pump therapy is the restoration of the portal-peripheral insulin gradient of the normal physiology. Uptake in clinical practice is limited to specialized centers and selected patient populations. Areas covered: Implantable pump therapy is discussed, including technical aspects, rationale for its use, and glycemic and non-glycemic effects. Target populations, summaries of clinical studies and issues related to implantable pump therapy are highlighted. Limitations of implantable pump therapy and its future outlook in clinical practice are presented. Expert opinion: Although intraperitoneal insulin delivery appears closer to the normal physiology, technical, pharmacological, and costs barriers prevent a wider adoption. Evidence from clinical studies remains scarce and inconclusive. As a consequence, the use of implantable pump therapy will be confined to a small population unless considerable technological progress is made and well-conducted studies can demonstrate glycemic and/or non-glycemic benefits justifying wider application.

  16. Integrated insulin pump therapy with continuous glucose monitoring for improved adherence: technology update.

    PubMed

    Tumminia, Andrea; Sciacca, Laura; Frittitta, Lucia; Squatrito, Sebastiano; Vigneri, Riccardo; Le Moli, Rosario; Tomaselli, Letizia

    2015-01-01

    Insulin pump therapy combined with real-time continuous glucose monitoring, known as sensor-augmented pump (SAP) therapy, has been shown to improve metabolic control and to reduce the rate of hypoglycemia in adults with type 1 diabetes compared to multiple daily injections or standard continuous subcutaneous insulin infusion. Glycemic variability is also reduced in patients on SAP therapy. This approach allows patients to monitor their glucose levels being informed of glycemic concentration and trend. Trained diabetic patients, therefore, can appropriately modify insulin infusion and/or carbohydrate intake in order to prevent hypo- or hyperglycemia. For these reasons, SAP therapy is now considered the gold standard for type 1 diabetes treatment. To be clinically effective, however, devices and techniques using advanced technology should not only have the potential to theoretically ameliorate metabolic control, but also be well accepted by patients in terms of satisfaction and health-related quality of life, because these factors will improve treatment adherence and consequently overall outcome. SAP therapy is generally well tolerated by patients; however, many clinical trials have identified significant noncompliance in the use of this device, most notably in the pediatric and adolescent populations. In this review we aim to analyze the main reasons for good or poor adherence to SAP therapy and to provide useful tips in order to fully benefit from this kind of novel therapeutic approach.

  17. Ramadan fasting in diabetes patients on insulin pump therapy augmented by continuous glucose monitoring: an observational real-life study.

    PubMed

    Khalil, Ali Bernard; Beshyah, Salem A; Abu Awad, Samar M; Benbarka, Mahmoud M; Haddad, Marcil; Al-Hassan, Dana; Kahwatih, Marwa; Nagelkerke, Nico

    2012-09-01

    Hypoglycemia during the daytime of Ramadan fasting is the most feared complication of diabetes. Insulin pump therapy has been proposed as the ideal "theoretical" method for insulin delivery. We report a prospective observational, single-center study of insulin-treated patients using insulin pump therapy during Ramadan 2011. Twenty-one patients (10 males and 11 females) were selected; median age was 26 years. They adjusted their insulin as per their usual practices. Outcome measures obtained before and during Ramadan included body weight, glycosylated hemoglobin, blood glucose, total insulin dose differences, overriding tendency, suspension time during fasting, and number of hypoglycemic episodes. The patients fasted for a median of 29 days. The observed changes during Ramadan were overall not significant quantitatively, but some trends were noted. The total insulin administered during Ramadan was not different from that in the pre-Ramadan period, but there was a redistribution of insulin over a 24-h period in relation to the changes in the daily lifestyle and eating patterns. Basal insulin was decreased during the daytime by 5-20% from before Ramadan and increased during the nighttime. The mean change in the overall amount of basal insulin was not significant. A larger than usual amount of insulin bolus was given at the meals Iftar, Fowala, and Suhur; the change in the total amount of bolus insulin as a percentage change from total insulin was also not significant. No major hypoglycemic episodes were reported. Minor hypoglcemic episodes were equally distributed between daytime and nighttime and were managed by either basal insulin adjustment or suspension from the pump. This study confirms the advantages provided by insulin pump use in patients with diabetes were enhanced by the use of continuous glucose monitoring. We provided more evidence-based advice on how best to adjust the insulin pump during fasting.

  18. [Insulin-sulfonylurea combination therapy in secondary therapy failure with sulfonylurea compounds. Randomized study between evening and morning intermediary insulin administration using the Novo Pen semi-automatic insulin injector].

    PubMed

    Stradner, F; Pieber, T; Toplak, H; Schreiber, U; Pfeiffer, K P

    1990-07-10

    In 28 type II diabetics with secondary failure of sulfonylurea treatment, the efficacy and safety of combined therapy with insulin and glibenclamide were investigated. Patients were randomized in two groups and treated for 16 weeks either with insulin Novo Protaphan HM Penfill (100 IU/ml "bed time") and 10 mg of glibenclamide in the morning (group A), or with insulin Novo Actraphan HM Penfill 100 IU/ml in the morning combined with two 5 mg doses of glibenclamide at lunchtime and in the evening (group B). Subsequently a dropout trial of sulfonylurea was performed in half of the patients. Mean blood glucose levels were lowered in the whole group of patients from 13.5 +/- 1.8 mmol/l to 8.8 +/- 2.3 mmol/l after 8 weeks and 8.7 +/- 1.8 mmol/l after 16 weeks, and the HbAlc from 10.1 +/- 1.2% to 8.4 +/- 1.0% and 7.8 +/- 1.0% respectively. After a glibenclamide dropout period of one or two weeks in 14 of the patients, the mean blood glucose level rose significantly by 2.8 +/- 2.6 mmol/l. Only 2 patients did not show this increase. The mean insulin consumption was 13 +/- 3 IU after 8 weeks and 14 +/- 5 IU after 16 weeks respectively, and the incidence of hypoglycemia one in 12 weeks of treatment. The combination of glibenclamide and insulin (administered with the Novo Pen injector) is a safe and effective form of therapy in secondary failure of sulfonylurea, and is well accepted due to the mild start into insulin therapy.

  19. The effect of exercise-intensity on skeletal muscle stress kinase and insulin protein signaling

    PubMed Central

    Trewin, Adam; Levinger, Itamar; Shaw, Christopher S.; Stepto, Nigel K.

    2017-01-01

    Background Stress and mitogen activated protein kinase (SAPK) signaling play an important role in glucose homeostasis and the physiological adaptation to exercise. However, the effects of acute high-intensity interval exercise (HIIE) and sprint interval exercise (SIE) on activation of these signaling pathways are unclear. Methods Eight young and recreationally active adults performed a single cycling session of HIIE (5 x 4 minutes at 75% Wmax), SIE (4 x 30 second Wingate sprints), and continuous moderate-intensity exercise work-matched to HIIE (CMIE; 30 minutes at 50% of Wmax), separated by a minimum of 1 week. Skeletal muscle SAPK and insulin protein signaling were measured immediately, and 3 hours after exercise. Results SIE elicited greater skeletal muscle NF-κB p65 phosphorylation immediately after exercise (SIE: ~40%; HIIE: ~4%; CMIE; ~13%; p < 0.05) compared to HIIE and CMIE. AS160Ser588 phosphorylation decreased immediately after HIIE (~-27%; p < 0.05), and decreased to the greatest extent immediately after SIE (~-60%; p < 0.05). Skeletal muscle JNK (~42%; p < 0.05) and p38 MAPK (~171%; p < 0.05) phosphorylation increased, and skeletal muscle AktSer473 phosphorylation (~-32%; p < 0.05) decreased, to a similar extent immediately after all exercise protocols. AS160Ser588 phosphorylation was similar to baseline three hours after SIE (~-12%; p > 0.05), remained lower 3 hours after HIIE (~-34%; p < 0.05), and decreased 3 hours after CMIE (~-33%; p < 0.05). Conclusion Despite consisting of less total work than CMIE and HIIE, SIE proved to be an effective stimulus for the activation of stress protein kinase signaling pathways linked to exercise-mediated adaptation of skeletal muscle. Furthermore, post-exercise AS160Ser588 phosphorylation decreased in an exercise-intensity and post-exercise time-course dependent manner. PMID:28182793

  20. Incretin-based therapy in combination with basal insulin: a promising tactic for the treatment of type 2 diabetes.

    PubMed

    Vora, J; Bain, S C; Damci, T; Dzida, G; Hollander, P; Meneghini, L F; Ross, S A

    2013-02-01

    Incretin therapies such as dipeptidyl peptidase-4 inhibitors (DPP-4Is) and GLP-1 receptor agonists (GLP-1RAs) have become well-established treatments for type 2 diabetes. Both drug classes reduce blood glucose through physiological pathways mediated by the GLP-1 receptor, resulting in glucose-dependent enhancement of residual insulin secretion and inhibition of glucagon secretion. In addition, the GLP-1RAs reduce gastrointestinal motility and appear to have appetite-suppressing actions and, so, are often able to produce clinically useful weight loss. The glucose-dependency of their glucagon-inhibiting and insulin-enhancing effects, together with their weight-sparing properties, make the incretin therapies a logical proposition for use in combination with exogenous basal insulin therapy. This combination offers the prospect of an additive or synergistic glucose-lowering effect without a greatly elevated risk of hypoglycaemia compared with insulin monotherapy, and any insulin-associated weight gain might also be mitigated. Furthermore, the incretin therapies can be combined with metformin, which is usually continued when basal insulin is introduced in type 2 diabetes. Although the combination of incretin and insulin therapy is currently not addressed in internationally recognized treatment guidelines, several clinical studies have assessed its use. The data, summarized in this review, are encouraging and show that glycaemic control is improved and weight gain is limited or reversed (especially with the combined use of GLP-1RAs and basal insulin), and that the use of an incretin therapy can also greatly reduce insulin dose requirements. The addition of basal insulin to established incretin therapy is straightforward, but insulin dose adjustment (though not discontinuation) is usually necessary if the sequence is reversed.

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

    PubMed

    2017-03-30

    Objective To compare the effectiveness of insulin pumps with multiple daily injections for adults with type 1 diabetes, with both groups receiving equivalent training in flexible insulin treatment.Design Pragmatic, multicentre, open label, parallel group, cluster randomised controlled trial (Relative Effectiveness of Pumps Over MDI and Structured Education (REPOSE) trial).Setting Eight secondary care centres in England and Scotland.Participants Adults with type 1 diabetes who were willing to undertake intensive insulin treatment, with no preference for pumps or multiple daily injections. Participants were allocated a place on established group training courses that taught flexible intensive insulin treatment ("dose adjustment for normal eating," DAFNE). The course groups (the clusters) were then randomly allocated in pairs to either pump or multiple daily injections.Interventions Participants attended training in flexible insulin treatment (using insulin analogues) structured around the use of pump or injections, followed for two years.Main outcome measures The primary outcomes were a change in glycated haemoglobin (HbA1c) values (%) at two years in participants with baseline HbA1c value of ≥7.5% (58 mmol/mol), and the proportion of participants achieving an HbA1c value of <7.5%. Secondary outcomes included body weight, insulin dose, and episodes of moderate and severe hypoglycaemia. Ancillary outcomes included quality of life and treatment satisfaction.Results 317 participants (46 courses) were randomised (156 pump and 161 injections). 267 attended courses and 260 were included in the intention to treat analysis, of which 235 (119 pump and 116 injection) had baseline HbA1c values of ≥7.5%. Glycaemic control and rates of severe hypoglycaemia improved in both groups. The mean change in HbA1c at two years was -0.85% with pump treatment and -0.42% with multiple daily injections. Adjusting for course, centre, age, sex, and accounting for missing values, the

  2. Planning and delivery of intensity-modulated radiation therapy.

    PubMed

    Yu, Cedric X; Amies, Christopher J; Svatos, Michelle

    2008-12-01

    Intensity modulated radiation therapy (IMRT) is an advanced form of external beam radiation therapy. IMRT offers an additional dimension of freedom as compared with field shaping in three-dimensional conformal radiation therapy because the radiation intensities within a radiation field can be varied according to the preferences of locations within a given beam direction from which the radiation is directed to the tumor. This added freedom allows the treatment planning system to better shape the radiation doses to conform to the target volume while sparing surrounding normal structures. The resulting dosimetric advantage has shown to translate into clinical advantages of improving local and regional tumor control. It also offers a valuable mechanism for dose escalation to tumors while simultaneously reducing radiation toxicities to the surrounding normal tissue and sensitive structures. In less than a decade, IMRT has become common practice in radiation oncology. Looking forward, the authors wonder if IMRT has matured to such a point that the room for further improvement has diminished and so it is pertinent to ask what the future will hold for IMRT. This article attempts to look from the perspective of the current state of the technology to predict the immediate trends and the future directions. This article will (1) review the clinical experience of IMRT; (2) review what we learned in IMRT planning; (3) review different treatment delivery techniques; and finally, (4) predict the areas of advancements in the years to come.

  3. Resistance Exercise Reduces Body Fat and Insulin During Androgen-Deprivation Therapy for Prostate Cancer.

    PubMed

    Winters-Stone, Kerri M; Dieckmann, Nathan; Maddalozzo, Gianni F; Bennett, Jill A; Ryan, Christopher W; Beer, Tomasz M

    2015-07-01

    To determine whether exercise could reduce biomarkers of cancer progression in prostate cancer survivors (PCSs) on androgen-deprivation therapy (ADT). Randomized, controlled trial. Oregon Health and Science University School of Nursing. 51 PCSs randomized to one year of resistance and impact training or a stretching control group. The authors investigated changes in body composition and cancer-related biomarkers, and the influence of age and fat loss on changes in biomarkers. Body composition (total fat, trunk fat, and lean mass), insulin, insulin-like growth factor-1, and sex hormone-binding globulin. In the 36 PCSs with baseline and 12-month data, total fat (p = 0.02) and trunk fat (p = 0.06) mass decreased in the training group compared to gains in controls. Loss of total and trunk fat each mediated the relationship between groups and one-year change in insulin (p < 0.05). Age moderated the insulin response to exercise where insulin reductions were smaller with increasing age (p = 0.03). Resistance and impact exercise may reduce body fat among PCSs undergoing ADT, in turn exerting an insulin-lowering effect. Nurses should counsel PCSs to exercise to reduce the risk of obesity and associated conditions, including cancer progression.

  4. Advances in endonasal low intensity laser irradiation therapy

    NASA Astrophysics Data System (ADS)

    Jiao, Jian-Ling; Liu, Timon C.; Liu, Jiang; Cui, Li-Ping; Liu, Song-hao

    2005-07-01

    Endonasal low intensity laser therapy (ELILT) began in China in 1998. Now in China it is widely applied to treat hyperlipidemia and brain diseases such as Alzheimer's disease, Parkinson's disease, insomnia, poststroke depression, intractable headache, ache in head or face, cerebral thrombosis, acute ischemic cerebrovascular disease, migraine, brain lesion and mild cognitive impairment. There are four pathways mediating EILILT, Yangming channel, autonomic nervous systems and blood cells. Two unhealth acupoints of Yangming channal inside nose might mediate the one as is low intensity laser acupuncture. Unbalance autonomic nervous systems might be modulated. Blood cells might mediate the one as is intravascular low intensity laser therapy. These three pathways are integrated in ELILT so that serum amyloid β protein, malformation rate of erythrocyte, CCK-8, the level of viscosity at lower shear rates and hematocrit, or serum lipid might decrease, and melanin production/SOD activity or β endorphin might increase after ELILT treatment. These results indicate ELILT might work, but it need to be verified by randomized placebo-controlled trial.

  5. The U.K. service level audit of insulin pump therapy in adults.

    PubMed

    White, H D; Goenka, N; Furlong, N J; Saunders, S; Morrison, G; Langridge, P; Paul, P; Ghatak, A; Weston, P J

    2014-04-01

    The National Institute for Health and Clinical Excellence (NICE) published guidelines for the use of continuous subcutaneous insulin infusion in 2008 (technology appraisal 151). The first U.K.-wide insulin pump audit took place in 2012 with the aim of determining adherence to the guidance issued in NICE technology appraisal 151. The results of the adult service level audit are reported here. All centres providing continuous subcutaneous insulin infusion services to adults with diabetes in the U.K. were invited to participate. Audit metrics were aligned to technology appraisal 151. Data entry took place online using a DiabetesE formatted data collection tool. One hundred and eighty-three centres were identified as delivering adult continuous subcutaneous insulin infusion services in the U.K., of which 178 (97.3%) participated in the audit. At the time of the audit, 13 428 adults were using insulin pump therapy, giving an estimated prevalence of use of 6%. Ninety-three per cent of centres did not report any barriers in obtaining funding for patients who fulfilled NICE criteria. The mean number of consultant programmed activities dedicated to continuous subcutaneous insulin infusion services was 0.96 (range 0-8), mean whole-time equivalent diabetes specialist nurses was 0.62 (range 0-3) and mean whole-time equivalent dietitian services was 0.3 (range 0-2), of which 39, 61 and 60%, respectively, were not formally funded. The prevalence of continuous subcutaneous insulin infusion use in the U.K. falls well below the expectation of NICE (15-20%) and that of other European countries (> 15%) and the U.S.A. (40%). This may be attributable, in part, to lack of healthcare professional time needed for identification and training of new pump therapy users. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

  6. [Hormone replacement therapy with transdermal estradiol lowers insulin-cortisol and lipoproteins levels in postmenopausal women].

    PubMed

    Basurto, Lourdes; Saucedo, Renata; Ochoa, Raquel; Hernández, Marcelino; Zárate, Arturo

    2002-10-01

    Increased levels of circulating insulin and cortisol, interpreted as part of aging process, have been associated with an increase risk of developing cardiovascular disease and diabetes mellitus. Because estrogens affect insulin balance, hypoestrogenism in menopausal women may lead to elevations in both insulin and cortisol. The purpose of the present study was to determine the effect of transdermal estradiol administration on the insulin-cortisol binomial. A prospective study was carried out in 30 menopausal women aged 48 to 55 yr, receiving transdermal estradiol 50 micrograms/day during three months. Ten healthy menopausal women (49 to 58 yr) were the control group. Serum levels of cortisol, insulin, lipoproteins, and leptin were quantified by specific assays before and after 3 months of transdermal estradiol therapy. Baseline cortisol levels decreased significantly from 143.4 +/- 10.6 ng/mL to 110.2 +/- 6.7 ng/mL (M +/- SE) (p < 0.001) after 3 months of transdermal estradiol. In parallel, augmented baseline insulin levels diminished significantly from 26.1 +/- 2.0 microlitersU/mL to 21.7 +/- 1.2; (M +/- SE) (p < 0.05). Glucose level were unaffected by this therapy, but it was restored to normal the augmented baseline levels of both triglycerides and low-density cholesterol. Total cholesterol and high-density-cholesterol as well as circulating leptin were unchanged. Transdermal estrogen induced-decrease in circulating cortisol, insulin, triglycerides, and low-density cholesterol to normal values may have a beneficial metabolic effect in menopausal women.

  7. High-dose insulin therapy attenuates systemic inflammatory response in coronary artery bypass grafting patients.

    PubMed

    Albacker, Turki; Carvalho, George; Schricker, Thomas; Lachapelle, Kevin

    2008-07-01

    Cardiac surgery with cardiopulmonary bypass (CPB) induces an acute phase reaction that is implicated in the pathogenesis of several postoperative complications. Studies have shown that proinflammatory cytokines are increased by acute hyperglycemia. Recent evidence suggests that insulin has antiinflammatory properties. Therefore, we hypothesized that high-dose insulin therapy would attenuate the systemic inflammatory response to cardiopulmonary bypass and surgery in coronary artery bypass patients while maintaining normoglycemia. A total of 52 patients who presented for elective coronary artery bypass were randomized to receive intraoperative intravenous insulin infusion, titrated to maintain blood glucose concentrations less than 180 mg/dL (group I, n = 25), or receive intraoperative fixed high dose of intravenous insulin infusion (5 mU/kg/min) with dextrose 20% infused separately to maintain a blood glucose level between 70 and 110 mg/dL (group II, n = 27). Blood samples were collected at different time points to determine tumor necrosis factor alpha (TNFalpha), interleukin 6 and 8 (IL6 and IL8), and complement factor 3 and 4 (C3 and C4). Patients in both groups had similar preoperative characteristics. Patients in the high-dose insulin group had higher blood insulin concentrations and tighter blood glucose control. There were lower levels of IL6 (150 pg/dL vs 245 pg/dL, p = 0.03), IL-8 (49 pg/dL vs 74 pg/dL, p = 0.05), and TNFalpha (2.2 pg/dL vs 3.0 pg/dL, p = 0.04) in group II in the early postoperative period. High-dose insulin therapy blunts the early postoperative surge in inflammatory response to CPB as reflected by decreased levels of IL6, IL8, and TNFalpha.

  8. 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

  9. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes.

    PubMed

    Holman, Rury R; Thorne, Kerensa I; Farmer, Andrew J; Davies, Melanie J; Keenan, Joanne F; Paul, Sanjoy; Levy, Jonathan C

    2007-10-25

    Adding insulin to oral therapy in type 2 diabetes mellitus is customary when glycemic control is suboptimal, though evidence supporting specific insulin regimens is limited. In an open-label, controlled, multicenter trial, we randomly assigned 708 patients with a suboptimal glycated hemoglobin level (7.0 to 10.0%) who were receiving maximally tolerated doses of metformin and sulfonylurea to receive biphasic insulin aspart twice daily, prandial insulin aspart three times daily, or basal insulin detemir once daily (twice if required). Outcome measures at 1 year were the mean glycated hemoglobin level, the proportion of patients with a glycated hemoglobin level of 6.5% or less, the rate of hypoglycemia, and weight gain. At 1 year, mean glycated hemoglobin levels were similar in the biphasic group (7.3%) and the prandial group (7.2%) (P=0.08) but higher in the basal group (7.6%, P<0.001 for both comparisons). The respective proportions of patients with a glycated hemoglobin level of 6.5% or less were 17.0%, 23.9%, and 8.1%; respective mean numbers of hypoglycemic events per patient per year were 5.7, 12.0, and 2.3; and respective mean weight gains were 4.7 kg, 5.7 kg, and 1.9 kg. Rates of adverse events were similar among the three groups. A single analogue-insulin formulation added to metformin and sulfonylurea resulted in a glycated hemoglobin level of 6.5% or less in a minority of patients at 1 year. The addition of biphasic or prandial insulin aspart reduced levels more than the addition of basal insulin detemir but was associated with greater risks of hypoglycemia and weight gain. (Current Controlled Trials number, ISRCTN51125379 [controlled-trials.com].). Copyright 2007 Massachusetts Medical Society.

  10. Type 2 Diabetes Mellitus, Oral Diabetic Medications, Insulin Therapy, and Overall Breast Cancer Risk

    PubMed Central

    Ahmadieh, Hala; Azar, Sami T.

    2013-01-01

    Breast cancer is among the most common cancers worldwide. Diabetes is an important chronic health problem associated with insulin resistance, increased insulin level, changes in growth hormones and factors, and activation of mitogen-activating protein kinase (MAPK) pathways, leading to an increased breast cancer risk. This paper looked at the epidemiologic studies of the association between type 2 diabetes and risk of breast cancer and its effect on overall cancer-specific survival. The combined evidence overall supported a modest association between type 2 diabetes and the risk of breast cancer, which was found to be more prevalent among postmenopausal women. Effect of oral diabetics and insulin therapy on breast cancer risk was also evaluated. It was found that metformin and thiazolidinones tended to have a protective role. Metformin therapy trials for its use as an adjuvant for breast cancer treatment are still ongoing. Sulfonylurea and insulin therapy were found to be mildly associated with increased overall cancers. No evidence or studies evaluated the association of DPPIV inhibitors and GLP 1 agonists with breast cancer risk because of their recent introduction into the management of diabetes. PMID:23401790

  11. Cortical thinning in type 2 diabetes mellitus and recovering effects of insulin therapy.

    PubMed

    Chen, Zhiye; Sun, Jie; Yang, Yang; Lou, Xin; Wang, Yulin; Wang, Yan; Ma, Lin

    2015-02-01

    The purpose of this study was to explore the brain structural changes in type 2 diabetes and the effect of insulin on the brain using a surface-based cortical thickness analysis. High-resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MRI were obtained from 11 patients with type 2 diabetes before and after insulin therapy. The cortical thickness over the entire brain was calculated, and cross-sectional and longitudinal surface-based cortical thickness analyses were also performed. Regional cortical thinning was demonstrated in the middle temporal gyrus, posterior cingulate gyrus, precuneus, right lateral occipital gyrus and entorhinal cortex bilaterally for patients with type 2 diabetes mellitus compared with normal controls. Cortical thickening was seen in the middle temporal gyrus, entorhinal cortex and left inferior temporal gyrus bilaterally after patients underwent 1 year of insulin therapy. These findings suggest that insulin therapy may have recovering effects on the brain cortex in type 2 diabetes mellitus. The precise mechanism should be investigated further.

  12. [The doctor-patient relationship in intensive therapy].

    PubMed

    Szulc, Roman

    2008-01-01

    The doctor-patient and doctor-patient's family relationships require skills of interpersonal communication, which is particularly important in intensive therapy. Unfortunately, such skills are not routinely taught and inadequacies are enormous. Communication skills are essential for decision-making and outcomes of therapy. The communication-related education should be obligatory and include abilities to use the linguistic and extra-linguistic signs suitable for the given circumstances. The former ought to have linguistic, psychological and social effects. The latter should involve gestures, voice modulation, facial expressions or even silence, if need be. ITU patients and their families expect physicians to behave appropriately and to provide them with competent emotional support and cooperation.

  13. Intensity of continuous renal replacement therapy in acute kidney injury.

    PubMed

    Palevsky, Paul M

    2009-01-01

    The intensity of continuous renal replacement therapy (CRRT) is generally assessed on the basis of small solute clearance with dosing usually expressed in terms of total effluent volume per unit time (e.g., ml/kg/hour). Although several clinical trials have suggested an improvement in survival with higher doses of CRRT, results have not been consistent across all studies. The results of recent trials of intensity of CRRT are reviewed. The largest and most recent trials suggest that there is no additional benefit to using effluent flow rates in excess of 20 ml/kg/hour, although earlier studies suggested improved survival with doses of 35 to 45 ml/kg/hour.

  14. Linear algebraic methods applied to intensity modulated radiation therapy.

    PubMed

    Crooks, S M; Xing, L

    2001-10-01

    Methods of linear algebra are applied to the choice of beam weights for intensity modulated radiation therapy (IMRT). It is shown that the physical interpretation of the beam weights, target homogeneity and ratios of deposited energy can be given in terms of matrix equations and quadratic forms. The methodology of fitting using linear algebra as applied to IMRT is examined. Results are compared with IMRT plans that had been prepared using a commercially available IMRT treatment planning system and previously delivered to cancer patients.

  15. Prolonged intermittent renal replacement therapy in the intensive care unit.

    PubMed

    Bellomo, R; Baldwin, I; Fealy, N

    2002-12-01

    To present a review on the use of prolonged intermittent renal replacement therapy in the intensive care patient. Articles and abstracts reporting the use of renal replacement therapy. Standard intermittent haemodialysis (IHD) has significant shortcomings in the treatment of the acute renal failure (ARF) of critical illness. These shortcomings include haemodynamic instability, the need to remove excess fluid over a short period of time, the episodic nature of small solute control, the limited ability to achieve middle molecular weight solute control and the episodic nature of acid-base control. Over the last 20 years, these limitations have stimulated the evolution and increased application of continuous renal replacement therapy (CRRT) which provides major biochemical, biological and physiological advantages compared with IHD, although it remains unclear as to whether such advantages translate into a survival advantage. However, CRRT is technically demanding, requires supervision 24 hr per day and is often associated with the need for continuous anticoagulation, which, in some patients, might be undesirable. In some institutions, CRRT changes the nurse to patient ratio from 1:2 to 1:1, an alteration which has cost implications and might affect resource availability for other patients. Accordingly, techniques which prolong the duration of intermittent therapy and avoid the need for 24 hr treatment may offer "best value" in the management of ARF in the intensive care unit (ICU). These techniques will be referred to as prolonged intermittent renal replacement therapies (PIRRT) in this article. They are characterised by several fundamental principles: 1. Use of a modified or standard dialysis machines, 2. Use of diffusion, convection or any combination of the two, 3. Application of a decreased intensity of solute removal compared with IHD, 4. Extended duration of treatment beyond the typical 3 or 4 hr of standard IHD (hence the term prolonged) but not beyond an 8

  16. Risk factors for discontinuation of insulin pump therapy in pediatric and young adult patients.

    PubMed

    Kostev, Karel; Rockel, Timo; Rosenbauer, Joachim; Rathmann, Wolfgang

    2014-12-01

    Previous studies have shown that only a small number of pediatric and young adult patients discontinue pump therapy, but risk factors for discontinuation are unclear. To identify characteristics of pediatric and young adult patients with pump therapy which are associated with discontinuation of treatment. Retrospective cohort study using a representative nationwide database (LRx; IMS Health) in Germany covering >80% of all prescriptions to members of statutory health insurances in 2008-2011. All patients (age group <25 years) with new prescriptions of insulin pumps were identified (2009-2010) and were followed for 12 months. Overall, 2452 new pump users were identified, of whom 177 (7.2%) switched to other forms of insulin therapy within 12 months. In multivariate logistic regression, younger age (<6 years; reference 18 to <25 years: Odds ratio, OR, 95% CI: 0.36; 0.17-0.74) and use of teflon needles (reference steel needles: OR, 95% CI: 0.59; 0.41-0.83) were related to a lower odds of pump discontinuation. A non-significant trend was found for male sex (OR, 95% CI: 0.75; 0.52-1.08). Prescriptions of thyroid therapeutics (ATC H03A: OR, 95% CI: 1.79; 1.23-2.61) and antiepileptics (N03: OR, 95% CI: 3.14; 1.49-6.59) were significantly associated with discontinuation of pump therapy. About 93% of pediatric and young adult patients maintained insulin pump therapy within 12 months. Age <6 years, male sex and teflon needle use were associated with a lower risk of discontinuation. Thyroid therapy (indicating autoimmunity) and antiepileptic drug prescriptions were associated with a higher likelihood for discontinuation of insulin pump treatment. Copyright © 2014 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  17. Calculation of the intake of three intense sweeteners in young insulin-dependent diabetics.

    PubMed

    Garnier-Sagne, I; Leblanc, J C; Verger, P

    2001-07-01

    In 1994, European Directive 94/35/CE authorised the use as food additives of five intense sweeteners for which Acceptable Daily Intakes (ADI) were established. The same directive stipulated that member states should organise a monitoring system to determine the consumption of these substances. Diabetic children are normally considered to constitute a group with a high consumption of sweeteners (European Commission, 1998. Report on Methodology for the Monitoring of Food Additives Intake across the European Union. Report of the Scientific Cooperation, Task 4.2 SCOOP/INT/REPORT/2. European Commission Directorate General III, Brussels.). A stepwise approach to the food additive intake in the general population had shown that three of the five authorised intense sweeteners (aspartame, saccharin and acesulfame K) are used at particularly high levels in sugar-free foods and are also very commonly utilised as table-top sweeteners. This paper presents the results of a food intake survey conducted in a group of French, insulin-dependent children in 1997, aimed at estimating the Theoretical Maximum Daily Intake (TMDI) for these three sweeteners and comparing this with the relevant ADI values. A 5-day diary questionnaire was used to estimate the intake of sugar-free, artificially sweetened foods and table-top sweeteners. When assessing the intake of each additive, all sugar-free products were assumed to be sweetened using a single sweetener at its maximum authorised level. This study was performed in five age groups, and based on the mean and 97.5th percentile of the distribution of consumption, demonstrated that it was unlikely that total exposure could rise above the ADI.

  18. Segmentation and leaf sequencing for intensity modulated arc therapy

    SciTech Connect

    Gladwish, Adam; Oliver, Mike; Craig, Jeff; Chen, Jeff; Bauman, Glenn; Fisher, Barbara; Wong, Eugene

    2007-05-15

    A common method in generating intensity modulated radiation therapy (IMRT) plans consists of a three step process: an optimized fluence intensity map (IM) for each beam is generated via inverse planning, this IM is then segmented into discrete levels, and finally, the segmented map is translated into a set of MLC apertures via a leaf sequencing algorithm. To date, limited work has been done on this approach as it pertains to intensity modulated arc therapy (IMAT), specifically in regards to the latter two steps. There are two determining factors that separate IMAT segmentation and leaf sequencing from their IMRT equivalents: (1) the intrinsic 3D nature of the intensity maps (standard 2D maps plus the angular component), and (2) that the dynamic multileaf collimator (MLC) constraints be met using a minimum number of arcs. In this work, we illustrate a technique to create an IMAT plan that replicates Tomotherapy deliveries by applying IMAT specific segmentation and leaf-sequencing algorithms to Tomotherapy output sinograms. We propose and compare two alternative segmentation techniques, a clustering method, and a bottom-up segmentation method (BUS). We also introduce a novel IMAT leaf-sequencing algorithm that explicitly takes leaf movement constraints into consideration. These algorithms were tested with 51 angular projections of the output leaf-open sinograms generated on the Hi-ART II treatment planning system (Tomotherapy Inc.). We present two geometric phantoms and 2 clinical scenarios as sample test cases. In each case 12 IMAT plans were created, ranging from 2 to 7 intensity levels. Half were generated using the BUS segmentation and half with the clustering method. We report on the number of arcs produced as well as differences between Tomotherapy output sinograms and segmented IMAT intensity maps. For each case one plan for each segmentation method is chosen for full Monte Carlo dose calculation (NumeriX LLC) and dose volume histograms (DVH) are calculated

  19. [Hospital infections caused by Pseudomonas aeruginosa. Significance in intensive therapy].

    PubMed

    Sidorenko, S V; Gel'fand, E B; Mamontova, O A

    1999-01-01

    The significance of P. aeruginosa as an agent of hospital infections in intensive care departments is determined by high prevalence of this microorganism, its natural and acquired resistance to antibiotics of various groups, and severity of the infection it induces. The resistance of P. aeruginosa to antibiotics is different in different regions. Among the strains isolated in Moscow in intensive care wards for newborns 9% were resistant to meropenem, 10% to amicacine, 15% to imipramine, 16% to cefepime, 37% to ceftasidime, 45% to piperacylline/tasobactam, 45% to ciprofloxacine, and 60% to gentamicin; 1.5% of these strains were resistant to all tested antibiotics. High prevalence of antibiotic resistance among P. aeruginosa impedes the choice of drugs for empirical antibiotic therapy and increases the significance of microbiological diagnosis. Even if an agent is sensitive to such antibiotics as semisynthetic penicillines and aminoglycosides, their use as monotherapy in infections caused by P. aeruginosa is ineffective. Carbapenemes, III- IV generations cefalosporines, and fluoroquinolones can be used as mono therapy.

  20. Intensity-modulated arc therapy: principles, technologies and clinical implementation

    NASA Astrophysics Data System (ADS)

    Yu, Cedric X.; Tang, Grace

    2011-03-01

    Intensity-modulated arc therapy (IMAT) was proposed by Yu (1995 Phys. Med. Biol. 40 1435-49) as an alternative to tomotherapy. Over more than a decade, much progress has been made. The advantages and limitations of the IMAT technique have also been better understood. In recent years, single-arc forms of IMAT have emerged and become commercially adopted. The leading example is the volumetric-modulated arc therapy (VMAT), a single-arc form of IMAT that delivers apertures of varying weights with a single-arc rotation that uses dose-rate variation of the treatment machine. With commercial implementation of VMAT, wide clinical adoption has quickly taken root. However, there remains a lack of general understanding for the planning of such arc treatments, as well as what delivery limitations and compromises are made. Commercial promotion and competition add further confusion for the end users. It is therefore necessary to provide a summary of this technology and some guidelines on its clinical implementation. The purpose of this review is to provide a summary of the works from the radiotherapy community that led to wide clinical adoption, and point out the issues that still remain, providing some perspective on its further developments. Because there has been vast experience in IMRT using multiple intensity-modulated fields, comparisons between IMAT and IMRT are also made in the review within the areas of planning, delivery and quality assurance.

  1. Factors associated with glycemic control in adult type 1 diabetes patients treated with insulin pump therapy.

    PubMed

    Matejko, Bartłomiej; Skupien, Jan; Mrozińska, Sandra; Grzanka, Małgorzata; Cyganek, Katarzyna; Kiec-Wilk, Beata; Malecki, Maciej T; Klupa, Tomasz

    2015-02-01

    Continuous subcutaneous insulin infusion (CSII) by insulin pump seems to improve glycemia and quality of life as compared to conventional insulin therapy in type 1 diabetes (T1DM). However, while many T1DM subjects achieve excellent glycemic control, some others cannot reach recommended goals. In a retrospective analysis, we searched for factors associated with glycemic control in T1DM patients treated with insulin pump therapy. Data from 192 patients (133 women and 59 men) treated with personal insulin pumps at the Department of Metabolic Diseases, University Hospital, Krakow, Poland were analyzed. Sources of information included medical records, memory read-outs from insulin pumps and data from glucose meters. Univariate, multivariate linear and logistic regression analysis for the association with hemoglobin A1c (HbA1c) level were performed. The mean age of the subjects was 28.9 (±11.2) years, the mean duration of T1DM-14.6 (±7.6) years, mean body mass index-23.5 (±3.1) kg/m2. The mean HbA1c level in the entire study group was 7.4% (57 mmol/mol). In the multivariate linear regression analysis, HbA1c correlated with the mean number of daily blood glucose measurements, number of hypoglycemic episodes per 100 blood glucose measurements, age at the examination, and continuous glucose monitoring system use. Multivariate logistic regression analysis for reaching the therapeutic target of HbA1c<7.0% (53 mmol/mol) showed that the independent predictors of achieving this goal included the same four variables. In a large clinical observation, we identified that patient-related and technological factors associated with glycemic control in adult pump-treated T1DM subjects.

  2. [Renal replacement therapy in Intensive Care Units in Catalonia (Spain)].

    PubMed

    Aguirre-Bermeo, H; Tomasa, T; Navas, A; Xirgu, J; Catalán-Ibars, R M; Morillas, J; Cuartero, M; Manciño, J M; Roglán, A

    2015-01-01

    To assess the indications, settings and techniques used in renal replacement therapy (RRT) in Intensive Care Units (ICUs). A prospective, multicenter observational study was carried out. Intensive Care Units. All patients admitted to ICUs during the two-month study period in 2011 who required RRT. None. Patient demographic characteristics, baseline clinical data, RRT technique and materials used. Thirty-three patients were analyzed. RRT was started within the first 24hours after ICU admission in 17 of the 33 patients (52%). At the start of RRT, 18% of the patients (n=6) presented grade R on the RIFLE acute kidney injury (AKI) scale. The most common disorder associated with AKI was multiple organ dysfunction syndrome (64%; n=21). At the start of RRT, most patients (76%; n=25) presented hemodynamic instability, while the remaining 24% (n=8) were considered hemodynamically stable. The most common RRT technique in hemodynamically stable patients was continuous renal replacement therapy (CRRT) (63%; n=5). CRRT was the technique of choice in all 25 of the hemodynamically unstable patients (100%). Anticoagulation was used in 55% (n=18) of the patients. In most cases (61%, n=20), RRT was administered through the right femoral vein. In 84% (n=28) of the patients, the ultrafiltration effluent flow rate was ≤ 35ml/kg/h. The ICU physicians in this study followed current RRT guidelines. CRRT was preferred over intermittent renal replacement therapy, regardless of patient hemodynamic status. Copyright © 2013 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

  3. Prone breast intensity modulated radiation therapy: 5-year results.

    PubMed

    Osa, Etin-Osa O; DeWyngaert, Keith; Roses, Daniel; Speyer, James; Guth, Amber; Axelrod, Deborah; Fenton Kerimian, Maria; Goldberg, Judith D; Formenti, Silvia C

    2014-07-15

    To report the 5-year results of a technique of prone breast radiation therapy delivered by a regimen of accelerated intensity modulated radiation therapy with a concurrent boost to the tumor bed. Between 2003 and 2006, 404 patients with stage I-II breast cancer were prospectively enrolled into 2 consecutive protocols, institutional trials 03-30 and 05-181, that used the same regimen of 40.5 Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5 Gy (total dose 48 Gy). All patients were treated after segmental mastectomy and had negative margins and nodal assessment. Patients were set up prone: only if lung or heart volumes were in the field was a supine setup attempted and chosen if found to better spare these organs. Ninety-two percent of patients were treated prone, 8% supine. Seventy-two percent had stage I, 28% stage II invasive breast cancer. In-field lung volume ranged from 0 to 228.27 cm(3), mean 19.65 cm(3). In-field heart volume for left breast cancer patients ranged from 0 to 21.24 cm(3), mean 1.59 cm(3). There was no heart in the field for right breast cancer patients. At a median follow-up of 5 years, the 5-year cumulative incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95% confidence interval [CI] 0.65%-1.04%). The 5-year cumulative incidence of regional recurrence was 0.53% (95% CI 0.41%-0.69%), and the 5-year overall cumulative death rate was 1.28% (95% CI 0.48%-3.38%). Eighty-two percent (95% CI 77%-85%) of patients judged their final cosmetic result as excellent/good. Prone accelerated intensity modulated radiation therapy with a concomitant boost results in excellent local control and optimal sparing of heart and lung, with good cosmesis. Radiation Therapy Oncology Group protocol 1005, a phase 3, multi-institutional, randomized trial is ongoing and is evaluating the equivalence of a similar dose and fractionation approach to standard 6-week radiation therapy with a

  4. Prone Breast Intensity Modulated Radiation Therapy: 5-Year Results

    SciTech Connect

    Osa, Etin-Osa O.; DeWyngaert, Keith; Roses, Daniel; Speyer, James; Guth, Amber; Axelrod, Deborah; Fenton Kerimian, Maria; Goldberg, Judith D.; Formenti, Silvia C.

    2014-07-15

    Purpose: To report the 5-year results of a technique of prone breast radiation therapy delivered by a regimen of accelerated intensity modulated radiation therapy with a concurrent boost to the tumor bed. Methods and Materials: Between 2003 and 2006, 404 patients with stage I-II breast cancer were prospectively enrolled into 2 consecutive protocols, institutional trials 03-30 and 05-181, that used the same regimen of 40.5 Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5 Gy (total dose 48 Gy). All patients were treated after segmental mastectomy and had negative margins and nodal assessment. Patients were set up prone: only if lung or heart volumes were in the field was a supine setup attempted and chosen if found to better spare these organs. Results: Ninety-two percent of patients were treated prone, 8% supine. Seventy-two percent had stage I, 28% stage II invasive breast cancer. In-field lung volume ranged from 0 to 228.27 cm{sup 3}, mean 19.65 cm{sup 3}. In-field heart volume for left breast cancer patients ranged from 0 to 21.24 cm{sup 3}, mean 1.59 cm{sup 3}. There was no heart in the field for right breast cancer patients. At a median follow-up of 5 years, the 5-year cumulative incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95% confidence interval [CI] 0.65%-1.04%). The 5-year cumulative incidence of regional recurrence was 0.53% (95% CI 0.41%-0.69%), and the 5-year overall cumulative death rate was 1.28% (95% CI 0.48%-3.38%). Eighty-two percent (95% CI 77%-85%) of patients judged their final cosmetic result as excellent/good. Conclusions: Prone accelerated intensity modulated radiation therapy with a concomitant boost results in excellent local control and optimal sparing of heart and lung, with good cosmesis. Radiation Therapy Oncology Group protocol 1005, a phase 3, multi-institutional, randomized trial is ongoing and is evaluating the equivalence of a similar dose and

  5. Influence Of Low Intensity Laser Therapy On Diabetic Polyneuropathy

    NASA Astrophysics Data System (ADS)

    Abdel-Raoof, N. A.; Elnhas, N. G.; Elsayed, I. M.

    2011-09-01

    Diabetic peripheral neuropathy is a consequence of diabetes-mediated impairment of blood flow, and resultant hypoxia of nerves that may develop within 10 years of the onset of diabetes in 40-50% of people with type 1 or type 2 diabetes. Low Intensity Laser Therapy (LILT) has been advocated for the treatment of chronic pain disorders as blood flow is an important determinant for pain relief. Comparing the effect of Helium-Neon Laser therapy versus Infrared laser therapy on blood vessels diameter and flow as well as level of sensation for neuropathy. Twenty diabetic patients suffering from neuropathy were enrolled in the study with age 45-55 years. They were assigned randomly into two equal groups in number; Group A underwent an application of He-Neon laser while Group B underwent an application of Infrared laser. Both groups received laser for 2 months. Blood flow velocity, and blood vessel diameter were investigated by using duplex Doppler ultrasound and peripheral neuropathy parameters were investigated by Semmes-Weinstein monofilament assessment. The results revealed that He-Neon laser as well as Infrared laser groups showed significant improvement in blood flow velocity, blood vessel diameter & neuropathy tested parameters after treatment but there was no significance difference between the two types of LILT. LILT is a safe, non-invasive and drug free method for improving blood flow & sensation in patients suffering from diabetic polyneuropathy in addition to preventing one of the most threatening microvascular complications of diabetes.

  6. Safety and efficacy of a glucagon-like peptide-1 receptor agonist added to basal insulin therapy versus basal insulin with or without a rapid-acting insulin in patients with type 2 diabetes: results of a meta-analysis.

    PubMed

    Wysham, Carol H; Lin, Jay; Kuritzky, Louis

    2017-05-01

    To consolidate the evidence from randomized controlled trials evaluating the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as add-on to basal insulin therapy in type 2 diabetes (T2D) patients. We searched the EMBASE® and NCBI PubMed (Medline) databases and relevant congress abstracts for randomized controlled trials evaluating the efficacy and safety of GLP-1 RAs as add-on to basal insulin compared with basal insulin with or without rapid-acting insulin (RAI) through 23 May 2016. The pooled data were analyzed using a random-effects meta-analysis model. A subanalysis was performed for trials investigating basal insulin plus GLP-1 RAs versus basal insulin plus RAI. Of the 2617 retrieved records, 19 randomized controlled trials enrolling 7,053 patients with T2D were included. Compared with basal insulin ± RAI, reduction in glycated hemoglobin (HbA1c) from baseline (difference in means: -0.48% [95% confidence interval (CI), -0.67 to -0.30]; p < 0.0001) and weight loss (-2.60 kg [95% CI, -3.32 to -1.89]; p < 0.0001) were significantly greater with basal insulin plus GLP-1 RA. The subanalysis similarly showed significant results for change in HbA1c from baseline and for weight loss, as well as a significantly lower risk of symptomatic hypoglycemia in patients treated with basal insulin plus GLP-1 RA versus basal insulin plus RAI (odds ratio, 0.52 [95% CI, 0.42 to 0.64]; p < 0.0001). Addition of GLP-1 RA to basal insulin provided improved glycemic control, led to weight reduction and similar hypoglycemia rates versus an intensified insulin strategy; however, symptomatic hypoglycemia rates were significantly lower when compared with a basal insulin plus RAI.

  7. Randomized trial comparing exercise therapy, alternating cold and hot therapy, and low intensity laser therapy for chronic lumbar muscle strain

    NASA Astrophysics Data System (ADS)

    Liu, Xiaoguang; Li, Jie; Liu, Timon Chengyi; Yuan, Jianqin; Luo, Qingming

    2008-12-01

    The purpose of this study was to compare the effects of exercise therapy, alternating cold and hot (ACH) therapy and low intensity laser (LIL) therapy in patients with chronic lumbar muscle strain (CLMS). Thirty-two patients were randomly allocated to four groups: exercise group, ACH group, LIL group, and combination group of exercise, ACH and LIL, eight in each group. Sixteen treatments were given over the course of 4 weeks. Lumbar muscle endurance, flexion and lateral flexion measures, visual analogue scale (VAS) and lumbar disability questionnaire (LDQ) were used in the clinical and functional evaluations before, immediately after, and 4 weeks after treatment. It was found that the values of endurance, VAS and LDQ in all groups were significantly improved from before to after treatment (P < 0.01). The combination group showed significantly larger reduction on pain level and functional disability than the other groups immediately and 4 weeks after treatment (P < 0.01). Pain level reduced significantly more in the ACH group than in the exercise group or the LIL group immediately and 4 weeks after treatment (P < 0.05). Lumbar muscle endurance and spinal ranges of motion in all groups were improved after treatment but there was no significant difference between any therapy groups. In conclusion, exercise therapy, ACH therapy and LIL therapy were effective in the treatment of CLMS. ACH therapy was more effective than exercise therapy or LIL therapy. The combination therapy of exercise, ACH and LIL had still better rehabilitative effects on CLMS.

  8. The effect of an education programme (MEDIAS 2 ICT) involving intensive insulin treatment for people with type 2 diabetes.

    PubMed

    Hermanns, Norbert; Kulzer, Bernhard; Maier, Berthold; Mahr, Marina; Haak, Thomas

    2012-02-01

    In a randomized, multi-centre trial, the effect of an education programme (MEDIAS 2 ICT) involving intensive insulin treatment for people with type 2 diabetes was compared with an established education programme as an active comparator condition (ACC). We investigated whether MEDIAS 2 ICT was non-inferior to ACC in overall glycaemic control. Secondary outcomes were the diabetes-related distress, diabetes knowledge, quality of life, self-care behavior, lipids, blood pressure and weight. 186 subjects were randomized. After a six month follow-up the mean HbA1c decrease was 0.37% (from 8.2±1.1% to 7.8±1.5%) in the ACC and 0.63% (from 8.5±1.5% to 7.9±1.2%) in MEDIAS 2 ICT. The mean difference between both groups was -0.26% (95% CI -0.63 to -0.14) in favor of MEDIAS 2 ICT. This result was within the predefined limit for non-inferiority. Diabetes-related distress was significantly more reduced in MEDIAS 2 ICT (-3.4±7.1) than in ACC (0.4±9.0; p=0.31). MEDIAS 2 ICT is as effective in lowering HbA1c as previously established education programmes, but showed superiority in reducing diabetes-related distress. MEDIAS 2 ICT provides an alternative for education of people with type 2 diabetes treated by multiple injection therapy. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  9. Comparison of intensity modulated x-ray therapy and intensity modulated proton therapy for selective subvolume boosting: a phantom study

    PubMed Central

    Flynn, R T; Barbee, D L; Mackie, T R; Jeraj, R

    2009-01-01

    Selective subvolume boosting can theoretically improve tumour control probability while maintaining normal tissue complication probabilities similar to those of uniform dose distributions. In this work the abilities of intensity modulated x-ray therapy (IMXT) and intensity modulated proton therapy (IMPT) to deliver boosts to multiple subvolumes of varying size and proximities are compared in a thorough phantom study. IMXT plans were created using the step-and-shoot (IMXT-SAS) and helical tomotherapy (IMXT-HT) methods. IMPT plans were created with the spot scanning (IMPT-SS) and distal gradient tracking (IMPT-DGT) methods. IMPT-DGT is a generalization of the distal edge tracking method designed to reduce the number of proton beam spots required to deliver non-uniform dose distributions relative to IMPT-SS. The IMPT methods were delivered over both 180° and 360° arcs. The IMXT-SAS and IMPT-SS methods least and most optimally satisfied the non-uniform dose prescriptions, respectively. The IMPT delivery methods reduced normal tissue integral dose by a factor of about two relative to the IMXT delivery methods, regardless of the delivery arc. The IMPT-DGT method reduced the number of proton beam spots by a factor of about three relative to the IMPT-SS method. PMID:17921573

  10. 3D treatment planning and intensity-modulated radiation therapy.

    PubMed

    Purdy, J A

    1999-10-01

    Three-dimensional (3D) image-based treatment planning and new delivery technologies have spurred the implementation of external beam radiation therapy techniques, in which the high-dose region is conformed much more closely to the target volume than previously possible, thus reducing the volume of normal tissues receiving a high dose. This form of external beam irradiation is referred to as 3D conformal radiation therapy (3DCRT). 3DCRT is not just an add-on to the current radiation oncology process; it represents a radical change in practice, particularly for the radiation oncologist. Defining target volumes and organs at risk in 3D by drawing contours on CT images on a slice-by-slice basis, as opposed to drawing beam portals on a simulator radiograph, can be challenging, because radiation oncologists are generally not well trained in cross-sectional imaging. Currently, the 3DCRT approach will increase the time and effort required by physicians inexperienced with 3D treatment planning. Intensity-modulated radiation therapy (IMRT) is a more advanced form of 3DCRT, but there is considerable developmental work remaining. The instrumentation and methods used for IMRT quality assurance procedures and testing are not well established. Computer optimization cost functions are too simplistic, and thus time-consuming. Subjective plan evaluation by the radiation oncologist is still the norm. In addition, many fundamental questions regarding IMRT remain unanswered. For example, the radiobiophysical consequences of altered time-dose-fraction are unknown. Also, the fact that there is much greater dose heterogeneity for both the target and normal critical structures with IMRT compared to traditional irradiation techniques challenges current radiation oncology planning principles. However, this new process of planning and treatment delivery shows significant potential for improving the therapeutic ratio. In addition, while inefficient today, these systems, when fully developed

  11. Effect of sensor-augmented insulin pump therapy and automated insulin suspension vs standard insulin pump therapy on hypoglycemia in patients with type 1 diabetes: a randomized clinical trial.

    PubMed

    Ly, Trang T; Nicholas, Jennifer A; Retterath, Adam; Lim, Ee Mun; Davis, Elizabeth A; Jones, Timothy W

    2013-09-25

    Hypoglycemia is a critical obstacle to the care of patients with type 1 diabetes. Sensor-augmented insulin pump with automated low-glucose insulin suspension has the potential to reduce the incidence of major hypoglycemic events. To determine the incidence of severe and moderate hypoglycemia with sensor-augmented pump with low-glucose suspension compared with standard insulin pump therapy. A randomized clinical trial involving 95 patients with type 1 diabetes, recruited from December 2009 to January 2012 in Australia. Patients were randomized to insulin pump only or automated insulin suspension for 6 months. The primary outcome was the combined incidence of severe (hypoglycemic seizure or coma) and moderate hypoglycemia (an event requiring assistance for treatment). In a subgroup, counterregulatory hormone responses to hypoglycemia were assessed using the hypoglycemic clamp technique. Of the 95 patients randomized, 49 were assigned to the standard-pump (pump-only) therapy and 46 to the low-glucose suspension group. The mean (SD) age was 18.6 (11.8) years; duration of diabetes, 11.0 (8.9) years; and duration of pump therapy, 4.1 (3.4) years. The baseline rate of severe and moderate hypoglycemic events in the pump-only group was 20.7 vs 129.6 events per 100 patient months in the low-glucose suspension group. After 6 months of treatment, the event rates decreased from 28 to 16 in the pump-only group vs 175 to 35 in the low-glucose suspension group. The adjusted incidence rate per 100 patient-months was 34.2 (95% CI, 22.0-53.3) for the pump-only group vs 9.5 (95% CI, 5.2-17.4) for the low-glucose suspension group. The incidence rate ratio was 3.6 (95% CI, 1.7-7.5; P <.001). There was no change in glycated hemoglobin in either group: mean, 7.4 (95% CI, 7.2-7.6) to 7.4 (95% CI, 7.2-7.7) in the pump-only group vs mean, 7.6 (95%, CI, 7.4-7.9) to 7.5 (95% CI, 7.3-7.7) in the low-glucose suspension group. Counterregulatory hormone responses to hypoglycemia were not changed

  12. Transitioning insulin pump therapy from the outpatient to the inpatient setting: a review of 6 years' experience with 253 cases.

    PubMed

    Cook, Curtiss B; Beer, Karen A; Seifert, Karen M; Boyle, Mary E; Mackey, Patricia A; Castro, Janna C

    2012-09-01

    We reviewed the care of a large cohort of patients with diabetes mellitus on insulin pump therapy who required an inpatient stay. Records were reviewed of patients hospitalized between January 1, 2006, and December 31, 2011. A total of 136 patients using insulin pumps had 253 hospitalizations. Mean (standard deviation) patient age was 55 (16) years, diabetes duration was 29 (15) years, and pump duration was 6 (5) years. Insulin pump therapy was continued in 164 (65%) hospitalizations. Adherence to core process measures improved over time: by 2011, 100% of cases had an endocrinology consultation, 100% had the required insulin pump order set completed, and 94% had documentation of the signed agreement specifying patient responsibilities for continued use of the technology while hospitalized. Documentation of the insulin pump flow sheet also increased but could still be located in only 64% of cases by the end of 2011. Mean glucose was not significantly different among patients who remained on insulin pump therapy compared to those for whom it was discontinued (p > .1), but episodes of severe hyperglycemia (>300 mg/dl) and hypoglycemia (<40 mg/dl) were significantly less common among pump users. No pump site infections, mechanical pump failures, or episodes of diabetic ketoacidosis were observed among patients remaining on therapy. With appropriate patient selection and usage guidelines, most patients using insulin pumps can safely have their therapy transitioned to the inpatient setting. Further study is needed to determine whether this approach can be translated to other hospital settings. © 2012 Diabetes Technology Society.

  13. Transitioning Insulin Pump Therapy from the Outpatient to the Inpatient Setting: A Review of 6 Years' Experience with 253 Cases

    PubMed Central

    Cook, Curtiss B.; Beer, Karen A.; Seifert, Karen M.; Boyle, Mary E.; Mackey, Patricia A.; Castro, Janna C.

    2012-01-01

    Background We reviewed the care of a large cohort of patients with diabetes mellitus on insulin pump therapy who required an inpatient stay. Methods Records were reviewed of patients hospitalized between January 1, 2006, and December 31, 2011. Results A total of 136 patients using insulin pumps had 253 hospitalizations. Mean (standard deviation) patient age was 55 (16) years, diabetes duration was 29 (15) years, and pump duration was 6 (5) years. Insulin pump therapy was continued in 164 (65%) hospitalizations. Adherence to core process measures improved over time: by 2011, 100% of cases had an endocrinology consultation, 100% had the required insulin pump order set completed, and 94% had documentation of the signed agreement specifying patient responsibilities for continued use of the technology while hospitalized. Documentation of the insulin pump flow sheet also increased but could still be located in only 64% of cases by the end of 2011. Mean glucose was not significantly different among patients who remained on insulin pump therapy compared to those for whom it was discontinued (p > .1), but episodes of severe hyperglycemia (>300 mg/dl) and hypoglycemia (<40 mg/dl) were significantly less common among pump users. No pump site infections, mechanical pump failures, or episodes of diabetic ketoacidosis were observed among patients remaining on therapy. Conclusions With appropriate patient selection and usage guidelines, most patients using insulin pumps can safely have their therapy transitioned to the inpatient setting. Further study is needed to determine whether this approach can be translated to other hospital settings. PMID:23063024

  14. Access of children and adolescents with type 1 diabetes to insulin pump therapy has greatly increased in France since 2001.

    PubMed

    Sulmont, V; Lassmann-Vague, V; Guerci, B; Hanaire, H; Leblanc, H; Leutenegger, E; Mihaileanu, M; Tubiana-Rufi, N

    2011-02-01

    Insulin pump therapy is an emerging option in the management of type 1 diabetes (T1D), but it often remains unused. For this reason, in 2007, a French national survey was carried out to update the frequency of insulin pump use in the paediatric population compared with a previous survey done in 2001. The present survey was performed in hospital departments involved in paediatric diabetes management (n = 67) and in adult departments involved in adolescent diabetes management (n = 113). The number of T1D children (age < 18 years) treated in each department, with or without the use of an insulin pump, and the number of insulin pump therapies initiated during the previous year were collected. A total of 60 paediatric and 28 adult centres responded, involving 9073 T1D children and adolescents (93% in paediatric departments). Of these patients, 1461 (16%) were treated by insulin pump, 89% of which were managed in paediatric centres. However, pump use was more frequent in adult than in paediatric centres (32% versus 18%, respectively). Also, 38% of insulin pumps were initiated during the year prior to the survey. In addition, in 2001, 140 children were treated with insulin pump in 13 paediatric centres (versus 56 centres in 2007). The number of centres using insulin pump therapy for diabetic children and the number of children treated by insulin pump were increased fourfold and 10-fold, respectively, from 2001 to 2007, indicating greater access to pump therapy in the French paediatric population. The present survey is still ongoing to evaluate the decision-making criteria that influence the initiation of insulin pump therapy in T1D paediatric patients. Copyright © 2010. Published by Elsevier Masson SAS.

  15. Effectiveness of a serious game for medical education on insulin therapy: a pilot study.

    PubMed

    Diehl, Leandro A; Gordan, Pedro A; Esteves, Roberto Z; Coelho, Izabel C M M

    2015-10-01

    We report the preliminary assessment of InsuOnline©, a serious game designed for medical education on insulin therapy. We conducted a pilot study with 41 undergraduate medical students and Internal Medicine residents to assess the educational effectiveness of InsuOnline©, as compared to a traditional educational activity (lecture, cases discussion). Knowledge, skills and beliefs on insulin therapy were evaluated by a questionnaire applied before, immediately after, and 3 months after both interventions. Mean knowledge/skills score was improved from 68% to 89% in traditional education group (n = 23; p < 0.001), and from 61% to 90% in game group (n = 18; p < 0.001). After 3 months, mean score decreased (to 80% in traditional education group, and to 78% in game group; p < 0.001 for both) but remained significantly higher than at baseline in both groups (p < 0.001 for both). Although mean score was lower in game group than in traditional education group at baseline (p = 0.04), no difference remained between groups either immediately or 3 months post-intervention. Score increment was better with the game (29%) than with traditional education (21%; p = 0.04). Beliefs improved in the game group only. InsuOnline© is at least as effective as a traditional educational activity for medical education on insulin therapy, and it can a good option for large-scale continuing medical education on diabetes.

  16. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial.

    PubMed

    Craft, Suzanne; Baker, Laura D; Montine, Thomas J; Minoshima, Satoshi; Watson, G Stennis; Claxton, Amy; Arbuckle, Matthew; Callaghan, Maureen; Tsai, Elaine; Plymate, Stephen R; Green, Pattie S; Leverenz, James; Cross, Donna; Gerton, Brooke

    2012-01-01

    regions and insulin-minimized progression. No treatment-related severe adverse events occurred. These results support longer trials of intranasal insulin therapy for patients with amnestic mild cognitive impairment and patients with AD. Trial Registration  clinicaltrials.gov Identifier: NCT00438568.

  17. Computerized intensive insulin dosing can mitigate hypoglycemia and achieve tight glycemic control when glucose measurement is performed frequently and on time

    PubMed Central

    2009-01-01

    Introduction Control of blood glucose (BG) in critically ill patients is considered important, but is difficult to achieve, and often associated with increased risk of hypoglycemia. We examined the use of a computerized insulin dosing algorithm to manage hyperglycemia with particular attention to frequency and conditions surrounding hypoglycemic events. Methods This is a retrospective analysis of adult patients with hyperglycemia receiving intravenous (IV) insulin therapy from March 2006 to December 2007 in the intensive care units of 2 tertiary care teaching hospitals. Patients placed on a glycemic control protocol using the Clarian GlucoStabilizer™ IV insulin dosing calculator with a target range of 4.4-6.1 mmol/L were analyzed. Metrics included time to target, time in target, mean blood glucose ± standard deviation, % measures in hypoglycemic ranges <3.9 mmol/L, per-patient hypoglycemia, and BG testing interval. Results 4,588 ICU patients were treated with the GlucoStabilizer to a BG target range of 4.4-6.1 mmol/L. We observed 254 severe hypoglycemia episodes (BG <2.2 mmol/L) in 195 patients, representing 0.1% of all measurements, and in 4.25% of patients or 0.6 episodes per 1000 hours on insulin infusion. The most common contributing cause for hypoglycemia was measurement delay (n = 170, 66.9%). The median (interquartile range) time to achieve the target range was 5.9 (3.8 - 8.9) hours. Nearly all (97.5%) of patients achieved target and remained in target 73.4% of the time. The mean BG (± SD) after achieving target was 5.4 (± 0.52) mmol/L. Targeted blood glucose levels were achieved at similar rates with low incidence of severe hypoglycemia in patients with and without diabetes, sepsis, renal, and cardiovascular disease. Conclusions Glycemic control to a lower glucose target range can be achieved using a computerized insulin dosing protocol. With particular attention to timely measurement and adjustment of insulin doses the risk of hypoglycemia experienced

  18. Computerized intensive insulin dosing can mitigate hypoglycemia and achieve tight glycemic control when glucose measurement is performed frequently and on time.

    PubMed

    Juneja, Rattan; Roudebush, Corbin P; Nasraway, Stanley A; Golas, Adam A; Jacobi, Judith; Carroll, Joni; Nelson, Deborah; Abad, Victor J; Flanders, Samuel J

    2009-01-01

    Control of blood glucose (BG) in critically ill patients is considered important, but is difficult to achieve, and often associated with increased risk of hypoglycemia. We examined the use of a computerized insulin dosing algorithm to manage hyperglycemia with particular attention to frequency and conditions surrounding hypoglycemic events. This is a retrospective analysis of adult patients with hyperglycemia receiving intravenous (IV) insulin therapy from March 2006 to December 2007 in the intensive care units of 2 tertiary care teaching hospitals. Patients placed on a glycemic control protocol using the Clarian GlucoStabilizer IV insulin dosing calculator with a target range of 4.4-6.1 mmol/L were analyzed. Metrics included time to target, time in target, mean blood glucose +/- standard deviation, % measures in hypoglycemic ranges <3.9 mmol/L, per-patient hypoglycemia, and BG testing interval. 4,588 ICU patients were treated with the GlucoStabilizer to a BG target range of 4.4-6.1 mmol/L. We observed 254 severe hypoglycemia episodes (BG <2.2 mmol/L) in 195 patients, representing 0.1% of all measurements, and in 4.25% of patients or 0.6 episodes per 1000 hours on insulin infusion. The most common contributing cause for hypoglycemia was measurement delay (n = 170, 66.9%). The median (interquartile range) time to achieve the target range was 5.9 (3.8 - 8.9) hours. Nearly all (97.5%) of patients achieved target and remained in target 73.4% of the time. The mean BG (+/- SD) after achieving target was 5.4 (+/- 0.52) mmol/L. Targeted blood glucose levels were achieved at similar rates with low incidence of severe hypoglycemia in patients with and without diabetes, sepsis, renal, and cardiovascular disease. Glycemic control to a lower glucose target range can be achieved using a computerized insulin dosing protocol. With particular attention to timely measurement and adjustment of insulin doses the risk of hypoglycemia experienced can be minimized.

  19. Vitamin E induces regular structure and stability of human insulin, more intense than vitamin D3.

    PubMed

    Soleymani, Hossein; Saboury, Ali A; Moosavi-Movahedi, Ali A; Rahmani, Fatemeh; Maleki, Javad; Yousefinejad, Saeid; Maghami, Parvaneh

    2016-12-01

    Changes in human environment and lifestyle over the last century have caused a dramatic increase in the occurrence of diabetes. Research of past decades illustrated that vitamin D and E have a key role in the improvement of diabetes by reducing oxidative stress, protein glycosylation, insulin resistance and also improving beta cell function. Binding properties and conformational changes of human insulin upon interaction with vitamins D3 and E (α-tocopherol) were investigated by spectroscopy, differential scanning calorimetry (DSC) and molecular dynamic simulation. Tyrosine fluorescence quenching studies indicates changes in the human insulin conformation in the presence of vitamins. Binding constants of vitamins D3 and E for human insulin were determined to be 2.7 and 1.5 (×10(-5)M(-1)) and the corresponding average numbers of binding sites were determined to be 1.3 and 1.2, respectively. Far- and near-UV circular dichroism studies showed that vitamin E can significantly change the secondary and tertiary structures of human insulin via an increase in the content of α-helix structure. Results of DSC showed that both vitamins D3 and E stabilize the structure of human insulin. Molecular dynamic simulation results indicated that vitamin D3 decreases the helical and strand structural contents of human insulin, but vitamin E stabilizes more regular secondary structures such as helical and strand structural contents as shown by experimental results.

  20. Effect of nutrition and atherogenic index on the occurrence and intensity of insulin resistance.

    PubMed

    Ostrowska, Lucyna; Witczak, Katarzyna; Adamska, Edyta

    2013-01-01

    Diet is one of the factors that can stimulate genetic predisposition and, in consequence, lead to insulin resistance. An adequate supply of nutrients and energy-rich diet as well as increased physical activity are the most effective methods to prevent metabolic disorders. The objective of this study was to determine whether there are any associations between nutrition and the occurrence of insulin resistance. The study included 143 individuals. Fasting glucose and insulin levels were measured and the HOMA-IR index was calculated for each patient. Nondiabetic patients were divided into the study and control groups. We conducted anthropometric measurements (body mass, height, and waist circumference), biochemical analysis (fasting glucose and insulin), and dietary interview. We observed a negative correlation between the percentage of sucrose in the diet and the HOMA-IR value, and a positive correlation between the percentage of protein intake and the HOMA-IR value. Moreover, there was a significantly higher intake of lactose in men without insulin resistance compared with those with insulin resistance. The results encourage to conduct further, more detailed research involving a larger group of patients to better understand associations between dietary content and insulin resistance.

  1. The psychiatric aspects of cardiac intensive therapy: a review.

    PubMed

    Bowden, P

    1975-05-01

    The post cardiotomy state is typically delirious and although organic factors are important it is multi-determined. Cerebral ischaemia has been implicated in the development of psychological disorder after resuscitation but longer term neurotic disorders also occur. Affective disturbances, particularly depression, are associated with the coronary care experience. The following conditions are directly related to an increased incidence of psychological disorder: age, loss of sleep, sensory deprivation, stressful experiences, pre-operative morbidity (both physical and mental), the severity of both surgical trauma and the post-operative medical state. For both the staff who administer intensive therapy and the patient who receives it there are unique psychological hazards, the management of which depends largely on mutual understanding and support.

  2. [Dosimetric verification of the intensity modulated radiation therapy].

    PubMed

    Zhang, Yuhai; Gao, Yang

    2010-05-01

    To research the method of dosimetric verification of the intensity modulated radiation therapy (IMRT). The IMRT treatment plans were designed by Eclipse TPS and were implemented in Varian ClinacIX LA with 6MV X-ray. The absolute point doses were measured using a PTW 0.6 cc ion chamber with UNIDOS E dosimeter and the planes dose distributions were measured using PTW 2D-Array ion chamber in the phantom. The error between the measured dose and calculated dose in the interesting points was less than 3%. The points passed ratio was more than 90% in gamma analysis method (3 mm 13%) about the plane dose distribution verification. The method of dosimetric verification of IMRT is reliable and efficient in the implementation.

  3. Palliative intensity modulated radiation therapy for symptomatic adrenal metastasis.

    PubMed

    Mod, H; Patel, V

    2013-05-01

    Metastasis to the adrenal glands is quite common; especially from melanomas, breast, lung, renal and gastro-intestinal tumours. The most common tumour found in the adrenals in post mortem series is a metastatic tumour; incidence ranging from 13 to 27%. The diagnosis of adrenal metastasis is now more common and easier due to staging and subsequent follow up with Computed tomography /Magnetic resonance imaging and or positron emission tomography-computed tomography imaging studies. Most of the times these metastatic lesions are clinically occult and those that do have clinical symptoms complain of pain, nausea, vomiting and early satiety. We irradiated a patient of non small cell lung cancer with adrenal metastasis with palliative Intensity Modulated Radiation Therapy and achieved a good response in terms of pain relief, stable disease and no side effects of the treatment.

  4. Basic studies on intravascular low-intensity laser therapy

    NASA Astrophysics Data System (ADS)

    Liu, Timon Cheng-Yi; Duan, Rui; Wang, Shuang-Xi; Liu, Jiang; Cui, Li-Ping; Jin, Hua; Liu, Song-Hao

    2006-09-01

    Intravascular low intensity laser therapy (ILILT) was originally put forward in USA in 1982, but popularized in Russia in 1980s and in China in 1990s, respectively. A randomized placebo-controlled study has shown ILILT clinical efficacy in patients suffering from rheumatoid arthritis. As Chinese therapeutic applications of ILILT were the most widely in the world, its basic research, such as intracellular signal transduction research, blood research in vitro, animal blood research in vivo, human blood research in vivo and traditional Chinese medicine research, was also very progressive in China. Its basic studies will be reviewed in terms of the biological information model of photobiomodulation in this paper. ILILT might work in view of its basic studies, but the further randomized placebo-controlled trial and the further safety research should be done.

  5. Start of insulin therapy in patients with type 2 diabetes mellitus promotes the influx of macrophages into subcutaneous adipose tissue.

    PubMed

    Jansen, H J; Stienstra, R; van Diepen, J A; Hijmans, A; van der Laak, J A; Vervoort, G M M; Tack, C J

    2013-12-01

    Insulin therapy in patients with type 2 diabetes mellitus is accompanied by weight gain characterised by an increase in abdominal fat mass. The expansion of adipose tissue mass is generally paralleled by profound morphological and inflammatory changes. We hypothesised that the insulin-associated increase in fat mass would also result in changes in the morphology of human subcutaneous adipose tissue and in increased inflammation, especially when weight gain was excessive. We investigated the effects of weight gain on adipocyte size, macrophage influx, and mRNA expression and protein levels of key inflammatory markers within the adipose tissue in patients with type 2 diabetes mellitus before and 6 months after starting insulin therapy. As expected, insulin therapy significantly increased body weight. At the level of the subcutaneous adipose tissue, insulin treatment led to an influx of macrophages. When comparing patients gaining no or little weight with patients gaining >4% body weight after 6 months of insulin therapy, both subgroups displayed an increase in macrophage influx. However, individuals who had gained weight had higher protein levels of monocyte chemoattractant protein-1, TNF-α and IL-1β after 6 months of insulin therapy compared with those who had not gained weight. We conclude that insulin therapy in patients with type 2 diabetes mellitus improved glycaemic control but also induced body weight gain and an influx of macrophages into the subcutaneous adipose tissue. In patients characterised by a pronounced insulin-associated weight gain, the influx of macrophages into the adipose tissue was accompanied by a more pronounced inflammatory status. ClinicalTrials.gov: NCT00781495. The study was funded by European Foundation for the Study of Diabetes and the Dutch Diabetes Research Foundation.

  6. Insulin Therapy Improves Adeno-Associated Virus Transduction of Liver and Skeletal Muscle in Mice and Cultured Cells.

    PubMed

    Carrig, Sean; Bijjiga, Enoch; Wopat, Mitchell J; Martino, Ashley T

    2016-11-01

    Adeno-associated virus (AAV) gene transfer is a promising treatment for genetic abnormalities. Optimal AAV vectors are showing success in clinical trials. Gene transfer to skeletal muscle and liver is being explored as a potential therapy for some conditions, that is, α1-antitrypsin (AAT) disorder and hemophilia B. Exploring approaches that enhance transduction of liver and skeletal muscle, using these vectors, is beneficial for gene therapy. Regulating hormones as an approach to improve AAV transduction is largely unexplored. In this study we tested whether insulin therapy improves liver and skeletal muscle gene transfer. In vitro studies demonstrated that the temporary coadministration (2, 8, and 24 hr) of insulin significantly improves AAV2-CMV-LacZ transduction of cultured liver cells and differentiated myofibers, but not of lung cells. In addition, there was a dose response related to this improved transduction. Interestingly, when insulin was not coadministered with the virus but given 24 hr afterward, there was no increase in the transgene product. Insulin receptor gene (INSR) expression levels were increased 5- to 13-fold in cultured liver cells and differentiated myofibers when compared with lung cells. Similar INSR gene expression profiles occurred in mouse tissues. Insulin therapy was performed in mice, using a subcutaneously implanted insulin pellet or a high-carbohydrate diet. Insulin treatment began just before intramuscular delivery of AAV1-CMV-schFIX or liver-directed delivery of AAV8-CMV-schFIX and continued for 28 days. Both insulin augmentation therapies improved skeletal muscle- and liver-directed gene transduction in mice as seen by a 3.0- to 4.5-fold increase in human factor IX (hFIX) levels. The improvement was observed even after the insulin therapy ended. Monitoring insulin showed that insulin levels increased during the brief period of rAAV delivery and during the entire insulin augmentation period (28 days). This study demonstrates

  7. Early Detection of Infusion Set Failure During Insulin Pump Therapy in Type 1 Diabetes.

    PubMed

    Cescon, Marzia; DeSalvo, Daniel J; Ly, Trang T; Maahs, David M; Messer, Laurel H; Buckingham, Bruce A; Doyle, Francis J; Dassau, Eyal

    2016-11-01

    Insulin infusion set failure resulting in prolonged hyperglycemia or diabetic ketoacidosis can occur with pump therapy in type 1 diabetes. Set failures are frequently characterized by variable and unpredictable patterns of increasing glucose values despite increased insulin infusion. Early detection may minimize the risk of prolonged hyperglycemia, an important consideration for automated insulin delivery and closed-loop applications. A novel algorithm designed to alert the patient to the onset of infusion set failure was developed based upon continuous glucose sensor values and insulin delivered from an insulin pump. The method was calibrated on 12 weeks of infusion set wear without failures recorded by 4 patients in ambulatory conditions and prospectively validated on 18 weeks of infusion set wear with and without failures belonging to 9 other subjects in ambulatory conditions. The algorithm, evaluated retrospectively, identified a failure 2.52 ± 1.91 days ahead of the actual event as recorded by the clinical team, corresponding to 50% sensitivity, 66% specificity and 55% accuracy. If set failure alarms had been activated in real time, the average time >180 mg/dl would be reduced from 82.7 ± 40.9 hours/week/subject (without alarm) to 58.8 ± 31.1 hours/week/subject (with alarm), corresponding to a potential 29% reduction in time spent >180mg/dl. The proposed method for early detection of infusion set failure based on glucose sensor and insulin data demonstrated favorable results on retrospective data and may be implemented as an additional safeguard in a future fully automated closed-loop system. © 2016 Diabetes Technology Society.

  8. Effect of deferoxamine therapy on insulin resistance in end-stage renal disease patients with iron overload.

    PubMed

    Alnahal, Alsayed Ahmed; Tahan, Magdy; Fathy, Aymen; Fathy, Tamer

    2014-07-01

    Cardiovascular diseases are a common cause of morbidity and mortality in subjects on regular hemodialysis. Insulin resistance is associated with increased cardiovascular diseases. Elevated serum ferritin is linked to insulin resistance. The aim of this work is to study the effect of desferoxamine therapy on some of the cardiovascular risk factors such as fasting insulin, B-cell function, insulin resistance, glucose, HbA1c%, lipid profile, blood pressure and carotid intima media thickness (CAIMT). Our study included ten subjects on regular hemodialysis with elevated serum ferritin. We measured the fasting serum glucose, HbA1c%, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), fasting lipid profile, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and complete blood count (CBC). Statistically significant decreases in fasting serum insulin, B-cell function, glucose, HbA1c% and HOMA-IR were noted after deferoxamine therapy. No statistically significant difference was seen with regard to lipid profile, blood pressure and CAIMT. Iron overload increases insulin resistance and cardiovascular risk in hemodialysis subjects. Correction of anemia by iron therapy should keep target ferritin as per guidelines. Further studies are needed to determine the safest ferritin level among hemodialysis subjects.

  9. Low Intensity Laser Therapy Applied in the Healing of Wounds

    NASA Astrophysics Data System (ADS)

    Kahn, Fred; Matthews, Jeffrey

    2009-06-01

    Objective: The aim of this study was to determine the outcomes of Low Intensity Laser Therapy (LILT) on wound healing for patients presenting with pain, compromised neurological and physical function and tissue damage associated with vascular/diabetic ulcerations of the lower extremity. Methods: A retrospective case review of six patients treated with LILT (GaAlAs SLD, 660 nm, 750 mW, 3.6 J/cm2; GaAlAs SLD, 840 nm, 1,500 mW, 6.48 J/cm2; GaAlAs laser, 830 nm, 75 mW, 270 J/cm2) was conducted of clinical features including pain, measured by visual analogue scale (VAS), motor function, measured by range of motion (ROM) and visual outcome, measured by wound dimensions for six patients (n = 6; 5 males, 1 female; age = 67.83 years). Results: Significant progress with regard to alleviation of pain (ΔVAS = -5), improvements in motor function (ΔROM = +40%), epithelialization (wound closure rate = 3%/week) and complete wound closure was achieved. No recurrence of pathology at least one month post cessation of therapy was evident (x¯% reduction in wound area = 100%). Conclusions: LILT achieved consistent, effective and clear endpoints, was cost effective, created no adverse effects and ultimately led to the salvage of extremities.

  10. Pitfalls in normalization for intensity-modulated radiation therapy planning

    SciTech Connect

    Williams, Greg . E-mail: greg.williams@hci.utah.edu; Tobler, Matt; Leavitt, Dennis

    2005-01-01

    Three-dimensional (3D) treatment planning often involves complex combinations of beam energies, treatment fields, and beam modifying devices. Even when a plan is devised that meets many treatment-planning objectives, limitations in the planner's ability to further adjust beam characteristics may require the radiation dose prescription to be normalized to an isodose level that best covers the target volume. While these normalizations help meet the volume coverage goals, they also result in adjustment of the dose delivered to the normal tissues and must be carefully evaluated. Intensity-modulated radiation therapy (IMRT) treatment planning allows combinations of complex dose patterns, in order to achieve the desired treatment planning goals. These dose patterns are created by defining a set of treatment planning objectives and then allowing the treatment planning computer to create intensity patterns, through the use of moving multileaf collimation that will meet the requested goals. Often, when an IMRT treatment plan is created that meets many of the treatment planning goals but falls short of volume coverage requirements, the planner is tempted to apply normalization principles similar to those utilized with 3D treatment planning. Again, these normalizations help meet the volume coverage goals, but unlike 3D planning situations, may result in avoidable delivery of additional doses to the normal tissues. The focus of this study is to evaluate the effect of application of normalization for IMRT planning using multiple patient situations. Recommendations would favor re-optimization over normalization in most planning situations.

  11. Robust PET-guided intensity-modulated radiation therapy

    SciTech Connect

    Li, H.; Bissonnette, J. P.; Purdie, T.; Chan, T. C. Y.

    2015-08-15

    Purpose: Functional image guided intensity-modulated radiation therapy has the potential to improve cancer treatment quality by basing treatment parameters such as heterogeneous dose distributions information derived from imaging. However, such heterogeneous dose distributions are subject to imaging uncertainty. In this paper, the authors develop a robust optimization model to design plans that are desensitized to imaging uncertainty. Methods: Starting from the pretreatment fluorodeoxyglucose-positron emission tomography scans, the authors use the raw voxel standard uptake values (SUVs) as input into a series of intermediate functions to transform the SUV into a desired dose. The calculated desired doses were used as an input into a robust optimization model to generate beamlet intensities. For each voxel, the authors assume that the true SUV cannot be observed but instead resides in an interval centered on the nominal (i.e., observed) SUV. Then the authors evaluated the nominal and robust solutions through a simulation study. The simulation considered the effect of the true SUV being different from the nominal SUV on the quality of the treatment plan. Treatment plans were compared on the metrics of objective function value and tumor control probability (TCP). Results: Computational results demonstrate the potential for improvements in tumor control probability and deviation from the desired dose distribution compared to a nonrobust model while maintaining acceptable tissue dose. Conclusions: Robust optimization can help design treatment plans that are more stable in the presence of image value uncertainties.

  12. Insulin therapy contributes to the increased risk of colorectal cancer in diabetes patients: a meta-analysis

    PubMed Central

    2013-01-01

    Background Recent epidemiological studies suggest that treatment with insulin may promote cancer growth. The present systematic review and meta-analysis of published observational studies was conducted to assess the risk of cancer during treatment with insulin. Materials and methods A compressive search was conducted through MEDLINE, PubMed, Web of Science, EMBASE, and Chinese Biomedical Literature databases (CBM). Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated with a random-effects model. Results A total of four studies with one case-controls study and three cohort studies comparing the insulin therapy and colorectal cancer susceptibility were identified. When all four studies were analyzed, the summary RRs were 1.61 (95% CI = 1.18–1.35) in a random-effects model for individuals with insulin therapy, compared with individuals without insulin therapy, which suggests a statistically significant association between insulin use and colorectal cancer. Conclusions Our findings provides the evidence that insulin therapy may contribute to the risk of colorectal cancer. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9339731010859509 PMID:24175949

  13. Flexible eating and flexible insulin dosing in patients with diabetes: Results of an intensive self-management course.

    PubMed

    Lowe, J; Linjawi, S; Mensch, M; James, K; Attia, J

    2008-06-01

    To evaluate the outcomes of an established programme to teach patients to match their insulin dose to their carbohydrate intake. A prospective observational study in Australia (Newcastle, NSW) of 137 consecutive patients with type 1 (n=82) or type 2 diabetes (n=55) over two successive years. Four educational principles were used to teach intensive insulin management and diabetes self-care skills including: carbohydrate counting and insulin dose adjustment, exercise, appropriate treatment of hypoglycaemia and hyperglycaemia, managing sickness, problem solving, communication with health professionals, goal setting, and the importance of support. Outcomes included changes at 4 and 12 months in HbA1c, self-efficacy measured by a diabetes empowerment scale (DES), diabetes specific quality of life (ADDQoL), and problem solving. Both intention to treat and efficacy analyses were performed. Diabetes-related quality of life and diabetes problem solving skills improved significantly. Excluding 16 people who failed to adopt intensive insulin management and 24 who started with an HbA1c less than 7%, intention to treat analysis showed the average HbA1c fell from 8.7% initially to 8.1% at 12 months and the number of people with an HbA1c of less than 8% rose from 67 (48.9%) before the program to 86 (62.8%) afterwards. An intensive diabetes self-management program led to improvements in HbA1c, empowerment, and quality of life that were largely sustained at 1 year. This is all the more remarkable given that the intervention was once only, entailed no long-term follow-up, and took place in normal clinical operations.

  14. Supporting patients with type 1 diabetes using continuous subcutaneous insulin infusion therapy: Difficulties, disconnections, and disarray.

    PubMed

    Perry, Lin; James, Steven; Gallagher, Robyn; Dunbabin, Janet; Steinbeck, Katharine; Lowe, Julia

    2017-08-01

    Use of continuous subcutaneous insulin infusion therapy in type 1 diabetes management is high. However, the incorporation of this technology into self-care is not without challenges, and the support of an appropriately skilled health care team is recommended. This study aimed to examine the support context for patients using continuous subcutaneous insulin infusion therapy from the health care professional perspective, as well as contextual influences for health care professionals and their patients. This ethnographic qualitative study was undertaken in New South Wales, Australia. Recruitment occurred using a snowball sampling technique, beginning with members of an established diabetes service group. Data were collected through the use of semistructured interviews undertaken by telephone and analysed using thematic analysis. Data were obtained from 26 interviews with staff from diverse professional backgrounds. An overarching theme of difficulties, disconnections, and disarray emerged, with findings indicating that participants perceived difficulties in relation to shortages of health care professional continuous subcutaneous insulin infusion-related expertise, and disconnected and disarrayed service structures and process, with barriers to access to these devices. Individual health care professionals were left to manage somehow or opted not to engage with related care. Findings provide insights from health care professionals' perspectives into the complexity of providing support for patients using continuous subcutaneous insulin infusion therapy across diverse contexts, and provide a platform for further research and service development. The need for consistent and coordinated care, and the infrastructure to facilitate this, flags an opportunity to drive integration of care and teamworking across as well as within settings and disciplines. © 2017 John Wiley & Sons, Ltd.

  15. 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

  16. Comparison of one-year costs of type 2 diabetes treatment with insulin glargine or insulin detemir in a basal supported oral therapy (BOT) in Germany.

    PubMed

    Pscherer, S; Dietrich, E S; Dippel, F-W; Neilson, A R

    2010-02-01

    A one-year cost analysis comparing basal insulin analogues glargine (IG, Lantus) versus detemir (ID, Levemir) in combination with oral antidiabetic drugs (basal supported oral therapy; BOT) in insulin naive Type 2 diabetes patients in Germany based on the results of a randomized controlled clinical trial (RCT). The trial demonstrated equivalent treatment efficacy. Total direct diabetes treatment costs were estimated from the perspective of the German statutory health insurance (SHI) for the time horizon of one-year. Simulated resources included medication (insulin, oral antidiabetic drugs) and consumable items (needles, blood glucose test strips and lancets). Initial and final insulin doses per kg body weight and proportion of patients with once/twice daily insulin injection were taken from the above mentioned RCT. Unit costs were taken from official German price lists and sources. Deterministic-(DTA) and probabilistic sensitivity analyses (PSA) on resource use and unit costs were performed to test robustness of the results. Average annual treatment costs per patient (base case) were euro 849 for glargine and euro 1,334 for detemir resulting in cost savings of euro 486 per patient per year (36%). Costs of insulins were euro 469 (IG) and euro 746 (ID). Costs of consumable items amounted at euro 380 (IG) and euro 588 (ID) respectively. Sensitivity analyses confirmed the findings in favor of insulin glargine. PSA results found cost savings ranging from euro 429 to euro 608 (5th/95th percentiles). The current model estimated that insulin glargine was associated with lower annual treatment costs of euro 486 (36%) compared to the use of insulin detemir while the same glycemic control is expected to be achieved.

  17. The effects of black cohosh therapies on lipids, fibrinogen, glucose and insulin.

    PubMed

    Spangler, Leslie; Newton, Katherine M; Grothaus, Louis C; Reed, Susan D; Ehrlich, Kelly; LaCroix, Andrea Z

    2007-06-20

    Black cohosh (Actaea racemosa) is an herb commonly used to treat menopausal symptoms. Little is known about its effect on other physiologic parameters that could result in untoward events. This study examines the effect of black cohosh on lipids, fibrinogen, glucose and insulin. Three hundred and fifty-one, 45-55 years old, peri or post-menopausal women experiencing vasomotor symptoms participated in a 3-month, double blind trial with randomization to: (1) black cohosh (160 mg daily); (2) multibotanical including black cohosh (200 mg daily); (3) multibotanical plus soy diet counseling; (4) conjugated equine estrogen .625 mg, with or without medroxyprogesterone acetate 2.5mg daily, for women with or without a uterus, respectively; (5) placebo. Baseline and month 3 total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol (calculated), triglyceride, insulin, glucose, and fibrinogen serum concentrations were measured in 310 women. Baseline information was also collected on medical history, demographic characteristics, and diet. There were no statistically significant differences in the adjusted mean change from baseline to 3 months between the herbal groups and placebo in total cholesterol, LDL, HDL, triglycerides, glucose, and insulin. Adjusted fibrinogen levels appear to increase in the multibotanical treatment group in comparison with the other herbal groups and placebo overall (P = .02), but there was no statistically significant difference in the pairwise test against placebo (P = .11). Black cohosh containing therapies had no demonstrable effects on lipids, glucose, insulin or fibrinogen.

  18. Insulin therapy in burn patients does not contribute to hepatic triglyceride production.

    PubMed Central

    Aarsland, A; Chinkes, D L; Sakurai, Y; Nguyen, T T; Herndon, D N; Wolfe, R R

    1998-01-01

    Lipid kinetics were studied in six severely burned patients who were treated with a high dose of exogenous insulin plus glucose to promote protein metabolism. The patients were 20+/-2-yr-old (SD) with 63+/-8% total body surface area burned. They were studied in a randomized order (a) in the fed state on the seventh day of a control period (C) of continuous high-carbohydrate enteral feeding alone, and (b) on the seventh day of enteral feeding plus exogenous insulin (200 pmol/h = 28 U/h) with extra glucose given as needed to avoid hypoglycemia (I+G). Despite a glucose delivery rate approximately 100% in excess of energy requirements, the following lipid parameters were unchanged: (a) total hepatic VLDL triglyceride (TG) secretion rate (0.165+/-0.138 [C] vs. 0.154+/- 0.138 mmol/kg . d-1 [I+G]), (b) plasma TG concentration (1.58+/-0.66 [C] vs. 1. 36+/-0.41 mmol/liter [I+G]), and (c) plasma VLDL TG concentration (0. 68+/-0.79 [C] vs. 0.67+/- 0.63 mmol/liter [I+G]). Instead, the high-carbohydrate delivery in conjunction with insulin therapy increased the proportion of de novo-synthesized palmitate in VLDL TG from 13+/-5% (C) to 34+/-14% (I+G), with a corresponding decreased amount of palmitate from lipolysis. In association with the doubling of the secretion rate of de novo-synthesized fatty acid (FA) in VLDL TG during insulin therapy (P > 0.5), the relative amount of palmitate and stearate increased from 35+/-5 to 44+/-8% and 4+/-1 to 7+/-2%, respectively, in VLDL TG, while the relative concentration of oleate and linoleate decreased from 43+/-5 to 37+/-6% and 8+/-4% to 2+/-2%, respectively. A 15-fold increase in plasma insulin concentration did not change the rate of release of FA into plasma (8.22+/-2.86 [C] vs. 8.72+/-6.68 mmol/kg.d-1 [I+G]. The peripheral release of FA represents a far greater potential for hepatic lipid accumulation in burn patients than the endogenous hepatic fat synthesis, even during excessive carbohydrate intake in conjunction with insulin

  19. Clinical recommendations in the management of the patient with type 1 diabetes on insulin pump therapy in the perioperative period: a primer for the anaesthetist.

    PubMed

    Partridge, H; Perkins, B; Mathieu, S; Nicholls, A; Adeniji, K

    2016-01-01

    Insulin pump therapy is increasingly common in patients with type 1 diabetes. Many of these patients will require surgery at some point in their lifetime. Few doctors will have experience of managing these patients, and little evidence exists to assist in the development of guidelines for patients with insulin pump therapy, undergoing surgery.It is clear that during emergency surgery insulin pump therapy is not appropriate and should be discontinued, but patients undergoing some elective surgery can and should continue insulin pump therapy, without any adverse effect on their blood sugar control, or on the outcome of their surgery. Individual hospitals need to formalize guidance on the management of patients receiving continuous subcutaneous insulin therapy, to allow patients the choice to continue their therapy during surgery. This expert opinion presents anaesthetists with a suggested clinical framework to help facilitate continued insulin pump therapy, during elective surgery and into the postoperative period.

  20. Are patients with type 2 diabetes reluctant to start insulin therapy? An examination of the scope and underpinnings of psychological insulin resistance in a large, international population.

    PubMed

    Polonsky, William H; Hajos, Tibor R S; Dain, Marie-Paule; Snoek, Frank J

    2011-06-01

    To examine the scope and underpinnings of psychological insulin resistance (PIR) across eight Western nations, with special attention to the potential influence of beliefs about insulin and broader patient beliefs regarding medications and diabetes. A total of 1400 subjects with insulin-naïve, type 2 diabetes across eight nations completed an online survey. The survey assessed willingness to start insulin, beliefs about insulin and current medications, and diabetes-related emotional distress. The majority of respondents were male (59.3%), mean age was 51.6 years and mean diabetes duration was 6.1 years. A total of 17.2% reported they would be unwilling to start insulin (the PIR group), while 34.7% were ambivalent and 48.1% indicated they would be willing to do so. Marked differences by country were apparent, with PIR ranging from 5.9% (Spain) to 37.3% (Italy). Both unwilling and ambivalent patients reported significantly more negative (p < 0.001; p < 0.05) and fewer positive beliefs (p < 0.001; p < 0.01) about starting insulin, more negative feelings about their current medications (p < 0.01, p < 0.001), and more diabetes-related distress (p < 0.001; p < 0.05) than willing patients. Unwilling patients also reported significantly more negative (p < 0.05) and fewer positive beliefs (p < 0.001) about starting insulin than ambivalent patients. These are the first data demonstrating the prevalence of PIR across Western nations. PIR is strongly linked to positive and negative insulin beliefs, and may also reflect a broader discomfort with medications and with diabetes in general. Of note, however, PIR is a marker of behavioral intent only; it is not known whether this predicts actual behavior at the time when insulin is prescribed. When addressing patients who are reluctant to initiate insulin therapy, clinicians may find it valuable to inquire about their beliefs about insulin and their current medications.

  1. Combined therapy with insulin and growth hormone in 17 patients with type-1 diabetes and growth disorders.

    PubMed

    Zucchini, Stefano; Iafusco, Dario; Vannelli, Silvia; Rabbone, Ivana; Salzano, Giuseppina; Pozzobon, Gabriella; Maghnie, Mohamad; Cherubini, Valentino; Bizzarri, Carla; Bonfanti, Riccardo; D'Annunzio, Giuseppe; Lenzi, Lorenzo; Maggio, Maria Cristina; Marigliano, Marco; Scaramuzza, Andrea; Tumini, Stefano; Iughetti, Lorenzo

    2014-01-01

    Combined growth hormone (GH) and insulin therapy is rarely prescribed by pediatric endocrinologists. We investigated the attitude of Italian physicians to prescribing that therapy in the case of short stature and type-1 diabetes (T1DM). A questionnaire was sent and if a patient was identified, data on growth and diabetes management were collected. Data from 42 centers (84%) were obtained. Of these, 29 centers reported that the use of combined therapy was usually avoided. A total of 17 patients were treated in 13 centers (GH was started before T1DM onset in 9 patients and after the onset of T1DM in 8). Height SDS patterns during GH therapy in the 11 patients affected by GH deficiency ranged from -0.3 to +3.1 SDS. In the 8 diabetic patients in whom GH was added subsequently, mean insulin dose increased during the first 6 months of therapy from 0.7 ± 0.2 to 1.0 ± 0.2 U/kg (p = 0.004). HbA1c was unchanged during the first 6 months of combined therapy. Most Italian physicians do not consider prescribing the combined GH-insulin therapy in diabetic children with growth problems. However, the results of the 17 patients identified would confirm that the combined therapy was feasible and only caused mild insulin resistance. GH therapy was effective in promoting growth in most patients and did not affect diabetes metabolic control.

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

    PubMed

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

    2017-06-01

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

  3. Dosimetrically Triggered Adaptive Intensity Modulated Radiation Therapy for Cervical Cancer

    SciTech Connect

    Lim, Karen; Stewart, James; Kelly, Valerie; Xie, Jason; Brock, Kristy K.; Moseley, Joanne; Cho, Young-Bin; Fyles, Anthony; Lundin, Anna; Rehbinder, Henrik; Löf, Johan; Jaffray, David A.; Milosevic, Michael

    2014-09-01

    Purpose: The widespread use of intensity modulated radiation therapy (IMRT) for cervical cancer has been limited by internal target and normal tissue motion. Such motion increases the risk of underdosing the target, especially as planning margins are reduced in an effort to reduce toxicity. This study explored 2 adaptive strategies to mitigate this risk and proposes a new, automated method that minimizes replanning workload. Methods and Materials: Thirty patients with cervical cancer participated in a prospective clinical study and underwent pretreatment and weekly magnetic resonance (MR) scans over a 5-week course of daily external beam radiation therapy. Target volumes and organs at risk (OARs) were contoured on each of the scans. Deformable image registration was used to model the accumulated dose (the real dose delivered to the target and OARs) for 2 adaptive replanning scenarios that assumed a very small PTV margin of only 3 mm to account for setup and internal interfractional motion: (1) a preprogrammed, anatomy-driven midtreatment replan (A-IMRT); and (2) a dosimetry-triggered replan driven by target dose accumulation over time (D-IMRT). Results: Across all 30 patients, clinically relevant target dose thresholds failed for 8 patients (27%) if 3-mm margins were used without replanning. A-IMRT failed in only 3 patients and also yielded an additional small reduction in OAR doses at the cost of 30 replans. D-IMRT assured adequate target coverage in all patients, with only 23 replans in 16 patients. Conclusions: A novel, dosimetry-triggered adaptive IMRT strategy for patients with cervical cancer can minimize the risk of target underdosing in the setting of very small margins and substantial interfractional motion while minimizing programmatic workload and cost.

  4. Commissioning of Peacock System for intensity-modulated radiation therapy.

    PubMed

    Saw, C B; Ayyangar, K M; Thompson, R B; Zhen, W; Enke, C A

    2001-01-01

    The Peacock System was introduced to perform tomographic intensity-modulated radiation therapy (IMRT). Commissioning of the Peacock System included the alignment of the multileaf intensity-modulating collimator (MIMiC) to the beam axis, the alignment of the RTA device for immobilization, and checking the integrity of the CRANE for indexing the treatment couch. In addition, the secondary jaw settings, couch step size, and transmission through the leaves were determined. The dosimetric data required for the CORVUS planning system were divided into linear accelerator-specific and MIMiC-specific. The linear accelerator-specific dosimetric data were relative output in air, relative output in phantom, percent depth dose for a range of field sizes, and diagonal dose profiles for a large field size. The MIMiC-specific dosimetric data were the in-plane and cross-plane dose profiles of a small and a large field size to derive the penumbra fit. For each treatment unit, the Beam Utility software requires the data be entered into the CORVUS planning system in modular forms. These modules were treatment unit information, angle definition, configuration, gantry and couch angles range, dosimetry, results, and verification plans. After the appropriate machine data were entered, CORVUS created a dose model. The dose model was used to create known simple dose distribution for evaluation using the verification tools of the CORVUS. The planned doses for phantoms were confirmed using an ion chamber for point dose measurement and film for relative dose measurement. The planning system calibration factor was initially set at 1.0 and will be changed after data on clinical cases are acquired. The treatment unit was released for clinical use after the approval icon was checked in the verification plans module.

  5. 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.

  6. [Medium-term results of a Day Hospital insulin therapy program for patients with type 2 diabetes mellitus].

    PubMed

    Quirós, Carmen; Amor, Antonio J; de Hollanda, Ana M; Yago, Gemma; Ara, Pilar; Conget, Ignacio

    2014-03-20

    The profile of the patient with type 2 diabetes mellitus (DM2) who requires insulin therapy is very diverse as are the results of this intervention and short/middle-term patient management. We evaluated the midterm results of an outpatient program starting insulin therapy with≥2 insulin injections/day in terms of metabolic control in different groups of patients. We analyzed prospectively 131 patients with DM2, without previous insulin treatment, who were prescribed treatment with≥2 insulin injections/day and who were enrolled in a specific ambulatory program in order to start insulin therapy in a Day Hospital for 6 months. The initial glycosylated hemoglobin (HbA1c) was 11.3 (2.3) % and decreased to 6.3 (1.4) % in 6 months, with HbA1c<7% in 72.5% of them. The group of recently diagnosed patients (<3 months, symptomatic severe hyperglycemia, D-group) were younger (57.1 [10.8] vs 64.2 [12.1] years; P<.01) and had a higher starting HbA1c (12.1 [1.8] vs 10.5 [2.5] %; P<.001) than patients included in the program for oral antidiabetic drugs' failure (F-group). At the end of the program 50% of D-group patients did not need insulin (6.3% on F-group [P<.001]). There were no significant differences in either of 2 groups at study ends according to the final treatment scheme. Counselling patients with DM2 to start insulin with more than one injection per day in Day Hospital setting achieves and maintains a good metabolic control in the medium term in different patient profiles. Among symptomatic and recently diagnosed patients, insulin therapy can be stopped in 50% of them at the medium term. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  7. Intensification of insulin therapy in patients with type 2 diabetes mellitus: An algorithm for basal-bolus therapy

    PubMed Central

    2012-01-01

    The incidence of diabetes mellitus is projected to continue to increase worldwide over the next 20 years leading to increased costs in the management of the disease and its associated co-morbidities. Insulin replacement is one of many treatment options that can help to bring about near normoglycemia in the patient with type 2 diabetes mellitus (T2DM). Glycemic control as close to normoglycemia as possible can help to reduce the risk of microvascular and macrovascular complications, yet less than one-half of patients with T2DM achieve glycemic targets as recommended by practice guidelines. The purpose of this review is to provide guidance to primary care physicians for the initiation and intensification of basal-bolus insulin therapy in patients with T2DM. Two treatment algorithms that can be both patient- and physician-driven are proposed: a stepwise approach and a multiple daily injections approach. Evidence shaping the two approaches will be discussed alongside management issues that surround the patient treated with insulin: hypoglycemia, weight gain, patient education, and quality of life. PMID:22822902

  8. High Intensity Laser Therapy (HILT) versus TENS and NSAIDs in low back pain: clinical study

    NASA Astrophysics Data System (ADS)

    Zati, Allesandro; Fortuna, Damiano; Valent, A.; Filippi, M. V.; Bilotta, Teresa W.

    2004-09-01

    Low back pain, caused by lumbar disc herniation, is prevalently treated with a conservative approach. In this study we valued the efficacy of High Intensity Laser Therapy (HILT), compared with accepted therapies such as TENS and NSAIDs. Laser therapy obtained similar results in the short term, but better clinical effect over time than TENS and NSAIDs. In conclusion high intensity laser therapy appears to be a interesting new treatment, worthy of further research.

  9. Intensity-Modulated Radiation Therapy in Childhood Ependymoma

    SciTech Connect

    Schroeder, Thomas M.; Chintagumpala, Murali; Okcu, M. Fatih; Chiu, J. Kam; Teh, Bin S.; Woo, Shiao Y.; Paulino, Arnold C.

    2008-07-15

    Purpose: To determine the patterns of failure after intensity-modulated radiation therapy (IMRT) for localized intracranial ependymoma. Methods and Materials: From 1994 to 2005, 22 children with pathologically proven, localized, intracranial ependymoma were treated with adjuvant IMRT. Of the patients, 12 (55%) had an infratentorial tumor and 14 (64%) had anaplastic histology. Five patients had a subtotal resection (STR), as evidenced by postoperative magnetic resonance imaging. The clinical target volume encompassed the tumor bed and any residual disease plus margin (median dose 54 Gy). Median follow-up for surviving patients was 39.8 months. Results: The 3-year overall survival rate was 87% {+-} 9%. The 3-year local control rate was 68% {+-} 12%. There were six local recurrences, all in the high-dose region of the treatment field. Median time to recurrence was 21.7 months. Of the 5 STR patients, 4 experienced recurrence and 3 died. Patients with a gross total resection had significantly better local control (p = 0.024) and overall survival (p = 0.008) than those with an STR. At last follow-up, no patient had developed visual loss, brain necrosis, myelitis, or a second malignancy. Conclusions: Treatment with IMRT provides local control and survival rates comparable with those in historic publications using larger treatment volumes. All failures were within the high-dose region, suggesting that IMRT does not diminish local control. The degree of surgical resection was shown to be significant for local control and survival.

  10. Monte Carlo dose verification for intensity-modulated arc therapy

    NASA Astrophysics Data System (ADS)

    Li, X. Allen; Ma, Lijun; Naqvi, Shahid; Shih, Rompin; Yu, Cedric

    2001-09-01

    Intensity-modulated arc therapy (IMAT), a technique which combines beam rotation and dynamic multileaf collimation, has been implemented in our clinic. Dosimetric errors can be created by the inability of the planning system to accurately account for the effects of tissue inhomogeneities and physical characteristics of the multileaf collimator (MLC). The objective of this study is to explore the use of Monte Carlo (MC) simulation for IMAT dose verification. The BEAM/DOSXYZ Monte Carlo system was implemented to perform dose verification for the IMAT treatment. The implementation includes the simulation of the linac head/MLC (Elekta SL20), the conversion of patient CT images and beam arrangement for 3D dose calculation, the calculation of gantry rotation and leaf motion by a series of static beams and the development of software to automate the entire MC process. The MC calculations were verified by measurements for conventional beam settings. The agreement was within 2%. The IMAT dose distributions generated by a commercial forward planning system (RenderPlan, Elekta) were compared with those calculated by the MC package. For the cases studied, discrepancies of over 10% were found between the MC and the RenderPlan dose calculations. These discrepancies were due in part to the inaccurate dose calculation of the RenderPlan system. The computation time for the IMAT MC calculation was in the range of 20-80 min on 15 Pentium-III computers. The MC method was also useful in verifying the beam apertures used in the IMAT treatments.

  11. [The intensive care gallbladder as shock organ: symptoms and therapy].

    PubMed

    Rimkus, C; Kalff, J C

    2013-03-01

    Acute acalculous cholecystitis (AAC) represents a severe disease in critically ill patients. The pathogenesis of acute necroinflammatory gallbladder disease is multifactorial and intensive care unit (ICU) patients show multiple risk factors. In addition AAC is difficult to diagnose because of the vague physical and non-specific technical findings. Only the combination of clinical and technical findings including the challenging physical examination of critically ill patients, laboratory results and ultrasound or computed tomography (CT) scan, will lead to the diagnosis. The condition of AAC has a rapid progress to gallbladder necrosis, gangrene and perforation and these complications are reflected in the high morbidity and mortality rates, therefore, therapy should be promptly initiated. If there are no clinical contraindications for an operative approach cholecystectomy is the definitive treatment and both open and laparoscopic procedures have been used. In unstable, critically ill patients percutaneous cholecystostomy should be immediately performed. In addition, transpapillary endoscopic drainage is also possible if there are contraindications for percutaneous cholecystostomy. Patients who fail to improve or deteriorate following interventional drainage should be reconsidered for cholecystectomy. Due to the fact that more than 90 % of patients treated with percutaneous cholecystostomy showed no recurrence of symptoms during a period of more than 1 year, it is still unclear if percutaneous cholecystostomy is the definitive treatment of AAC for unstable patients or if delayed cholecystectomy is still necessary.

  12. Intensity modulated radiation therapy for breast cancer: current perspectives

    PubMed Central

    Buwenge, Milly; Cammelli, Silvia; Ammendolia, Ilario; Tolento, Giorgio; Zamagni, Alice; Arcelli, Alessandra; Macchia, Gabriella; Deodato, Francesco; Cilla, Savino; Morganti, Alessio G

    2017-01-01

    Background Owing to highly conformed dose distribution, intensity modulated radiation therapy (IMRT) has the potential to improve treatment results of radiotherapy (RT). Postoperative RT is a standard adjuvant treatment in conservative treatment of breast cancer (BC). The aim of this review is to analyze available evidence from randomized controlled trials (RCTs) on IMRT in BC, particularly in terms of reduction of side effects. Methods A literature search of the bibliographic database PubMed, from January 1990 through November 2016, was performed. Only RCTs published in English were included. Results Ten articles reporting data from 5 RCTs fulfilled the selection criteria and were included in our review. Three out of 5 studies enrolled only selected patients in terms of increased risk of toxicity. Three studies compared IMRT with standard tangential RT. One study compared the results of IMRT in the supine versus the prone position, and one study compared standard treatment with accelerated partial breast IMRT. Three studies reported reduced acute and/or late toxicity using IMRT compared with standard RT. No study reported improved quality of life. Conclusion IMRT seems able to reduce toxicity in selected patients treated with postoperative RT for BC. Further analyses are needed to better define patients who are candidates for this treatment modality. PMID:28293119

  13. Mobile telecare system for intensive insulin treatment and patient education. First applications for newly diagnosed type 1 diabetic patients.

    PubMed

    Ładyzyński, P; Wójcicki, J M; Krzymień, J; Foltyński, P; Migalska-Musiał, K; Tracz, M; Karnafel, W

    2006-11-01

    The aim of the work was to develop and to evaluate the clinical efficiency of a mobile telecare system implementing teleconsultations based on the continuous transmission of patient-collected data directly to the physician and to the clinic. The developed TeleMed system consists of the patients' and the diabetologist's mobile units, the diabetologist's clinic and home workstations and the clinical server. The evaluation of the system was performed on a group of 13 newly diagnosed type 1 diabetic patients, during a single-arm study with 3-days run-in period, including a one-day intensive educational program, and 3-week study period, when the intensive insulin treatment was conducted without visits of patients to the clinic. The MBG dropped from 7.2 +/- 1.7 mmol/L before the study to 6.1 +/- 1.0 mmol/L in the third week of the study (P = 0.02) and the J-index from 30.2+/-19.2 to 19.7+/-7.7 (P = 0.04). Hemoglobin A1c decreased from 11.8 +/- 3.3% to 8.6 +/- 1.2% (P = 0.0002) in one month. The total daily insulin dose declined from 39.9 +/- 8.5 U to 20.0 +/- 9.6 U (P = 0.000006). The number of hypoglycemia episodes per patient per day decreased by 66% (P = 0.08) and the number of hyperglycemia episodes was reduced by 47% (P < 0.0001). The TeleMed facilitates not only efficient realization of the intensive insulin treatment but also successful remote patient training and education. No formal patient satisfaction study was done. However, some of the findings indicate that the application of the developed system increases patient self-confidence and quality of life.

  14. Psychological and metabolic improvement after an outpatient teaching program for functional intensified insulin therapy (FIT).

    PubMed

    Langewitz, W; Wössmer, B; Iseli, J; Berger, W

    1997-09-01

    To be the master of their disease and not its slave is the ultimate goal of many patients with diabetes. Intensified functional insulin therapy (FIT) helps to establish this goal by an intensive patient education: each patient learns in five small-group sessions how s/he reacts to standardized challenges of glucose homeostasis (e.g. 24 h fasting; physical exercise; various carbohydrate loads). We investigated in 43 patients with long-standing diabetes type 1 (mean age: 33 +/- 10 years; mean duration of diabetes: 15 +/- 10 years) whether FIT improves quality of life, influences metabolic control and doctor-patient relationship. The following instruments were used: diabetes specific quality of life questionnaire (DQOL), hierarchical distance and cohesion between doctor and patient (FAST), anxiety and depression (HAD). Pre and post intervention values were compared with paired t-tests. HbA1c and number of hypoglycaemic episodes were also assessed 1 year after FIT and 1 year prior to FIT. Metabolic control was improved: HbA1c in the year before FIT: 6.72 +/- 1.35; 4 months before FIT: 6.61 +/- 1.46; 4 months after FIT: 6.29 +/- 1.09 (P < 0.05 compared to 4 months before FIT); 1 year after FIT: 6.46 +/- 1.12 (n.s. compared to 1 year before FIT). Dissatisfaction with life decreases from 33.3 +/- 8.0 to 28.5 +/- 7.7 (P < 0.001). Moments free of disease-specific strain increase from 74.3 +/- 13.9 to 78.1 +/- 16.1 (P = 0.07). Hierarchical distance between doctor and patient decreases from 1.1 +/- to 0.6 +/- 0.8 (P < 0.001), cohesion increases from 9.3 +/- 1.5 to 9.9 +/- 1.1 (P < 0.001). Anxiety and depression both decreases significantly: anxiety, 6.5 +/- 3.3-->4.6 +/- 3.2 (P < 0.001); depression, 2.7 +/- 2.5-->1.5 +/- 1.6 (P < 0.001). The number of patients with severe hypoglycaemic episodes (level 4) decreases from five (11.6%) to one (2.3%) after intervention (P < 0.05). In conclusion, FIT enhances quality of life in diabetic individuals. It helps to establish a less

  15. Improved Glycemic Control in Intensively Treated Adult Subjects with Type 1 Diabetes Using Insulin Guidance Software

    PubMed Central

    Bookout, Tevin R.; McFann, Kim K.; Kelly, William C.; Beatson, Christie; Ellis, Samuel L.; Gutin, Raymond S.; Gottlieb, Peter A.

    2008-01-01

    Abstract Background Management of type 1 diabetes could be significantly improved with the availability of computerized insulin algorithms for home use. Methods This was a 1-year open label randomized control trial involving 123 adult subjects with type 1 diabetes (hemoglobin A1c values 7.5–11%) assigned to either the insulin guidance software (ACCU-CHEK® [Roche, Indianapolis, IN] Advisor) for personal data assistant (experimental group) or the control group. The primary aim of the study was to see if subjects using insulin dosing advisor software will improve glucose control over 1 year. The principal end point was an improvement in A1c at 6 and 12 months by ≥0.4%. Results Baseline demographics were similar in the two groups. Mean A1c was 8.54 ± 0.11% in the control group and 8.42 ± 0.11% (P = 0.4265) in the experimental group. The mean A1c was significantly lower from 3 to 12 months in the experimental group (P < 0.02). A1c reduction of ≥0.6% was maintained at 12 months in the experimental group. Also, a significantly higher number of subjects achieved A1c <7.5% in the experimental group from 3 to 9 months. Within target range glycemia (70–150 mg/dL) was higher in the experimental group at 3–9 months without any change in insulin dose or weight. Above target range glycemia was lower in the experimental group throughout the study. Frequency of testing per day was higher in the experimental group. Nocturnal hypoglycemia was not different between groups; however, the experimental group experienced more severe hypoglycemic events. Conclusions This is the first report that shows improved glycemic control can be maintained over 12 months in patients with type 1 diabetes by using Advisor with no change in insulin dose and weight. PMID:18715213

  16. Intensive Versus Distributed Aphasia Therapy: A Nonrandomized, Parallel-Group, Dosage-Controlled Study.

    PubMed

    Dignam, Jade; Copland, David; McKinnon, Eril; Burfein, Penni; O'Brien, Kate; Farrell, Anna; Rodriguez, Amy D

    2015-08-01

    Most studies comparing different levels of aphasia treatment intensity have not controlled the dosage of therapy provided. Consequently, the true effect of treatment intensity in aphasia rehabilitation remains unknown. Aphasia Language Impairment and Functioning Therapy is an intensive, comprehensive aphasia program. We investigated the efficacy of a dosage-controlled trial of Aphasia Language Impairment and Functioning Therapy, when delivered in an intensive versus distributed therapy schedule, on communication outcomes in participants with chronic aphasia. Thirty-four adults with chronic, poststroke aphasia were recruited to participate in an intensive (n=16; 16 hours per week; 3 weeks) versus distributed (n=18; 6 hours per week; 8 weeks) therapy program. Treatment included 48 hours of impairment, functional, computer, and group-based aphasia therapy. Distributed therapy resulted in significantly greater improvements on the Boston Naming Test when compared with intensive therapy immediately post therapy (P=0.04) and at 1-month follow-up (P=0.002). We found comparable gains on measures of participants' communicative effectiveness, communication confidence, and communication-related quality of life for the intensive and distributed treatment conditions at post-therapy and 1-month follow-up. Aphasia Language Impairment and Functioning Therapy resulted in superior clinical outcomes on measures of language impairment when delivered in a distributed versus intensive schedule. The therapy progam had a positive effect on participants' functional communication and communication-related quality of life, regardless of treatment intensity. These findings contribute to our understanding of the effect of treatment intensity in aphasia rehabilitation and have important clinical implications for service delivery models. © 2015 American Heart Association, Inc.

  17. Simultaneous beam geometry and intensity map optimization in intensity-modulated radiation therapy.

    PubMed

    Lee, Eva K; Fox, Tim; Crocker, Ian

    2006-01-01

    In current intensity-modulated radiation therapy (IMRT) plan optimization, the focus is on either finding optimal beam angles (or other beam delivery parameters such as field segments, couch angles, gantry angles) or optimal beam intensities. In this article we offer a mixed integer programming (MIP) approach for simultaneously determining an optimal intensity map and optimal beam angles for IMRT delivery. Using this approach, we pursue an experimental study designed to (a) gauge differences in plan quality metrics with respect to different tumor sites and different MIP treatment planning models, and (b) test the concept of critical-normal-tissue-ring--a tissue ring of 5 mm thickness drawn around the planning target volume (PTV)--and its use for designing conformal plans. Our treatment planning models use two classes of decision variables to capture the beam configuration and intensities simultaneously. Binary (0/1) variables are used to capture "on" or "off" or "yes" or "no" decisions for each field, and nonnegative continuous variables are used to represent intensities of beamlets. Binary and continuous variables are also used for each voxel to capture dose level and dose deviation from target bounds. Treatment planning models were designed to explicitly incorporate the following planning constraints: (a) upper/lower/mean dose-based constraints, (b) dose-volume and equivalent-uniform-dose (EUD) constraints for critical structures, (c) homogeneity constraints (underdose/overdose) for PTV, (d) coverage constraints for PTV, and (e) maximum number of beams allowed. Within this constrained solution space, five optimization strategies involving clinical objectives were analyzed: optimize total intensity to PTV, optimize total intensity and then optimize conformity, optimize total intensity and then optimize homogeneity, minimize total dose to critical structures, minimize total dose to critical structures and optimize conformity simultaneously. We emphasize that the

  18. Characteristics Predictive for a Successful Switch from Insulin Analogue Therapy to Oral Hypoglycemic Agents in Patients with Type 2 Diabetes

    PubMed Central

    Kim, Gyuri; Lee, Yong-ho; Kang, Eun Seok; Cha, Bong-Soo; Lee, Hyun Chul

    2016-01-01

    Purpose The objective of this study was to investigate clinical and laboratory parameters that could predict which patients could maintain adequate glycemic control after switching from initial insulin therapy to oral hypoglycemic agents (OHAs) among patients with type 2 diabetes (T2D). Materials and Methods We recruited 275 patients with T2D who had been registered in 3 cohorts of initiated insulin therapy and followed up for 33 months. The participants were divided into 2 groups according to whether they switched from insulin to OHAs (Group I) or not (Group II), and Group I was further classified into 2 sub-groups: maintenance on OHAs (Group IA) or resumption of insulin (Group IB). Results Of 275 patients with insulin initiation, 63% switched to OHAs (Group I) and 37% continued insulin (Group II). Of these, 44% were in Group IA and 19% in Group IB. The lowest tertile of baseline postprandial C-peptide-to-glucose ratio (PCGR), higher insulin dose at switching to OHAs, and higher HbA1c level at 6 months after switching to OHAs were all associated with OHA failure (Group IB; p=0.001, 0.046, and 0.014, respectively). The lowest tertile of PCGR was associated with ultimate use of insulin (Group IB and Group II; p=0.029). Conclusion Higher baseline level of PCGR and lower HbA1c levels at 6 months after switching to OHAs may be strong predictors for the successful maintenance of OHAs after switching from insulin therapy in Korean patients with T2D. PMID:27593867

  19. Low intensity laser therapy accelerates muscle regeneration in aged rats

    PubMed Central

    Vatansever, Fatma; Rodrigues, Natalia C.; Assis, Livia L.; Peviani, Sabrina S.; Durigan, Joao L.; Moreira, Fernando M.A.; Hamblin, Michael R.; Parizotto, Nivaldo A.

    2013-01-01

    Background Elderly people suffer from skeletal muscle disorders that undermine their daily activity and quality of life; some of these problems can be listed as but not limited to: sarcopenia, changes in central and peripheral nervous system, blood hypoperfusion, regenerative changes contributing to atrophy, and muscle weakness. Determination, proliferation and differentiation of satellite cells in the regenerative process are regulated by specific transcription factors, known as myogenic regulatory factors (MRFs). In the elderly, the activation of MRFs is inefficient which hampers the regenerative process. Recent studies found that low intensity laser therapy (LILT) has a stimulatory effect in the muscle regeneration process. However, the effects of this therapy when associated with aging are still unknown. Objective This study aimed to evaluate the effects of LILT (λ=830 nm) on the tibialis anterior (TA) muscle of aged rats. Subjects and methods The total of 56 male Wistar rats formed two population sets: old and young, with 28 animals in each set. Each of these sets were randomly divided into four groups of young rats (3 months of age) with n=7 per group and four groups of aged rats (10 months of age) with n=7 per group. These groups were submitted to cryoinjury + laser irradiation, cryoinjury only, laser irradiation only and the control group (no cryoinjury/no laser irradiation). The laser treatment was performed for 5 consecutive days. The first laser application was done 24 h after the injury (on day 2) and on the seventh day, the TA muscle was dissected and removed under anesthesia. After this the animals were euthanized. Histological analyses with toluidine blue as well as hematoxylin-eosin staining (for counting the blood capillaries) were performed for the lesion areas. In addition, MyoD and VEGF mRNA was assessed by quantitative polymerase chain reaction. Results The results showed significant elevation (p<0.05) in MyoD and VEGF genes expression levels

  20. Prioritized efficiency optimization for intensity modulated proton therapy.

    PubMed

    Müller, Birgit S; Wilkens, Jan J

    2016-12-07

    A high dosimetric quality and short treatment time are major goals in radiotherapy planning. Intensity modulated proton therapy (IMPT) plans obtain dose distributions of great conformity but often result in long delivery times which are typically not incorporated into the optimization process. We present an algorithm to optimize delivery efficiency of IMPT plans while maintaining plan quality, and study the potential trade-offs of these interdependent objectives. The algorithm is based on prioritized optimization, a stepwise approach to implemented objectives. First the quality of the plan is optimized. The second step of the prioritized efficiency optimization (PrEfOpt) routine offers four alternatives for reducing delivery time: minimization of the total spot weight sum (A), maximization of the lowest spot intensity of each energy layer (B), elimination of low-weighted spots (C) or energy layers (D). The trade-off between dosimetric quality (step I) and treatment time (step II) is controlled during the optimization by option-dependent parameters. PrEfOpt was applied to a clinical patient case, and plans for different trade-offs were calculated. Delivery times were simulated for two virtual facilities with constant and variable proton current, i.e. independent and dependent on the optimized spot weight distributions. Delivery times decreased without major degradation of plan quality; absolute time reductions varied with the applied method and facility type. Minimizing the total spot weight sum (A) reduced times by 28% for a similar plan quality at a constant current (changes of minimum dose in the target  <1%). For a variable proton current, eliminating low-weighted spots (C) led to remarkably faster delivery (16%). The implementation of an efficiency-optimization step into the optimization process can yield reduced delivery times with similar plan qualities. A potential clinical application of PrEfOpt is the generation of multiple plans with different trade

  1. Prioritized efficiency optimization for intensity modulated proton therapy

    NASA Astrophysics Data System (ADS)

    Müller, Birgit S.; Wilkens, Jan J.

    2016-12-01

    A high dosimetric quality and short treatment time are major goals in radiotherapy planning. Intensity modulated proton therapy (IMPT) plans obtain dose distributions of great conformity but often result in long delivery times which are typically not incorporated into the optimization process. We present an algorithm to optimize delivery efficiency of IMPT plans while maintaining plan quality, and study the potential trade-offs of these interdependent objectives. The algorithm is based on prioritized optimization, a stepwise approach to implemented objectives. First the quality of the plan is optimized. The second step of the prioritized efficiency optimization (PrEfOpt) routine offers four alternatives for reducing delivery time: minimization of the total spot weight sum (A), maximization of the lowest spot intensity of each energy layer (B), elimination of low-weighted spots (C) or energy layers (D). The trade-off between dosimetric quality (step I) and treatment time (step II) is controlled during the optimization by option-dependent parameters. PrEfOpt was applied to a clinical patient case, and plans for different trade-offs were calculated. Delivery times were simulated for two virtual facilities with constant and variable proton current, i.e. independent and dependent on the optimized spot weight distributions. Delivery times decreased without major degradation of plan quality; absolute time reductions varied with the applied method and facility type. Minimizing the total spot weight sum (A) reduced times by 28% for a similar plan quality at a constant current (changes of minimum dose in the target  <1%). For a variable proton current, eliminating low-weighted spots (C) led to remarkably faster delivery (16%). The implementation of an efficiency-optimization step into the optimization process can yield reduced delivery times with similar plan qualities. A potential clinical application of PrEfOpt is the generation of multiple plans with different trade

  2. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group.

    PubMed Central

    Malmberg, K.

    1997-01-01

    OBJECTIVES: To test the hypothesis that intensive metabolic treatment with insulin-glucose infusion followed by multidose insulin treatment in patients with diabetes mellitus and acute myocardial infarction improves the prognosis. DESIGN: Patients with diabetes mellitus and acute myocardial infarction were randomly allocated standard treatment plus insulin-glucose infusion for at least 24 hours followed by multidose insulin treatment or standard treatment (controls). SUBJECTS: 620 patients were recruited, of whom 306 received intensive insulin treatment and 314 served as controls. MAIN OUTCOME MEASURE: Long term all cause mortality. RESULTS: The mean (range) follow up was 3.4 (1.6-5.6) years. There were 102 (33%) deaths in the treatment group compared with 138 (44%) deaths in the control group (relative risk (95% confidence interval) 0.72 (0.55 to 0.92); P = 0.011). The effect was most pronounced among the predefined group that included 272 patients without previous insulin treatment and at a low cardiovascular risk (0.49 (0.30 to 0.80); P = 0.004). CONCLUSION: Insulin-glucose infusion followed by intensive subcutaneous insulin in diabetic patients with acute myocardial infarction improves long term survival, and the effect seen at one year continues for at least 3.5 years, with an absolute reduction in mortality of 11%. This means that one life was saved for nine treated patients. The effect was most apparent in patients who had not previously received insulin treatment and who were at a low cardiovascular risk. PMID:9169397

  3. Combined MMF and insulin therapy prevents renal injury in experimental diabetic rats.

    PubMed

    Wu, Xiaoyan; Zha, Dongqing; Xiang, Guangsheng; Zhang, Bo; Xiao, Shu-Yuan; Jia, Ruhan

    2006-12-01

    Conventional therapies for diabetic mellitus are not effective in preventing the progression from early diabetic nephropathy (DN) to end-stage renal disease. The role of inflammation in the pathogenesis of DN has been implicated both clinically and experimentally, which provides an alternative therapeutic target for DN. Anti-inflammatory impact of mycophenolate mofetil (MMF) alone and in combination with insulin had been observed in a rat model of experimental DN. In this study, the diabetic rats were subjected to different treatments. Compared to control, the expression levels of CD68, NGF, and NF-kappaB p65, as determined immunohistochemically, were elevated in diabetic rats. Treatment with combined MMF/insulin is associated with a significant reduction in renal tissue of NGF and NF-kappaB p65 expression, macrophage infiltration. It also partially improved the renal function and attenuated renal hypertrophy at early stage of DN. CD68 was found to positively correlate with urinary albumin excretion and NGF. The combined use of MMF/insulin seemed to offer more protections in rats with experimental diabetic renal injury, and the protective effects of MMF might be due to its anti-inflammatory actions through inhibition of NF-kappaB activation and reduction of T cells and macrophage infiltration and/or other kidney chemokine productions.

  4. Overcoming barriers to glycemic control in African Americans with type-2 diabetes: benefits of insulin therapy.

    PubMed Central

    Marshall, Merville C.

    2007-01-01

    A disproportionate number of African-American men and women are affected by obesity and diabetes. The documented rate of poor glycemic control in the African-American population may contribute to the high rate of morbidity and mortality due to diabetes observed in these patients. Since the benefits of strict glycemic control have been demonstrated in multiple large trials, the aim of treatment should be to achieve the goals set forth by the American Diabetes Association. Insulin remains an essential therapeutic agent for helping patients achieve glycemic control and preventing long-term comorbidities. However, barriers to insulin therapy exist for both the physician and patient. Strategies to counter this resistance include identifying barriers to treatment, restoring the patient's sense of control, utilizing simple regimens, and reviewing the benefits of insulin and the risk of hypoglycemia. In treating African-American patients with diabetes, providers of various racial and ethnic backgrounds may maximize treatment efficacy by attempting to understand and practice culturally competent care. PMID:17722663

  5. Insulin resistance and medial prefrontal gyrus metabolism in women receiving hormone therapy.

    PubMed

    Rasgon, Natalie L; Kenna, Heather A; Wroolie, Tonita E; Williams, Katherine E; DeMuth, Bevin N; Silverman, Daniel H S

    2014-07-30

    Insulin resistance (IR) is a putative risk factor for cognitive decline and dementia, and has been shown to impede neuronal glucose metabolism in animal models. This post hoc study focused on metabolic changes in the medial prefrontal region, a brain region exhibiting decline years before documented cognitive changes, relative to high or low IR status in a cohort of postmenopausal women at risk for dementia who were randomized to continue or discontinue existing stable hormone therapy (HT) for 2 years. Subjects were dichotomized into high and low IR groups based on the homeostatic model assessment of insulin resistance, which was within clinically normal limits for the group as a whole at both baseline and 2-year follow-up. Results showed that high and low IR groups showed significant differences in metabolic decline of the medial prefrontal gyrus, regardless of HT randomization group. However, HT randomization was predictive of metabolic decline only in women with low HOMA (homeostatic assessment of insulin resistance). Performance in working memory was consistent with observed metabolic changes. These results suggest IR may be an independent moderator of regional metabolic changes, while protective metabolic effects of HT are most apparent in those at low-end range of IR. If replicated in future studies, these findings will help to better understand the interaction between putative risk and protective factors, and further delineate cohort postmenopausal women who may benefit from HT.

  6. Effect of combined hormonal and insulin therapy on the steroid hormone receptors and growth factors signalling in diabetic mice prostate.

    PubMed

    Fávaro, Wagner J; Cagnon, Valéria H A

    2010-12-01

    Diabetes causes harmful effects on prostatic morphology and function. However, there still are doubts about the occurrence of various diseases in the prostate, as well as abnormal angiogenesis in relation to diabetes. Thus, the aim of this study was to correlate and quantify the level of the steroid hormone receptors and the angiogenic and antiangiogenic factors in non-obese diabetic mice (Nod) after combined hormonal and insulin therapy. Sixty mice were divided into six groups after 20 days of diabetes: the control group received 0.9% NaCl, as did the diabetic group. The diabetic-insulin group received insulin, the diabetic-testosterone group received testosterone cypionate, the diabetic-oestrogen group received 17β-oestradiol, and the diabetic-insulin-testosterone-oestrogen group received insulin, testosterone and oestrogen simultaneously. After 20 days, the ventral lobe was processed for immunocytochemical and hormonal analyses. The results showed that the lowest serum testosterone and androgen receptor levels were found in the diabetic group and the highest testosterone and androgen receptor levels in the diabetic-insulin-testosterone-oestrogen group. The serum oestrogen level and its receptor showed changes opposite to those of testosterone and its receptor. The endostatin reactivity was mainly decreased in diabetic mice. The greatest IGFR-1 and VEGF reactivities occurred in diabetic mice. Thus, diabetes led to the prostatic hormonal imbalance, affecting molecular dynamics and angiogenesis in this organ. Combined insulin and steroid hormone therapy partially restored the hormonal and angiogenic imbalance caused by diabetes.

  7. Survey of resident education in intensity-modulated radiation therapy.

    PubMed

    Malik, Renuka; Oh, Julia L; Roeske, John C; Mundt, Arno J

    2005-06-01

    Intensity-modulated radiation therapy (IMRT) has been gaining increasing popularity among practicing physicians in the U.S., but the extent to which radiation oncology residents are taught the principles of this technology and are trained to use IMRT remains unknown. In this paper, we assessed the current level of resident education in IMRT in the United States. Chief residents at all 77 accredited radiation oncology programs were sent a 13-question survey addressing formal didactics and hands-on experience in IMRT. The survey assessed the frequency, subject, and format of IMRT didactics. Questions also addressed the number of IMRT patients and anatomical sites treated, resident involvement in the IMRT process, and the intent of IMRT use. Finally, residents were asked for their opinions on their IMRT education. Sixty-one surveys (79%) were completed. Overall, forty-three respondents (71%) reported receiving formal IMRT didactics, with nearly one-third reporting extensive didactics (> or = 3 lectures/seminars et cetera per year). The most common didactic formats were lectures (95%) and journal clubs (63%), most commonly supervised by physicists (98%). Involvement by physicians and radiobiologists were reported by 63% and 7% of respondents, respectively. Overall, 87% of respondents had hands-on IMRT training, with nearly one-half having treated > 25 patients. The most common sites treated were head and neck (94%) and prostate (81%). Involvement in all aspects of the IMRT process was common, particularly target and tissue delineation (98%) and plan evaluation (93%). Most respondents (79%) with hands-on experience reported receiving formal didactics. However, nearly one-third received no or only minimal formal didactics. The percentage of respondents desiring increased IMRT didactics and hands-on experience were 70% and 47%, respectively. Our results suggest that the great majority of radiation oncology residents in the United States are currently exposed to didactics

  8. Intensity Modulated Radiation Therapy With Dose Painting to Treat Rhabdomyosarcoma

    SciTech Connect

    Yang, Joanna C.; Dharmarajan, Kavita V.; Wexler, Leonard H.; La Quaglia, Michael P.; Happersett, Laura; Wolden, Suzanne L.

    2012-11-01

    Purpose: To examine local control and patterns of failure in rhabdomyosarcoma patients treated with intensity modulated radiation therapy (RT) with dose painting (DP-IMRT). Patients and Methods: A total of 41 patients underwent DP-IMRT with chemotherapy for definitive treatment. Nineteen also underwent surgery with or without intraoperative RT. Fifty-six percent had alveolar histologic features. The median interval from beginning chemotherapy to RT was 17 weeks (range, 4-25). Very young children who underwent second-look procedures with or without intraoperative RT received reduced doses of 24-36 Gy in 1.4-1.8-Gy fractions. Young adults received 50.4 Gy to the primary tumor and lower doses of 36 Gy in 1.8-Gy fractions to at-risk lymph node chains. Results: With 22 months of median follow-up, the actuarial local control rate was 90%. Patients aged {<=}7 years who received reduced overall and fractional doses had 100% local control, and young adults had 79% (P=.07) local control. Three local failures were identified in young adults whose primary target volumes had received 50.4 Gy in 1.8-Gy fractions. Conclusions: DP-IMRT with lower fractional and cumulative doses is feasible for very young children after second-look procedures with or without intraoperative RT. DP-IMRT is also feasible in adolescents and young adults with aggressive disease who would benefit from prophylactic RT to high-risk lymph node chains, although dose escalation might be warranted for improved local control. With limited follow-up, it appears that DP-IMRT produces local control rates comparable to those of sequential IMRT in patients with rhabdomyosarcoma.

  9. A Novel Insulin/Glucose Model after a Mixed-Meal Test in Patients with Type 1 Diabetes on Insulin Pump Therapy

    PubMed Central

    Marchetti, Luca; Reali, Federico; Dauriz, Marco; Brangani, Corinna; Boselli, Linda; Ceradini, Giulia; Bonora, Enzo; Bonadonna, Riccardo C.; Priami, Corrado

    2016-01-01

    Current closed-loop insulin delivery methods stem from sophisticated models of the glucose-insulin (G/I) system, mostly based on complex studies employing glucose tracer technology. We tested the performance of a new minimal model (GLUKINSLOOP 2.0) of the G/I system to characterize the glucose and insulin dynamics during multiple mixed meal tests (MMT) of different sizes in patients with type 1 diabetes (T1D) on insulin pump therapy (continuous subcutaneous insulin infusion, CSII). The GLUKINSLOOP 2.0 identified the G/I system, provided a close fit of the G/I time-courses and showed acceptable reproducibility of the G/I system parameters in repeated studies of identical and double-sized MMTs. This model can provide a fairly good and reproducible description of the G/I system in T1D patients on CSII, and it may be applied to create a bank of “virtual” patients. Our results might be relevant at improving the architecture of upcoming closed-loop CSII systems. PMID:27824066

  10. Lower dose basal insulin infusion has positive effect on glycaemic control for children with type I diabetes on continuous subcutaneous insulin infusion therapy.

    PubMed

    Schulten, Ron J; Piet, Jessica; Bruijning, Patricia Cjl; de Waal, Wouter J

    2017-02-01

    The aim of our study was to explore a possible relationship between proportion of basal insulin dose (%BD/T) and glycaemic control in children with type I diabetes on continuous subcutaneous insulin infusion (CSII) therapy. All patients under the age of 18 with type I diabetes mellitus, treated in a general hospital in Utrecht, The Netherlands, who were on CSII therapy between 2000 and 2011 were selected for inclusion. All data as recorded during outpatient visits were retrospectively collected from patients' charts. Analyses were performed using R Statistical Software. Data of 847 outpatient visits of 78 patients [31 males (39.7%) and 47 females (60.3%)] were analyzed. Mean age at diagnosis was 7.1 ± 3.7 yr, mean age at start of pump therapy 10.1 ± 3.8 yr. Mean HbA1c before pump start was 8.3 ± 1.0%, median BMI standard deviation score for age and gender was 0.64 (-1.89-3.79). Median follow-up time per patient was 29 months with an average of 10 visits (range: 3-25). Multivariate analysis revealed that a change of 10% in %BD/T resulted in a decrease or increase of HbA1c of 0.22% [95% confidence interval (CI): 0.15-0.29). No significant effect was observed from SDS BMI, sex, or duration of diabetes. Low dose basal insulin infusion as a percentage of total insulin dose has a positive effect on metabolic outcome as expressed in HbA1c-levels. A change of 10% in %BD/T results in a decrease or increase of HbA1c of 0.22%. This supports the tendency to aim at the lowest basal insulin requirements in pump setting strategy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Switching to basal-bolus insulin therapy is effective and safe in long-term type 2 diabetes patients inadequately controlled with other insulin regimens.

    PubMed

    Vinagre, Irene; Sánchez-Hernández, Juan; Sánchez-Quesada, José Luis; María, Miguel Ángel; de Leiva, Alberto; Pérez, Antonio

    2013-05-01

    To assess in standard clinical practice the feasibility, efficacy, and safety of switching patients with long-standing type 2 diabetes (T2DM) and poor or unstable blood glucose control to basal-bolus insulin therapy. This was a prospective, single center study including 37 patients with T2DM (age 65±8 years, 62.2% men, body mass index 28.8±6.2 kg/m2, diabetes duration 18±8 years) with poor or unstable glycemic control, who were switched to a basal-bolus insulin regimen with glargine and rapid-acting insulin analogue at the discretion of their physicians. After a group-structured outpatient diabetes training program, patients were followed in a clinical practice setting for 6 months. Clinical and biochemical variables were collected before switching and at 3 and 6 months. After switching to basal-bolus therapy, glycosylated hemoglobin (HbA1c) decreased from 9±1.2% to 8.1±1.2% (p<0.001) at 3 months and to 8.0±1.2% at 6 months (p<0.001) without changing total daily insulin dose. The proportion of patients with HbA1c ≥ 9% decreased from 51% to 13.8% at 3 months and to 18.9% at 6 months respectively. There was a single episode of severe hypoglycemia. No changes were seen in body weight and quality of life. The size of LDL (low density lipoprotein) particles significantly increased at 3 and 6 months, while all other lipid parameters remained unchanged. Our study confirmed that basal-bolus insulin therapy is feasible, effective, and safe in patients with long-standing T2DM, and does not impair their quality of life. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  12. Changes in N400 Topography Following Intensive Speech Language Therapy for Individuals with Aphasia

    ERIC Educational Resources Information Center

    Wilson, K. Ryan; O'Rourke, Heather; Wozniak, Linda A.; Kostopoulos, Ellina; Marchand, Yannick; Newman, Aaron J.

    2012-01-01

    Our goal was to characterize the effects of intensive aphasia therapy on the N400, an electrophysiological index of lexical-semantic processing. Immediately before and after 4 weeks of intensive speech-language therapy, people with aphasia performed a task in which they had to determine whether spoken words were a "match" or a "mismatch" to…

  13. [Modalities of breast cancer irradiation in 2016: Aims and indications of intensity modulated radiation therapy].

    PubMed

    Bourgier, C; Fenoglietto, P; Lemanski, C; Ducteil, A; Charissoux, M; Draghici, R; Azria, D

    2016-10-01

    Irradiation techniques for breast cancer (arctherapy, tomotherapy) are evolving and intensity-modulated radiation therapy is being increasingly considered for the management of these tumours. Here, we propose a review of intensity-modulated radiation therapy planning issues, clinical toxicities and indications for breast cancer.

  14. Changes in N400 Topography Following Intensive Speech Language Therapy for Individuals with Aphasia

    ERIC Educational Resources Information Center

    Wilson, K. Ryan; O'Rourke, Heather; Wozniak, Linda A.; Kostopoulos, Ellina; Marchand, Yannick; Newman, Aaron J.

    2012-01-01

    Our goal was to characterize the effects of intensive aphasia therapy on the N400, an electrophysiological index of lexical-semantic processing. Immediately before and after 4 weeks of intensive speech-language therapy, people with aphasia performed a task in which they had to determine whether spoken words were a "match" or a "mismatch" to…

  15. Effectiveness of basal-supported oral therapy (BOT) using insulin glargine in patients with poorly controlled type 2 diabetes.

    PubMed

    Suzuki, Daisuke; Umezono, Tomoya; Miyauchi, Masaaki; Kimura, Moritsugu; Yamamoto, Naoyuki; Tanaka, Eitaro; Kuriyama, Yusuke; Sato, Hiroki; Miyatake, Han; Kondo, Masumi; Toyoda, Masao; Fukagawa, Masafumi

    2012-07-20

    To determine the clinical usefulness of basal-supported oral therapy (BOT) using insulin glargine in Japanese patients with type 2 diabetes. We compared HbA1c levels, body weight, and insulin doses before the introduction of BOT and in the final month of the observation period in 122 patients with type 2 diabetes who received BOT with insulin glargine between October 2007 and July 2009. To exclude the possible effects of seasonal changes in glycemic control, 57 of the 122 patients were followed-up for one year and examined for changes in HbA1c levels, body weight, and insulin dose. Examination of all cases (n=122) showed a significant decrease in HbA1c (before BOT: 8.7±1.8, after: 7.1±1.1%), but no significant change in body weight (before: 63.1±16.1, after: 63.8±17.0 kg). The mean observation period was 10.5±6.4 months. Insulin doses were significantly increased during the study. HbA1c levels improved significantly in patients on non-insulin-secreting drugs (biguanide, α-glucosidase inhibitor and thiazolidine derivatives) than those on insulin-secreting drugs (SU agents and glinides). BOT with insulin glargine is a useful strategy that can achieve good glycemic control in clinical practice without causing serious hypoglycemia. The introduction of BOT before exhaustion of pancreatic β cells may increase its effectiveness.

  16. Response of circulating ghrelin levels to insulin therapy in children with newly diagnosed type 1 diabetes mellitus.

    PubMed

    Soriano-Guillén, Leandro; Barrios, Vicente; Lechuga-Sancho, Alfonso; Chowen, Julie A; Argente, Jesús

    2004-05-01

    Ghrelin is secreted primarily by the stomach, although other tissues such as the pancreas synthesize a minor proportion. The discovery of a new cell type that produces ghrelin in the human pancreas and that this organ expresses GHS-R opens new perspectives in the understanding of the control of glucose metabolism. We have studied 22 children with newly diagnosed type 1 diabetes mellitus at four different points: at diagnosis before insulin therapy, after 48-60 h of insulin therapy, and after 1 and 4 mo of insulin treatment. At each point circulating levels of ghrelin, leptin, IGF-I, IGF binding protein (IGFBP)-1, IGFBP-2, IGFBP-3, and glucose were determined. Ghrelin levels were significantly decreased at diagnosis (573 +/- 68 pg/mL, p < 0.01) compared with controls (867 +/- 38 pg/mL) and remained decreased after insulin therapy (d 2: 595 +/- 68 pg/mL; 1 mo: 590 +/- 61 pg/mL; 4 mo: 538 +/- 67 pg/mL) with no differences before or after insulin treatment. There was a negative correlation between ghrelin levels and body mass index at all of the study points, whereas a negative correlation between ghrelin and glucose concentrations was only observed after insulin therapy. No correlation between ghrelin and HbA1c was found at any point. A positive correlation between ghrelin and IGFBP-1 was found after insulin therapy, but no correlation with other members of the IGF system or leptin was found. In conclusion, these data could indicate a possible link between glucose concentrations and ghrelin; hence, the persisting low ghrelin levels in diabetic children may suggest a defensive mechanism against hyperglycemia.

  17. Nine days of intensive exercise training improves mitochondrial function but not insulin action in adult offspring of mothers with type 2 diabetes.

    PubMed

    Irving, Brian A; Short, Kevin R; Nair, K Sreekumaran; Stump, Craig S

    2011-07-01

    A close association between insulin resistance and reduced skeletal muscle oxidative capacity has been reported in adult offspring of people with type 2 diabetes (T2D), prompting a hypothesis that insulin resistance may result from mitochondrial dysfunction or vice versa. We determined whether 9 d of intensive exercise training ameliorates the mitochondrial dysfunction and insulin resistance in offspring of T2D. We compared the response to 9 d of intensive exercise training in eight (seven females, one male) healthy adult offspring of mothers with T2D with eight (six females, two males) nondiabetic controls. Skeletal muscle mitochondrial ATP production was assessed using a luciferase-based assay, and insulin sensitivity was measured using hyperinsulinemic-euglycemic clamps. Short-term intensive training increased skeletal muscle mitochondrial ATP production and citrate synthase activity similarly in both groups (P < 0.01). In contrast, whereas short-term intensive training reduced the fasting glucose (~5%, P = 0.035) and insulin levels (~40%, P = 0.011) as well as increased the glucose infusion rate during the hyperinsulinemic-euglycemic clamp (~50%, P = 0.028) among controls, no changes in these parameters were observed among offspring except for an increase in fasting glucose (~7%, P = 0.004). A short-term intensive exercise training program was equally effective at increasing skeletal muscle oxidative capacity in nondiabetic people and in the offspring of mothers with diabetes. In contrast, the exercise improved insulin sensitivity only in nondiabetic people but not in the offspring of T2D mothers, revealing dissociation between improvements in skeletal muscle mitochondrial function and insulin sensitivity. The exercise effect on mitochondrial function and insulin sensitivity seems to be mediated by different regulatory pathways.

  18. Response of non-insulin-dependent diabetic patients to an intensive program of diet and exercise.

    PubMed

    Barnard, R J; Lattimore, L; Holly, R G; Cherny, S; Pritikin, N

    1982-01-01

    To assess the effectiveness of the Pritikin program of diet and exercise for treating patients with non-insulin-dependent diabetes mellitus (NIDDM), data were obtained from 60 patients who completed the 26-day residential program. Of the 23 patients who were taking oral hypoglycemic agents upon entry, all but 2 were off medication by the end of the program. Of the 17 patients who were taking insulin, all but 4 were off medication at discharge. Two of the four had their insulin reduced by 50% while the remaining two had no major change in their insulin dosage. Fasting blood glucose was reduced from 194.9 +/- 10.1 to 144.6 +/- 7.1 mg/dl. Serum cholesterol was reduced from 225.4 +/- 5.7 to 181.7 +/- 4.9 mg/dl while triglycerides were reduced from 283.7 +/- 28.8 to 186.2 +/- 11.6 mg/dl. The group as a whole lost an average of 4.3 kg/body wt and achieved 40.5% of their desired weight loss. Maximum work capacity increased from 5.6 +/- 0.3 to 7.9 +/- 0.4 METs, while daily walking increased from 11.7 +/- 2.4 to 102.8 +/- 4.8 min/day. The decrease in fasting glucose was not correlated with weight loss (r = 0.24), increase in walking time (r = 0.00), or increase in MET capacity (r = 0.05). We conclude that the total program is an effective means for treating NIDDM patients. We also feel that the high-complex-carbohydrate, high-fiber, low-fat diet is of primary importance.

  19. Glycemic control and adherence to basal insulin therapy in Taiwanese patients with type 2 diabetes mellitus.

    PubMed

    Chien, Ming-Nan; Chen, Yen-Ling; Hung, Yi-Jen; Wang, Shu-Yi; Lu, Wen-Tsung; Chen, Chih-Hung; Lin, Ching-Ling; Huang, Tze-Pao; Tsai, Ming-Han; Tseng, Wei-Kung; Wu, Ta-Jen; Ho, Cheng; Lin, Wen-Yu; Chen, Bill; Chuang, Lee-Ming

    2016-11-01

    The aim of the present study was to assess the glycemic control, adherence and treatment satisfaction in a real-world setting with basal insulin therapy in type 2 diabetes patients in Taiwan. This was a multicenter, prospective, observational registry. A total of 836 patients with type 2 diabetes taking oral antidiabetic drugs with glycated hemoglobin (HbA1c) >7% entered the study. Basal insulin was given for 24 weeks. All treatment choices and medical instructions were at the physician's discretion to reflect real-life practice. After 24-week treatment, 11.7% of patients reached set HbA1c goals without severe hypoglycemia (primary effectiveness end-point). HbA1c and fasting blood glucose were significantly decreased from (mean ± SD) 10.1 ± 1.9% to 8.7 ± 1.7% (-1.4 ± 2.1%, P < 0.0001) and from 230.6 ± 68.8 mg/dL to 159.1 ± 55.6 mg/dL (-67.4 ± 72.3 mg/dL, P < 0.0001), respectively. Patients received insulin therapy at a frequency of nearly one shot per day on average, whereas self-monitoring of blood glucose was carried out approximately four times a week. Hypoglycemia was reported by 11.4% of patients, and only 0.7% of patients experienced severe hypoglycemia. Slight changes in weight (0.7 ± 2.4 kg) and a low incidence of adverse drug reactions (0.4%) were also noted. The score of 7-point treatment satisfaction rated by patients was significantly improved by 1.9 ± 1.7 (P < 0.0001). Basal insulin therapy was associated with a decrease in HbA1c and fasting blood glucose, and an improved treatment satisfaction. Most patients complied with physicians' instructions. The treatment was generally well tolerated by patients with type 2 diabetes, but findings pointed out the need to reinforce the early and appropriate uptitration to achieve treatment targets. © 2016 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

  20. From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

    NASA Astrophysics Data System (ADS)

    Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

    2005-05-01

    Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

  1. Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study

    SciTech Connect

    Lee, Katrina Lenards, Nishele; Holson, Janice

    2016-04-01

    The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient's neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to the hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient's data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain.

  2. Advances in Insulin Therapy: A Review of New Insulin Glargine 300 Units/mL in the Management of Diabetes.

    PubMed

    White, John R

    2016-04-01

    In Brief New insulin glargine 300 units/mL (Gla-300) is a formulation of insulin glargine that has a more constant pharmacokinetic profile with a prolonged duration of action. The EDITION clinical trial program showed that the use of Gla-300 leads to glycemic control comparable to that of insulin glargine 100 units/mL in a wide range of populations of people with diabetes. It is associated with comparable to less nocturnal confirmed or severe hypoglycemia and less weight gain, despite requiring a somewhat higher insulin dose than U-100. The distinct pharmacokinetic/pharmacodynamic and clinical profiles of Gla-300 may benefit a range of people with type 1 or type 2 diabetes.

  3. Volumetric intensity-modulated arc therapy vs conventional intensity-modulated radiation therapy in nasopharyngeal carcinoma: a dosimetric study

    PubMed Central

    White, Peter; Chan, Kit Chi; Cheng, Ka Wai; Chan, Ka Yiu; Chau, Ming Chun

    2013-01-01

    Dosimetric comparisons between RapidArc (RA) and conventional Intensity-Modulated Radiation Therapy (IMRT) techniques for nasopharyngeal carcinoma (NPC) were performed to address differences in dose coverage of the target, sparing of organs-at-risk (OARs), delivery of monitor units (MUs) and time, to assess whether the RA technique was more beneficial for treatment of NPC. Eight NPC patients (Stages I–IV), who had completed RA treatment, were selected for this study. Computed tomography data sets were re-planned using 7-fields fixed beam IMRT. Quantitative measurements of dose-endpoint values on the dose-volume histograms were carried out for evaluation of: (i) dose homogeneity (D5% – D95%); (ii) degree of conformity (CI95%); (iii) tumor control probability (TCP); (iv) doses to OARs; (v) normal tissue complication probability (NTCP); (vi) treatment time; and (vii) MUs. RA plans achieved better dose conformity and TCP in planning target volumes (PTVs). Target dose homogeneity was not as high as for IMRT plans. Doses to tempero-mandibular joints, clavicles, parotid glands and posterior neck, and their NTCPs were significantly lower in RA plans (P < 0.05). Mean doses to the brainstem and spinal cord were slightly lower in IMRT plans. RA plans allowed for a mean reduction in MUs by 78% (P = 0.006), and a four-fold reduction in treatment delivery times, relative to IMRT plans. RA plans showed superior, or comparable, target coverage and dose conformity in PTVs, but at the expense of inferior dose homogeneity. RA plans also achieved significant improvements in dose reduction to OARs and healthy tissue sparing. A significant reduction in treatment delivery time for RA treatment technique was also noted. PMID:23188186

  4. Effect of Rosiglitazone and Insulin Combination Therapy on Inflammation Parameters and Adipocytokine Levels in Patients with Type 1 DM

    PubMed Central

    Guclu, Metin; Oz Gul, Ozen; Cander, Soner; Unal, Oguzkaan; Ozkaya, Guven; Sarandol, Emre; Ersoy, Canan

    2015-01-01

    Aim. To investigate the efficacy of combined therapy of insulin and rosiglitazone on metabolic and inflammatory parameters, insulin sensitivity, and adipocytokine levels in patients with type 1 diabetes mellitus (type 1 DM). Material and Methods. A total of 61 adults with type 1 DM were randomly and prospectively assigned in open-label fashion to take insulin and rosiglitazone 4 mg/day (n = 30) or insulin alone (n = 31) for a period of 18 weeks while undergoing insulin therapy without acute metabolic complications. Results. Combination therapy did not significantly improve metabolic and inflammatory parameters, insulin sensitivity, and adiponectin levels. While leptin and resistin levels decreased in both groups (group 1: resistin 6.96 ± 3.06 to 4.99 ± 2.64, P = 0.006; leptin 25.8 ± 17.6 to 20.1 ± 12.55, P = 0.006; group 2: resistin 7.16 ± 2.30 to 5.57 ± 2.48, P = 0.031; leptin 16.72 ± 16.1 to 14.0 ± 13.4, P = 0.007) Hgb and fibrinogen levels decreased only in group 1 (Hgb 13.72 ± 1.98 to 13.16 ± 1.98, P = 0.015, and fibrinogen 4.00 ± 1.08 to 3.46 ± 0.90, P = 0.002). Patients in both groups showed weight gain and the incidence of hypoglycemia was not lower. Discussion. The diverse favorable effects of TZDs were not fully experienced in patients with type 1 DM. These results are suggesting that insulin sensitizing and anti-inflammatory characteristics of TZDs were likely to be more pronounced in patients who were not totally devoid of endogenous insulin secretion. PMID:26273677

  5. Extrapleural pneumonectomy, photodynamic therapy and intensity modulated radiation therapy for the treatment of malignant pleural mesothelioma.

    PubMed

    Du, Kevin L; Both, Stefan; Friedberg, Joseph S; Rengan, Ramesh; Hahn, Stephen M; Cengel, Keith A

    2010-09-01

    Intensity modulated radiation therapy (IMRT) has recently been proposed for the treatment of malignant pleural mesothelioma (MPM). Here, we describe our experience with a multimodality approach for the treatment of mesothelioma, incorporating extrapleural pneumonectomy, intraoperative photodynamic therapy and postoperative hemithoracic IMRT. From 2004-2007, we treated 11 MPM patients with hemithoracic IMRT, 7 of whom had undergone porfimer sodium-mediated PDT as an intraoperative adjuvant to surgical debulking. The median radiation dose to the planning treatment volume (PTV) ranged from 45.4-54.5 Gy. For the contralateral lung, V20 ranged from 1.4-28.5%, V5 from 42-100% and MLD from 6.8-16.5 Gy. In our series, 1 patient experienced respiratory failure secondary to radiation pneumonitis that did not require mechanical ventilation. Multimodality therapy combining surgery with increased doses of radiation using IMRT, and newer treatment modalities such as PDT , appears safe. Future prospective analysis will be needed to demonstrate efficacy of this approach in the treatment of malignant mesothelioma. Efforts to reduce lung toxicity and improve dose delivery are needed and provide the promise of improved local control and quality of life in a carefully chosen multidisciplinary approach.

  6. Effects of saxagliptin add-on therapy to insulin on blood glycemic fluctuations in patients with type 2 diabetes

    PubMed Central

    Li, Feng-fei; Jiang, Lan-lan; Yan, Reng-na; Zhu, Hong-hong; Zhou, Pei-hua; Zhang, Dan-feng; Su, Xiao-fei; Wu, Jin-dan; Ye, Lei; Ma, Jian-hua

    2016-01-01

    Abstract Background: To investigate whether saxagliptin add-on therapy to continuous subcutaneous insulin infusion (CSII) further improve blood glycemic control than CSII therapy in patients with newly diagnosed type 2 diabetes (T2D). Methods: This was a single-center, randomized, control, open-labeled trial. Newly diagnosed T2D patients were recruited between February 2014 and December 2015. Subjects were divided into saxagliptin add-on therapy to CSII group (n = 31) and CSII therapy group (n = 38). The treatment was maintained for 4 weeks. Oral glucose tolerance test was performed at baseline. Serum samples were obtained before and 30 and 120 minutes after oral administration for glucose, insulin, and C-peptide determination. Continuous glucose monitoring (CGM) was performed before and endpoint. Results: A total of 69 subjects were admitted. After 4-week therapy, CGM data showed that patients with saxagliptin add-on therapy exhibited further improvement of mean amplitude glycemic excursion (MAGE), the incremental area under curve of plasma glucose >7.8 and 10 mmol/L compared with that of control group. In addition, the hourly mean blood glucose concentrations, especially between 0000 and 0600 in patient with saxagliptin add-on therapy, were significantly lower compared with that of the control patients. Furthermore, patients in saxagliptin add-on group needed lower insulin dose to maintain euglycemic control. In addition, severe hypoglycemic episode was not observed from any group. Conclusion: Saxagliptin add-on therapy to insulin had the ability of further improve blood glycemic controlling, with lower insulin dose required by patients with T2D to maintain euglycemic controlling. PMID:27787387

  7. The Long Term Effectiveness of Intensive Stuttering Therapy: A Mixed Methods Study

    ERIC Educational Resources Information Center

    Irani, Farzan; Gabel, Rodney; Daniels, Derek; Hughes, Stephanie

    2012-01-01

    Purpose: The purpose of this study was to gain a deeper understanding of client perceptions of an intensive stuttering therapy program that utilizes a multi-faceted approach to therapy. The study also proposed to gain a deeper understanding about the process involved in long-term maintenance of meaningful changes made in therapy. Methods: The…

  8. The Long Term Effectiveness of Intensive Stuttering Therapy: A Mixed Methods Study

    ERIC Educational Resources Information Center

    Irani, Farzan; Gabel, Rodney; Daniels, Derek; Hughes, Stephanie

    2012-01-01

    Purpose: The purpose of this study was to gain a deeper understanding of client perceptions of an intensive stuttering therapy program that utilizes a multi-faceted approach to therapy. The study also proposed to gain a deeper understanding about the process involved in long-term maintenance of meaningful changes made in therapy. Methods: The…

  9. Comparative analysis of 60Co intensity-modulated radiation therapy

    NASA Astrophysics Data System (ADS)

    Fox, Christopher; Romeijn, H. Edwin; Lynch, Bart; Men, Chunhua; Aleman, Dionne M.; Dempsey, James F.

    2008-06-01

    In this study, we perform a scientific comparative analysis of using 60Co beams in intensity-modulated radiation therapy (IMRT). In particular, we evaluate the treatment plan quality obtained with (i) 6 MV, 18 MV and 60Co IMRT; (ii) different numbers of static multileaf collimator (MLC) delivered 60Co beams and (iii) a helical tomotherapy 60Co beam geometry. We employ a convex fluence map optimization (FMO) model, which allows for the comparison of plan quality between different beam energies and configurations for a given case. A total of 25 clinical patient cases that each contain volumetric CT studies, primary and secondary delineated targets, and contoured structures were studied: 5 head-and-neck (H&N), 5 prostate, 5 central nervous system (CNS), 5 breast and 5 lung cases. The DICOM plan data were anonymized and exported to the University of Florida optimized radiation therapy (UFORT) treatment planning system. The FMO problem was solved for each case for 5-71 equidistant beams as well as a helical geometry for H&N, prostate, CNS and lung cases, and for 3-7 equidistant beams in the upper hemisphere for breast cases, all with 6 MV, 18 MV and 60Co dose models. In all cases, 95% of the target volumes received at least the prescribed dose with clinical sparing criteria for critical organs being met for all structures that were not wholly or partially contained within the target volume. Improvements in critical organ sparing were found with an increasing number of equidistant 60Co beams, yet were marginal above 9 beams for H&N, prostate, CNS and lung. Breast cases produced similar plans for 3-7 beams. A helical 60Co beam geometry achieved similar plan quality as static plans with 11 equidistant 60Co beams. Furthermore, 18 MV plans were initially found not to provide the same target coverage as 6 MV and 60Co plans; however, adjusting the trade-offs in the optimization model allowed equivalent target coverage for 18 MV. For plans with comparable target coverage

  10. [Anesthesia and intensive therapy for a patient with mitochondrial myopathy].

    PubMed

    Breucking, E; Mortier, W; Lampert, R; Brandt, L

    1993-10-01

    Since 1983 we have been involved in the diagnostic work-up and emergency treatment of a female patient now 48 years old who has a mitochondrial myopathy resembling Luft's disease. The syndrome was first described in 1959, and in more detail in 1962, by Luft and et al., who reported a picture of hypermetabolism with high temperature, extreme sweating, tachycardia, dyspnoea at rest, polydipsia, polyphagia and irritability but normal thyroid function. In 1971 and 1976 Haydar and Di Mauro presented a second case and proposed treatment with chloramphenicol. Our patient has the third case of the syndrome reported so far: her case was initially published in 1987. CASE REPORT. Since her 17th year of life the patient had suffered from episodes of fever, tachycardia and sweating. At the age of 32 these attacks worsened, leading to unconsciousness and apnoea. The patient then had to be intubated, ventilated and sometimes resuscitated. The diagnosis of MH susceptibility and Luft's disease was made on biochemical grounds after the first muscle biopsy in 1983. Therapy with chloramphenicol failed. Therapy with beta blockers, vitamin C and K or E, coenzyme Q10 and a high-caloric diet was started in 1985. The patient was registered with an emergency service, which flew her to our ICU whenever she had a severe crisis. For milder episodes she was supplied with an oxygen breathing mask at home. Myalgia increased with the episodes starting in 1988, and the patient needed dantrolene infusions and analgesics at home. To facilitate venepuncture a Port-A-Cath system was implanted in 1987, which had to be removed four times due to infection and sepsis. A muscle biopsy was taken in Rotterdam, which revealed differences in mitochondrial function from the biochemical findings recorded in 1983 and not in keeping with Luft's disease. Unfortunately, the patient was not able to undergo further metabolic investigations or therapeutic trials. ANAESTHESIA. The patient received three local and six

  11. Insulin-like growth factor pathway: a link between androgen deprivation therapy (ADT), insulin resistance, and disease progression in patients with prostate cancer?

    PubMed

    Aggarwal, Rahul R; Ryan, Charles J; Chan, June M

    2013-07-01

    Androgen deprivation therapy (ADT) is standard of care for patients with metastatic hormone-sensitive prostate cancer (HSPC), yet through its induction of a hypogonadal state leads to metabolic perturbations, including insulin resistance (IR) and obesity. IR and obesity have been associated with an increased risk of progression to castrate-resistant prostate cancer (CRPC) and ultimately increased prostate cancer-specific mortality. On a molecular level, this association between obesity/IR and prostate cancer progression may be mediated by alterations in the insulin-like growth factor (IGF) axis, which has been shown to be up-regulated upon disease progression to CRPC. Targeting the IGF axis, either by anti-IGF therapy or via enhancement of peripheral insulin sensitivity, represents a viable therapeutic target in patients with prostate cancer. Using the development of IR and/or obesity may represent a clinically available biomarker that may predict those patients most likely to respond to such therapy, and warrants testing in future prospective clinical trials. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Effects of nonlinear ultrasound propagation on high intensity brain therapy.

    PubMed

    Pinton, Gianmarco; Aubry, Jean-Francois; Fink, Mathias; Tanter, Mickael

    2011-03-01

    As an ultrasound wave propagates nonlinearly, energy is transferred to higher frequencies where it is more strongly attenuated. Compared to soft tissue, the skull has strongly heterogeneous material parameters. The authors characterize with experiments and establish a numerical method that can describe the effects of the skull on the nonlinear components of ultrasonic wave propagation for application to high intensity focused ultrasound (HIFU) therapy in the brain. The impact of nonlinear acoustic propagation on heat deposition and thermal dose delivery is quantified and compared to linear assumptions by coupling an acoustic simulation with a heating model for brain tissue. A degassed dessicated human skull was placed in a water tank and insonified at 1 MPa with 7 mm transducer from a custom array designed for HIFU treatment. Two dimensional scans were performed preceding and following propagation through the skull with a calibrated hydrophone. Data from the scan preceding the skull were used as an input to a three dimensional finite difference time domain (FDTD) simulation that calculates the effects of diffraction, density, attenuation with linear dependence on frequency via relaxation mechanisms, and second order nonlinearity. A measured representation of the skull was used to determine the skull's acoustic properties. The validated acoustic model was used to determine the loss due to nonlinear propagation and then coupled to a finite difference simulation of the bioheat equation for two focal configurations at 3 and 7.5 cm from the skull surface. Prior to propagation through the skull, the second harmonic component was 19 dB lower than the fundamental, and the third harmonic component was 37 dB lower. Following the skull, the second harmonic component was 35 dB lower and the third harmonic was 55 dB lower. The simulation is in agreement with the measurements to within 0.5 dB across the considered frequency range and shows good agreement across the two

  13. Cotransplantation of adipose tissue-derived insulin-secreting mesenchymal stem cells and hematopoietic stem cells: a novel therapy for insulin-dependent diabetes mellitus.

    PubMed

    Vanikar, A V; Dave, S D; Thakkar, U G; Trivedi, H L

    2010-12-20

    Aims. Insulin dependent diabetes mellitus (IDDM) is believed to be an autoimmune disorder with disturbed glucose/insulin metabolism, requiring life-long insulin replacement therapy (IRT), 30% of patients develop end-organ failure. We present our experience of cotransplantation of adipose tissue derived insulin-secreting mesenchymal stem cells (IS-AD-MSC) and cultured bone marrow (CBM) as IRT for these patients. Methods. This was a prospective open-labeled clinical trial to test efficacy and safety of IS-AD-MSC+CBM co-transplantation to treat IDDM, approved by the institutional review board after informed consent in 11 (males : females: 7 : 4) patients with 1-24-year disease duration, in age group: 13-43 years, on mean values of exogenous insulin requirement of 1.14 units/kg BW/day, glycosylated hemoglobin (Hb1Ac): 8.47%, and c-peptide levels: 0.1 ng/mL. Intraportal infusion of xenogeneic-free IS-AD-MSC from living donors, subjected to defined culture conditions and phenotypically differentiated to insulin-secreting cells, with mean quantum: 1.5 mL, expressing Pax-6, Isl-1, and pdx-1, cell counts: 2.1 × 10(3)/μL, CD45(-)/90(+)/73(+):40/30.1%, C-Peptide level:1.8 ng/mL, and insulin level: 339.3  IU/mL with CBM mean quantum: 96.3 mL and cell counts: 28.1 × 10(3)/μL, CD45(-)/34(+):0.62%, was carried out. Results. All were successfully transplanted without any untoward effect. Over mean followup of 23 months, they had a decreased mean exogenous insulin requirement to 0.63 units/kgBW/day, Hb1Ac to 7.39%, raised serum c-peptide levels to 0.38 ng/mL, and became free of diabetic ketoacidosis events with mean 2.5 Kg weight gain on normal vegetarian diet and physical activities. Conclusion. This is the first report of treating IDDM with insulin-secreting-AD-MSC+CBM safely and effectively with relatively simple techniques.

  14. Acute High-Intensity Interval Exercise-Induced Redox Signaling Is Associated with Enhanced Insulin Sensitivity in Obese Middle-Aged Men.

    PubMed

    Parker, Lewan; Stepto, Nigel K; Shaw, Christopher S; Serpiello, Fabio R; Anderson, Mitchell; Hare, David L; Levinger, Itamar

    2016-01-01

    Background: Obesity and aging are associated with increased oxidative stress, activation of stress and mitogen activated protein kinases (SAPK), and the development of insulin resistance and metabolic disease. In contrast, acute exercise also increases oxidative stress and SAPK signaling, yet is reported to enhance insulin sensitivity and reduce the risk of metabolic disease. This study explored this paradox by investigating the effect of a single session of high-intensity interval-exercise (HIIE) on redox status, muscle SAPK and insulin protein signaling in eleven middle-aged obese men. Methods: Participants completed a 2 h hyperinsulinaemic-euglycaemic clamp at rest, and 60 min after HIIE (4 × 4 mins at 95% HRpeak; 2 min recovery periods), separated by 1-3 weeks. Results: Irrespective of exercise-induced changes to redox status, insulin stimulation both at rest and after HIIE similarly increased plasma superoxide dismutase activity, plasma catalase activity, and skeletal muscle 4-HNE; and significantly decreased plasma TBARS and hydrogen peroxide. The SAPK signaling pathways of p38 MAPK, NF-κB p65, and JNK, and the distal insulin signaling protein AS160(Ser588), were activated with insulin stimulation at rest and to a greater extent with insulin stimulation after a prior bout of HIIE. Higher insulin sensitivity after HIIE was associated with higher insulin-stimulated SOD activity, JNK, p38 MAPK and NF-κB phosphorylation (r = 0.63, r = 0.71, r = 0.72, r = 0.71; p < 0.05, respectively). Conclusion:These findings support a role for redox homeostasis and SAPK signaling in insulin-stimulated glucose uptake which may contribute to the enhancement of insulin sensitivity in obese men 3 h after HIIE.

  15. Acute High-Intensity Interval Exercise-Induced Redox Signaling Is Associated with Enhanced Insulin Sensitivity in Obese Middle-Aged Men

    PubMed Central

    Parker, Lewan; Stepto, Nigel K.; Shaw, Christopher S.; Serpiello, Fabio R.; Anderson, Mitchell; Hare, David L.; Levinger, Itamar

    2016-01-01

    Background: Obesity and aging are associated with increased oxidative stress, activation of stress and mitogen activated protein kinases (SAPK), and the development of insulin resistance and metabolic disease. In contrast, acute exercise also increases oxidative stress and SAPK signaling, yet is reported to enhance insulin sensitivity and reduce the risk of metabolic disease. This study explored this paradox by investigating the effect of a single session of high-intensity interval-exercise (HIIE) on redox status, muscle SAPK and insulin protein signaling in eleven middle-aged obese men. Methods: Participants completed a 2 h hyperinsulinaemic-euglycaemic clamp at rest, and 60 min after HIIE (4 × 4 mins at 95% HRpeak; 2 min recovery periods), separated by 1–3 weeks. Results: Irrespective of exercise-induced changes to redox status, insulin stimulation both at rest and after HIIE similarly increased plasma superoxide dismutase activity, plasma catalase activity, and skeletal muscle 4-HNE; and significantly decreased plasma TBARS and hydrogen peroxide. The SAPK signaling pathways of p38 MAPK, NF-κB p65, and JNK, and the distal insulin signaling protein AS160Ser588, were activated with insulin stimulation at rest and to a greater extent with insulin stimulation after a prior bout of HIIE. Higher insulin sensitivity after HIIE was associated with higher insulin-stimulated SOD activity, JNK, p38 MAPK and NF-κB phosphorylation (r = 0.63, r = 0.71, r = 0.72, r = 0.71; p < 0.05, respectively). Conclusion:These findings support a role for redox homeostasis and SAPK signaling in insulin-stimulated glucose uptake which may contribute to the enhancement of insulin sensitivity in obese men 3 h after HIIE. PMID:27695421

  16. Effect and cardiovascular safety of adding rosiglitazone to insulin therapy in type 2 diabetes: A meta-analysis

    PubMed Central

    Lu, Yu; Ma, Delin; Xu, Weijie; Shao, Shiying; Yu, Xuefeng

    2015-01-01

    Aims/Introduction Recently, the use of rosiglitazone has been limited or withdrawn from the market as a result of cardiovascular risk. However, theoretically adding rosiglitazone to insulin could help insulin to decrease the glucose level. The present meta-analysis was designed to investigate the effect and safety of adding rosiglitazone to insulin therapy in type 2 diabetes. Materials and Methods We searched published and unpublished databases through to March 2012. Randomized controlled trials (RCTs) comparing rosiglitazone in combination with insulin (RSG + INS) vs insulin alone (INS) in type 2 diabetes with outcomes including glycated hemoglobin levels, insulin dose, lipid parameters, blood pressure, edema and cardiovascular adverse events were selected. Results Nine RCTs with durations of 24–26 weeks involving 1,916 patients were included. The RSG + INS group showed significantly decreased glycated hemoglobin levels by 0.89% (P < 0.00001) with an 8.48-U reduction in daily insulin dose (P <0.00001). However, the risks of hypoglycemia and edema were more frequent in the RSG+INS group (P < 0.0001; P = 0.03, respectively). Total cholesterol level was significantly increased in the RSG+INS group (P < 0.00001), but none of the high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol or triglyceride levels were significantly different between groups. There were no significant differences between groups with regard to the risks of myocardial infarction, heart failure, cardiovascular death or all-cause death. Conclusions Rosiglitazone could help type 2 diabetes patients with poorly controlled glucose with insulin therapy to decrease glucose levels and reduce their daily insulin dose, but at the cost of increased total cholesterol level, hypoglycemia and edema risk. Compared with insulin therapy, adding rosiglitazone to insulin did not increase the risks of myocardial infarction, heart failure

  17. Nutritional therapy in paediatric intensive care units: a consensus statement of the Section of Paediatric Anaesthesia and Intensive Therapy the Polish Society of Anaesthesiology and Intensive Therapy, Polish Society of Neonatology and Polish Society for.

    PubMed

    Bartkowska-Śniatkowska, Alicja; Zielińska, Marzena; Świder, Magdalena; Bittner, Grażyna; Sarnowska-Wroczyńska, Irena; Witulska, Katarzyna; Migdał, Marek; Piotrowski, Andrzej; Bober-Olesińska, Krystyna; Kęsiak, Marcin; Lauterbach, Ryszard; Gawecka, Agnieszka; Danko, Mikołaj; Popińska, Katarzyna; Romanowska, Hanna; Szlagatys-Sidorkiewicz, Agnieszka; Toporowska-Kowalska, Ewa; Żyła, Aleksandra; Książyk, Janusz

    2015-01-01

    Providing nutritional therapy via the gastrointestinal tract in patients in paediatric intensive care units (PICUs) is an effective method for delivering energy and other nutrients. In the event of contraindications to using this method, it is necessary to commence parenteral nutrition. In the present study, methods for nutritional treatments in critically ill children are presented, depending on the clinical situation.

  18. Medical Nutrition Therapy Is Effective in the Management of Hypoglycemia Caused by Insulin Antibodies: A Case Report and Literature Review.

    PubMed

    Li, Rongrong; Mao, Jiangfeng; Yu, Kang; Wang, Lilin; Hu, Mingming; Xu, Lingling

    2016-01-01

    Autoimmune antibodies, induced by exogenous insulin preparations, may result in labile glucose control and frequent hypoglycemia in some rare cases. In addition to insulin cessation, immune suppressants and/or plasmapheresis have been used as the primary remedies for these patients. Some previous studies also indicate that the condition tends to remit spontaneously after discontinuation of insulin exposure. Because of this, the clinical importance of nutritional interventions and behavioral approaches, which may play a role in ameliorating the symptoms, should also be emphasized. Herein, we report on a 64-year-old man with hypoglycemia induced by insulin antibodies (IAs), whose hypoglycemic symptoms significantly improved after the implementation of nutrition therapy. This rare case expands our knowledge of the management of hypoglycemia, and for the first time highlights the significance of nutritional and lifestyle intervention in treatment of IA-induced hypoglycemia.

  19. [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.

  20. Clinical Experience with Insulin Glargine in Type 1 Diabetes

    PubMed Central

    Moser, Emily; Dain, Marie-Paule; Rodionova, Anastasia

    2010-01-01

    Abstract The Diabetes Control and Complications Trial (DCCT) demonstrated the importance of optimal glycemic control achieved through intensive insulin therapy in reducing the microvascular complications associated with type 1 diabetes. However, the DCCT, which was conducted prior to the availability of insulin analogs, also reported a significant increase in severe hypoglycemia with intensive versus conventional therapy. Insulin analogs were developed to aid patients in achieving better diabetes control by providing insulins with optimized pharmacokinetic and pharmacodynamic characteristics. Insulin glargine was the first long-acting insulin analog with a 24-h duration of action, offering once-daily injection, and has now been in clinical use for over 10 years. The authors performed a systematic search of EMBASE, MEDLINE, and Web of Science (Science Citation Index) to determine the efficacy of insulin glargine in type 1 diabetes in basal–bolus insulin regimens. Randomized controlled trials have demonstrated that glycemic control with insulin glargine is at least comparable to that with neutral protamine Hagedorn (NPH) insulin in adults and in children and adolescents, and with continuous subcutaneous insulin infusion in adults. However, these same trials show a significantly lower risk for hypoglycemia with insulin glargine compared with NPH insulin in adults. PMID:20969435

  1. Clinical experience with insulin glargine in type 1 diabetes.

    PubMed

    Garg, Satish; Moser, Emily; Dain, Marie-Paule; Rodionova, Anastasia

    2010-11-01

    The Diabetes Control and Complications Trial (DCCT) demonstrated the importance of optimal glycemic control achieved through intensive insulin therapy in reducing the microvascular complications associated with type 1 diabetes. However, the DCCT, which was conducted prior to the availability of insulin analogs, also reported a significant increase in severe hypoglycemia with intensive versus conventional therapy. Insulin analogs were developed to aid patients in achieving better diabetes control by providing insulins with optimized pharmacokinetic and pharmacodynamic characteristics. Insulin glargine was the first long-acting insulin analog with a 24-h duration of action, offering once-daily injection, and has now been in clinical use for over 10 years. The authors performed a systematic search of EMBASE, MEDLINE, and Web of Science (Science Citation Index) to determine the efficacy of insulin glargine in type 1 diabetes in basal-bolus insulin regimens. Randomized controlled trials have demonstrated that glycemic control with insulin glargine is at least comparable to that with neutral protamine Hagedorn (NPH) insulin in adults and in children and adolescents, and with continuous subcutaneous insulin infusion in adults. However, these same trials show a significantly lower risk for hypoglycemia with insulin glargine compared with NPH insulin in adults.

  2. Remission in models of type 1 diabetes by gene therapy using a single-chain insulin analogue

    NASA Astrophysics Data System (ADS)

    Lee, Hyun Chul; Kim, Su-Jin; Kim, Kyung-Sup; Shin, Hang-Cheol; Yoon, Ji-Won

    2000-11-01

    A cure for diabetes has long been sought using several different approaches, including islet transplantation, regeneration of β cells and insulin gene therapy. However, permanent remission of type 1 diabetes has not yet been satisfactorily achieved. The development of type 1 diabetes results from the almost total destruction of insulin-producing pancreatic β cells by autoimmune responses specific to β cells. Standard insulin therapy may not maintain blood glucose concentrations within the relatively narrow range that occurs in the presence of normal pancreatic β cells. We used a recombinant adeno-associated virus (rAAV) that expresses a single-chain insulin analogue (SIA), which possesses biologically active insulin activity without enzymatic conversion, under the control of hepatocyte-specific L-type pyruvate kinase (LPK) promoter, which regulates SIA expression in response to blood glucose levels. Here we show that SIA produced from the gene construct rAAV-LPK-SIA caused remission of diabetes in streptozotocin-induced diabetic rats and autoimmune diabetic mice for a prolonged time without any apparent side effects. This new SIA gene therapy may have potential therapeutic value for the cure of autoimmune diabetes in humans.

  3. [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.

  4. The psychophysiological effects of music therapy in intensive care units.

    PubMed

    Austin, Donna

    2010-04-01

    This article reviews the evidence for using music therapy with young people who are supported by mechanical ventilation. The author argues that music therapy is essential for developing a holistic approach focusing on the developmental level of a child or young person, as well as being an inexpensive, non-pharmacological, non-invasive therapy, with significant physiological and psychological benefits. She argues that more research is needed in this area to develop a sound evidence base on which guidelines to inform practice could be based.

  5. 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

  6. Effect of Insulin Therapy using Hyper-insulinemic Normoglycemic Clamp on Inflammatory Response in Brain Dead Organ Donors.

    PubMed

    Aljiffry, M; Hassanain, M; Schricker, T; Shaheen, M; Nouh, T; Lattermann, R; Salman, A; Wykes, L; Metrakos, P

    2016-05-01

    Brain death is a major stress that is associated with a massive inflammatory response and systemic hyperglycemia. Severe inflammation leads to increased graft immunogenicity and risk of graft dysfunction; while acute hyperglycemia aggravates the inflammatory response and increases the risk of morbidity and mortality. Insulin therapy not only controls hyperglycemia but also suppresses inflammation. The present study is to investigate the anti-inflammatory properties and the normoglycemia maintenance of high dose insulin on brain dead organ donors. 15 brain dead organ donors were divided into 2 groups, insulin treated (n=6) and controls (n=9). Insulin was provided for a minimum of 6 h using the hyperinsulinemic normoglycemic clamp technique. The changes of serum cytokines, including IL-6, IL-10, IL-1β, IL-8, TNFα, TGFα and MCP-1, were measured by suspension bead array immunoassay and glucose by a glucose monitor. Compared to controls, insulin treated donors had a significant lower blood glucose 4.8 (4-6.9) vs. 9 (5.6-11.7) mmol/L, p<0.01); the net decreases of pro-inflammatory cytokines, such as IL-6 and MCP-1, and the net increase of anti-inflammatory cytokine, such as IL-10, reached significant level in insulin treated donors compared with those in controls. High dose insulin therapy decreases the concentrations of inflammatory cytokines in brain dead donors and preserves normoglycemia. High dose of insulin may have anti-inflammatory effects in brain dead organ donors and therefore, improve the quality of donor organs and potentially improve outcomes. © Georg Thieme Verlag KG Stuttgart · New York.

  7. Insulin pens vs. vials and syringes: the pharmacist's role in individualizing therapy.

    PubMed

    Honebrink, Amy N; Peters, Chelsea R; Bright, David R

    2011-07-01

    As pharmacists strive for tighter glucose control in their patients, several considerations exist including the selection of insulin delivery administration methods. Traditionally, insulin administration using vials and syringes has been common, but insulin pens are also a viable option. Insulin pens have been shown to increase patient autonomy, which may impact adherence. Elderly patients, who may suffer from dexterity and visual impairment, have been shown to prefer insulin pens because they are easier to use. Although insulin pens are more expensive per mL, some patients may find an economic advantage with insulin pens based on copays and beyond-use dating. In long-term care settings, the additional cost of insulin pens may be offset by the reduced insulin-administration time. Pharmacists are well suited to advocate for their patients and to help select the insulin administration method that considers individual limitations and fiscal realities, and will best support the patient's disease management.

  8. Low-intensity voluntary running lowers blood pressure with simultaneous improvement in endothelium-dependent vasodilatation and insulin sensitivity in aged spontaneously hypertensive rats.

    PubMed

    Sun, Meng-Wei; Qian, Feng-Lei; Wang, Jian; Tao, Tao; Guo, Jing; Wang, Lie; Lu, Ai-Yun; Chen, Hong

    2008-03-01

    Our objective is to examine the effects of voluntary running at different intensity levels on blood pressure, endothelium-dependent vessel dysfunction and insulin resistance in aged spontaneously hypertensive rats (SHR) with severe hypertension. Ten-month-old male and female SHR with severe hypertension were assigned to voluntary running at either low intensity (30% of maximal aerobic velocity) or moderate intensity (60% of maximal aerobic velocity) on a motor-driven treadmill for 6 weeks, 20 min per day and 7 days per week. Age-matched Wistar-Kyoto rats and SHR were kept under sedentary conditions as controls. Blood pressure and heart rate were measured by the tail-cuff method. At the end of the exercise training, blood samples were collected for glucose, insulin and lipids assay, and aortae were isolated to examine their function in vitro. Low-intensity but not moderate-intensity running significantly lowered blood pressure in both male and female SHR (p<0.01). There was significant impairment in acetylcholine-induced vasorelaxation in SHR (p<0.01), which was improved by low-intensity training (p<0.05). Nitric oxide synthase blockade abrogated the improvement in endothelium-dependent relaxation. Hypertensive rats had elevated blood glucose and insulin levels with lowered insulin sensitivity that was ameliorated by low-intensity running. A significant increase in blood high-density lipoprotein (HDL)-cholesterol and a significant decrease in triglycerides were found in exercised SHR. In conclusion, low-intensity voluntary exercise lowers hypertension in aged SHR with severe hypertension. Exercise-induced simultaneous improvement in endothelium-dependent vessel relaxation and insulin sensitivity may act concomitantly in attenuating cardiovascular risk factors in aged hypertensive rats with significantly high blood pressure.

  9. Impact of machines on plan quality: volumetric modulated arc therapy and intensity modulated radiation therapy.

    PubMed

    Clemente, S; Cozzolino, M; Oliviero, C; Fiorentino, A; Chiumento, C; Fusco, V

    2014-02-01

    To evaluate the impact of different machines on plan quality using both intensity modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) techniques. Eight patients with squamous cell carcinoma of the oropharynx were selected at random. Plans were computed for IMRT and VMAT Smart Arc, using Pinnacle TPS for an Elekta (IMRT-E, VMAT-E) and Varian linac (IMRT-V, VMAT-V). A three-dose level prescription was used to deliver 70, 63 and 58.1 Gy to regions of macroscopic, microscopic high- and low-risk disease, respectively. All doses were given in 35 fractions. Comparisons were performed on dose-volume histogram data, monitor units (MU), and delivery time. VMAT-E plans resulted slightly MU efficient (-24 % p < 0.05) compared to VMAT-V while IMRT-V shortened delivery time (-19 % p < 0.05) compared to IMRT-E. All the delivery techniques resulted in equivalent target coverage in terms of D(98) % and D(2) %. For VMAT technique, a significant improvement of 7 % in homogeneity index (HI) for PTV58.1 was observed for Varian machine. A slight improvement in OARs sparing was observed with Elekta machine both for IMRT and VMAT techniques. Similar plan quality was observed for Elekta and Varian linacs, significant differences were observed in delivery efficiency, as MU number and delivery times, in favor of Elekta and Varian, respectively.

  10. 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

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

    PubMed

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

    2013-04-01

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

  12. 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

  13. Optimizing insulin pump therapy: the potential advantages of using a structured diabetes management program.

    PubMed

    Lange, Karin; Ziegler, Ralph; Neu, Andreas; Reinehr, Thomas; Daab, Iris; Walz, Marion; Maraun, Michael; Schnell, Oliver; Kulzer, Bernhard; Reichel, Andreas; Heinemann, Lutz; Parkin, Christopher G; Haak, Thomas

    2015-03-01

    Use of continuous subcutaneous insulin infusion (CSII) therapy improves glycemic control, reduces hypoglycemia and increases treatment satisfaction in individuals with diabetes. As a number of patient- and clinician-related factors can hinder the effectiveness and optimal usage of CSII therapy, new approaches are needed to address these obstacles. Ceriello and colleagues recently proposed a model of care that incorporates the collaborative use of structured SMBG into a formal approach to personalized diabetes management within all diabetes populations. We adapted this model for use in CSII-treated patients in order to enable the implementation of a workflow structure that enhances patient-physician communication and supports patients' diabetes self-management skills. We recognize that time constraints and current reimbursement policies pose significant challenges to healthcare providers integrating the Personalised Diabetes Management (PDM) process into clinical practice. We believe, however, that the time invested in modifying practice workflow and learning to apply the various steps of the PDM process will be offset by improved workflow and more effective patient consultations. This article describes how to implement PDM into clinical practice as a systematic, standardized process that can optimize CSII therapy.

  14. Introduction of a new health technology into a provincial health system: A case study of insulin pump therapy.

    PubMed

    Menon, Devidas; Stafinski, Tania; Nardelli, Alexa; Edwards, Alun

    2015-09-01

    Decisions on the introduction of new non-drug health technologies into healthcare are challenging. This article describes the introduction of insulin pump therapy for type 1 diabetes in Alberta, using an Access with Evidence Development (AED) approach. The organization and implementation of the AED, its current status, and lessons learned are described.

  15. Skeletal Effects of Growth Hormone and Insulin-like Growth Factor-I Therapy

    PubMed Central

    Lindsey, Richard C.; Mohan, Subburaman

    2015-01-01

    The growth hormone/insulin-like growth factor (GH/IGF) axis is critically important for the regulation of bone formation, and deficiencies in this system have been shown to contribute to the development of osteoporosis and other diseases of low bone mass. The GH/IGF axis is regulated by a complex set of hormonal and local factors which can act to regulate this system at the level of the ligands, receptors, IGF binding proteins (IGFBPs), or IGFBP proteases. A combination of in vitro studies, transgenic animal models, and clinical human investigations has provided ample evidence of the importance of the endocrine and local actions of both GH and IGF-I, the two major components of the GH/IGF axis, in skeletal growth and maintenance. GH- and IGF-based therapies provide a useful avenue of approach for the prevention and treatment of diseases such as osteoporosis. PMID:26408965

  16. Insulin-Like Growth Factor System in Cancer: Novel Targeted Therapies

    PubMed Central

    Brahmkhatri, Varsha P.; Prasanna, Chinmayi; Atreya, Hanudatta S.

    2015-01-01

    Insulin-like growth factors (IGFs) are essential for growth and survival that suppress apoptosis and promote cell cycle progression, angiogenesis, and metastatic activities in various cancers. The IGFs actions are mediated through the IGF-1 receptor that is involved in cell transformation induced by tumour. These effects depend on the bioavailability of IGFs, which is regulated by IGF binding proteins (IGFBPs). We describe here the role of the IGF system in cancer, proposing new strategies targeting this system. We have attempted to expand the general viewpoint on IGF-1R, its inhibitors, potential limitations of IGF-1R, antibodies and tyrosine kinase inhibitors, and IGFBP actions. This review discusses the emerging view that blocking IGF via IGFBP is a better option than blocking IGF receptors. This can lead to the development of novel cancer therapies. PMID:25866791

  17. Mortality and Other Important Diabetes-Related Outcomes With Insulin vs Other Antihyperglycemic Therapies in Type 2 Diabetes

    PubMed Central

    Poole, Chris D.; Evans, Marc; Peters, John R.; Morgan, Christopher Ll.

    2013-01-01

    Context: The safety of insulin in the treatment of type 2 diabetes mellitus (T2DM) has recently undergone scrutiny. Objective: The objective of the study was to characterize the risk of adverse events associated with glucose-lowering therapies in people with T2DM. Design and Setting: This was a retrospective cohort study using data from the UK General Practice Research Database, 2000–2010. Patients: Patients comprised 84 622 primary care patients with T2DM treated with one of five glucose-lowering regimens: metformin monotherapy, sulfonylurea monotherapy, insulin monotherapy, metformin plus sulfonylurea combination therapy, and insulin plus metformin combination therapy. There were 105 123 exposure periods. Main Outcome Measures: The risk of the first major adverse cardiac event, first cancer, or mortality was measured. Secondary outcomes included these individual constituents and microvascular complications. Results: In the same model, and using metformin monotherapy as the referent, the adjusted hazard ratio (aHR) for the primary end point was significantly increased for sulfonylurea monotherapy (1.436, 95% confidence interval [CI] 1.354–1.523), insulin monotherapy (1.808, 95% CI 1.630–2.005), and insulin plus metformin (1.309, 95% CI 1.150–1.491). In glycosylated hemoglobin/morbidity subgroups, patients treated with insulin monotherapy had aHRs for the primary outcome ranging from 1.469 (95% CI 0.978–2.206) to 2.644 (95% CI 1.896–3.687). For all secondary outcomes, insulin monotherapy had increased aHRs: myocardial infarction (1.954, 95% CI 1.479–2.583), major adverse cardiac events (1.736, 95% CI 1.441–2.092), stroke (1.432, 95% CI 1.159–1.771), renal complications (3.504, 95% CI 2.718–4.518), neuropathy (2.146, 95% CI 1.832–2.514), eye complications (1.171, 95% CI 1.057–1.298), cancer (1.437, 95% CI 1.234–1.674), or all-cause mortality (2.197, 95% CI 1.983–2.434). When compared directly, aHRs were higher for insulin monotherapy vs

  18. Increased serum levels of growth hormone and insulin-like growth factor-I associated with simultaneous decrease of circulating insulin in postmenopausal women receiving hormone replacement therapy.

    PubMed

    Fonseca, E; Ochoa, R; Galván, R; Hernández, M; Mercado, M; Zárate, A

    1999-01-01

    Decreases in circulating growth hormone (GH) and its main biological messenger insulin-like growth factor-I (IGF-I) have been interpreted as part of the aging process. Because estrogens participate in modulating GH synthesis and secretion, hypoestrogenism in menopausal women may lead to GH deficiency. The aim of the present study was to determine the effect of hormone replacement therapy (HRT) on both GH and IGF-I levels as well as insulin concentrations in 50 menopausal women. Patients were assigned randomly into two treatment groups of 25 each; one group received three cycles of conjugated equine estrogen (CEE) 0.625 mg/day for 21 days, and the other, 1.25 mg/day during 21 days. Each also received chlormadinone acetate for 5 days. There was a control group consisting of regularly menstruating women. In the menopausal women, HRT increased significantly (p < 0.001) the low levels of GH and IGF-I; on the contrary the baseline insulin levels declined (p < 0.001) with HRT. A significant linear correlation (r = 0.90) was found between GH and IGF-I as well as with estradiol levels (r = 0.74) in the group of menopausal women receiving CEE 0.625 mg/day. This group of patients had a significant correlation (r = -0.63) between insulin and estradiol levels. No correlation was observed in the group receiving CEE 1.25 mg/day. HRT restored GH, IGF-I, and insulin levels to normal values in all women. Further research needs to be done to establish the beneficial effect of HRT regarding the prevention of the metabolic effects presumably caused by derangement in the somatotropic axis associated with aging.

  19. Saxagliptin add-on therapy to insulin with or without metformin for type 2 diabetes mellitus: 52-week safety and efficacy.

    PubMed

    Barnett, Anthony H; Charbonnel, Bernard; Li, Jia; Donovan, Mark; Fleming, Douglas; Iqbal, Nayyar

    2013-10-01

    Achievement of glycemic control is an important objective in the management of type 2 diabetes mellitus (T2DM). The objective of this study was to evaluate the safety and efficacy of the dipeptidyl peptidase-4 inhibitor saxagliptin versus placebo as add-on therapy in patients with T2DM inadequately controlled with insulin alone or insulin plus metformin. This was a long-term (28-week) extension of a short-term (24-week), randomized, double-blind, parallel-group trial of saxagliptin 5 mg once daily versus placebo as add-on therapy to open-label insulin or insulin plus metformin therapy totaling 52 weeks of treatment. In contrast with the goal of maintaining a stable insulin dosage during the short-term phase, during the extension phase the insulin dosage was flexible and adjusted as deemed appropriate by the investigator. The study was conducted in a clinical practice setting, including family practice and hospital sites. Patients with T2DM aged 18-78 years with glycated hemoglobin (HbA1c) 7.5-11 % on a stable insulin regimen (30-150 U/day with or without metformin) for ≥8 weeks at screening were included in the study. Patients were stratified by metformin use and randomly assigned 2:1 to oral saxagliptin 5 mg (n = 304) or placebo (n = 151) once daily. All patients who completed the initial 24 weeks of treatment were eligible to participate in the 28-week extension, regardless of whether they had required rescue treatment. The main outcome measure was change in HbA1c from baseline to week 52. In general, the outcomes achieved at week 24 were sustained to week 52. Adjusted mean change from baseline HbA1c at week 52 was greater with saxagliptin (-0.75 %) versus placebo (-0.38 %); the adjusted between-group difference was -0.37 % (95 % CI -0.55 to -0.19); between-group differences were similar in patients treated with metformin (-0.37 % [95 % CI -0.59 to -0.15]) and without metformin (-0.37 % [95 % CI -0.69 to -0.04]). At week 52, a greater proportion of patients

  20. Intensive Stuttering Modification Therapy: A Multidimensional Assessment of Treatment Outcomes

    ERIC Educational Resources Information Center

    Blomgren, Michael; Roy, Nelson; Callister, Thomas; Merrill, Ray M.

    2005-01-01

    Nineteen adults who stutter participated in a 3-week intensive stuttering modification treatment program (the Successful Stuttering Management Program [SSMP]). A series of 14 fluency and affective-based measures were assessed before treatment, immediately after treatment, and 6 months after treatment. Measures included stuttering frequency; the…

  1. Effectiveness of Intensive, Group Therapy for Teenagers Who Stutter

    ERIC Educational Resources Information Center

    Fry, Jane; Millard, Sharon; Botterill, Willie

    2014-01-01

    Background: Treatment of adolescents who stutter is an under-researched area that would benefit from greater attention. Aims: To investigate whether an intensive treatment programme for older teenagers who stutter, aged over 16 years of age, is effective in reducing overt and covert aspects of stuttering. Methods & Procedures: A…

  2. Effectiveness of Intensive, Group Therapy for Teenagers Who Stutter

    ERIC Educational Resources Information Center

    Fry, Jane; Millard, Sharon; Botterill, Willie

    2014-01-01

    Background: Treatment of adolescents who stutter is an under-researched area that would benefit from greater attention. Aims: To investigate whether an intensive treatment programme for older teenagers who stutter, aged over 16 years of age, is effective in reducing overt and covert aspects of stuttering. Methods & Procedures: A…

  3. Intensive Stuttering Modification Therapy: A Multidimensional Assessment of Treatment Outcomes

    ERIC Educational Resources Information Center

    Blomgren, Michael; Roy, Nelson; Callister, Thomas; Merrill, Ray M.

    2005-01-01

    Nineteen adults who stutter participated in a 3-week intensive stuttering modification treatment program (the Successful Stuttering Management Program [SSMP]). A series of 14 fluency and affective-based measures were assessed before treatment, immediately after treatment, and 6 months after treatment. Measures included stuttering frequency; the…

  4. Effect of combined hormonal and insulin therapy on the steroid hormone receptors and growth factors signalling in diabetic mice prostate

    PubMed Central

    Fávaro, Wagner J; Cagnon, Valéria H A

    2010-01-01

    Diabetes causes harmful effects on prostatic morphology and function. However, there still are doubts about the occurrence of various diseases in the prostate, as well as abnormal angiogenesis in relation to diabetes. Thus, the aim of this study was to correlate and quantify the level of the steroid hormone receptors and the angiogenic and antiangiogenic factors in non-obese diabetic mice (Nod) after combined hormonal and insulin therapy. Sixty mice were divided into six groups after 20 days of diabetes: the control group received 0.9% NaCl, as did the diabetic group. The diabetic-insulin group received insulin, the diabetic-testosterone group received testosterone cypionate, the diabetic-oestrogen group received 17β-oestradiol, and the diabetic-insulin–testosterone–oestrogen group received insulin, testosterone and oestrogen simultaneously. After 20 days, the ventral lobe was processed for immunocytochemical and hormonal analyses. The results showed that the lowest serum testosterone and androgen receptor levels were found in the diabetic group and the highest testosterone and androgen receptor levels in the diabetic-insulin–testosterone–oestrogen group. The serum oestrogen level and its receptor showed changes opposite to those of testosterone and its receptor. The endostatin reactivity was mainly decreased in diabetic mice. The greatest IGFR-1 and VEGF reactivities occurred in diabetic mice. Thus, diabetes led to the prostatic hormonal imbalance, affecting molecular dynamics and angiogenesis in this organ. Combined insulin and steroid hormone therapy partially restored the hormonal and angiogenic imbalance caused by diabetes. PMID:21039986

  5. Closed-loop insulin therapy improves glycemic control in children aged <7 years: a randomized controlled trial.

    PubMed

    Dauber, Andrew; Corcia, Liat; Safer, Jason; Agus, Michael S D; Einis, Sara; Steil, Garry M

    2013-02-01

    To assess the possibility of improving nocturnal glycemic control as well as meal glycemic response using closed-loop therapy in children aged <7 years. This was a randomized controlled crossover trial comparing closed-loop with standard open-loop insulin pump therapy performed in an inpatient clinical research center. Ten subjects aged <7 years with type 1 diabetes for >6 months treated with insulin pump therapy were studied. Closed-loop therapy and standard open-loop therapy were compared from 10:00 p.m. to 12:00 p.m. on 2 consecutive days. The primary outcome was plasma glucose time in range (110-200 mg/dL) during the night (10:00 p.m.-8:00 a.m.). Secondary outcomes included peak postprandial glucose levels, incidence of hypoglycemia, degree of hyperglycemia, and prelunch glucose levels. A trend toward a higher mean nocturnal time within target range was noted for closed- versus open-loop therapy, although not reaching statistical significance (5.3 vs. 3.2 h, P = 0.12). There was no difference in peak postprandial glucose or number of episodes of hypoglycemia. There was significant improvement in time spent >300 mg/dL overnight with closed-loop therapy (0.18 vs. 1.3 h, P = 0.035) and the total area under the curve of glucose >200 mg/dL (P = 0.049). Closed-loop therapy returned prelunch blood glucose closer to target (189 vs. 273 mg/dL on open loop, P = 0.009). Closed-loop insulin delivery decreases the severity of overnight hyperglycemia without increasing the incidence of hypoglycemia. The therapy is better able to reestablish target glucose levels in advance of a subsequent meal. Younger children with type 1 diabetes may reap significant benefits from closed-loop therapy.

  6. Defective Insulin Signalling, Mediated by Inflammation, Connects Obesity to Alzheimer Disease; Relevant Pharmacological Therapies and Preventive Dietary Interventions.

    PubMed

    Rodriguez-Casado, Arantxa; Toledano-Díaz, Adolfo; Toledano, Adolfo

    2017-01-01

    Recent evidence suggests that obesity, besides being a risk factor for cardiovascular events, also increases the risk of Alzheimer's disease. Insulin resistance is common in all cases of obesity and appears to be the linkage between both diseases. Obesity, often associated with excessive fat and sugar intake, represents a preclinical stage toward insulin resistance during which nutrition intervention is likely to have maximum effect. In this way, healthy lifestyles lifetime to prevent obesity-related modifiable risk factors such as inflammation, oxidative stress and metabolic disorders could be simultaneously beneficial for preserving cognition and controlling the Alzheimer's disease. This review relates extensive research literature on facts linking nutrients and dietary patterns to obesity and Alzheimer's disease. In addition briefly presents molecular mechanisms involved in obesity- induced insulin resistance and the contribution of peripheral inflammatory and defective insulin signalling pathways, as well as ectopic lipids accumulation to Alzheimer's development through brain inflammation, neuronal insulin resistance, and cognitive dysfunction seen in Alzheimer's disease. The work relates current and emerging pharmacological and non-pharmacological therapies for the management of obesity, insulin resistance and Alzheimer's considering them as disorders with common molecular features. The findings of this review validate the importance of some nutritional interventions as possible approach to prevent or delay simultaneously progression of Alzheimer's disease and obesity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Anabolic Effect of Insulin Therapy on the Bone: Osteoprotegerin and Osteocalcin Up-Regulation in Streptozotocin-Induced Diabetic Rats.

    PubMed

    Bortolin, Raul Hernandes; Freire Neto, Francisco Paulo; Arcaro, Carlos Alberto; Bezerra, João Felipe; da Silva, Flávio Santos; Ururahy, Marcela Abbott Galvão; Souza, Karla Simone da Costa; Lima, Valeria Morgiana Gualberto Duarte Moreira; Luchessi, André Ducati; Lima, Francisco Pignataro; Lia Fook, Marcus Vinicius; da Silva, Bartolomeu Jorge; Almeida, Maria das Graças; Abreu, Bento João; de Rezende, Luciana Augusto; de Rezende, Adriana Augusto

    2017-03-01

    Type 1 diabetes mellitus (T1DM) is associated with several skeletal alterations, particularly in conditions of poor glycaemic control. Insulin therapy is the major conservative treatment for T1DM; however, the effects of this hormone on bone markers of T1DM rats are limited, and the regulatory mechanisms remain elusive. Therefore, the evaluation of molecular and non-molecular parameters in a chronic animal model of T1DM-induced bone loss, treated with and without insulin, may help in elucidating the insulin mechanisms. Male Wistar rats were assigned into three groups: control, T1DM (T1DM rats induced with streptozotocin [STZ] at 40 mg/kg intravenously) and T1DM plus insulin therapy (T1DMI). After 8 weeks, we evaluated the serum biochemical, tibia histomorphometric and biomechanical parameters, as well as the gene expression of the receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and osteocalcin (OC) of femur mRNA. Compared with T1DM, the T1DMI group showed less bone loss, which was revealed by the increased trabecular width (TbWi, p < 0.001) and trabecular bone area (BAr, p < 0.01), reduced trabecular separation (TbSp, p < 0.01) and increased Young's modulus (p < 0.05). Moreover, molecular analyses indicated that the expression of OPG and OC was up-regulated (p < 0.001 and p < 0.05, respectively). In summary, the up-regulation of OPG and OC in the T1DMI group supports an anabolic effect of insulin, which was demonstrated by the maintenance of bone architecture and flexibility. These results suggest that insulin therapy may prevent T1DM-induced bone loss via the effects on the bone formation.

  8. Characterization of Insulin-Secreting Porcine Bone Marrow Stromal Cells Ex Vivo and Autologous Cell Therapy In Vivo.

    PubMed

    Do, Hai Van Thi; Loke, Wan Ting; Kee, Irene; Liang, Vivienne; David, Sebastian J; Gan, Shu Uin; Lee, Sze Sing; Ng, Wai Har; Koong, Heng Nung; Ong, Hock Soo; Lee, Kok Onn; Calne, Roy Y; Kon, Oi Lian

    2015-01-01

    Cell therapy could potentially meet the need for pancreas and islet transplantations in diabetes mellitus that far exceeds the number of available donors. Bone marrow stromal cells are widely used in clinical trials mainly for their immunomodulatory effects with a record of safety. However, less focus has been paid to developing these cells for insulin secretion by transfection. Although murine models of diabetes have been extensively used in gene and cell therapy research, few studies have shown efficacy in large preclinical animal models. Here we report optimized conditions for ex vivo expansion and characterization of porcine bone marrow stromal cells and their permissive expression of a transfected insulin gene. Our data show that these cells resemble human bone marrow stromal cells in surface antigen expression, are homogeneous, and can be reproducibly isolated from outbred Yorkshire-Landrace pigs. Porcine bone marrow stromal cells were efficiently expanded in vitro to >10(10) cells from 20 ml of bone marrow and remained karyotypically normal during expansion. These cells were electroporated with an insulin expression plasmid vector with high efficiency and viability, and secreted human insulin and C-peptide indicating appropriate processing of proinsulin. We showed that autologous insulin-secreting bone marrow stromal cells implanted and engrafted in the liver of a streptozotocin-diabetic pig that modeled type 1 diabetes resulted in partial, but significant, improvement in hyperglycemia that could not be ascribed to regeneration of endogenous β-cells. Glucose-stimulated insulin secretion in vivo from implanted cells in the treated pig was documented by a rise in serum human C-peptide levels during intravenous glucose tolerance tests. Compared to a sham-treated control pig, this resulted in significantly reduced fasting hyperglycemia, a slower rise in serum fructosamine, and prevented weight loss. Taken together, this study suggests that bone marrow stromal

  9. 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

  10. Description of an Intensive Dialectical Behavior Therapy Program for Multidiagnostic Clients with Eating Disorders

    ERIC Educational Resources Information Center

    Federici, Anita; Wisniewski, Lucene; Ben-Porath, Denise

    2012-01-01

    The authors describe an intensive outpatient dialectical behavior therapy (DBT) program for multidiagnostic clients with eating disorders who had not responded adequately to standard, empirically supported treatments for eating disorders. The program integrates DBT with empirically supported cognitive behavior therapy approaches that are well…

  11. Physical Therapy Observation and Assessment in the Neonatal Intensive Care Unit

    ERIC Educational Resources Information Center

    Byrne, Eilish; Campbell, Suzann K.

    2013-01-01

    This article presents the elements of the Observation and Assessment section of the Infant Care Path for Physical Therapy in the Neonatal Intensive Care Unit (NICU). The types of physical therapy assessments presented in this path are evidence-based and the suggested timing of these assessments is primarily based on practice knowledge from expert…

  12. Physical Therapy Observation and Assessment in the Neonatal Intensive Care Unit

    ERIC Educational Resources Information Center

    Byrne, Eilish; Campbell, Suzann K.

    2013-01-01

    This article presents the elements of the Observation and Assessment section of the Infant Care Path for Physical Therapy in the Neonatal Intensive Care Unit (NICU). The types of physical therapy assessments presented in this path are evidence-based and the suggested timing of these assessments is primarily based on practice knowledge from expert…

  13. Description of an Intensive Dialectical Behavior Therapy Program for Multidiagnostic Clients with Eating Disorders

    ERIC Educational Resources Information Center

    Federici, Anita; Wisniewski, Lucene; Ben-Porath, Denise

    2012-01-01

    The authors describe an intensive outpatient dialectical behavior therapy (DBT) program for multidiagnostic clients with eating disorders who had not responded adequately to standard, empirically supported treatments for eating disorders. The program integrates DBT with empirically supported cognitive behavior therapy approaches that are well…

  14. Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes.

    PubMed

    de Boer, Ian H; Sun, Wanjie; Cleary, Patricia A; Lachin, John M; Molitch, Mark E; Steffes, Michael W; Zinman, Bernard

    2011-12-22

    An impaired glomerular filtration rate (GFR) leads to end-stage renal disease and increases the risks of cardiovascular disease and death. Persons with type 1 diabetes are at high risk for kidney disease, but there are no interventions that have been proved to prevent impairment of the GFR in this population. In the Diabetes Control and Complications Trial (DCCT), 1441 persons with type 1 diabetes were randomly assigned to 6.5 years of intensive diabetes therapy aimed at achieving near-normal glucose concentrations or to conventional diabetes therapy aimed at preventing hyperglycemic symptoms. Subsequently, 1375 participants were followed in the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. Serum creatinine levels were measured annually throughout the course of the two studies. The GFR was estimated with the use of the Chronic Kidney Disease Epidemiology Collaboration formula. We analyzed data from the two studies to determine the long-term effects of intensive diabetes therapy on the risk of impairment of the GFR, which was defined as an incident estimated GFR of less than 60 ml per minute per 1.73 m(2) of body-surface area at two consecutive study visits. Over a median follow-up period of 22 years in the combined studies, impairment of the GFR developed in 24 participants assigned to intensive therapy and in 46 assigned to conventional therapy (risk reduction with intensive therapy, 50%; 95% confidence interval, 18 to 69; P=0.006). Among these participants, end-stage renal disease developed in 8 participants in the intensive-therapy group and in 16 in the conventional-therapy group. As compared with conventional therapy, intensive therapy was associated with a reduction in the mean estimated GFR of 1.7 ml per minute per 1.73 m(2) during the DCCT study but during the EDIC study was associated with a slower rate of reduction in the GFR and an increase in the mean estimated GFR of 2.5 ml per minute per 1.73 m(2) (P<0.001 for

  15. Delivery confirmation of bolus electron conformal therapy combined with intensity modulated x-ray therapy

    SciTech Connect

    Kavanaugh, James A.; Hogstrom, Kenneth R.; Fontenot, Jonas P.; Henkelmann, Gregory; Chu, Connel; Carver, Robert A.

    2013-02-15

    Purpose: The purpose of this study was to demonstrate that a bolus electron conformal therapy (ECT) dose plan and a mixed beam plan, composed of an intensity modulated x-ray therapy (IMXT) dose plan optimized on top of the bolus ECT plan, can be accurately delivered. Methods: Calculated dose distributions were compared with measured dose distributions for parotid and chest wall (CW) bolus ECT and mixed beam plans, each simulated in a cylindrical polystyrene phantom that allowed film dose measurements. Bolus ECT plans were created for both parotid and CW PTVs (planning target volumes) using 20 and 16 MeV beams, respectively, whose 90% dose surface conformed to the PTV. Mixed beam plans consisted of an IMXT dose plan optimized on top of the bolus ECT dose plan. The bolus ECT, IMXT, and mixed beam dose distributions were measured using radiographic films in five transverse and one sagittal planes for a total of 36 measurement conditions. Corrections for film dose response, effects of edge-on photon irradiation, and effects of irregular phantom optical properties on the Cerenkov component of the film signal resulted in high precision measurements. Data set consistency was verified by agreement of depth dose at the intersections of the sagittal plane with the five measured transverse planes. For these same depth doses, results for the mixed beam plan agreed with the sum of the individual depth doses for the bolus ECT and IMXT plans. The six mean measured planar dose distributions were compared with those calculated by the treatment planning system for all modalities. Dose agreement was assessed using the 4% dose difference and 0.2 cm distance to agreement. Results: For the combined high-dose region and low-dose region, pass rates for the parotid and CW plans were 98.7% and 96.2%, respectively, for the bolus ECT plans and 97.9% and 97.4%, respectively, for the mixed beam plans. For the high-dose gradient region, pass rates for the parotid and CW plans were 93.1% and 94

  16. The effects of high intensity laser therapy on pain and function in patients with knee osteoarthritis.

    PubMed

    Kim, Gook-Joo; Choi, Jioun; Lee, Sangyong; Jeon, Chunbae; Lee, Kwansub

    2016-11-01

    [Purpose] The purpose of this study was to examine the effects of high intensity laser therapy (HILT) on pain and function in patients with knee osteoarthritis. [Subjects and Methods] In this study, an experiment was conducted on 20 subjects who were divided into the control group (n=10), which would receive conservative physical therapy (CPT), and the experimental group (n=10), which would receive effects of high intensity laser therapy after conservative physical therapy. All patients received their respective therapies three times each week over a four-week period. In terms of the intensity of the high intensity laser therapy, it was applied to each patient in the tibia and femoral epicondyle for five minutes while the patient's knee joint was bent at around 30° and the separation distance between the handpiece and the skin was maintained at around 1 cm. The visual analogue scale was used to measure pain, and the Korean Western Ontario and McMaster Universities Osteoarthritis Index was used for functional evaluations. [Results] The comparison of differences in the measurements taken before and after the experiment within each group showed a statistically significant decline in both the VAS and the K-WOMAC. The comparison of the two groups showed that the high intensity laser therapy group had statistically significant lower scores in both the visual analogue scale and the Korean Western Ontario and McMaster Universities Osteoarthritis Index than the conservative physical therapy group. [Conclusion] High intensity laser therapy is considered an effective non-surgical intervention for reducing pain in patients with knee osteoarthritis and helping them to perform daily activities.

  17. The effects of high intensity laser therapy on pain and function in patients with knee osteoarthritis

    PubMed Central

    Kim, Gook-Joo; Choi, Jioun; Lee, Sangyong; Jeon, Chunbae; Lee, Kwansub

    2016-01-01

    [Purpose] The purpose of this study was to examine the effects of high intensity laser therapy (HILT) on pain and function in patients with knee osteoarthritis. [Subjects and Methods] In this study, an experiment was conducted on 20 subjects who were divided into the control group (n=10), which would receive conservative physical therapy (CPT), and the experimental group (n=10), which would receive effects of high intensity laser therapy after conservative physical therapy. All patients received their respective therapies three times each week over a four-week period. In terms of the intensity of the high intensity laser therapy, it was applied to each patient in the tibia and femoral epicondyle for five minutes while the patient’s knee joint was bent at around 30° and the separation distance between the handpiece and the skin was maintained at around 1 cm. The visual analogue scale was used to measure pain, and the Korean Western Ontario and McMaster Universities Osteoarthritis Index was used for functional evaluations. [Results] The comparison of differences in the measurements taken before and after the experiment within each group showed a statistically significant decline in both the VAS and the K-WOMAC. The comparison of the two groups showed that the high intensity laser therapy group had statistically significant lower scores in both the visual analogue scale and the Korean Western Ontario and McMaster Universities Osteoarthritis Index than the conservative physical therapy group. [Conclusion] High intensity laser therapy is considered an effective non-surgical intervention for reducing pain in patients with knee osteoarthritis and helping them to perform daily activities. PMID:27942148

  18. Application of Histogram Analysis in Radiation Therapy (HART) in Intensity Modulation Radiation Therapy (IMRT) Treatments

    NASA Astrophysics Data System (ADS)

    Pyakuryal, Anil

    2009-03-01

    A carcinoma is a malignant cancer that emerges from epithelial cells in structures through out the body.It invades the critical organs, could metastasize or spread to lymph nodes.IMRT is an advanced mode of radiation therapy treatment for cancer. It delivers more conformal doses to malignant tumors sparing the critical organs by modulating the intensity of radiation beam.An automated software, HART (S. Jang et al.,2008,Med Phys 35,p.2812) was used for efficient analysis of dose volume histograms (DVH) for multiple targets and critical organs in four IMRT treatment plans for each patient. IMRT data for ten head and neck cancer patients were exported as AAPM/RTOG format files from a commercial treatment planning system at Northwestern Memorial Hospital (NMH).HART extracted DVH statistics were used to evaluate plan indices and to analyze dose tolerance of critical structures at prescription dose (PD) for each patient. Mean plan indices (n=10) were found to be in good agreement with published results for Linac based plans. The least irradiated volume at tolerance dose (TD50) was observed for brainstem and the highest volume for larynx in SIB treatment techniques. Thus HART, an open source platform, has extensive clinical implications in IMRT treatments.

  19. Adherence to Insulin Pen Therapy Is Associated with Reduction in Healthcare Costs Among Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Chandran, Arthi; Bonafede, Machaon K.; Nigam, Sonali; Saltiel-Berzin, Rita; Hirsch, Laurence J.; Lahue, Betsy J.

    2015-01-01

    Background Type 2 diabetes mellitus is a chronic metabolic disorder that poses a significant economic burden on the US healthcare system associated with direct and indirect medical costs, loss of productivity, and premature mortality. Objectives To determine whether increased adherence to therapy among patients with type 2 diabetes who use an insulin pen is associated with reduced healthcare costs, and to describe the overall healthcare costs of patients with type 2 diabetes. Methods This retrospective claims database analysis used the Truven Health MarketScan Commercial and Medicare Supplemental databases to identify patients diagnosed with type 2 diabetes with at least 1 insulin pen prescription claim between January 2006 and September 2010. Insulin pen adherence was measured using the medication possession ratio (MPR). The cost outcomes included all-cause and type 2 diabetes–related costs by type of service (ie, inpatient, outpatient medical, outpatient pharmacy), which were calculated in 2011 US dollars. Insulin adherence and overall healthcare costs were evaluated over the 12-month postindex period. Results A total of 32,361 patients met the study inclusion criteria, with an average MPR of 0.63 (standard deviation [SD], 0.29). Overall, patients with type 2 diabetes who used an insulin pen had an average annual healthcare cost of $19,612, which was driven by inpatient costs (37.2%) and outpatient pharmacy costs (24.4%). There is a significant difference in the average annual per-patient healthcare expenditures between the least adherent group (MPR <0.20; 11.0% of patients) and the most adherent group (MPR >0.80; 34.6% of patients) $26,310 versus $23,839, respectively (P = .007). Patients with the greatest insulin adherence had higher overall pharmacy costs than patients with the lowest insulin adherence ($10,174 vs $5395, respectively; P <.001). Conclusions The total healthcare expenditures of patients with type 2 diabetes who utilized insulin pens decreased

  20. Adherence to Insulin Pen Therapy Is Associated with Reduction in Healthcare Costs Among Patients with Type 2 Diabetes Mellitus.

    PubMed

    Chandran, Arthi; Bonafede, Machaon K; Nigam, Sonali; Saltiel-Berzin, Rita; Hirsch, Laurence J; Lahue, Betsy J

    2015-05-01

    Type 2 diabetes mellitus is a chronic metabolic disorder that poses a significant economic burden on the US healthcare system associated with direct and indirect medical costs, loss of productivity, and premature mortality. To determine whether increased adherence to therapy among patients with type 2 diabetes who use an insulin pen is associated with reduced healthcare costs, and to describe the overall healthcare c