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  1. Glimepiride combined with morning insulin glargine, bedtime neutral protamine hagedorn insulin, or bedtime insulin glargine in patients with type 2 diabetes. A randomized, controlled trial.

    Science.gov (United States)

    Fritsche, Andreas; Schweitzer, Matthias Axel; Häring, Hans-Ulrich

    2003-06-17

    Patients with type 2 diabetes are often treated with oral antidiabetic agents plus a basal insulin. To investigate the efficacy and safety of glimepiride combined with either morning or bedtime insulin glargine or bedtime neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes. Open-label, randomized, controlled trial. 111 centers in 13 European countries. 695 patients with type 2 diabetes who were previously treated with oral antidiabetic agents. Randomization to treatment with morning insulin glargine, bedtime NPH insulin, or bedtime insulin glargine for 24 weeks in addition to 3 mg of glimepiride. The insulin dose was titrated by using a predefined regimen to achieve fasting blood glucose levels of 5.56 mmol/L or lower (weight. Hemoglobin A(1c) levels improved by -1.24% (two-sided 90% CI, -1.10% to -1.38%) with morning insulin glargine, by -0.96% (CI, -0.81% to -1.10%) with bedtime insulin glargine, and by -0.84% (CI, -0.69% to -0.98%) with bedtime NPH insulin. Hemoglobin A(1c) improvement was more pronounced with morning insulin glargine than with NPH insulin (0.40% [CI, 0.23% to 0.58%]; P = 0.001) or bedtime insulin glargine (0.28% [CI, 0.11% to 0.46%]; P = 0.008). Baseline to end-point fasting blood glucose levels improved similarly in all three groups. Nocturnal hypoglycemia was less frequent with morning (39 of 236 patients [17%]) and bedtime insulin glargine (52 of 227 patients [23%]) than with bedtime NPH insulin (89 of 232 patients [38%]) (P bedtime insulin glargine than with glimepiride in combination with bedtime NPH insulin in patients with type 2 diabetes. Morning insulin glargine provided better glycemic control than did bedtime insulin glargine or bedtime NPH insulin.

  2. Clinical Pharmacokinetics and Pharmacodynamics of Insulin Glargine 300 U/mL.

    Science.gov (United States)

    Clements, Jennifer N; Threatt, Tiffaney; Ward, Eileen; Shealy, Kayce M

    2017-05-01

    Concentrated insulin analogs have recently been approved and are available for clinical use in the management of diabetes mellitus. One new product is insulin glargine U-300 (Sanofi), a basal concentrated insulin of 300 U/mL. Several studies have been conducted and completed evaluating blood samples for the pharmacokinetics of insulin glargine U-300 and euglycemic clamp procedures for the pharmacodynamics. This concentrated insulin has a low within-day variability and high day-to-day reproducibility, allowing for a more constant and prolonged duration of action, compared with insulin glargine U-100 (100 U/mL). Insulin glargine U-300 is equally effective, when compared with insulin glargine U-100 for glycemic control in patients with type 1 and 2 diabetes mellitus. Insulin glargine U-300 has a similar efficacy profile to insulin glargine U-100 for glycemic control, yet with lower rates of nocturnal and severe hypoglycemia. Insulin glargine U-300 can be considered an acceptable basal insulin for patients with type 1 and 2 diabetes mellitus, and it has a potential role among patients who are naïve to insulin therapy or require titration of basal insulin. Titration of insulin glargine U-300 would result in less volume and a lower risk of hypoglycemia, compared with insulin glargine U-100. This article evaluates and summarizes the pharmacokinetics and pharmacodynamics of insulin glargine U-300, for patients with type 1 or 2 diabetes mellitus, and summarizes its application to clinical practice.

  3. Real-world therapeutic benefits of patients on insulin glargine versus NPH insulin.

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    Fiesselmann, Albrecht; Wiesner, Tobias; Fleischmann, Holger; Bramlage, Peter

    2016-10-01

    The addition of a single injection of insulin to the oral drugs (basal supported oral therapy; BOT) has been shown to greatly reduce blood glucose levels. The intermediate-acting NPH insulin (NPH) and the long-acting insulin glargine (Lantus(®)) have been compared for use in BOT in numerous clinical trials; however, their efficacy and safety in a real-life setting have not been described. TIP (therapeutic benefits of patients on insulin glargine vs. NPH insulin being poorly controlled on prior short-time basal-insulin supported therapy with NPH insulin or insulin glargine) is a non-interventional, multicentre, observational study over 24 weeks. A total of 2629 patients were enrolled and 1931 were fully evaluable (1614 insulin glargine, 303 NPH insulin). Propensity scoring (PSM) was used to match 570 patients into 2 similar cohorts of 285 patients. In the PSM cohort, a slightly greater reduction in FBG and HbA1c levels was seen in the insulin glargine group compared to the NPH group. A weight loss, which was slightly more pronounced in insulin glargine patients despite receiving a lower insulin dose relative to the NPH group, was seen in both the groups. Additionally, hypoglycaemia, including nocturnal and severe events, was more prevalent in the patients receiving BOT with NPH. The occurrence of new micro- or macro-vascular complications and adverse events was low for both groups. A large proportion of patients changed from NPH therapy to insulin glargine therapy during the study, which was mainly attributable to insufficient glucose modulation. Improvements in quality of life and treatment satisfaction were found for both types of insulin. This observational study provides evidence from a real-life setting that BOT with insulin glargine provides slightly greater reductions in weight, FBG and HbA1c levels, with a lower risk of hypoglycaemia than patients receiving NPH. This conclusion indicates that insulin glargine may be preferable to NPH insulin for BOT.

  4. Comparison of insulin degludec with insulin glargine in insulin-naive subjects with Type 2 diabetes

    DEFF Research Database (Denmark)

    Rodbard, H W; Cariou, B; Zinman, B

    2013-01-01

    The aim of this study was to compare long-term safety and efficacy of the basal insulin analogue degludec with glargine in insulin-naive subjects with Type 2 diabetes.......The aim of this study was to compare long-term safety and efficacy of the basal insulin analogue degludec with glargine in insulin-naive subjects with Type 2 diabetes....

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

    Science.gov (United States)

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

    2007-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Pešić Milica

    2007-01-01

    Full Text Available Background/Aim. Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin for basal insulin supply in patients with type 1 diabetes. Methods. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IIT were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15; 2. NPH insulin twice daily (n = 15; 3. insulin glargine once daily (n = 18. Meal time insulin aspart was continued in all groups. Results. Fasting blood glucose (FBG was lower in the glargine group (7.30±0.98 mmol/l than in the twice daily NPH group (7.47±1.06 mmol/l, but without significant difference. FBG was significantly higher in the once daily NPH group (8.44±0.85 mmol/l; p < 0.05. HbA1c after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72±0.86% to 6.87±0.50%, as well as in the twice daily NPH group (from 7.80±0.83% to 7.01±0.63%. Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56±2.09 than in both NPH groups (9.0±1.65 in twice daily NPH group and 8.13±1.30 in other NPH group (episodes/patients-month, p < 0.05. Conclusion. Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbA1c and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

  7. Insulin glargine and cancer risk in patients with diabetes: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xulei Tang

    Full Text Available AIM: The role of insulin glargine as a risk factor for cancer is controversial in human studies. The aim of this meta-analysis was to evaluate the relationship between insulin glargine and cancer incidence. METHODS: All observational studies and randomized controlled trials evaluating the relationship of insulin glargine and cancer risk were identified in PubMed, Embase, Web of Science, Cochrane Library and the Chinese Biomedical Medical Literature Database, through March 2012. Odds ratios (ORs with corresponding 95% confidence interval (CI were calculated with a random-effects model. Confidence in the estimates of the obtained effects (quality of evidence was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: A total of 11 studies including 448,928 study subjects and 19,128 cancer patients were finally identified for the meta-analysis. Insulin glargine use was associated with a lower odds of cancer compared with non-glargine insulin use (OR 0.81, 95% CI 0.68 to 0.98, P = 0.03; very low-quality evidence. Glargine did not increase the odds of breast cancer (OR 0.99, 95% CI 0.68 to 1.46, P = 0.966; very low-quality evidence. Compared with non-glargine insulin, no significant association was found between insulin glargine and prostate cancer, pancreatic cancer and respiratory tract cancer. Insulin glargine use was associated with lower odds of other site-specific cancer. CONCLUSIONS: Results from the meta-analysis don't support the link between insulin glargine and an increased risk of cancer and the confidence in the estimates of the effects is very low. Further studies are needed to examine the relation between insulin glargine and cancer risk, especially breast cancer.

  8. Insulin glargine 300 U/ml in the management of diabetes: clinical utility and patient perspectives

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    de Galan BE

    2016-10-01

    Full Text Available Bastiaan E de Galan Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands Abstract: There is ongoing interest in optimizing basal insulin treatment by developing insulins with a flat pharmacological profile, a long duration of action (typically beyond 24 hours and minimum day-to-day variation. Glargine-300 is a modified form of the long-acting insulin analog glargine in that it has been concentrated at 300 units/mL rather than the conventional 100 units/mL. Glargine-300 has a longer duration of action and a flatter pharmacological profile than original glargine-100. This property allows for more flexibility around the timing of administration, when injected once per day. Open-label studies in patients with diabetes have shown that treatment with glargine-300 achieves comparable glycemic control compared to treatment with glargine-100, albeit with consistently higher insulin requirements. These studies also showed that treatment with glargine-300 was associated with lower risks of nocturnal hypoglycemia in patients with type 2 diabetes, particularly those already on insulin, whereas data are mixed in insulin-naïve patients with type 2 diabetes or in patients with type 1 diabetes. Treatment with glargine-300 did not appear to affect the risk of overall hypoglycemia, whereas studies lacked sufficient power to investigate the effect on the risk of severe hypoglycemia. Future studies need to establish the role of glargine-300 in the treatment of diabetes alongside the other new long-acting insulin analog, insulin degludec, which was recently introduced to the market. Keywords: insulin glargine-300, type 1 diabetes, type 2 diabetes, hypoglycemia, HbA1c, patient-reported outcomes

  9. Addition of neutral protamine lispro insulin or insulin glargine to oral type 2 diabetes regimens for patients with suboptimal glycemic control: a randomized trial.

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    Esposito, Katherine; Ciotola, Miryam; Maiorino, Maria Ida; Gualdiero, Roberto; Schisano, Bruno; Ceriello, Antonio; Beneduce, Flora; Feola, Giovanni; Giugliano, Dario

    2008-10-21

    Injection of long-acting insulin at bedtime is a common therapeutic approach for patients with type 2 diabetes that is poorly controlled with oral regimens. Neutral protamine lispro (NPL) insulin has demonstrated better glycemic control and similar incidence of hypoglycemic events than that of neutral protamine Hagedorn insulin. To compare the clinical efficacy and safety of bedtime NPL insulin or insulin glargine in patients with type 2 diabetes who had suboptimal glycemic control while receiving stable doses of metformin and sulfonylurea. Open-label, randomized trial. Teaching hospital (Azienda Ospedaliera Universitaria, Second University of Naples), Naples, Italy. 116 adults receiving stable doses of metformin plus sulfonylurea for longer than 90 days with hemoglobin A(1c) (HbA(1c)) levels of 7.5% to 10% and fasting plasma glucose levels of 6.7 mmol/L or greater (> or =120 mg/dL). 10 IU of NPL insulin or insulin glargine injected subcutaneously at bedtime with weekly dose titrations to target fasting glucose levels less than 5.6 mmol/L (weight. Twenty patients in each group had continuous glucose monitoring for 3 consecutive days before adding insulin and at week 36. Improvement in HbA(1c) levels was similar in both groups (1.83% and 1.89% for NPL and glargine, respectively). The difference between the groups was 0.06 percentage point (95% CI, -0.1 to 0.15 percentage points). Secondary outcomes did not differ between groups. Hemoglobin A(1c) levels less than 7% occurred in 62% of patients receiving NPL and 64% of patients receiving glargine (difference, 2.0 percentage points [CI, -1.1 to 5.0 percentage points]). Fasting plasma glucose levels less than 5.6 mmol/L (<100 mg/dL) occurred in 40% of patients receiving NPL and 41% of patients receiving glargine (difference, 1.0 percentage point [CI, -0.9 to 3.0 percentage points]). Any hypoglycemic event occurred in 74% of patients receiving NPL and 67% of patients receiving glargine (difference, 7 percentage points

  10. Insulin glargine 300 U/mL in the management of diabetes: clinical utility and patient perspectives

    NARCIS (Netherlands)

    Galan, B.E. de

    2016-01-01

    There is ongoing interest in optimizing basal insulin treatment by developing insulins with a flat pharmacological profile, a long duration of action (typically beyond 24 hours) and minimum day-to-day variation. Glargine-300 is a modified form of the long-acting insulin analog glargine in that it

  11. Insulin detemir versus insulin glargine for type 2 diabetes mellitus

    NARCIS (Netherlands)

    Swinnen, Sanne G.; Simon, Airin C. R.; Holleman, Frits; Hoekstra, Joost B.; DeVries, J. Hans

    2011-01-01

    Chronically elevated blood glucose levels are associated with significant morbidity and mortality. Many diabetes patients will eventually require insulin treatment to maintain good glycaemic control. There are still uncertainties about the optimal insulin treatment regimens for type 2 diabetes, but

  12. Meta-Analysis of Maternal and Neonatal Outcomes Associated with the Use of Insulin Glargine versus NPH Insulin during Pregnancy

    Directory of Open Access Journals (Sweden)

    Jacques Lepercq

    2012-01-01

    Full Text Available As glargine, an analog of human insulin, is increasingly used during pregnancy, a meta-analysis assessed its safety in this population. A systematic literature search identified studies of gestational or pregestational diabetes comparing use of insulin glargine with human NPH insulin, with at least 15 women in both arms. Data was extracted for maternal outcomes (weight at delivery, weight gain, 1st/3rd trimester HbA1c, severe hypoglycemia, gestation/new-onset hypertension, preeclampsia, and cesarean section and neonatal outcomes (congenital malformations, gestational age at delivery, birth weight, macrosomia, LGA, 5 minute Apgar score >7, NICU admissions, respiratory distress syndrome, neonatal hypoglycemia, and hyperbilirubinemia. Relative risk ratios and weighted mean differences were determined using a random effect model. Eight studies of women using glargine (331 or NPH (371 were analyzed. No significant differences in the efficacy and safety-related outcomes were found between glargine and NPH use during pregnancy.

  13. Evaluation of immunogenicity of LY2963016 insulin glargine compared with Lantus® insulin glargine in patients with type 1 or type 2 diabetes mellitus.

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    Ilag, L L; Deeg, M A; Costigan, T; Hollander, P; Blevins, T C; Edelman, S V; Konrad, R J; Ortmann, R A; Pollom, R K; Huster, W J; Zielonka, J S; Prince, M J

    2016-02-01

    To compare the immunogenicity profiles and the potential effects on clinical outcomes of LY2963016 insulin glargine (LY IGlar) and Lantus® insulin glargine (IGlar), products with identical primary amino acid sequences, in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM). To assess immunogenicity, anti-insulin glargine antibodies (measured as percent binding) were compared between treatments in 52-week (open-label) and 24-week (double-blind) randomized studies in total study populations of patients with T1DM (N = 535) and T2DM (N = 756), respectively, and two subgroups of patients with T2DM: insulin-naïve patients and those reporting prestudy IGlar treatment (prior IGlar). Relationships between insulin antibody levels and clinical outcomes were assessed using analysis of covariance and partial correlations. Insulin antibody levels were assessed using Wilcoxon rank sum. Treatment comparisons for treatment-emergent antibody response (TEAR) and incidence of detectable antibodies were analysed using Fisher's exact test. No significant treatment differences were observed for insulin antibody levels, incidence of detectable anti-insulin glargine antibodies, or incidence of TEAR [overall and endpoint, by last-observation-carried-forward (LOCF)] in patients with T1DM or patients with T2DM, including the insulin-naïve subgroup. A statistically significant difference was noted in the overall incidence of detectable antibodies but not at endpoint (LOCF) nor in TEAR for the prior IGlar subgroup of patients with T2DM. Insulin antibody levels were low (2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  14. Insulin analogues dosing and costs - comparing real-life daily doses of insulin detemir and insulin glargine in type 2 diabetes patients

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    Jakobsen Marie

    2012-09-01

    Full Text Available Abstract Background The uncertainties regarding dose similarities between basal long-acting insulin analogues remain. Recent real-world studies indicate dose similarities between insulin detemir and insulin glargine, but further studies are still warranted. The aim of this study was to compare real-life daily doses of insulin detemir and insulin glargine in type 2 diabetes patients when administered once daily. Methods We analysed 536 patient cases from general practice (63% and endocrinological outpatient clinics (37%. A self-administered questionnaire completed by the treating physician was used to obtain data on patient characteristics (gender, age, weight, height, latest HbA1c-value, daily doses, administration of and number of years treated with insulin detemir and insulin glargine, concomitant insulin use and use of non-insulin anti-diabetic medication. Both bivariate analyses and multivariate regression analyses were applied to examine whether there were differences in the daily doses of insulin detemir and insulin glargine. Results There was no significant difference in the mean daily doses of insulin detemir (0.414 U/kg and insulin glargine (0.416 U/kg (p = 0.4341. In multivariate regression analyses, age and BMI had a significant influence on daily insulin dose with the dose increasing 0.003 U/kg (p = 0.0375 and 0.008 U/kg (p = 0.0003 with every 1 increment in age and BMI, respectively. Conclusions Dose similarities between insulin detemir and insulin glargine were seen in type 2 diabetes patients when administered once daily. Thus, the use of insulin detemir and insulin glargine is not associated with different medical costs if the price and treating algorithm are similar.

  15. Comparison of Insulin Detemir and Insulin Glargine for Hospitalized Patients on a Basal-Bolus Protocol

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    Sondra Davis

    2017-04-01

    Full Text Available BACKGROUND: The primary purpose of this study is to determine whether insulin detemir is equivalent to insulin glargine in controlling hyperglycemia for the adult hospitalized patient on a basal-bolus treatment regimen. METHODS: A retrospective study was conducted at two acute care hospitals within the same health system. Patients from both facilities who were initiated on a basal-bolus subcutaneous insulin regimen were included in the study. The basal-bolus regimen consisted of three components: basal, bolus, and corrective insulin with only the data from the first seven days analyzed. Once the basal-bolus protocol was initiated, all previous glycemic agents were discontinued. The target glycemic goal of the study was 100–180 mg/dL. RESULTS: In both groups, 50% of the patients had achieved the target glycemic control goal (100–180 mg/dL by day 2 (p = 0.3. However, on the seventh or last day of basal-bolus treatment, whichever came first, 36.36% of patients receiving insulin detemir (n = 88 achieved the blood glucose reading goal compared to 52.00% in patients receiving insulin glargine (n = 100 (p = 0.03. This corresponded to an adjusted odds ratio of 2.12 (1.08 to 4.15, p = 0.03. The adjusting variables were provider type, whether the patient was hospitalized within 30 days prior and diagnosis of stroke. The mean blood glucose readings for the insulin glargine and the insulin detemir groups while on basal-bolus therapy were 200 mg/dL and 215 mg/dL, respectively (p = 0.05. The total number of blood glucose readings less than 70 mg/dL and less than 45 mg/dL was very low and there were no differences in number of episodes with hypoglycemia between the two groups. CONCLUSION: There was not a statistical difference between the two groups at 2 days, however there was on the seventh day or the last day of basal-bolus treatment. There were nonsignificant hypoglycemia events between basal insulin groups and the results for the last or seventh day

  16. Predictors of nonsevere and severe hypoglycemia during glucose-lowering treatment with insulin glargine or standard drugs in the ORIGIN trial

    National Research Council Canada - National Science Library

    Riddle, MC

    2015-01-01

    Hypoglycemia is a leading risk of glucose-lowering therapy. Treatment with insulin glargine compared with standard care early in the course of dysglycemia in the Outcome Reduction with an Initial Glargine Intervention (ORIGIN...

  17. Evaluation of exenatide versus insulin glargine for the impact on endothelial functions and cardiovascular risk markers.

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    Gurkan, Eren; Tarkun, Ilhan; Sahin, Tayfun; Cetinarslan, Berrin; Canturk, Zeynep

    2014-12-01

    To demonstrate the efficacy of exenatide versus insulin glargine on endothelial functions and cardiovascular risk markers. Thirty-four insulin and incretin-naive patients with type 2 diabetes mellitus (body mass index 25-45 kg/m(2)) who received metformin for at least two months were randomized to exenatide or insulin glargine treatment arms and followed-up for 26 weeks. Measurements of endothelial functions were done by ultrasonography, cardiovascular risk markers by serum enzyme-linked immunosorbent assay, and total body fat mass by bioimpedance. Levels of high sensitivity-C-reactive protein and endothelin-1 decreased (27.5% and 18.75%, respectively) in the exenatide arm. However, in the insulin glargine arm, fibrinogen, monocyte chemoattractant protein-1, leptin and endothelin-1 levels (13.4, 30.2, 47.5, and 80%, respectively) increased. Post-treatment flow mediated dilatation and endothelium independent vascular responses were significantly higher in both arms (p=0.0001, p=0.0001). Positive correlation was observed between the changes in body weight and endothelium-independent vasodilatation, leptin, plasminogen activator inhibitor type 1 and endothelin-1 in both arms (r=0.376, r=0.507, r=0.490, r=0.362, respectively). Insulin glargine improved endothelial functions, without leading to positive changes in cardiovascular risk markers. Exenatide treatment of 26 weeks resulted in reduced body weight and improvement in certain cardiovascular risk markers and endothelial functions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Effect of insulin glargine on glycemic control in adolescents with type 1-diabetes

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    Hassan M. Mona

    2015-06-01

    Conclusion: The present study encourages the use of insulin glargine in the presence of significant hypoglycemia and glucose variability, with close monitoring of diet and weight. Cost effectiveness and effect on HbA1c and quality of life need further longitudinal studies with larger numbers.

  19. High dose human insulin and insulin glargine promote T24 bladder cancer cell proliferation via PI3K-independent activation of Akt.

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    Liu, S; Li, Y; Lin, T; Fan, X; Liang, Y; Heemann, U

    2011-02-01

    This study was to investigate the effects of human insulin and insulin glargine on proliferation of T24 human bladder cancer cells and the implication of the PI3K/Akt and MEK/ERK1/2 pathways. After exposure to insulin or glargine at the indicated concentrations for certain time courses, in the absence or presence of inhibitor for MEK (PD98059) or PI3K (LY294002), T24 cell proliferation was evaluated by CCK-8 assay. Phosphorylation of Akt and ERK1/2 was analyzed by Western blot. Insulin and glargine similarly induced phosphorylation of Akt and slight increases in T24 cell proliferation at 10-100IU/L. LY294002 remarkably reduced T24 cell proliferation in all groups. However, in the presence of LY294002, cell growth was still promoted by insulin and glargine relative to LY294002-treated group. Accordingly, LY294002 profoundly reduced protein levels of pAkt, while insulin and glargine increased pAkt in T24 cells pretreated with LY294002 as compared with cells treated with LY294002 alone. PD98059 reduced pERK while enhanced T24 cell proliferation. Insulin and glargine increased pERK at 15, 30, 60 min, not at 24h. High dose human insulin and insulin glargine similarly promoted T24 bladder cancer cell proliferation via PI3K-independent activation of Akt. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  20. Efficacy of switching from premixed insulin to insulin glargine regimen in Type 2 diabetes mellitus patients with different islet functions.

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    Wang, Yong-Bo; Wang, Shuang; Bai, Ran; Du, Jian-Ling; Xing, Qian; Ba, Ying; Yang, Yu; Zhang, Xue-Yan; Shi, Chun-Hong; Yao, Jun-Jie

    2014-08-01

    The present study evaluated the efficacy of switching from premixed insulin or an insulin analogue to insulin glargine plus oral antidiabetic drugs (OADs) in patients with type 2 diabetes mellitus (T2DM). The feasibility and suitability of the regimen to the patients was examined based on islet function. Patients with T2DM (n=30) treated with stable doses of premixed insulin or an insulin analogue for eight weeks were divided into two groups according to islet function. Group A had a 2 h of C peptide (2hCP)/fasting C peptide (FCP) ratio ≤3, whereas group B had a 2hCP/FCP ratio >3. Eight weeks following the switch to insulin glargine plus OADs, a significant decrease in fasting blood glucose (FBG), 2 h postprandial blood glucose (2hPBG) and glycosylated‑haemoglobin (HbA1c) were observed in the two groups, with effective rates of 75, 42.9 and 39.3%, respectively. A distinct reduction in the insulin dose was particularly evident in group B. There was a marked decrease in FBG in group A, more so than that observed in group B. By contrast, the decrease in HbA1c was more evident in group B following the switch. A larger number of patients in group B had HbA1c≤7.0%, compared with group A. No difference in the incidence of hypoglycaemia and change of body weight were observed. Following the switch to insulin glargine plus OADs, patients with T2DM demonstrated improved blood glucose control and reduced insulin dosage. The results revealed that this switch in regimen is more suitable for patients with T2DM with 2hCP/FCP>3 and that administration of insulin glargine plus OADs is more efficacious for patients with T2DM with increased FBG levels.

  1. Long-term efficacy of insulin glargine therapy with an educational programme in type 1 diabetes patients in clinical practice.

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    Schreiber, Stephan A; Russmann, Anika

    2007-12-01

    To investigate the effect of initiating insulin glargine (glargine: LANTUS), a once-daily basal insulin analogue, plus an educational programme, on glycaemic control and body weight in patients with type 1 diabetes in clinical practice. A retrospective analysis of the medical records of 65 patients (mean age: 40.7 +/- 13.3 years) with type 1 diabetes was performed. Patients had previously been treated with NPH insulin (NPH; n = 54) or NPH insulin + lente insulin (NPH + lente; n = 11) and then received glargine once daily (bedtime), plus short-acting prandial insulin, for 30 months. Before initiation of glargine, patients participated in a diabetes educational programme and then received physician consultations throughout the study. Metabolic control, body weight and severe hypoglycaemia data were analysed at 9 and 30 months. Following initiation of glargine, patients showed a decrease in HbA(1c) from 7.29 +/- 1.1% to 7.06 +/- 1.0%; p weight was observed in the overall group. No episodes of severe hypoglycaemia (blood glucose weight gain versus previous treatment with NPH insulin or insulin lente. Further studies in a larger cohort of patients would help to confirm these results.

  2. Cardiovascular and Other Outcomes Postintervention With Insulin Glargine and Omega-3 Fatty Acids (ORIGINALE).

    Science.gov (United States)

    2016-05-01

    The Outcome Reduction With Initial Glargine Intervention (ORIGIN) trial reported neutral effects of insulin glargine on cardiovascular outcomes and cancers and reduced incident diabetes in high-cardiovascular risk adults with dysglycemia after 6.2 years of active treatment. Omega-3 fatty acids had neutral effects on cardiovascular outcomes. The ORIGIN and Legacy Effects (ORIGINALE) study measured posttrial effects of these interventions during an additional 2.7 years. Surviving ORIGIN participants attended up to two additional visits. The hazard of clinical outcomes during the entire follow-up period from randomization was calculated. Of 12,537 participants randomized, posttrial data were analyzed for 4,718 originally allocated to insulin glargine (2,351) versus standard care (2,367), and 4,771 originally allocated to omega-3 fatty acid supplements (2,368) versus placebo (2,403). Posttrial, small differences in median HbA1c persisted (glargine 6.6% [49 mmol/mol], standard care 6.7% [50 mmol/mol], P = 0.025). From randomization to the end of posttrial follow-up, no differences were found between the glargine and standard care groups in myocardial infarction, stroke, or cardiovascular death (1,185 vs. 1,165 events; hazard ratio 1.01 [95% CI 0.94-1.10]; P = 0.72); myocardial infarction, stroke, cardiovascular death, revascularization, or hospitalization for heart failure (1,958 vs. 1,910 events; 1.03 [0.97-1.10]; P = 0.38); or any cancer (524 vs. 529 events; 0.99 [0.88-1.12]; P = 0.91) or between omega-3 and placebo groups in cardiovascular death (688 vs. 700; 0.98 [0.88-1.09]; P = 0.68) or other outcomes. During >6 years of treatment followed by >2.5 years of observation, insulin glargine had neutral effects on health outcomes and salutary effects on metabolic control, whereas omega-3 fatty acid supplementation had no effect. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and

  3. Glycemic control with insulin glargine plus insulin glulisine versus premixed insulin analogues in real-world practices: a cost-effectiveness study with a randomized pragmatic trial design.

    Science.gov (United States)

    Levin, Philip A; Zhang, Quanwu; Mersey, James H; Lee, Francis Y; Bromberger, Lee A; Bhushan, Madhu; Bhushan, Rajat

    2011-07-01

    Cost can be an important consideration, along with safety and efficacy, in deciding the most appropriate treatment for patients with type 2 diabetes. Both basal-bolus and premixed insulin analogue regimens are widely used in clinical practice; however, limited information is available regarding cost-effectiveness. The goal of this study was to compare glycemic control, cost-effectiveness, and quality of life effects of insulin glargine plus insulin glulisine (glargine/glulisine) versus premixed insulin analogues in real-world clinical practice. Adults with type 2 diabetes (glycosylated hemoglobin [HbA(1c)] ≥7.0%) at 3 US endocrinology centers were randomly assigned to receive either glargine/glulisine or premixed insulin analogues and continued treatment following the centers' usual practice. HbA(1c), weight, insulin dose, concomitant oral antidiabetic drug (OAD) usage, and hypoglycemia were evaluated at baseline and 3, 6, and 9 months. Medication costs, including costs for all insulin or OAD regimens, were estimated using published wholesale acquisition costs. A total of 197 patients were randomized to receive glargine/glulisine therapy (n = 106) or premixed analogue therapy (n = 91). Overall, the mean age was 56 years, the mean duration of diabetes was 13 years, with a mean HbA(1c) of 9.25% and mean BMI of 35.8 kg/m(2) at baseline. Patients randomized to receive glargine/glulisine had a greater mean HbA(1c) reduction from baseline (-2.3%) than patients receiving a premixed analogue regimen (-1.7%). Adjusted mean follow-up HbA(1c) was 6.9% versus 7.5%, respectively (difference, -0.59%; P < 0.01). The glargine/glulisine group also used a lower mean number of OADs (0.86 vs 1.14; difference, -0.28; P = 0.04) but had a higher weight (240 vs 235 lb; difference, 4.55 lb; P = 0.03) than the premixed analogue group at follow-up. There were no significant differences in daily insulin dose and rates of hypoglycemia. Overall medication costs per 1.0% reduction in HbA(1c

  4. A novel insulin combination of insulin degludec and insulin aspart achieves a more stable overnight glucose profile than insulin glargine: results from continuous glucose monitoring in a proof-of-concept trial

    NARCIS (Netherlands)

    Liebl, A.; Davidson, J.; Mersebach, H.; Dykiel, P.; Tack, C.J.J.; Heise, T.

    2013-01-01

    PURPOSE: Insulin degludec coformulated with insulin aspart (as IDegAsp) can cover 24 h basal insulin and postprandial insulin requirements after a main meal with one injection. We compared glycemic stability following IDegAsp or insulin glargine (IGlar) given before the evening meal in patients with

  5. Non-inferiority of insulin glargine versus insulin detemir on blood glucose variability in type 1 diabetes patients: a multicenter, randomized, crossover study.

    Science.gov (United States)

    Renard, Eric; Dubois-Laforgue, Danièle; Guerci, Bruno

    2011-12-01

    This study compared the effects of insulin glargine and insulin detemir on blood glucose variability under clinical practice conditions in patients with type 1 diabetes (T1D) using glulisine as the mealtime insulin. This was a multicenter, crossover trial in 88 randomized T1D patients: 54 men and 34 women, 46.8±13.7 years old, with a duration of diabetes of 18±9 years and hemoglobin A1c level of 7.1±0.7%. The per-protocol population included 78 patients: 44 received glargine/detemir and 34 detemir/glargine in the first/second 16-week period, respectively. The primary end point was the coefficient of variation (CV) of fasting blood glucose (FBG). Secondary end points included variability of pre-dinner blood glucose, mean amplitude of glycemic excursions, mean of daily differences, and doses and number of daily insulin injections. The non-inferiority criterion was an insulin glargine/insulin detemir FBG CV ratio with a 95% confidence interval (CI) upper limit ≤1.25. The non-inferiority criterion was satisfied with a mean value of 1.016 (95% CI=0.970-1.065). Intention-to-treat analysis confirmed the non-inferiority with a 95% CI upper limit=1.062. No significant differences were found on secondary objectives, but there was a trend to higher doses and number of daily injections with insulin detemir. A total of eight (four glargine and four detemir) patients reported nine serious adverse events (including one severe episode of hypoglycemia). None of them was considered as related to basal insulins. Serious adverse events led to treatment discontinuation in two patients of the detemir group and none in the glargine group. In T1D patients under clinical practice conditions, insulin glargine was non-inferior to insulin detemir regarding blood glucose variability, as assessed by CV of FBG.

  6. Exposure to excess insulin (glargine) induces type 2 diabetes mellitus in mice fed on a chow diet.

    Science.gov (United States)

    Yang, Xuefeng; Mei, Shuang; Gu, Haihua; Guo, Huailan; Zha, Longying; Cai, Junwei; Li, Xuefeng; Liu, Zhenqi; Cao, Wenhong

    2014-06-01

    We have previously shown that insulin plays an important role in the nutrient-induced insulin resistance. In this study, we tested the hypothesis that chronic exposure to excess long-acting insulin (glargine) can cause typical type 2 diabetes mellitus (T2DM) in normal mice fed on a chow diet. C57BL/6 mice were treated with glargine once a day for 8 weeks, followed by evaluations of food intake, body weight, blood levels of glucose, insulin, lipids, and cytokines, insulin signaling, histology of pancreas, ectopic fat accumulation, oxidative stress level, and cholesterol content in mitochondria in tissues. Cholesterol content in mitochondria and its association with oxidative stress in cultured hepatocytes and β-cells were also examined. Results show that chronic exposure to glargine caused insulin resistance, hyperinsulinemia, and relative insulin deficiency (T2DM). Treatment with excess glargine led to loss of pancreatic islets, ectopic fat accumulation in liver, oxidative stress in liver and pancreas, and increased cholesterol content in mitochondria of liver and pancreas. Prolonged exposure of cultured primary hepatocytes and HIT-TI5 β-cells to insulin induced oxidative stress in a cholesterol synthesis-dependent manner. Together, our results show that chronic exposure to excess insulin can induce typical T2DM in normal mice fed on a chow diet. © 2014 The authors.

  7. MEK1 and MEK2 differentially regulate human insulin- and insulin glargine-induced human bladder cancer T24 cell proliferation.

    Science.gov (United States)

    Liu, Shan-Ying; Liang, Ying; Lin, Tian-Xin; Su, Fang; Liang, Wei-Wen; Uwe, Heemann; Li, Yan

    2012-12-01

    Increased risk of bladder cancer has been reported in diabetic patients. This study was to investigate the roles of mitogen-activated protein kinase kinase (MEK) 1 and 2 in the regulation of human insulin- and insulin glargine-induced proliferation of human bladder cancer T24 cells. In the absence or presence of a selective inhibitor for MEK1 (PD98059) or a specific siRNA for MEK2 (siMEK2), with or without addition of insulin or glargine, T24 cell proliferation was evaluated by cell counting kit (CCK)-8 assay. Protein expression of MEK2, phosphorylation of ERK1/2 and Akt was analyzed by Western blotting. T24 cell proliferation was promoted by PD98059 at 5 - 20 µmol/L, inhibited by siMEK2 at 25 - 100 nmol/L. PD98059 and siMEK2 remarkably reduced phosphorylated ERK1/2. Insulin- and glargine-induced T24 cell proliferation was enhanced by PD98059, suppressed while not blocked by siMEK2. Insulin- and glargine-induced ERK1/2 activation was blocked by PD98059 or siMEK2 treatment, whereas activation of Akt was not affected. MEK1 inhibits while MEK2 contributes to normal and human insulin- and insulin glargine-induced human bladder cancer T24 cell proliferation.

  8. Concentrations of insulin glargine and its metabolites during long-term insulin therapy in type 2 diabetic patients and comparison of effects of insulin glargine, its metabolites, IGF-I, and human insulin on insulin and IGF-I receptor signaling

    NARCIS (Netherlands)

    A.J. Varewijck (Aimee); H. Yki-Jarvinen (Hannele); R. Schmidt (Reinhold); N. Tennagels (Norbert); J.A.M.J.L. Janssen (Joseph)

    2013-01-01

    textabstractWe investigated 1) the ability of purified glargine (GLA), metabolites 1 (M1) and 2 (M2), IGF-I, and NPH insulin to activate the insulin receptor (IR)-A and IR-B and IGF-I receptor (IGF-IR) in vitro; 2) plasma concentrations of GLA, M1, and M2 during longterm insulin therapy in type 2

  9. Evaluation of the cost effectiveness of exenatide versus insulin glargine in patients with sub-optimally controlled Type 2 diabetes in the United Kingdom

    Directory of Open Access Journals (Sweden)

    Tetlow Anthony P

    2008-08-01

    Full Text Available Abstract Objective Exenatide belongs to a new therapeutic class in the treatment of diabetes (incretin mimetics, allowing glucose-dependent glycaemic control in Type 2 diabetes. Randomised controlled trial data suggest that exenatide is as effective as insulin glargine at reducing HbA1c in combination therapy with metformin and sulphonylureas; with reduced weight but higher incidence of adverse gastrointestinal events. The objective of this study is to evaluate the cost effectiveness of exenatide versus insulin glargine using RCT data and a previously published model of Type 2 diabetes disease progression that is based on the United Kingdom Prospective Diabetes Study; the perspective of the health-payer of the United Kingdom National Health Service. Methods The study used a discrete event simulation model designed to forecast the costs and health outcome of a cohort of 1,000 subjects aged over 40 years with sub-optimally-controlled Type 2 diabetes, following initiation of either exenatide, or insulin glargine, in addition to oral hypoglycaemic agents. Sensitivity analysis for a higher treatment discontinuation rate in exenatide patients was applied to the cohort in three different scenarios; (1 either ignored or (2 exenatide-failures excluded or (3 exenatide-failures switched to insulin glargine. Analyses were undertaken to evaluate the price sensitivity of exenatide in terms of relative cost effectiveness. Baseline cohort profiles and effectiveness data were taken from a published randomised controlled trial. Results The relative cost-effectiveness of exenatide and insulin glargine was tested under a variety of conditions, in which insulin glargine was dominant in all cases. Using the most conservative of assumptions, the cost-effectiveness ratio of exenatide vs. insulin glargine at the current UK NHS price was -£29,149/QALY (insulin glargine dominant and thus exenatide is not cost-effective when compared with insulin glargine, at the current

  10. Insulin glargine 300 units/mL: a guide for healthcare professionals involved in the management of diabetes.

    Science.gov (United States)

    Strong, Jodi; Kruger, Davida; Novak, Lucia

    2017-04-01

    Insulin glargine 300 units/mL: Insulin glargine 300 units/mL (Gla-300) is a formulation of insulin glargine that delivers the same number of insulin units in one-third of the injectable volume of insulin glargine 100 units/mL (Gla-100). Glucose control: Recently approved in the United States and in Europe for use in type 1 and type 2 diabetes, Gla-300 has a more constant and evenly distributed glucose-lowering effect compared with Gla-100, with a duration of action beyond 24 hours and lower within-day and between-day intra-individual variability in blood glucose levels. These benefits translate into predictable and sustained glucose control from a once-daily injection, with potential for fewer hypoglycemia episodes and less weight gain. Case studies are presented to highlight the potential clinical benefits and considerations associated with initiating treatment with Gla-300 in people with type 1 and type 2 diabetes.

  11. A comparison of the pharmacodynamic profiles of insulin detemir and insulin glargine: a single dose clamp study in people with type 2 diabetes.

    Science.gov (United States)

    Luzio, S D; Dunseath, G J; Atkinson, M D; Owens, D R

    2013-12-01

    The pharmacodynamic properties of a single dose of 0.5 U/kg insulin detemir and insulin glargine were compared during two 24-h isoglycaemic clamps, one week apart. The order of treatments was randomised. At approximately 0830 h, persons with T2DM received subcutaneous administration of a 0.5 U/kg dose of either insulin detemir or insulin glargine into the anterior abdominal wall. Plasma glucose was measured at 10-min intervals throughout the 24-h clamp period and isoglycaemia was maintained by variable infusion of 20% glucose. Glucose infusion rates (GIR) and plasma C-peptide were determined throughout each 24-h period. Eleven persons with type 2 diabetes (8 male) with mean (SD) age 58.5 years (8.5), BMI 30.8 kg/m² (2.8) and HbA1c 7.5% (0.6) were studied. Plasma glucose remained constant during the clamp (CV: insulin detemir 3.7%; insulin glargine 3.8%). Following injection of insulin detemir, GIR increased, reaching a mean peak of 2.29 mg/kg/min (95% CI 1.64, 2.94) at 11.6h (range 8.9 to 14.3) compared to 1.71 mg/kg/min (95% CI 1.4, 2.0) at 10.2 h (8.1 to 12.3) for insulin glargine (P=0.025 for GIR(max)). Plasma C-peptide decreased during the study period, remaining significantly lower than the fasting level at the study end after both analogues, insulin detemir (P=0.01) and insulin glargine (P=0.02). In persons with T2DM, no difference in duration of action following a single subcutaneous dose of insulin detemir and insulin glargine could be observed. Insulin detemir showed greater between subject variability and achieved a significantly higher maximum GIR than insulin glargine. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  12. Treatment with the long-acting insulin analogues detemir or glargine during pregnancy in women with type 1 diabetes

    DEFF Research Database (Denmark)

    Callesen, Nicoline F; Mathiesen, Jonathan Michael; Ringholm, Lene

    2013-01-01

    Objective: To compare glycaemic control and pregnancy outcome in women with type 1 diabetes treated with the long-acting insulin analogues detemir or glargine. Methods: Retrospective study of singleton pregnancies from 2007 to 2011 in women with type 1 diabetes with a single living fetus at 22 we...

  13. One-year treatment with exenatide vs. Insulin Glargine: Effects on postprandial glycemia, lipid profiles, and oxidative stress

    NARCIS (Netherlands)

    Bunck, M.C.M.; Corner, A.; Eliasson, B.; Heine, R.J.; Shaginian, R.M.; Wu, Y.; Yan, P.; Smith, U.; Yki-Jarvinen, H.; Diamant, M.; Taskinen, M.R.

    2010-01-01

    Objective: The objective of the present study was to investigate the effects of one-year treatment with exenatide or Insulin Glargine, followed by a 5-week off-drug period, on postprandial lipidaemia, glycaemia and measures of oxidative stress. Methods: Sixty-nine metformin-treated patients with

  14. A short-term cost-utility analysis of insulin degludec versus insulin glargine U100 in patients with type 1 or type 2 diabetes in Denmark.

    Science.gov (United States)

    Pollock, R F; Tikkanen, C K

    2017-03-01

    Insulin degludec is an insulin analog with an ultra-long duration of action that exhibits less intra-patient variability in its glucose-lowering activity, and reduces nocturnal, overall, and severe hypoglycemia relative to insulin glargine. The aim of the present study was to evaluate the cost-effectiveness of insulin degludec relative to insulin glargine in patients with: type 1 diabetes (T1D), type 2 diabetes receiving basal-only therapy (T2DBOT), and type 2 diabetes receiving basal-bolus therapy (T2DBB) in Denmark. A short-term (1 year) cost-utility model was developed to model insulin use, non-severe and severe hypoglycemia, and self-monitoring of blood glucose in patients using insulin degludec and insulin glargine from the perspective of a Danish healthcare payer. Where possible, data were derived from Danish patients with diabetes and meta-analyses of clinical trials comparing insulin degludec with insulin glargine. Using these characteristics, the model estimated costs and quality-adjusted life years (QALYs) gained for the two insulin regimens in each of the three diabetes populations. Insulin degludec dominated insulin glargine (i.e. reduced costs while improving quality-adjusted life expectancy) in patients with T1D and patients with type 2 diabetes using a basal-only insulin regimen. In the T2DBB cohort, insulin degludec was associated with an incremental cost-effectiveness ratio of DKK 221,063 per QALY gained, which would be considered cost-effective at a willingness-to-pay threshold of EUR 30,000 (∼DKK 224,000) per QALY gained. Sensitivity analysis showed that results were most affected by changes in hypoglycemia rate ratio assumptions, but were broadly insensitive to changes in individual input parameters. Insulin degludec reduces incidence of hypoglycemia and improves quality-of-life in patients with diabetes. Over a 1-year time horizon, insulin degludec resulted in cost savings relative to insulin glargine in T1D and T2DBOT cohorts, while being

  15. Potential formula for the calculation of starting and incremental insulin glargine doses: ALOHA subanalysis.

    Science.gov (United States)

    Kadowaki, Takashi; Ohtani, Tetsuya; Naito, Yusuke; Odawara, Masato

    2012-01-01

    Pragmatic methods for dose optimization are required for the successful basal management in daily clinical practice. To derive a useful formula for calculating recommended glargine doses, we analyzed data from the Add-on Lantus® to Oral Hypoglycemic Agents (ALOHA) study, a 24-week observation of Japanese type 2 diabetes patients. The patients who initiated insulin glargine in basal-supported oral therapy (BOT) regimen (n = 3506) were analyzed. The correlations between average changes in glargine dose and HbA1c were calculated, and its regression formula was estimated from grouped data categorized by baseline HbA1c levels. Starting doses of the background-subgroup achieving the HbA1c target with a last-observed dose above the average were compared to an assumed optimal starting dose of 0.15 U/kg/day. The difference in regression lines between background-subgroups was examined. A formula for determining the optimal starting and titration doses was thereby derived. The correlation coefficient between changes in dose and HbA1c was -0.9043. The estimated regression line formula was -0.964 × change in HbA1c+2.000. A starting dose of 0.15 U/kg/day was applicable to all background-subgroups except for patients with retinopathy (0.120 U/kg/day) and/or with eGFR<60 mL/min/1.73 m(2) (0.114 U/kg/day). Additionally, women (0.135 U/kg/day) and patients with sulfonylureas (0.132 U/kg/day) received a slightly decreased starting dose. We suggest a simplified and pragmatic dose calculation formula for type 2 diabetes patients starting glargine BOT optimal daily dose at 24 weeks  =  starting dose (0.15×weight) + incremental dose (baseline HbA1c - target HbA1c+2). This formula should be further validated using other samples in a prospective follow-up, especially since several patient groups required lower starting doses.

  16. Potential formula for the calculation of starting and incremental insulin glargine doses: ALOHA subanalysis.

    Directory of Open Access Journals (Sweden)

    Takashi Kadowaki

    Full Text Available BACKGROUND: Pragmatic methods for dose optimization are required for the successful basal management in daily clinical practice. To derive a useful formula for calculating recommended glargine doses, we analyzed data from the Add-on Lantus® to Oral Hypoglycemic Agents (ALOHA study, a 24-week observation of Japanese type 2 diabetes patients. METHODOLOGY/PRINCIPAL FINDINGS: The patients who initiated insulin glargine in basal-supported oral therapy (BOT regimen (n = 3506 were analyzed. The correlations between average changes in glargine dose and HbA1c were calculated, and its regression formula was estimated from grouped data categorized by baseline HbA1c levels. Starting doses of the background-subgroup achieving the HbA1c target with a last-observed dose above the average were compared to an assumed optimal starting dose of 0.15 U/kg/day. The difference in regression lines between background-subgroups was examined. A formula for determining the optimal starting and titration doses was thereby derived. The correlation coefficient between changes in dose and HbA1c was -0.9043. The estimated regression line formula was -0.964 × change in HbA1c+2.000. A starting dose of 0.15 U/kg/day was applicable to all background-subgroups except for patients with retinopathy (0.120 U/kg/day and/or with eGFR<60 mL/min/1.73 m(2 (0.114 U/kg/day. Additionally, women (0.135 U/kg/day and patients with sulfonylureas (0.132 U/kg/day received a slightly decreased starting dose. CONCLUSIONS/SIGNIFICANCE: We suggest a simplified and pragmatic dose calculation formula for type 2 diabetes patients starting glargine BOT optimal daily dose at 24 weeks  =  starting dose (0.15×weight + incremental dose (baseline HbA1c - target HbA1c+2. This formula should be further validated using other samples in a prospective follow-up, especially since several patient groups required lower starting doses.

  17. Improved glycemic control with insulin glargine versus pioglitazone as add-on therapy to sulfonylurea or metformin in patients with uncontrolled type 2 diabetes mellitus.

    Science.gov (United States)

    Meneghini, Luigi F; Traylor, Louise; Schwartz, Sherwyn L

    2010-01-01

    To compare glycemic control with add-on insulin glargine versus pioglitazone treatment in patients with type 2 diabetes. This 48-week, multicenter, parallel-group, open-label study randomized 389 adults with poorly controlled type 2 diabetes (glycated hemoglobin A1c [A1C], 8.0% to 12.0%), despite > or =3 months of sulfonylurea or metformin monotherapy, to receive add-on therapy with insulin glargine or pioglitazone. Outcomes included A1C change from baseline to end point (primary), percentage of patients achieving A1C levels pioglitazone (-2.48% versus -1.86%, respectively; 95% confidence interval, -0.93 to -0.31; P = .0001, 48-week modified intent-to-treat population). Insulin glargine also yielded significantly greater reductions in fasting plasma glucose at all time points (end point difference, -34.9 mg/dL; 95% confidence interval, -47.6 to -22.2; Ppioglitazone, insulin glargine resulted in a lower overall incidence of possibly related treatment-emergent adverse events (12.0% versus 20.7%) and fewer study discontinuations (2.2% versus 9.1%), but a higher rate (per patient-year) of confirmed clinically relevant hypoglycemic episodes (blood glucose metformin monotherapy had failed resulted in significantly greater improvements in glycemic control in comparison with the addition of pioglitazone. Although severe hypoglycemia was more frequent in patients with insulin glargine therapy, hypoglycemic events occurred in <5% of patients in the insulin glargine treatment group.

  18. Converting continuous insulin infusion to subcutaneous insulin glargine after cardiac surgery using percentage-based versus weight-based dosing: a pilot trial.

    Science.gov (United States)

    Silinskie, Kevin M; Kirshner, Ronald; Hite, Mindee S

    2013-01-01

    Most studies report using percentage of total daily insulin (TDI) for converting therapy from continuous insulin infusion to subcutaneous insulin in cardiac surgery patients. Few studies have evaluated the efficacy of using body weight to calculate the basal insulin dose. To compare the efficacy and safety of dosing insulin glargine by weight versus percentage of TDI in cardiac surgery patients transitioning from continuous insulin infusion to subcutaneous insulin. We conducted a prospective, randomized, open-label, pilot study. Study patients who had a preoperative weight less than 100 kg and were receiving at least 6 hours of a continuous insulin infusion were randomized to receive either 50% of their TDI requirement or 0.5 units/kg of glargine as a one-time dose 2 hours before stopping the continuous insulin infusion. All patients were administered subcutaneous corrective insulin. Blood glucose monitoring occurred before each meal, at bedtime, and with morning laboratory tests for 24 hours after administration of the glargine dose. A total of 200 blood glucose measurements were performed in each group. The percentage of blood glucose measurements in target range (80-140 mg/dL) was similar between the weight-based group and the percentage-based group (66% vs 64%, p = 0.75). Median blood glucose after transition was 120 mg/dL (interquartile range [IQR] 99-147) in the weight-based group compared to 127 mg/dL (IQR 107-149; p = 0.03) in the percentage-based group. The median glargine dose was higher in the weight-based group (41 units; IQR 36-44) than in the weight-based group (24 units; IQR 14-30, p weight proved to be safe, but larger scale studies are needed before adopting weight-based dosing in this patient population.

  19. Comparison of a Multiple Daily Insulin Injection Regimen (Glargine or Detemir Once Daily Plus Prandial Insulin Aspart and Continuous Subcutaneous Insulin Infusion (Aspart in Short-Term Intensive Insulin Therapy for Poorly Controlled Type 2 Diabetes Patients

    Directory of Open Access Journals (Sweden)

    Wen-shan Lv

    2013-01-01

    Full Text Available Aims. To examine the potential differences between multiple daily injection (MDI regimens based on new long-acting insulin analogues (glargine or detemir plus prandial insulin aspart and continuous subcutaneous insulin aspart infusion (CSII in patients with poorly controlled type 2 diabetes. Methods. Patients (n=119 with poorly controlled type 2 diabetes of a duration exceeding five years were randomly assigned into three groups: Group A treated with CSII using insulin aspart; Group B treated with glargine-based MDI and Group C treated with detemir-based MDI. Results. Good glycemic control was achieved by patients in Group A in a significantly shorter duration than patients in Groups B and C. Total daily insulin, basal insulin dose and dose per kg body weight in Group A were significantly less than those in Groups B and C. Daily blood glucose fluctuation in Group A was significantly less than that in Groups B and C. There were no differences between Groups B and C. Conclusions. Aspart-based CSII may achieve good blood glucose control with less insulin doses over a shorter period compared with glargine or detemir-based MDI. No differences between glargine- and detemir-based MDI were detected in poorly controlled subjects with type 2 diabetes.

  20. Insulin glargine 300 U/mL for basal insulin therapy in type 1 and type 2 diabetes mellitus.

    Science.gov (United States)

    Lau, Ip Tim; Lee, Ka Fai; So, Wing Yee; Tan, Kathryn; Yeung, Vincent Tok Fai

    2017-01-01

    To review published clinical studies on the efficacy and safety of new insulin glargine 300 units/mL (Gla-300), a new long-acting insulin analog, for the treatment of type 1 and type 2 diabetes mellitus (T1DM, T2DM). Data sources comprised primary research articles on Gla-300, including pharmacodynamic, pharmacokinetic, and clinical studies. In pharmacodynamic and pharmacokinetic studies, Gla-300 showed a flatter time-action profile and longer duration of action than Gla-100. Noninferiority of Gla-300 versus Gla-100 for lowering of glycated hemoglobin was demonstrated in Phase III clinical studies covering a range of T1DM and T2DM patient populations. Over 6-12 months of follow-up, Gla-300 consistently showed comparable glycemic efficacy with less hypoglycemia vs Gla-100, even during the first 8 weeks of treatment. Although titrated insulin doses were 11%-17% higher with Gla-300 vs Gla-100, changes in body weight were similar or favored Gla-300. Clinical studies provide evidence that the pharmacodynamic and pharmacokinetic properties of Gla-300 may translate into clinical benefits in both T1DM and T2DM. Gla-300 may provide a new option for people initiating basal insulin, those requiring higher basal insulin doses, those with T1DM, and those who may be at increased risk for hypoglycemia, such as people with chronic kidney disease, the elderly, and those with cardiovascular comorbidities.

  1. Insulin Detemir Causes Lesser Weight Gain in Comparison to Insulin Glargine: Role on Hypothalamic NPY and Galanin

    Directory of Open Access Journals (Sweden)

    Mohammad Ishraq Zafar

    2014-01-01

    Full Text Available Objective. Compared with other insulin analogues, insulin detemir induces less weight gain. This study investigated whether this effect was achieved by influencing the hypothalamic appetite regulators neuropeptide Y (NPY and galanin (GAL. Methods. Type  2 diabetic rat models were established with a high-fat diet and intraperitoneal injection of STZ. All rats were divided into NC, DM, DM+DE and DM+GLA groups. Glycemic levels of all study groups were checked at study onset and after 4 weeks of insulin treatment. Food intake and body weight were monitored during treatment. After 4 weeks, the hypothalamus of rats was examined for NPY and GAL mRNA and protein expression. Results. After 4 weeks of treatment, compared with the DM+GLA group, the DM+DE group exhibited less food intake (P<0.05 and less weight gain (P<0.05, but showed similar glycemic control. The expression of hypothalamic NPY and GAL at both mRNA and protein level were significantly lower (P<0.05 in the DM+DE group. Conclusion. Insulin detemir decreased food intake in type 2 diabetic rats, which led to reduced weight gain when compared to insulin glargine treatment. This effect is likely due to downregulation of hypothalamic NPY and GAL.

  2. Insulin glargine 300 U/mL for basal insulin therapy in type 1 and type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Lau IT

    2017-06-01

    Full Text Available Ip Tim Lau,1 Ka Fai Lee,2 Wing Yee So,3 Kathryn Tan,4 Vincent Tok Fai Yeung5 1Department of Medicine, Tseung Kwan O Hospital, 2Department of Medicine and Geriatrics, Kwong Wah Hospital, 3Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, 4Department of Medicine, Queen Mary Hospital, University of Hong Kong, 5Department of Medicine and Geriatrics, Our Lady of Maryknoll Hospital, Hong Kong, China Objective: To review published clinical studies on the efficacy and safety of new insulin glargine 300 units/mL (Gla-300, a new long-acting insulin analog, for the treatment of type 1 and type 2 diabetes mellitus (T1DM, T2DMMaterials and methods: Data sources comprised primary research articles on Gla-300, including pharmacodynamic, pharmacokinetic, and clinical studies.Results: In pharmacodynamic and pharmacokinetic studies, Gla-300 showed a flatter time–action profile and longer duration of action than Gla-100. Noninferiority of Gla-300 versus Gla-100 for lowering of glycated hemoglobin was demonstrated in Phase III clinical studies covering a range of T1DM and T2DM patient populations. Over 6–12 months of follow-up, Gla-300 consistently showed comparable glycemic efficacy with less hypoglycemia vs Gla-100, even during the first 8 weeks of treatment. Although titrated insulin doses were 11%–17% higher with Gla-300 vs Gla-100, changes in body weight were similar or favored Gla-300.Conclusion: Clinical studies provide evidence that the pharmacodynamic and pharmacokinetic properties of Gla-300 may translate into clinical benefits in both T1DM and T2DM. Gla-300 may provide a new option for people initiating basal insulin, those requiring higher basal insulin doses, those with T1DM, and those who may be at increased risk for hypoglycemia, such as people with chronic kidney disease, the elderly, and those with cardiovascular comorbidities. Keywords: diabetes mellitus, long-acting insulin, insulin glargine

  3. Risk of cancer in patients on insulin glargine and other insulin analogues in comparison with those on human insulin : Results from a large population-based follow-up study

    NARCIS (Netherlands)

    R. Ruiter (Rikje); L.E. Visser (Loes); J.W.W. Coebergh (Jan Willem); M.P.P. van Herk-Sukel (Myrthe); H.R. Haak; P.H. Geelhoed-Duijvestijn; S.M.J.M. Straus (Sabine); R.M.C. Herings (Ron); B.H.Ch. Stricker (Bruno)

    2012-01-01

    textabstractAims/hypothesis Several publications suggest an association between certain types of insulin and cancer, but with conflicting results. We investigated whether insulin glargine (A21Gly,B31Arg,B32Arg human insulin) is associated with an increased risk of cancer in a large population-based

  4. Starting bedtime glargine versus NPH insulin in poorly controlled type 2 diabetic patients with various hyperglycemia types (fasting type or postprandial type)

    OpenAIRE

    Vähätalo, Markku A.; Viikari, Jorma; Rönnemaa, Tapani

    2013-01-01

    Our aim was to compare the effects of an intermediate acting human insulin (NPH) and a long-acting insulin analog, insulin glargine, in insulin naïve type 2 diabetes patients, stratified by the type of hyperglycemia (fasting or postprandial type). Based on different action profiles, we hypothesized that patients having different hyperglycemia types would react differently when treated with these insulins. This is a post hoc analysis of the Lanmet study data. The Lanmet study was a randomized,...

  5. Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO): an open randomised controlled trial

    DEFF Research Database (Denmark)

    Bretzel, R.G.; Nuber, U.; Landgraf, W.

    2008-01-01

    .54 (4.48) kg. The improvement of treatment satisfaction was greater for insulin glargine than for insulin lispro (mean difference 3.13; 95% CI 2.04-4.22). INTERPRETATION: A therapeutic regimen involving the addition of either basal or prandial insulin analogue is equally effective in lowering......BACKGROUND: As type 2 diabetes mellitus progresses, oral hypoglycaemic agents often fail to maintain blood glucose control and insulin is needed. We investigated whether the addition of once-daily insulin glargine is non-inferior to three-times daily prandial insulin lispro in overall glycaemic...... hypoglycaemic agents were randomly assigned to either insulin glargine taken once daily at the same time every day or to insulin lispro administered three times per day. The primary objective was to compare the change in haemoglobin A(1c) from baseline to endpoint (week 44) between the two regimens...

  6. The effects of basal insulin peglispro vs. insulin glargine on lipoprotein particles by NMR and liver fat content by MRI in patients with diabetes.

    Science.gov (United States)

    Orchard, Trevor J; Cariou, Bertrand; Connelly, Margery A; Otvos, James D; Zhang, Shuyu; Antalis, Caryl J; Ivanyi, Tibor; Hoogwerf, Byron J

    2017-06-06

    In Phase 2/3 studies of basal insulin peglispro (BIL) compared to insulin glargine, patients with type 1 or type 2 diabetes previously treated with insulin and randomized to BIL had an increase in serum triglycerides (TGs). To further understand lipoprotein changes, a lipid substudy which included liver fat content was designed to assess relationships among the measured variables for each diabetes cohort and compare the hepato-preferential insulin BIL to glargine. In three cohorts of patients with diabetes (type 1, type 2 insulin naïve, and type 2 previously on insulin; n = 652), liver fat content (LFC) was determined by magnetic resonance imaging (MRI) and blood lipids were analyzed by nuclear magnetic resonance (NMR) spectroscopy at baseline, 26 and 52 weeks of treatment. Apolipoproteins, adiponectin, and other lipid parameters were also measured. Descriptive statistics were done, as well as correlation analyses to look for relationships among LFC and lipoproteins or other lipid measures. In patients with type 1 diabetes treated with BIL, but not glargine, small LDL and medium and large VLDL subclass concentrations increased from baseline. In patients with type 2 diabetes previously on insulin and treated with BIL, large VLDL concentration increased from baseline. In insulin naïve patients with type 2 diabetes treated with BIL, there were very few changes, while in those treated with glargine, small LDL and large VLDL decreased from baseline. Baseline LFC correlated significantly in one or more cohorts with baseline large VLDL, small LDL, VLDL size, and Apo C3. Changes in LFC by treatment showed generally weak correlations with lipoprotein changes, except for positive correlations with large VLDL and VLDL size. Adiponectin was higher in patients with type 1 diabetes compared to patients with type 2 diabetes, but decreased with treatment with both BIL and glargine. The lipoprotein changes were in line with the observed changes in serum TGs; i.e., the cohorts

  7. Effect of insulin analogues on insulin/IGF1 hybrid receptors: increased activation by glargine but not by its metabolites M1 and M2.

    Directory of Open Access Journals (Sweden)

    Cécile Pierre-Eugene

    Full Text Available BACKGROUND: In diabetic patients, the pharmacokinetics of injected human insulin does not permit optimal control of glycemia. Fast and slow acting insulin analogues have been developed, but they may have adverse properties, such as increased mitogenic or anti-apoptotic signaling. Insulin/IGF1 hybrid receptors (IR/IGF1R, present in most tissues, have been proposed to transmit biological effects close to those of IGF1R. However, the study of hybrid receptors is difficult because of the presence of IR and IGF1R homodimers. Our objective was to perform the first study on the pharmacological properties of the five marketed insulin analogues towards IR/IGF1R hybrids. METHODOLOGY: To study the effect of insulin analogues on IR/IGF1R hybrids, we used our previously developed Bioluminescence Resonance Energy Transfer (BRET assay that permits specific analysis of the pharmacological properties of hybrid receptors. Moreover, we have developed a new, highly sensitive BRET-based assay to monitor phophatidylinositol-3 phosphate (PIP(3 production in living cells. Using this assay, we performed a detailed pharmacological analysis of PIP(3 production induced by IGF1, insulin and insulin analogues in living breast cancer-derived MCF-7 and MDA-MB231 cells. RESULTS: Among the five insulin analogues tested, only glargine stimulated IR/IGF1R hybrids with an EC50 that was significantly lower than insulin and close to that of IGF1. Glargine more efficiently stimulated PIP(3 production in MCF-7 cells but not in MDA-MB231 cells as compared to insulin. In contrast, glargine metabolites M1 and M2 showed lower potency for hybrid receptors stimulation, PIP(3 production, Akt and Erk1/2 phosphorylation and DNA synthesis in MCF-7 cells, compared to insulin. CONCLUSION: Glargine, possibly acting through IR/IGF1R hybrids, displays higher potency, whereas its metabolites M1 and M2 display lower potency than insulin for the stimulation of proliferative/anti-apoptotic pathways in

  8. Randomized Trial of Long-Acting Insulin Glargine Titration Web Tool (LTHome) Versus Enhanced Usual Therapy of Glargine Titration (INNOVATE Trial).

    Science.gov (United States)

    Bajaj, Harpreet S; Venn, Karri; Ye, Chenglin; Aronson, Ronnie

    2016-10-01

    Basal insulin titration in the real world is often unsuccessful. LTHome, a web tool, applies a rules engine-based algorithm providing insulin titration advice directly to the patient. This pilot, randomized trial evaluates basal insulin glargine titration by LTHome compared to enhanced usual therapy ([EUT]-diabetes education program) over 12 weeks. Important inclusion criteria: 18-75 years, type 2 diabetes, computer literacy, and HbA1c >7.0%. Trial protocol was approved by ethics board. We randomized 139 subjects. The achievement of primary composite outcome (four out of seven fasting plasma glucose [FPG] within 5-7.2 mmol/L + mean for three consecutive FPG within 5-7.2 mmol/L + no severe hypoglycemia) was 15% in LTHome versus 41% in EUT (noninferiority not met, P-value = 0.92). Other outcomes were similar between the LTHome and EUT arms: alternate composite outcome achievement (last five FPG mean within the range of 5-7.2 mmol/L + no hypoglycemia, 47% and 51%, P = 0.73); A1c reduction (-1.0% and -1.1%, P = 0.66); proportion achieving A1c ≤7% (14% and 20%, P = 0.36); and hypoglycemia incidence (31% and 37%, P = 0.4), respectively. Patient satisfaction score improvements were greater in LTHome versus EUT (change in fear of hypoglycemia score P = 0.04 and change in diabetes distress score P = 0.04). The mean number of additional healthcare provider visits was 0.13 for LTHome and 1.22 for EUT (P INNOVATE trial suggests clinical utility of LTHome compared to EUT in real-life settings. Further research is needed to evaluate the efficacy and safety of automated insulin titration algorithms.

  9. Efficacy and Safety of Insulin Glargine 300 U/mL Versus Insulin Glargine 100 U/mL in High-Risk and Low-Risk Patients with Type 2 Diabetes Stratified Using Common Clinical Performance Measures.

    Science.gov (United States)

    Lingvay, Ildiko; Chao, Jason; Dalal, Mehul R; Meneghini, Luigi F

    2017-05-01

    To determine whether previously reported reductions in hypoglycemia associated with insulin glargine 300 U/mL (Gla-300) compared with insulin glargine 100 U/mL (Gla-100) are impacted by patient risk category in type 2 diabetes (T2D), clinical performance measures based on the Healthcare Effectiveness Data and Information Set (HEDIS) were applied to patient-level data from the EDITION 2 and EDITION 3 clinical trials that compared Gla-300 and Gla-100. In this post hoc analysis, patients were stratified as low risk (LR) if patients were 300 achieving the composite endpoint compared with Gla-100 in both the LR and HR patient cohorts, regardless of prior insulin experience. A similar trend was observed for the composite endpoint of HbA1c target without nocturnal hypoglycemia. There is a consistent, nonsignificant trend suggesting that Gla-300 might reduce the burden of hypoglycemia compared with Gla-100 in patients with T2D irrespective of whether they are classed as LR or HR based on age- and National Committee for Quality Assurance Healthcare Effectiveness Data and Information Set-derived comorbidities.

  10. A comparison of biphasic insulin aspart and insulin glargine administered with oral antidiabetic drugs in type 2 diabetes mellitus--a systematic review and meta-analysis.

    Science.gov (United States)

    Rys, P; Wojciechowski, P; Siejka, S; Małecki, P; Hak, L; Malecki, M T

    2014-03-01

    It is uncertain whether the addition of biphasic insulin analogues to oral antidiabetic drugs (OADs) is as effective and safe as basal insulin in patients with type 2 diabetes mellitus (T2DM). We performed a systematic review to compare glycaemic control and selected clinical outcomes in T2DM patients inadequately controlled with OADs whose treatment was intensified by adding biphasic insulin aspart (BIAsp 30) or insulin glargine (IGlar). The analysis included randomised controlled trials (RCTs) identified by a systematic literature search in medical databases (MEDLINE, EMBASE, The Cochrane Library and other sources) up to March 2013. Studies met the inclusion criteria if they compared BIAsp 30 vs. IGlar added to at least one OAD in T2DM patients. Trials applying different OADs in both treatment arms were also included. Results were presented as weighted mean difference (WMD) or odds ratio (OR) with a 95% confidence interval (CI). Five trials, including a total number of 1758 patients followed up from 24 to 28 weeks, were identified. Quantitative synthesis demonstrated that BIAsp 30 reduced HbA1c level more efficiently than IGlar [5 RCTs; WMD (95% CI): -0.21% (-0.35%, -0.08%)]. Differences were observed in favour of BIAsp for lower mean prandial glucose increment [3 RCTs; WMD (95% CI): -14.70 mg/dl (-20.09, -9.31)]; no difference was observed for fasting plasma glucose [3 RCTs; WMD (95% CI): 7.09 mg/dl (-15.76, 29.94)]. We found no evidence for higher risk of overall [2 RCTs; 63% vs. 51%; OR = 1.77 (0.91; 3.44)] and severe hypoglycaemic episodes [4 RCTs; 0.98% vs. 1.12%; OR (95% CI) = 0.88 (0.31, 2.53)] in the BIAsp 30 group as compared with IGlar group. Twice-daily administration of BIAsp 30 resulted in larger weight gain [2 RCTs; WMD (95% CI) = 1.78 kg (1.04; 2.52)]. BIAsp 30 added to OAD therapy results in a better glycaemic control as compared with IGlar in T2DM patients. BIAsp 30 use is associated with slightly larger weight gain but no rise in risk

  11. Once-daily insulin glargine administration in the morning compared to bedtime in combination with morning glimepiride in patients with type 2 diabetes: an assessment of treatment flexibility.

    Science.gov (United States)

    Standl, E; Maxeiner, S; Raptis, S

    2006-03-01

    To compare the incidence of nocturnal hypoglycemia and glycemic control following bedtime or morning insulin glargine (LANTUS; glargine) plus glimepiride. In this 24-week, multinational, open, randomized study, 624 patients with type 2 diabetes poorly controlled on oral therapy received morning or bedtime glargine plus morning glimepiride (2, 3 or 4 mg) titrated to a target fasting blood glucose level bedtime (13.0 VS. 14.9 % of patients; between-treatment difference -1.9 %; one-sided 95 % confidence interval -100 %; 2.84 %). At endpoint, similar improvements in glycemic control were observed with morning compared to bedtime glargine: HbA1c: -1.65 +/- 1.21 VS. -1.57 +/- 1.16 %; p = 0.42; fasting blood glucose: -4.25 +/- 2.82 VS. -4.48 +/- 2.75 mmol/l; p = 0.08. The endpoint mean daily glargine dose was comparable (34.7 +/- 17.4 VS. 32.4 +/- 17.0 IU; p = 0.15), and there was no significant between-treatment difference in the change in body weight (2.1 VS. 1.8 kg; p = 0.39). Once-daily glargine can be administered in a flexible morning or bedtime regimen (plus morning glimepiride) to achieve good glycemic control without any difference in hypoglycemia.

  12. Economic evaluation of the treatment of type 2 diabetes with insulin glargine based on the LAPTOP trial.

    Science.gov (United States)

    Janka, Hans Uwe; Högy, Barbara

    2008-05-01

    In the LAPTOP trial, combination therapy with once-daily insulin glargine + oral antidiabetic agents glimepiride and metformin (BOT) was compared to twice-daily premixed insulin (CT). BOT was safer and more effective than CT. Cost analysis of both regimens were compared over a 1-year period. Analyses were performed from the perspective of the German statutory health insurance. Costs per patient per year were on average 236euro lower for BOT than for CT therapy. Economic advantage for BOT was robust to variation of expenses within a range of at least +/-20%. Insulin utilisation and prices were the major cost drivers, followed by costs associated with monitoring of blood glucose levels. Cost analysis of the LAPTOP trial suggest that BOT is more cost effective alternative to CT.

  13. Comparison of tofogliflozin 20 mg and ipragliflozin 50 mg used together with insulin glargine 300 U/ml using continuous glucose monitoring (CGM): A randomized crossover study.

    Science.gov (United States)

    Takeishi, Soichi; Tsuboi, Hiroki; Takekoshi, Shodo

    2017-08-18

    To investigate whether sodium glucose co-transporter 2 inhibitors (SGLT2i), tofogliflozin or ipragliflozin, achieve optimal glycemic variability, when used together with insulin glargine 300 U/mL (Glargine 300). Thirty patients with type 2 diabetes were randomly allocated to 2 groups. For the first group: After admission, tofogliflozin 20 mg was administered; Fasting plasma glucose (FPG) levels were titrated using an algorithm and stabilized at 80 mg/dL level with Glargine 300 for 5 days; Next, glucose levels were continuously monitored for 2 days using continuous glucose monitoring (CGM); Tofogliflozin was then washed out over 5 days; Subsequently, ipragliflozin 50 mg was administered; FPG levels were titrated using the same algorithm and stabilized at 80 mg/dL level with Glargine 300 for 5 days; Next, glucose levels were continuously monitored for 2 days using CGM. For the second group, ipragliflozin was administered prior to tofogliflozin, and the same regimen was maintained. Glargine 300 and SGLT2i were administered at 8:00 AM. Data collected on the second day of measurement (mean amplitude of glycemic excursion [MAGE], average daily risk range [ADRR]; on all days of measurement) were analyzed. Area over the glucose curve (300 during basal insulin therapy.

  14. A pilot study to examine the feasibility of insulin glargine in subjects with impaired fasting glucose, impaired glucose tolerance or new-onset type 2 diabetes.

    Science.gov (United States)

    Marbury, T C; Schwartz, S; Rosenberg, M A; Jariwala, N; Becker, R H A; Johnston, P S

    2008-05-01

    People with early type 2 diabetes and pre-diabetes (impaired glucose tolerance [IGT] and/or impaired fasting glucose [IFG]) are at risk of hyperglycaemia-related complications, including cardiovascular disease. Insulin, traditionally reserved as late treatment in type 2 diabetes, may also be a useful therapy in this population. We examined the short-term efficacy and tolerability of insulin glargine (glargine) in individuals with early or pre-type 2 diabetes. In this multicentre, double-blind, placebo-controlled, randomized, parallel group, 12-day study, subjects with IGT/IFG (n=9), newly diagnosed type 2 diabetes (n=9) or normal glucose tolerance (n=3) (confined to a clinical research unit taking a prescribed diet) were randomized to once-daily glargine (n=16) or placebo (saline; n=5) at bedtime. Dose was titrated to achieve target fasting blood glucose (FBG) 80-95 mg/dL. Over the treatment period, mean FBG decreased in glargine-treated subjects (from 100.0+/-18.8 to 85.6+/-18.4 mg/dL), but was unchanged in placebo-treated subjects (from 112.5+/-10.6 to 111.3+/-17.5 mg/dL). Mean eight-point blood glucose value decreased by 9.7 mg/dL in the glargine group, but increased by 8.1 mg/dL in the placebo group. Mean post-exercise blood glucose was similar before and after glargine treatment, but increased after placebo treatment. Five subjects receiving glargine experienced 16 mild symptomatic hypoglycaemia episodes; however, no hypoglycaemia occurred during exercise. Mean body weight decreased in both the glargine (-0.44 kg) and placebo (-0.25 kg) groups, in line with dietary restrictions. The results of this pilot study suggest that glargine can be used by people with IFG, IGT or new-onset type 2 diabetes for management of hyperglycaemia with low risk of hypoglycaemia. However titration of insulin in people on dietary restrictions should be more cautious as they may be more prone to hypoglycaemia. Further studies are warranted to determine the clinical benefits of this

  15. The Mobile Insulin Titration Intervention (MITI) for Insulin Glargine Titration in an Urban, Low-Income Population: Randomized Controlled Trial Protocol.

    Science.gov (United States)

    Levy, Natalie; Moynihan, Victoria; Nilo, Annielyn; Singer, Karyn; Bernik, Lidia S; Etiebet, Mary-Ann; Fang, Yixin; Cho, James; Natarajan, Sundar

    2015-03-13

    Patients on insulin glargine typically visit a clinician to obtain advice on how to adjust their insulin dose. These multiple clinic visits can be costly and time-consuming, particularly for low-income patients. It may be feasible to achieve insulin titration through text messages and phone calls with patients instead of face-to-face clinic visits. The objectives of this study are to (1) evaluate if the Mobile Insulin Titration Intervention (MITI) is clinically effective by helping patients reach their optimal dose of insulin glargine, (2) determine if the intervention is feasible within the setting and population, (3) assess patient satisfaction with the intervention, and (4) measure the costs associated with this intervention. This is a pilot study evaluating an approach to insulin titration using text messages and phone calls among patients with insulin-dependent type 2 diabetes in the outpatient medical clinic of Bellevue Hospital Center, a safety-net hospital in New York City. Patients will be randomized in a 1:1 ratio to either the MITI arm (texting/phone call intervention) or the usual-care arm (in-person clinic visits). Using a Web-based platform, weekday text messages will be sent to patients in the MITI arm, asking them to text back their fasting blood glucose values. In addition to daily reviews for alarm values, a clinician will rereview the texted values weekly, consult our physician-approved titration algorithm, and call the patients with advice on how to adjust their insulin dose. The primary outcome will be whether or not a patient reaches his/her optimal dose of insulin glargine within 12 weeks. Recruitment for this study occurred between June 2013 and December 2014. We are continuing to collect intervention and follow-up data from our patients who are currently enrolled. The results of our data analysis are expected to be available in 2015. This study explores the use of widely-available text messaging and voice technologies for insulin titration

  16. New insulin glargine 300 Units · mL-1 provides a more even activity profile and prolonged glycemic control at steady state compared with insulin glargine 100 Units · mL-1.

    Science.gov (United States)

    Becker, Reinhard H A; Dahmen, Raphael; Bergmann, Karin; Lehmann, Anne; Jax, Thomas; Heise, Tim

    2015-04-01

    To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of a new insulin glargine comprising 300 units · mL(-1) (Gla-300), compared with insulin glargine 100 units · mL(-1) (Gla-100) at steady state in people with type 1 diabetes. A randomized, double-blind, crossover study (N = 30) was conducted, applying the euglycemic clamp technique over a period of 36 h. In this multiple-dose to steady-state study, participants received once-daily subcutaneous administrations of either 0.4 (cohort 1) or 0.6 units · kg(-1) (cohort 2) Gla-300 for 8 days in one treatment period and 0.4 units · kg(-1) Gla-100 for 8 days in the other. Here we focus on the results of a direct comparison between 0.4 units · kg(-1) of each treatment. PK and PD assessments performed on the last treatment day included serum insulin measurements using a radioimmunoassay and the automated euglycemic glucose clamp technique over 36 h. At steady state, insulin concentration (INS) and glucose infusion rate (GIR) profiles of Gla-300 were more constant and more evenly distributed over 24 h compared with those of Gla-100 and lasted longer, as supported by the later time (∼ 3 h) to 50% of the area under the serum INS and GIR time curves from time zero to 36 h post dosing. Tight blood glucose control (≤ 105 mg · dL(-1)) was maintained for approximately 5 h longer (median of 30 h) with Gla-300 compared with Gla-100. Gla-300 provides more even steady-state PK and PD profiles and a longer duration of action than Gla-100, extending blood glucose control well beyond 24 h. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  17. Effects of exenatide on cardiac function, perfusion, and energetics in type 2 diabetic patients with cardiomyopathy: a randomized controlled trial against insulin glargine.

    Science.gov (United States)

    Chen, Weena J Y; Diamant, Michaela; de Boer, Karin; Harms, Hendrik J; Robbers, Lourens F H J; van Rossum, Albert C; Kramer, Mark H H; Lammertsma, Adriaan A; Knaapen, Paul

    2017-05-19

    Multiple bloodglucose-lowering agents have been linked to cardiovascular events. Preliminary studies showed improvement in left ventricular (LV) function during glucagon-like peptide-1 receptor agonist administration. Underlying mechanisms, however, are unclear. The purpose of this study was to investigate myocardial perfusion and oxidative metabolism in type 2 diabetic (T2DM) patients with LV systolic dysfunction as compared to healthy controls. Furthermore, effects of 26-weeks of exenatide versus insulin glargine administration on cardiac function, perfusion and oxidative metabolism in T2DM patients with LV dysfunction were explored. Twenty-six T2DM patients with LV systolic dysfunction (cardiac magnetic resonance (CMR) derived LV ejection fraction (LVEF) of 47 ± 13%) and 10 controls (LVEF of 59 ± 4%, P efficiency, measured using [ 11 C]acetate PET and CMR derived stroke volume, were not different between the groups. Eleven patients in the exenatide group and 12 patients in the insulin glargine group completed the trial. Systemic metabolic control was improved after both treatments, although, no changes in cardiac function, perfusion and metabolism were seen after exenatide or insulin glargine. T2DM patients with LV systolic dysfunction did not have altered myocardial efficiency as compared to healthy controls. Exenatide or insulin glargine had no effects on cardiac function, perfusion or oxidative metabolism. Trial registration NCT00766857.

  18. Safety and Efficacy of Once-Weekly Exenatide Compared With Insulin Glargine Titrated to Target in Patients With Type 2 Diabetes Over 84 Weeks

    NARCIS (Netherlands)

    Diamant, M.; Van Gaal, L.; Stranks, S.; Guerci, B.; MacConell, L.; Haber, H.; Scism-Bacon, J.; Trautmann, M.

    2012-01-01

    OBJECTIVE - We recently reported that after 26 weeks, exenatide once weekly (EQW) resulted in superior A1C reduction, reduced hypoglycemia, and progressive weight loss compared with daily insulin glargine (IG) in patients with type 2 diabetes who were taking metformin alone or with sulfonylurea.

  19. Le médicament du mois. Insuline glargine 300 U/mL (Toujeo®)

    OpenAIRE

    SCHEEN, André

    2016-01-01

    Résumé : Cet article présente une nouvelle formulation d’insuline glargine concentrée à 300 U/mL (Gla-300), commercialisée sous le nom de Toujeo®, disponible dans un stylo-injecteur prérempli SoloStar™ amélioré, pour le traitement du diabète de type 1 et de type 2 chez l’adulte. Outre une concentration trois fois plus élevée que celle de l’insuline Lantus® (100 U/mL ou Gla-100), les profils pharmacocinétique et pharmacodynamique de Gla-300 sont plus plats et plus longs (au-delà de 24 heures),...

  20. Cost comparison of insulin glargine with insulin detemir in a basal-bolus regime with mealtime insulin aspart in type 2 diabetes in Germany

    Directory of Open Access Journals (Sweden)

    Dippel, Franz-Werner

    2010-01-01

    Full Text Available Objective: To compare the treatment costs of insulin glargine (IG; Lantus® to detemir (ID; Levemir®, both combined with bolus insulin aspart (NovoRapid® in type 2 diabetes (T2D in Germany. Methods: Cost comparison was based on data of a 1-year randomised controlled trial [1]. IG was administered once daily and ID once (57% of patients or twice daily (43% according to treatment response. At the end of the trial, mean daily basal insulin doses were 0.59 U/kg (IG and 0.82 U/kg (ID. Aspart doses were 0.32 U/kg (IG and 0.36 U/kg (ID. Costs were calculated from the German statutory health insurance (SHI perspective using official 2008 prices. Sensitivity analyses were performed to test robustness of the results. Results: Annual basal and bolus insulin costs per patient were € 1,473 (IG and € 1,940 (ID. The cost of lancets and blood glucose test strips were € 1,125 (IG and € 1,286 (ID. Annual costs for needles were € 393 (IG and € 449 (ID. The total annual cost per patient of administering IG was € 2,991 compared with € 3,675 for ID, translating into a 19% annual cost difference of € 684/patient. Base case results were robust to varying assumptions for insulin dose, insulin price, change in weight and proportion of ID once daily administrations. Conclusion: IG and ID basal-bolus regimes have comparative safety and efficacy, based on the Hollander study, IG however may represent a significantly more cost saving option for T2D patients in Germany requiring basal-bolus insulin analogue therapy with potential annual cost savings of € 684/patient compared to ID.

  1. Chronic Kidney Disease, Basal Insulin Glargine, and Health Outcomes in People with Dysglycemia: The ORIGIN Study.

    Science.gov (United States)

    Papademetriou, Vasilios; Nylen, Eric S; Doumas, Michael; Probstfield, Jeff; Mann, Johannes F E; Gilbert, Richard E; Gerstein, Hertzel C

    2017-12-01

    Early stages of chronic kidney disease are associated with an increased cardiovascular risk in patients with established type 2 diabetes and macrovascular disease. The role of early stages of chronic kidney disease on macrovascular outcomes in prediabetes and early type 2 diabetes mellitus is not known. In the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial, the introduction of insulin had no effect on cardiovascular outcomes compared with standard therapy. In this post hoc analysis of ORIGIN, we compared cardiovascular outcomes in subjects without to those with mild (Stages 1-2) or moderate chronic kidney disease (Stage 3). Τwo co-primary composite cardiovascular outcomes were assessed. The first was the composite end point of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes; and the second was a composite of any of these events plus a revascularization procedure, or hospitalization for heart failure. Several secondary outcomes were prespecified, including microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers. Complete renal function data were available in 12,174 of 12,537 ORIGIN participants. A total of 8114 (67%) had no chronic kidney disease, while 4060 (33%) had chronic kidney disease stage 1-3. When compared with nonchronic kidney disease participants, the risk of developing the composite primary outcome (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) in those with mild to moderate chronic kidney disease was 87% higher; hazard ratio (HR) 1.87; 95% confidence interval (CI), 1.71-2.04 (P chronic kidney disease 1-3 was also associated with a greater than twofold higher risk for both all-cause mortality (HR 2.17; 95% CI, 1.98-2.38; P chronic kidney disease had significantly higher risk for nonfatal myocardial infarction (50%), nonfatal stroke (68%), any stroke (84%), the above composite primary end point plus revascularization or heart failure requiring

  2. The cost-effectiveness of exenatide twice daily (BID) vs insulin lispro three times daily (TID) as add-on therapy to titrated insulin glargine in patients with type 2 diabetes

    NARCIS (Netherlands)

    Gordon, J.; McEwan, P.; Sabale, U.; Kartman, B.; Wolffenbuttel, B. H. R.

    2016-01-01

    Objective: To evaluate the cost-effectiveness of exenatide twice daily (BID) vs bolus insulin lispro three times daily (TID) as add-on therapy when glycemic control is sub-optimal with titrated basal insulin glargine and metformin. Methods: The analysis was based on the recent 4B Study, which

  3. Starting bedtime glargine versus NPH insulin in poorly controlled type 2 diabetic patients with various hyperglycemia types (fasting type or postprandial type).

    Science.gov (United States)

    Vähätalo, Markku A; Viikari, Jorma; Rönnemaa, Tapani

    2014-04-01

    Our aim was to compare the effects of an intermediate acting human insulin (NPH) and a long-acting insulin analog, insulin glargine, in insulin naïve type 2 diabetes patients, stratified by the type of hyperglycemia (fasting or postprandial type). Based on different action profiles, we hypothesized that patients having different hyperglycemia types would react differently when treated with these insulins. This is a post hoc analysis of the Lanmet study data. The Lanmet study was a randomized, 36-week controlled insulin initiation study in type 2 diabetes patients. 109 subjects with baseline HbA1c >8.0% (64 mmol/mol) completed the study. The patients were divided into two groups according to fasting glucose (mmol/l)/HbA1c (%) ratio. Patients with a ratio ≥1.3 were defined as having fasting type and those with a ratio weight, and final insulin dose. Independently of insulin type, compared to patients with postprandial type hyperglycemia, those with fasting type hyperglycemia had 2.1 kg/m(2) greater initial BMI (p = 0.044), gained 2.0 kg more weight (p = 0.020, adjusted for baseline BMI p = 0.035), and had 36% greater final insulin dose/kg (p = 0.001). With respect to hyperglycemia type, there was no difference between NPH and glargine in their effects on HbA1c. When starting bedtime insulin in type 2 diabetes patients, those with fasting type hyperglycemia are prone to greater weight gain. Hyperglycemia type does not help in identifying patients who would benefit specially from either NPH insulin or insulin glargine.

  4. Randomized clinical trial of the efficacy and safety of insulin glargine vs. NPH insulin as basal insulin for the treatment of glucocorticoid induced hyperglycemia using continuous glucose monitoring in hospitalized patients with type 2 diabetes and respiratory disease.

    Science.gov (United States)

    Ruiz de Adana, María S; Colomo, Natalia; Maldonado-Araque, Cristina; Fontalba, María I; Linares, Francisca; García-Torres, Francisca; Fernández, Rosario; Bautista, Carmen; Olveira, Gabriel; de la Cruz, José L; Rojo-Martínez, Gemma; Valdés, Sergio

    2015-11-01

    To investigate the clinical efficacy and safety of insulin glargine compared with NPH insulin as basal insulin for the management of corticosteroid-induced hyperglycemia in hospitalized people with type 2 diabetes (T2DM) and respiratory disease. Randomized, two-arm parallel group, clinical trial undertaken from February 2011 to November 2012 on the pneumology ward of the Hospital Regional Universitario de Málaga (Spain), involving 53 participants with T2DM treated with medium/high doses of intermediate-acting corticosteroids. Participants were randomly assigned to receive one single dose of insulin glargine or NPH insulin in three equally divided doses before each meal as basal insulin within a basal-bolus insulin protocol. The intervention lasted six days or until discharge if earlier. No significant differences were seen between groups during the study in mean blood glucose (11.43±3.44 mmol/l in glargine vs. 11.88±2.94 mmol/l in NPH, p=0.624), and measures of glucose variability (standard deviation 3.27±1.16 mmol/l vs. 3.61±0.99 mmol/l, p=0.273; coefficient of variation 1.55±0.33 mmol/l vs. 1.72±0.39 mmol/l, p=0.200). Results from CGM were concordant with those obtained with capillary blood glucose reading. The length of hospital stay was also similar between groups (8.2±2.8 days vs. 9.8±3.4 days, p=0.166) There was a non significant trend for lower episodes of mild (4 vs. 8, p=0.351) and severe hypoglycemia (0 vs. 3, p=0.13) in the glargine group. The results of this study showed that insulin glargine and NPH insulin are equally effective in a basal-bolus insulin protocol to treat glucocorticoid-induced hyperglycemia in people with T2DM on a pneumology ward. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Low within- and between-day variability in exposure to new insulin glargine 300 U/ml.

    Science.gov (United States)

    Becker, R H A; Nowotny, I; Teichert, L; Bergmann, K; Kapitza, C

    2015-03-01

    To characterize the variability in exposure and metabolic effect of insulin glargine 300 U/ml (Gla-300) at steady state in people with type 1 diabetes (T1DM). A total of 50 participants with T1DM underwent two 24-h euglycaemic clamps in steady-state conditions after six once-daily administrations of 0.4 U/kg Gla-300 in a double-blind, randomized, two-treatment, two-period, crossover clamp study. Participants were randomized to receive Gla-300 as a standard cartridge formulation in the first treatment period, and as a formulation with enhanced stability through polysorbate-20 addition in the second treatment period, or vice versa. This design allowed the assessment of bioequivalence between formulations and, subsequently, within- and between-day variability. The cumulative exposure and effect of Gla-300 developed linearly over 24 h, and were evenly distributed across 6- and 12-h intervals. Diurnal fluctuation in exposure (within-day variability) was low; the peak-to-trough ratio of insulin concentration profiles was 300 provides predictable, evenly distributed 24-h coverage as a result of low fluctuation and high reproducibility in insulin exposure, and appears suitable for effective basal insulin use. © 2014 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  6. New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using oral agents and basal insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 2).

    Science.gov (United States)

    Yki-Järvinen, Hannele; Bergenstal, Richard; Ziemen, Monika; Wardecki, Marek; Muehlen-Bartmer, Isabel; Boelle, Emmanuelle; Riddle, Matthew C

    2014-12-01

    To compare the efficacy and safety of new insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in people with type 2 diabetes using basal insulin (≥42 units/day) plus oral antihyperglycemic drugs (OADs). EDITION 2 was a multicenter, open-label, two-arm study. Adults receiving basal insulin plus OADs were randomized to Gla-300 or Gla-100 once daily for 6 months. The primary end point was change in HbA1c. The main secondary end point was percentage of participants with one or more nocturnal confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycemic events from week 9 to month 6. Randomized participants (n = 811) had a mean (SD) HbA₁c of 8.24% (0.82) and BMI of 34.8 kg/m(2) (6.4). Glycemic control improved similarly with both basal insulins; least squares mean (SD) reduction from baseline was -0.57% (0.09) for Gla-300 and -0.56% (0.09) for Gla-100 (mean difference -0.01% [95% CI -0.14 to 0.12]), with 10% higher dose of Gla-300. Less nocturnal confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycemia was observed with Gla-300 from week 9 to month 6 (relative risk 0.77 [95% CI 0.61-0.99]; P = 0.038) and during the first 8 weeks. Fewer nocturnal and any time (24 h) hypoglycemic events were reported during the entire 6-month period. Weight gain was lower with Gla-300 than with Gla-100 (P = 0.015). No between-treatment differences in safety parameters were identified. Gla-300 was as effective as Gla-100 and associated with a lower risk of hypoglycemia during the night and at any time of the day. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  7. New insulin glargine 300 units/mL versus glargine 100 units/mL in people with type 2 diabetes using basal and mealtime insulin: glucose control and hypoglycemia in a 6-month randomized controlled trial (EDITION 1).

    Science.gov (United States)

    Riddle, Matthew C; Bolli, Geremia B; Ziemen, Monika; Muehlen-Bartmer, Isabel; Bizet, Florence; Home, Philip D

    2014-10-01

    To compare the efficacy and safety of new insulin glargine 300 units/mL (Gla-300) with glargine 100 units/mL (Gla-100) in people with type 2 diabetes on basal insulin (≥42 units/day) plus mealtime insulin. EDITION 1 (NCT01499082) was a 6-month, multinational, open-label, parallel-group study. Adults with glycated hemoglobin A1c (HbA1c) 7.0-10.0% (53-86 mmol/mol) were randomized to Gla-300 or Gla-100 once daily with dose titration seeking fasting plasma glucose 4.4-5.6 mmol/L. Primary end point was HbA1c change from baseline; main secondary end point was percentage of participants with one or more confirmed (≤3.9 mmol/L) or severe nocturnal hypoglycemia from week 9 to month 6. Participants (n = 807) had mean age 60 years, diabetes duration 16 years, BMI 36.6 kg/m(2), and HbA1c 8.15% (65.6 mmol/mol). HbA1c reduction was equivalent between regimens; least squares mean difference -0.00% (95% CI -0.11 to 0.11) (-0.00 mmol/mol [-1.2 to 1.2]). Fewer participants reported one or more confirmed (≤3.9 mmol/L) or severe nocturnal hypoglycemic events between week 9 and month 6 with Gla-300 (36 vs. 46% with Gla-100; relative risk 0.79 [95% CI 0.67-0.93]; P 300 in the first 8 weeks of treatment. No between-treatment differences in tolerability or safety were identified. Gla-300 controls HbA1c as well as Gla-100 for people with type 2 diabetes treated with basal and mealtime insulin but with consistently less risk of nocturnal hypoglycemia. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  8. New insulin glargine 300 U/ml compared with glargine 100 U/ml in insulin-naïve people with type 2 diabetes on oral glucose-lowering drugs: a randomized controlled trial (EDITION 3).

    Science.gov (United States)

    Bolli, G B; Riddle, M C; Bergenstal, R M; Ziemen, M; Sestakauskas, K; Goyeau, H; Home, P D

    2015-04-01

    To compare the efficacy and safety of new insulin glargine 300 U/ml (Gla-300) with that of glargine 100 U/ml (Gla-100) in insulin-naïve people with type 2 diabetes using oral glucose-lowering drugs. The EDITION 3 study was a multicentre, open-label, parallel-group study. Participants were randomized to Gla-300 or Gla-100 once daily for 6 months, discontinuing sulphonylureas and glinides, with a dose titration aimed at achieving pre-breakfast plasma glucose concentrations of 4.4-5.6 mmol/l (80-100 mg/dl). The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline to month 6. The main secondary endpoint was percentage of participants with ≥1 nocturnal confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemia from week 9 to month 6. Other measures of glycaemia and hypoglycaemia, weight change and insulin dose were assessed. Randomized participants (n = 878) had a mean (standard deviation) age of 57.7 (10.1) years, diabetes duration 9.8 (6.4) years, body mass index 33.0 (6.7) kg/m(2) and HbA1c 8.54 (1.06) % [69.8 (11.6) mmol/mol]. HbA1c levels decreased by equivalent amounts with the two treatments; the least squares mean difference in change from baseline was 0.04 [95% confidence interval (CI) -0.09 to 0.17] % or 0.4 (-1.0 to 1.9) mmol/mol. Numerically fewer participants reported ≥1 nocturnal confirmed (≤3.9 mmol/l) or severe hypoglycaemia from week 9 to month 6 [relative risk (RR) 0.89 (95% CI 0.66 to 1.20)] with Gla-300 versus Gla-100; a significantly lower risk of hypoglycaemia with this definition was found over the 6-month treatment period [RR 0.76 (95% CI 0.59 to 0.99)]. No between-treatment differences in adverse events were identified. Gla-300 is as effective as Gla-100 in reducing HbA1c in insulin-naïve people with type 2 diabetes, with lower hypoglycaemia risk. © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  9. Attenuated Suppression of Lipolysis Explains Increases in Triglyceride Secretion and Concentration with Basal Insulin Peglispro (BIL) Relative to Insulin Glargine Treatment in Patients with Type 1 Diabetes

    DEFF Research Database (Denmark)

    Johansen, Rakel Fuglsang; Søndergaard, Esben; Linnebjerg, Helle

    2017-01-01

    AIMS: In patients with type 1 diabetes, basal insulin peglispro (BIL) lowers weight and increases plasma triglycerides (TG) and hepatic fat relative to insulin glargine (GL). To explain this, we hypothesised that BIL's attenuated peripheral effects may include increased free fatty acid flux...... to the liver, causing increased VLDL-TG secretion and lipid oxidation, and decreased TG adipose tissue deposition. MATERIALS AND METHODS: In this open-label, randomised, 2-period crossover study, 14 patients with type 1 diabetes received once-daily, individualised, stable BIL or GL doses for 3 weeks. Palmitate.......90), respectively. The difference in LS means (95% CI) for VLDL-TG storage rate was -0.36 (-0.83, 0.12). CONCLUSIONS: BIL-treated patients had higher effective lipolysis, VLDL-TG secretion and VLDL-TG concentration versus GL, explaining the increased plasma TG concentrations reported previously. Data support...

  10. Ease of Use of the Insulin Glargine 300 U/mL Pen Injector in Insulin-Naïve People With Type 2 Diabetes.

    Science.gov (United States)

    Pohlmeier, Harald; Berard, Lori; Brulle-Wohlhueter, Claire; Wu, Junlong; Dahmen, Raphael; Nowotny, Irene; Klonoff, David

    2017-03-01

    Insulin glargine 300 U/mL (Gla-300) contains the same active ingredient as glargine 100 U/mL (Gla-100), and provides the same number of units in one-third of the volume. The SoloSTAR(®) injector pen has been modified to ensure accurate administration of this reduced volume and to improve user experience. Insulin- and pen-naïve adults with type 2 diabetes (T2DM) inadequately controlled with oral antihyperglycemic drugs, who had glycated hemoglobin (HbA1c) levels of 7.0-11.0 % (53-97 mmol/mol) were studied. They received once-daily Gla-300 in this 4-week, multicenter, open-label, single-arm study (NCT02227212). Ease of use/ease of learning (the primary endpoint), glycemic control, safety, and reliability of the disposable (prefilled) Gla-300 injector pen (secondary endpoints) were evaluated. At week 4, 95.0% of 40 participating subjects assessed the pen as excellent/good and none as poor/very poor; 97.5% would recommend it to others. Total Diabetes Treatment Satisfaction Questionnaire scores were stable throughout the study. Mean (SD) fasting plasma glucose levels decreased from 166.1 (35.0) mg/dL at baseline to 124.2 (41.1) mg/dL at week 4. No product technical complaints (PTCs) or adverse events (AEs) related to PTCs were reported. The number of subjects experiencing hypoglycemic events of any kind and the incidence of AEs were low. No serious AEs were reported. The Gla-300 injector pen is easy to use and easy to learn to use, with demonstrable reliability and high degrees of acceptance and treatment satisfaction. Once-daily Gla-300 basal insulin treatment was well tolerated and effective in pen- and insulin-naïve adult T2DM subjects.

  11. Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU): a randomised controlled trial

    DEFF Research Database (Denmark)

    Russell-Jones, D; Vaag, A; Schmitz, O

    2009-01-01

    Hg; -4.5 mmHg difference, 95% CI 6.8, -2.2; p = 0.0001) but not vs placebo (p = 0.0791). Rates of hypoglycaemic episodes (major, minor and symptoms only, respectively) were 0.06, 1.2 and 1.0 events/patient/year, respectively, in the liraglutide group (vs 0, 1.3, 1.8 and 0, 1.0, 0.5 with glargine......AIMS/HYPOTHESIS: The aim of the study was to compare the efficacy and safety of liraglutide in type 2 diabetes mellitus vs placebo and insulin glargine (A21Gly,B31Arg,B32Arg human insulin), all in combination with metformin and glimepiride. METHODS: This randomised (using a telephone or web...

  12. Systematic review and meta-analysis of randomized clinical trials comparing efficacy and safety outcomes of insulin glargine with NPH insulin, premixed insulin preparations or with insulin detemir in type 2 diabetes mellitus.

    Science.gov (United States)

    Rys, Przemyslaw; Wojciechowski, Piotr; Rogoz-Sitek, Agnieszka; Niesyczyński, Grzegorz; Lis, Joanna; Syta, Albert; Malecki, Maciej T

    2015-08-01

    A variety of basal insulin preparations are used to treat patients with type 2 diabetes mellitus (T2DM). We aimed to summarize scientific evidence on relative efficacy and safety of insulin glargine (IGlar) and other insulins in T2DM. A systematic review was carried out in major medical databases up to December 2012. Relevant studies compared efficacy and safety of IGlar, added to oral drugs (OAD) or/and in combination with bolus insulin, with protamine insulin (NPH) or premixed insulin (MIX) in the same regimen, as well as with insulin detemir (IDet), in T2DM. Target HbA1c level without hypoglycemic events was considered the primary endpoint. Twenty eight RCTs involving 12,669 T2DM patients followed for 12-52 weeks were included in quantitative analysis. IGlar + OAD use was associated with higher probability of reaching target HbA1c level without hypoglycemia as compared to NPH + OAD (RR = 1.32 [1.09, 1.59]) or MIX without OAD (RR = 1.61 [1.22, 2.13]) and similar effect as IDet + OAD (RR = 1.07 [0.87, 1.33]) and MIX + OAD (RR = 1.09 [0.86, 1.38]). IGlar + OAD demonstrated significantly lower risk of symptomatic hypoglycemia as compared to NPH + OAD (RR = 0.89 [0.83, 0.96]), MIX + OAD (RR = 0.75 [0.68, 0.83]) and MIX without OAD(RR = 0.75 [0.68, 0.83]), but not with IDet + OAD (RR = 0.99 [0.90, 1.08]). In basal-bolus regimens, IGlar demonstrated similar proportion of T2DM patients achieving target HbA1c as compared to NPH (RR = 1.14 [0.91, 1.44]) but higher than MIX (RR = 1.26 [1.12, 1.42) or IDet (RR = 1.38 [1.11, 1.72]). The risk of severe hypoglycemia was lower in IGlar than in NPH (RR = 0.77 [0.63, 0.94]), with no differences in comparison with MIX (RR = 0.74 [0.46, 1.20]) and IDet (RR = 1.10 [0.54, 2.25]). IGlar + OAD has comparable safety profile to NPH, with less frequent adverse events leading to treatment discontinuation than MIX + OAD (RR = 0.41 [0.22, 0.76]) and IDet + OAD (RR = 0.40 [0.24, 0.69]). Also severe adverse reactions were less common for IGlar

  13. Does a patient-managed insulin intensification strategy with insulin glargine and insulin glulisine provide similar glycemic control as a physician-managed strategy? Results of the START (Self-Titration With Apidra to Reach Target) Study: a randomized noninferiority trial.

    Science.gov (United States)

    Harris, Stewart B; Yale, Jean-François; Berard, Lori; Stewart, John; Abbaszadeh, Babak; Webster-Bogaert, Susan; Gerstein, Hertzel C

    2014-01-01

    OBJECTIVE Diabetes self-management is universally regarded as a foundation of diabetes care. We determined whether comparable glycemic control could be achieved by self-titration versus physician titration of a once-daily bolus insulin dose in patients with type 2 diabetes who are unable to achieve optimal glycemia control with a basal insulin. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes, an HbA1c level >7% (53 mmol/mol), and either nocturnal hypoglycemia episodes or an insufficient basal insulin glargine level (with or without oral agents) to achieve a fasting plasma glucose level ≤6 mmol/L (108 mg/dL) were studied. Participants all had bolus insulin glulisine added at breakfast and were allocated to either algorithm-guided patient self-titration or physician titration. The primary outcome was an HbA1c level ≤7% (53 mmol/mol) without severe hypoglycemia. RESULTS After a mean (SD) follow-up of 159.4 days (36.2 days), 28.4% of participants in the self-titration arm vs. 21.2% in the physician titration arm achieved an HbA1c level of ≤7% (53 mmol/mol) without severe hypoglycemia (between-group absolute difference 7.2%; 95% CI -3.2 to 17.7). The lower end of this 95% confidence interval was within the predetermined noninferiority boundary of -5% (P noninferiority = 0.011). CONCLUSIONS In stable patients with type 2 diabetes who are receiving doses of basal insulin glargine who require bolus insulin, a simple bolus insulin patient-managed titration algorithm is as effective as a physician-managed algorithm.

  14. Real-World Data Collection Regarding Titration Algorithms for Insulin Glargine in Patients With Type 2 Diabetes Mellitus

    Science.gov (United States)

    Pfützner, Andreas; Stratmann, Bernd; Funke, Klaus; Pohlmeier, Harald; Rose, Ludger; Sieber, Jochen; Flacke, Frank; Tschoepe, Diethelm

    2016-01-01

    The primary objective of this study was to collect data regarding the effectiveness of different dose titration algorithms (TAs) for optimization or initiation of basal insulin supported oral therapy (BOT) in patients with type 2 diabetes. A total of 50 patients were enrolled in this trial (17 women, 33 men, age 63 ± 8 years, HbA1c 7.9 ± 0.8%). The investigator decided on an individual basis to apply any of 4 standard TAs: standard (S: fasting glucose target 90-130 mg/dL, n = 39), standard-fast titration (S-FT: 90-130 mg/dL, larger dose increments at FBG titration. HbA1c improved from 7.9 ± 0.8% to 7.5 ± 0.7% (P < .001). In total, 1300 dose decisions were made (1192 according to the TA and 108 by the physicians independently from the TA in 29 patients [58% of study population]). Reasons for TA-overruling dosing decisions were hypoglycemic events (14 mild/4 moderate) in 9 patients. In the majority of these cases (89.8%), the physician recommended continuation of the previous dose or a higher dose. The majority of FBG values were within the respective target range after 4 weeks. In conclusion, the insulin glargine TAs delivered safe dose recommendations with a low risk of hypoglycemia, which successfully led to a stable dose in the vast majority of patients. PMID:27325389

  15. Insulin degludec versus insulin glargine U100 for patients with type 1 or type 2 diabetes in the US: a budget impact analysis with rebate tables.

    Science.gov (United States)

    Lane, Wendy S; Weatherall, James; Gundgaard, Jens; Pollock, Richard F

    2017-10-12

    Drug rebates are almost universally negotiated privately between the manufacturer and the payer in the US. The aim of the present study was to illustrate the use of a "rebate table" to improve the transparency and utility of published budget impact analyses in the US by modeling ranges of hypothetical rebates for two comparators. Worked examples were conducted to illustrate the budgetary implications of using insulin degludec (IDeg) relative to insulin glargine (IGlar) U100 in patients with type 1 or 2 diabetes. A short-term (1-year) budget impact model was developed to evaluate the costs of switching to IDeg from IGlar in patients with type 1 or 2 diabetes on basal-bolus and basal-only insulin, respectively. The analysis used insulin dose and hypoglycemia data from recent randomized trials, data on the prevalence of diabetes, and estimates of the proportion of patients using each insulin regimen. The model was configured to run multiple rebate scenarios to generate a rebate table in a hypothetical 1 million member commercial plan. Relative to IGlar, IDeg resulted in reductions in non-severe and severe hypoglycemia incidence and costs both in patients with type 1 and patients with type 2 diabetes. Insulin acquisition costs were higher, and respective rebates of 7.3% and 10.6% were required for IDeg to break-even with IGlar at the full list price. Incremental per member per month IDeg costs without a rebate were USD 0.04 in type 1 diabetes and USD 0.80 in type 2 diabetes. Using IDeg instead of IGlar at list price could result in a modest increase in costs when considering insulin and hypoglycemia costs alone, but modest incremental rebates with IDeg would result in cost neutrality relative to IGlar. In addition, IDeg would result in reduced incidence of severe and non-severe hypoglycemia.

  16. Efficacy and safety of insulin degludec three times a week versus insulin glargine once a day in insulin-naive patients with type 2 diabetes: results of two phase 3, 26 week, randomised, open-label, treat-to-target, non-inferiority trials

    NARCIS (Netherlands)

    Zinman, Bernard; DeVries, J. Hans; Bode, Bruce; Russell-Jones, David; Leiter, Lawrence A.; Moses, Alan; Johansen, Thue; Ratner, Robert

    2013-01-01

    Results of an exploratory phase 2 study showed that insulin degludec, a basal insulin with an action profile of longer than 42 h, provided similar glycaemic control when injected three times a week (IDeg 3TW) to once-daily insulin glargine (IGlar OD). To provide further evidence, we did two phase 3

  17. Effect of pioglitazone versus insulin glargine on cardiac size, function, and measures of fluid retention in patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Groop Leif

    2009-03-01

    Full Text Available Abstract Background Both insulin and thiazolidinediones (TZDs are effective in the treatment of hyperglycaemia and amelioration of insulin resistance in type 2 diabetes but have side effects including weight gain and fluid retention. The use of TZDs has been further hampered by the risk of adverse cardiovascular events including heart failure. The present study evaluated the effect of pioglitazone or insulin glargine on cardiac function and size as well as on surrogate markers of fluid retention such as weight, haemoglobin and natriuretic peptides. Methods Thirty patients with inadequate glycaemic control on metformin and sulfonylurea were randomised to receive add-on therapy with insulin glargine or pioglitazone for 26 weeks. Echocardiographic data and blood samples were collected from the two groups before the start of the treatment and after 26 weeks. Left ventricular end-diastolic and left atrial end-systolic volumes were quantified, weight measured and blood samples analyzed. Results After 26 weeks of treatment, the changes in HbA1c, weight and haemoglobin were similar between the two groups. HDL increased significantly in the pioglitazone group. While there was an increase in natriuretic peptides in the pioglitazone group (NT-proBNP 11.4 ± 19.6 to 22.8 ± 44.0, p = 0.046, the difference between the treatment groups was not significant. Left ventricular end-diastolic volume increased by 11% and left atrial end-systolic volume by 17% in the pioglitazone group (Both, p Conclusion This randomised pilot-study showed that six-month treatment with pioglitazone induced significant increases in natriuretic peptides and alterations of cardiac size. These changes were not observed with insulin glargine, which also is known to induce fluid retention. Larger randomised trials are warranted to confirm these findings.

  18. Study of optimal basal insulin glargine dose requirement in Indian population as an add on therapy to oral hypoglycaemic agents to achieve target fasting blood glucose levels.

    Science.gov (United States)

    Agarwal, S K; Singh, B K; Wadhwa, Roopak

    2013-09-01

    Optimal dosing of basal insulin is needed to achieve target fasting blood glucose and to avoid hypoglycaemia on the other hand in patients of type 2 diabetes on bedtime basal insulin and daytime sulfonylureas. This is an open label, randomised prospective study done in 40 type 2 diabetics having uncontrolled diabetes. Statistical analysis was performed by the SPSS programme for windows, version 17.0. Continuous variables are presented as mean +/- SD, and categorical variables are presented as absolute numbers and percentage. Data were checked for normality before statistical analysis. Normally distributed continuous variables were compared from baseline to 12th week using paired t-test. The average dose requirement of insulin glargine was 33.55 +/- 11.94 units (mean +/- SD). The average insulin glargine dose requirement per kg body weight was 0.48 +/- 0.17 units/kg body weight. The range of insulin dose was 0.23 to 0.96 units/kg body weight. Dose titration is patient specific and should be done in order to achieve target fasting blood glucose.

  19. Predictors of nonsevere and severe hypoglycemia during glucose-lowering treatment with insulin glargine or standard drugs in the ORIGIN trial.

    Science.gov (United States)

    2015-01-01

    Hypoglycemia is a leading risk of glucose-lowering therapy. Treatment with insulin glargine compared with standard care early in the course of dysglycemia in the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial provides information on the frequency and predictors of hypoglycemia in this setting. A total of 12,537 people with high cardiovascular risk and dysglycemia treated with one or no oral glucose-lowering agents were randomized to add glargine titrated to a fasting glucose level of ≤5.3 mmol/L (≤95 mg/dL) or to use standard therapies. Independent associations of both nonsevere hypoglycemia (symptomatic and confirmed with a glucose level of ≤3 mmol/L [≤54 mg/dL]) and severe hypoglycemia with characteristics at baseline, treatment allocation, and average HbA1c were assessed by Cox proportional hazards models. During a median follow-up period of 6.2 years, 28% of participants reported nonsevere hypoglycemia, and 3.8% reported severe hypoglycemia. Prior use of a sulfonylurea and allocation to glargine independently predicted a higher risk for both categories of participants. Nonsevere events were independently associated with younger age, lower BMI, the presence of diabetes, and higher baseline HbA1c level. Severe events were associated with older age, hypertension, higher serum creatinine level, and lower cognitive function, but not baseline glycemic status. Progressively higher on-treatment HbA1c level was associated with a lower risk of nonsevere events in both treatment groups; a lower risk of severe events in the glargine group, and a higher risk of severe events with standard care. Hypoglycemia was relatively uncommon in the ORIGIN trial, but was more frequent with sulfonylurea use at baseline and allocation to glargine. Nonsevere and severe events were associated with different clinical characteristics, awareness of which may guide individualized therapy. © 2015 by the American Diabetes Association. Readers may use this article

  20. TITRATION: A Randomized Study to Assess 2 Treatment Algorithms with New Insulin Glargine 300 units/mL.

    Science.gov (United States)

    Yale, Jean-François; Berard, Lori; Groleau, Mélanie; Javadi, Pasha; Stewart, John; Harris, Stewart B

    2017-10-01

    It was uncertain whether an algorithm that involves increasing insulin dosages by 1 unit/day may cause more hypoglycemia with the longer-acting insulin glargine 300 units/mL (GLA-300). The objective of this study was to compare safety and efficacy of 2 titration algorithms, INSIGHT and EDITION, for GLA-300 in people with uncontrolled type 2 diabetes mellitus, mainly in a primary care setting. This was a 12-week, open-label, randomized, multicentre pilot study. Participants were randomly assigned to 1 of 2 algorithms: they either increased their dosage by 1 unit/day (INSIGHT, n=108) or the dose was adjusted by the investigator at least once weekly, but no more often than every 3 days (EDITION, n=104). The target fasting self-monitored blood glucose was in the range of 4.4 to 5.6 mmol/L. The percentages of participants reaching the primary endpoint of fasting self-monitored blood glucose ≤5.6 mmol/L without nocturnal hypoglycemia were 19.4% (INSIGHT) and 18.3% (EDITION). At week 12, 26.9% (INSIGHT) and 28.8% (EDITION) of participants achieved a glycated hemoglobin value of ≤7%. No differences in the incidence of hypoglycemia of any category were noted between algorithms. Participants in both arms of the study were much more satisfied with their new treatment as assessed by the Diabetes Treatment Satisfaction Questionnaire. Most health-care professionals (86%) preferred the INSIGHT over the EDITION algorithm. The frequency of adverse events was similar between algorithms. A patient-driven titration algorithm of 1 unit/day with GLA-300 is effective and comparable to the previously tested EDITION algorithm and is preferred by health-care professionals. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

  1. Quality of Life of Patients with Type 1 Diabetes Mellitus Using Insulin Analog Glargine Compared with NPH Insulin: A Systematic Review and Policy Implications.

    Science.gov (United States)

    Almeida, Paulo H R F; Silva, Thales B C; de Assis Acurcio, Francisco; Guerra Júnior, Augusto A; Araújo, Vania E; Diniz, Leonardo M; Godman, Brian; Almeida, Alessandra M; Alvares, Juliana

    2018-01-10

    Insulin analog glargine (GLA) has been available as one of the therapeutic options for patients with type 1 diabetes mellitus to enhance glycemic control. Studies have shown that a decrease in the frequency of hypoglycemic episodes improves the quality of life (QoL) of diabetic patients. However, there are appreciable acquisition cost differences between different insulins. Consequently, there is a need to assess their impact on QoL to provide future guidance to health authorities. A systematic review of multiple databases including Medline, LILACS, Cochrane, and EMBASE databases with several combinations of agreed terms involving randomized controlled trials and cohorts, as well as manual searches and gray literature, was undertaken. The primary outcome measure was a change in QoL. The quality of the studies and the risk of bias was also assessed. Eight studies were eventually included in the systematic review out of 634 publications. Eight different QoL instruments were used (two generic, two mixed, and four specific), in which the Diabetes Treatment Satisfaction Questionnaire (DTSQ) was the most used. The systematic review did not consistently show any significant difference overall in QoL scores, whether as part of subsets or combined into a single score, with the use of GLA versus neutral protamine Hagedorn (NPH) insulin. Only in patient satisfaction measured by DTSQ was a better result consistently seen with GLA versus NPH insulin, but not using the Well-being Inquiry for Diabetics (WED) scale. However, none of the cohort studies scored a maximum on the Newcastle-Ottawa scale for quality, and they generally were of moderate quality with bias in the studies. There was no consistent difference in QoL or patient-reported outcomes when the findings from the eight studies were collated. In view of this, we believe the current price differential between GLA and NPH insulin in Brazil cannot be justified by these findings.

  2. Budget impact of treating commercially insured type 1 and type 2 diabetes patients in the United States with insulin degludec compared to insulin glargine.

    Science.gov (United States)

    Weatherall, James; Bloudek, Lisa; Buchs, Sarah

    2017-02-01

    To quantify the annual budget impact if all US commercially insured type 1 diabetes mellitus patients on basal-bolus therapy (T1DMBBT), type 2 diabetes mellitus patients on basal-oral therapy (T2DMBOT), and type 2 diabetes mellitus patients on basal-bolus therapy (T2DMBBT) switched from insulin glargine (IGlar) to insulin degludec (IDeg). A short-term (1 year) budget impact model was developed to evaluate the costs of IDeg vs. IGlar in three treatment groups (T1DMBBT, insulin-naïve T2DMBOT, and T2DMBBT) through a simulation for a potential US health plan population of 35 million. The analysis captured direct medical costs associated with insulin treatment (insulin, needles, and self-monitored glucose testing) and costs related to managing hypoglycemic episodes. There were a total of 59,780 T1DMBBT patients, 383,145 T2DMBOT patients, and 171,325 T2DMBBT patients expected to be using long-acting insulin. A sensitivity analysis on the entire US population was also conducted. Among T1DMBBT patients, IDeg was associated with an annual cost savings of -$357.13 per patient per year (PPPY), driven primarily by reduced insulin utilization. IDeg was also found to be cost saving among T2DMBOT patients (-$1206.61 PPPY), driven primarily by reductions in the cost of treating severe hypoglycemic episodes. Among T2DMBBT patients, IDeg was associated with an additional cost to the plan of $1420.04 PPPY; however, this result was driven by a higher insulin dose for IDeg compared to IGlar. Overall, IDeg demonstrated cost savings of $240 million per year, which accounted for total cost savings of 3.5% vs. IGlar. The results of this analysis suggest that the reduced insulin utilization and fewer hypoglycemic episodes associated with IDeg may translate into reduced costs for payers. The model is limited by simplification of a complex disease state and assumptions surrounding disease state, treatment patterns, and costs. Therefore, results may not accurately reflect actual health plans

  3. Switching to multiple daily injection therapy with glulisine improves glycaemic control, vascular damage and treatment satisfaction in basal insulin glargine-injected diabetic patients.

    Science.gov (United States)

    Yanagisawa, Katsuyuki; Ashihara, Junya; Obara, Shinji; Wada, Norio; Takeuchi, Masayoshi; Nishino, Yuri; Maeda, Sayaka; Ishibashi, Yuji; Yamagishi, Sho-ichi

    2014-11-01

    Basal and bolus insulin therapy is required for strict blood control in diabetic patients, which could lead to prevention of vascular complications in diabetes. However, the optimal combination regimen is not well established. Fifty-nine diabetic patients (49 type 1 and 10 type 2; 52.9 ± 13.3 years old) whose blood glucose levels were uncontrolled (HbA1c  > 6.2%) by combination treatment of basal insulin glargine with multiple daily pre-meal injections of bolus short-acting insulin [aspart (n = 19), lispro (n = 37) and regular human insulin (n = 3)] for at least 8 weeks were enrolled in this study. We examined whether glycaemic control and vascular injury were improved by replacement of short-acting insulin with glulisine. Patient satisfaction was assessed with Diabetes Treatment Satisfaction Questionnaire. Although bolus and basal insulin doses were almost unchanged before and after replacement therapy, switching to glulisine insulin for 24 weeks significantly decreased level of HbA1c , advanced glycation end products (AGEs), soluble receptor for AGEs (sRAGE), monocyte chemoattractant protein-1 (MCP-1) and urinary albumin excretion. In multiple stepwise regression analysis, change in MCP-1 values from baseline (ΔMCP-1) was a sole determinant of log urinary albumin excretion. ΔAGEs and ΔsRAGE were independently correlated with each other. The relationship between ΔMCP-1 and ΔsRAGE was marginally significant (p = 0.05). Replacement of short-acting insulin by glulisine significantly increased Diabetes Treatment Satisfaction Questionnaire scores. Our present study suggests that combination therapy of glargine with multiple daily pre-meal injections of glulisine might show superior efficacy in controlling blood glucose, preventing vascular damage and improving treatment satisfaction in diabetic patients. Copyright © 2014 John Wiley & Sons, Ltd.

  4. Safety and efficacy of a basal-plus regimen with insulin glargine and insulin glulisine for elderly patients with high cardiovascular risk and type 2 diabetes mellitus.

    Science.gov (United States)

    Gómez-Huelgas, R; Sabán-Ruiz, J; García-Román, F J; Quintela-Fernández, N; Seguí-Ripoll, J M; Bonilla-Hernández, M V; Romero-Meliá, G

    2017-05-01

    To assess the safety and efficacy of a basal-plus (BP) regimen with insulin glargine (as basal insulin) and insulin glulisine (as prandial insulin) with the main meal for elderly patients with type 2 diabetes mellitus (DM2) and high cardiovascular risk, following standard clinical practice. An observational, retrospective study was conducted in 21 centres of internal medicine in Spain. The study included patients aged 65 years or older with DM2, undergoing treatment with a BP regimen for 4 to 12 months before inclusion in the study and a diagnosis of cardiovascular disease or high cardiovascular risk. The primary endpoint was the change in glycated haemoglobin (HbA1c) from the introduction of the glulisine to inclusion in the study. The study included 198 patients (mean age, 74±6.4 years; males, 52%). After at least 4 months of treatment with the BP regimen, started with the addition of glulisine, the mean HbA1c value decreased significantly (9±1.5% vs. 7.7±1.1%; P<.001), and almost 24% of the patients reached HbA1c levels of 7.5-8%. Furthermore, blood glucose levels under fasting conditions decreased significantly (190.6±73.2mg/dl vs. 138.9±38.2mg/dl; P<.001). A total of 35 patients (17.7%) had some hypoglycaemia during the month prior to the start of the study, and 2 cases (1.01%) of severe hypoglycaemia were detected. The BP strategy could significantly improve blood glucose control in patients 65 years of age or older with DM2 and high cardiovascular risk and is associated with a low risk of severe hypoglycaemia. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  5. Glycaemic control and hypoglycaemia in people with type 2 diabetes switching from twice-daily basal insulin to once-daily insulin glargine 300 U/mL or insulin glargine 100 U/mL (EDITION 1 and EDITION 2 subgroup analysis).

    Science.gov (United States)

    Roussel, Ronan; d'Emden, Michael C; Fisher, Miles; Ampudia-Blasco, F Javier; Stella, Peter; Bizet, Florence; Cali, Anna M G; Wysham, Carol H

    2017-07-24

    In this post hoc analysis we compared glycaemic control and hypoglycaemia between insulin glargine 300 U/mL (Gla-300) and glargine 100 U/mL (Gla-100) administered once daily in people with type 2 diabetes (T2DM) from the EDITION 1 (basal plus mealtime insulin) and EDITION 2 (basal insulin plus oral antihyperglycaemic drugs) trials who were previously receiving twice-daily insulin. At randomization, 16.9% and 20.0% of people in EDITION 1 and 2, respectively, were receiving twice-daily basal insulin. Glycated haemoglobin change from baseline to Month 6 was similar over 6 months with Gla-300 or Gla-100 (least squares mean difference -0.01%; 95% confidence interval [CI] -0.27 to 0.24] in EDITION 1 and 0.16%; 95% CI -0.25 to 0.57, in EDITION 2). Participants previously receiving twice-daily insulin in EDITION 1 had a lower risk of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia with Gla-300 vs Gla-100 at night (00:00-05:59 hours), but not at any time (24 hours); in EDITION 2 the risk was reduced at night and any time (24 hours). In conclusion, Gla-300 provided similar glycaemic control with less hypoglycaemia compared with Gla-100 in people with T2DM switching from twice-daily to once-daily basal insulin. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  6. Glycaemic control and hypoglycaemia during 12 months of randomized treatment with insulin glargine 300 U/mL versus glargine 100 U/mL in people with type 1 diabetes (EDITION 4).

    Science.gov (United States)

    Home, Philip D; Bergenstal, Richard M; Bolli, Geremia B; Ziemen, Monika; Rojeski, Maria; Espinasse, Melanie; Riddle, Matthew C

    2017-06-29

    Insulin glargine 300 U/mL (Gla-300) offers a flatter pharmacodynamic profile than insulin glargine 100 U/mL (Gla-100). We have compared these insulins over 1 year in people with type 1 diabetes (T1DM). EDITION 4 was a 6-month, multicentre, randomized, open-label phase 3 study. People with T1DM who completed the 6 months continued randomized Gla-300 or Gla-100 once daily, morning or evening, for a further 6 months. Among 549 participants randomized, 444 completed the 12-month study period (Gla-300, 80%; Gla-100, 82%). Mean HbA1c decreased similarly from baseline to month 12 in the 2 treatment groups (difference, 0.02 [95% CI, -0.13 to 0.17]) %-units [0.2 (-1.5 to 1.9) mmol/mol]), to a mean of 7.86 %-units (62.4 mmol/mol) in both groups. For morning vs evening injection, there was no difference in HbA1c change over 12 months for Gla-100, but a significantly larger decrease in HbA1c was observed in the Gla-300 morning group than in the Gla-300 evening group (difference, -0.25 [-0.47 to -0.04] %-units [-2.7 (-5.2 to -0.4) mmol/mol]). Mean glucose from the 8-point SMPG profiles decreased from baseline, and was similar between the 2 treatment groups. Basal insulin dose was 20% higher with Gla-300 than with Gla-100, while hypoglycaemia event rates, analysed at night, over 24 hours, or according to different glycaemic thresholds, did not differ between treatment groups, regardless of injection time. Adverse event profiles did not differ between groups. In T1DM, Gla-300 provides glucose control comparable to that of Gla-100, and can be given at any time of day. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  7. Use of a temporary "solubilizing" peptide tag for the Fmoc solid-phase synthesis of human insulin glargine via use of regioselective disulfide bond formation.

    Science.gov (United States)

    Hossain, Mohammed Akhter; Belgi, Alessia; Lin, Feng; Zhang, Suode; Shabanpoor, Fazel; Chan, Linda; Belyea, Chris; Truong, Hue-Trung; Blair, Amy R; Andrikopoulos, Sof; Tregear, Geoffrey W; Wade, John D

    2009-07-01

    Solid-phase peptide synthesis has been refined to a stage where efficient preparation of long and complex peptides is now achievable. However, the postsynthesis handling of poorly soluble peptides often remains a significant hindrance to their purification and further use. Several synthetic schemes have been developed for the preparation of such peptides containing modifications to aid their solubility. However, these require the use of complex chemistry or yield non-native sequences. We describe a simple approach based on the use of penta-lysine "tags" that are linked to the C-terminus of the peptide of interest via a base-labile linker. After ready purification of the now freely solubilized peptide, the "tag" is removed by simple, brief base treatment giving the native sequence in much higher overall yield. The applicability of the method was demonstrated by the novel preparation of insulin glargine via solid-phase synthesis of each of the two chains--including the notoriously poorly soluble A-chain--followed by their combination in solution via regioselective disulfide bond formation. At the conclusion of the chain combination, the solubilizing peptide tag was removed from the A-chain to provide synthetic human glargine in nearly 10% overall yield. This approach should facilitate the development of new insulin analogues as well as be widely applicable to the improved purification and acquisition of otherwise poorly soluble synthetic peptides.

  8. A Review of the Clinical Efficacy and Safety of Insulin Degludec and Glargine 300 U/mL in the Treatment of Diabetes Mellitus.

    Science.gov (United States)

    Woo, Vincent C

    2017-08-01

    The treatment of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) using insulin is not ideal at this time. Despite advances made with basal insulin analogues, many individuals achieve less than optimal glycemic control or are at risk for hypoglycemia. Currently available basal insulin analogues do not deliver steady, peakless, continuous insulin for >24 hours and are associated with adverse events, including hypoglycemia. The objective of this paper was to review the clinical efficacy and safety of upcoming long-acting insulin analogues such as insulin degludec and insulin glargine 300 U/mL (Gla-300). A comprehensive literature search of PubMed and Google Scholar was conducted from 1966 to 2015. The search included randomized controlled trials that specifically assessed the efficacy and safety of insulin degludec and Gla-300 in patients with T1DM and T2DM. The efficacy of insulin degludec and Gla-300 in achieving glycemic control has been reported in clinical trials in adults with T1DM and T2DM. Not only did a large number of patients succeed in meeting glycosylated hemoglobin targets, but they also experienced reductions in hypoglycemic events. These 2 therapies are associated with a reduced risk of nocturnal hypoglycemia and are generally well tolerated. The long-acting insulin analogues insulin degludec and Gla-300 are promising therapies in the treatment of T1DM and T2DM. Their improved insulin delivery for >24 hours offers glycemic control with a good safety profile. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  9. Cost-effectiveness analysis of exenatide twice daily (BID) vs insulin glargine once daily (QD) as add-on therapy in Chinese patients with Type 2 diabetes mellitus inadequately controlled by oral therapies.

    Science.gov (United States)

    Deng, Jing; Gu, Shuyan; Shao, Hui; Dong, Hengjin; Zou, Dajin; Shi, Lizheng

    2015-01-01

    To estimate cost-effectiveness of exenatide twice daily (BID) vs insulin glargine once daily (QD) as add-on therapy in Chinese type 2 diabetes patients not well controlled by oral anti-diabetic (OAD) agents. The Cardiff model was populated with data synthesized from three head-to-head randomized clinical trials of up to 30 weeks in China comparing exenatide BID vs insulin glargine as add-on therapies to oral therapies in the Chinese population. The Cardiff model generated outputs including macrovascular and microvascular complications, diabetes-specific mortality, costs, and quality-adjusted life years (QALYs). Cost and QALYs were estimated with a time horizon of 40 years at a discount rate of 3% from a societal perspective. Compared with insulin glargine plus OAD treatments, patients on exenatide BID plus OAD gained 1.88 QALYs, at an incremental cost saving of Chinese Renminbi (RMB) 114,593 (i.e., cost saving of RMB 61078/QALY). The cost-effectiveness results were robust to various sensitivity analyses including probabilistic sensitivity analysis. The variables with the most impact on incremental cost-effectiveness ratio included HbA1c level at baseline, health utilities decrement, and BMI at baseline. Compared with insulin glargine QD, exenatide BID as add-on therapy to OAD is a cost-effective treatment in Chinese patients inadequately controlled by OAD treatments.

  10. Incidence and predictors of hypoglycemia in Japanese patients with type 2 diabetes treated by insulin glargine and oral antidiabetic drugs in real-life: ALOHA post-marketing surveillance study sub-analysis.

    Science.gov (United States)

    Odawara, Masato; Kadowaki, Takashi; Naito, Yusuke

    2014-02-15

    Add-on Lantus® to Oral Hypoglycemic Agents (ALOHA), an observational, non-interventional, 24-week post-marketing surveillance study in Japanese patients with type 2 diabetes (T2DM) having uncontrolled glycemic control, demonstrated that basal supported oral therapy (BOT) with insulin glargine was an effective and safe treatment in real-life clinical practice. We performed subgroup analysis to identify incidence and predictors associated with risk of hypoglycemia. Among 4219 patients with T2DM, 3732 patients were insulin-naïve and 487 patients were insulin non-naïve who switched from other insulin to insulin glargine. All hypoglycemic episodes were counted by physicians' documentation based on patients' reports. Relationships between baseline patient characteristics and glargine-related hypoglycemic episodes were examined by univariate and multivariate analysis. Among 4219 patients, 44 (1.0%) patients experienced hypoglycemic episodes (41 insulin-naïve patients; 3 insulin non-naïve patients), with a rate of incidence 0.035 episodes/patient-years. Majority of patients with hypoglycemia (37 of 44) had just one hypoglycemic episode during study period. Among insulin-naïve patients, incidence of hypoglycemia differed significantly depending on age, diabetic complications, estimated glomerular filtration rate (eGFR), and postprandial plasma glucose (P <0.05). In a multivariate adjusted model, poor renal function (eGFR <60 mL/min/1.73 m2) was a statistically significant risk factor (P < 0.05). Our results suggest that BOT using insulin glargine is an option of insulin therapy with 1% risk of hypoglycemia in patients with T2DM with inadequate glycemic control. Patients with low renal function might need a careful follow-up.

  11. Impact of patient and treatment characteristics on glycemic control and hypoglycemia in patients with type 2 diabetes initiated to insulin glargine or NPH: A post hoc, pooled, patient-level analysis of 6 randomized controlled trials.

    Science.gov (United States)

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

    2017-02-01

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

  12. Better glycaemic control and less hypoglycaemia with insulin glargine 300 U/mL vs glargine 100 U/mL: 1-year patient-level meta-analysis of the EDITION clinical studies in people with type 2 diabetes.

    Science.gov (United States)

    Ritzel, Robert; Roussel, Ronan; Giaccari, Andrea; Vora, Jiten; Brulle-Wohlhueter, Claire; Yki-Järvinen, Hannele

    2017-09-01

    To investigate the efficacy and safety of insulin glargine 300 U/mL (Gla-300) vs insulin glargine 100 U/mL (Gla-100) over 12 months in a patient-level meta-analysis, using data from the EDITION studies in people with type 2 diabetes (T2DM). EDITION 1, 2 and 3 were multicentre, randomized, open-label, 2-arm, parallel-group, treat-to-target phase IIIa studies. Similar study designs and endpoints enabled a meta-analysis to be conducted. Reductions in glycated haemoglobin (HbA1c) were better sustained over 12 months with Gla-300 than with Gla-100 (least squares [LS] mean difference in change from baseline: -0.10 % [95% confidence interval {CI} -0.18 to -0.02] or -1.09 mmol/mol [95% CI -2.01 to -0.20]; P = .0174). Risk of confirmed (≤3.9 mmol/L) or severe hypoglycaemia was 15% lower with Gla-300 vs Gla-100 at night (relative risk 0.85 [95% CI 0.77-0.92]) and 6% lower at any time of day (relative risk 0.94 [95% CI 0.90-0.98]). Rates of hypoglycaemia were 18% lower with Gla-300 vs Gla-100 at night (rate ratio 0.82 [95% CI 0.67-0.99]), but comparable at any time of day. HbA1c 300 than with Gla-100 (relative risk 1.24 [95% CI 1.03-1.50]). Severe hypoglycaemia was rare; in both treatment groups the incidence of events at any time of day was ≤3.6%, while rates were ≤0.08 events per participant-year. In a broad population of people with T2DM over 12 months, use of Gla-300 provided more sustained glycaemic control and significantly lower hypoglycaemia risk at night and at any time of day compared with Gla-100. © 2017 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  13. Dosing of insulin glargine to achieve the treatment target in Japanese type 2 diabetes on a basal supported oral therapy regimen in real life: ALOHA study subanalysis.

    Science.gov (United States)

    Odawara, Masato; Ohtani, Tetsuya; Kadowaki, Takashi

    2012-07-01

    AIM/INTRODUCTION: Subsample analysis was performed to examine whether dose optimization of insulin glargine (Lantus(®); Sanofi-Aventis K.K., Tokyo, Japan) contributed to achieving a target glycosylated hemoglobin (HbA1c) (ALOHA) study, a 24-week observational study of Japanese type 2 diabetes patients. We investigated the conditions of optimal dose titration by identifying patient background of dose-achiever and non-achiever subgroups. The insulin-naive patients (n=3,180) were categorized into four groups depending on their HbA1c and insulin glargine dose at 24 weeks: patients with HbA1c <7.0% and dose <8.5 U/day (Group 1), HbA1c <7.0% and dose ≥8.5 U/day (Group 2), HbA1c ≥7.0% and dose <8.5 U/day (Group 3), and HbA1c ≥7.0% and dose ≥8.5 U/day (Group 4). The greatest reduction in HbA1c was observed in Group 2 (-2.7%, P<0.001 vs. Group 3 or 4). Fasting plasma glucose (FPG) in Group 2 at 24 weeks (113.3 mg/dL) was significantly lower than in either Group 3 or 4 (135.4 mg/dL and 150.0 mg/dL, respectively; P<0.001 for both). The starting dose and the change of insulin glargine dose were significantly greater in Group 2 than in Group 3 (0.142 vs. 0.086 U/kg/day [P<0.001] and +5.0 vs. +1.1 U/day [P<0.001], respectively), whereas the baseline HbA1c levels and body mass index were comparable (9.3% vs. 9.4% and 23.5 kg/m(2) vs. 23.3 kg/m(2), respectively). Our results suggest that appropriate starting dosage and subsequent dose adjustment are essential to achieve target HbA1c (<7%) and that the FPG level should be decreased to be 110 mg/dL or below for this achievement.

  14. Efficacy and Safety of Once-Daily Insulin Degludec/Insulin Aspart versus Insulin Glargine (U100 for 52 Weeks in Insulin-Naïve Patients with Type 2 Diabetes: A Randomized Controlled Trial.

    Directory of Open Access Journals (Sweden)

    Ajay Kumar

    Full Text Available The efficacy and safety of insulin degludec/insulin aspart (IDegAsp once daily (OD compared with insulin glargine U100 (IGlar OD over 52 weeks in insulin-naïve adults with type 2 diabetes mellitus (T2DM was investigated.In this open-label, parallel-group treat-to-target trial, participants were randomized (1:1 to receive IDegAsp OD (breakfast, n = 266 or IGlar OD (as per label, n = 264. Participants then entered a 26-week extension phase (IDegAsp OD, n = 192; IGlar OD, n = 221. The primary endpoint was change from baseline to Week 26 in HbA1c.After 26 and 52 weeks, mean HbA1c decreased to similar levels in both groups. After 52 weeks, the mean estimated treatment difference was -0.08% (-0.26, 0.09 95%CI, confirming the non-inferiority of IDegAsp OD versus IGlar OD evaluated at Week 26. After 52 weeks, there was a similar reduction in mean fasting plasma glucose in both treatment groups. The rate of confirmed hypoglycemic episodes was 86% higher (p < 0.0001 whereas the rate of nocturnal hypoglycemia was 75% lower (p < 0.0001 for IDegAsp versus IGlar.Nocturnal-confirmed hypoglycemia was higher with IGlar whereas overall and diurnal hypoglycemia were higher with IDegAsp dosed at breakfast. These results highlight the importance of administration of IDegAsp with the main meal of the day, tailored to the individual patient's needs.ClinicalTrials.gov: NCT01045707 [core] and NCT01169766 [ext].

  15. Initiation of insulin glargine in patients with Type 2 diabetes in suboptimal glycaemic control positively impacts health-related quality of life. A prospective cohort study in primary care

    DEFF Research Database (Denmark)

    Hajós, Tibor R S; Pouwer, F; de Grooth, R

    2011-01-01

    AIMS: To study prospectively the impact of initiating insulin glargine in suboptimally controlled insulin-naïve patients with Type 2 diabetes on health-related quality of life in relation to glycaemic control. METHODS: Insulin-naïve Dutch patients with Type 2 diabetes in suboptimal glycaemic...... completed self-report health-related quality of life measures, including emotional well-being (World Health Organization-5 well-being index), fear of hypoglycaemia (Hypoglycaemia Fear Survey) and diabetes symptom distress (Diabetes Symptom Checklist-revised). Data were analysed using generalized estimating...... of this observational study demonstrate combined glycaemic and health-related quality of life benefits of initiating insulin glargine in patients with Type 2 diabetes in routine primary care....

  16. Achieve control: a pragmatic clinical trial of insulin glargine 300 U/mL versus other basal insulins in insulin-naïve patients with type 2 diabetes.

    Science.gov (United States)

    Oster, Gerry; Sullivan, Sean D; Dalal, Mehul R; Kazemi, Mahmood R; Rojeski, Maria; Wysham, Carol H; Sung, Jennifer; Johnstone, Bryan; Cali, Anna M G; Wei, L J; Traylor, Louise; Anhalt, Henry; Hull, Michelle; Van Vleet, John; Meneghini, Luigi F

    2016-11-01

    This study aims to compare the effectiveness of insulin glargine 300 U/mL (Gla-300) with its accompanying patient support program with that of other basal insulin and available patient support programs in patients with type 2 diabetes (T2D) in a real-world setting in terms of achieving HEDIS (Healthcare Effectiveness Data and Information Set) individualized glycemic targets without documented symptomatic hypoglycemia. Achieve Control is a US-based, multicenter, randomized, open-label, active-controlled, parallel group pragmatic Phase IV trial in insulin-naïve patients with T2D uncontrolled on ≥2 oral antidiabetes drugs (OAD) and/or glucagon-like peptide-1 receptor antagonists (GLP-1 RA). Inclusion criteria include a diagnosis of T2D, age ≥18 years, and glycated hemoglobin (HbA1c) between 8.0% and 11.0%. Patients will be assigned to either the Gla-300 or other basal insulin group. The primary end point is the proportion of patients achieving HEDIS HbA1c targets (300 versus other basal insulins in terms of patient outcomes, experiences, and perceptions, and its impact on healthcare resource utilization and cost. www.clinicaltrials.gov identifier is NCT02451137.

  17. iGlarLixi: A Fixed-Ratio Combination of Insulin Glargine 100 U/mL and Lixisenatide for the Treatment of Type 2 Diabetes.

    Science.gov (United States)

    Goldman, Jennifer; Trujillo, Jennifer M

    2017-11-01

    To review the safety and efficacy of iGlarLixi, a titratable fixed-ratio combination of insulin glargine 100 U/mL (iGlar) and lixisenatide, a glucagon-like peptide-1 receptor agonist. A literature search of MEDLINE for all English-language primary articles through June 2016, using the terms LixiLan, iGlarLixi and insulin glargine and lixisenatide, and a search of abstracts presented at the 2016 Scientific Sessions of the American Diabetes Association were performed. All studies assessing the efficacy and/or safety of iGlarLixi were evaluated. iGlarLixi has been approved in the United States for glycemic control in people with type 2 diabetes (T2D) inadequately controlled with basal insulin (<60 U/d) or lixisenatide. In clinical trials, iGlarLixi was associated with significantly greater reductions from baseline in glycated hemoglobin A 1C (A1C) than iGlar or lixisenatide alone. Reductions in postprandial glucose were also greater with iGlarLixi than with iGlar or lixisenatide. iGlarLixi was weight neutral compared with the weight gain with iGlar and loss with lixisenatide alone, and there was no increase in hypoglycemia with iGlarLixi compared with iGlar despite the greater A1C reduction. Gastrointestinal events, frequently associated with lixisenatide, were less common with iGlarLixi. Potential drawbacks of iGlarLixi include reduced flexibility in dosing and the absence of long-term efficacy and safety data. iGlarLixi is a titratable fixed-ratio combination that shows improved efficacy and comparable or improved safety outcomes relative to its separate constituents, offering an alternative approach to intensification of therapy in T2D.

  18. Optimizing Glycemic Control Through Titration of Insulin Glargine 100 U/mL: A Review of Current and Future Approaches with a Focus on Asian Populations.

    Science.gov (United States)

    Deerochanawong, Chaicharn; Bajpai, Shailendra; Dwipayana, I Made Pande; Hussein, Zanariah; Mabunay, Maria Aileen; Rosales, Reynaldo; Tsai, Shih-Tzer; Tsang, Man Wo

    2017-12-01

    Various data have demonstrated inadequate glycemic control amongst Asians with type 2 diabetes mellitus (T2DM), possibly on account of suboptimal titration of basal insulin-an issue which needs to be further examined. Here we review the available global and Asia-specific data on titration of basal insulin, with a focus on the use of insulin glargine 100 U/mL (Gla-100). We also discuss clinical evidence on the efficacy and safety of titrating Gla-100, different approaches to titration, including some of the latest technological advancements, and guidance on the titration of basal insulin from international and local Asian guidelines. The authors also provide their recommendations for the initiation and titration of basal insulin for Asian populations. Discussion of the data included in this review and in relation to the authors' clinical experience with treating T2DM in Asian patients is also included. Briefly, clinical studies demonstrate the achievement of adequate glycemic control in adults with T2DM through titration of Gla-100. However, studies investigating approaches to titration, specifically in Asian populations, are lacking and need to be conducted. Given that the management of insulin therapy is a multidisciplinary team effort involving endocrinologists, primary care physicians, nurse educators, and patients, greater resources and education targeted at these groups are needed regarding the optimal titration of basal insulin. Technological advancements in the form of mobile or web-based applications for automated dose adjustment can aid different stakeholders in optimizing the dose of basal insulin, enabling a larger number of patients in Asia to reach their target glycemic goals with improved outcomes.

  19. The cost-effectiveness of exenatide twice daily (BID) vs insulin lispro three times daily (TID) as add-on therapy to titrated insulin glargine in patients with type 2 diabetes.

    Science.gov (United States)

    Gordon, J; McEwan, P; Sabale, U; Kartman, B; Wolffenbuttel, B H R

    2016-12-01

    To evaluate the cost-effectiveness of exenatide twice daily (BID) vs bolus insulin lispro three times daily (TID) as add-on therapy when glycemic control is sub-optimal with titrated basal insulin glargine and metformin. The analysis was based on the recent 4B Study, which compared exenatide BID and lispro TID as add-on therapies in subjects with type 2 diabetes insufficiently controlled, despite titrated insulin glargine. The Cardiff Diabetes Model was used to simulate patient costs and health benefits beyond the 4B Study. The Swedish healthcare perspective was adopted for this analysis; costs are reported in €EUR to aid interpretation. The main outcome measure was the cost per quality-adjusted life-year (QALY) gained with exenatide BID compared to lispro TID. Exenatide BID was associated with an incremental cost of €1,270 and a QALY increase of +0.64 compared with lispro TID over 40 years. The cost per QALY gained with exenatide BID compared with lispro TID was €1,971, which is within conventional limits of cost-effectiveness. Cost-effectiveness results were generally robust to alternative assumptions and values for key model parameters. Extrapolation of trial data over the longer term can be influenced by modeling and parameter uncertainty. Cost-effectiveness results were generally insensitive to alternative values of key model input parameters and across scenarios. The addition of exenatide BID rather than insulin lispro to basal insulin is associated with similar or better clinical outcomes. Illustrated from the Swedish healthcare perspective, analysis with the Cardiff Diabetes Model demonstrated that exenatide BID represents a cost-effective treatment alternative to lispro TID as add-on therapy in type 2 diabetes patients insufficiently controlled on basal insulin.

  20. Glycaemic control and hypoglycaemia with insulin glargine 300 U/mL compared with glargine 100 U/mL in Japanese adults with type 2 diabetes using basal insulin plus oral anti-hyperglycaemic drugs (EDITION JP 2 randomised 12-month trial including 6-month extension).

    Science.gov (United States)

    Terauchi, Y; Koyama, M; Cheng, X; Sumi, M; Riddle, M C; Bolli, G B; Hirose, T

    2017-04-19

    To compare insulin glargine 300 U/mL (Gla-300) with glargine 100 U/mL (Gla-100) in Japanese adults with uncontrolled type 2 diabetes on basal insulin and oral anti-hyperglycaemic drugs over 12 months. EDITION JP 2 was a randomised, open-label, phase 3 study. Following a 6-month treatment period, participants continued receiving previously assigned once daily Gla-300 or Gla-100, plus oral anti-hyperglycaemic drugs, in a 6-month extension period. Glycaemic control, hypoglycaemia and adverse events were assessed. The 12-month completion rate was 88% for Gla-300 and 96% for Gla-100, with comparable reasons for discontinuation. Mean HbA1c decrease from baseline to month 12 was 0.3% in both groups. Annualised rates of confirmed (≤3.9mmol/L [≤70mg/dL]) or severe hypoglycaemia were lower with Gla-300 than Gla-100 (nocturnal [00:00-05:59h]: rate ratio 0.41; 95% confidence interval: 0.18 to 0.92; anytime [24h]: rate ratio 0.64; 95% confidence interval: 0.44 to 0.94). Cumulative number of hypoglycaemic events was lower with Gla-300 than Gla-100. Adverse event profiles were comparable between treatments. Over 12 months, Gla-300-treated participants achieved sustained glycaemic control and experienced less hypoglycaemia, particularly at night, versus Gla-100, supporting 6-month results. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  1. Replacing Insulin Glargine with Neutral Protamine Hagedorn (NPH) Insulin in a Subpopulation of Study Subjects in the Action to Control Cardiovascular Risk in Diabetes (ACCORD): Effects on Blood Glucose Levels, Hypoglycemia and Patient Satisfaction.

    Science.gov (United States)

    Berard, Lori; Cameron, Brett; Woo, Vincent; Stewart, John

    2015-08-01

    To ensure patient safety when replacing insulin glargine (IG) with neutral protamine Hagedorn (NPH) insulin and to determine differences in blood glucose control, frequency of hypoglycemia, insulin dosing, health resource utilization and quality of life between users of IG and NPH insulin. A single-site, open-label, randomized, 6-month comparative study of 66 patients from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Randomization was 1:1 to receive IG or NPH insulin. Data regarding blood glucose control, insulin dosage adjustment and recording of hypoglycemia episodes were obtained through telephone calls; office visits were conducted to measure weight, glycated hemoglobin, fasting plasma glucose and blood glucose profile. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was used to measure patients' satisfaction with their diabetes treatment. Rates of symptomatic hypoglycemia did not differ significantly between groups: 37.5±2.2 for the IG group and 31.1±2.1 for the NPH group. However, patients treated with NPH insulin had higher frequencies of severe hypoglycemia (6.1±0.9) compared with 2.7±0.6 for the IG group. A significant difference in changes in glycated hemoglobin (A1C) was observed between the groups: the mean ± standard error A1C decreases from baseline were -0.34%±0.11 for the IG group, vs -0.01%±0.10 for the NPH insulin group. The data obtained from the DTSQ showed greater treatment satisfaction in the IG group compared with the NPH insulin group. Switching from IG to NPH insulin resulted in more than double the rate of severe hypoglycemias and led to decreased metabolic control. Greater treatment satisfaction was observed with IG, compared with NPH insulin, as measured by change from baseline in the DTSQ scores. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  2. Patient-led versus physician-led titration of insulin glargine in patients with uncontrolled type 2 diabetes: a randomized multinational ATLAS study.

    Science.gov (United States)

    Garg, Satish K; Admane, Karim; Freemantle, Nick; Odawara, Masato; Pan, Chang-Yu; Misra, Anoop; Jarek-Martynowa, Iwona R; Abbas-Raza, Syed; Mirasol, Roberto C; Perfetti, Riccardo

    2015-02-01

    Self-adjustment of insulin dose is commonly practiced in Western patients with type 2 diabetes but is usually not performed in Asian patients. This multinational, 24-week, randomized study compared patient-led with physician-led titration of once-daily insulin glargine in Asian patients with uncontrolled type 2 diabetes who were on 2 oral glucose-lowering agents. Patient-led (n = 275) or physician-led (n = 277) subjects followed the same dose-titration algorithm guided by self-monitored fasting blood glucose (FBG; target, 110 mg/dL [6.1 mmol/L]). The primary endpoint was change in mean glycated hemoglobin (HbA1c) at week 24 in the patient-led versus physician-led titration groups. Patient-led titration resulted in a significantly higher drop in HbA1c value at 24 weeks when compared with physician-led titration (-1.40% vs. -1.25%; mean difference, -0.15; 95% confidence interval, -0.29 to 0.00; P = .043). Mean decrease in FBG was greatest in the patient-led group (-2.85 mmol/L vs. -2.48 mmol/L; P = .001). The improvements in HbA1c and FBG were consistent across countries, with similar improvements in treatment satisfaction in both groups. Mean daily insulin dose was higher in the patient-led group (28.9 units vs. 22.2 units; Ptitration achieved near-target blood glucose levels in Asian patients with uncontrolled type 2 diabetes who were on 2 oral glucose-lowering drugs, demonstrating that Asian patients can self-uptitrate insulin dose effectively when guided.

  3. Efficacy and safety of weight-based insulin glargine dose titration regimen compared with glucose level- and current dose-based regimens in hospitalized patients with type 2 diabetes: a randomized, controlled study.

    Science.gov (United States)

    Li, Xiaowei; Du, Tao; Li, Wangen; Zhang, Tong; Liu, Haiyan; Xiong, Yifeng

    2014-09-01

    Insulin glargine is widely used as basal insulin. However, published dose titration regimens for insulin glargine are complex. This study aimed to compare the efficacy and safety profile of a user-friendly, weight-based insulin glargine dose titration regimen with 2 published regimens. A total of 160 hospitalized patients with hyperglycemia in 3 medical centers were screened. Our inclusion criteria included age 18 to 80 years and being conscious. Exclusion criteria included pregnancy or breast-feeding and hepatic or renal dysfunction. A total of 149 patients were randomly assigned to receive weight-based, glucose level-based, or dose-based insulin glargine dose titration regimen between January 2011 and February 2013. The initial dose of insulin glargine was 0.2 U/kg. In the weight-based regimen (n = 49), the dose was titrated by increments of 0.1 U/kg daily. In the glucose level-based regimen (n = 51), the dose was titrated by 2, 4, 6, or 8 U daily when fasting blood glucose (FBG) was, respectively, between 7.0 and 7.9, 8.0 and 8.9, 9.0 and 9.9, or ≥10 mmol/L. In the current dose-based regimen (n = 49), titration was by daily increments of 20% of the current dose. The target FBG in all groups was ≤7.0 mmol/L. The incidence of hypoglycemia was recorded. One-way ANOVA and χ(2) test were used to compare data between the 3 groups. All but 1 patient who required additional oral antidiabetic medication completed the study. The mean (SD) time to achieve target FBG was 3.2 (1.2) days with the weight-based regimen and 3.7 (1.5) days with the glucose level-based regimen (P = 0.266). These times were both shorter than that achieved with the current dose-based regimen (4.8 [2.8] days; P = 0.0001 and P = 0.005, respectively). The daily doses of insulin glargine at the study end point were 0.43 (0.13) U/kg with the weight-based regimen, 0.50 (0.20) U/kg with the glucose level-based regimen, and 0.47 (0.23) U/kg with the current dose-based regimen (P = 0.184). The incidence

  4. Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial.

    Science.gov (United States)

    Aroda, Vanita R; Bain, Stephen C; Cariou, Bertrand; Piletič, Milivoj; Rose, Ludger; Axelsen, Mads; Rowe, Everton; DeVries, J Hans

    2017-05-01

    Several pharmacological treatment options are available for type 2 diabetes; however, many patients do not achieve optimum glycaemic control and therefore new therapies are necessary. We assessed the efficacy and safety of semaglutide, a glucagon-like peptide-1 (GLP-1) analogue in clinical development, compared with insulin glargine in patients with type 2 diabetes who were inadequately controlled with metformin (with or without sulfonylureas). We did a randomised, open-label, non-inferiority, parallel-group, multicentre, multinational, phase 3a trial (SUSTAIN 4) at 196 sites in 14 countries. Eligible participants were insulin-naive patients with type 2 diabetes, aged 18 years and older, who had insufficient glycaemic control with metformin either alone or in combination with a sulfonylurea. We randomly assigned participants (1:1:1) to either subcutaneous once-weekly 0·5 mg or 1·0 mg semaglutide (doses reached after following a fixed dose-escalation regimen) or once-daily insulin glargine (starting dose 10 IU per day, then titrated weekly to a pre-breakfast self-measured plasma glucose target of 4·0-5·5 mmol/L [72-99 mg/dL]) for 30 weeks. In all treatment groups, previous background metformin and sulfonylurea treatment was continued throughout the trial. We did the randomisation using an interactive voice or web response system. The primary endpoint was change in mean HbA1c from baseline to week 30 and the confirmatory secondary endpoint was the change in mean bodyweight from baseline to week 30. We assessed efficacy and safety in the modified intention-to-treat population (mITT; all randomly assigned participants who were exposed to at least one dose of study drug) and used a margin of 0·3% to establish non-inferiority in HbA1c reduction. This trial is registered with ClinicalTrials.gov, number NCT02128932. Between Aug 4, 2014, and Sept 3, 2015, we randomly assigned 1089 participants to treatment; the mITT population consisted of 362 participants assigned to

  5. Glucagon-like peptide 1 receptor agonist therapy is more efficacious than insulin glargine for poorly controlled type 2 diabetes: A systematic review and meta-analysis.

    Science.gov (United States)

    Liu, Fu-peng; Dong, Jian-jun; Yang, Qing; Xue, Xian-zhong; Ren, Zhong-fa; Gan, Yi-zhang; Liao, Lin

    2015-05-01

    The aim of the present study was to compare the reported efficacy and safety of glucagon-like peptide-l receptor agonist (GLP-1RA) and insulin glargine (IGlar) for poorly controlled type 2 diabetes. Medline, EMBASE, Cochrane Library, and clinicaltrials.gov were carried out. References and cited papers of relevant articles were also checked. Seven trials met the inclusion criteria. GLP-1RA showed equivalent or superior efficacy to IGlar for reducing hemoglobin A1c (HbA1c), with a greater proportion of patients achieving HbAlc<7%. GLP-1RA also favored decreased body weight, total cholesterol (TC), low-density lipoprotein (LDL), and systolic blood pressure (SBP). Serious adverse events were uncommon and not significantly different. More patients taking GLP-1RA experienced gastrointestinal complications: nausea, diarrhea, and vomiting. Severe hypoglycemia events were rare, and minor hypoglycemia was less common for GLP-1RA. GLP-1RA showed greater efficacy compared to IGlar for type 2 diabetes, and it may also prove beneficial for other diabetes-associated characteristics, including obesity, hypertension, and hyperlipidemia. © 2014 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

  6. A Comparison of the Effects of the GLP-1 Analogue Liraglutide and Insulin Glargine on Endothelial Function and Metabolic Parameters: A Randomized, Controlled Trial Sapporo Athero-Incretin Study 2 (SAIS2.

    Directory of Open Access Journals (Sweden)

    Hiroshi Nomoto

    Full Text Available GLP-1 improves hyperglycemia, and it has been reported to have favorable effects on atherosclerosis. However, it has not been fully elucidated whether GLP-1 is able to improve endothelial function in patients with type 2 diabetes. Therefore, we investigated the efficacy of the GLP-1 analogue, liraglutide on endothelial function and glycemic metabolism compared with insulin glargine therapy.In this multicenter, prospective randomized parallel-group comparison study, 31 diabetic outpatients (aged 60.3 ± 10.3 years with HbA1c levels of 8.6 ± 0.8% with current metformin and/or sulfonylurea treatment were enrolled and randomly assigned to receive liraglutide or glargine therapy once daily for 14 weeks. Flow mediated dilation (FMD, a comprehensive panel of hemodynamic parameters (Task Force Monitor, and serum metabolic markers were assessed before and after the treatment period.A greater reduction (worsening in %FMD was observed in the glargine group, although this change was not statistically different from the liraglutide group (liraglutide; 5.7 to 5.4%, glargine 6.7 to 5.7%. The augmentation index, C-peptide index, derivatives of reactive oxygen metabolites and BMI were significantly improved in the liraglutide group. Central systolic blood pressure and NT-proBNP also tended to be improved in the liraglutide-treated group, while improvements in HbA1c levels were similar between groups. Cardiac index, blood pressure and most other metabolic parameters were not different.Regardless of glycemic improvement, early liraglutide therapy did not affect endothelial function but may provide favorable effects on beta-cell function and cardioprotection in type 2 diabetics without advanced atherosclerosis.UMIN Clinical Trials Registry System as trial ID UMIN000005331.

  7. Effectiveness and safety of basal supported oral therapy with insulin glargine, in Japanese insulin-naive, type 2 diabetes patients, with or without microvascular complications: subanalysis of the observational, non-interventional, 24-week follow-up Add-on Lantus® to Oral Hypoglycemic Agents (ALOHA) study.

    Science.gov (United States)

    Odawara, Masato; Kadowaki, Takashi; Naito, Yusuke

    2015-01-01

    The aim of this study is to evaluate effectiveness and safety of basal supported oral therapy (BOT) using insulin glargine in insulin-naive Japanese patients, with and without microvascular complications. This sub-group analysis of observational, non-interventional ALOHA study, assessed changes in glycemic parameters and glargine dose, at 24weeks or at glargine discontinuation. Count of hypoglycemic episodes was based on physicians' documentation of patient reports. Patients were stratified according to presence/absence of microvascular complications, at baseline. Relationships between baseline patient characteristics and achievement of HbA1c <7% were examined by multivariate regression analysis. A total of 3631 patients, included during 2007-2009, were stratified in sub-groups: no complications (n= 1889), retinopathy (n=318), neuropathy (n=297), nephropathy (n=356), retinopathy+neuropathy (n= 174), retinopathy+nephropathy (n=154), neuropathy+nephropathy (n=142), and retinopathy+neuropathy+nephropathy (n=301). Changes in HbA1c, fasting and postprandial plasma glucose, and glargine daily dose were similar among patients with and without complications. Response-rate for achieving HbA1c <7.0% was highest in patients without complications (19.1%). In multivariate analysis, patients without complications showed significantly higher odds of attaining HbA1c <7%, independent of diabetes duration and baseline HbA1c levels. Patients with retinopathy+nephropathy had the lowest response-rate (8.8%) and highest hypoglycemic-rate (3.2%). Japanese insulin-naive patients without complications, on BOT with glargine, show higher chances of attaining HbA1c <7.0% than those with complications. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Régimen con insulina lispro mix 25 versus insulina glargina para la diabetes tipo 2 Starting an insulin regimen with insulin lispro mix 25 versus glargine insulin for type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Laura Fernández Landó

    2012-06-01

    Full Text Available La información sobre el inicio de regímenes de insulina en poblaciones específicas con diabetes tipo 2 (DT2 es limitada. Se comparó eficacia y seguridad de dos regímenes de inicio: insulina lispro mix 25 (LM25 e insulina glargina basal (GL. Se evaluaron 193 pacientes no tratados previamente con insulina, en la fase de iniciación de 24 semanas del ensayo DURABLE; edades: 30-79 años, DT2 controlada inadecuadamente (HbA1c > 7.0% con = 2 medicaciones orales antidiabéticas (MOAs, aleatorizados para LM25 (25% de insulina lispro, 75% de insulina lispro protamina en suspensión dos veces/día, o GL (insulina glargina basal una vez/ día, a las MOAs previas. La eficacia primaria se midió por HbA1c a las 24 semanas. Se midió eficacia secundaria por: proporción de pacientes que alcanzaron HbA1c= 6.5% y= 7.0%, cambio en peso corporal, valores de automonitoreo glucémico e índices de hipoglucemia. LM25 demostró mayor reducción de la HbA1c (- 2.4% ± 0.16 vs. -2.0% ± 0.16, P = 0.002, mayor proporción de pacientes alcanzaron HbA1c= 7.0% (P = 0.012 y niveles de glucemia menores después del desayuno (P = 0.028 y de la cena (P = 0.011, y a las 3 a.m. (P = 0.005 comparada con GL. La glucemia en ayunas (GA y la proporción de pacientes que alcanzaron una HbA1c= 6.5% fueron similares. En ambos grupos hubo aumento del peso corporal, mayor en la valoración final con LM25 (6.35 kg vs. 4.23 kg, P Information on starting insulin regimens in specific populations with type 2 diabetes (T2D is limited. This analysis compared efficacy and safety of two starter insulin regimens: insulin lispro mix 25 (LM25 and basal insulin glargine (GL in patients from Argentina. This post-hoc analysis evaluated 193 insulin-naïve patients who participated in the DURABLE trial 24-week initiation phase. Patients 30-79 years with T2D inadequately controlled (HbA1c > 7.0% with = 2 oral antihyperglycemic medications (OAMs, were randomized to add LM25 (25% insulin lispro, 75

  9. Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta-analysis.

    Science.gov (United States)

    Freemantle, Nick; Chou, Engels; Frois, Christian; Zhuo, Daisy; Lehmacher, Walter; Vlajnic, Aleksandra; Wang, Hongwei; Chung, Hsing-Wen; Zhang, Quanwu; Wu, Eric; Gerrits, Charles

    2016-02-15

    To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM). This was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO. Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed. 41 studies were included; 25 studies comprised the main analysis population: patients on basal insulin-supported oral therapy (BOT). Change in glycated haemoglobin (HbA1c) was comparable between Gla-300 and detemir (difference: -0.08; 95% credible interval (CrI): -0.40 to 0.24), neutral protamine Hagedorn (NPH; 0.01; -0.28 to 0.32), degludec (-0.12; -0.42 to 0.20) and premixed insulin (0.26; -0.04 to 0.58). Change in body weight was comparable between Gla-300 and detemir (0.69; -0.31 to 1.71), NPH (-0.76; -1.75 to 0.21) and degludec (-0.63; -1.63 to 0.35), but significantly lower compared with premixed insulin (-1.83; -2.85 to -0.75). Gla-300 was associated with a significantly lower nocturnal hypoglycaemia rate versus NPH (risk ratio: 0.18; 95% CrI: 0.05 to 0.55) and premixed insulin (0.36; 0.14 to 0.94); no significant differences were noted in Gla-300 versus detemir (0.52; 0.19 to 1.36) and degludec (0.66; 0.28 to 1.50). Differences in documented symptomatic hypoglycaemia rates of Gla-300 versus detemir (0.63; 0.19 to 2.00), NPH (0.66; 0.27 to 1.49) and degludec (0.55; 0.23 to 1.34) were not significant. Extensive sensitivity analyses supported the robustness of these findings. NMA comparisons are useful in the absence of direct randomised controlled data. This NMA suggests that Gla-300 is also associated with a significantly lower risk of nocturnal hypoglycaemia compared with NPH and premixed insulin, with glycaemic control comparable to

  10. Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta-analysis

    Science.gov (United States)

    Freemantle, Nick; Chou, Engels; Frois, Christian; Zhuo, Daisy; Lehmacher, Walter; Vlajnic, Aleksandra; Wang, Hongwei; Chung, Hsing-wen; Zhang, Quanwu; Wu, Eric; Gerrits, Charles

    2016-01-01

    Objective To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM). Design This was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO. Outcome measures Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed. Results 41 studies were included; 25 studies comprised the main analysis population: patients on basal insulin-supported oral therapy (BOT). Change in glycated haemoglobin (HbA1c) was comparable between Gla-300 and detemir (difference: −0.08; 95% credible interval (CrI): −0.40 to 0.24), neutral protamine Hagedorn (NPH; 0.01; −0.28 to 0.32), degludec (−0.12; −0.42 to 0.20) and premixed insulin (0.26; −0.04 to 0.58). Change in body weight was comparable between Gla-300 and detemir (0.69; −0.31 to 1.71), NPH (−0.76; −1.75 to 0.21) and degludec (−0.63; −1.63 to 0.35), but significantly lower compared with premixed insulin (−1.83; −2.85 to −0.75). Gla-300 was associated with a significantly lower nocturnal hypoglycaemia rate versus NPH (risk ratio: 0.18; 95% CrI: 0.05 to 0.55) and premixed insulin (0.36; 0.14 to 0.94); no significant differences were noted in Gla-300 versus detemir (0.52; 0.19 to 1.36) and degludec (0.66; 0.28 to 1.50). Differences in documented symptomatic hypoglycaemia rates of Gla-300 versus detemir (0.63; 0.19to 2.00), NPH (0.66; 0.27 to 1.49) and degludec (0.55; 0.23 to 1.34) were not significant. Extensive sensitivity analyses supported the robustness of these findings. Conclusions NMA comparisons are useful in the absence of direct randomised controlled data. This NMA suggests that Gla-300 is also associated with a significantly lower risk of nocturnal hypoglycaemia

  11. Exenatide with Metformin Ameliorated Visceral Adiposity and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Xuan Du

    2018-01-01

    Full Text Available Background. To study the effectiveness of exenatide with metformin and sequential treatment with exenatide and glargine added to metformin and their influence on insulin sensitivity and adipose distribution. Methods. 20 newly diagnosed obese type 2 diabetic patients were enrolled, and 2-month washout treatment of metformin, 6-month exenatide treatment, and 6-month glargine treatment were administrated sequentially accompanied with previous metformin. Glucolipid metabolic parameters were compared among groups. Adipose distribution was quantified with computerized tomography according to anatomy, dividing into visceral adipose tissue (VAT and subcutaneous adipose tissue (SAT, adding up to total adipose tissue (TAT. Results. The 6-month exenatide treatment dramatically ameliorated the glucose and lipid profile, improved insulin sensitivity, and mainly decreased VAT and also the ratio of VAT/SAT (RVS. The following 6-month glargine treatment increased VAT. The whole 12-month sequential treatment with exenatide and glargine added to metformin basically improved the insulin sensitivity and glucolipid control though VAT rebounded at the end, however without deteriorating the other parameters. Conclusion. Exenatide is an ideal treatment for obese type 2 diabetic patients in the aspect of adipose tissue distribution. Sequential treatment of exenatide and glargine could be an alternative for low-income patients who cannot afford GLP-1 agonist for long time. This trial is registered with ChiCTR-OOC-17013679.

  12. Drug-use patterns of initially prescribed insulin detemir and insulin glargine in the Netherlands; A comparative analysis using pharmacy data from IADB.nl

    NARCIS (Netherlands)

    Visser, S.T.; Vegter, S.; Boersma, C.; De Grooth, R.; Postma, M.J.

    2010-01-01

    OBJECTIVES: Newer long-acting insulin analogs have shown to result in several treatment improvements if compared with NPH insulins. Promising results from clinical trials require confirmation from observational settings reflecting potential “real-life” benefits. Therefore, the current study aimed to

  13. Evaluation of the Short-Term Cost-Effectiveness of IDegLira Versus Continued Up-Titration of Insulin Glargine U100 in Patients with Type 2 Diabetes in the USA.

    Science.gov (United States)

    Hunt, Barnaby; Mocarski, Michelle; Valentine, William J; Langer, Jakob

    2017-04-01

    Effective glycemic control can reduce the risk of complications and their related costs in type 2 diabetes mellitus (T2DM). However, many patients fail to reach glycemic targets, often because of adverse effects of treatment (including hypoglycemia or weight gain). The present analysis evaluated the short-term cost-effectiveness of IDegLira versus continued up-titration of insulin glargine U100 in patients with T2DM failing to achieve glycemic control on basal insulin in the US setting. The cost per patient achieving treatment target (cost of control) was assessed for various single and composite endpoints for the entire trial population and in patients with baseline glycated hemoglobin (HbA1c) >8.0% and HbA1c >9.0%. The proportions of patients achieving treatment targets were analyzed using data obtained in the DUAL V study. Costs were accounted based on published wholesale acquisition costs. When assessing the full trial population, IDegLira was associated with lower annual cost of control than continued up-titration of insulin glargine U100 for patients achieving HbA1c ≤6.5% without confirmed hypoglycemia (by $10,608), HbA1c ≤6.5% without weight gain (by $29,215), and HbA1c ≤6.5% without confirmed hypoglycemia and weight gain (by $57,351). A similar pattern was observed when multifactorial treatment targets were based on achieving a glycemic target of 7.0%. When only HbA1c was considered, IDegLira was associated with a lower cost per patient achieving HbA1c ≤6.5% (by $3306) but cost of control was equivalent for a target of HbA1c 8.0% and HbA1c >9.0%, IDegLira was associated with a lower cost of control for all treatment targets. The significantly greater clinical efficacy in terms of bringing patients to treatment targets identified in the DUAL V study results in lower cost of control values for IDegLira versus continued up-titration of insulin glargine U100 in the USA. This suggests IDegLira is a cost-effective treatment option in the USA. Novo Nordisk

  14. Day-to-Day and Within-Day Variability in Glucose-Lowering Effect Between Insulin Degludec and Insulin Glargine (100 U/mL and 300 U/mL): A Comparison Across Studies.

    Science.gov (United States)

    Heise, Tim; Kaplan, Kadriye; Haahr, Hanne L

    2017-09-01

    Insulin degludec (IDeg) has significantly lower day-to-day and within-day variability compared to insulin glargine (IGlar) 100U/mL (U100) and 300U/mL (U300). Here, we report post hoc assessments to confirm the robustness of these observations while accounting for potential experimental confounders. Two euglycemic clamp studies in type 1 diabetes patients, comparing IDeg to IGlar-U100 (Study A, parallel design, 54 patients; Study B, crossover, 22 patients) and one study comparing IDeg to IGlar-U300 (Study C, crossover, 57 patients), all dosed at 0.4U/kg, were evaluated. Pharmacodynamic parameters were assessed at steady state from glucose infusion rate (GIR) profiles following three 24-hour euglycemic clamps in Studies A (162 clamps) and C (342 clamps), and one 42-hour clamp in Study B (44 clamps). Pooled data (Studies A and B) showed that IDeg had an even distribution of glucose-lowering effect over the 24-hour dosing interval that was consistent with Study C. IGlar-U100 showed a constant decrease in glucose-lowering effect over 24 hours while IGlar-U300 had a lower effect in the middle of the dosing interval (6-18 hours). Relative within-day variability of IDeg was 40% and 37% lower than IGlar-U100 and -U300, respectively. Exclusion of profiles with low response in Study C (19/342 clamps) did not impact the difference in the distribution of glucose-lowering effect or within-day variability. Day-to-day variability was significantly lower with IDeg compared to IGlar-U100 and -U300 based on smoothed and unsmoothed GIR data. Significantly lower relative within-day and day-to-day variability was confirmed irrespective of experimental considerations for IDeg compared to IGlar-U100 and IGlar-U300.

  15. Comparison of thrice-daily premixed insulin (insulin lispro premix) with basal-bolus (insulin glargine once-daily plus thrice-daily prandial insulin lispro) therapy in east Asian patients with type 2 diabetes insufficiently controlled with twice-daily premixed insulin: an open-label, randomised, controlled trial.

    Science.gov (United States)

    Jia, Weiping; Xiao, Xinhua; Ji, Qiuhe; Ahn, Kyu-Jeung; Chuang, Lee-Ming; Bao, Yuqian; Pang, Can; Chen, Lei; Gao, Fei; Tu, Yinfang; Li, Pengfei; Yang, Jun

    2015-04-01

    Unlike in western countries, premixed insulin is widely used as the starter insulin in Asian patients instead of basal insulin. The use of basal-bolus therapy as an intensification regimen is not common in Asia despite poor glycaemic control after starting insulin therapy. An alternative insulin intensification regimen with a similar efficacy and safety profile to basal-bolus therapy, but of higher convenience, is urgently needed. The efficacy and safety of insulin lispro mix thrice-daily was compared with basal-bolus therapy in Asian patients with type 2 diabetes who were insufficiently controlled on twice-daily premixed insulin. This open-label, randomised, active comparator-controlled, parallel-group trial was done at 24 centres in China, Taiwan, and South Korea. Patients with type 2 diabetes who were inadequately controlled on twice-daily premixed insulin were randomly assigned (1:1) to receive either insulin lispro mix (mix 50 before breakfast and lunch plus mix 25 before dinner) or basal-bolus therapy (insulin glargine at bedtime plus prandial insulin lispro thrice-daily) for 24 weeks. Randomisation was done by a computer-generated random sequence and was stratified by country or region and baseline HbA1c. Treatment assignments were masked from the study team assessing outcomes but not from investigators and patients. The primary outcome was change from baseline in HbA1c at week 24 in all randomly assigned patients who received at least one dose of study drug. Analysis was by modified intention to treat, with the per-protocol population used as a supportive analysis. This study is registered with ClinicalTrials.gov, number NCT01175811. Between Feb 7, 2011, and Nov 7, 2012, 402 patients were enrolled (199 in the premix group, 203 in the basal-bolus group) and 399 were included in the primary analysis (197 in the premix group, 202 in the basal-bolus group). HbA1c change at week 24 was -1.1% for both treatment groups. The least squares mean difference between

  16. Evaluation of a new reusable insulin pen (ClikSTAR) in Canadian patients with type 1 and type 2 diabetes mellitus receiving insulin glargine.

    Science.gov (United States)

    Gottesman, Irving; Perron, Patrice; Berard, Lori; Stewart, John; Basso, Nils; Mettimano, Kim; Elliott, Thomas

    2012-10-01

    The objective of this Canadian observational study was to assess the safety and patient satisfaction with the ClikSTAR(®) (sanofi-aventis, Frankfurt am Main, Germany) reusable insulin pen in clinical practice. Patients with diabetes (n=2,517) were recruited from 103 sites, provided with the ClikSTAR pen, and instructed to report product technical complaints (PTCs), product technical failures (PTFs), and adverse events (AEs) over 6-12 weeks of use. A patient subgroup (n = 301) completed a pen use questionnaire at 12 weeks. The risk acceptance criterion was that no validated PTF led to a serious AE (SAE). PTFs were PTCs having a confirmed technical deficiency. Patients (68.5% with type 2 diabetes) had a mean age of 56.2 years, and 92.5% were insulin pen users. In total, 84 PTCs were reported by 79 (3.1%) patients. Most PTCs were due to pen handling errors. PTCs from 12 patients were possibly related to AEs, three of which were SAEs; none was confirmed to be due to a PTF. The single reported PTF was not related to an AE/SAE. In the substudy, 97.0% and 95.3% of patients rated "ease of learning" and "ease of use" of the ClikSTAR pen as excellent or good, respectively. Mean scores for patient satisfaction, convenience, flexibility, and recommendations of current treatment on the Diabetes Treatment Satisfaction Questionnaire (change version) had positive changes ranging from 1.0 to 1.8. With ClikSTAR, PTCs were infrequent, and there were no PTFs associated with AEs, demonstrating that the pen is reliable and safe with high levels of patient acceptance and satisfaction.

  17. Placing the Outcome Reduction with an Initial Glargine Intervention ...

    African Journals Online (AJOL)

    ORIGIN) trial were presented at the American Diabetes Association meeting in June 2012. The purpose of this study was to assess whether there would be any reduction in cardiovascular (CV) events if insulin glargine was started early in the course ...

  18. Comparison of Insulin Glargine 300 Units/mL and 100 Units/mL in Adults With Type 1 Diabetes: Continuous Glucose Monitoring Profiles and Variability Using Morning or Evening Injections.

    Science.gov (United States)

    Bergenstal, Richard M; Bailey, Timothy S; Rodbard, David; Ziemen, Monika; Guo, Hailing; Muehlen-Bartmer, Isabel; Ahmann, Andrew J

    2017-04-01

    The objective of this study was to compare glucose control in participants with type 1 diabetes receiving insulin glargine 300 units/mL (Gla-300) or glargine 100 units/mL (Gla-100) in the morning or evening, in combination with mealtime insulin. In this 16-week, exploratory, open-label, parallel-group, two-period crossover study (clinicaltrials.gov identifier NCT01658579), 59 adults with type 1 diabetes were randomized (1:1:1:1) to once-daily Gla-300 or Gla-100 given in the morning or evening (with crossover in the injection schedule). The primary efficacy end point was the mean percentage of time in the target glucose range (80-140 mg/dL), as measured using continuous glucose monitoring (CGM), during the last 2 weeks of each 8-week period. Additional end points included other CGM glycemic control parameters, hypoglycemia (per self-monitored plasma glucose [SMPG]), and adverse events. The percentage of time within the target glucose range was comparable between the Gla-300 and Gla-100 groups. There was significantly less increase in CGM-based glucose during the last 4 h of the 24-h injection interval for Gla-300 compared with Gla-100 (least squares mean difference -14.7 mg/dL [95% CI -26.9 to -2.5]; P = 0.0192). Mean 24-h glucose curves for the Gla-300 group were smoother (lower glycemic excursions), irrespective of morning or evening injection. Four metrics of intrasubject interstitial glucose variability showed no difference between Gla-300 and Gla-100. Nocturnal confirmed (300 participants than for Gla-100 participants (4.0 vs. 9.0 events per participant-year; rate ratio 0.45 [95% CI 0.24-0.82]). Less increase in CGM-based glucose levels in the last 4 h of the 24-h injection interval, smoother average 24-h glucose profiles irrespective of injection time, and reduced nocturnal hypoglycemia were observed with Gla-300 versus Gla-100. © 2017 by the American Diabetes Association.

  19. INSULIN THERAPY TODAY

    Directory of Open Access Journals (Sweden)

    Saša Živić

    2002-05-01

    Full Text Available The insulin classification regarding the duration of its effect gradually be-comes outdated; it is necessary to speak first about the insulin therapy regimes. The intensified insulin therapy regarding the type of multiple daily insulin injections be-comes an indisputable standard. The progress in the "protein engineering" with the formation of a wide spectrum of insulin analogues provides for moving forward to-wards modern diabetology and the concept of strict individualization of the insulin therapy. The experience becomes a pattern in creating two existing formulas of the insulin "short" analogues, namely HUMALAG with the replacement of the proline and lysinane places with those of 28 and 29, and NOVORAPID with aspartic acid at the 28th place in the B chain. The most recent long-effect analogues are created by amino acid changes with the glycine residual at the position A21 and two ariginines added to the positions B31 and B32 - insulin "glargin" - LANTUS. The development of short and long effect analogues imposed the logical need for formulating "new" fixed insulin combination's as well. New combination's are made of two kinds of ac-tual insulin, namely, the fast-effect analogues of the aspart type or lystroinsulin and protamine-retarded preparations - neutral protamine - lystroinsulin. Three kinds of combinations are made.

  20. Complexation study on no-carrier-added astatine with insulin: A candidate radiopharmaceutical

    Energy Technology Data Exchange (ETDEWEB)

    Lahiri, Susanta [Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700 064 (India)], E-mail: susanta.lahiri@saha.ac.in; Roy, Kamalika [Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700 064 (India); Sen, Souvik [Berhampur Sadar Hospital, Berhampur, Murshidabad 742 101 (India)

    2008-12-15

    No-carrier-added astatine radionuclides produced in the {sup 7}Li-irradiated lead matrix were separated from bulk lead nitrate target by complexing At with insulin, followed by dialysis. The method offers simultaneous separation of At from lead as well as its complexation with insulin. The At-insulin complex might be a potential radiopharmaceutical in the treatment of hepatocellular carcinoma. The stability of At-insulin complex was checked by dialysis against deionized water and Ringer lactate (RL) solution. It has been found that the half-life of At-insulin complex is about {approx}12 h, when dialyzed against deionized water and is only 6 h, when dialyzed against RL solution having the same composition as blood serum. The 6 h half-life of this Insulin-At complex is perfect for killing cancer cells from external cell surfaces as the half-life of internalization of insulin molecule inside the cell is 7-12 h.

  1. Intranasal insulin prevents anesthesia-induced hyperphosphorylation of tau in 3xTg-AD mice

    Directory of Open Access Journals (Sweden)

    Yanxing eChen

    2014-05-01

    Full Text Available Background: It is well documented that elderly individuals are at increased risk of cognitive decline after anesthesia. General anesthesia is believed to be a risk factor for Alzheimer’s disease (AD. Recent studies suggest that anesthesia may increase the risk for cognitive decline and AD through promoting abnormal hyperphosphorylation of tau, which is crucial to neurodegeneration seen in AD. Methods: We treated 3xTg-AD mice, a commonly used transgenic mouse model of AD, with daily intranasal administration of insulin (1.75U/day for one week. The insulin- and control-treated mice were then anesthetized with single intraperitoneal injection of propofol (250 mg/kg body weight. Tau phosphorylation and tau protein kinases and phosphatases in the brains of mice 30 min and two hours after propofol injection were then investigated by using Western blots and immunohistochemistry.Results: Propofol strongly promoted hyperphosphorylation of tau at several AD-related phosphorylation sites. Intranasal administration of insulin attenuated propofol-induced hyperphosphorylation of tau, promoted brain insulin signaling, and led to up-regulation of protein phosphatase 2A, a major tau phosphatase in the brain. Intranasal insulin also resulted in down-regulation of several tau protein kinases, including cyclin-dependent protein kinase 5, calcium/calmodulin-dependent protein kinase II, and c-Jun N-terminal kinase. Conclusion: Our results demonstrate that pretreatment with intranasal insulin prevents AD-like tau hyperphosphorylation. These findings provide the first evidence supporting that intranasal insulin administration might be used for the prevention of anesthesia-induced cognitive decline and increased risk for AD and dementia.

  2. Combination therapy in type 2 diabetes mellitus: adding empagliflozin to basal insulin

    Directory of Open Access Journals (Sweden)

    Andrew Ahmann

    2015-11-01

    Full Text Available Type 2 diabetes mellitus (T2DM management is complex, with few patients successfully achieving recommended glycemic targets with monotherapy, most progressing to combination therapy, and many eventually requiring insulin. Sodium glucose cotransporter 2 (SGLT2 inhibitors are an emerging class of antidiabetes agents with an insulin-independent mechanism of action, making them suitable for use in combination with any other class of antidiabetes agents, including insulin. This review evaluates a 78-week, randomized, double-blind, placebo-controlled trial investigating the impact of empagliflozin, an SGLT2 inhibitor, as add-on to basal insulin in patients with inadequate glycemic control on basal insulin, with or without metformin and/or a sulfonylurea. Empagliflozin added on to basal insulin resulted in significant and sustained reductions in glycated hemoglobin (HbA1c levels compared with placebo. Empagliflozin has previously been shown to induce weight loss, and was associated with sustained weight loss in this study. This combination therapy was well tolerated, with similar levels of hypoglycemic adverse events in the empagliflozin and placebo groups over the 78-week treatment period. Urinary tract infections and genital infections, side effects associated with SGLT2 inhibitors, were reported more commonly in the empagliflozin group; however, such events led to treatment discontinuation in very few patients. These findings suggest that, with their complementary mechanisms of action, empagliflozin added on to basal insulin may be a useful treatment option in patients on basal insulin who need additional glycemic control without weight gain.

  3. Carcinogenicity of insulin analogues

    NARCIS (Netherlands)

    Braak, Sebastiaan Johannes ter

    2015-01-01

    There is epidemiological evidence that the use of some insulin analogues by diabetic patients is correlated with an increased cancer risk. In vitro exposure experiments revealed that insulin glargine (LANTUS) was the only commercial insulin analogue with an increased mitogenic potential. In the

  4. Effect of Added Carbohydrates on Glycemic and Insulin Responses to Children’s Milk Products

    Directory of Open Access Journals (Sweden)

    Jennie Brand-Miller

    2013-01-01

    Full Text Available Powdered milk products for children (Growing Up Milk Powders or GUMPs containing added carbohydrates such as glucose and sucrose are now well established in parts of Asia. We surveyed GUMPs in Malaysia and Indonesia to determine the content of added carbohydrates. The ingredient lists and nutrition information panels were used to calculate the percentage of declared carbohydrates contributed by added carbohydrates and a subset of seven products was tested for their glycemic index (GI and insulin responses in healthy adults. The glycemic load for each product was calculated. In total, 58 products (n = 24 in Malaysia and n = 34 in Indonesia were surveyed. Added carbohydrate content (excluding fibre ranged from 0 to 21.5 g per serve. Milk powders without added sources of carbohydrate had similar GI values to standard liquid whole milk. Products containing maltodextrins, corn or glucose syrups increased the GI by more than 2-fold, and glycemic load (GL by 7-fold compared to milk powders with no added carbohydrates. Insulin responses were significantly but not strongly correlated with glucose responses (r = 0.32, p < 0.006. Children’s milk powders containing higher levels of added carbohydrate ingredients elicit higher glucose and insulin responses than liquid or powdered whole milk.

  5. Effect of added carbohydrates on glycemic and insulin responses to children’s milk products.

    Science.gov (United States)

    Brand-Miller, Jennie; Atkinson, Fiona; Rowan, Angela

    2013-01-10

    Powdered milk products for children (Growing Up Milk Powders or GUMPs) containing added carbohydrates such as glucose and sucrose are now well established in parts of Asia. We surveyed GUMPs in Malaysia and Indonesia to determine the content of added carbohydrates. The ingredient lists and nutrition information panels were used to calculate the percentage of declared carbohydrates contributed by added carbohydrates and a subset of seven products was tested for their glycemic index (GI) and insulin responses in healthy adults. The glycemic load for each product was calculated. In total, 58 products (n = 24 in Malaysia and n = 34 in Indonesia) were surveyed. Added carbohydrate content (excluding fibre) ranged from 0 to 21.5 g per serve. Milk powders without added sources of carbohydrate had similar GI values to standard liquid whole milk. Products containing maltodextrins, corn or glucose syrups increased the GI by more than 2-fold, and glycemic load (GL) by 7-fold compared to milk powders with no added carbohydrates. Insulin responses were significantly but not strongly correlated with glucose responses (r = 0.32, p carbohydrate ingredients elicit higher glucose and insulin responses than liquid or powdered whole milk.

  6. Oral Hypoglycemic Agents Added to Insulin Monotherapy for Type 2 Diabetes

    NARCIS (Netherlands)

    Vos, Rimke C.; Rutten, Guy E.H.M.

    2017-01-01

    Clinical Question: Among patients with type 2 diabetes mellitus who do not achieve optimal glycemic control with insulin monotherapy, is the addition of oral hypoglycemic agents associated with benefits (measured by lowering of hemoglobin A1c) or adverse effects? Bottom Line: Adding a sulfonylurea

  7. Efficacy and Safety of Degludec versus Glargine in Type 2 Diabetes

    DEFF Research Database (Denmark)

    Marso, Steven P; McGuire, Darren K; Zinman, Bernard

    2017-01-01

    received degludec than among those who received basal insulin glargine. However, data are lacking on the cardiovascular safety of degludec. METHODS: We randomly assigned 7637 patients with type 2 diabetes to receive either insulin degludec (3818 patients) or insulin glargine U100 (3819 patients) once daily......BACKGROUND: Degludec is an ultralong-acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. Previous open-label studies have shown lower day-to-day variability in the glucose-lowering effect and lower rates of hypoglycemia among patients who......, or nonfatal stroke) with a prespecified noninferiority margin of 1.3. Adjudicated severe hypoglycemia, as defined by the American Diabetes Association, was the prespecified, multiplicity-adjusted secondary outcome. RESULTS: Of the patients who underwent randomization, 6509 (85.2%) had established...

  8. Insulin Glargine (rDNA origin) Injection

    Science.gov (United States)

    ... It also stops the liver from producing more sugar.Over time, people who have diabetes and high blood sugar can develop serious or ... exercise, quitting smoking), and regularly checking your blood sugar may help to manage your diabetes and improve your health. This therapy may also ...

  9. Adding pioglitazone to insulin containing regimens in type 2 diabetes: systematic review and meta-analysis.

    Directory of Open Access Journals (Sweden)

    Christine Clar

    Full Text Available BACKGROUND: Type 2 diabetes is treated in a stepwise manner, progressing from diet and physical activity to oral antidiabetic agents and insulin. The oral agent pioglitazone is licensed for use with insulin when metformin is contraindicated or not tolerated. This systematic review and meta-analysis investigates the extent to which adding pioglitazone to insulin-containing regimens produces benefits in terms of patient-relevant outcomes. METHODOLOGY/PRINCIPAL FINDINGS: Medline, Embase, and the Cochrane Library were searched for randomised controlled trials comparing pioglitazone in combination with any insulin-containing regimen in comparison with the same insulin regimen alone in patients with type 2 diabetes. Outcomes investigated included HbA1c, hypoglycaemia, weight, and adverse events. Studies were selected, assessed and summarised according to standard systematic review methodology and in a meta-analysis. We included eight trials that examined the benefits of adding pioglitazone to an insulin regimen and studied a total of 3092 patients with type 2 diabetes. All studies included patients with previously inadequate glucose control. Trial duration was between 12 weeks and 34.5 months. The trials used pioglitazone doses of up to 45 mg/day. In our meta-analysis, the mean reduction in HbA1c was 0.58% (95% CI: -0.70, -0.46, p<0.00001. Hypoglycaemic episodes were slightly more frequent in the pioglitazone arms (relative risk 1.27; 95% CI: 0.99, 1.63, p = 0.06. Where reported, HDL-cholesterol tended to be increased with pioglitazone. Patients on pioglitazone tended to gain more weight than those who were not, with an average difference of almost 3 kg. Peripheral oedema was more frequent in the pioglitazone groups. None of the studies reported on fractures in women, and data on cardiovascular events were inconclusive, with most studies being too short or too small to assess these long-term outcomes. CONCLUSIONS/SIGNIFICANCE: When added to insulin

  10. Is there peripheral or ovarian insulin action alteration in broiler breeder hens fed ad libitum?

    Science.gov (United States)

    Métayer, S; Tesseraud, S; Cassy, S; Taouis, M; Williams, J; Picard, M; Rideau, N

    2006-06-01

    We investigated whether a change in peripheral glucose homeostasis, a local change in the insulin-related ovarian regulatory system, or both occurred in ad libitum-fed broiler breeder hens compared with feed-restricted counterparts. Feed-restricted (R, from 5 to 16 wk of age) and ad libitum-fed (A) hens from a standard commercial line (S) and an experimental dwarf genotype (E) were studied. Basal and stimulated plasma insulin and glucose concentrations were measured during the prebreeding and laying periods. In the basal state (after 16 h fasting) plasma glucose concentrations were significantly lower in SA chickens (-5% at 17 wk, -7.5% at 32 wk) compared with EA, SR, and ER chickens, with no difference in plasma insulin concentrations (n = 16). In 17-wk-old SA birds, 30 min after oral glucose loading, plasma glucose concentrations increased significantly compared with the basal state and were also significantly lower as compared with SR but did not differ significantly from EA and ER. Plasma insulin concentrations did not differ significantly between genotypes or regimens (n = 16). A potential modification of intracellular mediators involved in the regulation of cell growth and survival in small follicles that were overrecruited in SA compared with SR was also investigated in SA and SR hens at 32 wk. There was no effect of food restriction in phospho-Akt, Akt, phospho-ERK, and phospho-S6 in the small white ovarian follicles (n = 6) in the basal state and after 30 min of refeeding. In conclusion, the present study does not demonstrate any evidence of glucose intolerance during the prebreeding period, specific change in the ovarian small follicle insulin signalling pathway, or both, in laying broiler breeders fed ad libitum compared with feed-restricted hens.

  11. Somatostatin modulates insulin-degrading-enzyme metabolism: implications for the regulation of microglia activity in AD.

    Directory of Open Access Journals (Sweden)

    Grazia Tundo

    Full Text Available The deposition of β-amyloid (Aβ into senile plaques and the impairment of somatostatin-mediated neurotransmission are key pathological events in the onset of Alzheimer's disease (AD. Insulin-degrading-enzyme (IDE is one of the main extracellular protease targeting Aβ, and thus it represents an interesting pharmacological target for AD therapy. We show that the active form of somatostatin-14 regulates IDE activity by affecting its expression and secretion in microglia cells. A similar effect can also be observed when adding octreotide. Following a previous observation where somatostatin directly interacts with IDE, here we demonstrate that somatostatin regulates Aβ catabolism by modulating IDE proteolytic activity in IDE gene-silencing experiments. As a whole, these data indicate the relevant role played by somatostatin and, potentially, by analogue octreotide, in preventing Aβ accumulation by partially restoring IDE activity.

  12. The Effect of Basal Analog Insulin on the Glycemic Variability in Type 2 Diabetics

    Directory of Open Access Journals (Sweden)

    Soner Cander

    2014-06-01

    Full Text Available Purpose: The aim of this study was to investigate the effect of insulin detemir and glargine on glycemic variability as determined by capillary blood glucose measurements in Type 2 diabetics treated with oral antidiabetic drugs. Material and Method: A total of 64 insulin-naive type 2 diabetics with a HbA1c level of 7.5%-10% were included in the study. The patients were randomized into 3 groups according to the basal insulin analog started; Group 1 (n=22 was started on once-daily detemir, Group 2 (n=22 twice-daily detemir, and Group 3 (n=20 insulin glargine. Basal insulin doses were titrated according to the morning/evening fasting capillary blood glucose levels. Standard deviations of the 8-point intraday fasting and postprandial blood glucose values were compared. Results: The fasting blood glucose intraday standard deviation values showed an improvement of 22.4% in Group 1, 21.4% in Group 2, and 26.4% in Group 3, while the intraday standard deviation for the postprandial values showed an improvement of 14.4%, 15.2%, and 38.7%, respectively (p>0.05. The standard deviation values did not show statistical significance when the groups were compared with each other. Baseline HbA1c values and insulin doses negatively correlated with the glycemic variability. Dicussion: Basal insulin added to treatment in Type 2 diabetics provided an improvement of 14.4% to 38.7% in glycemic variability. There was no significant difference between insulin glargine and detemir regarding this effect. Turk Jem 2014; 2: 33-38

  13. Use of glargine in pregnant women with type 1 diabetes mellitus: a case-control study.

    Science.gov (United States)

    Imbergamo, Maria P; Amato, Marco C; Sciortino, Giovanna; Gambina, Massimo; Accidenti, Maria; Criscimanna, Angela; Giordano, Carla; Galluzzo, Aldo

    2008-08-01

    Insulin glargine is a once-daily basal insulin analog with prolonged duration of action and absence of an evident peak. Glargine is associated with reduced frequency of hypoglycemic episodes (mostly nocturnal) as well as effective glycemic control. Maintenance of good metabolic control before conception and throughout pregnancy is essential to lower the risk of fetal malformations. Glargine might be a valuable alternative in the management of pregnancies complicated by diabetes mellitus. However, because its clinical utility has not been established, the use of glargine is not currently recommended during pregnancy. The aim of this study was to retrospectively evaluate (years 2004-2007) the effectiveness and safety of insulin glargine compared with neutral protamine Hagedorn (NPH) in women affected by type 1 diabetes mellitus (T1DM) during pregnancy. The study comprised pregnant women affected by T1DM who were followed up in the Diabetes and Pregnancy Outpatient Clinic at the University of Palermo, Palermo, Italy, within 8 +/- 3.4 weeks subsequent to a positive pregnancy test. All patients with T1DM were treated with conventional basal-bolus insulin therapy (aspart or lispro analogs at the 3 main meals plus glargine or NPH at bedtime). Healthy pregnant women were used as controls for fetal and neonatal parameters. Patients were consecutively enrolled. In all women, metabolic status was determined daily by mean glycemic values (2-hour postprandial blood glucose) and glycosylated hemoglobin (HbA1c) values (at 3-month intervals). Fetal measurements (90th centiles of the head circumference, abdomen circumference, and femoral length) were evaluated by ultrasound at second and third trimesters. Weight and femoral length were assessed at birth, and neonates were classified according to the fetal growth curve for the Italian population (90th centile = large for gestational age (LGA). A total of 73 pregnant women (30 with T1DM and 43 healthy [control]) were included in the

  14. Insulin analogues: have they changed insulin treatment and improved glycaemic control?

    DEFF Research Database (Denmark)

    Madsbad, Sten

    2002-01-01

    . This is probably the main explanation for the absence of improvement in overall glycaemic control when compared with regular human insulin. A tendency to a reduction in hypoglycaemic events during treatment with fast-acting analogues has been observed in most studies. Recent studies have indicated that NPH insulin...... in a long half-life with a residual activity of about 50% 24 h after injection. Insulin glargine is a peakless insulin and studies in both type 1 and type 2 diabetic patients indicate that glargine improves fasting blood glucose control and reduces the incidence of nocturnal hypoglycaemia. Surprisingly...

  15. Insulin

    Science.gov (United States)

    ... 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 ...

  16. Patterns of postprandial hyperglycemia after basal insulin therapy: individual and regional differences.

    Science.gov (United States)

    Shaefer, Charles; Reid, Timothy; DiGenio, Andres; Vlajnic, Aleksandra; Zhou, Rong; Ameer, Barbara; Riddle, Matthew

    2015-03-01

    Treatment of postprandial hyperglycemia could be needed when basal insulin added to oral therapy does not maintain glycated haemoglobin (HbA1C ) targets in type 2 diabetes mellitus. Knowing individual and regional patterns of postprandial hyperglycemia in this setting might improve therapeutic decisions. Patient-level self-monitored blood glucose data were pooled from six studies of insulin glargine for patients with HbA1C  ≥ 7.0% after 24 weeks. Percentages of participants with highest daily postprandial blood glucose and greatest postprandial increments after each of the three daily meals were calculated and compared between four geographical regions; USA, Canada, Germany, and other European countries. For 494 participants (mean age 60.1 years, diabetes duration 9.6 years, and BMI 29.8 kg/m(2) ), mean endpoint HbA1C was 7.8%. On insulin glargine treatment, highest postprandial blood glucose most often occurred post-dinner (44% of participants) and greatest postprandial increments post-breakfast (46% of participants) in all regions. Participants with greatest postprandial increments post-breakfast were older and experienced less HbA1C improvement with insulin glargine than those with greatest postprandial increments after other meals. Post-breakfast and post-dinner postprandial blood glucose was higher in the USA and Canada versus Germany, and in the USA versus Other European countries (all p < 0.05). Postprandial increments after dinner were greater in the USA versus all other regions. Generally, highest postprandial blood glucose follows dinner and greatest postprandial increments follow breakfast. Variations in patient characteristics and eating patterns might underlie differences both within and between regions. Awareness of regional differences and evaluation of an individual's typical eating pattern might facilitate appropriate prandial therapy. Copyright © 2014 John Wiley & Sons, Ltd.

  17. Adding to the spectrum of insulin sensitive populations for mixed meal tolerance test glucose reliability assessment.

    Science.gov (United States)

    Paglialunga, Sabina; Guerrero, Angelica; Roessig, Julie M; Rubin, Paul; Dehn, Clayton A

    2016-01-01

    As a measure of insulin sensitivity, the mixed meal tolerance test (MMTT) is a simple technique that can provide robust results. The assay consists of examining plasma glucose, insulin and C-peptide prior to and following the consumption of a test meal. While this procedure has been used in clinical research for several years, there is no set standard protocol, and only until recently has the reliability of this assay been thoroughly evaluated in prediabetes and type 2 diabetes subjects. Interestingly, the results from this recent study demonstrated stronger MMTT reliability for the prediabetes and diabetes cohorts compared to obese controls. This finding suggests that the obese control group may have more inherent variability in glucose response during a meal challenge likely due to compensatory influences typically observed in non-diabetic insulin-resistant subjects. Furthermore, this study raises the question whether the MMTT assay is reliable in a non-obese cohort. Therefore, to promote the standardization of this technique and contribute to the band of insulin sensitive populations, we employed the same methodology and test meal as the reference study to evaluate the MMTT reliability in healthy and overweight men. Indeed, the interclass coefficient revealed high glucose response repeatability during the MMTT in insulin-sensitive men. Overall, the MMTT is a reliable test across a range of insulin sensitivity including healthy men. However, we propose further investigation may be required to fully define the utility of this methodology in obese non-diabetic insulin-resistant populations.

  18. No Effect of Added Sugar Consumed at Median American Intake Level on Glucose Tolerance or Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Joshua Lowndes

    2015-10-01

    Full Text Available Excess sugar consumption may promote adverse changes in hepatic and total body insulin resistance. Debate continues over the effects of sugars at more typically consumed levels and whether the identity of the sugar consumed is important. In the present study participants (20–60 years old were randomly assigned to one of five groups, three that consumed low fat milk with added fructose containing sugars in amounts equivalent to the 50th percentile of fructose consumption (US, one which consumed low-fat milk sweetened with glucose, and one unsweetened low-fat milk control group. The intervention lasted ten weeks. In the entire study population there was less than 1 kg increase in weight (73.6 ±13.0 vs. 74.5 ± 13.3 kg, p < 0.001, but the change in weight was comparable among groups (p > 0.05. There were no changes in fasting glucose (49 ± 0.4 vs. 5.0 ± 0.5 mmol/L, insulin (56.9 ± 38.9 vs. 61.8 ± 50.0 pmol/L, or insulin resistance, as measured by the Homeostasis Model Assessment method (1.8 ± 1.3 vs. 2.0 ± 1.5, all p > 0.05. These data suggest that added sugar consumed at the median American intake level does not produce changes in measures of insulin sensitivity or glucose tolerance and that no sugar has more deleterious effects than others.

  19. Long-acting insulin allergy in a diabetic child.

    Science.gov (United States)

    Mastrorilli, Carla; Rizzuti, Laura; Cangelosi, Antonina Marta; Iovane, Brunella; Chiari, Giovanni; Caffarelli, Carlo

    2017-06-01

    Insulin allergy has been uncommon since the introduction of human recombinant insulin preparations; the prevalence is 2.4%. Insulin injection could elicit immediate reactions, which are usually induced by an IgE-mediated mechanism, within the first hour after drug administration. In the present study, we describe the case of a child who experienced immediate urticaria after long-acting insulin injection. A 9-year-old girl affected by type I diabetes mellitus referred a history of three episodes of urticaria 30 min after insulin subcutaneous injection. During the first week of insulin therapy, she developed generalized immediate urticaria twice after long-acting insulin glargine first and then once after insulin degludec administration. Symptoms resolved within a few hours after treatment with oral antihistamine. She tolerated rapid insulin lispro. Her personal allergological history was negative. Skin prick tests with degludec, glargine and detemir were performed, showing negative results. Intradermal 1:100000-diluted tests were immediately positive for both degludec and glargine but not for detemir. In light of these findings, detemir was administered without any reaction. Our results show that detemir is tolerated by patients with clinical hypersensitivity reactions to degludec and glargine. Although reactions could be attributable to additives allergy, such as zinc or metacresol, this was excluded since all three preparations contain the same components. So, insulin itself acted as offending allergen. Detemir differs from degludec and glargine in a few aminoacids. Therefore, it is possible that the conformational rather than the linear epitope may be responsible for the reaction. This result suggests integrating intradermal tests in the diagnostic flowchart for insulin allergy. Insulin allergy should always be suspected in patients with immediate symptoms after drug injection. As allergologic work-up, prick by prick test and intradermal test to insulin

  20. Effect of Added Carbohydrates on Glycemic and Insulin Responses to Children?s Milk Products

    OpenAIRE

    Jennie Brand-Miller; Fiona Atkinson; Angela Rowan

    2013-01-01

    Powdered milk products for children (Growing Up Milk Powders or GUMPs) containing added carbohydrates such as glucose and sucrose are now well established in parts of Asia. We surveyed GUMPs in Malaysia and Indonesia to determine the content of added carbohydrates. The ingredient lists and nutrition information panels were used to calculate the percentage of declared carbohydrates contributed by added carbohydrates and a subset of seven products was tested for their glycemic index (GI) and in...

  1. Switching from basal or basal-bolus insulin to biphasic insulin aspart 30: Results from the Indian cohort of the A 1 chieve study

    Directory of Open Access Journals (Sweden)

    Arpandev Bhattacharyya

    2014-01-01

    Full Text Available Aim: To determine the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30 therapy in the Indian patients with type 2 diabetes previously on basal or basal-bolus insulin therapies. Materials and Methods: Patients switching from insulin glargine, neutral protamine Hagedorn (NPH insulin, or basal-bolus insulin to BIAsp 30 in the Indian cohort of the A 1 chieve study were included. Safety and efficacy of treatment was evaluated over 24 weeks. Results: A total of 422 patients (pre-study basal-bolus insulin, 49; NPH insulin, 157; insulin glargine, 216 switched to BIAsp 30. Pre-study insulin doses were 0.61 ± 0.26 U/kg, 0.34 ± 0.2 U/kg and 0.40 ± 0.21 U/kg and the mean week 24 BIAsp 30 doses were 0.50 ± 0.21 U/kg, 0.35 ± 0.15 U/kg and 0.42 ± 0.16 U/kg in the prior basal-bolus insulin, NPH insulin and insulin glargine groups, respectively. No serious adverse drug reactions, major or nocturnal hypoglycemia were reported. The proportion of patients experiencing overall hypoglycemia was significantly lower from baseline (5.6% to week 24 (1.0% in the pre-study insulin-glargine group and appeared to be lower in pre-study NPH insulin and basal-bolus insulin groups. Glycemic control improved significantly from baseline week 24 in the pre-study NPH insulin and insulin-glargine groups (P < 0.001, while it appeared to improve in the pre-study basal-bolus group. Quality of life was positively impacted after 24 weeks in all 3 groups. Conclusion: The switch from basal or basal-bolus insulin to BIAsp 30 was safe, well tolerated and improved the glycemic control in this Indian cohort.

  2. Insulin degludec is a new ultra-long-acting insulin analogue

    Directory of Open Access Journals (Sweden)

    Ivan Ivanovich Dedov

    2014-06-01

    Full Text Available Achieving optimal glycemic control is an important aspect of preventing and slowing the progression of diabetes-associated complications, and reducing the cost of their treatment. Long-acting insulin analogues, glargine and detemir, provide better metabolic control with reduced risk of hypoglycaemia as compared to NPH insulin. However, fear of hypoglycaemia and weight gain, as well as the complexity of regimen, are still the most important barriers to well-timed initiation and intensification of insulin therapy. Insulin degludec (Tresiba® is a new ultra-long-acting insulin analogue. After subcutaneous injection degludec forms repository of soluble multi-hexamers, which are gradually absorbed to the bloodstream, providing a flat, stable antihyperglycemic effect lasting more than 42 h, and low intra-individual variability as opposed to currently used basal insulin analogues, insulin glargine and insulin detemir. In the seven randomized, open label, controlled phase 3 trials lasting 26 or 52 weeks, using treat-to-target (no more non-inferiority design, insulin degludec provided glycemic control similar to that of insulin glargine with lower risk of nocturnal hypoglycaemia and good safety profile in patients with type 1 or 2 diabetes. Furthermore, trials examining a flexible dosing regimen of insulin degludec in patients with type 1 or 2 diabetes have shown that it is possible to vary the injection time without compromising glycemic control or safety of the therapy.

  3. Sitagliptin added to previously taken antidiabetic agents on insulin resistance and lipid profile: a 2-year study evaluation.

    Science.gov (United States)

    Derosa, Giuseppe; Ragonesi, Pietro Dario; Fogari, Elena; Cicero, Arrigo Francesco Giuseppe; Bianchi, Lucio; Bonaventura, Aldo; Romano, Davide; Maffioli, Pamela

    2014-04-01

    The aim of this study was to evaluate whether the positive effects of sitagliptin on glycemic control and insulin resistance were maintained also after 2 years of therapy and whether sitagliptin could be effective also in improving lipid profile. In this randomized, double-blind, placebo-controlled trial, 205 patients with type 2 diabetes in therapy with different antidiabetic drugs were randomized to add sitagliptin 100 mg once a day or placebo to their current therapy. We evaluated at the baseline and after 6, 12, 18, and 24 months the following parameters: body mass index, glycated hemoglobin (HbA1c ), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (Tg). Sitagliptin, added to previously taken antidiabetic agents, proved to be effective in improving glycemic profile, reducing HbA1c by -17.5%, FPG by -12.7%, PPG by -20.5%. Regarding insulin resistance, sitagliptin decreased FPI by -8.3% and HOMA-IR by -20.0%, confirming that what have been already reported in short-term studies can be applied also after 2 years of treatment. Sitagliptin also reduced body weight by -4.3%. Our study also showed the positive effect of sitagliptin on lipid profile; in particular, sitagliptin decreased TC by -13.3%, LDL-C by -20.4%, and Tg by -32.3%, and also increased HDL-C by + 13.6%. Sitagliptin proved to be effective on glycemic profile and insulin resistance even after 2 years of therapy and to be effective in improving body weight and lipid profile. © 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.

  4. A randomized clinical trial comparing the effect of basal insulin and inhaled mealtime insulin on glucose variability and oxidative stress

    NARCIS (Netherlands)

    Siegelaar, S. E.; Kulik, W.; van Lenthe, H.; Mukherjee, R.; Hoekstra, J. B. L.; DeVries, J. H.

    2009-01-01

    To assess the effect of three times daily mealtime inhaled insulin therapy compared with once daily basal insulin glargine therapy on 72-h glucose profiles, glucose variability and oxidative stress in type 2 diabetes patients. In an inpatient crossover study, 40 subjects with type 2 diabetes were

  5. Insulin use and persistence in patients with type 2 diabetes adding mealtime insulin to a basal regimen: a retrospective database analysis

    Directory of Open Access Journals (Sweden)

    Torres Amelito M

    2011-01-01

    Full Text Available Abstract Background The objective of this study was to characterize insulin use and examine factors associated with persistence to mealtime insulin among patients with type 2 diabetes (T2D on stable basal insulin therapy initiating mealtime insulin therapy. Methods Insulin use among patients with T2D initiating mealtime insulin was investigated using Thomson Reuters MarketScan® research databases from July 2001 through September 2006. The first mealtime insulin claim preceded by 6 months with 2 claims for basal insulin was used as the index event. A total of 21 months of continuous health plan enrollment was required. Patients were required to have a second mealtime insulin claim during the 12-month follow-up period. Persistence measure 1 defined non-persistence as the presence of a 90-day gap in mealtime insulin claims, effective the date of the last claim prior to the gap. Persistence measure 2 required 1 claim per quarter to be persistent. Risk factors for non-persistence were assessed using logistic regression. Results Patients initiating mealtime insulin (n = 4752; 51% male, mean age = 60.3 years primarily used vial/syringe (87% and insulin analogs (60%. Patients filled a median of 2, 3, and 4 mealtime insulin claims at 3, 6, and 12 months, respectively, with a median time of 76 days between refills. According to measure 1, persistence to mealtime insulin was 40.7%, 30.2%, and 19.1% at 3, 6, and 12 months, respectively. Results for measure 2 were considerably higher: 74.3%, 55.3%, and 42.2% of patients were persistent at 3, 6, and 12 months, respectively. Initiating mealtime insulin with human insulin was a risk factor for non-persistence by both measures (OR Conclusions Mealtime insulin use and persistence were both considerably lower than expected, and were significantly lower for human insulin compared to analogs.

  6. Could recombinant insulin compounds contribute to adenocarcinoma progression by stimulating local angiogenesis?

    NARCIS (Netherlands)

    Rensing, K.L.; Houttuijn Bloemendaal, F.M.; Weijers, E.M.; Richel, D.J.; Büller, H.R.; Koolwijk, P.; van der Loos, C.M.; Twickler, T.B.; von der Thüsen, J.H.

    2010-01-01

    Negative effects on the progression of adenocarcinomas by hyperinsulinaemia and the insulin analogue glargine (A21Gly,B31Arg,B32Arg human insulin) have recently been suggested. Most actions of this insulin analogue have hitherto been explained by direct stimulation of growth potential of neoplastic

  7. Correlation of presentation of insulin with surface I-Ad and A alpha and A beta mRNA expression by cloned B lymphoma hybridoma variants.

    Science.gov (United States)

    Bernard, N F; Reid, P C; Phillips, M L; Delovitch, T L

    1988-10-01

    We investigated the relationship between Ia expression and antigen presentation in cloned B cells, using variants of TA3 antigen presenting cells. Two TA3 subclones were selected as high presenters and 5 as low presenters of insulin to pork insulin/I-Ad restricted T cells. All TA3 subclones express the surface I-Ak, I-Ek, I-Ad and I-Ed Ia antigens characteristic of the parental cell line. However, surface I-Ad levels correlated best with the ability to present insulin, since high presenters express 2- to 4-fold more I-Ad than low presenters. High presenters possess 2- to 4-times more A alpha and A beta Ia mRNA than low presenters and also transcribe these mRNAs 2- to 5-fold faster than most low presenters. Thus, the correlation noted between I-Ad surface density and capacity to present insulin by our panel of TA3 variants is regulated at the level of transcription and not translation of I-Ad specific mRNAs.

  8. Real-world clinical responses in patients with type 2 diabetes mellitus adding exenatide BID (EBID) or mealtime insulin to basal insulin: a retrospective study using electronic medical record data.

    Science.gov (United States)

    Lang, Kathleen; Nguyen, Hiep; Huang, Huan; Bauer, Elise; Levin, Philip

    2018-02-02

    Exenatide twice daily (EBID) and mealtime insulin are effective add-on therapies to basal insulin for type 2 diabetes patients in clinical trials. This study used electronic medical record (EMR) data to evaluate analogous real-world clinical responses. Adult patients initiating EBID or mealtime insulin as add-on to basal insulin during January 2008 - March 2013 were identified in a U.S. EMR database. EBID patients were propensity score matched 1:1 to mealtime insulin patients. Cohorts were followed for 12 months before (baseline) and 6 months after the index. A1C, hypoglycemic events, change in weight and other clinical measures were evaluated, by A1C attainment level (<6.5, <7, <7.5, <8, <9%) and baseline A1C. 1,249 EBID patients were matched to 1,249 mealtime insulin patients. During follow-up, the percent reaching A1C levels was similar for EBID vs. mealtime insulin cohorts for all attainment levels (<7%: 27.8% vs. 24.2%; <9%: 79.7% vs. 79.2%; p = NS). The percent reaching A1C <7% was similar for both cohorts with different baseline A1C. EBID patients had less hypoglycemia at all attainment levels (3.1% vs. 11.1% [<6.5%]; 2.5% vs. 4.7% [<9%]; all p < 0.03) and more weight loss (-9.0 vs. -3.2 lb [<6.5%]; -3.4 vs. +0.8 lb [<9%]; all p < 0.01). EBID added to basal insulin was as effective in a real-world setting as mealtime insulin added to basal insulin in reducing A1C, with less weight gain and less hypoglycemia for a wide range of A1C attainment levels and baseline values.

  9. Basal insulin or premix analogue therapy in type 2 diabetes patients.

    Science.gov (United States)

    Raskin, Philip R; Hollander, Priscilla A; Lewin, Andrew; Gabbay, Robert A; Bode, Bruce; Garber, Alan J

    2007-01-01

    We sought to compare the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) given twice daily with once-daily insulin glargine in patients with type 2 diabetes beginning insulin therapy and who did not use thiazolidinediones, which are contraindicated with insulin in the European Union, in a subpopulation (N=157) of the INITIATE study. At baseline, HbA(1c) was >/=8.0% on >/=1000 mg/day metformin alone or in combination with other oral antidiabetic drugs (OADs; e.g. sulphonylurea or alpha-glucosidase inhibitors). Metformin was adjusted up to 2550 mg/day and other OADs were discontinued. Starting insulin doses were subsequently adjusted weekly for 26 weeks by algorithm-directed titration. The proportion of patients achieving a HbA(1c) below 7.0% at 28 weeks was greater with BIAsp 30 than with insulin glargine (65% vs 41%, P=0.003). The mean reduction in HbA(1c) was greater for BIAsp 30 than for insulin glargine: -2.89+/-1.6% vs -2.46+/-1.6%, respectively (P=0.035). Postprandial glucose increments were lower for the BIAsp 30 group after breakfast (P=0.003) and dinner (P=0.033); post-lunch values were not significantly different. No major hypoglycemic episodes were recorded. Nocturnal hypoglycemia was reported by 25% of subjects in the BIAsp 30 group and by 10% in the insulin glargine group (P=0.021). Weight gain was 5.6+/-4.6 and 3.0+/-4.3 kg (P=0.0004) for BIAsp 30 and insulin glargine, respectively. BIAsp 30, given twice daily in combination with metformin, was more effective than insulin glargine, given once daily in combination with metformin, at controlling blood glucose in insulin-naïve patients with type 2 diabetes, but was associated with increased weight gain and minor hypoglycemic events.

  10. Consumption of added sugars from liquid but not solid sources predicts impaired glucose homeostasis and insulin resistance among youth at risk of obesity.

    Science.gov (United States)

    Wang, Jiawei; Light, Kelly; Henderson, Mélanie; O'Loughlin, Jennifer; Mathieu, Marie-Eve; Paradis, Gilles; Gray-Donald, Katherine

    2014-01-01

    Little is known about longitudinal associations between added sugar consumption (solid and liquid sources) and glucose-insulin homeostasis among youth. Caucasian children (8-10 y) with at least one obese biological parent were recruited in the QUébec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort (n = 630) and followed-up 2 y later (n = 564). Added sugars were assessed by 3 24-h dietary recalls at baseline. Two-year changes were examined in multivariate linear regression models, adjusting for baseline level, age, sex, Tanner stage, energy intake, fat mass (dual-energy X-ray absorptiometry), and physical activity (7 d accelerometer). Added sugar intake in either liquid or solid sources was not related to changes in adiposity measures (fat mass, body mass index, or waist circumference). However, a higher consumption (10 g/d) of added sugars from liquid sources was associated with 0.04 mmol/L higher fasting glucose, 2.3 pmol/L higher fasting insulin, 0.1 unit higher homeostasis model assessment of insulin resistance (HOMA-IR), and 0.4 unit lower Matsuda-insulin sensitivity index (Matsuda-ISI) in all participants (P sugars from solid sources. Overweight/obese children at baseline had greater increases in adiposity indicators, fasting insulin, and HOMA-IR and decreases in Matsuda-ISI during those 2 y than normal-weight children. Consumption of added sugars from liquid or solid sources was not associated with changes in adiposity, but liquid added sugars were a risk factor for the development of impaired glucose homeostasis and insulin resistance over 2 y among youth at risk of obesity.

  11. Insulin analogues: have they changed insulin treatment and improved glycaemic control?

    DEFF Research Database (Denmark)

    Madsbad, Sten

    2002-01-01

    To improve insulin therapy, new insulin analogues have been developed. Two fast-acting analogues with a more rapid onset of effect and a shorter duration of action combined with a low day-to-day variation in absorption rate are now available. Despite this favourable time-action profile most studi......, the new fast-acting analogues have not achieved the expected commercial success, which emphasises the need for new strategies for basal insulin supplementation, exercise, diet and blood glucose monitoring....... in a long half-life with a residual activity of about 50% 24 h after injection. Insulin glargine is a peakless insulin and studies in both type 1 and type 2 diabetic patients indicate that glargine improves fasting blood glucose control and reduces the incidence of nocturnal hypoglycaemia. Surprisingly...

  12. Use of insulin in type 2 diabetes: what we learned from recent clinical trials on the benefits of early insulin initiation.

    Science.gov (United States)

    Hanefeld, M

    2014-12-01

    The majority of people with type 2 diabetes mellitus (T2DM) require insulin therapy to maintain HbA(1c) levels diabetes, and demonstrated a neutral effect on CV outcomes with long-term use of insulin glargine early in the course of diabetes, with a low rate of severe hypoglycaemia and modest weight gain. The EARLY, GLORY and EASIE studies also demonstrated that insulin use earlier in the treatment pathway led to improved glycaemic control, reduced weight gain and fewer hypoglycaemic episodes than when insulin was added later in the course of disease. The beneficial effect of early transient intensive insulin therapy (TIIT) at diagnosis has been demonstrated in a number of trials; it rapidly limits the damage caused by gluco- and lipotoxicity, improving residual β-cell function and potentially slowing disease progression. The evidence suggests that people newly diagnosed with T2DM and HbA(1c) > 9% should be given early TIIT to achieve normoglycaemia within weeks, after which standard care should then be adopted. Insulin use earlier in the treatment pathway should be considered, as it reduces the risk of hypoglycaemia as well as allows β-cell rest, which can help preserve β-cell function.

  13. Does hypoglycaemia affect the improvement in QoL after the transition to insulin in people with type 2 diabetes?

    NARCIS (Netherlands)

    Wieringa, T. H.; de Wit, M.; Twisk, J. W. R.; Snoek, F. J.

    2018-01-01

    Quality of Life (QoL) of insulin-naïve people with type 2 diabetes mellitus (T2DM) improves after transition to insulin. Little is known about the role of hypoglycaemia in this context. Secondary analyses of the Study of the Psychological Impact in Real care of Initiating insulin glargine Treatment

  14. Transition from intravenous insulin to subcutaneous long-acting insulin in critical care patients on enteral or parenteral nutrition.

    Science.gov (United States)

    Ramos, Analía; Zapata, Lluis; Vera, Paula; Betbese, Antoni J; Pérez, Antonio

    2017-12-01

    The optimal initial dose of subcutaneous (SC) insulin after intravenous (IV) infusion is controversial, especially in patients receiving continuous enteral nutrition (EN) or total parenteral nutrition (TPN). The aim of this study was to evaluate the strategy used at our hospital intensive care unit (ICU) in patients switched from IV insulin to SC insulin glargine while receiving EN or TPN. A retrospective analysis was made of 27 patients on EN and 14 on TPN switched from IV infusion insulin to SC insulin. The initial dose of SC insulin was estimated as 50% of the daily IV insulin requirements, extrapolated from the previous 12h. A corrective dose of short-acting insulin (lispro) was used when necessary. Mean blood glucose (BG) level during SC insulin treatment was 136±35mg/dL in the EN group and 157±37mg/dL in the TPN group (p=0.01). In the TPN group, mean BG was >180mg/dL during the first three days after switching, and a 41% increase in the glargine dose was required to achieve the target BG. In the EN group, mean BG remained <180mg/dL throughout the days of transition and the dose of glargine remained unchanged. In the transition from IV to SC insulin therapy, initial insulin glargine dose estimated as 50% of daily IV insulin requirements is adequate for patients on EN, but inadequate in those given TPN. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Insulin treatment and breast cancer risk; A systematic review of in vitro, animal and epidemiological evidence

    NARCIS (Netherlands)

    Bronsveld, Heleen K.|info:eu-repo/dai/nl/371740819; Ter Braak, Bas; Karlstad, Øystein; Vestergaard, Peter; Starup-Linde, Jakob; Bazelier, Marloes T.|info:eu-repo/dai/nl/341589802; de Bruin, Marieke|info:eu-repo/dai/nl/270270906; De Boer, Anthonius|info:eu-repo/dai/nl/075097346; Siezen, Christine L.E.; Van De Water, Bob; Van Der Laan, Jan Willem; Schmidt, Marjanka K.

    2015-01-01

    Background: In 2009, the concern has been raised that insulin analogues, especially insulin glargine, might increase risk of (breast) cancer. Many in vitro and epidemiological and some animal studies have been performed, but there is still no clarity on this issue. Objectives: The aim of this study

  16. Impact of race/ethnicity on efficacy and safety of two starter insulin regimens in patients with type 2 diabetes : A posthoc analysis of the DURABLE trial

    NARCIS (Netherlands)

    Davidson, Jaime A.; Wolffenbuttel, Bruce H.; Arakaki, Richard F.; Caballero, A. Enrique; Jiang, Honghua H.; Hardin, Dana S.

    2013-01-01

    OBJECTIVE: To explore the impact of race/ethnicity on efficacy and safety of twice-daily insulin lispro mix 75/25 (LM75/25; 75% lispro protamine suspension, 25% insulin lispro) and once daily insulin glargine (GL). DESIGN, SETTING, PATIENTS: More than 2,000 Patients with type 2 diabetes enrolled in

  17. Metformin added to intensive insulin therapy reduces plasma levels of glycated but not oxidized low‑density lipoprotein in young patients with type 1 diabetes and obesity in comparison with insulin alone: a pilot study.

    Science.gov (United States)

    Burchardt, Paweł; Zawada, Agnieszka; Tabaczewski, Piotr; Naskręt, Dariusz; Kaczmarek, Jolanta; Marcinkaniec, Justyna; Wierusz-Wysocka, Bogna; Wysocki, Henryk

    2013-01-01

    There are scarce data about the effect of metformin on lipid profile in patients with type 1 diabetes. The present study is the first prospective clinical trial evaluating the effect of combined therapy of metformin and insulin on the pool of oxidized and glycated low‑density lipoproteins (LDL) in young patients with type 1 diabetes and concomitant obesity. A total of 33 obese patients with type 1 diabetes treated with intensive insulin therapy were randomized into a group where metformin was added. The remaining 19 patients continued to receive intensive insulin therapy (control group). In all patients, lipid profile and glycemia were assessed using routine laboratory tests. Oxidized and glycated LDL were measured using commercially available kits. Laboratory tests were performed at baseline and at a control visit after 6 months of treatment. A significant decrease in the levels of glycated hemoglobin, fasting plasma glucose, postprandial glucose, average glucose, triglycerides, glycated LDL, and body mass index was observed in the group receiving combined therapy. A similar decrease was not observed in the control group. The remaining lipid parameters were not changed during follow‑up in any of the groups. Addition of metformin to intensive insulin therapy in young obese patients with type 1 diabetes results in a significant reduction of glycated LDL levels. This can be possibly explained by better glucose control, which improved insulin sensitivity of the peripheral tissues and reduced body mass in this patient group.

  18. 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.

    Science.gov (United States)

    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 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 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.

  19. [Effect of tongluo xingnao effervescent tablet on learning and memory of AD rats and expression of insulin-degrading enzyme in hippocampus].

    Science.gov (United States)

    Zhang, Yin-Jie; Dai, Yuan; Hu, Yong; Ma, Yun-Tong; Xu, Shi-Jun; Wang, Yong-Yan

    2013-09-01

    To study the effect of Tongluo Xingnao effervescent tablet on learning and memory of dementia rats induced by injection of Abeta25-35 in hippocampus and expression of insulin-degrading enzyme in hippocampus, in order to provide basis for preventing and treating senile dementia. The dementia rat model was established by injecting Abeta25-35 in hippocampus. The rats were divided into the model control group, the Aricept (1.4 mg x kg(-1)) group, and Tongluo Xingnao effervescent tablet high dose (7.56 g x kg(-1)), middle dose (3.78 g x kg(-1)) and low dose (1.59 g x kg(-1)) groups. A sham operation group was established by injecting normal saline in hippocampus. The rats were orally given drugs for 90 days, once a day. Their learning and memory were tested by using Morris water maze. Immunohistochemistry and image analysis were utilized for a quantitative analysis on the expression of insulin-degrading enzyme in hippocampus. Tongluo Xingnao effervescent tablet could significantly shorten the escape latency of rats in the directional navigation test, prolong the retention time in the first quadrant dwell, decrease the retention time in the third quadrant dwell, increase the frequency of crossing the platform, show a more notable statistical significance than the model control group (P hippocampus, promote the expression of insulin-degrading enzyme in hippocampus, and show a more notable statistical significance than the model control group (P learning and memory capacity of AD rats and promoting the expression of insulin-degrading enzyme in hippocampus. Its effect in promoting intelligence will be related to increased insulin-degrading enzyme in hippocampus.

  20. Insulin and Its Cardiovascular Effects: What Is the Current Evidence?

    Science.gov (United States)

    Dongerkery, Sahana Pai; Schroeder, Pamela R; Shomali, Mansur E

    2017-10-23

    In this article, we examine the nature of the complex relationship between insulin and cardiovascular disease. With metabolic abnormalities comes increased risk for cardiovascular complications. We discuss the key factors implicated in development and progression of cardiovascular disease, its relationship to insulin therapy, and what can be learned from large, recent cardiovascular outcome studies. Preclinical studies suggest that insulin has positive effects of facilitating glucose entry into cells and maintaining euglycemia and negative effects of favoring obesity and atherogenesis under certain conditions. Confounding this relationship is that cardiovascular morbidity is linked closely to duration and control of diabetes, and insulin is often used in patients with diabetes of longer duration. However, more recent clinical studies examining the cardiovascular safety of insulin therapy have been reassuring. Diabetes and cardiovascular outcomes are closely linked. Many studies have implicated insulin resistance and hyperinsulinemia as a major factor for poor cardiovascular outcomes. Additional studies link the anabolic effects of therapeutic insulin to weight gain, along with hypoglycemia, which may further aggravate cardiovascular risk in this population. Though good glycemic control has been shown to improve microvascular risks in type 1 and type 2 diabetes, what are the known cardiovascular effects of insulin therapy? The ORIGIN trial suggests at least a neutral effect of the basal insulin glargine on cardiovascular outcomes. Recent studies have demonstrated that ultra-long-acting insulin analogs like insulin degludec are non-inferior to insulin glargine with regard to cardiovascular outcomes.

  1. Treatment with insulin (analogues) and breast cancer risk in diabetics; a systematic review and meta-analysis of in vitro, animal and human evidence

    DEFF Research Database (Denmark)

    Bronsveld, Heleen K; ter Braak, Bas; Karlstad, Øystein

    2015-01-01

    , the pooled analysis of 13 epidemiological studies did not show evidence for an association between insulin glargine treatment and an increased breast cancer risk (HR 1.04; 95 % CI 0.91-1.17; p=0.49) versus no glargine in patients with diabetes mellitus. It has to be taken into account that the number......INTRODUCTION: Several studies have suggested that anti-diabetic insulin analogue treatment might increase cancer risk. The aim of this study was to review the postulated association between insulin and insulin analogue treatment and breast cancer development, and plausible mechanisms. METHOD...... to a limited number of reported estimates, a meta-analysis was performed for glargine only. A comprehensive overview was composed for in vitro and animal studies. Protein and gene expression was analysed for the cell lines most frequently used in the included in vitro studies. RESULTS: In total 16 in vitro, 5...

  2. The HOMA-Adiponectin (HOMA-AD) Closely Mirrors the HOMA-IR Index in the Screening of Insulin Resistance in the Brazilian Metabolic Syndrome Study (BRAMS)

    Science.gov (United States)

    Cassani, Roberta Soares Lara; Forti, Adriana Costa e; Pareja, José Carlos; Tambascia, Marcos Antonio; Geloneze, Bruno

    2016-01-01

    Background The major adverse consequences of obesity are associated with the development of insulin resistance (IR) and adiposopathy. The Homeostasis Model Assessment-Adiponectin (HOMA-AD) was proposed as a modified version of the HOMA1-IR, which incorporates adiponectin in the denominator of the index. Objectives To evaluate the performance of the HOMA-AD index compared with the HOMA1-IR index as a surrogate marker of IR in women, and to establish the cutoff value of the HOMA-AD. Subjects/Methods The Brazilian Metabolic Syndrome Study (BRAMS) is a cross-sectional multicenter survey. The data from 1,061 subjects met the desired criteria: 18–65 years old, BMI: 18.5–49.9 Kg/m² and without diabetes. The IR was assessed by the indexes HOMA1-IR and HOMA-AD (total sample) and by the hyperglycemic clamp (n = 49). Metabolic syndrome was defined using the IDF criteria. Results For the IR assessed by the clamp, the HOMA-AD demonstrated a stronger coefficient of correlation (r = -0.64) compared with the HOMA1-IR (r = -0.56); p 0.05). The optimal cutoff identified for the HOMA-AD for the diagnosis of IR was 0.95. Conclusions The HOMA-AD index was demonstrated to be a useful surrogate marker for detecting IR among adult women and presented a similar performance compared with the HOMA1-IR index. These results may assist physicians and researchers in determining which method to use to evaluate IR in light of the available facilities. PMID:27490249

  3. The Effects of Transition from Bedtime to Morning Glargine Administration in Patients with Poorly Regulated Type 1 Diabetes Mellitus: Croatian Pilot Study.

    Science.gov (United States)

    Gradiser, Marina; Bilic-Curcic, Ines; Djindjic, Boris; Berkovic, Maja Cigrovski

    2015-12-01

    The objective of this study was to compare differences in glucoregulation, frequency of hypoglycemic episodes, glucose variability and lipid profiles of inpatients with poorly regulated type 1 diabetes mellitus (T1DM) after evening versus morning glargine application. Eighteen patients with poorly regulated T1DM, glycated hemoglobin (Hba1c) levels ≥7% and frequent nocturnal and/or morning hypoglycemic episodes were included in this study. There was a 12-week screening phase where patients continued their usual insulin regimen and were encouraged to achieve optimal glycemic control; however, all patients maintained HbA1c values ≥7% and continued to have frequent nocturnal and/or morning hypoglycemic events and were therefore transitioned to morning application of insulin glargine for 12 weeks. The primary outcome was to investigate changes in HbA1c values 12 weeks after the transition. The secondary outcome was to evaluate the effect of transition on glucose variability, incidence of hypoglycemic episodes, insulin doses, lipid profile and weight. Data were analyzed using paired Student's t test and Pearson correlation. After the transition, there was no significant change in total daily dose of basal insulin (p 0.114) and the average body weight remained unchanged, while significant reduction of HbA1c was present (8.02 ± 0.5 vs. 7.4 ± 0.3%) (p weight. These effects were associated with the time of application, but not with the insulin dose.

  4. Effects of Extended-Release Niacin Added to Simvastatin/Ezetimibe on Glucose and Insulin Values in AIM-HIGH.

    Science.gov (United States)

    Goldberg, Ronald B; Bittner, Vera A; Dunbar, Richard L; Fleg, Jerome L; Grunberger, George; Guyton, John R; Leiter, Lawrence A; McBride, Ruth; Robinson, Jennifer G; Simmons, Debra L; Wysham, Carol; Xu, Ping; Boden, William E

    2016-07-01

    Niacin is an antidyslipidemic agent that may cause blood sugar elevation in patients with diabetes, but its effects on glucose and insulin values in nondiabetic statin-treated subjects with cardiovascular disease and at high risk for diabetes are less well known. This was a prespecified, intent-to-treat analysis of the Atherothrombosis Intervention in Metabolic syndrome with low high-density lipoprotein/high triglycerides: Impact on Global Health outcomes trial which randomized 3,414 participants at 92 centers in the US and Canada to extended-release niacin (ERN) plus simvastatin/ezetimibe (ERN) or simvastatin/ezetimibe plus placebo (Placebo). Baseline and annual fasting glucose and insulin values were measured. Those experiencing an adverse event indicative of diabetes or starting medications for diabetes were considered to have confirmed diabetes. In addition, nondiabetic subjects with 2 annual follow-up glucose measurements were categorized into normal, impaired fasting glucose or newly diagnosed diabetes (presumed or confirmed) states. Compared with placebo, ERN increased annual fasting glucose from baseline to 1 year in both those with normal (7.9 ± 15.8 vs 4.3 ± 10.3 mg/dL; P < .001) and impaired fasting glucose (4.1 ± 18.7 vs 1.4 ± 14.9; P < .02) and increased insulin levels. Both effects waned over the next 2 years. There were less consistent effects in those with baseline diabetes. There was an increased risk of progressing from normal to presumed or confirmed impaired fasting glucose (ERN 197/336) cases (58.6%) vs placebo 135/325 cases (41.5%; P < .001) over time, but no difference in diabetes development in the 2 treatment groups except in those with normal fasting glucose at baseline. The addition of ERN to simvastatin/ezetimibe had marginal effects on glycemia in those with diabetes at baseline, and there was a trend toward increased development of new-onset diabetes. In addition, ERN increased the risk of developing impaired fasting glucose, which

  5. Adição de insulina ao meio crioprotetor seminal de garanhões Mangalarga Marchador Adding insulin to frozen seminal extender from Mangalarga Marchador stallions

    Directory of Open Access Journals (Sweden)

    Bruno Fagundes

    2010-02-01

    Full Text Available Objetivou-se verificar o efeito da adição de insulina (0,1; 1 ou 10 UI/mL ao diluente de congelamento convencional por meio de análise computadorizada das características de motilidade espermática (CASA, funcionalidade da membrana plasmática, por meio de choque hiposmótico, e integridade de membrana acrossomal, avaliada pelo teste FITC/PSA. Não houve efeito significativo da adição de 0,1 e 1 UI/mL de insulina na análise imediata após o descongelamento sobre os parâmetros de motilidade e cinemática espermática, porém o nível de 10 UI/mL de insulina promoveu redução desses parâmetros.Success rates in equine sperm cryopreservation are lower than in other domestic species. The objective of this study was to verify the effect of adding 0.1 IU/mL, 1 IU/mL and 10 IU/mL insulin to conventional frozen extender using computerized analysis of sperm motility (CASA, plasma membrane functionality by hypo-osmotic shock and acrossomal membrane integrity through the FITC/PSA assay. No difference was observed in treatment with 0.1 and 1 IU/mL after thawing in the analysis of motility and kinematic sperm parameters. However, when 10 IU/mL insulin was used there was a reduction in these parameters.

  6. Basal insulin analogues in the treatment of diabetes mellitus: What progress have we made?

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2015-01-01

    Full Text Available Over the past few decades, continuous progress has been made in the development of insulin therapy. Basal insulins were developed around 60 years ago. However, existing basal insulins were found to have limitations. An ideal basal insulin should have the following properties viz. longer duration of action, a flat time-action profile, low day-to-day glycaemic variability, and the potential for flexible dosing. Basal insulins have advanced over the years, from lectin and neutral protamine Hagedorn to the currently available insulin degludec. Currently, the focus is on developing a basal insulin that can give coverage for the entire day, with lesser variability and flexible administration. Insulin degludec has been a significant leap in that direction. In addition, U300 insulin glargine and pegylated lispro represent further developments in basal insulin pharmacotherapeutics.

  7. Differences in bioactivity between human insulin and insulin analogues approved for therapeutic use- compilation of reports from the past 20 years

    Directory of Open Access Journals (Sweden)

    Werner Haim

    2011-06-01

    Full Text Available Abstract In order to provide comprehensive information on the differences in bioactivity between human insulin and insulin analogues, published in vitro comparisons of human insulin and the rapid acting analogues insulin lispro (Humalog®, insulin aspart ( NovoRapid®, insulin glulisine (Apidra®, and the slow acting analogues insulin glargine (Lantus®, and insulin detemir (Levemir® were gathered from the past 20 years (except for receptor binding studies. A total of 50 reports were retrieved, with great heterogeneity among study methodology. However, various differences in bioactivity compared to human insulin were obvious (e.g. differences in effects on metabolism, mitogenesis, apoptosis, intracellular signalling, thrombocyte function, protein degradation. Whether or not these differences have clinical bearings (and among which patient populations remains to be determined.

  8. The Mobile Insulin Titration Intervention (MITI) for Insulin Adjustment in an Urban, Low-Income Population: Randomized Controlled Trial.

    Science.gov (United States)

    Levy, Natalie; Moynihan, Victoria; Nilo, Annielyn; Singer, Karyn; Bernik, Lidia S; Etiebet, Mary-Ann; Fang, Yixin; Cho, James; Natarajan, Sundar

    2015-07-17

    Diabetes patients are usually started on a low dose of insulin and their dose is adjusted or "titrated" according to their blood glucose levels. Insulin titration administered through face-to-face visits with a clinician can be time consuming and logistically burdensome for patients, especially those of low socioeconomic status (SES). Given the wide use of mobile phones among this population, there is the potential to use short message service (SMS) text messaging and phone calls to perform insulin titration remotely. The goals of this pilot study were to (1) evaluate if our Mobile Insulin Titration Intervention (MITI) intervention using text messaging and phone calls was effective in helping patients reach their optimal insulin glargine dose within 12 weeks, (2) assess the feasibility of the intervention within our clinic setting and patient population, (3) collect data on the cost savings associated with the intervention, and (4) measure patient satisfaction with the intervention. This was a pilot study evaluating an intervention for patients requiring insulin glargine titration in the outpatient medical clinic of Bellevue Hospital Center in New York City. Patients in the intervention arm received weekday SMS text messages from a health management platform requesting their fasting blood glucose values. The clinic's diabetes nurse educator monitored the texted responses on the platform website each weekday for alarm values. Once a week, the nurse reviewed the glucose values, consulted the MITI titration algorithm, and called patients to adjust their insulin dose. Patients in the usual care arm continued to receive their standard clinic care for insulin titration. The primary outcome was whether a patient reached his/her optimal insulin glargine dose within 12 weeks. A total of 61 patients consented and were randomized into the study. A significantly greater proportion of patients in the intervention arm reached their optimal insulin glargine dose than patients in

  9. Improvement of both fasting and postprandial glycemic control by the two-step addition of miglitol and mitiglinide to basal insulin therapy: a pilot study.

    Science.gov (United States)

    Ihana, Noriko; Tsujimoto, Tetsuro; Yamamoto-Honda, Ritsuko; Kishimoto, Miyako; Kajio, Hiroshi; Noto, Hiroshi; Kakei, Masafumi; Noda, Mitsuhiko

    2014-01-01

    Combination therapy consisting of basal insulin and oral hypoglycemic agents (OHAs) is effective for the treatment of type 2 diabetes (T2DM) that cannot be adequately controlled using OHAs alone. Though basal insulin with metformin or sulfonylurea is an effective therapy, it cannot reduce postprandial glycemia without the risk of hypoglycemia. We examined a two-step regimen consisting of the addition of postprandial hypoglycemic agents (an alpha-glucosidase inhibitor and a glinide) in patients whose T2DM was poorly controlled using basal insulin therapy. Inpatients between the ages of 30-79 years who had T2DM and an HbA1c level of more than 7.0% were recruited. The patients were treated with once-daily insulin glargine with or without metformin, depending on the patient's age and renal function. Insulin glargine was titrated to achieve a target fasting glucose level of 70-130 mg/dL as a first step (STEP0). If the 2-hour postprandial glucose (PBG) level was higher than the target of 180 mg/dL, miglitol treatment (150 mg/day) was initiated, with dose adjustments (75-225 mg) allowed depending on abdominal symptoms and the PBG (STEP1). If the PBG of the patients remained higher than the target after 3 days of treatment, mitiglinide (30 mg/day, titrated up to 60 mg) was added (STEP2). We then evaluated the proportion of patients who achieved the target PBG before and after the two-step regimen. Continuous Glucose Monitoring (CGM) was performed throughout the two-step protocol in most of the patients. Of the 16 patients who were recruited (median age, 67.0 [58.0-71.0] years; body mass index, 25.0 [22.0-27.9] kg/m(2); HbA1c level at admission, 9.1% [8.35-10.4%]), 1 patient (6.25%) achieved the target PBG at STEP 0 and 14 patients (87.5%) had achieved the target PBG at the end of the treatment protocol (P = 0.002). CGM showed a significant decrease in the glucose level at each step of the protocol. The standard deviations in the CGM glucose levels for 24

  10. Replacement of Refined Starches and Added Sugars with Egg Protein and Unsaturated Fats Increases Insulin Sensitivity and Lowers Triglycerides in Overweight or Obese Adults with Elevated Triglycerides.

    Science.gov (United States)

    Maki, Kevin C; Palacios, Orsolya M; Lindner, Emily; Nieman, Kristin M; Bell, Marjorie; Sorce, Jennifer

    2017-07-01

    Background: Hypertriglyceridemia is a common condition in the United States and is often associated with other metabolic disturbances, including insulin resistance, metabolic syndrome, and a predominance of small dense LDL particles. Objective: The objective of this trial was to evaluate the effects of a combination of egg protein (Epro) and unsaturated fatty acids (UFAs) substituted for refined starches and added sugars on insulin sensitivity (primary outcome) and other cardiometabolic health markers in overweight or obese adults with elevated triglyceride (TG) concentrations. Methods: Subjects with elevated TG concentrations were given test foods prepared by using Epro powder (∼8% of energy) and vegetable oil (∼8% of energy; Epro and UFA condition) or test foods prepared by using refined starch and sugar (∼16% of energy; carbohydrate condition) in a randomized, double-blind, controlled-feeding, crossover trial (3 wk/condition, 2-wk washout). The Matsuda insulin sensitivity index (MISI), fasting lipids, and other cardiometabolic health markers were assessed at baseline and the end of each diet condition. Responses were compared by using repeated-measures ANCOVA. Results: Twenty-five participants [11 men, 14 women; mean ± SEM: age, 46.3 ± 2.4 y; body mass index (in kg/m 2 ), 31.8 ± 1.0] with a median (interquartile range limits) fasting serum TG concentration of 173 mg/dL (159, 228 mg/dL) completed the trial. The MISI value increased 18.1% ± 8.7% from baseline during the Epro and UFA condition and decreased 5.7% ± 6.2% from baseline during the carbohydrate condition ( P < 0.001). The disposition index increased 23.8% ± 20.8% during the Epro and UFA condition compared with a decrease of 16.3% ± 18.8% during carbohydrate ( P = 0.042) and LDL peak particle size increased 0.12 nm (-0.12, 0.28 nm) with Epro and UFA compared with a decrease of 0.15 nm (-0.33, 0.12 nm) with carbohydrate ( P = 0.019). TG and VLDL cholesterol concentrations were lowered by 18

  11. Dgroup: DG01801 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Insulin lispro (USP/INN); Insulin lispro (genetical recombination) (JAN) ... D04475 ... Insulin aspart (USAN/INN); Insulin aspart (genet...ical recombination) (JAN) ... D04540 ... Insulin glulisine (USAN/INN); Insulin glulisine (genetica...250 ... Insulin glargine (USAN/INN); Insulin glargine (genetical recombination) (JP17); Insulin glargine (genetica...l recombination) injection (JP17); Insulin glargine (genetical recombination [Insulin glargin biosimilar ...1] (JAN); Insulin glargine (genetical recombination) [Insulin glargin biosimilar

  12. Cancer risk among insulin users

    DEFF Research Database (Denmark)

    But, Anna; De Bruin, Marie L.; Bazelier, Marloes T.

    2017-01-01

    AIMS/HYPOTHESIS: The aim of this work was to investigate the relationship between use of certain insulins and risk for cancer, when addressing the limitations and biases involved in previous studies. METHODS: National Health Registries from Denmark (1996-2010), Finland (1996-2011), Norway (2005......-2010) and Sweden (2007-2012) and the UK Clinical Practice Research Datalink database (1987-2013) were used to conduct a cohort study on new insulin users (N = 327,112). By using a common data model and semi-aggregate approach, we pooled individual-level records from five cohorts and applied Poisson regression...... models. For each of ten cancer sites studied, we estimated the rate ratios (RRs) by duration (≤0.5, 0.5-1, 1-2, 2-3, 3-4, 4-5, 5-6 and >6 years) of cumulative exposure to insulin glargine or insulin detemir relative to that of human insulin. RESULTS: A total of 21,390 cancer cases occurred during a mean...

  13. Update on insulin treatment for dogs and cats: insulin dosing pens and more

    Directory of Open Access Journals (Sweden)

    Thompson A

    2015-04-01

    Full Text Available Ann Thompson,1 Patty Lathan,2 Linda Fleeman3 1School of Veterinary Science, The University of Queensland, Gatton, QLD, Australia; 2College of Veterinary Medicine Mississippi State University, Starkville, MS, USA; 3Animal Diabetes Australia, Melbourne, VIC, Australia Abstract: Insulin therapy is still the primary therapy for all diabetic dogs and cats. Several insulin options are available for each species, including veterinary registered products and human insulin preparations. The insulin chosen depends on the individual patient's requirements. Intermediate-acting insulin is usually the first choice for dogs, and longer-acting insulin is the first choice for cats. Once the insulin type is chosen, the best method of insulin administration should be considered. Traditionally, insulin vials and syringes have been used, but insulin pen devices have recently entered the veterinary market. Pens have different handling requirements when compared with standard insulin vials including: storage out of the refrigerator for some insulin preparations once pen cartridges are in use; priming of the pen to ensure a full dose of insulin is administered; and holding the pen device in place for several seconds during the injection. Many different types of pen devices are available, with features such as half-unit dosing, large dials for visually impaired people, and memory that can display the last time and dose of insulin administered. Insulin pens come in both reusable and disposable options. Pens have several benefits over syringes, including improved dose accuracy, especially for low insulin doses. Keywords: diabetes, mellitus, canine, feline, NPH, glargine, porcine lente

  14. Adding once-daily lixisenatide for type 2 diabetes inadequately controlled by established basal insulin: a 24-week, randomized, placebo-controlled comparison (GetGoal-L)

    National Research Council Canada - National Science Library

    Riddle, Matthew C; Aronson, Ronnie; Home, Philip; Marre, Michel; Niemoeller, Elisabeth; Miossec, Patrick; Ping, Lin; Ye, Jenny; Rosenstock, Julio

    2013-01-01

    ...). We conducted a double-blind, parallel-group, placebo-controlled trial. Patients (n = 495) with established basal insulin therapy but inadequate glycemic control were randomized to add lixisenatide 20 μ...

  15. Cost-effectiveness of insulin analogs from the perspective of the Brazilian public health system

    Directory of Open Access Journals (Sweden)

    Maurílio de Souza Cazarim

    2017-11-01

    Full Text Available ABSTRACT Human insulin is provided by the Brazilian Public Health System (BPHS for the treatment of diabetes, however, legal proceedings to acquire insulin analogs have burdened the BPHS health system. The aim of this study was to perform a cost-effectiveness analysis to compare insulin analogs and human insulins. This is a pharmacoeconomic study of cost-effectiveness. The direct medical cost related to insulin extracted from the Ministry of Health drug price list was considered. The clinical results, i.e. reduction in glycated hemoglobin (HbA1c, were extracted by meta-analysis. Different scenarios were structured to measure the uncertainties regarding the costs and reduction in HbA1c. Decision tree was developed for sensitivity of Incremental Cost Effectiveness Ratio (ICER. A total of fifteen scenarios were structured. Given the best-case scenario for the insulin analogs, the insulins aspart, lispro, glargine and detemir showed an ICER of R$ 1,768.59; R$ 3,308.54; R$ 11,718.75 and R$ 2,685.22, respectively. In all scenarios in which the minimum effectiveness was proposed, lispro, glargine and detemir were dominant strategies. Sensitivity analysis showed that the aspart had R$ 3,066.98 [95 % CI: 2339.22; 4418.53] and detemir had R$ 6,163.97 [95% CI: 3919.29; 11401.57] for incremental costs. We concluded there was evidence that the insulin aspart is the most cost-effective.

  16. Special considerations with insulin therapy in older adults with diabetes mellitus.

    Science.gov (United States)

    Mooradian, Arshag D

    2011-06-01

    Aging is associated with alterations in insulin secretion and action. However, aging per se does not alter the pharmacokinetics of commercially available insulin and its analogues. Insulin therapy in older adults is complicated by psychosocial and physiological changes of aging. Several new insulin and insulin analogue preparations are now available for clinical use. Used as prandial (e.g. insulin lispro, insulin aspart or insulin glulisine) and basal insulin (e.g. insulin glargine, insulin detemir), these analogues simulate physiological insulin profiles more closely than the older conventional insulins. The availability of multiple insulin products provides new opportunities to achieve control of diabetes mellitus. The choice of initial insulin therapy can be made based on blood glucose profiles. Overall, these profiles can be divided into three general patterns that include: (i) round-the-clock hyperglycaemia; (ii) fasting hyperglycaemia with daytime euglycaemia; and (iii) daytime hyperglycaemia with normal fasting blood glucose levels. The prescription of insulin is a dynamic process, and the insulin regimen should be adjusted based on individual response. The goal of diabetes care in older adults is to enhance quality of life without subjecting individuals to complicated treatment regimens that may interfere with their independence in carrying out daily activities.

  17. Insulin Resistance in Alzheimer's Disease

    Science.gov (United States)

    Dineley, Kelly T; Jahrling, Jordan B; Denner, Larry

    2014-01-01

    Insulin is a key hormone regulating metabolism. Insulin binding to cell surface insulin receptors engages many signaling intermediates operating in parallel and in series to control glucose, energy, and lipids while also regulating mitogenesis and development. Perturbations in the function of any of these intermediates, which occur in a variety of diseases, cause reduced sensitivity to insulin and insulin resistance with consequent metabolic dysfunction. Chronic inflammation ensues which exacerbates compromised metabolic homeostasis. Since insulin has a key role in learning and memory as well as directly regulating ERK, a kinase required for the type of learning and memory compromised in early Alzheimer's disease (AD), insulin resistance has been identified as a major risk factor for the onset of AD. Animal models of AD or insulin resistance or both demonstrate that AD pathology and impaired insulin signaling form a reciprocal relationship. Of note are human and animal model studies geared toward improving insulin resistance that have led to the identification of the nuclear receptor and transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) as an intervention tool for early AD. Strategic targeting of alternate nodes within the insulin signaling network has revealed disease-stage therapeutic windows in animal models that coalesce with previous and ongoing clinical trial approaches. Thus, exploiting the connection between insulin resistance and AD provides powerful opportunities to delineate therapeutic interventions that slow or block the pathogenesis of AD. PMID:25237037

  18. Effect of metformin added to insulin on glycemic control among overweight/obese adolescents with type 1 diabetes: A randomized clinical trial

    Science.gov (United States)

    Previous studies assessing the effect of metformin on glycemic control in adolescents with type 1 diabetes have produced inconclusive results. To assess the efficacy and safety of metformin as an adjunct to insulin in treating overweight adolescents with type 1 diabetes. Multicenter (26 pediatric en...

  19. Insulin analogues versus human insulin in type 1 diabetes: direct and indirect meta-analyses of efficacy and safety

    Directory of Open Access Journals (Sweden)

    Andréia Cristina Conegero Sanches

    2013-09-01

    Full Text Available All patients with Diabetes Mellitus (DM receive insulin therapy. In this study, we evaluated the efficacy, safety and tolerability of human insulin and insulin analogues. We performed a systematic review of the literature and a meta-analysis according to the Cochrane Collaboration methodology. In the absence of clinical studies comparing insulins, we performed a mixed treatment comparison to establish the differences between the active treatments. We included studies published from 1995 to 2010. HbA1c results, episodes of hypoglycemia and nocturnal hypoglycemia data were extracted and analyzed. Thirty-five randomized clinical trials were selected after examining the abstract and a full text review. These studies included 4,206 patients who received long-acting insulin analogues and 5,733 patients who received short-acting insulin analogues. Pooled data regarding efficacy indicated no significant differences in HbA1c values between glargine or detemir (once daily and NPH insulin. However, a twice-daily dose of detemir produced differences in HbA1c values that favored detemir (-0.14% [95% CI: -0.21 to -0.08]; p<0.0001; I²=0%. Direct and indirect comparisons are consistent and show that there were no significant differences between human insulin and insulin analogues in efficacy or safety. Our results indicate that long- and short-acting insulin analogues offer few clinical advantages over conventional human insulin.

  20. INFLUENCE OF BETA-BLOCKERS ON INSULIN RESISTANCE IN PATIEN TS WITH DIABETES MELLITUS TYPE 2

    Directory of Open Access Journals (Sweden)

    Nataša Đinđić

    2011-12-01

    Full Text Available The insulin resistance is present when the concentration of insulin is normal and biological response is decreased. The most frequent metabolic change that was detected during anti-hypertension therapy is a change in the insulin resistance. Beta-blockers are generally accompanied by the deterioration of metabolic control in patients with diabetes. It is considered that using certain beta-blockers in hypertension therapy in patients with diabetes mellitus type 2 (DM type 2 can significantly influence the insulin resistance. Taking into consideration the latest knowledge on pharmaco-dynamics of insulin analogues and beta -blockers, by observing the parameters of glycoregulation, it would be of great interest and practical significance to determine the following influence of beta - blockers and their selectivity on the insulin resistance in patients with DM type 2 and hypertension. The research was conducted at the Endocrinology Clinic of the Clinical Centre Niš, and it included 60 patients with diagnosed diabetes mellitus type 2. After collecting anamnesis data, clinical and laboratory research performance, all patients were divided into two therapy groups: first group, 30 patients that were administered the therapy based on insulin glargine and second group, 30 patients that were administered the therapy based on insulin glargine and blocker divided into two therapy subgroups: 15 patients that were administered the therapy based on insulin glargine and carvedilol and 15 patients that were administered the therapy based on insulin glargine and metoprolol. Higher values of glycaemia and glycolised haemoglobin were found in patients receiving therapy based on beta–blocker (p<0.05. Therapy group treated with metoprolol had higher average values of glycaemia and HbA1C, compared to the group treated with carvedilol. The obtained difference was not statistically significant. Is confirmed that the group of patients to which beta–blockers had been

  1. Insulin Secretagogues

    Science.gov (United States)

    ... the Spikes Is mealtime insulin right for you? Insulin Secretagogues September 2017 Download PDFs English Espanol Editors ... Additional Resources Affordable Insulin Project FDA What are insulin secretagogues? Insulin secretagogues are one type of medicine ...

  2. A retrospective review of insulin requirements in patients using U-500 insulin hospitalized to a Veterans Affairs Hospital.

    Science.gov (United States)

    Kedia, Rohit; Desouza, Cyrus; Smith, Lynette M; Shivaswamy, Vijay

    2017-05-01

    The aim of this study was to compare the changes in the total daily dose (TDD) of insulin of patients on U-500 insulin; before hospitalization, during hospitalization and six weeks after discharge. A retrospective chart review of veterans with type 2 diabetes receiving U-500 insulin in the ambulatory setting and who were admitted between 2012 and 2015 was performed. During hospitalization, patients were transitioned to receive U-100 insulin (detemir or glargine for basal and aspart for bolus). Paired t-tests were conducted to compare TDD of insulin during hospitalization to prior to admission and at six week of follow-up. The average hemoglobin A1c at the time of hospital admission was 8.3±1.5% (n=20). The average TDD of insulin during hospitalization (124±67units) was significantly less than prior to admission (295±123units) and at six week follow-up (310±105units). The average glucose during hospitalization was 180±36mg/dL. Hypoglycemia was less than 0.5%. We showed that patients received significantly less total daily insulin while hospitalized compared to their insulin doses in the ambulatory setting, and we demonstrate that patients receiving U-500 insulin can be safely transitioned to U-100 insulin while hospitalized, with minimal hypoglycemia. Published by Elsevier Inc.

  3. Insulin and Insulin Resistance

    Science.gov (United States)

    2005-01-01

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

  4. Use of Insulin Analogues in Children and Adolescents: Topical Issues and Possibilities for Achieving Optimal Type 1 Diabetes Mellitus Compensation

    Directory of Open Access Journals (Sweden)

    О.A. Budreyko

    2013-02-01

    Full Text Available The review contains an analysis of the data of numerous scientific studies on the results of use of insulin analogues in comprehensive treatment of type 1 diabetes mellitus in children and adolescents. Problem of mitogenic potential of insulin preparations and ways to prevent its realization in clinical practice is discussed. Advisability of the use of insulin analogues glulisine and glargine in children and adolescents is substantiated for achievement of optimal compensation of carbohydrate metabolism due to their high efficiency and adequate level of safety, confirmed by the regulations of international consensuses (ISPAD and IDF.

  5. Biological effects of insulin and its analogs on cancer cells with different insulin family receptor expression.

    Science.gov (United States)

    Sciacca, Laura; Cassarino, Maria Francesca; Genua, Marco; Vigneri, Paolo; Giovanna Pennisi, Maria; Malandrino, Pasqualino; Squatrito, Sebastiano; Pezzino, Vincenzo; Vigneri, Riccardo

    2014-11-01

    Hyperinsulinemia is a likely cause of the increased cancer incidence and mortality in diabetic patients, but its role is difficult to define in vivo. Previous in vitro studies testing the mitogenic potential of insulin and its analogs provided incomplete and sometimes contradictory results. To better evaluate cancer cell responsiveness to insulin, to its analogs and to IGF-I, we measured under identical experimental conditions cell proliferation, invasiveness, and foci formation in six cancer cell lines with different insulin receptor family expression levels. The cancer cells studied have a different expression of insulin receptor (IR), its isoforms (IR-A and IR-B), and of the IGF-I receptor. The data indicate that insulin stimulates proliferation in all cancer cell lines, invasiveness in some, and foci formation in none. Cancer cell responses to insulin (and IGF-I) are not related to receptor expression levels; moreover, hormone-stimulated proliferation and invasiveness are not correlated. IGF-I is a more potent stimulator than insulin in most but not all cancer cell lines. Insulin analogs including M1 and M2 Glargine metabolites stimulate cancer cells similar to insulin. However, exceptions occur for specific analogs in particular cancer cells. In conclusion, in vitro insulin is an effective growth factor for all cancer cells but the biological response to insulin cannot be predicted on the basis of receptor expression levels. In the clinical setting, these observations should be taken in account when deciding treatment for diabetic patients who are at risk of undiscovered cancer or survivors of oncological diseases. © 2014 Wiley Periodicals, Inc.

  6. Insulin Basics

    Science.gov (United States)

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

  7. Intensification of IDegAsp Twice Daily (Adding Insulin Aspart vs. Switching To Basal-Bolus): Exploratory Randomized Trial in Type 2 Diabetes.

    Science.gov (United States)

    Bebakar, Wan Mohamaed Wan; Chaykin, Louis; Hersløv, Malene Lundgren; Rasmussen, Søren

    2017-02-01

    In a preceding trial comparing two different titration schemes, insulin degludec/insulin aspart (IDegAsp) showed good efficacy for achieving HbA1c TID). A 26-week, randomized, open-label, phase 3b, treat-to-target trial in which 40 patients with T2D who had not reached target HbA1c ≤7.0% following previous 26-week treatment intensification with IDegAsp BID ±3 oral antidiabetic agents (OADs) were randomized (1:1) to receive IDegAsp BID + IAsp OD (n = 20) or IDeg OD + IAsp TID (n = 20). Mean baseline HbA1c was 7.9% in the IDegAsp BID + IAsp OD group and 7.7% in the IDeg OD + IAsp TID group. After 26 weeks, the estimated mean change in HbA1c from baseline was 0.05% points in the IDegAsp BID + IAsp OD group and -0.49% points for IDeg OD + IAsp TID: estimated treatment difference (ETD) [95% confidence interval] 0.54% [0.09; 0.99], p = 0.021. Few achieved HbA1c TID groups (five patients). Fasting plasma glucose, hypoglycemia, and adverse events were similar between groups. When used as intensification regimens in patients who failed to achieve target HbA1c during 26-week IDegAsp BID treatment, HbA1c improvements were numerically greater with IDeg OD + IAsp TID compared with IDegAsp BID + IAsp OD. No new safety issues were identified. However, the small, selective sample means clinical generalizations should be made with caution. Novo Nordisk. CLINICALTRIALS. NCT01814137.

  8. Insulin-like growth factor I and glucagon-like peptide-2 responses to fasting followed by controlled or ad libitum refeeding in rats

    DEFF Research Database (Denmark)

    Nelson, David W; Murali, Sangita G; Liu, Xiaowen

    2008-01-01

    for 48 h and then refed for 2 or 4 days by continuous intravenous or intragastric infusion or ad libitum feeding. Fasting induced significant decreases in body weight, plasma concentrations of IGF-I and bioactive GLP-2, jejunal mucosal cellularity (mass, protein, DNA, and villus height), IGF-I m...

  9. Review of biphasic insulin aspart in the treatment of type 1 and 2 diabetes

    Directory of Open Access Journals (Sweden)

    Nazia Raja-Khan

    2008-01-01

    Full Text Available Nazia Raja-Khan, Sarah S Warehime, Robert A GabbayDivision of Endocrinology, Diabetes, and Metabolism, Penn State Institute for Diabetes and Obesity, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USABackground: Insulin is an effective treatment for achieving glycemic control and preventing complications in patients with diabetes. In order to make insulin therapy more acceptable to patients, newer formulations of insulin have been developed, such as biphasic insulins. Biphasic insulins conveniently provide both prandial and basal insulin in a single injection. One of the most well-studied biphasic insulins is biphasic insulin aspart 70/30.Objective: Our goal was to review the current literature on the safety and efficacy of biphasic insulin aspart in type 1 and type 2 diabetes.Methods: A MEDLINE search was conducted using the terms “biphasic insulin aspart” to identify clinical studies and reviews.Results: Biphasic insulin aspart more effectively reduces post-prandial glucose compared to other biphasic insulins and basal insulins. Compared to biphasic insulin aspart, fasting glucose levels are lower with NPH, similar with glargine, and similar or lower with biphasic human insulin. Treat-to-target trials have shown that a goal HbA1c below 6.5 or 7% can be achieved with biphasic insulin aspart. The risk of hypoglycemia is similar to or less than that seen with other biphasic insulins or NPH insulin.Conclusion: Biphasic insulin aspart 70/30 is a safe and effective treatment option for patients with diabetes.Keywords: biphasic insulin aspart, insulin, diabetes

  10. Long-acting Insulin Analogs Effect on gh/igf Axis of Children with Type 1 Diabetes: a Randomized, Open-label, Two-period, Cross-over Trial.

    Science.gov (United States)

    Cherubini, V; Pintaudi, B; Iannilli, A; Pambianchi, M; Ferrito, L; Nicolucci, A

    2016-05-01

    Growth hormone (GH) secretion is increased in pre-pubertal children with type 1 diabetes and GH excess produces insulin resistance. Early-morning insulinopenia contributes to lower insulin-like growth factor (IGF-I) levels and to GH hypersecretion. To evaluate differences in GH/IGF-I axis of pre-pubertal children with type 1 diabetes treated with glargine or detemir as long-acting insulin analogues, which was the main outcome measure, and to compare insulin effects in obtaining good metabolic control. Children with type 1 diabetes. This was a 32-week, randomized, open-label, two-period, cross-over comparison between bedtime glargine and twice-daily detemir insulin, involving pre-pubertal children in care at a diabetes pediatric centre. After a 8-week-run-in period subjects were randomized to bedtime glargine or twice-daily detemir insulin administration. After a 12-week period treatments were inverted and continued for additional 12 weeks. Overall, 15 pre-pubertal children (53.3% males, mean age 8.6±1.5 years, duration of diabetes 4.2±1.5 years) completed the study. Groups did not differ for GH/IGF axis and HbA1c levels. Treatment with glargine was associated with lower fasting glucose values than treatment with detemir (8.1±1.5 vs. 8.2±1.7 mmol/L, p=0.01). Incidence rate of hypoglycemia was not different between insulin treatments (IRR=1.18, 95%CI 1.00-1.38; p=0.07). Detemir treatment was associated with a higher increase in body weight (p=0.008) and height (p=0.02) when compared with glargine. Detemir and glargine not show significant differential effects on the GH/IGFI axis. The greater weight gain and height associated with detemir treatment, apparently not related to the level of pubertal growth, deserve further investigation. © Georg Thieme Verlag KG Stuttgart · New York.

  11. Glucagon-like peptide-1 receptor agonists as add-on therapy to basal insulin in patients with type 2 diabetes: a systematic review

    Directory of Open Access Journals (Sweden)

    Berlie H

    2012-07-01

    Full Text Available Helen Berlie, Kathryn M Hurren, Nicole R PinelliEugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI, USAAbstract: The prevalence of obesity and diabetes continues to rise in the US. Glucagon-like peptide-1 receptor agonist (GLP-1RA is an effective treatment option for type 2 diabetes mellitus (T2DM that promotes weight loss. Common and effective treatment options added to metformin therapy (basal insulin, sulfonylureas, and pioglitazone contribute to weight gain, which makes the addition of GLP-1RAs advantageous. Exenatide was the first agent in this class and has recently been approved for use in combination with insulin glargine by the US Food and Drug Administration and the European Medicines Agency. Until recently, there was a lack of data examining basal insulin combined with these agents. The main purpose of this article is to review the prospective interventional data on the safety and efficacy of GLP-1RAs (exenatide, liraglutide, albiglutide, lixisenatide combined with basal insulin therapy in nonpregnant adults with T2DM. Databases searched were PubMed, Cochrane Central Register of Controlled Trials and the Database of Systematic Reviews (inception to January 2012. Abstracts presented at relevant diabetes and endocrine meetings from 2009 to 2011 were also reviewed, as were reference lists of identified publications. A total of five studies met the criteria and were included in the review. Data from these studies demonstrated that this combination therapy offers advantages for the treatment of diabetes, such as additional lowering of A1c without major risk for hypoglycemia, lower basal insulin requirements, decreased postprandial glucose levels (with or without fasting plasma glucose decreases, and weight loss, or at the very least, less weight gain. However, the gastrointestinal side effects and high cost of these agents may limit their use. This review demonstrates that adding a GLP-1RA to an

  12. Influence of the dynamics of body weight on the risk factors of cardiovascular disease in patients with type 2 diabetes during the first year of insulin treatment

    Directory of Open Access Journals (Sweden)

    T S Dzhavakhishvili

    2013-03-01

    Full Text Available The aim of the present study was to investigate whether insulin treatment-induced weight gain had an adverse impact on cardiovascular risk factors in insulin-treated type 2 diabetic patients during the first year after initiating insulin therapy when insulin analogues or human insulins are used. A total of 157 patients with newly insulinized type 2 diabetes were included in the study. The patients were divided in two groups. First group consisted of subjects (mean age 57 [45; 73], duration of diabetes of 10 years [4; 16] who had received long-acting basal (glargine, detemir, premixed (biphasic insulin aspart 30, Humalog Mix 25 or short-acting (aspart, lispro insulin analogues. Patients from second group (mean age 59 [46; 75], duration of diabetes of 10 years [5; 15] were treated with intermediate-acting basal (Protophane, Humulin NPH insulin, premixed (biphasic human insulin 30, Humulin M3 and regular (Actrapid, Humulin R human insulins. Our study has shown that insulin-induced weight gain may not adversely affect cardiovascular risk factors, particularly, lipid profile, in insulin-treated type 2 diabetic patients during the first year after initiating insulin therapy. Use of insulin analogues for treatment of type 2 diabetes patients results in better glycaemic control, significant declines in blood lipid concentrations, less increase in waist circumference compared with human insulins during the first year after initiating insulin therapy.

  13. Incorporating a Generic Model of Subcutaneous Insulin Absorption into the AIDA v4 Diabetes Simulator 3. Early Plasma Insulin Determinations

    Science.gov (United States)

    Lehmann, Eldon D.; Tarín, Cristina; Bondia, Jorge; Teufel, Edgar; Deutsch, Tibor

    2009-01-01

    Introduction AIDA is an interactive educational diabetes simulator that has been available without charge via the Internet for over 12 years. Recent articles have described the incorporation of a novel generic model of insulin absorption into AIDA as a way of enhancing its capabilities. The basic model components to be integrated have been overviewed, with the aim being to provide simulations of regimens utilizing insulin analogues, as well as insulin doses greater than 40 IU (the current upper limit within the latest release of AIDA [v4.3a]). Some preliminary calculated insulin absorption results have also recently been described. Methods This article presents the first simulated plasma insulin profiles from the integration of the generic subcutaneous insulin absorption model, and the currently implemented model in AIDA for insulin disposition. Insulin absorption has been described by the physiologically based model of Tarín and colleagues. A single compartment modeling approach has been used to specify how absorbed insulin is distributed in, and eliminated from, the human body. To enable a numerical solution of the absorption model, a spherical subcutaneous depot for the injected insulin dose has been assumed and spatially discretized into shell compartments with homogeneous concentrations, having as its center the injection site. The number of these compartments will depend on the dose and type of insulin. Insulin inflow arises as the sum of contributions to the different shells. For this report the first bench testing of plasma insulin determinations has been done. Results Simulated plasma insulin profiles are provided for currently available insulin preparations, including a rapidly acting insulin analogue (e.g., lispro/Humalog or aspart/Novolog), a short-acting (regular) insulin preparation (e.g., Actrapid), intermediate-acting insulins (both Semilente and neutral protamine Hagedorn types), and a very long-acting insulin analogue (e.g., glargine/Lantus), as

  14. Cost-effectiveness of intermediate or long-acting insulin versus Exenatide in type 2 diabetes mellitus patients not optimally controlled on dual oral diabetes medications

    Directory of Open Access Journals (Sweden)

    Edwards KL

    2006-09-01

    Full Text Available Objective: To better understand exenatide’s role in the treatment of type 2 diabetes, this analysis assessed its cost-effectiveness in comparison to an intermediate (NPH and long-acting insulin (glargine. Exenatide is a recently approved medication for the treatment of type 2 diabetes for use in addition to frequently used oral diabetes medications. Methods: Two studies were identified by a Medline search (1996-Oct 2005 that were similar in study duration, baseline glycemic control, population size, and primary outcomes to appropriately assess the cost-effectiveness of either insulin in comparison to exenatide on both glycemic and weight control. Results: Both NPH and glargine appear to be more cost effective than exenatide with respect to glycemic control (incremental CE ratios -1,968 and -65,520 respectively. Exenatide appears to be more cost effective for reductions in body weight than either NPH (CE ratio 235 or glargine (CE ratio 128. Conclusions Compared to intermediate and long-acting insulin therapies, exenatide does not appear to be as cost effective for the treatment of type 2 diabetes.

  15. Insulin Therapy

    Science.gov (United States)

    ... Your Health Resources Drugs, Procedures & Devices Prescription Medicines Insulin Therapy Insulin Therapy Share Print When you digest food, your ... you eat into glucose (a form of sugar). Insulin allows this glucose to enter all the cells ...

  16. Comparative efficacy and safety of antidiabetic drug regimens added to metformin monotherapy in patients with type 2 diabetes: a network meta-analysis.

    Directory of Open Access Journals (Sweden)

    Elizabeth S Mearns

    Full Text Available When first line therapy with metformin is insufficient for patients with type 2 diabetes (T2D, the optimal adjunctive therapy is unclear. We assessed the efficacy and safety of adjunctive antidiabetic agents in patients with inadequately controlled T2D on metformin alone.A search of MEDLINE and CENTRAL, clinicaltrials.gov, regulatory websites was performed. We included randomized controlled trials of 3-12 months duration, evaluating Food and Drug Administration or European Union approved agents (noninsulin and long acting, once daily basal insulins in patients experiencing inadequate glycemic control with metformin monotherapy (≥ 1500 mg daily or maximally tolerated dose for ≥ 4 weeks. Random-effects network meta-analyses were used to compare the weighted mean difference for changes from baseline in HbA1c, body weight (BW and systolic blood pressure (SBP, and the risk of developing hypoglycemia, urinary (UTI and genital tract infection (GTI.Sixty-two trials evaluating 25 agents were included. All agents significantly reduced HbA1c vs. placebo; albeit not to the same extent (range, 0.43% for miglitol to 1.29% for glibenclamide. Glargine, sulfonylureas (SUs and nateglinide were associated with increased hypoglycemia risk vs. placebo (range, 4.00-11.67. Sodium glucose cotransporter-2 (SGLT2 inhibitors, glucagon-like peptide-1 analogs, miglitol and empagliflozin/linagliptin significantly reduced BW (range, 1.15-2.26 kg whereas SUs, thiazolindinediones, glargine and alogliptin/pioglitazone caused weight gain (range, 1.19-2.44 kg. SGLT2 inhibitors, empagliflozin/linagliptin, liraglutide and sitagliptin decreased SBP (range, 1.88-5.43 mmHg. No therapy increased UTI risk vs. placebo; however, SGLT2 inhibitors were associated with an increased risk of GTI (range, 2.16-8.03.Adding different AHAs to metformin was associated with varying effects on HbA1c, BW, SBP, hypoglycemia, UTI and GTI which should impact clinician choice when selecting adjunctive

  17. Degludec: the new ultra-long insulin analogue.

    Science.gov (United States)

    Tambascia, Marcos Antonio; Eliaschewitz, Freddy Goldberg

    2015-01-01

    The development of extended-action insulin analogues was motivated by the unfavorable pharmacokinetic (PK) profile of the conventional long-acting insulin formulations, generally associated with marked inter and intra patient variability and site- and dose-dependent effect variation. The new ultra-long insulin analogue degludec (IDeg) has the same amino acid sequence as human insulin except for the removal of threonine in the position 30 of the B chain (Des-B30, "De") and the attachment, via a glutamic acid linker ("glu"), of a 16-carbon fatty diacid (hexadecanoic diacid, "dec") to lysine in the position 29 of the B chain. These modifications allow that, after changing from the pharmaceutical formulation to the subcutaneous environment, IDeg precipitates in the subcutaneous tissue, forming a depot that undergoes a highly predictable gradual dissociation. Thus, once-daily dosing of IDeg results in a low peak: trough ratio, with consequent low intra-individual variability and plasmatic concentrations less critically dependent upon the time of injections. The clinical development program of IDeg (BEGIN) was comprised of 9 therapeutic confirmatory trials of longer duration (26-52 weeks) and showed that the efficacy of IDeg is comparable to insulin glargine in type 1 (T1D) and type 2 (T2D) diabetes patients across different age, body mass index and ethnic groups. This new ultra-long insulin analogue presents as advantages flexibility in dose timing and lower risk of hypoglycemia.

  18. Effects of Substitution, and Adding of Carbohydrate and Fat to Whey-Protein on Energy Intake, Appetite, Gastric Emptying, Glucose, Insulin, Ghrelin, CCK and GLP-1 in Healthy Older Men—A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Caroline Giezenaar

    2018-01-01

    Full Text Available Protein-rich supplements are used widely for the management of malnutrition in the elderly. We reported previously that the suppression of energy intake by whey protein is less in older than younger adults. The aim was to determine the effects of substitution, and adding of carbohydrate and fat to whey protein, on ad libitum energy intake from a buffet meal (180–210 min, gastric emptying (3D-ultrasonography, plasma gut hormone concentrations (0–180 min and appetite (visual analogue scales, in healthy older men. In a randomized, double-blind order, 13 older men (75 ± 2 years ingested drinks (~450 mL containing: (i 70 g whey protein (280 kcal; ‘P280’; (ii 14 g protein, 28 g carbohydrate, 12.4 g fat (280 kcal; ‘M280’; (iii 70 g protein, 28 g carbohydrate, 12.4 g fat (504 kcal; ‘M504’; or (iv control (~2 kcal. The caloric drinks, compared to a control, did not suppress appetite or energy intake; there was an increase in total energy intake (drink + meal, p < 0.05, which was increased most by the M504-drink. P280- and M504-drink ingestion were associated with slower a gastric-emptying time (n = 9, lower ghrelin, and higher cholecystokinin (CCK and glucagon-like peptide-1 (GLP-1 than M280 (p < 0.05. Glucose and insulin were increased most by the mixed-macronutrient drinks (p < 0.05. In conclusion, energy intake was not suppressed, compared to a control, and particularly whey protein, affected gastric emptying and gut hormone responses.

  19. Effects of metformin on body weight in patients with type 2 diabetes mellitus,receiving insulin analogue treatment

    Directory of Open Access Journals (Sweden)

    T I Romantsova

    2013-03-01

    Full Text Available Aims. To study the dynamics of body weight, waist circumference, blood lipid and insulin demand in patients with type 2 diabetes mellitus (T2DM during first year of combined treatment with metformin and insulin analogues, compared with insulin analogue monotherapy.Materials and Methods. We examined 78 patients with T2DM on newly initiated insulin therapy, including 54 females and 24 males. Median age was 56 [51.0; 64.0] years, median disease duration – 9 [6.8;14.0] years. Participants were subdivided in two groups. First group was comprised of 48 subjects (33 females and 15 males, who received monotherapy with insulin analogues (glargine, de- temir, biphasic Aspart 30 and Humalog Mix 25 or rapid-acting lispro and aspart. Second group included 30 patients (18 females and12 males, who were treated with combined therapy (insulin analogues plus metformin. We measured HbA1c, plasma lipid composition, BMI, waist circumference and insulin demand initially and after one year of follow-up.Results. We showed that combined therapy vs. insulin monotherapy allows better glycemic compensation while reducing insulin demand and lowering risks for weight gain.Conclusions. Combined insulin analogue plus metformin treatment delivers better metabolic control in patients with T2DM and is as- sociated with lower risks for body weight gain and increase in insulin demand against monotherapy with insulin analogues.

  20. Design of ultra-stable insulin analogues for the developing world

    Directory of Open Access Journals (Sweden)

    Michael A Weiss

    2013-01-01

    Full Text Available The engineering of insulin analogues illustrates the application of structure-based protein design to clinical medicine. Such design has traditionally been based on structures of wild-type insulin hexamers in an effort to optimize the pharmacokinetic (PK and pharmacodynamic properties of the hormone. Rapid-acting insulin analogues (in chronological order of their clinical introduction, Humalog ® [Eli Lilly & Co.], Novolog ® [Novo-Nordisk], and Apidra ® [Sanofi-Aventis] exploit the targeted destabilization of subunit interfaces to facilitate capillary absorption. Conversely, long-acting insulin analogues exploit the stability of the insulin hexamer and its higher-order self-assembly within the subcutaneous depot to enhance basal glycemic control. Current products either operate through isoelectric precipitation (insulin glargine, the active component of Lantus ® ; Sanofi-Aventis or employ an albumin-binding acyl tether (insulin detemir, the active component of Levemir ® ; Novo-Nordisk. Such molecular engineering has often encountered a trade-off between PK goals and product stability. Given the global dimensions of the diabetes pandemic and complexity of an associated cold chain of insulin distribution, we envisage that concurrent engineering of ultra-stable protein analogue formulations would benefit the developing world, especially for patients exposed to high temperatures with inconsistent access to refrigeration. We review the principal mechanisms of insulin degradation above room temperature and novel molecular approaches toward the design of ultra-stable rapid-acting and basal formulations.

  1. HOW TO START AND OPTIMISE INSULIN THERAPY

    African Journals Online (AJOL)

    intimidating, as understanding how and when to use insulin is vital to diabetes management and ... for the insulin resistance. In the United ..... No change. 3.3 - 4.3. - 2. <3.3. - 4. *Average over 3 days. Mooradian AD et al. Ann Intern Med 2006;145:125-. 134. Table v. Titration schedule premix insulin therapy. Fasting glucose ...

  2. Initiating insulin therapy in children and adolescents with type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Subhash Kumar Wangnoo

    2015-01-01

    Full Text Available The primary clinical goals to be achieved with insulin initiation are elimination of ketosis and hyperglycemia with prevention of chronic complications. Insulin therapy is the mainstay in management of type 1 diabetes, which should be aimed at achieving good glycemic control, with achievement of hemoglobin A1c (HbA1c <7.5%, pre-meal self-monitored blood glucose (SMBG of 90-130 mg/dL, bed time SMBG of 100-140 mg/dL, mean blood glucose level of 120-160 mg/dL and no ketonuria. Two classes of insulin are available for use in T1DM viz. bolus/prandial insulins (rapid-acting insulins and short-acting insulins and basal insulins (intermediate-acting insulin and long-acting insulin. Insulin glargine and glulisine can be used in children above 6 years, lispro in children above 3 years and detemir and aspart in children above 2 years. The caution for hypoglycemia should be exercised while prescribing them. Degludec is currently not approved for pediatric use. The initial insulin regimen should comprise of ≥2 daily bolus and ≥1 basal insulin injections. Insulin intensification would be required if the initial regimen fails, which can be achieved by increasing frequency of long and rapid acting insulin analogues. The American Diabetes Association guidelines recommend HbA1c targets of <8.0% for children <6 years of age, ≤7.5% for children 6 to 12 years of age, and ≤7.0% for adolescents, 12-18 years of age. However, the evidence is now in favor of a single target HbA1c of ≤7.5% for all children and adolescents <19 years of age.

  3. Hairy AdS solitons

    Energy Technology Data Exchange (ETDEWEB)

    Anabalón, Andrés, E-mail: andres.anabalon@uai.cl [Departamento de Ciencias, Facultad de Artes Liberales and Facultad de Ingeniería y Ciencias, Universidad Adolfo Ibáñez, Av. Padre Hurtado 750, Viña del Mar (Chile); Astefanesei, Dumitru, E-mail: dumitru.astefanesei@pucv.cl [Instituto de Física, Pontificia Universidad Católica de Valparaíso, Casilla 4059, Valparaíso (Chile); Choque, David, E-mail: brst1010123@gmail.com [Instituto de Física, Pontificia Universidad Católica de Valparaíso, Casilla 4059, Valparaíso (Chile); Universidad Técnica Federico Santa María, Av. España 1680, Valparaíso (Chile)

    2016-11-10

    We construct exact hairy AdS soliton solutions in Einstein-dilaton gravity theory. We examine their thermodynamic properties and discuss the role of these solutions for the existence of first order phase transitions for hairy black holes. The negative energy density associated to hairy AdS solitons can be interpreted as the Casimir energy that is generated in the dual filed theory when the fermions are antiperiodic on the compact coordinate.

  4. The role of insulin detemir in overweight type 2 diabetes management

    Directory of Open Access Journals (Sweden)

    Yared N Demssie

    2009-06-01

    Full Text Available Yared N Demssie1, Naveed Younis2, Handrean Soran31Department of Diabetes and Endocrinology, Salford Royal Foundation NHS Trust, Salford, UK; 2Department of Medicine, University Hospital South Manchester Foundation NHS Trust, Wythenshawe, Manchester, UK; 3University Department of Medicine, Central Manchester and Manchester Children’s NHS Foundation Trust, Manchester, UKAbstract: The recent evidence-based shift towards an algorithm of early initiation and aggressive titration of insulin therapy in the management of type 2 diabetes requires the use of an effective insulin formulation that is both safe and acceptable to patients and physicians alike. The advent of the long-acting insulin analogues, insulin detemir and glargine, in the last decade has revolutionized insulin therapy in type 2 diabetes. Their unique pharmacokinetic and pharmacodynamic properties have offered tangible advantage over the conventional intermediate and long-acting insulin preparations in terms of improving glucose control as well as reducing risk of hypoglycemia and weight gain. This review focuses on the pharmacodynamic properties of the long-acting insulin analogue detemir, the outcome of studies on its relative efficacy and safety as well as its proposed place in the management of type 2 diabetes.Keywords: insulin detemir, type 2 diabetes, overweight

  5. Alternative signaling network activation through different insulin receptor family members caused by pro-mitogenic antidiabetic insulin analogues in human mammary epithelial cells.

    Science.gov (United States)

    ter Braak, Bas; Wink, Steven; Koedoot, Esmee; Pont, Chantal; Siezen, Christine; van der Laan, Jan Willem; van de Water, Bob

    2015-07-19

    Insulin analogues are designed to have improved pharmacokinetic parameters compared to regular human insulin. This provides a sustained control of blood glucose levels in diabetic patients. All novel insulin analogues are tested for their mitogenic side effects, however these assays do not take into account the molecular mode of action of different insulin analogues. Insulin analogues can bind the insulin receptor and the insulin-like growth factor 1 receptor with different affinities and consequently will activate different downstream signaling pathways. Here we used a panel of MCF7 human breast cancer cell lines that selectively express either one of the isoforms of the INSR or the IGF1R. We applied a transcriptomics approach to assess the differential transcriptional programs activated in these cells by either insulin, IGF1 or X10 treatment. Based on the differentially expressed genes between insulin versus IGF1 and X10 treatment, we retrieved a mitogenic classifier gene set. Validation by RT-qPCR confirmed the robustness of this gene set. The translational potential of these mitogenic classifier genes was examined in primary human mammary cells and in mammary gland tissue of mice in an in vivo model. The predictive power of the classifier genes was evaluated by testing all commercial insulin analogues in the in vitro model and defined X10 and glargine as the most potent mitogenic insulin analogues. We propose that these mitogenic classifier genes can be used to test the mitogenic potential of novel insulin analogues as well as other alternative molecules with an anticipated affinity for the IGF1R.

  6. Efficacy and safety of the glucagon-like peptide-1 receptor agonist liraglutide added to insulin therapy in poorly regulated patients with type 1 diabetes-a protocol for a randomised, double-blind, placebo-controlled study

    DEFF Research Database (Denmark)

    Dejgaard, Thomas Fremming; Knop, Filip Krag; Tarnow, Lise

    2015-01-01

    INTRODUCTION: Intensive insulin therapy is recommended for the treatment of type 1 diabetes (T1D). Hypoglycaemia and weight gain are the common side effects of insulin treatment and may reduce compliance. In patients with insulin-treated type 2 diabetes, the addition of glucagon-like peptide-1 re...... Protection Agency. The study will be carried out under the surveillance and guidance of the good clinical practice (GCP) unit at Copenhagen University Hospital Bispebjerg in accordance with the ICH-GCP guidelines and the Helsinki Declaration. TRIAL REGISTRATION NUMBER: NCT01612468....

  7. Cerebral insulin, insulin signaling pathway, and brain angiogenesis.

    Science.gov (United States)

    Zeng, Yi; Zhang, Le; Hu, Zhiping

    2016-01-01

    Insulin performs unique non-metabolic functions within the brain. Broadly speaking, two major areas of these functions are those related to brain endothelial cells and the blood-brain barrier (BBB) function, and those related to behavioral effects, like cognition in disease states (Alzheimer's disease, AD) and in health. Recent studies showed that both these functions are associated with brain angiogenesis. These findings raise interesting questions such as how they are linked to each other and whether modifying brain angiogenesis by targeting certain insulin signaling pathways could be an effective strategy to treat dementia as in AD, or even to help secure healthy longevity. The two canonical downstream pathways involved in mediating the insulin signaling pathway, the phosphoinositide-3 kinase (PI3K), and mitogen-activated protein kinase (MAPK) cascades, in the brain are supposed to be similar to those in the periphery. PI3K and MAPK pathways play important roles in angiogenesis. Both are involved in stimulating hypoxia inducible factor (HIF) in angiogenesis and could be activated by the insulin signaling pathway. This suggests that PI3K and MAPK pathways might act as cross-talk between the insulin signaling pathway and the angiogenesis pathway in brain. But the cerebral insulin, insulin signaling pathway, and the detailed mechanism in the connection of insulin signaling pathway, brain angiogenesis pathway, and healthy aging or dementias are still mostly not clear and need further studies.

  8. How Much Is Short-Term Glucose Prediction in Type 1 Diabetes Improved by Adding Insulin Delivery and Meal Content Information to CGM Data? A Proof-of-Concept Study.

    Science.gov (United States)

    Zecchin, Chiara; Facchinetti, Andrea; Sparacino, Giovanni; Cobelli, Claudio

    2016-09-01

    In type 1 diabetes (T1D) management, short-term glucose prediction can allow to anticipate therapeutic decisions when hypo/hyperglycemia is imminent. Literature prediction methods mainly use past continuous glucose monitoring (CGM) readings. Sophisticated algorithms can use information on insulin delivered and meal carbohydrate (CHO) content. The quantification of how much insulin and CHO information improves glucose prediction is missing in the literature and is investigated, in an open-loop setting, in this proof-of-concept study. We adopted a versatile literature prediction methodology able to utilize a variety of inputs. We compared predictors that use (1) CGM; (2) CGM and insulin; (3) CGM and CHO; and (4) CGM, insulin, and CHO. Data of 15 T1D subjects in open-loop setup were used. Prediction was evaluated via absolute error and temporal gain focusing on meal/night periods. The relative importance of each individual input of the predictor was evaluated with a sensitivity analysis. For a prediction horizon (PH) ≥ 30 minutes, insulin and CHO information improves prediction accuracy of 10% and double the temporal gain during the 2 hours following the meal. During the night the 4 methods did not give statistically different results. When PH ≥ 45 minutes, the influence of CHO information on prediction is 5-fold that of insulin. In an open-loop setting, with PH ≥ 30 minutes, information on CHO and insulin improves short-term glucose prediction in the 2-hour time window following a meal, but not during the night. CHO information improves prediction significantly more than insulin. © 2016 Diabetes Technology Society.

  9. Effects of a combination butaphosphan and cyanocobalamin product and insulin on ketosis resolution and milk production.

    Science.gov (United States)

    Gordon, J L; Duffield, T F; Herdt, T H; Kelton, D F; Neuder, L; LeBlanc, S J

    2017-04-01

    The objective of this study was to determine the effects of butaphosphan-cyanocobalamin (B+C), glargine insulin, and propylene glycol on resolution of ketosis and average daily milk yield after treatment. Cows from 16 herds in Ontario, Canada, and 1 herd in Michigan were tested at weekly intervals between 3 and 16 DIM. Ketosis was defined as blood β-hydroxybutyrate (BHB) ≥1.2 mmol/L. All ketotic cows were given a baseline treatment of 3 d of 300 g of propylene glycol orally. Animals were then randomly assigned to treatment with 3 doses of either 25 mL of B+C or 25 mL of saline placebo and 1 dose of either 2 mL (200 IU) of glargine insulin or 2 mL of saline placebo in a 2 × 2 factorial arrangement. Outcomes of interest on all farms were ketosis cure (blood BHB ketosis cure (blood BHB ketosis diagnosis were 2.1 times more likely (95% CI = 1.2 to 3.7) to be cured if treated with B+C. Animals in lactation 3 or higher that had blood glucose concentrations ketosis treatment in animals with blood glucose ketosis diagnosis. It also suggests that blood glucose concentration may be an important predictor of success of ketosis treatment. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  10. [New insulin types in type 1 diabetes mellitus].

    Science.gov (United States)

    Mesa, Jordi

    2015-07-20

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

  11. Globular adiponectin ameliorates metabolic insulin resistance via AMPK-mediated restoration of microvascular insulin responses.

    Science.gov (United States)

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W; Barrett, Eugene J; Cao, Wenhong; Liu, Zhenqi

    2015-09-01

    Adiponectin is an adipokine with anti-inflammatory and anti-diabetic properties. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance in obesity and diabetes. Insulin resistance is present in muscle microvasculature and this may contribute to decreased insulin delivery to, and action in, muscle. In this study we examined whether adiponectin ameliorates metabolic insulin resistance by affecting muscle microvascular recruitment. We demonstrated that a high-fat diet induces vascular adiponectin and insulin resistance but globular adiponectin administration can restore vascular insulin responses and improve insulin's metabolic action via an AMPK- and nitric oxide-dependent mechanism. This suggests that globular adiponectin might have a therapeutic potential for improving insulin resistance and preventing cardiovascular complications in patients with diabetes via modulation of microvascular insulin responses. Hypoadiponectinaemia is closely associated with endothelial dysfunction and insulin resistance, and microvasculature plays a critical role in the regulation of insulin action in muscle. Here we tested whether adiponectin replenishment could improve metabolic insulin sensitivity in male rats fed a high-fat diet (HFD) via the modulation of microvascular insulin responses. Male Sprague-Dawley rats were fed either a HFD or low-fat diet (LFD) for 4 weeks. Small resistance artery myograph changes in tension, muscle microvascular recruitment and metabolic response to insulin were determined. Compared with rats fed a LFD, HFD feeding abolished the vasodilatory actions of globular adiponectin (gAd) and insulin on pre-constricted distal saphenous arteries. Pretreatment with gAd improved insulin responses in arterioles isolated from HFD rats, which was blocked by AMP-activated protein kinase (AMPK) inhibition. Similarly, HFD abolished microvascular responses to either gAd or insulin and decreased insulin-stimulated glucose disposal by

  12. Insulin degludec, a long-acting once-daily basal analogue for type 1 and type 2 diabetes mellitus.

    Science.gov (United States)

    Berard, Lori; MacNeill, Gail

    2015-02-01

    Here, we discuss certain practical issues related to use of insulin degludec, a new long-acting basal insulin analogue. Degludec provides uniform ("peakless") action that extends over more than 24 hours and is highly consistent from dose to dose. Like the 2 previously available basal analogues (detemir and glargine), degludec is expected to simplify dose adjustment and enable patients to reach their glycemic targets with reduced risk of hypoglycemia. Phase 3 clinical trials involving type 1 and type 2 diabetes have demonstrated that degludec was noninferior to glargine in allowing patients to reach a target glycated hemoglobin (A1C) of 7%, and nocturnal hypoglycemia occurred significantly less frequently with degludec. In addition, when dosing intervals vary substantially from day to day, degludec continues to be effective and to maintain a low rate of nocturnal hypoglycemia. Degludec thus has the potential to reduce risk of nocturnal hypoglycemia, to enhance the flexibility of the dosing schedule and to improve patient and caregiver confidence in the stability of glycemic control. A dedicated injector, the FlexTouch prefilled pen, containing degludec 200 units/mL, will be recommended for most patients with type 2 diabetes. Degludec will also be available as 100 units/mL cartridges, to be used in the NovoPen 4 by patients requiring smaller basal insulin doses, including most patients with type 1 diabetes. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  13. Adding Ajax

    CERN Document Server

    Powers, Shelley

    2007-01-01

    Ajax can bring many advantages to an existing web application without forcing you to redo the whole thing. This book explains how you can add Ajax to enhance, rather than replace, the way your application works. For instance, if you have a traditional web application based on submitting a form to update a table, you can enhance it by adding the capability to update the table with changes to the form fields, without actually having to submit the form. That's just one example.Adding Ajax is for those of you more interested in extending existing applications than in creating Rich Internet Applica

  14. Insulin detemir for the treatment of obese patients with type 2 diabetes

    Science.gov (United States)

    Hollander, Priscilla A

    2012-01-01

    The risk for developing type 2 diabetes (T2DM) is greater among obese individuals. Following onset of the disease, patients with T2DM become more likely to be afflicted with diabetic micro- and macrovascular complications. Decreasing body weight has been shown to lower glycosylated hemoglobin and improve other metabolic parameters in patients with T2DM. Medications used to lower blood glucose may increase body weight in patients with T2DM and this has been repeatedly shown to be the case for conventional, human insulin formulations. Insulin detemir is a neutral, soluble, long-acting insulin analog in which threonine-30 of the insulin B-chain is deleted, and the C-terminal lysine is acetylated with myristic acid, a C14 fatty acid chain. Insulin detemir binds to albumin, a property that enhances its pharmacokinetic/pharmacodynamic profile. Results from clinical trials have demonstrated that treatment with insulin detemir is associated with less weight gain than either insulin glargine or neutral protamine Hagedorn insulin. There are many potential reasons for the lower weight gain observed among patients treated with insulin detemir, including lower risk for hypoglycemia and therefore decreased defensive eating due to concern about this adverse event, along with other effects that may be related to the albumin binding of this insulin that may account for lower within-patient variability and consistent action. These might include faster transport across the blood–brain barrier, induction of satiety signaling in the brain, and preferential inhibition of hepatic glucose production versus peripheral glucose uptake. Experiments in diabetic rats have also indicated that insulin detemir increases adiponectin levels, which is associated with both weight loss and decreased eating. PMID:22291472

  15. Insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control

    NARCIS (Netherlands)

    Vos, Rimke C; van Avendonk, Mariëlle JP; Jansen, Hanneke; Goudswaard, Alexander N; van den Donk, Maureen; Gorter, Kees; Kerssen, Anneloes; Rutten, Guy EHM

    2016-01-01

    BACKGROUND: It is unclear whether people with type 2 diabetes mellitus on insulin monotherapy who do not achieve adequate glycaemic control should continue insulin as monotherapy or can benefit from adding oral glucose-lowering agents to the insulin therapy. OBJECTIVES: To assess the effects of

  16. Dgroup: DG01636 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available analogue, fast-acting ... D04477 ... Insulin lispro (USP/INN); Insulin lispro (genetical recombination) (JAN) ... ... ... D04475 ... Insulin aspart (USAN/INN); Insulin aspart (genetical recombination) (JAN) ... D04540 ... Insulin glu...lisine (USAN/INN); Insulin glulisine (genetical recombination) (JAN) ... DG01797 ... Insulin analogue, long-acting ... D03250 ... Insulin glargine (USAN/INN); Insulin glargine (genetical recombinat...ion) (JP17); Insulin glargine (genetical recombination) injection (JP17); Insulin glargine (genetical recomb

  17. Insulin Test

    Science.gov (United States)

    ... involves changes in diet and lifestyle. The American Diabetes Association recommends losing excess weight, getting regular amounts of moderate intensity physical activity, and increasing dietary fiber to lower blood insulin levels and increase the ...

  18. Insulin Test

    Science.gov (United States)

    ... to come strictly from animal sources (cow and pig pancreas cells). Most insulin used today is synthetic, ... developing type 2 diabetes , hypertension , hyperlipidemia , and/or heart disease several years down the road. Abdominal obesity, ...

  19. Is insulin diluted when stored in water?

    Science.gov (United States)

    Plager, Phillip; Nurie, Kadiro; Omann, Trevor; Moran, Antoinette; Piloya, Thereza; Bahendeka, Silver; Sunni, Muna

    2017-05-01

    Insulin storage is a challenge in resource-poor countries. In Uganda, patients were noted to store insulin vials by submerging them in water. To examine whether withdrawing insulin from a vial without adding air back causes a vacuum which allows water to enter the vial, resulting in insulin dilution. Seven hundred units of insulin were withdrawn from forty 10 mL vials of 100 units/mL insulin [20 neutral protamine hagedorn (NPH), 20 regular]. In half, air was added back. The vials were weighed (baseline). Half of the vials (10 with added air, 10 without) were submerged in water for 24 h and then air-dried for 24 h. Vials that were not submerged sat at room temperature for 48 h. All vials were weighed 48 h from baseline. Addition of air did not impact the change in weight after submersion (air added: -0.002 ± 0.001 g or -0.2 ± 0.1 unit; no air added: -0.003 ± 0.000 g or -0.3 ± 0 unit, p = 0.57). In a subset of vials in which an additional 240 units were withdrawn before submersion for another 24 h, there was still no difference in weight change in those vials with air added (p = 0.2). Withdrawing insulin from a vial without adding air did not result in uptake of water or dilution of insulin in the submerged vial, although it made drawing up the insulin easier. This study did not address the larger concern of bacterial contamination of the rubber stopper during water storage. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Anti-insulin antibody test

    Science.gov (United States)

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

  1. Different impacts of acylated and non-acylated long-acting insulin analogs on neural functions in vitro and in vivo.

    Science.gov (United States)

    Tsuneki, Hiroshi; Yoshida, Hitomi; Endo, Kosuke; Mori, Norihiko; Hosoh, Shuji; Tsuda, Masaaki; Wada, Tsutomu; Sasaoka, Toshiyasu

    2017-07-01

    Centrally administered insulin improves cognitive functions in patients with Alzheimer's disease; however, it remains unknown whether long-acting insulin analogs exert more pronounced effects than insulin. In the present study, we directly compared the effects of insulin and its analogs on neural functions in vitro and in vivo. Cultured rat cerebral cortical neurons were treated with insulin, insulin glargine U100 (Gla), insulin detemir (Det), or insulin degludec (Deg). Moreover, these drugs were intracerebroventricularly administered to mice. Their efficacies were evaluated by biochemical and behavioral analyses. In cultured neurons, insulin, Gla, and Det increased phosphorylation of Akt and enhanced gene expression of brain-derived neurotrophic factor to a similar extent, although Deg was less effective. The effects of Det and Deg, but not insulin and Gla were suppressed by addition of albumin. When the drug was centrally administered, the increasing effects of insulin on the Akt phosphorylation were comparable to those of Gla but greater than those of Det in hippocampus and cerebral cortex of diabetic db/db and non-diabetic db/m+ mice. Moreover, insulin and Gla enhanced memory functions in Y-maze test and suppressed depression-like behavior in forced swim test in normal mice to a similar extent, and these effects were more potent than those of Det. Insulin and Gla have greater impacts on central nervous system than insulin analogs with high albumin sensitivity, such as Det and Deg. These pharmacological profiles should be taken into account for developing an insulin-based therapy to treat Alzheimer's disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Insulin degludec as an ultralong-acting basal insulin once a day: a systematic review

    Directory of Open Access Journals (Sweden)

    Wang F

    2012-07-01

    Full Text Available Fei Wang,1 Justine Surh,1 Manmeet Kaur21University of Connecticut School of Pharmacy, Department of Pharmacy Practice, Storrs, 2Joslin Diabetes Center Affiliate, Hospital of Central Connecticut, New Britain, CT, USABackground: Insulin degludec (IDeg is a neutral, ultralong-acting new generation basal insulin analog developed by NovoNordisk currently in Phase III clinical development. IDeg offers a duration of action of more than 42 hours in adults, much longer than current basal insulin formulations.Objective: The aim of this review is to assess the efficacy and safety data of IDeg in the treatment of type 1 and type 2 diabetes mellitus.Methods: Relevant English language articles from 2010 to 2012 were identified through MEDLINE, PubMed, EMBASE, Scopus, BIOSIS, and Google Scholar. Online conference proceedings of the 71st ADA Scientific Sessions and the 47th EASD Annual Meeting were reviewed. Studies were compared in terms of their study designs, primary and secondary efficacy parameters, and tolerability data.Results: There are a total of nine published trials investigating the clinical efficacy and safety of IDeg in over 3000 subjects with type 1 and 2 diabetes. Only three trials were published in full. All were open-label, randomized multicenter trials with durations of 16 to 52 weeks. IDeg and coformulations of IDeg with insulin aspart (IAsp were compared to insulin glargine (IGlar, detemir, and biphasic IAsp 30 (BIAsp 30.Conclusion: Based upon the available evidence, there appear to be no reported differences between IDeg and IGlar, detemir, or BIAsp 30 in the reduction of the primary efficacy end-points of HbA1c and mean fasting plasma glucose (FPG concentrations. Only flexible dosing of IDeg provided a significant reduction in FPG compared to IGlar. IDeg demonstrated a significant reduction in nocturnal hypoglycemia in type 1 diabetes. In type 2 diabetes, IDeg reduced the incidence of hypoglycemia by 18% and 58% compared to IGlar and

  3. Long-acting insulins alter milk composition and metabolism of lactating dairy cows.

    Science.gov (United States)

    Winkelman, L A; Overton, T R

    2013-01-01

    This study investigated the effect of 2 different types of long-acting insulin on milk production, milk composition, and metabolism in lactating dairy cows. Multiparous cows (n=30) averaging 88 d in milk were assigned to one of 3 treatments in a completely randomized design. Treatments consisted of control (C), Humulin-N (H; Eli Lilly and Company, Indianapolis, IN), and insulin glargine (L). The H and L treatments were administered twice daily at 12-h intervals via subcutaneous injection for 10d. Cows were milked twice daily, and milk composition was determined every other day. Mammary biopsies were conducted on d 11, and mammary proteins extracted from the biopsies were analyzed by Western blot for components of insulin and mammalian target of rapamycin signaling pathways. Treatment had no effect on dry matter intake or milk yield. Treatment with both forms of long-acting insulin increased milk protein content and tended to increase milk protein yield over the 10-d treatment period. Analysis of milk N fractions from samples collected on d 10 of treatment suggested that cows administered L tended to have higher yields of milk protein fractions than cows administered H. Milk fat content and yield tended to be increased for cows administered long-acting insulins. Lactose content and yields were decreased by treatment with long-acting insulins. Administration of long-acting insulins, particularly L, tended to shift milk fatty acid composition toward increased short- and medium-chain fatty acids and decreased long-chain fatty acids. Plasma concentrations of glucose and urea N were lower for cows administered long-acting insulins; interactions of treatment and sampling time were indicative of more pronounced effects of L than H on these metabolites. Concentrations of nonesterified fatty acids and insulin were increased in cows administered long-acting insulins. Decreased concentrations of urea N in both plasma and milk suggested more efficient use of N in cows

  4. Diabetes and Insulin

    Science.gov (United States)

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

  5. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... After Your Baby is Born Monogenic Diabetes Prediabetes & Insulin Resistance What is insulin? Insulin is a hormone made in the pancreas, ... body absorb glucose and use it for energy. Insulin's Role in Blood Glucose Control When blood glucose ...

  6. Insulin dysfunction and Tau pathology

    Directory of Open Access Journals (Sweden)

    Noura eEl Khoury

    2014-02-01

    Full Text Available The neuropathological hallmarks of Alzheimer's disease (AD include senile plaques of β-amyloid (Aβ peptides (a cleavage product of the Amyloid Precursor Protein, or APP and neurofibrillary tangles (NFT of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF. NFT pathology is important since it correlates with the degree of cognitive impairment in AD.Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99% is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease.Insulin dysfunction, manifested by diabetes mellitus (DM might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM and type 2 diabetes (T2DM are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment.Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting on Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia.

  7. Differential Treatment Response to Insulin Intensification Therapy: A Post Hoc Analysis of a Randomized Trial Comparing Premixed and Basal-Bolus Insulin Regimens.

    Science.gov (United States)

    Shi, Li Xin; Li, Peng Fei; Hou, Jia Ning

    2017-08-01

    Identification of subgroups of patients that may benefit most from certain treatment is important because individual treatment response varies due to multiple contributing factors. The present study used the subgroup identification based on the differential effect search (SIDES) algorithm to identify subgroups with different treatment responses to insulin intensification therapies. This was a post hoc analysis of a 24-week, multicenter, open-label, randomized, parallel study comparing prandial premixed therapy (PPT) to basal-bolus therapy (BBT). Patients with type 2 diabetes mellitus were randomized to PPT (insulin lispro mix 50/50 thrice daily with meals) or BBT (glargine at bedtime plus mealtime insulin lispro) insulin intensification therapies. The SIDES algorithm was used to identify the subgroups from at-goal patients [glycated hemoglobin (HbA1c) comparable between PPT and BBT groups. The SIDES algorithm identified patients with race other than Caucasian (i.e., African-American, Asian, and Hispanic) and baseline fasting blood glucose (FBG) Company. Clinicaltrials.gov ID number: NCT00110370.

  8. Insulin-Induced Electrophysiology Changes in Human Pleura Are Mediated via Its Receptor

    Science.gov (United States)

    Kouritas, V. K.; Ioannou, M.; Foroulis, C. N.; Desimonas, N.; Evaggelopoulos, K.; Gourgoulianis, K. I.; Molyvdas, P. A.; Hatzoglou, C.

    2010-01-01

    Background. Insulin directly changes the sheep pleural electrophysiology. The aim of this study was to investigate whether insulin induces similar effects in human pleura, to clarify insulin receptor's involvement, and to demonstrate if glibenclamide (hypoglycemic agent) reverses this effect. Methods. Human parietal pleural specimens were mounted in Ussing chambers. Solutions containing insulin or glibenclamide and insulin with anti-insulin antibody, anti-insulin receptor antibody, and glibenclamide were used. The transmesothelial resistance (R TM) was determined. Immunohistochemistry for the presence of Insulin Receptors (IRa, IRb) was also performed. Results. Insulin increased R TM within 1st min (P = .016), when added mesothelially which was inhibited by the anti-insulin and anti-insulin receptor antibodies. Glibenclamide also eliminated the insulin-induced changes. Immunohistochemistry verified the presence of IRa and IRb. Conclusion. Insulin induces electrochemical changes in humans as in sheep via interaction with its receptor. This effect is abolished by glibenclamide. PMID:20814548

  9. Insulin Resistance

    DEFF Research Database (Denmark)

    Jensen, Benjamin Anderschou Holbech

    Insulin resistance (IR) is escalating with alarming pace and is no longer restricted to westernized countries. As a forerunner for some of the most serious threats to human health including metabolic syndrome, cardiovascular diseases, and type 2-diabetes, the need for new treatment modalities...

  10. Successful Management of Insulin Allergy and Autoimmune Polyendocrine Syndrome Type 4 with Desensitization Therapy and Glucocorticoid Treatment: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Joselyn Rojas

    2014-01-01

    Full Text Available Introduction. Insulin allergy is a rare complication of insulin therapy, especially in type 1 diabetes mellitus (T1DM. Key manifestations are hypersensitivity-related symptoms and poor metabolic control. T1DM, as well as insulin allergy, may develop in the context of autoimmune polyendocrine syndrome (APS, further complicating management. Case Report. A 17-year-old male patient, diagnosed with T1DM, was treated with various insulin therapy schemes over several months, which resulted in recurrent anaphylactoid reactions and poor glycemic control, after which he was referred to our Endocrinology and Immunology Department. A prick test was carried out for all commercially available insulin presentations and another insulin scheme was designed but proved unsuccessful. A desensitization protocol was started with Glargine alongside administration of Prednisone, which successfully induced tolerance. Observation of skin lesions typical of vitiligo prompted laboratory workup for other autoimmune disorders, which returned positive for autoimmune gastritis/pernicious anemia. These findings are compatible with APS type 4. Discussion. To our knowledge, this is the first documented case of insulin allergy in type 4 APS, as well as this particular combination in APS. Etiopathogenic components shared by insulin allergy and APS beg for further research in immunogenetics to further comprehend pathophysiologic aspects of these diseases.

  11. Fixed-ratio combination therapy with GLP-1 receptor agonist liraglutide and insulin degludec in people with type 2 diabetes

    DEFF Research Database (Denmark)

    Østergaard, Lauge; Frandsen, Christian Seerup; Dejgaard, Thomas Fremming

    2017-01-01

    INTRODUCTION: A fixed combination of basal insulin degludec and glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide (IDegLira; 50 units degludec/1.8 mg liraglutide) has been developed as a once daily injection for the treatment of type 2 diabetes (T2D). In the phase 3a trial programme ......Lira combines the clinical advantages of basal insulin and GLP-1RA treatment, and is a treatment strategy that could improve the management of patients with T2D....... "Dual action of liraglutide and insulin degludec in type 2 diabetes" (DUAL™), five trials of 26 weeks duration and one trial of 32 weeks duration have evaluated the efficacy and safety of IDegLira compared with administration of insulin degludec, insulin glargine, liraglutide alone or placebo. Areas...... groups; however, gastrointestinal side effects were fewer with IDegLira compared with liraglutide treatment alone. A limitation of the DUAL™ development programme is that patients receiving basal insulin doses in excess of 50 units were excluded from the studies. Expert Commentary: In conclusion, IDeg...

  12. Insulin alters the permeability of sheep pleura.

    Science.gov (United States)

    Kouritas, V K; Hatzoglou, C; Ioannou, M; Gourgoulianis, K I; Molyvdas, P A

    2010-05-01

    Insulin promotes ion transportation across epithelia, mainly kidneys, leading to water and electrolyte abnormalities, possibly causing 'insulin oedema syndrome', which rarely presents as pleural effusion. Direct stimulation of sheep pleura by insulin and the possible electrophysiology mechanisms involved were investigated. Sheep visceral and parietal pleural specimens were mounted between Ussing chambers. Insulin solutions (10 (-9) to 10 (-5) M), L-NAME, Nitroprussid sodium, amiloride and ouabain were used. Trans-mesothelial Resistance was determined. Immunohistochemistry for presence of Insulin Receptors was performed. Insulin increased Trans-mesothelial Resistance within 1st minute when added mesothelially of visceral (p=0.008) and parietal pleura (p=0.046) for concentrations higher than 10 (-7) M. L-NAME or Nitroprussid sodium didn't but amiloride and ouabain inhibited insulin's effect. Immunohistochemistry revealed the presence of Insulin Receptors. Insulin changes the permeability of sheep pleura by altering its electrophysiology and may interfere in pleural effusion formation. Involvement of Insulin Receptors may be suggested.

  13. The Insuline Analogues

    OpenAIRE

    Garrido Carrasco, Elizabeth; Servicio de Endocrinología, Hospital Nacional Edgardo Rebagliati Martins, Lima, Perú

    2014-01-01

    Insulin analogues are a new pharmaceutical family, designed to overcome deficiencies that still exist with the rDNA insulin. There are rapid-acting insulin analogues such as lispro insulin and insulin aspart. They avoid postprandial and nocturnal hypoglycemia. There are also intermediate-acting insulin analogues like NPL and Mix 25 (a mixture between NPL and lispro), which join the neutral protamine insulin length of action and the fast onset of the rapid-acting analogue lispro. Finally, ther...

  14. IGF1 and IGF2 specificities to the two insulin receptor isoforms are determined by insulin receptor amino acid 718.

    Directory of Open Access Journals (Sweden)

    Mie Andersen

    Full Text Available Alanine scan of insulin receptor (IR-B exon 11 and site-directed mutagenesis of amino acid 718 in human IR-A and IR-B were performed. Ligand affinities to wild type and mutated receptors were studied by displacement of radioactive insulin in binding assay on secreted soluble midi receptors or solubilized semi-purified full length receptors stably expressed in Baby Hamster Kidney cells. Phosphorylation of IR in response to insulin, IGF1 and IGF2 was measured using ELISA.Insulin, insulin detemir and insulin glargine maximally showed two fold differences in affinity for human IR-A and IR-B, but IGF1 and IGF2 had up to 10 fold preference for IR-A. Alanine scan of exon 11 revealed that position 718 is important for low IGF1 affinity to IR-B. Mutational analysis of amino acid residue 718 in IR-A and IR-B demonstrated that charge is important for IGF1 and IGF2 affinity but not important for insulin affinity. The affinity of IGF1 and IGF2 for the mutant IR-A P718K was comparable to the wild type IR-B whereas the affinity of IGF1 and IGF2 for the mutant IR-B K718P was comparable to the wild type IR-A. Changes in affinity were also reflected in the IR activation pattern.Mutating position 718 in human IR-B to the proline found at position 718 in human IR-A increased IGF1 and IGF2 affinity to a level comparable to IR-A and mutating position 718 in IR-A to the lysine found at position 718 in IR-B decreased IGF1 and IGF2 affinity to a level comparable to IR-B, whereas a negatively charged glutamate did not. These changes in the affinities were also reflected in the IR phosphorylation pattern, meaning that position 718 is important for both affinity and activation of the receptor. It should be emphasized that none of the mutations affected insulin affinity, indicating that the mutations did not alter the overall receptor structure and that the effect is ligand specific.

  15. Comparison of the influence of oral antidiabetic drug and combined with basal insulin treatment on diabetic control and micro-inflammatory state in type 2 diabetes mellitus patients

    Directory of Open Access Journals (Sweden)

    Gang Wu

    2016-06-01

    Full Text Available Objective: To investigate the influence of oral antidiabetic drug and combined with basal insulin treatment on diabetic control and micro-inflammatory state in type 2 diabetes mellitus patients. Methods: From May 2014 to June 2015, 128 cases of Type 2 diabetes mellitus were recruited and divided randomly into two groups as observation group and control group. The observation group was given metformin (Glucophage, 0.25 tid plus basal insulin (glargine treatment, while the control group was given metformin (Glucophage, initial dose of 0.25 tid; the largest total dose of 2 g plus other non-euglycemic OADs necessarily for 6 months to adjust dose and control blood glucose at target. The diabetic control indexes, islet function and micro-inflammatory factors were detected and analyzed. Results: After 6 months of medication, the observation group showed significantly lower level of FPG, and HbA1cthan the control group. While AUCc-p, HOMA-β and HOMA-IR of the observation group showed significant difference compared to that of the control group after treatment. Also the microinflammatory indexes including hs-CRP, IGF-1, IL-6 and TNF-α of the observation group after treatment were significantly lower than the control group . Conclusions: Type 2 diabetes given metformin plus glargine not only could control and steady blood glucose, but also significant decrease the micro-inflammation state.

  16. Assessment of hypoglycaemia during basal insulin therapy: Temporal distribution and risk of events using a predefined or an expanded definition of nocturnal events.

    Science.gov (United States)

    Riddle, M C; Bolli, G B; Avogaro, A; Álvarez, M G; Merino-Trigo, A; Boëlle-Le Corfec, E; Home, P D

    2017-12-11

    To describe in type 2 diabetes the 24-hour distribution of hypoglycaemia and compare the frequency of nocturnal events based on a predefined nocturnal window or an expanded interval, using illustrative data for two insulin glargine formulations. Temporal distribution of hypoglycaemic events was assessed descriptively and by profile using participant-level data from three randomized trials comparing insulin glargine 300 U/mL (Gla-300) and 100 U/mL (Gla-100). Risk of hypoglycaemia and annualized event rates were compared for the predefined nocturnal interval (00:00 to 05:59h) and an expanded window (22:00h to the pre-breakfast glucose measurement). Confirmed (≤3.9mmol/L [≤70 mg/dL]) or severe hypoglycaemic events were reported most frequently between 06:00 and 10:00 h with both insulins. Nearly threefold more events were identified using the expanded nocturnal interval. Risk of ≥1 nocturnal event was 25% lower with Gla-300 than Gla-100 with the predefined, and 16% lower with the expanded interval; annualized event rates were 31% and 24% lower with the predefined and expanded window, respectively. The between-insulin difference in number of nocturnal events depended markedly on the chosen nocturnal interval (556 vs. 1145 fewer events with Gla-300 using the predefined vs. expanded interval). The predefined 00:00-05:59h nocturnal interval excluded many hypoglycaemic events occurring during the actual overnight interval. While Gla-300 reduced hypoglycaemic events versus Gla-100 (regardless of the interval considered), the results obtained using the expanded window better reflect the clinical experience of people treated with basal insulin. Copyright © 2017. Published by Elsevier Masson SAS.

  17. Safety and efficacy of the nonsystemic chewable complex carbohydrate dietary supplement PAZ320 on postprandial glycemia when added to oral agents or insulin in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Trask, Laura E; Kasid, Natasha; Homa, Karen; Chaidarun, Sushela

    2013-01-01

    Our primary objective was to evaluate the effect of the dietary supplement PAZ320 on postprandial glucose excursion. PAZ320 is derived from glucomannan and acts by blocking carbohydrate hydrolyzing enzymes and by binding to ingested polysaccharides. Endpoints included area under the curve during postprandial glucose excursion (gAUC) and adverse reactions. In an open-label, sequential dose-escalation, prospective study, we examined the efficacy and safety of PAZ320 in 24 subjects with type 2 diabetes treated with oral agents and/or insulin. Subjects consumed 75 g jasmine rice alone or with low-dose (8 g) or high-dose (16 g) PAZ320. A real-time blinded continuous glucose monitor (CGM) was used to assess 3-hour postprandial glycemia. We found that 45% of subjects responded to high-dose PAZ320 as evidenced by a decrease in gAUC of 40% compared to baseline in a dose-dependent manner. The effect of PAZ320 does not correlate with duration of diabetes and seems to work regardless of concurrent diabetes medications. The responders had higher postmeal glucose elevation at baseline, while the nonresponders showed no effect or paradoxic glucose response to PAZ320. There was no severe hypoglycemia, and the gastrointestinal side effects were mild. PAZ320 may be useful as an adjunct to decrease postprandial glycemia in type 2 diabetes, although patients should verify its effect on postprandial glucose due to a possible paradoxic response. Its safety profile is reassuring. Further study is required to determine its long-term effects on glycated hemoglobin (HbA1c) and to further define which subpopulation may respond to PAZ320.

  18. Apolipoprotein E4 Impairs Neuronal Insulin Signaling by Trapping Insulin Receptor in the Endosomes.

    Science.gov (United States)

    Zhao, Na; Liu, Chia-Chen; Van Ingelgom, Alexandra J; Martens, Yuka A; Linares, Cynthia; Knight, Joshua A; Painter, Meghan M; Sullivan, Patrick M; Bu, Guojun

    2017-09-27

    Diabetes and impaired brain insulin signaling are linked to the pathogenesis of Alzheimer's disease (AD). The association between diabetes and AD-associated amyloid pathology is stronger among carriers of the apolipoprotein E (APOE) ε4 gene allele, the strongest genetic risk factor for late-onset AD. Here we report that apoE4 impairs neuronal insulin signaling in human apoE-targeted replacement (TR) mice in an age-dependent manner. High-fat diet (HFD) accelerates these effects in apoE4-TR mice at middle age. In primary neurons, apoE4 interacts with insulin receptor and impairs its trafficking by trapping it in the endosomes, leading to impaired insulin signaling and insulin-stimulated mitochondrial respiration and glycolysis. In aging brains, the increased apoE4 aggregation and compromised endosomal function further exacerbate the inhibitory effects of apoE4 on insulin signaling and related functions. Together, our study provides novel mechanistic insights into the pathogenic mechanisms of apoE4 and insulin resistance in AD. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Insulin Resistance

    DEFF Research Database (Denmark)

    Jensen, Benjamin Anderschou Holbech

    Insulin resistance (IR) is escalating with alarming pace and is no longer restricted to westernized countries. As a forerunner for some of the most serious threats to human health including metabolic syndrome, cardiovascular diseases, and type 2-diabetes, the need for new treatment modalities...... with IR independent of weight gain. In conclusion, the data presented in the current thesis, supported by a thorough review of available literature, advocate that 1) Inflammation is a triggering event fueling IR; 2) Commensal microbes can, when mistreated, aggravate IR and glucose intolerance; and 3) Diet...

  20. The longitudinal association between glycaemic control and health-related quality of life following insulin therapy optimisation in type 2 diabetes patients. A prospective observational study in secondary care

    DEFF Research Database (Denmark)

    Hajós, Tibor R S; Pouwer, F; de Grooth, R

    2012-01-01

    PURPOSE: To test whether improvement in glycosylated haemoglobin (HbA(1c)) as a marker of glycaemic control, following intensifying insulin therapy, is associated with improvements in HRQoL. METHODS: Dutch sub-optimally controlled (HbA(1c) > 7%) type 2 diabetes patients (N = 447, mean age 59 ± 11......) initiated insulin glargine therapy. Data were collected at baseline, 3 and 6 months, and included HbA(1c) and measures of HRQoL: diabetes symptom distress (Diabetes Symptom Checklist-revised; DSC-r), fear of hypoglycaemia (Hypoglycaemia Fear Survey; HFS-w) and emotional well-being (WHO-5 wellbeing index...... of optimising insulin therapy and improvement in HRQoL in type 2 diabetes patients has been observed. A weak, yet significant longitudinal association was found between improved HbA(1c) and emotional well-being and diabetes symptom distress....

  1. IDegLira Versus Alternative Intensification Strategies in Patients with Type 2 Diabetes Inadequately Controlled on Basal Insulin Therapy

    DEFF Research Database (Denmark)

    Freemantle, Nick; Mamdani, Muhammad; Vilsbøll, Tina

    2015-01-01

    glycated hemoglobin (HbA1c) and other outcomes. METHODS: A pooled analysis of five completed Novo Nordisk randomized clinical trials in patients with type 2 diabetes inadequately controlled on basal insulin was used to compare indirectly IDegLira (N = 199) with: addition of liraglutide to basal insulin (N...... = 225) [glucagon-like peptide-1 receptor agonist (GLP-1RA) add-on strategy]; basal-bolus (BB) insulin [insulin glargine (IGlar) + insulin aspart] (N = 56); or up-titration of IGlar (N = 329). A supplementary analysis was performed with the BB arm including patients who received IGlar or IDeg as basal...... of study, differences between IDegLira and BB or up-titrated IGlar, respectively, were as follows: reduction in HbA1c -0.30%, 95% confidence interval (-0.58; -0.01) and -0.65% (-0.83; -0.47); change in body weight -6.89 kg (-7.92; -5.86) and -4.04 kg (-4.69; -3.40) all in favor of IDegLira. Confirmed...

  2. Análogos de insulina Insulin analogues

    Directory of Open Access Journals (Sweden)

    Manuel E. Licea Puig

    2006-12-01

    diabetes mellitus (DM. The recombinant technology of deoxyribonucleic acid (DNA has allowed the development of human insulin; however, this has not totally solved the problems related to immunogenecity, among other problems. Therefore, the new technologies are applied to create insulin analogues. It is our purpose to review relevant pharmacological and clinical aspects related to the insulin analogues, as well as their usefulness in the treatment of DM. The insulin analogues result from biochemical modifications of human insulin. These modifications of the insulin molecule alter not only the absorption, but also the beginning and duration of the action, which offer advantages over the conventional insulins. At present, there are three rapid acting insulin analogues: insulin lispro, insulin aspart and glulisine; and three long acting analogues; glargine, detemir and albulin. Albulin is the latest long acting analogue reported. At present, it is being subjected to various in vitro and in vivo studies. Besides, there have been developed diverse formulations where the rapid acting insulin analogues are premixed with the long acting analogues. The rapid acting insulin analogues have showed a modest global benefit against the conventional insulins in type 1 diabetics. The long acting analogues focus their attention in those persons with DM with nocturnal hypoglycemic episodes. Longer term studies are necessary to confirm the safety and benefits of these preparations, as well as to determine their effect on the micro- and macroangiopathic complications of DM.

  3. Clinical utility of insulin and insulin analogs

    Science.gov (United States)

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

    2013-01-01

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

  4. Inflammation and Insulin Resistance

    OpenAIRE

    de Luca, Carl; Olefsky, Jerrold M.

    2007-01-01

    Obesity-induced chronic inflammation is a key component in the pathogenesis of insulin resistance and the Metabolic syndrome. In this review, we focus on the interconnection between obesity, inflammation and insulin resistance. Pro-inflammatory cytokines can cause insulin resistance in adipose tissue, skeletal muscle and liver by inhibiting insulin signal transduction. The sources of cytokines in insulin resistant states are the insulin target tissue themselves, primarily fat and liver, but t...

  5. Degludec, a new ultra-long-acting basal insulin for the treatment of diabetes mellitus type 1 and 2: advances in clinical research.

    Science.gov (United States)

    Muñoz Torres, Manuel

    2014-03-01

    Degludec is the most recent molecule of the ultra-long-acting basal insulin analogues approved for human use. It forms soluble multihexamers which after subcutaneous injection are converted into monomers, and are thus slowly and continuously absorbed into the bloodstream. This absorption mechanism confers degludec an ultra-long and stable action profile, with no concentration peaks. This paper discusses the most recent studies in patients with type 1 and 2 diabetes mellitus, which showed degludec to be non inferior in decreasing HbA1c, ensuring optimum glycemic control similar to that achieved with insulin glargine or detemir. Degludec also had an improved safety profile, as it was associated to a significantly lower rate of nocturnal hypoglycemia in both types of diabetes and to a potentially lower overall hypoglycemia rate in type 2 DM. Degludec also opens the possibility to use more flexible regimens. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

  6. Increased skeletal muscle capillarization enhances insulin sensitivity

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Laub, Lasse; Vedel, Kenneth

    2014-01-01

    . Skeletal muscle specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist Prazosin to the drinking water of Sprague Dawley rats (n=33) while 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-week Prazosin treatment, which ensured...... that Prazosin was cleared from the blood stream. Whole-body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue specific insulin sensitivity was assessed by administration of 2-deoxy-[(3)H]-Glucose during the plateau phase of the clamp. Whole-body...

  7. Insulin sensitizer prevents and ameliorates experimental type 1 diabetes.

    Science.gov (United States)

    Valitsky, Michael; Hoffman, Amnon; Unterman, Terry; Bar-Tana, Jacob

    2017-12-01

    Insulin-dependent type-1 diabetes (T1D) is driven by autoimmune β-cell failure, whereas systemic resistance to insulin is considered the hallmark of insulin-independent type-2 diabetes (T2D). In contrast to this canonical dichotomy, insulin resistance appears to precede the overt diabetic stage of T1D and predict its progression, implying that insulin sensitizers may change the course of T1D. However, previous attempts to ameliorate T1D in animal models or patients by insulin sensitizers have largely failed. Sensitization to insulin by MEthyl-substituted long-chain DICArboxylic acid (MEDICA) analogs in T2D animal models surpasses that of current insulin sensitizers, thus prompting our interest in probing MEDICA in the T1D context. MEDICA efficacy in modulating the course of T1D was verified in streptozotocin (STZ) diabetic rats and autoimmune nonobese diabetic (NOD) mice. MEDICA treatment normalizes overt diabetes in STZ diabetic rats when added on to subtherapeutic insulin, and prevents/delays autoimmune T1D in NOD mice. MEDICA treatment does not improve β-cell insulin content or insulitis score, but its efficacy is accounted for by pronounced total body sensitization to insulin. In conclusion, potent insulin sensitizers may counteract genetic predisposition to autoimmune T1D and amplify subtherapeutic insulin into an effective therapeutic measure for the treatment of overt T1D. Copyright © 2017 the American Physiological Society.

  8. Axion wormholes in AdS compactifications

    Science.gov (United States)

    Hertog, Thomas; Trigiante, Mario; Van Riet, Thomas

    2017-06-01

    We find regular axionic Euclidean wormhole solutions in Type IIB string theory compactified on {AdS}_5× {S}^5/{Z}_k . AdS/CFT enables a precise derivation of the axion content of the Euclidean theory, placing the string theory embedding of the wormholes on firm footing. This further sharpens the paradox posed by these solutions.

  9. Metformin potentiates the antigluconeogenic action of insulin.

    Science.gov (United States)

    Wollen, N; Bailey, C J

    1988-01-01

    The interaction of metformin and insulin in the control of hepatic gluconeogenesis was examined in isolated hepatocytes from 48h starved rats using lactate (10(-2) mol/l) with pyruvate (10(-3) mol/l) as substrate. During 1 h incubations in the absence of added insulin, 10(-2) and 10(-3) mol/l metformin reduced gluconeogenesis by 65% and 59% respectively, but lower concentrations of metformin were not effective. Insulin alone (10(-6)-10(-8) mol/l) reduced (37%-16%) gluconeogenesis. The effect of insulin was enhanced (further reductions of 11%-24%) by 5 x 10(-4) mol/l metformin, although this concentration of metformin was not effective in the absence of insulin. At lower insulin concentrations (10(-9) and 10(-10) mol/l) which did not significantly affect gluconeogenesis alone, 5 x 10(-4) mol/l metformin decreased gluconeogenesis (32% and 28% respectively). At 10(-10) mol/l insulin, metformin concentrations of 10(-3)-10(-7) mol/l decreased gluconeogenesis by 60-20%. The results suggest that therapeutic concentrations of metformin may act synergistically with physiological concentrations of insulin to suppress hepatic gluconeogenesis.

  10. Peripheral Insulin Doesn’t Alter Appetite of Broiler Chicks

    Directory of Open Access Journals (Sweden)

    Lei Liu

    2016-09-01

    Full Text Available An experiment was conducted to investigate the effect of peripheral insulin treatment on appetite in chicks. Six-d-age chicks with ad libitum feeding or fasting for 3 h before injection received a subcutaneous injection of 0, 1, 3, 5, 10, or 20 IU of insulin or vehicle (saline. The results showed peripheral insulin treatment (1 to 20 IU did not alter significantly the feed intake in chicks under either ad libitum feeding or fasting conditions within 4 h (p>0.05. Compared with the control, plasma glucose concentration was significantly decreased after insulin treatment of 3, 5, 10, and 20 IU for 4 h in chicks with ad libitum feeding (p0.05. All results suggest peripheral administration of insulin has no effect on appetite in chicks.

  11. [Adverse reactions to insulin].

    Science.gov (United States)

    Liñana, J J; Montoro, F J; Hernández, M D; Basomba, A

    1997-07-01

    The prevalence of allergic reactions to insuline has decreased during the last few years. Probably this is due to the use of the newly-developed recombinant human insuline. At present, adverse reactions to insuline occur in 5-10% of patients on therapy with insuline. Adverse reactions may be local (more frequent) or systemic (rare). Insuline resistance consists in a different type of immunological reaction. Diagnosis of allergy to insuline is based on clinical history and cutaneous and serological tests. Treatment depends upon the severity of the reaction. When insuline is indispensable despite a previous allergic reaction, a desensitization protocol may be implemented.

  12. Insulin causes insulin-receptor internalization in human erythrocyte ghosts.

    OpenAIRE

    Kelleher, R S; Murray, E F; Peterson, S W

    1987-01-01

    The effect of incubation with insulin on insulin-receptor internalization by erythrocyte ghosts was investigated. The number of surface insulin receptors decreased by 30-40% after incubation of ghosts with insulin. Total insulin-receptor binding to solubilized ghosts was the same in insulin-incubated and control ghosts, whereas insulin binding to an internal vesicular fraction was substantially increased in insulin-incubated ghosts. Our findings suggest that erythrocyte-ghost insulin receptor...

  13. Insulin and the Brain

    Directory of Open Access Journals (Sweden)

    Grosu Cristina

    2017-12-01

    Full Text Available The brain represents an important site for the action of insulin. Besides the traditionally known importance in glucoregulation, insulin has significant neurotrophic properties and influences the brain activity: insulin influences eating behavior, regulates the storage of energy and several aspects concerning memory and knowledge. Insulin resistance and hyperinsulinism could be associated with brain aging, vascular and metabolic pathologies. Elucidating the pathways and metabolism of brain insulin could have a major impact on future targeted therapies.

  14. Polarised Black Holes in AdS

    CERN Document Server

    Costa, Miguel S.; Oliveira, Miguel; Penedones, João; Santos, Jorge E.

    2016-05-03

    We consider solutions in Einstein-Maxwell theory with a negative cosmological constant that asymptote to global $AdS_{4}$ with conformal boundary $S^{2}\\times\\mathbb{R}_{t}$. At the sphere at infinity we turn on a space-dependent electrostatic potential, which does not destroy the asymptotic $AdS$ behaviour. For simplicity we focus on the case of a dipolar electrostatic potential. We find two new geometries: (i) an $AdS$ soliton that includes the full backreaction of the electric field on the $AdS$ geometry; (ii) a polarised neutral black hole that is deformed by the electric field, accumulating opposite charges in each hemisphere. For both geometries we study boundary data such as the charge density and the stress tensor. For the black hole we also study the horizon charge density and area, and further verify a Smarr formula. Then we consider this system at finite temperature and compute the Gibbs free energy for both $AdS$ soliton and black hole phases. The corresponding phase diagram generalizes the Hawkin...

  15. Determination of human insulin and its analogues in human blood using liquid chromatography coupled to ion mobility mass spectrometry (LC-IM-MS).

    Science.gov (United States)

    Thomas, Andreas; Schänzer, Wilhelm; Thevis, Mario

    2014-01-01

    The qualitative and quantitative determination of insulin from human blood samples is an emerging topic in doping controls as well as in other related disciplines (e.g. forensics). Beside the therapeutic use, insulin represents a prohibited, performance enhancing substance in sports drug testing. In both cases accurate, sensitive, specific, and unambiguous determination of the target peptide is of the utmost importance. The challenges concerning identifying insulins in blood by liquid chromatography coupled to ion mobility mass spectrometry (LC-IM-MS) are detecting the basal concentrations of approximately 0.2 ng/mL and covering the hyperinsulinaemic clamps at > 3 ng/mL simultaneously using up to 200 μL of plasma or serum. This is achieved by immunoaffinity purification of the insulins with magnetic beads and subsequent separation by micro-scale liquid chromatography coupled to ion mobility / high resolution mass spectrometry. The method includes human insulin as well as the synthetic or animal analogues insulin aspart, glulisine, glargine, detemir, lispro, bovine, and porcine insulin. The method validation shows reliable results considering specificity, limit of detection (0.2 ng/mL except for detemir: 0.8 ng/mL), limit of quantification (0.5 ng/mL for human insulin), precision (CV  0.99), recovery, accuracy (>90%), robustness (plasma/serum), and ion suppression. For quantification of human insulin a labelled internal standard ([[(2) H10 ]-Leu(B6,B11,B15,B17) ] - human Insulin) is introduced. By means of the additional ion mobility separation of the different analogues, the chromatographic run time is shortened to 8 min without losing specificity. As proof-of-concept, the procedure was successfully applied to different blood specimens from diabetic patients receiving recombinant synthetic analogues. Copyright © 2014 John Wiley & Sons, Ltd.

  16. Cotransplantation of Adipose Tissue-Derived Insulin-Secreting Mesenchymal Stem Cells and Hematopoietic Stem Cells: A Novel Therapy for Insulin-Dependent Diabetes Mellitus

    OpenAIRE

    A V Vanikar; Dave, S. D.; Thakkar, U. G.; H L Trivedi

    2010-01-01

    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 s...

  17. Alteration in insulin action

    DEFF Research Database (Denmark)

    Tanti, J F; Gual, P; Grémeaux, T

    2004-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterised by a decrease in insulin effect on glucose transport in muscle and adipose tIssue. Tyrosine phosphorylation of insulin receptor substrate 1 (IRS......-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine...... to phosphorylate these serine residues have been identified. These exciting results suggest that serine phosphorylation of IRS-1 is a possible hallmark of insulin resistance in biologically insulin responsive cells or tIssues. Identifying the pathways by which "diabetogenic" factors activate IRS-1 kinases...

  18. Current status of AdS instability

    CERN Multimedia

    CERN. Geneva

    2016-01-01

    arXiv:1403.6471 and thoroughly developed in arXiv:1407.6273. On the other hand the negative cosmological constant allows for the existence of stable, time-periodic, asymptotically AdS solutions of Einstein equations [arXiv:1303.3186].

  19. AdS braneworld with Backreaction

    CERN Document Server

    Bilic, Neven

    2014-01-01

    We review the tachyon model derived from the dynamics of a 3-brane moving in the AdS5 bulk. The bulk geometry is based on the Randall-Sundrum II model extended to include the radion. The effective tachyon Lagrangian is modified due to the back-reaction of the brane on the bulk geometry.

  20. Lorentzian AdS, Wormholes and Holography

    CERN Document Server

    Arias, Raul E; Silva, Guillermo A

    2011-01-01

    We investigate the structure of two point functions for the QFT dual to an asymptotically Lorentzian AdS-wormhole. The bulk geometry is a solution of 5-dimensional second order Einstein Gauss Bonnet gravity and causally connects two asymptotically AdS space times. We revisit the GKPW prescription for computing two-point correlation functions for dual QFT operators O in Lorentzian signature and we propose to express the bulk fields in terms of the independent boundary values phi_0^\\pm at each of the two asymptotic AdS regions, along the way we exhibit how the ambiguity of normalizable modes in the bulk, related to initial and final states, show up in the computations. The independent boundary values are interpreted as sources for dual operators O^\\pm and we argue that, apart from the possibility of entanglement, there exists a coupling between the degrees of freedom leaving at each boundary. The AdS_(1+1) geometry is also discussed in view of its similar boundary structure. Based on the analysis, we propose a ...

  1. Suicide by Insulin?

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_165701.html Suicide by Insulin? Self-harm and suicidal behavior may ... higher rates of depression, the researchers explained. And suicide or suicide attempts using insulin or other diabetes ...

  2. Insulin C-peptide

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003701.htm Insulin C-peptide test To use the sharing features ... a product that is created when the hormone insulin is produced and released into the body. The ...

  3. High-mix insulins

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2015-01-01

    Full Text Available Premix insulins are commonly used insulin preparations, which are available in varying ratios of different molecules. These drugs contain one short- or rapid-acting, and one intermediate- or long-acting insulin. High-mix insulins are mixtures of insulins that contain 50% or more than 50% of short-acting insulin. This review describes the clinical pharmacology of high-mix insulins, including data from randomized controlled trials. It suggests various ways, in which high-mix insulin can be used, including once daily, twice daily, thrice daily, hetero-mix, and reverse regimes. The authors provide a rational framework to help diabetes care professionals, identify indications for pragmatic high-mix use.

  4. Insulin pump (image)

    Science.gov (United States)

    The catheter at the end of the insulin pump is inserted through a needle into the abdominal ... with diabetes. Dosage instructions are entered into the pump's small computer and the appropriate amount of insulin ...

  5. Classifying insulin regimens

    DEFF Research Database (Denmark)

    Neu, A; Lange, K; Barrett, T

    2015-01-01

    defined. The proposed new classification for insulin management will be comprehensive, simple, and catchy. Currently available terms were included. This classification may offer the opportunity to compare therapeutic strategies without the currently existing confusion on the insulin regimen....

  6. Glycemic control and long-acting insulin analog utilization in patients with type 2 diabetes.

    Science.gov (United States)

    Heintjes, Edith M; Thomsen, Trine L; Penning-van Beest, Fernie J A; Christensen, Torsten E; Herings, Ron M C

    2010-04-01

    The objective was to compare glycemic control, insulin utilization, and body weight in patients with type 2 diabetes (T2D) initiated on insulin detemir (IDet) or insulin glargine (IGlar) in a real-life setting in the Netherlands. Insulin-naïve patients with T2D, starting treatment with IDet or IGlar between January 1, 2004 and June 30, 2008, were selected from the PHARMO data network. Glycemic control (hemoglobin A1c [HbA1c]), target rates (HbA1c <7%), daily insulin dose, and weight gain were analyzed comparing IDet and IGlar for patients with available HbA1c levels both at baseline and at 1-year follow-up. Analysis of all eligible patients (AEP) and a subgroup of patients without treatment changes (WOTC) in the follow-up period were adjusted for patient characteristics, propensity scores, and baseline HbA1c. A total of 127 IDet users and 292 IGlar users were included in the WOTC analyses. The mean HbA1c dropped from 8.4%-8.6% at baseline to 7.4% after 1 year. Patients at HbA1c goal increased from 9% at baseline to 32% for IDet and 11% to 35% for IGlar, which was not significantly different (OR 0.75, 95% CI 0.46, 1.24). Weight gain (n=90) was less among IDet users (+0.4 kg) than among IGlar users (+1.1 kg), albeit not significant. The AEP analysis (252 IDet + 468 IGlar users) showed similar results with 33%-36% at goal (OR 0.81, 95% CI 0.57, 1.16), and median daily insulin doses of 25 IU/day (P=0.70). There was no significant difference between users of IDet and IGlar with respect to glycemic control and insulin dose in a real-life setting. The low proportion of patients on target at baseline may indicate that insulin therapy is initiated too late. Moreover, the observation that one-third of the patients reached HbA1c target at follow-up may indicate that basal insulin analogs are not titrated intensively enough.

  7. Baby Skyrmions in AdS

    Energy Technology Data Exchange (ETDEWEB)

    Elliot-Ripley, Matthew; Winyard, Thomas [Department of Mathematical Sciences, Durham University,South Rd, Durham (United Kingdom)

    2015-09-01

    We study the baby Skyrme model in a pure AdS background without a mass term. The tail decays and scalings of massless radial solutions are demonstrated to take a similar form to those of the massive flat space model, with the AdS curvature playing a similar role to the flat space pion mass. We also numerically find minimal energy solutions for a range of higher topological charges and find that they form concentric ring-like solutions. Popcorn transitions (named in analogy with studies of toy models of holographic QCD) from an n layer to an n+1-layer configuration are observed at topological charges 9 and 27 and further popcorn transitions for higher charges are predicted. Finally, a point-particle approximation for the model is derived and used to successfully predict the ring structures and popcorn transitions for higher charge solitons.

  8. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel

    2014-01-01

    OBJECTIVE: Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN...... albuminuria. This finding suggests that reduced insulin sensitivity either is simply related to or might causally contribute to the initial pathogenesis of albuminuria....

  9. Glycosphingolipids and insulin resistance

    NARCIS (Netherlands)

    Langeveld, Mirjam; Aerts, Johannes M. F. G.

    2009-01-01

    Obesity is associated with an increased risk for insulin resistance, a state characterized by impaired responsiveness of liver, muscle and adipose tissue to insulin. One class of lipids involved in the development of insulin resistance are the (glyco)sphingolipids. Ceramide, the most simple

  10. AdS solutions through transgression

    Energy Technology Data Exchange (ETDEWEB)

    Donos, A. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Theory Group; Gauntlett, J.P. [Imperial College, London (United Kingdom). Blackett Lab.]|[Imperial College, London (United Kingdom). The Institute for Mathematical Sciences; Kim, Nakwoo [Kyung Hee Univ., Seoul (Korea). Dept. of Physics and Research Inst. of Basic Science

    2008-07-15

    We present new classes of explicit supersymmetric AdS{sub 3} solutions of type IIB supergravity with non-vanishing five-form flux and AdS{sub 2} solutions of D=11 supergravity with electric four-form flux. The former are dual to two-dimensional SCFTs with (0,2) supersymmetry and the latter to supersymmetric quantum mechanics with two supercharges. We also investigate more general classes of AdS{sub 3} solutions of type IIB supergravity and AdS{sub 2} solutions of D=11 supergravity which in addition have non-vanishing three-form flux and magnetic four-form flux, respectively. The construction of these more general solutions makes essential use of the Chern-Simons or ''transgression'' terms in the Bianchi identity or the equation of motion of the field strengths in the supergravity theories. We construct infinite new classes of explicit examples and for some of the type IIB solutions determine the central charge of the dual SCFTs. The type IIB solutions with non-vanishing three-form flux that we construct include a two-torus, and after two T-dualities and an S-duality, we obtain new AdS3 solutions with only the NS fields being non-trivial. (orig.)

  11. Bioactives in Blueberries Improve Insulin Sensitivity in Obese, Insulin-Resistant Men and Women1234

    Science.gov (United States)

    Stull, April J.; Cash, Katherine C.; Johnson, William D.; Champagne, Catherine M.; Cefalu, William T.

    2010-01-01

    Dietary supplementation with whole blueberries in a preclinical study resulted in a reduction in glucose concentrations over time. We sought to evaluate the effect of daily dietary supplementation with bioactives from blueberries on whole-body insulin sensitivity in men and women. A double-blinded, randomized, and placebo-controlled clinical study design was used. After screening to resolve study eligibility, baseline (wk 0) insulin sensitivity was measured on 32 obese, nondiabetic, and insulin-resistant subjects using a high-dose hyperinsulinemic-euglycemic clamp (insulin infusion of 120 mU(861 pmol)⋅m−2⋅min−1). Serum inflammatory biomarkers and adiposity were measured at baseline. At the end of the study, insulin sensitivity, inflammatory biomarkers, and adiposity were reassessed. Participants were randomized to consume either a smoothie containing 22.5 g blueberry bioactives (blueberry group, n = 15) or a smoothie of equal nutritional value without added blueberry bioactives (placebo group, n = 17) twice daily for 6 wk. Both groups were instructed to maintain their body weight by reducing ad libitum intake by an amount equal to the energy intake of the smoothies. Participants’ body weights were evaluated weekly and 3-d food records were collected at baseline, the middle, and end of the study. The mean change in insulin sensitivity improved more in the blueberry group (1.7 ± 0.5 mg⋅kg FFM−1⋅min−1) than in the placebo group (0.4 ± 0.4 mg⋅kg FFM−1⋅min−1) (P = 0.04). Insulin sensitivity was enhanced in the blueberry group at the end of the study without significant changes in adiposity, energy intake, and inflammatory biomarkers. In conclusion, daily dietary supplementation with bioactives from whole blueberries improved insulin sensitivity in obese, nondiabetic, and insulin-resistant participants. PMID:20724487

  12. Comparison of Insulin Lispro Protamine Suspension with NPH Insulin in Pregnant Women with Type 2 and Gestational Diabetes Mellitus: Maternal and Perinatal Outcomes

    Directory of Open Access Journals (Sweden)

    Antonietta Colatrella

    2013-01-01

    Full Text Available Insulin therapy is still the gold standard in diabetic pregnancy. Insulin lispro protamine suspension is an available basal insulin analogue. Aim. To study pregnancy outcomes of women with type 2 and gestational diabetes mellitus when insulin lispro protamine suspension or human NPH insulin was added to medical nutrition therapy and/or short-acting insulin. Methods. In this retrospective study, for maternal outcome we recorded time and mode of delivery, hypertension, glycaemic control (fasting blood glucose and HbA1c, hypoglycemias, weight increase, and insulin need. For neonatal outcome birth weight and weight class, congenital malformations was recorded and main neonatal complications. Two-tail Student's t-test and chi-square test were performed when applicable; significant P<0.05. Results. Eighty-nine pregnant women (25 with type 2 diabetes and 64 with gestational diabetes mellitus; 53 under insulin lispro protamine suspension and 36 under human NPH insulin were recruited. Maternal and neonatal outcomes were quite similar between the two therapeutic approaches; however, insulin need was higher in NPH. At the end of pregnancy, eight women with gestational diabetes continued to use only basal insulin analogue. Conclusions. Pregnancy outcome in type 2 and gestational diabetes mellitus with insulin lispro protamine suspension was similar to that with NPH insulin, except for a lower insulin requirement.

  13. Predicting AD conversion

    DEFF Research Database (Denmark)

    Liu, Yawu; Mattila, Jussi; Ruiz, Miguel �ngel Mu�oz

    2013-01-01

    To compare the accuracies of predicting AD conversion by using a decision support system (PredictAD tool) and current research criteria of prodromal AD as identified by combinations of episodic memory impairment of hippocampal type and visual assessment of medial temporal lobe atrophy (MTA) on MRI...

  14. Metformin and insulin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Vigneri, R.; Gullo, D.; Pezzino, V.

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific /sup 125/I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific /sup 125/I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded.

  15. [Insulin resistance in children].

    Science.gov (United States)

    Witek, Joanna; Witek, Przemysław; Pańkowska, Ewa

    2011-01-01

    Insulin resistance is characterized by decreased tissue sensitivity to insulin. The hallmark of insulin resistance is decreased tissue glucose uptake despite normal or elevated insulin concentration. There has been an upward trend in the incidence of insulin resistance in developed countries, although in pediatric population it is difficult to assess. Both genetic and environmental factors play an important role in the etiology of insulin resistance, namely increased diet caloricity and decreased physical activity. Gradually, this leads to adipose tissue build-up. The role of visceral adipose tissue is of particular importance, mainly due to its significant endocrine activity, leading to adverse metabolic effects. The most important consequences of insulin resistance in children include increased incidence of type 2 diabetes, atherogenic dyslipidemia and arterial hypertension, which lead to increased cardiovascular risk. Children with insulin resistance can develop nonalcoholic steatohepatitis and sleep apnea syndrome. In case of female pediatric patients a higher incidence of polycystic ovary syndrome (PCOS) is observed. Furthermore, the authors reviewed opinions on risk factors for insulin resistance, as well as direct and indirect insulin resistance assessment methods. The article presents the principles of primary and secondary prevention of insulin resistance in children, with particular allowance for dietary recommendations and recommendations to increase physical activity, and, in selected cases, current guidelines on pharmacological treatment.

  16. Adding more value to added-value

    DEFF Research Database (Denmark)

    Marian, Livia

    Recent studies reveal that consumers respond favourably to “organic plus” products with additional ethical attributes. The aim of the current study is to explore whether consumers would notice and value further improvements in the animal welfare standards than those imposed by the organic...... it is probably valued less than expected. The added attributes need to be thoroughly considered when developing and marketing “organic plus” products, as their effect on other product characteristics (e.g. high prices) can detract from their added value....

  17. Meal-induced increases in C-reactive protein, interleukin-6 and tumour necrosis factor α are attenuated by prandial + basal insulin in patients with Type 2 diabetes

    Science.gov (United States)

    Beisswenger, P J; Brown, W V; Ceriello, A; Le, N A; Goldberg, R B; Cooke, J P; Robbins, D C; Sarwat, S; Yuan, H; Jones, C A; Tan, M H

    2011-01-01

    Aim To determine if a regimen with prandial + basal insulin compared with basal insulin attenuates post-meal inflammatory and glycative biomarkers in patients with Type 2 diabetes. Methods This test-meal sub-study in the USA is from a previously reported clinical trial comparing the effect on glycaemic control of 24 weeks of thrice-daily pre-meal insulin lispro mix 50 (50% insulin lispro, 50% insulin lispro protamine suspension) or bedtime insulin glargine, both plus metformin. In the sub-study, glucose, insulin, triglycerides, high-sensitivity C-reactive protein, tumour necrosis factor α, interleukin-6, methylglyoxal and 3-deoxyglucosone were measured during the post-meal period of a mixed-meal breakfast at the final visit. Prandial + basal (n = 25) and basal (n = 21) insulin were administered at the same times as during the previous 24 weeks. Results Post-meal, the prandial + basal insulin group had significantly higher insulin, lower glucose and triglycerides, as well as lower high-sensitivity C-reactive protein, tumour necrosis factor α and interleukin-6, than the basal insulin group. Glucose incremental area under the concentration curve significantly correlated with high-sensitivity C-reactive protein, tumour necrosis factor α, interleukin-6, methylglyoxal and 3-deoxyglucosone incremental area under the concentration curve. Insulin incremental area under the concentration curve correlated inversely with high-sensitivity C-reactive protein and tumour necrosis factor α incremental area under the concentration curve. However, after adjusting for glucose incremental area under the concentration curve, these inverse correlations were no longer significant. Triglyceride incremental area under the concentration curve was not correlated with any biomarker incremental area under the concentration curve. Conclusions Controlling post-meal hyperglycaemia with prandial + basal insulin in patients with Type 2 diabetes attenuates meal-induced increases in high

  18. The effect of addition of liraglutide to high-dose intensive insulin therapy: a randomized prospective trial.

    Science.gov (United States)

    Lane, W; Weinrib, S; Rappaport, J; Hale, C

    2014-09-01

    Patients with type 2 diabetes and insulin resistance may require high insulin doses to control hyperglycaemia. The addition of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to basal insulin therapy has been shown to reduce insulin requirement while reducing insulin-associated weight gain [1,2]. The effect of GLP-1 RA therapy added to intensive (basal/bolus) insulin therapy has not been studied in a prospective trial. This trial evaluated the effect of the addition of liraglutide to high-dose intensive insulin therapy compared with standard insulin up-titration in obese insulin-resistant patients with type 2 diabetes requiring high-dose insulin therapy. Thirty-seven subjects with type 2 diabetes requiring >100 units of insulin daily administered either by continuous subcutaneous insulin infusion (CSII) or by multiple daily injections (MDIs) with or without metformin were randomized to receive either liraglutide plus insulin (LIRA) or intensive insulin only (controls). Liraglutide was initiated at 0.6 mg subcutaneously (sq) per day and increased to either 1.2 or 1.8 mg daily in combination with intensive insulin therapy. Controls received intensive insulin up-titration only. At 6 months, subjects receiving liraglutide plus insulin experienced statistically significant reductions in HbA1c, weight, insulin dose and glycaemic variability (GV) by continuous glucose monitor (CGM) compared with the control group receiving insulin only. Adding liraglutide to intensive high-dose (basal/bolus) insulin therapy results in greater improvement in glycaemic control than insulin therapy alone, with additional benefits of weight loss and reduced GV. © 2014 John Wiley & Sons Ltd.

  19. The political attack ad

    Directory of Open Access Journals (Sweden)

    Palma Peña-Jiménez, Ph.D.

    2011-01-01

    Full Text Available During election campaigns the political spot has a clear objective: to win votes. This message is communicated to the electorate through television and Internet, and usually presents a negative approach, which includes a direct critical message against the opponent, rather than an exposition of proposals. This article is focused on the analysis of the campaign attack video ad purposely created to encourage the disapproval of the political opponent among voters. These ads focus on discrediting the opponent, many times, through the transmission of ad hominem messages, instead of disseminating the potential of the political party and the virtues and manifesto of its candidate. The article reviews the development of the attack ad since its first appearance, which in Spain dates back to 1996, when the famous Doberman ad was broadcast, and examines the most memorable campaign attack ads.

  20. [Insulin therapy and sports].

    Science.gov (United States)

    Aigner, A

    1997-01-01

    Physical work effects a transitory enhanced affinity of insulin to its receptor in the stressed muscles and thereby a better efficiency. Therefore, in sports lasting for 30 min and more the basal and/or bolus doses of insulin have to be reduced in order to prevent hypoglycemia. An alternative supply of additional carbohydrates prior to physical work is often not practicable. Injections of insulin into areas of the body not involved in muscular work do not give sufficient warranty against hypoglycemic reactions. A new short-acting insulin-analogue (Lispro) shows a reduced effect on blood glucose levels after 3 h as compared to regular insulin. Therefore, it could be of advantage for insulin dependent diabetics doing their exercise at this time.

  1. Insulin aspart pharmacokinetics

    DEFF Research Database (Denmark)

    Rasmussen, Christian Hove; Roge, Rikke Meldgaard; Ma, Zhulin

    2014-01-01

    Background: Insulin aspart (IAsp) is used by many diabetics as a meal-time insulin to control postprandial glucose levels. As is the case with many other insulin types, the pharmacokinetics (PK), and consequently the pharmacodynamics (PD), is associated with clinical variability, both between...... to investigate and quantify the properties of the subcutaneous depot. Data from Brange et al. (1990) are used to determine the effects of insulin chemistry in subcutis on the absorption rate. Intravenous (i.v.) bolus and infusion PK data for human insulin are used to understand and quantify the systemic...... distribution and elimination (Porksen et al., 1997; Sjostrand et al., 2002). PK and PD profiles for type 1 diabetics from Chen et al. (2005) are analyzed to demonstrate the effects of IAsp antibodies in terms of bound and unbound insulin. PK profiles from Thorisdottir et al. (2009) and Ma et al. (2012b...

  2. Diabetes, insulin and exercise

    DEFF Research Database (Denmark)

    Richter, Erik; Galbo, H

    1986-01-01

    The metabolic and hormonal adaptations to single exercise sessions and to exercise training in normal man and in patients with insulin-dependent as well as non-insulin-dependent diabetes mellitus are reviewed. In insulin-dependent (type I) diabetes good metabolic control is best obtained...... of the patient's reaction to exercise is desirable, which necessitates frequent self-monitoring of plasma glucose. It may often be necessary to diminish the insulin dose before exercise, and/or to ingest additional carbohydrate during or after exercise. In non-insulin-dependent (type II) diabetes, exercise...... by a regular pattern of life which will lead to a fairly constant demand for insulin from day to day. Exercise is by nature a perturbation that makes treatment of diabetes difficult: Muscle contractions per se tend to decrease the plasma glucose concentration whereas the exercise-induced response of the so...

  3. Flexibility in insulin prescription

    Directory of Open Access Journals (Sweden)

    Sanjay Kalra

    2016-01-01

    Full Text Available This communication explores the concept of flexibility, a propos insulin preparations and insulin regimes used in the management of type 2 diabetes. The flexibility of an insulin regime or preparation is defined as their ability to be injected at variable times, with variable injection-meal time gaps, in a dose frequency and quantum determined by shared decision making, with a minimal requirement of glucose monitoring and health professional consultation, with no compromise on safety, efficiency and tolerability. The relative flexibility of various basal, prandial and dual action insulins, as well as intensive regimes, is compared. The biopsychosocial model of health is used to assess the utility of different insulins while encouraging a philosophy of flexible insulin usage.

  4. Effects of switching from prandial premixed insulin therapy to basal plus two times bolus insulin therapy on glycemic control and quality of life in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Ito, Hiroyuki; Abe, Mariko; Antoku, Shinichi; Omoto, Takashi; Shinozaki, Masahiro; Nishio, Shinya; Mifune, Mizuo; Togane, Michiko

    2014-01-01

    The effects of switching from prandial premixed insulin therapy (PPT) injected three times a day to basal plus two times bolus insulin therapy (B2B) on glycemic control and quality of life were investigated in patients with type 2 diabetes mellitus. The clinical course was prospectively observed during the first 16 weeks after switching to B2B (insulin glargine plus insulin glulisine before breakfast and dinner) in 27 subjects previously treated with PPT using 50/50 premixed insulin. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was administered at the start and end of the study. The glycated hemoglobin (HbA1c) level (8.3% ± 1.8% to 8.2% ± 1.1%) and the DTSQ score did not change between the start and end of the study. An improvement in HbA1c level was found in nine (33%) subjects. The change in HbA1c showed a significant negative correlation with baseline HbA1c, and was significantly better in patients with a baseline HbA1c >8.0% than in those with an HbA1c ≤ 8.0% (-0.9 ± 2.0 versus 0.3 ± 0.6, respectively, P = 0.02). The change in DTSQ score representing treatment satisfaction was significantly greater in patients whose HbA1c level was improved than in those in whom it was not (2.7 ± 3.6 versus -0.8 ± 3.5, P = 0.04). B2B was noninferior to PPT with regard to HbA1c levels in patients with type 2 diabetes mellitus. B2B should be considered particularly for subjects whose glycemic control is poor despite PPT.

  5. Twistor methods for AdS$_5$

    CERN Document Server

    Adamo, Tim; Williams, Jack

    2016-01-01

    We consider the application of twistor theory to five-dimensional anti-de Sitter space. The twistor space of AdS$_5$ is the same as the ambitwistor space of the four-dimensional conformal boundary; the geometry of this correspondence is reviewed for both the bulk and boundary. A Penrose transform allows us to describe free bulk fields, with or without mass, in terms of data on twistor space. Explicit representatives for the bulk-to-boundary propagators of scalars and spinors are constructed, along with twistor action functionals for the free theories. Evaluating these twistor actions on bulk-to-boundary propagators is shown to produce the correct two-point functions.

  6. History of insulin

    Directory of Open Access Journals (Sweden)

    Celeste C. Quianzon

    2012-07-01

    Full Text Available The advancement of diabetes treatment has gone from crude extracts of insulin and accidental discovery of sulfa-like drugs in antibiotics to the development of drugs based on improved understanding of the pathophysiology of diabetes mellitus. This article will review the history of the discovery and development of insulin. A companion focusing on non-insulin diabetes agents will follow in the next issue of JCHIMP.

  7. Insulin resistance and atherosclerosis

    OpenAIRE

    Semenkovich, Clay F.

    2006-01-01

    Considerable evidence supports the association between insulin resistance and vascular disease, and this has led to wide acceptance of the clustering of hyperlipidemia, glucose intolerance, hypertension, and obesity as a clinical entity, the metabolic syndrome. While insulin resistance, by promoting dyslipidemia and other metabolic abnormalities, is part of the proatherogenic milieu, it is possible that insulin resistance itself in the vascular wall does not promote atherosclerosis. Recent fi...

  8. Insulin, cognition, and dementia

    Science.gov (United States)

    Cholerton, Brenna; Baker, Laura D.; Craft, Suzanne

    2015-01-01

    Cognitive disorders of aging represent a serious threat to the social and economic welfare of current society. It is now widely recognized that pathology related to such conditions, particularly Alzheimer’s disease, likely begins years or decades prior to the onset of clinical dementia symptoms. This revelation has led researchers to consider candidate mechanisms precipitating the cascade of neuropathological events that eventually lead to clinical Alzheimer’s disease. Insulin, a hormone with potent effects in the brain, has recently received a great deal of attention for its potential beneficial and protective role in cognitive function. Insulin resistance, which refers to the reduced sensitivity of target tissues to the favorable effects of insulin, is related to multiple chronic conditions known to impact cognition and increase dementia risk. With insulin resistance-associated conditions reaching epidemic proportions, the prevalence of Alzheimer’s disease and other cognitive disorders will continue to rise exponentially. Fortunately, these chronic insulin-related conditions are amenable to pharmacological intervention. As a result, novel therapeutic strategies that focus on increasing insulin sensitivity in the brain may be an important target for protecting or treating cognitive decline. The following review will highlight our current understanding of the role of insulin in brain, potential mechanisms underlying the link between insulin resistance and dementia, and current experimental therapeutic strategies aimed at improving cognitive function via modifying the brain’s insulin sensitivity. PMID:24070815

  9. Análogos de insulina: relevancia clínica y perspectivas futuras The clinical relevance of insulin analogues and future perspectives

    Directory of Open Access Journals (Sweden)

    Jhon Jairo BejaranoRoncancio

    2012-12-01

    Full Text Available Desde la década de los noventa han sido diseñados análogos de insulina para el manejo de pacientes diabéticos usando técnicas de ADN recombinante. Las modificaciones de la molécula original de insulina humana les confieren una rápida, ultrarrápida y prolongada acción. Entre las insulinas ultra rápidas están la Aspártica, la Lispro y la Glulisina y entre las de acción prolongada están la Glargina y la Detemir. También se encuentran mezcladas con insulina humana NPH en diferentes proporciones. Aunque existen diferentes tipos de algoritmos terapéuticos, la insulinización sigue siendo una terapia artesanal basada en la experiencia del especialista tratante. La introducción de los análogos de insulina hace más factible el empleo de bolos correctores o dosis extra de insulina para reducir las hipoglicemias puntuales en cualquier momento del día y facilitar el manejo de los carbohidratos en la dieta.Insulin analogues have been engineered through recombinant DNA techniques for managing diabetic patients since the 1990s; modifications to the original human insulin molecule have made them rapid, ultrarapid and prolonged acting. Aspart, lispro and glulisine are ultrafast insulins and glargine and detemir are longacting ones. Such insulins may be premixed in formulations combining neutral protamine Hagedorn (NPH with regular human insulin (70%/30%. Different types of therapeutic algorithms are available nowadays but insulinisation remains a crafted therapy based on the treating specialist's experience. The introduction of insulin analogues enables using correction boluses or extra doses of insulin to reduce hypoglycaemia at any time of the day and facilitates handling carbohydrates in a particular patient's diet.

  10. Control of Muscle Mitochondria by Insulin Entails Activation of Akt2-mtNOS Pathway: Implications for the Metabolic Syndrome

    Science.gov (United States)

    Finocchietto, Paola; Barreyro, Fernando; Holod, Silvia; Peralta, Jorge; Franco, María C.; Méndez, Carlos; Converso, Daniela P.; Estévez, Alvaro; Carreras, Maria C.; Poderoso, Juan J.

    2008-01-01

    Background In the metabolic syndrome with hyperinsulinemia, mitochondrial inhibition facilitates muscle fat and glycogen accumulation and accelerates its progression. In the last decade, nitric oxide (NO) emerged as a typical mitochondrial modulator by reversibly inhibiting citochrome oxidase and oxygen utilization. We wondered whether insulin-operated signaling pathways modulate mitochondrial respiration via NO, to alternatively release complete glucose oxidation to CO2 and H2O or to drive glucose storage to glycogen. Methodology/Principal Findings We illustrate here that NO produced by translocated nNOS (mtNOS) is the insulin-signaling molecule that controls mitochondrial oxygen utilization. We evoke a hyperinsulinemic-normoglycemic non-invasive clamp by subcutaneously injecting adult male rats with long-lasting human insulin glargine that remains stable in plasma by several hours. At a precise concentration, insulin increased phospho-Akt2 that translocates to mitochondria and determines in situ phosphorylation and substantial cooperative mtNOS activation (+4–8 fold, Pinsulin metabolic effects on gastrocnemius muscles by direct electroporation of siRNA nNOS or empty vector in the two legs of the same animal, confirmed that in the silenced muscles disrupted mtNOS allows higher oxygen uptake and complete (U-14C)-glucose utilization respect to normal mtNOS in the vector-treated ones (respectively 37±3 vs 10±1 µmolO2/h.g tissue and 13±1 vs 7.2±1 µmol 3H2O/h.g tissue, Pinsulin depresses mitochondrial respiration in skeletal muscle via NO which permits substrates to be deposited as macromolecules; at discrete hyperinsulinemia, persistent mtNOS activation could contribute to mitochondrial dysfunction with insulin resistance and obesity and therefore, to the progression of the metabolic syndrome. PMID:18335029

  11. Metabolic consequences of incorrect insulin administration techniques in aging subjects with diabetes.

    Science.gov (United States)

    Gentile, Sandro; Agrusta, Mariano; Guarino, Giuseppina; Carbone, Lucia; Cavallaro, Vincenzo; Carucci, Iarba; Strollo, Felice

    2011-06-01

    Only few insulin-treated (IT) people with diabetes mellitus (DM) reach the target due to poor compliance and/or to sedentary lifestyle and/or to inadequate treatment regimen. The latter may be also brought about by often overlooked factors including insulin injection into altered skin areas, often brought about by incorrect habits, namely needle reutilization or poor compliance to the suggestion to continuously rotate skin injection areas. The aim of our study was to evaluate the rate of skin lesions within the sites commonly used for insulin injection in our IT DM patients and to verify whether a short-acting insulin analogue yielded different metabolic effects when injected in altered vs. normal skin areas. One hundred and eighty well-trained IT people with type 1 and type 2 DM (64 ± 15 years of age) consecutively referring to our unit underwent a standard clinical examination involving an accurate skin inspection protocol meant at looking for any alterations eventually affecting all possible injection sites, including bruising, multiple needle pricks and lipodystrophic nodules (LN). They were also tested for HPLC HbA1c determination and asked to fill in a standard questionnaire on injection habits. Furthermore, seven male, T1DM glulisine-glargine basal-bolus-treated patients in this group were randomly injected 10 IU glulisine into either normal skin (NS) or an LN by a nurse before a standard, 405 kcal breakfast, for blood glucose and free insulin determination at 0, 30, 45, 60, 75, 90, 120 and 150 min. More lesions were found in people over sixty (P 7.5% was found in patients with lesions (with an O.R. of 3.74) and further confirmed by data obtained from head-to-head comparison of insulin injection into an LN and NS. In fact, injection into an LN proved to impair and slow down insulin absorption, resulting in a higher absolute value and a larger variability of blood glucose levels than those observed by utilizing NS. This suggests us to pay more attention to

  12. Skil problemerne ad

    DEFF Research Database (Denmark)

    Kaspersen, Peter

    2007-01-01

    På grundlag af evalueringer og forskning i gymnasiereformen 2005 foreslås det at skille problemerne ad i forskellige niveauer. Herved kan der arbejdes med niveaudelte løsninger.......På grundlag af evalueringer og forskning i gymnasiereformen 2005 foreslås det at skille problemerne ad i forskellige niveauer. Herved kan der arbejdes med niveaudelte løsninger....

  13. Insulin Resistance and Alzheimer’s Disease: Bioenergetic Linkages

    Directory of Open Access Journals (Sweden)

    Bryan J. Neth

    2017-10-01

    Full Text Available Metabolic dysfunction is a well-established feature of Alzheimer’s disease (AD, evidenced by brain glucose hypometabolism that can be observed potentially decades prior to the development of AD symptoms. Furthermore, there is mounting support for an association between metabolic disease and the development of AD and related dementias. Individuals with insulin resistance, type 2 diabetes mellitus (T2D, hyperlipidemia, obesity, or other metabolic disease may have increased risk for the development of AD and similar conditions, such as vascular dementia. This association may in part be due to the systemic mitochondrial dysfunction that is common to these pathologies. Accumulating evidence suggests that mitochondrial dysfunction is a significant feature of AD and may play a fundamental role in its pathogenesis. In fact, aging itself presents a unique challenge due to inherent mitochondrial dysfunction and prevalence of chronic metabolic disease. Despite the progress made in understanding the pathogenesis of AD and in the development of potential therapies, at present we remain without a disease-modifying treatment. In this review, we will discuss insulin resistance as a contributing factor to the pathogenesis of AD, as well as the metabolic and bioenergetic disruptions linking insulin resistance and AD. We will also focus on potential neuroimaging tools for the study of the metabolic dysfunction commonly seen in AD with hopes of developing therapeutic and preventative targets.

  14. Probing crunching AdS cosmologies

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, S. Prem; Vaganov, Vladislav [Department of Physics, Swansea University,Singleton Park, Swansea SA2 8PP (United Kingdom)

    2016-02-03

    Holographic gravity duals of deformations of CFTs formulated on de Sitter spacetime contain FRW geometries behind a horizon, with cosmological big crunch singularities. Using a specific analytically tractable solution within a particular single scalar truncation of N=8 supergravity on AdS{sub 4}, we first probe such crunching cosmologies with spacelike radial geodesics that compute spatially antipodal correlators of large dimension boundary operators. At late times, the geodesics lie on the FRW slice of maximal expansion behind the horizon. The late time two-point functions factorise, and when transformed to the Einstein static universe, they exhibit a temporal non-analyticity determined by the maximal value of the scale factor ã{sub max}. Radial geodesics connecting antipodal points necessarily have de Sitter energy E≲ã{sub max}, while geodesics with E>ã{sub max} terminate at the crunch, the two categories of geodesics being separated by the maximal expansion slice. The spacelike crunch singularity is curved “outward” in the Penrose diagram for the deformed AdS backgrounds, and thus geodesic limits of the antipodal correlators do not directly probe the crunch. Beyond the geodesic limit, we point out that the scalar wave equation, analytically continued into the FRW patch, has a potential which is singular at the crunch along with complex WKB turning points in the vicinity of the FRW crunch. We then argue that the frequency space Green’s function has a branch point determined by ã{sub max} which corresponds to the lowest quasinormal frequency.

  15. Central insulin dysregulation and energy dyshomeostasis in two mouse models of Alzheimer's disease.

    Science.gov (United States)

    Velazquez, Ramon; Tran, An; Ishimwe, Egide; Denner, Larry; Dave, Nikhil; Oddo, Salvatore; Dineley, Kelly T

    2017-10-01

    Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide. While the causes of AD are not known, several risk factors have been identified. Among these, type two diabetes (T2D), a chronic metabolic disease, is one of the most prevalent risk factors for AD. Insulin resistance, which is associated with T2D, is defined as diminished or absent insulin signaling and is reflected by peripheral blood hyperglycemia and impaired glucose clearance. In this study, we used complementary approaches to probe for peripheral insulin resistance, central nervous system (CNS) insulin sensitivity and energy homeostasis in Tg2576 and 3xTg-AD mice, two widely used animal models of AD. We report that CNS insulin signaling abnormalities are evident months before peripheral insulin resistance. In addition, we find that brain energy metabolism is differentially altered in both mouse models, with 3xTg-AD mice showing more extensive changes. Collectively, our data suggest that early AD may reflect engagement of different signaling networks that influence CNS metabolism, which in turn may alter peripheral insulin signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Humanin: a novel central regulator of peripheral insulin action.

    Directory of Open Access Journals (Sweden)

    Radhika H Muzumdar

    2009-07-01

    Full Text Available Decline in insulin action is a metabolic feature of aging and is involved in the development of age-related diseases including Type 2 Diabetes Mellitus (T2DM and Alzheimer's disease (AD. A novel mitochondria-associated peptide, Humanin (HN, has a neuroprotective role against AD-related neurotoxicity. Considering the association between insulin resistance and AD, we investigated if HN influences insulin sensitivity.Using state of the art clamp technology, we examined the role of central and peripheral HN on insulin action. Continuous infusion of HN intra-cerebro-ventricularly significantly improved overall insulin sensitivity. The central effects of HN on insulin action were associated with activation of hypothalamic STAT-3 signaling; effects that were negated by co-inhibition of hypothalamic STAT-3. Peripheral intravenous infusions of novel and potent HN derivatives reproduced the insulin-sensitizing effects of central HN. Inhibition of hypothalamic STAT-3 completely negated the effects of IV HN analog on liver, suggesting that the hepatic actions of HN are centrally mediated. This is consistent with the lack of a direct effect of HN on primary hepatocytes. Furthermore, single treatment with a highly-potent HN analog significantly lowered blood glucose in Zucker diabetic fatty rats. Based upon the link of HN with two age-related diseases, we examined if there were age associated changes in HN levels. Indeed, the amount of detectable HN in hypothalamus, skeletal muscle, and cortex was decreased with age in rodents, and circulating levels of HN were decreased with age in humans and mice.We conclude that the decline in HN with age could play a role in the pathogenesis of age-related diseases including AD and T2DM. HN represents a novel link between T2DM and neurodegeneration and along with its analogues offers a potential therapeutic tool to improve insulin action and treat T2DM.

  17. The insulin sparing effect of metformin in insulin-treated diabetic patients.

    Science.gov (United States)

    Slama, G

    1991-05-01

    Since metformin became available for therapeutic utilisation, more than 30 years ago, it has been found that the compound was able to reduce hyperglycaemia in diabetic subjects without any stimulation of B cell secretion. The mechanism(s) of action of this drug has been better clarified these last 5-10 years even if all its aspects are not yet fully elucidated. What has been established, however, since the beginning of its clinical use, is that metformin can act in the presence of insulin in "facilitating" its effects. This had lead some authors to investigate the possible synergistic effect of metformin added to insulin therapy. Some studies have thus shown that insulin requirements were significantly decreased during the administration of biguanides, and effect which seemed to be maximal shortly after commencing the drug. Some authors have also claimed that biguanides smooth out blood glucose profiles in brittle diabetes, but this is denied by others. A decrease in insulin requirements may be of interest in diminishing peripheral hyperinsulinism and its possible consequences. It remains questionable whether the addition of metformin in the long term is to be recommended in Type 1 diabetic patients. However, such a clarification of decrease insulin requirements can help in the understanding of the clinical significance of metformin's actions in diabetes (impact on insulin resistance, receptor and post-receptor effects).

  18. Mobile ad hoc networking

    CERN Document Server

    John Wiley & Sons

    2004-01-01

    "Assimilating the most up-to-date information on research and development activities in this rapidly growing area, Mobile Ad Hoc Networking covers physical, data link, network, and transport layers, as well as application, security, simulation, and power management issues in sensor, local area, personal, and mobile ad hoc networks. Each of the book's sixteen chapters has been written by a top expert and discusses in-depth the most important topics in the field. Mobile Ad Hoc Networking is an excellent reference and guide for professionals seeking an in-depth examination of topics that also provides a comprehensive overview of the current state-of-the-art."--Jacket.

  19. The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy

    DEFF Research Database (Denmark)

    Battelino, T; Conget, I; Olsen, B

    2012-01-01

    The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes.......The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes....

  20. Antiproton-Decelerator (AD)

    CERN Multimedia

    Laurent Guiraud

    1998-01-01

    When the Low-Energy Antiproton Ring (LEAR) was stopped in 1996, because of its costly operation, a cheaper way of continuing low-energy antiproton physics was sought. The Antiproton-Collector (AC), added in 1987 to the Antiproton Accumulator (AA) to provide a tenfold intensity increase, was converted into the Antiproton-Decelerator (AD). Antiprotons from the target at 3.5 GeV/c are decelerated to 100 MeV/c, and fast-ejected to the experiments. Major changes were necessary. Above all, the conversion from a constant-field machine to one with a magnetic cycle, modulating the field by an impressive factor 35. New systems for stochastic and electron cooling had to be added. Beam diagnostics at an intensity of only 2E7 antiprotons was a challenge. In 2000, the AD began delivery of antiprotons to the experiments.

  1. Insulin initiation and intensification in patients with T2DM for the primary care physician

    Directory of Open Access Journals (Sweden)

    Unger J

    2011-06-01

    Full Text Available Jeff UngerCatalina Research Institute, Chino, CA, USAAbstract: Type 2 diabetes mellitus (T2DM is characterized by both insulin resistance and inadequate insulin secretion. All patients with the disease require treatment to achieve and maintain the target glycosylated hemoglobin (A1C level of 6.5%–7%. Pharmacological management of T2DM typically begins with the introduction of oral medications, and the majority of patients require exogenous insulin therapy at some point in time. Primary care physicians play an essential role in the management of T2DM since they often initiate insulin therapy and intensify regimens over time as needed. Although insulin therapy is prescribed on an individualized basis, treatment usually begins with basal insulin added to a background therapy of oral agents. Prandial insulin injections may be added if glycemic targets are not achieved. Treatments may be intensified over time using patient-friendly titration algorithms. The goal of insulin intensification within the primary care setting is to minimize patients' exposure to chronic hyperglycemia and weight gain, and reduce patients' risk of hypoglycemia, while achieving individualized fasting, postprandial, and A1C targets. Simplified treatment protocols and insulin delivery devices allow physicians to become efficient prescribers of insulin intensification within the primary care arena.Keywords: diabetes, basal, bolus, regimens, insulin analogs, structured glucose testing

  2. Differential effects of insulin injections and insulin infusions on levels ...

    African Journals Online (AJOL)

    Studies have shown that while injections of insulin cause an increase in fat mass, infusions of insulin increase fat mass. The aim of this paper was to test the hypothesis that if an increase in glycogen is an indicator of an impending increase in adipose mass, then insulin infusions should not increase glycogen, while insulin ...

  3. Insulin in diabetes prevention.

    Science.gov (United States)

    Ramiya, V K; Maclaren, N K

    1997-01-01

    Insulin-dependent diabetes (IDD) is a chronic immune-endocrine disease in which there is a progressive destruction of insulin-secreting pancreatic beta cells, caused primarily by autoreactive T cells. Many islet cell proteins including insulin, glutamic acid decarboxylase, and tyrosine phosphatase antigens (IA-2) are targeted by the autoimmune responses in IDD patients. Since its discovery 75 years ago, insulin has been the major player in the clinical management of hyperglycaemia in these patients. The morbidity and mortality associated with IDD derives mainly from the complications of the disease. However, routine insulin injections seldom achieve a consistent, near-normal glucose level, where multiple daily doses of the hormone involve considerable restrictions to a normal lifestyle. In terms of economics, the management of diabetes is expensive, and in the USA diabetes alone accounts for one seventh of the healthcare budget. These clinical, lifestyle and economic issues emphasize the need to investigate alternative preventative measures in IDD treatment. Recent reports suggest a pivotal role for insulin in various aspects of the immune system. In this study, insulin and B-chain were used to modulate autoimmune responses in non-obese diabetic mice, findings which have therapeutic implications in man.

  4. Low ethanol consumption increases insulin sensitivity in Wistar rats

    Directory of Open Access Journals (Sweden)

    D.T. Furuya

    2003-01-01

    Full Text Available Several human studies suggest that light-to-moderate alcohol consumption is associated with enhanced insulin sensitivity, but these studies are not free of conflicting results. To determine if ethanol-enhanced insulin sensitivity could be demonstrated in an animal model, male Wistar rats were fed a standard chow diet and received drinking water without (control or with different ethanol concentrations (0.5, 1.5, 3, 4.5 and 7%, v/v for 4 weeks ad libitum. Then, an intravenous insulin tolerance test (IVITT was performed to determine insulin sensitivity. Among the ethanol groups, only the 3% ethanol group showed an increase in insulin sensitivity based on the increase of the plasma glucose disappearance rate in the IVITT (30%, P<0.05. In addition, an intravenous glucose tolerance test (IVGTT was performed in control and 3% ethanol animals. Insulin sensitivity was confirmed in 3% ethanol rats based on the reduction of insulin secretion in the IVGTT (35%, P<0.05, despite the same glucose profile. Additionally, the 3% ethanol treatment did not impair body weight gain or plasma aspartate aminotransferase and alanine aminotransferase activities. Thus, the present study established that 3% ethanol in the drinking water for 4 weeks in normal rats is a model of increased insulin sensitivity, which can be used for further investigations of the mechanisms involved.

  5. [Therapeutic options for a type 2 diabetic patient not well controlled with metformin plus basal insulin].

    Science.gov (United States)

    Scheen, André J; Paquot, Nicolas

    2017-08-23

    In a patient with type 2 diabetes not well controlled with a basal insulin - metformin combination, several therapeutic options may be considered: intensifying insulin therapy with different schemes (appropriate titration using a more favourable basal insulin analogue, adding one, two or three rapid-acting insulin analogues, shift to two or three premix insulin injections), adding a dipeptidyl peptidase-4 inhibitor (gliptin) or an inhibitor of sodium-glucose cotransporters type 2 (gliflozin), or combining a glucagon-like peptide-1 receptor agonist with basal insulin. The choice should be made according the individual profile and preference of the patient, in a personalized approach, taking into account the advantages and disadvantages of each therapeutic solution.

  6. Effects of switching from prandial premixed insulin therapy to basal plus two times bolus insulin therapy on glycemic control and quality of life in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Ito H

    2014-04-01

    Full Text Available Hiroyuki Ito, Mariko Abe, Shinichi Antoku, Takashi Omoto, Masahiro Shinozaki, Shinya Nishio, Mizuo Mifune, Michiko ToganeDepartment of Diabetes, Metabolism and Kidney Disease, Edogawa Hospital, Tokyo, JapanBackground: The effects of switching from prandial premixed insulin therapy (PPT injected three times a day to basal plus two times bolus insulin therapy (B2B on glycemic control and quality of life were investigated in patients with type 2 diabetes mellitus.Methods: The clinical course was prospectively observed during the first 16 weeks after switching to B2B (insulin glargine plus insulin glulisine before breakfast and dinner in 27 subjects previously treated with PPT using 50/50 premixed insulin. The Diabetes Treatment Satisfaction Questionnaire (DTSQ was administered at the start and end of the study.Results: The glycated hemoglobin (HbA1c level (8.3%±1.8% to 8.2%±1.1% and the DTSQ score did not change between the start and end of the study. An improvement in HbA1c level was found in nine (33% subjects. The change in HbA1c showed a significant negative correlation with baseline HbA1c, and was significantly better in patients with a baseline HbA1c >8.0% than in those with an HbA1c ≤8.0% (−0.9±2.0 versus 0.3±0.6, respectively, P=0.02. The change in DTSQ score representing treatment satisfaction was significantly greater in patients whose HbA1c level was improved than in those in whom it was not (2.7±3.6 versus −0.8±3.5, P=0.04.Conclusion: B2B was noninferior to PPT with regard to HbA1c levels in patients with type 2 diabetes mellitus. B2B should be considered particularly for subjects whose glycemic control is poor despite PPT.Keywords: type 2 diabetes mellitus, insulin therapy, basal plus two times bolus insulin therapy, prandial premixed insulin therapy, Diabetes Treatment Satisfaction Questionnaire

  7. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    PRAKASH

    studies in β cell-specific IR knockout mice, which develop peripheral insulin resistance and diabetes, most probably due to the changes in the pattern of insulin secretion (Kulkarni et al 1999). FFA also affects downstream insulin signalling molecules. It inhibits insulin activation of IRS-1-associated PI3K activity in muscle.

  8. Randomized Trial of the Effects of Insulin and Metformin on Myocardial Injury and Stress in Diabetes Mellitus: A Post Hoc Exploratory Analysis.

    Science.gov (United States)

    Srivastava, Pratyaksh K; Pradhan, Aruna D; Cook, Nancy R; Ridker, Paul M; Everett, Brendan M

    2017-12-23

    Subclinical myocardial injury, as measured by high-sensitivity cardiac troponin T (hsTnT), and myocardial stress, as measured by N-terminal pro-B-type natriuretic peptide (NT-proBNP), are related to glycemic control in patients with type 2 diabetes mellitus, and are strong predictors of adverse cardiovascular outcomes. We sought to determine whether antihyperglycemic therapy improves measures of myocardial injury and myocardial stress in patients with type 2 diabetes mellitus. We randomized, in a 2×2 factorial fashion, 438 patients with type 2 diabetes mellitus to insulin glargine, metformin, the combination, or placebo and measured changes in NT-proBNP and hsTnT after 12 weeks of therapy. At baseline, the median (Q1-Q3) plasma concentration was 35.4 (15.7-86.3) ng/L for NT-proBNP and 6.7 (4.6-10.1) ng/L for hsTnT. The adjusted (95% confidence interval) change in NT-proBNP concentration was 20.7% (7.9-35.0) in the insulin arm compared with 0.13% (-10.8 to 12.5) in the no-insulin arm ( P =0.03 for comparison). These changes were not related to changes in fasting or postprandial glucose, glycated hemoglobin, weight, blood pressure, or inflammation. In the metformin arm, the adjusted change in NT-proBNP was 7.8% (-3.7 to 20.7) compared with 13.0% (0.72-26.8) in the no-metformin arm ( P =0.58). No significant changes in hsTnT concentrations were observed for any of the treatment arms. Insulin glargine was associated with a significant 20.7% increase in NT-proBNP, a marker of myocardial stress, after 12 weeks of therapy. No change in hsTnT, a marker of myocardial injury, was observed. The changes were independent of substantial improvements in glucose control. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00366301. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  9. AMPK and insulin action

    DEFF Research Database (Denmark)

    Frøsig, Christian; Jensen, Thomas Elbenhardt; Jeppesen, Jacob

    2013-01-01

    The 5'-AMP-activated protein kinase (AMPK) is considered "a metabolic master-switch" in skeletal muscle reducing ATP- consuming processes whilst stimulating ATP regeneration. Within recent years, AMPK has also been proposed as a potential target to attenuate insulin resistance, although the exact...... role of AMPK is not well understood. Here we hypothesized that mice lacking a2AMPK activity in muscle would be more susceptible to develop insulin resistance associated with ageing alone or in combination with high fat diet. Young (~4 month) or old (~18 month) wild type and muscle specific a2AMPK...... kinase-dead mice on chow diet as well as old mice on 17 weeks of high fat diet were studied for whole body glucose homeostasis (OGTT, ITT and HOMA-IR), insulin signaling and insulin-stimulated glucose uptake in muscle. We demonstrate that high fat diet in old mice results in impaired glucose homeostasis...

  10. Biphasic Insulin Analogues in Type 2 Diabetes: Expert Panel Recommendations

    Directory of Open Access Journals (Sweden)

    Sema Akalın

    2011-09-01

    of Biphasic Insulin Aspart 30 treatment has been published recently, these types of guidelines cannot always respond to all of the local requirements. Therefore, it is aimed to prepare a guideline to facilitate the use of Biphasic Insulin Aspart 30 in the right patient, at the right time and in the right manner, as well as to help the physicians. A guideline, aiming to contain current evidences and to meet local requirements, was developed in May and June 2010 by an expert panel composed of experienced endocrinologists working at different parts of Turkey. The guideline includes initial treatment, optimization of initiation dose, and intensification of Biphasic Insulin Aspart 30 during the disease progression. Although previously published global guidelines about initiation, intensification, dose division, dose addition and combination of Biphasic Insulin Aspart 30 with OADs is in applicable situation in general, the content is enlarged by adding some special conditions. Administration information presented in this article forms simply a suggestion rather than a strict recommendation. Since the treatment of every diabetic patient should be individualized, suggestions of this guideline do not have any obligatory power on physicians. Turk Jem 2011; 15: 65-70

  11. Dynamic ad hoc networks

    CERN Document Server

    Rashvand, Habib

    2013-01-01

    Motivated by the exciting new application paradigm of using amalgamated technologies of the Internet and wireless, the next generation communication networks (also called 'ubiquitous', 'complex' and 'unstructured' networking) are changing the way we develop and apply our future systems and services at home and on local, national and global scales. Whatever the interconnection - a WiMAX enabled networked mobile vehicle, MEMS or nanotechnology enabled distributed sensor systems, Vehicular Ad hoc Networking (VANET) or Mobile Ad hoc Networking (MANET) - all can be classified under new networking s

  12. Insulin and insulin signaling play a critical role in fat induction of insulin resistance in mouse

    Science.gov (United States)

    Ning, Jie; Hong, Tao; Yang, Xuefeng; Mei, Shuang; Liu, Zhenqi; Liu, Hui-Yu

    2011-01-01

    The primary player that induces insulin resistance has not been established. Here, we studied whether or not fat can cause insulin resistance in the presence of insulin deficiency. Our results showed that high-fat diet (HFD) induced insulin resistance in C57BL/6 (B6) mice. The HFD-induced insulin resistance was prevented largely by the streptozotocin (STZ)-induced moderate insulin deficiency. The STZ-induced insulin deficiency prevented the HFD-induced ectopic fat accumulation and oxidative stress in liver and gastrocnemius. The STZ-induced insulin deficiency prevented the HFD- or insulin-induced increase in hepatic expression of long-chain acyl-CoA synthetases (ACSL), which are necessary for fatty acid activation. HFD increased mitochondrial contents of long-chain acyl-CoAs, whereas it decreased mitochondrial ADP/ATP ratio, and these HFD-induced changes were prevented by the STZ-induced insulin deficiency. In cultured hepatocytes, we observed that expressions of ACSL1 and -5 were stimulated by insulin signaling. Results in cultured cells also showed that blunting insulin signaling by the PI3K inhibitor LY-294002 prevented fat accumulation, oxidative stress, and insulin resistance induced by the prolonged exposure to either insulin or oleate plus sera that normally contain insulin. Finally, knockdown of the insulin receptor prevented the oxidative stress and insulin resistance induced by the prolonged exposure to insulin or oleate plus sera. Together, our results show that insulin and insulin signaling are required for fat induction of insulin resistance in mice and cultured mouse hepatocytes. PMID:21586696

  13. Insulin and the Lung

    DEFF Research Database (Denmark)

    Singh, Suchita; Prakash, Y S; Linneberg, Allan

    2013-01-01

    Obesity, metabolic syndrome, and asthma are all rapidly increasing globally. Substantial emerging evidence suggests that these three conditions are epidemiologically and mechanistically linked. Since the link between obesity and asthma appears to extend beyond mechanical pulmonary disadvantage...... and highlights the molecular consequences of insulin-related metabolic signaling cascades that could adversely affect lung structure and function. Examples include airway smooth muscle proliferation and contractility and regulatory signaling networks that are associated with asthma. These aspects of insulin...

  14. Insulin and Glucagon

    DEFF Research Database (Denmark)

    Holst, Jens Juul; Holland, William; Gromada, Jesper

    2017-01-01

    In August 2016, several leaders in glucagon biology gathered for the European Association for the Study of Diabetes Hagedorn Workshop in Oxford, England. A key point of discussion focused on the need for basal insulin to allow for the therapeutic benefit of glucagon blockade in the treatment...... of the discussion as a consensus was reached. Agents that antagonize glucagon may be of great benefit for the treatment of diabetes; however, sufficient levels of basal insulin are required for their therapeutic efficacy....

  15. Antibody-Mediated Insulin Resistance: When Insulin and Insulin Receptor Act as Autoantigens in Humans.

    Science.gov (United States)

    Liminet, Christelle; Vouillarmet, Julien; Chikh, Karim; Disse, Emmanuel

    2016-10-01

    We report the case of a patient with diabetes presenting a severe insulin-resistance syndrome due to the production of insulin autoantibodies by a lymphocytic lymphoma. We describe the various mechanisms leading to the production of insulin autoantibodies and insulin receptor autoantibodies and review the therapeutic possibilities. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  16. The rise and fall of insulin signaling in Alzheimer's disease.

    Science.gov (United States)

    Chami, B; Steel, A J; De La Monte, S M; Sutherland, Greg T

    2016-06-01

    The prevalence of both diabetes and Alzheimer's disease (AD) are reaching epidemic proportions worldwide. Alarmingly, diabetes is also a risk factor for Alzheimer's disease. The AD brain is characterised by the accumulation of peptides called Aβ as plaques in the neuropil and hyperphosphorylated tau protein in the form of neurofibrillary tangles within neurons. How diabetes confers risk is unknown but a simple linear relationship has been proposed whereby the hyperinsulinemia associated with type 2 diabetes leads to decreased insulin signaling in the brain, with downregulation of the PI3K/AKT signalling pathway and its inhibition of the major tau kinase, glycogen synthase kinase 3β. The earliest studies of post mortem AD brain tissue largely confirmed this cascade of events but subsequent studies have generally found either an upregulation of AKT activity, or that the relationship between insulin signaling and AD is independent of glycogen synthase kinase 3β altogether. Given the lack of success of beta-amyloid-reducing therapies in clinical trials, there is intense interest in finding alternative or adjunctive therapeutic targets for AD. Insulin signaling is a neuroprotective pathway and represents an attractive therapeutic option. However, this incredibly complex signaling pathway is not fully understood in the human brain and particularly in the context of AD. Here, we review the ups and downs of the research efforts aimed at understanding how diabetes modifies AD risk.

  17. Insulin Resistance: Causes And Metabolic Implications | Igharo ...

    African Journals Online (AJOL)

    Insulin is an anabolic hormone that plays key roles in glucose metabolism. Insulin resistance is a decreased biological response to normal concentration of circulating insulin. In insulin resistance, normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. Insulin ...

  18. Adding and Deleting Images

    Science.gov (United States)

    Images are added via the Drupal WebCMS Editor. Once an image is uploaded onto a page, it is available via the Library and your files. You can edit the metadata, delete the image permanently, and/or replace images on the Files tab.

  19. What Value "Value Added"?

    Science.gov (United States)

    Richards, Andrew

    2015-01-01

    Two quantitative measures of school performance are currently used, the average points score (APS) at Key Stage 2 and value-added (VA), which measures the rate of academic improvement between Key Stage 1 and 2. These figures are used by parents and the Office for Standards in Education to make judgements and comparisons. However, simple…

  20. Adding an extra storey

    DEFF Research Database (Denmark)

    Engelmark, Jesper; Dahl, Torben; Melgaard, Ebbe

    2007-01-01

    of them had to be renovated after a shorter period. In stead of just replacing the original roof with a new one, it is now a days rather common to ad an extra storey where that is possible according to local planning. The reason is as a rule based on economical benefits, but very often this extra storey...

  1. Insulin deficiency exacerbates cerebral amyloidosis and behavioral deficits in an Alzheimer transgenic mouse model

    Directory of Open Access Journals (Sweden)

    Teng Wei-Ping

    2010-11-01

    Full Text Available Abstract Background Although increasing evidence has indicated that brain insulin dysfunction is a risk factor for Alzheimer disease (AD, the underlying mechanisms by which insulin deficiency may impact the development of AD are still obscure. Using a streptozotocin (STZ-induced insulin deficient diabetic AD transgenic mouse model, we evaluated the effect of insulin deficiency on AD-like behavior and neuropathology. Results Our data showed that administration of STZ increased the level of blood glucose and reduced the level of serum insulin, and further decreased the phosphorylation levels of insulin receptors, and increased the activities of glycogen synthase kinase-3α/β and c-Jun N-terminal kinase in the APP/PS1 mouse brain. We further showed that STZ treatment promoted the processing of amyloid-β (Aβ precursor protein resulting in increased Aβ generation, neuritic plaque formation, and spatial memory deficits in transgenic mice. Conclusions Our present data indicate that there is a close link between insulin deficient diabetes and cerebral amyloidosis in the pathogenesis of AD.

  2. Neuronal LRP1 regulates glucose metabolism and insulin signaling in the brain.

    Science.gov (United States)

    Liu, Chia-Chen; Hu, Jin; Tsai, Chih-Wei; Yue, Mei; Melrose, Heather L; Kanekiyo, Takahisa; Bu, Guojun

    2015-04-08

    Alzheimer's disease (AD) is a neurological disorder characterized by profound memory loss and progressive dementia. Accumulating evidence suggests that Type 2 diabetes mellitus, a metabolic disorder characterized by insulin resistance and glucose intolerance, significantly increases the risk for developing AD. Whereas amyloid-β (Aβ) deposition and neurofibrillary tangles are major histological hallmarks of AD, impairment of cerebral glucose metabolism precedes these pathological changes during the early stage of AD and likely triggers or exacerbates AD pathology. However, the mechanisms linking disturbed insulin signaling/glucose metabolism and AD pathogenesis remain unclear. The low-density lipoprotein receptor-related protein 1 (LRP1), a major apolipoprotein E receptor, plays critical roles in lipoprotein metabolism, synaptic maintenance, and clearance of Aβ in the brain. Here, we demonstrate that LRP1 interacts with the insulin receptor β in the brain and regulates insulin signaling and glucose uptake. LRP1 deficiency in neurons leads to impaired insulin signaling as well as reduced levels of glucose transporters GLUT3 and GLUT4. Consequently, glucose uptake is reduced. By using an in vivo microdialysis technique sampling brain glucose concentration in freely moving mice, we further show that LRP1 deficiency in conditional knock-out mice resulted in glucose intolerance in the brain. We also found that hyperglycemia suppresses LRP1 expression, which further exacerbates insulin resistance, glucose intolerance, and AD pathology. As loss of LRP1 expression is seen in AD brains, our study provides novel insights into insulin resistance in AD. Our work also establishes new targets that can be explored for AD prevention or therapy. Copyright © 2015 the authors 0270-6474/15/355851-09$15.00/0.

  3. Molecular biocoding of insulin

    Directory of Open Access Journals (Sweden)

    Lutvo Kuric

    2010-07-01

    Full Text Available Lutvo KuricNovi Travnik, Kalinska, Bosnia and Herzegovina Abstract: This paper discusses cyberinformation studies of the amino acid composition of insulin, in particular the identification of scientific terminology that could describe this phenomenon, ie, the study of genetic information, as well as the relationship between the genetic language of proteins and theoretical aspects of this system and cybernetics. The results of this research show that there is a matrix code for insulin. It also shows that the coding system within the amino acid language gives detailed information, not only on the amino acid “record”, but also on its structure, configuration, and various shapes. The issue of the existence of an insulin code and coding of the individual structural elements of this protein are discussed. Answers to the following questions are sought. Does the matrix mechanism for biosynthesis of this protein function within the law of the general theory of information systems, and what is the significance of this for understanding the genetic language of insulin? What is the essence of existence and functioning of this language? Is the genetic information characterized only by biochemical principles or it is also characterized by cyberinformation principles? The potential effects of physical and chemical, as well as cybernetic and information principles, on the biochemical basis of insulin are also investigated. This paper discusses new methods for developing genetic technologies, in particular more advanced digital technology based on programming, cybernetics, and informational laws and systems, and how this new technology could be useful in medicine, bioinformatics, genetics, biochemistry, and other natural sciences.Keywords: human insulin, insulin model, biocode, genetic code, amino acids

  4. INSULIN IN THE BRAIN: ITS PATHOPHYSIOLOGICAL IMPLICATIONS FOR STATES RELATED WITH CENTRAL INSULIN RESISTANCE, TYPE 2 DIABETES AND ALZHEIMER’S DISEASE

    Directory of Open Access Journals (Sweden)

    ENRIQUE eBLÁZQUEZ

    2014-10-01

    Full Text Available Although the brain has been considered an insulin-insensitive organ, recent reports on the location of insulin and its receptors in the brain have introduced new ways of considering this hormone responsible for several functions. The origin of insulin in the brain has been explained from peripheral or central sources, or both. Regardless of whether insulin is of peripheral origin or produced in the brain, this hormone may act through its own receptors present in the brain. The molecular events through which insulin functions in the brain are the same as those operating in the periphery. However, certain insulin actions are different in the CNS, such as hormone-induced glucose uptake due to a low insulin-sensitive GLUT-4 activity, and because of the predominant presence of GLUT-1 and GLUT-3. In addition, insulin in the brain contributes to the control of nutrient homeostasis, reproduction, cognition and memory, as well as to neurotrophic, neuromodulatory, and neuroprotective effects. Alterations of these functional activities may contribute to the manifestation of several clinical entities, such as central insulin resistance, type 2 diabetes (T2DM and Alzheimer’s disease (AD. A close association between T2DM and AD has been reported, to the extent that AD is twice more frequent in diabetic patients, and some authors have proposed the name type 3 diabetes for this association. There are links between AD and type 2 diabetes mellitus (T2DM through mitochondrial alterations and oxidative stress, altered energy and glucose metabolism, cholesterol modifications, dysfunctional protein OGlcNAcylation, formation of amyloid plaques, altered Aβ metabolism, and tau hyperphosphorylation. Advances in the knowledge of preclinical AD and T2DM may be a major stimulus for the development of treatment for preventing the pathogenic events of

  5. Modeling the Long-Term Cost-Effectiveness of IDegLira in Patients with Type 2 Diabetes Who are Failing To Meet Glycemic Targets on Basal Insulin Alone in The Netherlands.

    Science.gov (United States)

    Hunt, Barnaby; Glah, Divina; van der Vliet, Maarten

    2017-08-01

    Insulin degludec/liraglutide (IDegLira) is the first basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1 RA) in a single pen injection device, and a once-daily treatment option for patients with type 2 diabetes mellitus (T2DM) who are uncontrolled on basal insulin and require treatment intensification. The objective of this analysis was to evaluate the long-term cost-effectiveness of IDegLira versus basal-bolus therapy (insulin glargine U100 + 3× daily insulin aspart) for patients with T2DM uncontrolled on basal insulin [HbA1c >53 mmol/mol (>7%)] in the Netherlands. Cost-effectiveness analysis was performed using the validated IMS CORE Diabetes Model from a healthcare payer perspective. Outcomes were modeled over patient lifetimes in a cohort with baseline characteristics from the DUAL™ II trial. Treatment effect data were sourced from a statistical indirect comparison (pooled analysis) of IDegLira with basal-bolus therapy. Treatment with IDegLira resulted in mean increases in quality-adjusted life expectancy of 0.43 quality-adjusted life years versus basal-bolus therapy. Improved clinical outcomes resulted from fewer diabetes-related complications and a delayed time to their onset. IDegLira was associated with lower costs of EUR 4679 versus basal-bolus therapy, a result of lower pharmacy costs and avoided diabetes-related complications. Thus, IDegLira was dominant, i.e., both more effective and less costly than basal-bolus therapy. IDegLira is an effective treatment option to improve glycemic control without incurring an increased risk of hypoglycemia or weight gain. This analysis suggests that IDegLira is cost-effective versus basal-bolus therapy in patients with T2DM who are uncontrolled on basal insulin in the Netherlands. Novo Nordisk.

  6. Ads in Indonesia

    Directory of Open Access Journals (Sweden)

    Wulan Roro Retno

    2017-01-01

    Full Text Available Cosmetics industry created the beauty myth for women through advertising. A cosmetic ad in Indonesia has spread a new concept of white skin: East Asia beauty myth. The white concept of Asia white skin basically derived from colonial legacy. The purpose of the research was analyzing the beauty myth in Indonesia ads using postcolonial perspective. The principal result brought the discourse analysis and postcolonial perspective a new insight in communication research. Particularly on media and cultural studies. Major conclusions showed that the beauty myth since the Dutch colonial period never been change. The main concept is always in colonialism’s idea: “white is better”. The West is better than the East.

  7. Management job ads

    DEFF Research Database (Denmark)

    Holmgreen, Lise-Lotte

    2014-01-01

    jobs by discursively constructing job ads that appeal to both sexes. This argument is part of the broader field of corporate social responsibility, corporate citizenship, and stakeholder management, which involves discussions of the obligations of corporations to acknowledge and mitigate......The article asks whether it is not the responsibility of corporations to address the issue of women being underrepresented in Danish management jobs. In other words, it is argued that corporations should be encouraged to engage more actively in the recruitment of both men and women for management...... the increasingly widespread impact that their activities have on communities and social structures. The article emphasises the need for more active engagement on the part of corporations by analysing the discursive construction of preferred candidates in a small sample of Danish management job ads. By means...

  8. Adiponectin resistance precedes the accumulation of skeletal muscle lipids and insulin resistance in high-fat-fed rats.

    Science.gov (United States)

    Mullen, Kerry L; Pritchard, Janet; Ritchie, Ian; Snook, Laelie A; Chabowski, Adrian; Bonen, Arend; Wright, David; Dyck, David J

    2009-02-01

    High-fat (HF) diets can induce insulin resistance (IR) by altering skeletal muscle lipid metabolism. An imbalance between fatty acid (FA) uptake and oxidation results in intramuscular lipid accumulation, which can impair the insulin-signaling cascade. Adiponectin (Ad) is an insulin-sensitizing adipokine known to stimulate skeletal muscle FA oxidation and reduce lipid accumulation. Evidence of Ad resistance has been shown in obesity and following chronic HF feeding and may contribute to lipid accumulation observed in these conditions. Whether Ad resistance precedes and is associated with the development of IR is unknown. We conducted a time course HF feeding trial for 3 days, 2 wk, or 4 wk to determine the onset of Ad resistance and identify the ensuing changes in lipid metabolism and insulin signaling leading to IR in skeletal muscle. Ad stimulated FA oxidation (+28%, P increased, and insulin-stimulated phosphorylation of both protein kinase B and protein kinase B substrate 160 was blunted compared with control animals. After 4 wk of HF feeding, maximal insulin-stimulated glucose transport was impaired compared with control. Taken together, our results demonstrate that an early loss of Ad's stimulatory effect on FA oxidation precedes an increase in plasmalemmal FA transporters and the accumulation of intramuscular DAG and ceramide, blunted insulin signaling, and ultimately impaired maximal insulin-stimulated glucose transport in skeletal muscle induced by HF diets.

  9. Glucagon and insulin oscillatory self-administration in rats.

    Science.gov (United States)

    Jouhaneau, J

    1979-07-01

    In a previous work, it was shown that insulin was intravenously self-injected by rats. By the study here reported it was demonstrated that, in the same procedure, glucagon was not self-administered. However, when allowed to obtain either insulin or glucagon ad lib in a two lever procedure, rats established a sustained daily self-injection pattern of the two hormones. Mostly self-injection bouts occurred immediately before and after each meal with an insulin to glucagon ratio higher after than prior to the meal. Fifty-six and sixty-four percent of glucagon and insulin respectively were self-injected in coupled oscillatory bursts. In such alternated self-injections the amounts of the hyperglycemic and hypoglycemic agents obtained were positively correlated. These data indicate that rats might be able to learn and to carry out a behavioural regulation of blood glucose level.

  10. Insulin-induced translocation of IR to the nucleus in insulin responsive cells requires a nuclear translocation sequence.

    Science.gov (United States)

    Kesten, Dov; Horovitz-Fried, Miriam; Brutman-Barazani, Tamar; Sampson, Sanford R

    2018-04-01

    Insulin binding to its cell surface receptor (IR) activates a cascade of events leading to its biological effects. The Insulin-IR complex is rapidly internalized and then is either recycled back to the plasma membrane or sent to lysosomes for degradation. Although most of the receptor is recycled or degraded, a small amount may escape this pathway and migrate to the nucleus of the cell where it might be important in promulgation of receptor signals. In this study we explored the mechanism by which insulin induces IR translocation to the cell nucleus. Experiments were performed cultured L6 myoblasts, AML liver cells and 3T3-L1 adipocytes. Insulin treatment induced a rapid increase in nuclear IR protein levels within 2 to 5 min. Treatment with WGA, an inhibitor of nuclear import, reduced insulin-induced increases nuclear IR protein; IR was, however, translocated to a perinuclear location. Bioinformatics tools predicted a potential nuclear localization sequence (NLS) on IR. Immunofluorescence staining showed that a point mutation on the predicted NLS blocked insulin-induced IR nuclear translocation. In addition, blockade of nuclear IR activation in isolated nuclei by an IR blocking antibody abrogated insulin-induced increases in IR tyrosine phosphorylation and nuclear PKCδ levels. Furthermore, over expression of mutated IR reduced insulin-induced glucose uptake and PKB phosphorylation. When added to isolated nuclei, insulin induced IR phosphorylation but had no effect on nuclear IR protein levels. These results raise questions regarding the possible role of nuclear IR in IR signaling and insulin resistance. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Philosophia ad bellum

    Directory of Open Access Journals (Sweden)

    Yu. O. Loboda

    2014-06-01

    Full Text Available In the paper «Philosophia ad bellum» is being realized an attempt to classify philosophic approaches to the study of phenomenon of war by the analogy with the structure of «Just war theory» – 1. Philosophia ad bellum – «philosophy for war», where are investigated ways of using of philosophic methods of cognition in applied military sciences; 2. Philosophia supra bello – «philosophy above war», which investigates world­view, historic­philosophic, existential, logic­epistemological aspects of war; 3. Philosophia contra belli – «philosophy against war», where research of the essence of war gets its logical conclusion in grounding of the absurdity of thinking schemes which justify war as an act of violence. In the article was made historic­philosophic overview of the part «Philosophia ad bellum», where were showed tangent questions, which are considered by philosophic logic and theory of strategic intelligence. It was stated, that specialists if military intelligence admit the important role of researches in logic and theory of cognition in their professional work; were defined basic questions, which have the most essential interest for military professionals. There were analyzed ways of using of philosophic methods in developing military strategies, was made a conclusion that philosophy can be a basis of strategic failures and victories as well.

  12. Insulin aspart in diabetic pregnancy

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth R

    2008-01-01

    in insulin requirements during pregnancy necessitate short-acting insulins for postprandial control of hyperglycemia. The fast-acting insulin analogue insulin aspart has been tested in a large, randomized trial of pregnant women with Type 1 diabetes and offers benefits in control of postprandial......Pregnancy in women with diabetes is associated with an increased risk of obstetric complications and perinatal mortality. Maintenance of near-normal glycemia during pregnancy can bring the prevalence of fetal, neonatal and maternal complications closer to that of the nondiabetic population. Changes...... and no increase in insulin antibodies was found. Thus, the use of insulin aspart in pregnancy is regarded safe....

  13. Insulin Regulates the Activity of the High-Affinity Choline Transporter CHT.

    Directory of Open Access Journals (Sweden)

    Katherine J Fishwick

    Full Text Available Studies in humans and animal models show that neuronal insulin resistance increases the risk of developing Alzheimer's Disease (AD, and that insulin treatment may promote memory function. Cholinergic neurons play a critical role in cognitive and attentional processing and their dysfunction early in AD pathology may promote the progression of AD pathology. Synthesis and release of the neurotransmitter acetylcholine (ACh is closely linked to the activity of the high-affinity choline transporter protein (CHT, but the impact of insulin receptor signaling and neuronal insulin resistance on these aspects of cholinergic function are unknown. In this study, we used differentiated SH-SY5Y cells stably-expressing CHT proteins to study the effect of insulin signaling on CHT activity and function. We find that choline uptake activity measured after acute addition of 20 nM insulin is significantly lower in cells that were grown for 24 h in media containing insulin compared to cells grown in the absence of insulin. This coincides with loss of ability to increase phospho-Protein Kinase B (PKB/Akt levels in response to acute insulin stimulation in the chronic insulin-treated cells. Inhibition of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3-kinase in cells significantly lowers phospho-PKB/Akt levels and decreases choline uptake activity. We show total internal reflection microscopy (TIRF imaging of the dynamic movement of CHT proteins in live cells in response to depolarization and drug treatments. These data show that acute exposure of depolarized cells to insulin is coupled to transiently increased levels of CHT proteins at the cell surface, and that this is attenuated by chronic insulin exposure. Moreover, prolonged inhibition of PI3-kinase results in enhanced levels of CHT proteins at the cell surface by decreasing their rate of internalization.

  14. New Insulins and New Aspects in Insulin Delivery.

    Science.gov (United States)

    Woo, Vincent C

    2015-08-01

    The major abnormality in both type 1 and type 2 diabetes is insulin deficiency. The methods of replacing insulin have improved throughout the decades, but hypoglycemia is still the limiting factor for many individuals with diabetes, and it prevents them from achieving ideal glycemic targets. New insulin and newer delivery systems are being developed that can improve some of the limitations of current insulins or make the delivery of insulins more acceptable for some patients. Extending the duration of action of basal insulins and shortening the peak of fast-acting insulins may have advantages for individuals with diabetes. Different delivery systems may make insulin more acceptable to patients and may have other advantages, which may aid in attaining better glycemic control. Copyright © 2015 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  15. Improved insulin sensitivity after exercise: focus on insulin signaling

    DEFF Research Database (Denmark)

    Frøsig, Christian; Richter, Erik

    2009-01-01

    After a single bout of exercise, the ability of insulin to stimulate glucose uptake is markedly improved locally in the previously active muscles. This makes exercise a potent stimulus counteracting insulin resistance characterizing type 2 diabetes (T2D). It is believed that at least part...... of the mechanism relates to an improved ability of insulin to stimulate translocation of glucose transporters (GLUT4) to the muscle membrane after exercise. How this is accomplished is still unclear; however, an obvious possibility is that exercise interacts with the insulin signaling pathway to GLUT4...... translocation allowing for a more potent insulin response. Parallel to unraveling of the insulin signaling cascade, this has been investigated within the past 25 years. Reviewing existing studies clearly indicates that improved insulin action can occur independent of interactions with proximal insulin signaling...

  16. AdS 3-manifolds and Higgs bundles

    DEFF Research Database (Denmark)

    Alessandrini, Daniele; Li, Qiongling

    2017-01-01

    In this paper we investigate the relationships between closed AdS $3$-manifolds and Higgs bundles. We have a new way to construct AdS structures that allows us to see many of their properties explicitly, for example we can recover the very recent formula by Tholozan for their volume. We give natu...

  17. Dressing phases of AdS3/CFT2

    NARCIS (Netherlands)

    Borsato, R.; Olsson Sax, O.E.; Sfondrini, A.; Stefanski, B.; Torrielli, A.

    2013-01-01

    We determine the all-loop dressing phases of the AdS3/CFT2 integrable system related to type IIB string theory on AdS3×S3×T4 by solving the recently found crossing relations and studying their singularity structure. The two resulting phases present a novel structure with respect to the ones

  18. Development of insulin delivery systems.

    Science.gov (United States)

    Siddiqui, N I; Siddiqui, Ni; Rahman, S; Nessa, A

    2008-01-01

    Delivery system of insulin is vital for its acceptance and adherence to therapy for achieving the glycemic targets. Enormous developments have occurred in the delivery system of insulin during the last twenty years and each improvement was aimed at two common goals: patients convenience and better glycemic control. Till to date, the various insulin delivery systems are: syringes/vials, injection aids, jet injectors, transmucosal delivery, transdermal delivery, external insulin infusion pump, implantable insulin pumps, insulin pens and insulin inhalers. Syringe/vial is the oldest and conventional method, still widely used and relatively cheaper. Modern plastic syringes are disposable, light weight with microfine needle for patients convenience and comfort. Oral route could be the most acceptable and viable, if the barriers can be overcome and under extensive trial. Insulin pen device is an important milestone in the delivery system of insulin as it is convenient, discrete, painless, attractive, portable with flexible life style and improved quality of life. More than 80% of European diabetic patients are using insulin pen. Future digital pen will have better memory option, blood glucose monitoring system, insulin dose calculator etc. Insulin infusion pump is a good option for the children, busy patients with flexible lifestyle and those who want to avoid multiple daily injections. Pulmonary route of insulin delivery is a promising, effective, non-invasive and acceptable alternative method. Exubera, the world first insulin inhaler was approved by FDA in 28 January 2006. But due to certain limitations, it has been withdrawn from the market in October 2007. The main concern of inhaled insulin are: long term pulmonary safety issues, cost effectiveness and user friendly device. In future, more acceptable and cost effective insulin inhaler will be introduced. Newer avenues are under extensive trial for better future insulin delivery systems.

  19. Chemical and thermal stability of insulin

    DEFF Research Database (Denmark)

    Huus, Kasper; Havelund, Svend; Olsen, Helle B

    2006-01-01

    To study the correlation between the thermal and chemical stability of insulin formulations with various insulin hexamer ligands.......To study the correlation between the thermal and chemical stability of insulin formulations with various insulin hexamer ligands....

  20. PACAP stimulates insulin secretion but inhibits insulin sensitivity in mice

    NARCIS (Netherlands)

    Filipsson, K; Pacini, G; Scheurink, AJW; Ahren, B

    Although pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates insulin secretion, its net influence on glucose homeostasis in vivo has not been established. We therefore examined the action of PACAP-27 and PACAP-38 on insulin secretion, insulin sensitivity, and glucose disposal as

  1. Dual chitosan/albumin-coated alginate/dextran sulfate nanoparticles for enhanced oral delivery of insulin.

    Science.gov (United States)

    Lopes, Marlene; Shrestha, Neha; Correia, Alexandra; Shahbazi, Mohammad-Ali; Sarmento, Bruno; Hirvonen, Jouni; Veiga, Francisco; Seiça, Raquel; Ribeiro, António; Santos, Hélder A

    2016-06-28

    The potential of nanoparticles (NPs) to overcome the barriers for oral delivery of protein drugs have led to the development of platforms capable of improving their bioavailability. However, despite the progresses in drug delivery technologies, the success of oral delivery of insulin remains elusive and the disclosure of insulin mechanisms of absorption remains to be clarified. To overcome multiple barriers faced by oral insulin and to enhance the insulin permeability across the intestinal epithelium, here insulin-loaded alginate/dextran sulfate (ADS)-NPs were formulated and dual-coated with chitosan (CS) and albumin (ALB). The nanosystem was characterized by its pH-sensitivity and mucoadhesivity, which enabled to prevent 70% of in vitro insulin release in simulated gastric conditions and allowed a sustained insulin release following the passage to simulated intestinal conditions. The pH and time-dependent morphology of the NPs was correlated to the release and permeation profile of insulin. Dual CS/ALB coating of the ADS-NPs demonstrated augmented intestinal interactions with the intestinal cells in comparison to the uncoated-NPs, resulting in a higher permeability of insulin across Caco-2/HT29-MTX/Raji B cell monolayers. The permeability of the insulin-loaded ALB-NPs was reduced after the temperature was decreased and after co-incubation with chlorpromazine, suggesting an active insulin transport by clathrin-mediated endocytosis. Moreover, the permeability inhibition with the pre-treatment with sodium chlorate suggested that the interaction between glycocalix and the NPs was critical for insulin permeation. Overall, the developed nanosystem has clinical potential for the oral delivery of insulin and therapy of type 1 diabetes mellitus. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Oral Insulin - Fact or Fiction?

    Indian Academy of Sciences (India)

    Insulin is a major protein hormone secreted by the p-cells of the pancreas and is important for the control of diabetes. Insulin is usually administered to diabetic patients through subcutaneous injection. This mode of therapy has certain inherent disadvantages such as local pain, itching and insulin lipodystrophy around the ...

  3. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    Free fatty acids are known to play a key role in promoting loss of insulin sensitivity, thereby causing insulin resistance and type 2 diabetes. However, the underlying mechanism involved is still unclear. In searching for the cause of the mechanism, it has been found that palmitate inhibits insulin receptor (IR) gene expression, ...

  4. Molecular mechanisms of insulin resistance

    African Journals Online (AJOL)

    basis of insulin resistance could ultimately lead to a better understanding of the causation of these conditions and the design of rational therapy to ameliorate them. Here, particular attention is devoted to the initial events that follow the binding of insulin to its receptor, including changes in insulin receptor phosphorylation.

  5. THE USE OF ULTRA-LONG-ACTING INSULIN ANALOGUE DEGLUDEC IN TYPE 1 DIABETES MELLITUS IN CLINICAL PRACTICE: THE INFLUENCE ON QUALITY OF LIFE AND SATISFACTION WITH TREATMENT

    Directory of Open Access Journals (Sweden)

    M. F. Kalashnikova

    2016-01-01

    Full Text Available Background: Maintenance of stable glycemic control is an important prerequisite of effective treatment of patients with type 1 diabetes mellitus (DM. The ultra-long-acting basal insulin degludec allows for reduction of glycemic variability and for a substantial reduction in the rates of hypoglycemia with equivalent glycemic control. Evaluation of the impact of this novel insulin on diabetes-dependent quality of life and patient satisfactions with the treatment is necessary for comprehensive assessment of treatment efficacy.Aim: To study changes of glycated hemoglobin (HbA1c, rates of hypoglycemia, diabetes-dependent quality of life and treatment satisfaction in patients with type 1 DM, who have been switched to insulin degludec.Materials and methods: This open 12-week observational comparative study included 25  patients with type  1 DM (median age, 36 [20; 63] years, who were switched to insulin degludec in combination with a  ultra-short insulin analogue. The control group included 21 patients with type 1 DM (median age, 40 [23; 63] years, who continued their treatment with a long-acting insulin analogue glargine. At baseline and at week 12 after switching to insulin degludec, we assessed HbA1c level, mean insulin dose, depression score, diabetes-dependent quality of life and patient satisfaction with the treatment with the use of the Russian versions of the diabetes-specific questionnaires “Audit of Diabetes-Dependent Quality of life” (RuADDQoL, and “Diabetes Treatment Satisfaction Questionnaire” (DTSQ, respectively.Results: At 3 months, there was a significant reduction of the HbA1c levels in the main and the control groups to 7.57% (Ме 7.5 [7.1; 8.4]; р=0.03 and 8.18% (Ме 7.8% [7.4; 8.7]; р=0.04, respectively. The mean reduction of this parameter under treatment with degludec was slightly higher than under treatment with glargine (0.73 vs 0.57%, respectively, at 3 months the difference being statistically

  6. Value-Added Exchange Rates

    OpenAIRE

    Rudolfs Bems; Robert C. Johnson

    2012-01-01

    This paper updates the conceptual foundations for measuring real effective exchange rates (REERs) to allow for vertical specialization in trade. We derive a value-added REER describing how demand for the value added that a country produces changes as the price of its value added changes relative to competitors. We then compute this index for 42 countries from 1970-2009 using trade measured in value added terms and GDP deflators. There are substantial differences between value-added and conven...

  7. Insulin som trickster

    DEFF Research Database (Denmark)

    Lassen, Aske Juul

    2011-01-01

    grænser nedbrydes i en konstant penetrering af huden, når blodsukkeret måles eller insulinen indsprøjtes. Insulin analyseres som en tricksterfigur, der udøver et grænsearbejde på kroppen, leger med dens kategorier og vender forholdet mellem gift og medicin, frihed og ufrihed, kunstighed og naturlighed...

  8. Options for intensification of basal insulin in type 2 diabetes: Premeal insulin or short-acting GLP-1 receptor agonists?

    Science.gov (United States)

    Darmon, P; Raccah, D

    2015-12-01

    Type 2 diabetes is an evolutive disease with a progressive defect of beta-cell insulin secretion. This characteristic points to a need for treatment that takes into account such a natural history. When oral antidiabetic drugs fail to achieve the patient's target HbA1c level, basal insulin treatment is usually initiated and titrated in association with oral drugs to manage fasting hyperglycaemia. Over a period of time, it is enough to simply achieve the HbA1c target. However, when even a good fasting blood glucose level is no longer sufficient to control overall glycaemia, then prandial treatment must be combined with the titrated basal insulin to deal with the postprandial hyperglycaemia responsible for the elevation of HbA1c. Of the different therapeutic options now available for this, rapid-acting insulins and GLP-1 receptor agonists (RAs) can be used. Rapid-acting insulins can be added either at each meal, achieving full insulin supplementation with a basal-bolus regimen, or at the main meal only as a "basal-plus" regimen. Compared with the full basal-bolus, the basal-plus strategy is associated with fewer injections, yet provides similar efficacy in terms of HbA1c improvement, but with less weight gain and lower hypoglycaemic risk. As for GLP-1 RAs, numerous studies, and especially those using short-acting GLP-1 RAs, have demonstrated more pronounced effects on postprandial hyperglycaemia, good complementary effects with basal insulin, and significant improvement of HbA1c with no weight gain and a low risk of hypoglycaemia. Similarly, direct and indirect comparisons of the use of rapid-acting insulins and GLP-1 RAs to intensify basal insulin have shown comparable efficacy in terms of HbA1c control, but with less weight gain and fewer hypoglycaemic episodes with GLP-1 RAs. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  9. Insulin Resistance and Hypogonadism

    Directory of Open Access Journals (Sweden)

    Shahana Shermin

    2013-05-01

    Full Text Available Backgound: The number of hypogonads is increasing day by day. It may be due to sedentary life style with increased obesity, increased tension or stressed lifestyle among all groups of populations. Visceral obesity is associated with insulin resistance, diabetes mellitus and also with hypogonadism.Objective: This study was carried out to determine the proportion of insulin resistance among male subjects with hypogonadism in different age groups along with status of erectile quality among diabetics and non diabetics.Materials and method: This cross sectional study among 161 adult male subjects aged ≥ 20 to ≤ 60 years were purposively selected from Bangladesh Institute of Research and Rehabilitation in Diabetes Endocrine and Metabolic Disorders (BIRDEM, Dhaka, Bangladesh between May 2009 to September 2010. Glycemic status and insulin resistance (by HOMA-R were done and relevant history were documented.Results: The highest proportion (38.9% of hypogonadism was in ≥ 50 years age group whereas highest proportion (39.6% of the eugonads was in the age group of 40 to 49 years. More than half of the hypogonad subjects had weak erectile quality (54.0% which were followed by absent erectile quality in 32.7% and 13.3% subjects had normal erectile quality. Among the eugonad subjects 41.7% had normal erectile quality, 41.6% subjects had weak erectile quality and 16.7% subjects had no erectile quality. More than ninety percent of the hypogonad subjects and about 60% of the eugonad subjects had insulin resistance. The average HOMA-R was more in the subjects with hypogonadism with diabetes which was highly significant (p-value < 0.001.Conclusion: Hypogonadism is associated with insulin resistance.

  10. Wireless Ad Hoc Networks

    Directory of Open Access Journals (Sweden)

    Hong-Chuan Yang

    2007-01-01

    Full Text Available We study the energy-efficient configuration of multihop paths with automatic repeat request (ARQ mechanism in wireless ad hoc networks. We adopt a cross-layer design approach and take both the quality of each radio hop and the battery capacity of each transmitting node into consideration. Under certain constraints on the maximum tolerable transmission delay and the required packet delivery ratio, we solve optimization problems to jointly schedule the transmitting power of each transmitting node and the retransmission limit over each hop. Numerical results demonstrate that the path configuration methods can either significantly reduce the average energy consumption per packet delivery or considerably extend the average lifetime of the multihop route.

  11. New developments in insulin delivery.

    Science.gov (United States)

    Khan Ghilzai, Naushad M

    2003-03-01

    A vigorous research effort has been undertaken worldwide to replace injectable insulin by a more comfortable and painless delivery method. Several routes have been explored for their suitability with respect to insulin degradation in the human body. Considerable progress has been made in achieving the common goal for a convenient and equally effective insulin delivery. This article reviews the different routes available for insulin administration and the many successful developments that have been made in recent years for improving that particular route for a much better insulin delivery.

  12. Adipokines and Hepatic Insulin Resistance

    Science.gov (United States)

    Hassan, Waseem

    2013-01-01

    Obesity is a major risk factor for insulin resistance and type 2 diabetes. Adipose tissue is now considered to be an active endocrine organ that secretes various adipokines such as adiponectin, leptin, resistin, tumour necrosis factor-α, and interleukin-6. Recent studies have shown that these factors might provide a molecular link between increased adiposity and impaired insulin sensitivity. Since hepatic insulin resistance plays the key role in the whole body insulin resistance, clarification of the regulatory processes about hepatic insulin resistance by adipokines in rodents and human would seem essential in order to understand the mechanism of type 2 diabetes and for developing novel therapeutic strategies to treat it. PMID:23762871

  13. Selective Insulin Resistance in Adipocytes*

    Science.gov (United States)

    Tan, Shi-Xiong; Fisher-Wellman, Kelsey H.; Fazakerley, Daniel J.; Ng, Yvonne; Pant, Himani; Li, Jia; Meoli, Christopher C.; Coster, Adelle C. F.; Stöckli, Jacqueline; James, David E.

    2015-01-01

    Aside from glucose metabolism, insulin regulates a variety of pathways in peripheral tissues. Under insulin-resistant conditions, it is well known that insulin-stimulated glucose uptake is impaired, and many studies attribute this to a defect in Akt signaling. Here we make use of several insulin resistance models, including insulin-resistant 3T3-L1 adipocytes and fat explants prepared from high fat-fed C57BL/6J and ob/ob mice, to comprehensively distinguish defective from unaffected aspects of insulin signaling and its downstream consequences in adipocytes. Defective regulation of glucose uptake was observed in all models of insulin resistance, whereas other major actions of insulin such as protein synthesis and anti-lipolysis were normal. This defect corresponded to a reduction in the maximum response to insulin. The pattern of change observed for phosphorylation in the Akt pathway was inconsistent with a simple defect at the level of Akt. The only Akt substrate that showed consistently reduced phosphorylation was the RabGAP AS160 that regulates GLUT4 translocation. We conclude that insulin resistance in adipose tissue is highly selective for glucose metabolism and likely involves a defect in one of the components regulating GLUT4 translocation to the cell surface in response to insulin. PMID:25720492

  14. Insulin resistance and chronic inflammation

    Directory of Open Access Journals (Sweden)

    Natalia Matulewicz

    2016-12-01

    Full Text Available Insulin resistance is a condition of reduced biological response to insulin. Growing evidence indicates the role of the chronic low-grade inflammatory response in the pathogenesis of insulin resistance. Adipose tissue in obesity is characterized by increased lipolysis with the excessive release of free fatty acids, and is also a source of proinflammatory cytokines. Both these factors may inhibit insulin action. Proinflammatory cytokines exert their effect by stimulating major inflammatory NFκB and JNK pathways within the cells. Inflammatory processes in other insulin responsive tissues may also play a role in inducing insulin resistance. This paper is an overview of the chronic low-grade inflammation in adipose tissue, skeletal muscle, liver and endothelial cells during the development of insulin resistance.

  15. Insulin resistance and cognitive performance in type 2 diabetes - The Maastricht study.

    Science.gov (United States)

    Geijselaers, Stefan L C; Sep, Simone J S; Schram, Miranda T; van Boxtel, Martin P J; Henry, Ronald M A; Verhey, Frans R J; Kroon, Abraham A; Schaper, Nicolaas C; Dagnelie, Pieter C; van der Kallen, Carla J H; Stehouwer, Coen D A; Biessels, Geert Jan

    2017-05-01

    Type 2 diabetes, hyperinsulinemia, and insulin resistance are associated with cognitive impairment. Experimental studies indicate that insulin signaling in the brain is related to cognitive performance. Here we evaluated whether insulin-related variables contribute to the variance in cognitive performance among individuals with type 2 diabetes. A total of 806 individuals with type 2 diabetes (mean age 62±8years, HbA1c 6.9±1.1%) completed a neuropsychological test battery. Insulin-related variables evaluated were: fasting plasma insulin, C-peptide, and the Homeostasis Model Assessment (HOMA2-IR; in individuals without insulin treatment; n=641). The unadjusted coefficient of determination (R(2)), obtained from multiple linear regression analyses, was used to estimate the proportion of variance in cognition explained by insulin-related variables. Sex, age, and educational level together explained 18.0% (R(2)) of the variance in memory function, 26.5% in information processing speed, and 22.8% in executive function and attention. Fasting insulin, C-peptide, or HOMA2-IR did not increase the explained variance (maximum ΔR(2) 0.3%, P≥0.14). Similar results were obtained when insulin-related variables were added to models that additionally included glycemic control, cardiovascular risk factors, and depression. Our results show that measures of peripheral insulin resistance are unrelated to cognitive performance among individuals with adequately controlled type 2 diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Probing insulin bioactivity in oral nanoparticles produced by ultrasonication-assisted emulsification/internal gelation.

    Science.gov (United States)

    Lopes, Marlene A; Abrahim-Vieira, Bárbara; Oliveira, Claudia; Fonte, Pedro; Souza, Alessandra M T; Lira, Tammy; Sequeira, Joana A D; Rodrigues, Carlos R; Cabral, Lúcio M; Sarmento, Bruno; Seiça, Raquel; Veiga, Francisco; Ribeiro, António J

    2015-01-01

    Alginate-dextran sulfate-based particles obtained by emulsification/internal gelation technology can be considered suitable carriers for oral insulin delivery. A rational study focused on the emulsification and particle recovery steps was developed in order to reduce particles to the nanosize range while keeping insulin bioactivity. There was a decrease in size when ultrasonication was used during emulsification, which was more pronounced when a cosurfactant was added. Ultrasonication add-on after particle recovery decreased aggregation and led to a narrower nanoscale particle-size distribution. Insulin encapsulation efficiency was 99.3%±0.5%, attributed to the strong pH-stabilizing electrostatic effect between insulin and nanoparticle matrix polymers. Interactions between these polymers and insulin were predicted using molecular modeling studies through quantum mechanics calculations that allowed for prediction of the interaction model. In vitro release studies indicated well-preserved integrity of nanoparticles in simulated gastric fluid. Circular dichroism spectroscopy proved conformational stability of insulin and Fourier transform infrared spectroscopy technique showed rearrangements of insulin structure during processing. Moreover, in vivo biological activity in diabetic rats revealed no statistical difference when compared to nonencapsulated insulin, demonstrating retention of insulin activity. Our results demonstrate that alginate-dextran sulfate-based nanoparticles efficiently stabilize the loaded protein structure, presenting good physical properties for oral delivery of insulin.

  17. Periodontal disease decreases insulin sensitivity and insulin signaling.

    Science.gov (United States)

    Colombo, Natalia H; Shirakashi, Daisy J; Chiba, Fernando Y; Coutinho, Maria Sara de Lima; Ervolino, Edilson; Garbin, Cléa Adas Saliba; Machado, Ubiratan Fabres; Sumida, Doris H

    2012-07-01

    The purpose of this study is to investigate whether local inflammatory events, such as periodontal disease, are able to increase tumor necrosis factor-alpha (TNF-α) plasmatic concentration and decrease insulin sensitivity and insulin signaling in non-diabetic rats. Forty-eight male Wistar rats (2 months old) were divided into two groups, with either ligature-induced periodontal disease (LPD) or control conditions (CN). Experiments were performed in both groups 28 days after ligature placement. Plasmatic concentration of glycemia and TNF-α (n = 10) were analyzed by the glucose oxidase and enzyme-linked immunosorbent assay method, respectively. Insulin sensitivity (n = 7) was measured using the insulin tolerance test. Insulin signal transduction (n = 7) was measured by pp185 tyrosine phosphorylation status in insulin-sensitive tissues using the Western blotting method. The LPD group showed decreased insulin sensitivity (P 0.05). TNF-α plasmatic concentration was higher in LPD rats compared to CN rats. In addition, a decrease in the pp185 tyrosine phosphorylation status was observed after insulin stimulus in both white adipose and skeletal muscle tissues of the LPD group compared with the CN group. LPD is able to cause alterations to both insulin signaling and insulin sensitivity, probably because of the elevation of TNF-α plasmatic concentration. Thus, the present results emphasize the importance of the prevention of local inflammatory diseases, such as periodontitis, to prevent diabetes mellitus.

  18. Brain Insulin Resistance and Deficiency as Therapeutic Targets in Alzheimer's Disease

    Science.gov (United States)

    de la Monte, Suzanne M

    2012-01-01

    Alzheimer's disease [AD] is the most common cause of dementia in North America. Despite 30+ years of intense investigation, the field lacks consensus regarding the etiology and pathogenesis of sporadic AD, and therefore we still do not know the best strategies for treating and preventing this debilitating and costly disease. However, growing evidence supports the concept that AD is fundamentally a metabolic disease with substantial and progressive derangements in brain glucose utilization and responsiveness to insulin and insulin-like growth factor [IGF] stimulation. Moreover, AD is now recognized to be heterogeneous in nature, and not solely the end-product of aberrantly processed, misfolded, and aggregated oligomeric amyloid-beta peptides and hyperphosphorylated tau. Other factors, including impairments in energy metabolism, increased oxidative stress, inflammation, insulin and IGF resistance, and insulin/IGF deficiency in the brain should be incorporated into all equations used to develop diagnostic and therapeutic approaches to AD. Herein, the contributions of impaired insulin and IGF signaling to AD-associated neuronal loss, synaptic disconnection, tau hyperphosphorylation, amyloid-beta accumulation, and impaired energy metabolism are reviewed. In addition, we discuss current therapeutic strategies and suggest additional approaches based on the hypothesis that AD is principally a metabolic disease similar to diabetes mellitus. Ultimately, our ability to effectively detect, monitor, treat, and prevent AD will require more efficient, accurate and integrative diagnostic tools that utilize clinical, neuroimaging, biochemical, and molecular biomarker data. Finally, it is imperative that future therapeutic strategies for AD abandon the concept of uni-modal therapy in favor of multi-modal treatments that target distinct impairments at different levels within the brain insulin/IGF signaling cascades. PMID:22329651

  19. Metabolic implications when employing heavy pre- and post-exercise rapid-acting insulin reductions to prevent hypoglycaemia in type 1 diabetes patients: a randomised clinical trial.

    Directory of Open Access Journals (Sweden)

    Matthew D Campbell

    Full Text Available To examine the metabolic, gluco-regulatory-hormonal and inflammatory cytokine responses to large reductions in rapid-acting insulin dose administered prandially before and after intensive running exercise in male type 1 diabetes patients.This was a single centre, randomised, controlled open label study. Following preliminary testing, 8 male patients (24±2 years, HbA1c 7.7±0.4%/61±4 mmol.l-1 treated with insulin's glargine and aspart, or lispro attended the laboratory on two mornings at ∼08:00 h and consumed a standardised breakfast carbohydrate bolus (1 g carbohydrate.kg-1BM; 380±10 kcal and self-administered a 75% reduced rapid-acting insulin dose 60 minutes before 45 minutes of intensive treadmill running at 73.1±0.9% VO2peak. At 60 minutes post-exercise, patients ingested a meal (1 g carbohydrate.kg-1BM; 660±21 kcal and administered either a Full or 50% reduced rapid-acting insulin dose. Blood glucose and lactate, serum insulin, cortisol, non-esterified-fatty-acids, β-Hydroxybutyrate, and plasma glucagon, adrenaline, noradrenaline, IL-6, and TNF-α concentrations were measured for 180 minutes post-meal.All participants were analysed. All glycaemic, metabolic, hormonal, and cytokine responses were similar between conditions up to 60 minutes following exercise. Following the post-exercise meal, serum insulin concentrations were lower under 50% (p<0.05 resulting in 75% of patients experiencing hyperglycaemia (blood glucose ≥8.0 mmol.l-1; 50% n = 6, Full n = 3. β-Hydroxybutyrate concentrations decreased similarly, such that at 180 minutes post-meal concentrations were lower than rest under Full and 50%. IL-6 and TNF-α concentrations remained similar to fasting levels under 50% but declined under Full. Under 50% IL-6 concentrations were inversely related with serum insulin concentrations (r = -0.484, p = 0.017.Heavily reducing rapid-acting insulin dose with a carbohydrate bolus before, and a meal after intensive

  20. Addition of or switch to insulin therapy in people treated with glucagon-like peptide-1 receptor agonists: A real-world study in 66 583 patients.

    Science.gov (United States)

    Montvida, Olga; Klein, Kerenaftali; Kumar, Sudhesh; Khunti, Kamlesh; Paul, Sanjoy K

    2017-01-01

    Real world outcomes of addition or switch to insulin therapy in type 2 diabetes (T2DM) patients on glucagon-like paptide-1 receptor agonist (GLP-1RA) with inadequately controlled hyperglycaemia, are not known. Patients with T2DM (n = 66 583) with a minimum of 6 months of GLP-1RA treatment and without previous insulin treatment were selected. Those who added insulin (n = 39 599) or switched to insulin after GLP-1RA cessation (n = 4706) were identified. Adjusted changes in glycated haemoglobin (HbA1c), weight, systolic blood pressure (SBP), and LDL cholesterol were estimated over 24 months follow-up. Among those who continued with GLP-1RA treatment without adding or switching to insulin, the highest adjusted mean HbA1c change was achieved within 6 months, with no further glycaemic benefits observed during 24 months of follow-up. Addition of insulin within 6 months of GLP-1RA initiation was associated with 18% higher odds of achieving HbA1c insulin later. At 24 months, those who added insulin reduced HbA1c significantly by 0.55%, while no glycaemic benefit was observed in those who switched to insulin. Irrespective of intensification with insulin, weight, SBP and LDL cholesterol were significantly reduced by 3 kg, 3 mm Hg, and 0.2 mmol/L, respectively, over 24 months. Significant delay in intensification of treatment by addition of insulin is observed in patients with T2DM inadequately controlled with GLP-1RA. Earlier addition of insulin is associated with better glycaemic control, while switching to insulin is not clinically beneficial during 2 years of treatment. Non-responding patients on GLP-1RA would benefit from adding insulin therapy, rather than switching to insulin. © 2016 John Wiley & Sons Ltd.

  1. Serological analysis of human IgG and IgE anti-insulin antibodies by solid-phase radioimmunoassays

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, R.G.; Rendell, M.; Adkinson, N.F. Jr.

    1980-12-01

    A single solid-phase assay system which is useful for quantitative measurement of both IgG and IgE anti-insulin antibodies in human serum has been developed. Insulin-specific immunoglobulins are absorbed from human serum by excess quantities of insulin-agarose. After washes to remove unbound immunoglobulins, radioiodinated Staph A or rabbit anti-human IgE is added to detect bound IgG or IgE anbitodies, respectively.

  2. The Implication of the Brain Insulin Receptor in Late Onset Alzheimer’s Disease Dementia

    Directory of Open Access Journals (Sweden)

    Jaume Folch

    2018-01-01

    Full Text Available Alzheimer’s disease (AD is progressive neurodegenerative disorder characterized by brain accumulation of the amyloid β peptide (Aβ, which form senile plaques, neurofibrillary tangles (NFT and, eventually, neurodegeneration and cognitive impairment. Interestingly, epidemiological studies have described a relationship between type 2 diabetes mellitus (T2DM and this pathology, being one of the risk factors for the development of AD pathogenesis. Information as it is, it would point out that, impairment in insulin signalling and glucose metabolism, in central as well as peripheral systems, would be one of the reasons for the cognitive decline. Brain insulin resistance, also known as Type 3 diabetes, leads to the increase of Aβ production and TAU phosphorylation, mitochondrial dysfunction, oxidative stress, protein misfolding, and cognitive impairment, which are all hallmarks of AD. Moreover, given the complexity of interlocking mechanisms found in late onset AD (LOAD pathogenesis, more data is being obtained. Recent evidence showed that Aβ42 generated in the brain would impact negatively on the hypothalamus, accelerating the “peripheral” symptomatology of AD. In this situation, Aβ42 production would induce hypothalamic dysfunction that would favour peripheral hyperglycaemia due to down regulation of the liver insulin receptor. The objective of this review is to discuss the existing evidence supporting the concept that brain insulin resistance and altered glucose metabolism play an important role in pathogenesis of LOAD. Furthermore, we discuss AD treatment approaches targeting insulin signalling using anti-diabetic drugs and mTOR inhibitors.

  3. Insulin/receptor binding: the last piece of the puzzle? What recent progress on the structure of the insulin/receptor complex tells us (or not) about negative cooperativity and activation.

    Science.gov (United States)

    De Meyts, Pierre

    2015-04-01

    Progress in solving the structure of insulin bound to its receptor has been slow and stepwise, but a milestone has now been reached with a refined structure of a complex of insulin with a "microreceptor" that contains the primary binding site. The insulin receptor is a dimeric allosteric enzyme that belongs to the family of receptor tyrosine kinases. The insulin binding process is complex and exhibits negative cooperativity. Biochemical evidence suggested that insulin, through two distinct binding sites, crosslinks two receptor sites located on each α subunit. The structure of the unliganded receptor ectodomain showed a symmetrical folded-over conformation with an antiparallel disposition. Further work resolved the detailed structure of receptor site 1, both without and with insulin. Recently, a missing piece in the puzzle was added: the C-terminal portion of insulin's B-chain known to be critical for binding and negative cooperativity. Here I discuss these findings and their implications. © 2015 WILEY Periodicals, Inc.

  4. Value Added in English Schools

    OpenAIRE

    Andrew Ray; Tanya McCormack; Helen Evans

    2009-01-01

    Value-added indicators are now a central part of school accountability in England, and value-added information is routinely used in school improvement at both the national and the local levels. This article describes the value-added models that are being used in the academic year 2007–8 by schools, parents, school inspectors, and other professionals in local and national governments. The article outlines the development of value-added models in England following the introduction of national t...

  5. Insulin and Glucagon

    DEFF Research Database (Denmark)

    Holst, Jens Juul; Holland, William; Gromada, Jesper

    2017-01-01

    In August 2016, several leaders in glucagon biology gathered for the European Association for the Study of Diabetes Hagedorn Workshop in Oxford, England. A key point of discussion focused on the need for basal insulin to allow for the therapeutic benefit of glucagon blockade in the treatment...... of diabetes. Among the most enlightening experimental results presented were findings from studies in which glucagon receptor-deficient mice were administered streptozotocin to destroy pancreatic β cells or had undergone diphtheria toxin-induced β cell ablation. This article summarizes key features...... of the discussion as a consensus was reached. Agents that antagonize glucagon may be of great benefit for the treatment of diabetes; however, sufficient levels of basal insulin are required for their therapeutic efficacy....

  6. Alteration of brain insulin and leptin signaling promotes energy homeostasis impairment and neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Taouis Mohammed

    2011-09-01

    Full Text Available The central nervous system (CNS controls vital functions, by efficiently coordinating peripheral and central cascades of signals and networks in a coordinated manner. Historically, the brain was considered to be an insulin-insensitive tissue. But, new findings demonstrating that insulin is present in different regions of themammalian brain, in particular the hypothalamus and the hippocampus. Insulin acts through specific receptors and dialogues with numerous peptides, neurotransmitters and adipokines such as leptin. The cross-talk between leptin and insulin signaling pathways at the hypothalamic level is clearly involved in the control of energy homeostasis. Both hormones are anorexigenic through their action on hypothalamic arcuate nucleus by inducing the expression of anorexigenic neuropetides such as POMC (pro-opiomelanocortin, the precursor of aMSH and reducing the expression of orexigenic neuropeptide such as NPY (Neuropeptide Y. Central defect of insulin and leptin signaling predispose to obesity (leptin-resistant state and type-2 diabetes (insulin resistant state. Obesity and type-2 diabetes are associated to deep alterations in energy homeostasis control but also to other alterations of CNS functions as the predisposition to neurodegenerative diseases such as Alzheimer’s disease (AD. AD is a neurodegenerative disorder characterized by distinct hallmarks within the brain. Postmortem observation of AD brains showed the presence of parenchymal plaques due to the accumulation of the amyloid beta (AB peptide and neurofibrillary tangles. These accumulations result from the hyperphosphorylation of tau (a mictrotubule-interacting protein. Both insulin and leptin have been described to modulate tau phosphorylation and therefore in leptin and insulin resistant states may contribute to AD. The concentrations of leptin and insulin cerebrospinal fluid are decreased type2 diabetes and obese patients. In addition, the concentration of insulin in the

  7. [Insulin-requiring diabetes].

    Science.gov (United States)

    Leutenegger, M; Gross, A; Ostermann, G; Grulet, H; Pasqual, C; Dijoux, B

    1988-01-01

    The insulinorequiring diabetes is a notion which deserves a clear definition, essentially clinical, because it covers a wide range of physiopathological situations. The progressive degradation of Diabetes type II means a progressive discrepancy of insulinosecretion and above all an increase of insulinoresistance. The noxious part of chronical hyperglycemia is at present well known. The present therapeutical prospects tend to delay or limit insulinotherapy, by trying to obtain remission of insulinorequiring and some attempt to give a combined treatment associating insulin and hypoglycemic drugs.

  8. Value Added in English Schools

    Science.gov (United States)

    Ray, Andrew; McCormack, Tanya; Evans, Helen

    2009-01-01

    Value-added indicators are now a central part of school accountability in England, and value-added information is routinely used in school improvement at both the national and the local levels. This article describes the value-added models that are being used in the academic year 2007-8 by schools, parents, school inspectors, and other…

  9. The effects of GLP-1 analogues in obese, insulin-using type 2 diabetes in relation to eating behaviour

    NARCIS (Netherlands)

    de Boer, Stefanie Amarens; Lefrandt, Joop Daniel; Petersen, Japke Frida; Boersma, Hendrikus Hessel; Mulder, Douwe Johannes; Hoogenberg, Klaas

    Background Glucagon-like peptide-1 receptor agonists (GLP-1 RA) added to insulin in type 2 diabetes patients have shown to lower body weight, improve glycaemic control and reduce total daily insulin dose in short term studies, although the individual response greatly varies. Objective To evaluate

  10. Combining a GLP-1 receptor agonist and basal insulin: study evidence and practical considerations.

    Science.gov (United States)

    Carris, Nicholas W; Taylor, James R; Gums, John G

    2014-12-01

    Most patients with diabetes mellitus require multiple medications to achieve glycemic goals. Considering this and the increasing incidence of type 2 diabetes worldwide, the need for effective combination therapy is pressing. Basal insulin and glucagon-like peptide 1 (GLP-1) receptor agonists are frequently used to treat type 2 diabetes. Though both classes of medication are exclusively injectable, which may cause initial hesitation from providers, evidence for their combined use is substantial. This review summarizes the theoretical benefit, supporting evidence, and implementation of a combined basal insulin-GLP-1 receptor agonist regimen. Basal insulin added to a GLP-1 receptor agonist reduces hemoglobin A1c (HbA1c) without weight gain or significantly increased hypoglycemia. A GLP-1 receptor agonist added to basal insulin reduces HbA1c and body weight. Compared with the addition of meal-time insulin to basal insulin, a GLP-1 receptor agonist produces similar or greater reduction in HbA1c, weight loss instead of weight gain, and less hypoglycemia. Gastrointestinal adverse events are common with GLP-1 receptor agonists, especially during initiation and titration. However, combination with basal insulin is not expected to augment expected adverse events that come with using a GLP-1 receptor agonist. Basal insulin can be added to a GLP-1 receptor agonist with a slow titration to target goal fasting plasma glucose. In patients starting a GLP-1 receptor agonist, the dose of basal insulin should be decreased by 20 % in patients with an HbA1c ≤8 %. The evidence from 15 randomized prospective studies supports the combined use of a GLP-1 receptor agonist with basal insulin in a broad range of patients with uncontrolled type 2 diabetes.

  11. Clinical evidence and mechanistic basis for vildagliptin's effect in combination with insulin

    Directory of Open Access Journals (Sweden)

    Schweizer A

    2013-02-01

    Full Text Available Anja Schweizer,1 James E Foley,2 Wolfgang Kothny,2 Bo Ahrén31Novartis Pharma AG, Basel, Switzerland; 2Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 3Department of Clinical Sciences, Lund University, Lund, SwedenAbstract: Due to the progressive nature of type 2 diabetes, many patients need insulin as add-on to oral antidiabetic drugs (OADs in order to maintain adequate glycemic control. Insulin therapy primarily targets elevated fasting glycemia but is less effective to reduce postprandial hyperglycemia. In addition, the risk of hypoglycemia limits its effectiveness and there is a concern of weight gain. These drawbacks may be overcome by combining insulin with incretin-based therapies as these increase glucose sensitivity of both the α- and β-cells, resulting in improved postprandial glycemia without the hypoglycemia and weight gain associated with increasing the dose of insulin. The dipeptidyl peptidase-IV (DPP-4 inhibitor vildagliptin has also been shown to protect from hypoglycemia by enhancing glucagon counterregulation. The effectiveness of combining vildagliptin with insulin was demonstrated in three different studies in which vildagliptin decreased A1C levels when added to insulin therapy without increasing hypoglycemia. This was established with and without concomitant metformin therapy. Furthermore, the effectiveness of vildagliptin appears to be greater when insulin is used as a basal regimen as opposed to being used to reduce postprandial hyperglycemia, since improvement in insulin secretion likely plays a minor role when relatively high doses of insulin are administered before meals. This article reviews the clinical experience with the combination of vildagliptin and insulin and discusses the mechanistic basis for the beneficial effects of the combination. The data support the use of vildagliptin in combination with insulin in general and, in line with emerging clinical practice, suggest that treating patients with

  12. AdS Black Hole with Phantom Scalar Field

    Directory of Open Access Journals (Sweden)

    Limei Zhang

    2017-01-01

    Full Text Available We present an AdS black hole solution with Ricci flat horizon in Einstein-phantom scalar theory. The phantom scalar fields just depend on the transverse coordinates x and y, which are parameterized by the parameter α. We study the thermodynamics of the AdS phantom black hole. Although its horizon is a Ricci flat Euclidean space, we find that the thermodynamical properties of the black hole solution are qualitatively the same as those of AdS Schwarzschild black hole. Namely, there exists a minimal temperature and the large black hole is thermodynamically stable, while the smaller one is unstable, so there is a so-called Hawking-Page phase transition between the large black hole and the thermal gas solution in the AdS space-time in Poincare coordinates. We also calculate the entanglement entropy for a strip geometry dual to the AdS phantom black holes and find that the behavior of the entanglement entropy is qualitatively the same as that of the black hole thermodynamical entropy.

  13. Effect of normalization of fasting glucose by intensified insulin therapy and influence of eNOS polymorphisms on the incidence of restenosis after peripheral angioplasty in patients with type 2 diabetes: a randomized, open-label clinical trial.

    Science.gov (United States)

    Piatti, Pier Marco; Marone, Enrico; Mantero, Manuela; Setola, Emanuela; Galluccio, Elena; Lucotti, Pietro; Shehaj, Ermal; Villa, Valentina; Perticone, Francesca; Venturini, Massimo; Palini, Alessio; Airoldi, Flavio; Faglia, Ezio; Del Maschio, Alessandro; Colombo, Antonio; Chiesa, Roberto; Bosi, Emanuele; Monti, Lucilla D

    2013-06-01

    Primary objective was to evaluate whether an intensified insulin therapy (IIT) incorporating the target of normal fasting glucose and HbA1c levels could halve the incidence of restenosis/amputation/SCA/death at 6 months after peripheral angioplasty compared with standard care (SC) in patients with type 2 diabetes (DMT2) affected by critical limb ischemia (CLI). Forty-six consecutive patients with DMT2 and CLI were randomly assigned to a parallel, open-label study with IIT (basal-bolus glulisine + glargine administrations) or SC (glargine administration + oral antidiabetic drugs). A SNP of eNOS (rs753482-A>C) and circulating CD34(+) and CD34(+)KDR(+) progenitor cells were determined. At the end of the study, although HbA1c levels were lower in IIT than in SC (6.9 ± 1.3 % vs. 7.6 ± 1.2 %, p incidence of restenosis/amputation/SCA/death (52 and 65 %, respectively, odd ratio 0.59; CI 95 %: 0.21-1.62, p = 0.59). rs753482AC+CC as compared with rs753482AA increased the cumulative incidence of restenosis/amputation/SCA/death (79 and 42 %; odd ratio 5.3; CI 95 %: 1.41-19.5, p incidence of restenosis/amputation/SCA/death in DMT2 and CLI patients. These patients correspond to a class of fragile subjects at high risk of cardiovascular events, and new predictors of restenosis should be contemplated, such as of eNOS polymorphism, (rs753482-A>C SNP) and circulating endothelial progenitor cells.

  14. Therapeutic targets of brain insulin resistance in sporadic Alzheimer's disease.

    Science.gov (United States)

    de la Monte, Suzanne M

    2012-01-01

    Growing evidence supports roles for brain insulin and insulin-like growth factor (IGF) resistance and metabolic dysfunction in the pathogenesis of Alzheimer's disease (AD). Whether the underlying problem stems from a primary disorder of central nervous system (CNS) neurons and glia, or secondary effects of systemic diseases such as obesity, Type 2 diabetes, or metabolic syndrome, the end-results include impaired glucose utilization, mitochondrial dysfunction, increased oxidative stress, neuroinflammation, and the propagation of cascades that result in the accumulation of neurotoxic misfolded, aggregated, and ubiquitinated fibrillar proteins. This article reviews the roles of impaired insulin and IGF signaling to AD-associated neuronal loss, synaptic disconnection, tau hyperphosphorylation, amyloid-beta accumulation, and impaired energy metabolism, and discusses therapeutic strategies and lifestyle approaches that could be used to prevent, delay the onset, or reduce the severity of AD. Finally, it is critical to recognize that AD is heterogeneous and has a clinical course that fully develops over a period of several decades. Therefore, early and multi-modal preventive and treatment approaches should be regarded as essential.

  15. Insulin resistance in obesity can be reliably identified from fasting plasma insulin

    NARCIS (Netherlands)

    ter Horst, K. W.; Gilijamse, P. W.; Koopman, K. E.; de Weijer, B. A.; Brands, M.; Kootte, R. S.; Romijn, J. A.; Ackermans, M. T.; Nieuwdorp, M.; Soeters, M. R.; Serlie, M. J.

    2015-01-01

    Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely

  16. Insulin restores myocardial presynaptic sympathetic neuronal integrity in insulin-resistant diabetic rats.

    Science.gov (United States)

    Thackeray, James T; deKemp, Robert A; Beanlands, Rob S; DaSilva, Jean N

    2013-10-01

    Diabetes is associated with increased sympathetic activity, elevated norepinephrine, impaired heart rate variability, and the added risk of cardiovascular mortality. The temporal development of sympathetic neuronal dysfunction, response to therapy, and relation to ventricular function is not well characterized. Sympathetic neuronal integrity was serially investigated in high fat diet-fed streptozotocin diabetic rats using [(11)C]meta-hydroxyephedrine (HED) positron emission tomography at baseline, 8 weeks of diabetes, and after a further 8 weeks of insulin or insulin-sensitizing metformin therapy. Myocardial HED retention was reduced in diabetic rats (n = 16) compared to non-diabetics (n = 6) at 8 weeks by 52-57% (P = .01) with elevated plasma and myocardial norepinephrine levels. Echocardiography pulse-wave Doppler measurements demonstrated prolonged mitral valve deceleration and increased early-to-atrial filling velocity, consistent with diastolic dysfunction. Insulin but not metformin evoked recovery of HED retention and plasma norepinephrine (P < .05), whereas echocardiography measurements of diastolic function were not improved by either treatment. Relative expressions of norepinephrine reuptake transporter and β-adrenoceptors were lower in metformin-treated as compared to insulin-treated diabetic and non-diabetic rats. Diabetic rats exhibited depressed heart rate variability and impaired diastolic function which persisted despite insulin treatment. HED imaging provides sound estimation of sympathetic function. Effective glycemic control can recover sympathetic function in diabetic rats without the corresponding recovery of echocardiography indicators of diastolic dysfunction. HED positron emission tomography imaging may be useful in stratifying cardiovascular risk among diabetic patients and in evaluating the effect of glycemic therapy on the heart.

  17. Additional disulfide bonds in insulin

    DEFF Research Database (Denmark)

    Vinther, Tine N; Pettersson, Ingrid; Huus, Kasper

    2015-01-01

    The structure of insulin, a glucose homeostasis-controlling hormone, is highly conserved in all vertebrates and stabilized by three disulfide bonds. Recently, we designed a novel insulin analogue containing a fourth disulfide bond located between positions A10-B4. The N-terminus of insulin's B......-chain is flexible and can adapt multiple conformations. We examined how well disulfide bond predictions algorithms could identify disulfide bonds in this region of insulin. In order to identify stable insulin analogues with additional disulfide bonds, which could be expressed, the Cβ cut-off distance had...... in comparison to analogues with additional disulfide bonds that were more difficult to predict. In contrast, addition of the fourth disulfide bond rendered all analogues resistant to fibrillation under stress conditions and all stable analogues bound to the insulin receptor with picomolar affinities. Thus...

  18. Revisiting the thermodynamic relations in AdS /CMT models

    Science.gov (United States)

    Hyun, Seungjoon; Park, Sang-A.; Yi, Sang-Heon

    2017-03-01

    Motivated by the recent unified approach to the Smarr-like relation of anti-de Sitter (AdS) planar black holes in conjunction with the quasilocal formalism on conserved charges, we revisit the quantum statistical and thermodynamic relations of hairy AdS planar black holes. By extending the previous results, we identify the hairy contribution in the bulk and show that the holographic computation can be improved so that it is consistent with the bulk computation. We argue that the first law can be retained in its universal form and that the relation between the on-shell renormalized Euclidean action and its free energy interpretation in gravity may also be undeformed even with the hairy contribution in hairy AdS black holes.

  19. Asymptotically AdS spacetimes with a timelike Kasner singularity

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Jie [Racah Institute of Physics, The Hebrew University of Jerusalem, Jerusalem 91904 (Israel)

    2016-07-21

    Exact solutions to Einstein’s equations for holographic models are presented and studied. The IR geometry has a timelike cousin of the Kasner singularity, which is the less generic case of the BKL (Belinski-Khalatnikov-Lifshitz) singularity, and the UV is asymptotically AdS. This solution describes a holographic RG flow between them. The solution’s appearance is an interpolation between the planar AdS black hole and the AdS soliton. The causality constraint is always satisfied. The entanglement entropy and Wilson loops are discussed. The boundary condition for the current-current correlation function and the Laplacian in the IR is examined. There is no infalling wave in the IR, but instead, there is a normalizable solution in the IR. In a special case, a hyperscaling-violating geometry is obtained after a dimensional reduction.

  20. Insulin Resistance, Hyperglycemia, and Atherosclerosis

    OpenAIRE

    Bornfeldt, Karin E.; Tabas, Ira

    2011-01-01

    Progress in preventing atherosclerotic coronary artery disease (CAD) has been stalled by the epidemic of type 2 diabetes. Further advances in this area demand a thorough understanding of how two major features of type 2 diabetes, insulin resistance and hyperglycemia, impact atherosclerosis. Insulin resistance is associated with systemic CAD risk factors, but increasing evidence suggests that defective insulin signaling in atherosclerotic lesional cells also plays an important role. The role o...

  1. Impact of antidiabetic substances to development of insulin resistance and neurodegenerative changes in mouse models of type 2 diabetes

    OpenAIRE

    Mikulášková, Barbora

    2014-01-01

    Numerous epidemiological and experimental studies have shown that patients suffering from metabolic disorders such as type 2 diabetes mellitus (TDM2), insulin resistance or obesity are at a higher risk of cognitive functions impairment and developing Alzheimer's disease (AD). Impairment of insulin signalling in the brain could contribute to two pathological changes which leads to AD development that include insoluble senile plaques and neurofibrillary tangles, containing an abnormally hyperph...

  2. Insulin Resistance and Mitochondrial Dysfunction.

    Science.gov (United States)

    Gonzalez-Franquesa, Alba; Patti, Mary-Elizabeth

    2017-01-01

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

  3. Insulin Resistance and Mitochondrial Dysfunction

    DEFF Research Database (Denmark)

    Gonzalez-Franquesa, Alba; Patti, Mary-Elizabeth

    2017-01-01

    Insulin resistance precedes and predicts the onset of type 2 diabetes (T2D) in susceptible humans, underscoring its important role in the complex pathogenesis of this disease. Insulin resistance contributes to multiple tissue defects characteristic of T2D, including reduced insulin-stimulated glu......Insulin resistance precedes and predicts the onset of type 2 diabetes (T2D) in susceptible humans, underscoring its important role in the complex pathogenesis of this disease. Insulin resistance contributes to multiple tissue defects characteristic of T2D, including reduced insulin...... of defects in mitochondrial function (i.e., bioenergetics, biogenesis and dynamics). However, it remains uncertain whether mitochondrial dysfunction is primary (critical initiating defect) or secondary to the subtle derangements in glucose metabolism, insulin resistance, and defective insulin secretion...... present early in the course of disease development. In this chapter, we will present the evidence linking mitochondrial dysfunction and insulin resistance, and review the potential for mitochondrial targets as a therapeutic approach for T2D....

  4. Holography in Lovelock Chern-Simons AdS gravity

    Science.gov (United States)

    Cvetković, Branislav; Miskovic, Olivera; Simić, Dejan

    2017-08-01

    We analyze holographic field theory dual to Lovelock Chern-Simons anti-de Sitter (AdS) gravity in higher dimensions using first order formalism. We first find asymptotic symmetries in the AdS sector showing that they consist of local translations, local Lorentz rotations, dilatations and non-Abelian gauge transformations. Then, we compute 1-point functions of energy-momentum and spin currents in a dual conformal field theory and write Ward identities. We find that the holographic theory possesses Weyl anomaly and also breaks non-Abelian gauge symmetry at the quantum level.

  5. AdS5 magnetized solutions in minimal gauged supergravity

    Science.gov (United States)

    Blázquez-Salcedo, Jose Luis; Kunz, Jutta; Navarro-Lérida, Francisco; Radu, Eugen

    2017-08-01

    We construct a generalization of the AdS charged rotating black holes with two equal magnitude angular momenta in five-dimensional minimal gauged supergravity. In addition to the mass, electric charge and angular momentum, the new solutions possess an extra-parameter associated with a non-zero magnitude of the magnetic potential at infinity. In contrast with the known cases, these new black holes possess a non-trivial zero-horizon size limit which describes a one parameter family of spinning charged solitons. All configurations reported in this work approach asymptotically an AdS5 spacetime in global coordinates and are free of pathologies.

  6. AdS5 magnetized solutions in minimal gauged supergravity

    Directory of Open Access Journals (Sweden)

    Jose Luis Blázquez-Salcedo

    2017-08-01

    Full Text Available We construct a generalization of the AdS charged rotating black holes with two equal magnitude angular momenta in five-dimensional minimal gauged supergravity. In addition to the mass, electric charge and angular momentum, the new solutions possess an extra-parameter associated with a non-zero magnitude of the magnetic potential at infinity. In contrast with the known cases, these new black holes possess a non-trivial zero-horizon size limit which describes a one parameter family of spinning charged solitons. All configurations reported in this work approach asymptotically an AdS5 spacetime in global coordinates and are free of pathologies.

  7. Loops in AdS from conformal field theory

    Science.gov (United States)

    Aharony, Ofer; Alday, Luis F.; Bissi, Agnese; Perlmutter, Eric

    2017-07-01

    We propose and demonstrate a new use for conformal field theory (CFT) crossing equations in the context of AdS/CFT: the computation of loop amplitudes in AdS, dual to non-planar correlators in holographic CFTs. Loops in AdS are largely unexplored, mostly due to technical difficulties in direct calculations. We revisit this problem, and the dual 1 /N expansion of CFTs, in two independent ways. The first is to show how to explicitly solve the crossing equations to the first subleading order in 1 /N 2, given a leading order solution. This is done as a systematic expansion in inverse powers of the spin, to all orders. These expansions can be resummed, leading to the CFT data for finite values of the spin. Our second approach involves Mellin space. We show how the polar part of the four-point, loop-level Mellin amplitudes can be fully reconstructed from the leading-order data. The anomalous dimensions computed with both methods agree. In the case of ϕ 4 theory in AdS, our crossing solution reproduces a previous computation of the one-loop bubble diagram. We can go further, deriving the four-point scalar triangle diagram in AdS, which had never been computed. In the process, we show how to analytically derive anomalous dimensions from Mellin amplitudes with an infinite series of poles, and discuss applications to more complicated cases such as the N = 4 super-Yang-Mills theory.

  8. Double-blind, randomized, multicentre, and active comparator controlled investigation of the effect of pioglitazone, metformin, and the combination of both on cardiovascular risk in patients with type 2 diabetes receiving stable basal insulin therapy: the PIOCOMB study.

    Science.gov (United States)

    Hanefeld, Markolf; Pfützner, Andreas; Forst, Thomas; Kleine, Iris; Fuchs, Winfried

    2011-07-14

    We analyzed specific effects of an add-on therapy with pioglitazone compared to metformin and their combination in patients with basal insulin treatment on biomarkers of CV risk. In this double-blind, randomized, multicentre, active comparator controlled trial, 121 patients with type 2 diabetes were enrolled. Inclusions: treatment with basal insulin, HbA(1C) 6.5%-8.5%, age 30-75 years. After glargine therapy over 2 weeks for titration towards FBG ≤ 7.8 mmol/L, patients received either (A) bid 850 mg metformin (n = 42), (B) bid 15 mg pioglitazone (n = 40), or (C) 30 mg pioglitazone plus 1.7 g metformin (n = 39) over 6 months. Matrix Metal Proteinase 9 (MMP-9) was primary objective, together with biomarkers of CV risk. Pioglitazone (B) reduced MMP-9 versus baseline by 54.1 ± 187.1 ng/mL, with metformin (A) it was increased by 49.6 ± 336.2 ng/mL (p = 0.0345; B vs. A), and with the combination of both (C) it was decreased by 67.8 ± 231.4 ng/mL (A vs. C: p = 0.0416; B vs. C: p = 0.8695). After logarithmic transformation due to high variances the exploratory results showed significance for A vs. B (p = 0.0043) and for A vs. C (p = 0.0289).Insulin dosage was reduced by 7.3 units in group B (p pioglitazone but not of metformin reduces MMP-9, hs-CRP and increased insulin sensitivity and adiponectin in this study. The combination of both had no additional effect on inflammation. Pioglitazone is suggested to be a rational add-on therapy to basal insulin in patients with high CV risk.

  9. Metformin ameliorates high uric acid-induced insulin resistance in skeletal muscle cells.

    Science.gov (United States)

    Yuan, Huier; Hu, Yaqiu; Zhu, Yuzhang; Zhang, Yongneng; Luo, Chaohuan; Li, Zhi; Wen, Tengfei; Zhuang, Wanling; Zou, Jinfang; Hong, Liangli; Zhang, Xin; Hisatome, Ichiro; Yamamoto, Tetsuya; Cheng, Jidong

    2017-03-05

    Hyperuricemia occurs together with abnormal glucose metabolism and insulin resistance. Skeletal muscle is an important organ of glucose uptake, disposal, and storage. Metformin activates adenosine monophosphate-activated protein kinase (AMPK) to regulate insulin signaling and promote the translocation of glucose transporter type 4 (GLUT4), thereby stimulating glucose uptake to maintain energy balance. Our previous study showed that high uric acid (HUA) induced insulin resistance in skeletal muscle tissue. However, the mechanism of metformin ameliorating UA-induced insulin resistance in muscle cells is unknown and we aimed to determine it. In this study, differentiated C2C12 cells were exposed to UA (15 mg/dl), then reactive oxygen species (ROS) was detected with DCFH-DA and glucose uptake with 2-NBDG. The levels of phospho-insulin receptor substrate 1 (IRS1; Ser307), phospho-AKT (Ser473) and membrane GLUT4 were examined by western blot analysis. The impact of metformin on UA-induced insulin resistance was monitored by adding Compound C, an AMPK inhibitor, and LY294002, a PI3K/AKT inhibitor. Our data indicate that UA can increase ROS production, inhibit IRS1-AKT signaling and insulin-stimulated glucose uptake, and induce insulin resistance in C2C12 cells. Metformin can reverse this process by increasing intracellular glucose uptake and ameliorating UA-induced insulin resistance. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  10. Added Sugars and Cardiovascular Disease Risk in Children

    Science.gov (United States)

    Vos, Miriam B.; Kaar, Jill L.; Welsh, Jean A.; Van Horn, Linda V.; Feig, Daniel I.; Anderson, Cheryl A.M.; Patel, Mahesh J.; Munos, Jessica Cruz; Krebs, Nancy F.; Xanthakos, Stavra A.; Johnson, Rachel K.

    2017-01-01

    BACKGROUND Poor lifestyle behaviors are leading causes of preventable diseases globally. Added sugars contribute to a diet that is energy dense but nutrient poor and increase risk of developing obesity, cardiovascular disease, hypertension, obesity-related cancers, and dental caries. METHODS AND RESULTS For this American Heart Association scientific statement, the writing group reviewed and graded the current scientific evidence for studies examining the cardiovascular health effects of added sugars on children. The available literature was subdivided into 5 broad subareas: effects on blood pressure, lipids, insulin resistance and diabetes mellitus, nonalcoholic fatty liver disease, and obesity. CONCLUSIONS Associations between added sugars and increased cardiovascular disease risk factors among US children are present at levels far below current consumption levels. Strong evidence supports the association of added sugars with increased cardiovascular disease risk in children through increased energy intake, increased adiposity, and dyslipidemia. The committee found that it is reasonable to recommend that children consume ≤25 g (100 cal or ≈6 teaspoons) of added sugars per day and to avoid added sugars for children sugars most likely can be safely consumed in low amounts as part of a healthy diet, few children achieve such levels, making this an important public health target. PMID:27550974

  11. The evolutionary benefit of insulin resistance

    NARCIS (Netherlands)

    Soeters, Maarten R.; Soeters, Peter B.

    2012-01-01

    Insulin resistance is perceived as deleterious, associated with conditions as the metabolic syndrome, type 2 diabetes mellitus and critical illness. However, insulin resistance is evolutionarily well preserved and its persistence suggests that it benefits survival. Insulin resistance is important in

  12. Lacrimal gland primary acinar cell culture: the role of insulin

    Directory of Open Access Journals (Sweden)

    Leonardo Tannus Malki

    2016-04-01

    Full Text Available ABSTRACT Purpose: The goal of the present study was to establish a protocol for primary culture of lacrimal gland acinar cells (LGACs and to assess the effect of adding insulin to the culture media. Methods: LGACs were isolated and cultured from lacrimal glands of Wistar male rats. The study outcomes included cell number, viability, and peroxidase release over time and in response to three concentrations of insulin (0.5, 5.0, and 50.0 μg/mL. Results: In LGAC primary culture, cells started to form clusters by day 3. There was a time-response pattern of peroxidase release, which rose by day 6, in response to carbachol. Culture viability lasted for 12 days. An insulin concentration of 5.0 μg/mL in the culture medium resulted in higher viability and secretory capacity. Conclusions: The present method simplifies the isolation and culture of LGACs. The data confirmed the relevance of adding insulin to maintain LGACs in culture.

  13. Insulin resistance, insulin sensitization and inflammation in polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Dhindsa G

    2004-04-01

    Full Text Available It is estimated that 5-10% of women of reproductive age have polycystic ovarian syndrome (PCOS. While insulin resistance is not part of the diagnostic criteria for PCOS, its importance in the pathogenesis of PCOS cannot be denied. PCOS is associated with insulin resistance independent of total or fat-free body mass. Post-receptor defects in the action of insulin have been described in PCOS which are similar to those found in obesity and type 2 diabetes. Treatment with insulin sensitizers, metformin and thiazolidinediones, improve both metabolic and hormonal patterns and also improve ovulation in PCOS. Recent studies have shown that PCOS women have higher circulating levels of inflammatory mediators like C-reactive protein, tumour necrosis factor- , tissue plasminogen activator and plasminogen activator inhibitor-1 (PAI-1 . It is possible that the beneficial effect of insulin sensitizers in PCOS may be partly due to a decrease in inflammation.

  14. Black Hole Astrophysics in AdS Braneworlds

    CERN Document Server

    Emparan, R; Kaloper, Nemanja; Emparan, Roberto; Garcia-Bellido, Juan; Kaloper, Nemanja

    2003-01-01

    We consider astrophysics of large black holes localized on the brane in the infinite Randall-Sundrum model. Using their description in terms of a conformal field theory (CFT) coupled to gravity, deduced in Ref. [1], we show that they undergo a period of rapid decay via Hawking radiation of CFT modes. For example, a black hole of mass ${\\rm few} \\times M_\\odot$ would shed most of its mass in $\\sim 10^4 - 10^5$ years if the AdS radius is $L \\sim 10^{-1}$ mm, currently the upper bound from table-top experiments. Since this is within the mass range of X-ray binary systems containing a black hole, the evaporation enhanced by the hidden sector CFT modes could cause the disappearance of X-ray sources on the sky. This would be a striking signature of RS2 with a large AdS radius. Alternatively, for shorter AdS radii, the evaporation would be slower. In such cases, the persistence of X-ray binaries with black holes already implies an upper bound on the AdS radius of $L \\la 10^{-2}$ mm, an order of magnitude better than...

  15. Logarithmic AdS waves and Zwei-Dreibein gravity

    NARCIS (Netherlands)

    Bergshoeff, Eric A.; Goya, Andres F.; Merbis, Wout; Rosseel, Jan

    2014-01-01

    We show that the parameter space of Zwei-Dreibein Gravity (ZDG) in AdS(3) exhibits critical points, where massive graviton modes coincide with pure gauge modes and new 'logarithmic' modes appear, similar to what happens in New Massive Gravity. The existence of critical points is shown both at the

  16. Internet Advertising. Google AdWords versus Facebook Ads

    OpenAIRE

    Paul PAŞCU

    2014-01-01

    This article describes how to use the applications for Internet advertising, Google AdWords and Facebook Ads. Our attempt is to present the advantages and disadvantages of each of them, the costs and benefits, a useful aspect for companies that plan to start advertising campaigns on the Internet.

  17. Internet Advertising. Google AdWords versus Facebook Ads

    Directory of Open Access Journals (Sweden)

    Paul PAŞCU

    2014-05-01

    Full Text Available This article describes how to use the applications for Internet advertising, Google AdWords and Facebook Ads. Our attempt is to present the advantages and disadvantages of each of them, the costs and benefits, a useful aspect for companies that plan to start advertising campaigns on the Internet.

  18. Validation of the ORIGIN Cardiovascular Biomarker Panel and the Value of Adding Troponin I in Dysglycemic People.

    Science.gov (United States)

    Gerstein, Hertzel C; Paré, Guillaume; McQueen, Matthew J; Lee, Shun Fu; Hess, Sibylle

    2017-07-01

    Analyses of stored blood from the Outcomes Reduction with an Initial Glargine Intervention (ORIGIN) trial identified biomarkers that supplemented clinical risk factors for cardiovascular (CV) events or death. Their performance in participants with diabetes in the Heart Outcomes Prevention Evaluation (HOPE) study and the incremental value of adding high-sensitivity assays of serum troponin I (hsTnI) in the ORIGIN study were assessed. Levels of the 10 ORIGIN biomarkers for the composite CV outcome of myocardial infarction, stroke, or CV death were measured in 350 HOPE study participants with diabetes and stored serum that included all 77 who experienced this outcome. The effect of adding hsTnI levels to this panel, and the previously identified ORIGIN biomarkers for this composite outcome, this outcome, or revascularization or heart failure, and for mortality was also analyzed. Within the HOPE cohort, the ORIGIN biomarker panel increased the C statistic from 0.63 for clinical risk factors alone to 0.67 with the addition of the 10 biomarkers, and the net reclassification improvement was 0.14 (95% confidence interval, 0.01, 0.28). Within the ORIGIN cohort, hsTnI levels predicted all three outcomes during follow-up both alone, and independently of the other biomarkers, which all remained independent predictors of outcomes after inclusion of the hsTnI levels. The hsTnI level interacted with follow-up time such that it was a stronger predictor of earlier vs later events. The ORIGIN biomarkers predicted CV outcomes in the independent HOPE cohort. Adding hsTnI levels to the previously identified models in ORIGIN modestly improved their performance.

  19. Morning Circadian Misalignment during Short Sleep Duration Impacts Insulin Sensitivity.

    Science.gov (United States)

    Eckel, Robert H; Depner, Christopher M; Perreault, Leigh; Markwald, Rachel R; Smith, Mark R; McHill, Andrew W; Higgins, Janine; Melanson, Edward L; Wright, Kenneth P

    2015-11-16

    Short sleep duration and circadian misalignment are hypothesized to causally contribute to health problems including obesity, diabetes, metabolic syndrome, heart disease, mood disorders, cognitive impairment, and accidents. Here, we investigated the influence of morning circadian misalignment induced by an imposed short nighttime sleep schedule on impaired insulin sensitivity, a precursor to diabetes. Imposed short sleep duration resulted in morning wakefulness occurring during the biological night (i.e., circadian misalignment)-a time when endogenous melatonin levels were still high indicating the internal circadian clock was still promoting sleep and related functions. We show the longer melatonin levels remained high after wake time, insulin sensitivity worsened. Overall, we find a simulated 5-day work week of 5-hr-per-night sleep opportunities and ad libitum food intake resulted in ∼20% reduced oral and intravenous insulin sensitivity in otherwise healthy men and women. Reduced insulin sensitivity was compensated by an increased insulin response to glucose, which may reflect an initial physiological adaptation to maintain normal blood sugar levels during sleep loss. Furthermore, we find that transitioning from the imposed short sleep schedule to 9-hr sleep opportunities for 3 days restored oral insulin sensitivity to baseline, but 5 days with 9-hr sleep opportunities was insufficient to restore intravenous insulin sensitivity to baseline. These findings indicate morning wakefulness and eating during the biological night is a novel mechanism by which short sleep duration contributes to metabolic dysregulation and suggests food intake during the biological night may contribute to other health problems associated with short sleep duration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. The SWITCH study (sensing with insulin pump therapy to control HbA(1c))

    DEFF Research Database (Denmark)

    Conget, Ignacio; Battelino, Tadej; Giménez, Marga

    2011-01-01

    studies investigating the effect of real-time continuous glucose monitoring (CGM) combined with pump therapy on glycemic outcomes in type 1 diabetes are increasing. Pump therapy is well established as a "gold standard" for insulin delivery, offering improvements over multiple daily insulin...... injections. However, there is still a proportion of subjects using continuous subcutaneous insulin infusion in whom goals for metabolic control are far from achieved or benefits of this type of insulin therapy are transient. The SWITCH (Sensing With Insulin pump Therapy to Control HbA(1c) [hemoglobin A1c......]) study is a multicenter, randomized, controlled, crossover study to evaluate if adding CGM to experienced pump patients with suboptimal metabolic control will provide additional insight enabling clinical and therapeutic benefit....

  1. Chitosan/lecithin liposomal nanovesicles as an oral insulin delivery system.

    Science.gov (United States)

    Al-Remawi, Mayyas; Elsayed, Amani; Maghrabi, Ibrahim; Hamaidi, Mohammad; Jaber, Nisrein

    2017-05-01

    In the present work, insulin-chitosan polyelectrolyte complexes associated to lecithin liposomes were investigated as a new carrier for oral delivery of insulin. The preparation was characterized in terms of particle size, zeta potential and encapsulation efficiency. Surface tension measurements revealed that insulin-chitosan polyelectrolyte complexes have some degree of hydrophobicity and should be added to lecithin liposomal dispersion and not the vice versa to prevent their adsorption on the surface. Stability of insulin was enhanced when it was associated to liposomes. Significant reduction of blood glucose levels was noticed after oral administration of liposomal preparation to streptozotocin diabetic rats compared to control. The hypoglycemic activity was more prolonged compared to subcutaneously administered insulin.

  2. Exercise training and metformin, but not exercise training alone, decreases insulin production and increases insulin clearance in adults with prediabetes.

    Science.gov (United States)

    Viskochil, Richard; Malin, Steven K; Blankenship, Jennifer M; Braun, Barry

    2017-07-01

    Adding metformin to exercise does not augment the effect of training alone to boost whole body insulin sensitivity and lower circulating insulin concentrations. Although lower insulin concentrations (lower supply) following lifestyle and/or pharmacological interventions are primarily attributed to reductions in insulin secretion that match increases in peripheral insulin sensitivity (lower demand), it is unclear whether exercise and/or metformin exert direct effects on insulin production, extraction, or clearance. Thirty-six middle-aged, obese, sedentary adults with prediabetes were randomized to placebo (P), metformin (M), exercise and placebo (E+P), or exercise and metformin (E+M) for 12 wk. Fasting plasma proinsulin (an indicator of insulin production), C-peptide, insulin, and glucose were collected before and after the intervention. Peripheral insulin sensitivity (euglycemic clamp), hepatic insulin extraction, insulin clearance, body weight, and cardiorespiratory fitness were also measured. Fasting proinsulin was unchanged following P (19.4 ± 10.1 vs. 22.6 ± 15.0 pmol/l), E+P (15.1 ± 7.4 vs. 15.5 ± 7.4 pmol/l), or M (24.8 ± 18.9 vs. 16.7 ± 20.3 pmol/l) but was significantly reduced after E+M (18.6 ± 11.9 vs. 13.9 ± 6.7 pmol/l; P = 0.04). Insulin clearance was significantly greater following M (384.6 ± 19.4 vs. 477.4 ± 49.9; P = 0.03) and E+M (400.1 ± 32.0 vs. 482.9 ± 33.9; P = 0.02) but was unchanged in P or E+P. In this study, metformin combined with exercise training reduced circulating proinsulin, and both groups taking metformin increased insulin clearance. This suggests that adding metformin to exercise may augment or attenuate training effects depending on the outcome or organ system being assessed.NEW & NOTEWORTHY Exercise is increasingly viewed as medication, creating a need to understand its interactions with other common medications. Research suggests metformin, a widely prescribed diabetes

  3. PGBR extract ameliorates TNF-α induced insulin resistance in hepatocytes.

    Science.gov (United States)

    Chen, Fu-Chih; Shen, Kuo-Ping; Chen, Jin-Bor; Lin, Hui-Li; Hao, Chi-Long; Yen, Hsueh-Wei; Shaw, Shyh-Yu

    2018-01-01

    Pre-germinated brown rice (PGBR) could ameliorate metabolic syndrome, however, not much research estimates the effect of PGBR extract on insulin resistance. The aim of this study is to examine the effects of PGBR extract in TNF-α induced insulin resistance. HepG2 cells, hepatocytes, were cultured in DMEM medium and added with 5 μM insulin or with insulin and 30 ng/ml TNF-α or with insulin, TNF-α and PGBR extract (50, 100, 300 μg/ml). The glucose levels of the medium were decreased by insulin, demonstrating insulin promoted glucose uptake into cell. However, TNF-α inhibited glucose uptake into cells treated with insulin. Moreover, insulin increased the protein expressions of AMP-activated protein kinase (AMPK), insulin receptor substrate-1 (IRS-1), phosphatidylinositol-3-kinase-α (PI3K-α), serine/threonine kinase PI3K-linked protein kinase B (Akt/PKB), glucose transporter-2 (GLUT-2), glucokinase (GCK), peroxisome proliferator activated receptor-α (PPAR-α) and PPAR-γ. TNF-α activated p65 and MAPKs (JNK1/2 and ERK1/2) which worsened the expressions of AMPK, IRS-1, PI3K-α, Akt/PKB, GLUT-2, GCK, glycogen synthase kinase-3 (GSK-3), PPAR-α and PPAR-γ. Once this relationship was established, we added PGBR extract to cell with insulin and TNF-α. We found glucose levels of medium were lowered and that the protein expressions of AMPK, IRS-1, PI3K-α, Akt/PKB, GLUT-2, GCK, GSK-3, PPAR-α, PPAR-γ and p65, JNK1/2 were also recovered. In conclusion, this study found that TNF-α inhibited insulin stimulated glucose uptake and aggravated related proteins expressions, suggesting that it might cause insulin resistance. PGBR extract was found to ameliorate this TNF-α induced insulin resistance, suggesting that it might be used in the future to help control insulin resistance. Copyright © 2017. Published by Elsevier Taiwan.

  4. PGBR extract ameliorates TNF-α induced insulin resistance in hepatocytes

    Directory of Open Access Journals (Sweden)

    Fu-Chih Chen

    2018-01-01

    Full Text Available Pre-germinated brown rice (PGBR could ameliorate metabolic syndrome, however, not much research estimates the effect of PGBR extract on insulin resistance. The aim of this study is to examine the effects of PGBR extract in TNF-α induced insulin resistance. HepG2 cells, hepatocytes, were cultured in DMEM medium and added with 5 μM insulin or with insulin and 30 ng/ml TNF-α or with insulin, TNF-α and PGBR extract (50, 100, 300 μg/ml. The glucose levels of the medium were decreased by insulin, demonstrating insulin promoted glucose uptake into cell. However, TNF-α inhibited glucose uptake into cells treated with insulin. Moreover, insulin increased the protein expressions of AMP-activated protein kinase (AMPK, insulin receptor substrate-1 (IRS-1, phosphatidylinositol-3-kinase-α (PI3K-α, serine/threonine kinase PI3K-linked protein kinase B (Akt/PKB, glucose transporter-2 (GLUT-2, glucokinase (GCK, peroxisome proliferator activated receptor-α (PPAR-α and PPAR-γ. TNF-α activated p65 and MAPKs (JNK1/2 and ERK1/2 which worsened the expressions of AMPK, IRS-1, PI3K-α, Akt/PKB, GLUT-2, GCK, glycogen synthase kinase-3 (GSK-3, PPAR-α and PPAR-γ. Once this relationship was established, we added PGBR extract to cell with insulin and TNF-α. We found glucose levels of medium were lowered and that the protein expressions of AMPK, IRS-1, PI3K-α, Akt/PKB, GLUT-2, GCK, GSK-3, PPAR-α, PPAR-γ and p65, JNK1/2 were also recovered. In conclusion, this study found that TNF-α inhibited insulin stimulated glucose uptake and aggravated related proteins expressions, suggesting that it might cause insulin resistance. PGBR extract was found to ameliorate this TNF-α induced insulin resistance, suggesting that it might be used in the future to help control insulin resistance.

  5. Intradermal Insulin Delivery

    Science.gov (United States)

    Hultström, Michael; Roxhed, Niclas

    2014-01-01

    The incidence of insulinopenic diabetes mellitus is constantly increasing, and in addition, approximately a third of all hyperinsulinemic diabetic patients develop insulinopenia. Optimal glycemic control is essential to minimize the risk for diabetes-induced complications, but the majority of diabetic patients fail to achieve proper long-term glucose levels even in clinical trials, and even more so in clinical practice. Compliance with a treatment regimen is likely to be higher if the procedure is simple, painless, and discreet. Thus, insulin has been suggested for nasal, gastrointestinal, and inhalation therapy, but so far with considerable downsides in effect, side effects, or patient acceptance. The stratum corneum is the main barrier preventing convenient drug administration without the drawbacks of subcutaneous injections. Recently, devices with miniaturized needles have been developed that combine the simplicity and discretion of patch-based treatments, but with the potential of peptide and protein administration. As this review describes, initial comparisons with subcutaneous administration now suggest microneedle patches for active insulin delivery are efficient in maintaining glycemic control. Hollow microneedle technology could also prove to be efficient in systemic as well as local delivery of other macromolecular drugs, such as vaccines. PMID:24876605

  6. Effects of insulin on placental, fetal and maternal outcomes in gestational diabetes mellitus

    OpenAIRE

    Arshad, Rabia; Karim, Nasim; Ara Hasan, Jahan

    2014-01-01

    Objective: To observe the effects of exogenous insulin on placental, fetal and maternal outcomes in Gestational Diabetes Mellitus (GDM). Methods: After screening and diagnoses(WHO criteria) 30 GDM patients(Group A) were kept on diet control and 39 GDM (Group B) who did not achieve glycemic targets were added subcutaneous insulin. Term placental weight, size, shape, consistency, fibrinoid necrosis, hemorrhages, cord color, length of the cord, completeness of membranes, weight and condition of ...

  7. Insulin Signaling and Heart Failure

    Science.gov (United States)

    Riehle, Christian; Abel, E. Dale

    2016-01-01

    Heart failure is associated with generalized insulin resistance. Moreover, insulin resistant states such as type 2 diabetes and obesity increases the risk of heart failure even after adjusting for traditional risk factors. Insulin resistance or type 2 diabetes alters the systemic and neurohumoral milieu leading to changes in metabolism and signaling pathways in the heart that may contribute to myocardial dysfunction. In addition, changes in insulin signaling within cardiomyocytes develop in the failing heart. The changes range from activation of proximal insulin signaling pathways that may contribute to adverse left ventricular remodeling and mitochondrial dysfunction to repression of distal elements of insulin signaling pathways such as forkhead (FOXO) transcriptional signaling or glucose transport which may also impair cardiac metabolism, structure and function. This article will review the complexities of insulin signaling within the myocardium and ways in which these pathways are altered in heart failure or in conditions associated with generalized insulin resistance. The implications of these changes for therapeutic approaches to treating or preventing heart failure will be discussed. PMID:27034277

  8. The cardiovascular effects of insulin.

    Science.gov (United States)

    Younk, Lisa M; Lamos, Elizabeth M; Davis, Stephen N

    2014-07-01

    Cardiovascular disease remains one of the leading causes of morbidity and mortality in diabetes mellitus. A causal link between insulin, atherosclerosis and cardiovascular risk has been investigated at the basic science level and studied in large clinical trials. The cardiovascular actions of insulin and its role at the level of the endothelium will be reviewed. Cardiovascular outcomes in several large diabetes trials where insulin management was prominent will be summarized. The vascular actions of insulin are complex and mediated primarily via nitric oxide and endothelin-1. It appears that insulin resistance, rather than hyperinsulinemia itself, increases cardiovascular risk. In fact, hyperinsulinemia in the setting of normal beta cell function protects obese and insulin-resistant individuals from type 2 diabetes. Large clinical trials have supported that insulin management is not associated with increased adverse outcomes. A multifactorial approach targeting modifiable risk factors, including smoking cessation, blood pressure and lipid management, reduces cardiovascular risk. Therapy goals should be individualized and hypoglycemia, especially in individuals receiving insulin management, should be strictly avoided.

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

    Science.gov (United States)

    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

  10. Ultraviolet asymptotics for quasiperiodic AdS_4 perturbations

    CERN Document Server

    Craps, Ben; Jai-akson, Puttarak; Vanhoof, Joris

    2015-01-01

    Spherically symmetric perturbations in AdS-scalar field systems of small amplitude epsilon approximately periodic on time scales of order 1/epsilon^2 (in the sense that no significant transfer of energy between the AdS normal modes occurs) have played an important role in considerations of AdS stability. They are seen as anchors of stability islands where collapse of small perturbations to black holes does not occur. (This collapse, if it happens, typically develops on time scales of the order 1/epsilon^2.) We construct an analytic treatment of the frequency spectra of such quasiperiodic perturbations, paying special attention to the large frequency asymptotics. For the case of a self-interacting phi^4 scalar field in a non-dynamical AdS background, we arrive at a fairly complete analytic picture involving quasiperiodic spectra with an exponential suppression modulated by a power law at large mode numbers. For the case of dynamical gravity, the structure of the large frequency asymptotics is more complicated....

  11. Insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control.

    Science.gov (United States)

    Vos, Rimke C; van Avendonk, Mariëlle Jp; Jansen, Hanneke; Goudswaard, Alexander N; van den Donk, Maureen; Gorter, Kees; Kerssen, Anneloes; Rutten, Guy Ehm

    2016-09-18

    It is unclear whether people with type 2 diabetes mellitus on insulin monotherapy who do not achieve adequate glycaemic control should continue insulin as monotherapy or can benefit from adding oral glucose-lowering agents to the insulin therapy. To assess the effects of insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin monotherapy for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and reference lists of articles. The date of the last search was November 2015 for all databases. Randomised controlled clinical trials of at least two months' duration comparing insulin monotherapy with combinations of insulin with one or more oral glucose-lowering agent in people with type 2 diabetes. Two review authors independently selected trials, assessed risk of bias, extracted data and evaluated overall quality of the evidence using GRADE. We summarised data statistically if they were available, sufficiently similar and of sufficient quality. We performed statistical analyses according to the statistical guidelines in the Cochrane Handbook for Systematic Reviews of Interventions. We included 37 trials with 40 treatment comparisons involving 3227 participants. The duration of the interventions ranged from 2 to 12 months for parallel trials and two to four months for cross-over trials.The majority of trials had an unclear risk of bias in several risk of bias domains. Fourteen trials showed a high risk of bias, mainly for performance and detection bias. Insulin monotherapy, including once-daily long-acting, once-daily intermediate-acting, twice-daily premixed insulin, and basal-bolus regimens (multiple injections), was compared to insulin in combination with sulphonylureas (17 comparisons: glibenclamide

  12. Absence of Carbohydrate Response Element Binding Protein in Adipocytes Causes Systemic Insulin Resistance and Impairs Glucose Transport

    Directory of Open Access Journals (Sweden)

    Archana Vijayakumar

    2017-10-01

    Full Text Available Lower adipose-ChREBP and de novo lipogenesis (DNL are associated with insulin resistance in humans. Here, we generated adipose-specific ChREBP knockout (AdChREBP KO mice with negligible sucrose-induced DNL in adipose tissue (AT. Chow-fed AdChREBP KO mice are insulin resistant with impaired insulin action in the liver, muscle, and AT and increased AT inflammation. HFD-fed AdChREBP KO mice are also more insulin resistant than controls. Surprisingly, adipocytes lacking ChREBP display a cell-autonomous reduction in insulin-stimulated glucose transport that is mediated by impaired Glut4 translocation and exocytosis, not lower Glut4 levels. AdChREBP KO mice have lower levels of palmitic acid esters of hydroxy stearic acids (PAHSAs in serum, and AT. 9-PAHSA supplementation completely rescues their insulin resistance and AT inflammation. 9-PAHSA also normalizes impaired glucose transport and Glut4 exocytosis in ChREBP KO adipocytes. Thus, loss of adipose-ChREBP is sufficient to cause insulin resistance, potentially by regulating AT glucose transport and flux through specific lipogenic pathways.

  13. Insulin: discovery and controversy.

    Science.gov (United States)

    Rosenfeld, Louis

    2002-12-01

    During the first two decades of the 20th century, several investigators prepared extracts of pancreas that were often successful in lowering blood sugar and reducing glycosuria in test animals. However, they were unable to remove impurities, and toxic reactions prevented its use in humans with diabetes. In the spring of 1921, Frederick G. Banting, a young Ontario orthopedic surgeon, was given laboratory space by J.J.R. Macleod, the head of physiology at the University of Toronto, to investigate the function of the pancreatic islets. A student assistant, Charles Best, and an allotment of dogs were provided to test Banting's hypothesis that ligation of the pancreatic ducts before extraction of the pancreas, destroys the enzyme-secreting parts, whereas the islets of Langerhans, which were believed to produce an internal secretion regulating sugar metabolism, remained intact. He believed that earlier failures were attributable to the destructive action of trypsin. The name "insuline" had been introduced in 1909 for this hypothetic substance. Their experiments produced an extract of pancreas that reduced the hyperglycemia and glycosuria in dogs made diabetic by the removal of their pancreases. They next developed a procedure for extraction from the entire pancreas without the need for duct ligation. This extract, now made from whole beef pancreas, was successful for treating humans with diabetes. Facilitating their success was a development in clinical chemistry that allowed blood sugar to be frequently and accurately determined in small volumes of blood. Success with purification was largely the work of J.B. Collip. Yield and standardization were improved by cooperation with Eli Lilly and Company. When the Nobel Prize was awarded to Banting and Macleod for the discovery of insulin, it aggravated the contentious relationship that had developed between them during the course of the investigation. Banting was outraged that Macleod and not Best had been selected, and he

  14. Insulin sensitivity is normalized in the third generation (F3 offspring of developmentally programmed insulin resistant (F2 rats fed an energy-restricted diet

    Directory of Open Access Journals (Sweden)

    Martin John F

    2008-10-01

    Full Text Available Abstract Background/Aims The offspring and grandoffspring of female rats fed low protein diets during pregnancy and lactation, but fed nutritionally adequate diets thereafter, have been shown to exhibit altered insulin sensitivity in adulthood. The current study investigates the insulin sensitivity of the offspring and grandoffspring of female rats fed low protein diets during pregnancy, and then maintained on energy-restricted diets post weaning over three generations. Methods Female Sprague Dawley rats (F0 were mated with control males and protein malnourished during pregnancy/lactation. F1 offspring were then weaned to adequate but energy-restricted diets into adulthood. F1 dams were fed energy-restricted diets throughout pregnancy/lactation. F2 offspring were also fed energy-restricted diets post weaning. F2 pregnant dams were maintained as described above. Their F3 offspring were split into two groups; one was maintained on the energy-restricted diet, the other was maintained on an adequate diet consumed ad libitum post weaning. Results F2 animals fed energy-restricted diets were insulin resistant (p ad libitum postweaning diets (p Conclusion Maternal energy-restriction did not consistently program reduced insulin sensitivity in offspring over three consecutive generations. The reasons for this remain unclear. It is possible that the intergenerational transmission of developmentally programmed insulin resistance is determined in part by the relative insulin sensitivity of the mother during pregnancy/lactation.

  15. AdS sub 2 supergravity and superconformal quantum mechanics

    CERN Document Server

    Astorino, M; Klemm, D; Zanon, D

    2003-01-01

    We investigate the asymptotic dynamics of topological anti-de Sitter supergravity in two dimensions. Starting from the formulation as a BF theory, it is shown that the AdS sub 2 boundary conditions imply that the asymptotic symmetries form a super-Virasoro algebra. Using the central charge of this algebra in Cardy's formula, we exactly reproduce the thermodynamical entropy of AdS sub 2 black holes. Furthermore, we show that the dynamics of the dilaton and its superpartner reduces to that of superconformal transformations that leave invariant one chiral component of the stress tensor supercurrent of a two-dimensional conformal field theory. This dynamics is governed by a supersymmetric extension of the de Alfaro-Fubini-Furlan model of conformal quantum mechanics. Finally, two-dimensional de Sitter gravity is also considered, and the dS sub 2 entropy is computed by counting CFT states.

  16. Entropy function and attractors for AdS black holes

    CERN Document Server

    Morales, J F; Morales, Jose F.; Samtleben, Henning

    2006-01-01

    We apply Sen's entropy formalism to the study of the near horizon geometry and the entropy of asymptotically AdS black holes in gauged supergravities. In particular, we consider non-supersymmetric electrically charged black holes with AdS_2 xS^{d-2} horizons in U(1)^4 and U(1)^3 gauged supergravities in d=4 and d=5 dimensions, respectively. We study several cases including static/rotating, BPS and non-BPS black holes in Einstein as well as in Gauss-Bonnet gravity. In all examples, the near horizon geometry and black hole entropy are derived by extremizing the entropy function and are given entirely in terms of the gauge coupling, the electric charges and the angular momentum of the black hole.

  17. AdS gravity and the scalar glueball spectrum

    Energy Technology Data Exchange (ETDEWEB)

    Vento, Vicente [Departament de Fisica Teorica, Universitat de Valencia y Institut de Fisica Corpuscular, Consejo Superior de Investigaciones Cientificas, Burjassot (Valencia) (Spain)

    2017-09-15

    The scalar glueball spectrum has attracted much attention since the formulation of Quantum Chromodynamics. Different approaches give very different results for the glueball masses. We revisit the problem from the perspective of the AdS/CFT correspondence. (orig.)

  18. The Mixed Phase of Charged AdS Black Holes

    Directory of Open Access Journals (Sweden)

    Piyabut Burikham

    2016-01-01

    Full Text Available We study the mixed phase of charged AdS black hole and radiation when the total energy is fixed below the threshold to produce a stable charged black hole branch. The coexistence conditions for the charged AdS black hole and radiation are derived for the generic case when radiation particles carry charge. The phase diagram of the mixed phase is demonstrated for both fixed potential and charge ensemble. In the dual gauge picture, they correspond to the mixed phase of quark-gluon plasma (QGP and hadron gas in the fixed chemical potential and density ensemble, respectively. In the nuclei and heavy-ion collisions at intermediate energies, the mixed phase of exotic QGP and hadron gas could be produced. The mixed phase will condense and evaporate into the hadron gas as the fireball expands.

  19. Overexpression of protein tyrosine phosphatase 1B impairs glucose-stimulated insulin secretion in INS-1 cells.

    Science.gov (United States)

    Lu, Bin; Gu, Ping; Xu, Yixin; Ye, Xiaozhen; Wang, Yingzhijie; DU, Hong; Shao, Jiaqing

    2016-03-01

    Protein tyrosine phosphatase 1B (PTP1B) has been implicated as a negative regulator of insulin signaling. We reported previously that impaired glucose-stimulated insulin secretion (GSIS) in rats fed high-fat diet was associated with higher PTP1B protein levels in islets. The aim of the present study was to investigate the effect of increasing PTP1B on insulin secretion in β-cells. INS-1 cells were transduced with recombinant adenoviruses containing human PTP1B cDNA (Ad-PTP1B), or no exogenous gene (Ad-ctrl). The expression levels of PTP1B, insulin receptor (IR), insulin receptor substrate-1(IRS-1), glucokinase and glucose transporter-2 were evaluated by Western blot. Then insulin-stimulated IR and IRS tyrosine phosphorylation, and Akt pathway activation were measured. GSIS was also performed to evaluate INS-1 cells function. PTP1B expression level was increased 5.9-fold at 48h post-transduction. The overexpression of PTP1B had no effect on proliferation and apoptosis of INS-1 cells. Compared with control cells, INS-1 cells overexpressing PTP1B showed decrease in insulin-stimulated tyrosine phosphorylation of the insulin receptor (IR) and insulin receptor substrate-1(IRS-1) by 56.4% and 53.1%, respectively. In addition, Akt phosphorylation was reduced 59.6%. Moreover, in Ad-PTP1B-transduced cells, 16.7mM glucose caused a 1.6±0.2 fold increase (vs. 3.9±0.7 fold in nontransduced cells) in insulin secretion relative to secretion at 2.8mM glucose. Further analysis determined that overexpression of PTP1B induced down-regulated expression of glucokinase (42%) and glucose transporter-2 (48%). Our findings suggested that overexpression of PTP1B can inhibit GSIS in INS-1 cells through negatively regulating insulin signaling.

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

    Science.gov (United States)

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

    2016-08-01

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

  1. Conserved higher-spin charges in AdS4

    Directory of Open Access Journals (Sweden)

    O.A. Gelfond

    2016-03-01

    Full Text Available Gauge invariant conserved conformal currents built from massless fields of all spins in 4d Minkowski space–time and AdS4 are described in the unfolded dynamics approach. The current cohomology associated with non-zero conserved charges is found. The resulting list of charges is shown to match the space of parameters of the conformal higher-spin symmetry algebra in four dimensions.

  2. Generalised structures for N=1 AdS backgrounds

    Energy Technology Data Exchange (ETDEWEB)

    Coimbra, André [Institut für Theoretische Physik & Center for Quantum Engineering and Spacetime Research,Leibniz Universität Hannover,Appelstraße 2, 30167 Hannover (Germany); Strickland-Constable, Charles [Institut de physique théorique, Université Paris Saclay, CEA, CNRS, Orme des Merisiers, F-91191 Gif-sur-Yvette (France)

    2016-11-16

    We expand upon a claim made in a recent paper [http://arxiv.org/abs/1411.5721] that generic minimally supersymmetric AdS backgrounds of warped flux compactifications of Type II and M theory can be understood as satisfying a straightforward weak integrability condition in the language of E{sub d(d)}×ℝ{sup +} generalised geometry. Namely, they are spaces admitting a generalised G-structure set by the Killing spinor and with constant singlet generalised intrinsic torsion.

  3. Insulin gene polymorphisms in type 1 diabetes, Addison's disease and the polyglandular autoimmune syndrome type II

    Directory of Open Access Journals (Sweden)

    Hahner Stefanie

    2008-07-01

    Full Text Available Abstract Background Polymorphisms within the insulin gene can influence insulin expression in the pancreas and especially in the thymus, where self-antigens are processed, shaping the T cell repertoire into selftolerance, a process that protects from β-cell autoimmunity. Methods We investigated the role of the -2221Msp(C/T and -23HphI(A/T polymorphisms within the insulin gene in patients with a monoglandular autoimmune endocrine disease [patients with isolated type 1 diabetes (T1D, n = 317, Addison's disease (AD, n = 107 or Hashimoto's thyroiditis (HT, n = 61], those with a polyglandular autoimmune syndrome type II (combination of T1D and/or AD with HT or GD, n = 62 as well as in healthy controls (HC, n = 275. Results T1D patients carried significantly more often the homozygous genotype "CC" -2221Msp(C/T and "AA" -23HphI(A/T polymorphisms than the HC (78.5% vs. 66.2%, p = 0.0027 and 75.4% vs. 52.4%, p = 3.7 × 10-8, respectively. The distribution of insulin gene polymorphisms did not show significant differences between patients with AD, HT, or APS-II and HC. Conclusion We demonstrate that the allele "C" of the -2221Msp(C/T and "A" -23HphI(A/T insulin gene polymorphisms confer susceptibility to T1D but not to isolated AD, HT or as a part of the APS-II.

  4. ADS Bumblebee comes of age

    Science.gov (United States)

    Accomazzi, Alberto; Kurtz, Michael J.; Henneken, Edwin; Grant, Carolyn S.; Thompson, Donna M.; Chyla, Roman; McDonald, Steven; Shaulis, Taylor J.; Blanco-Cuaresma, Sergi; Shapurian, Golnaz; Hostetler, Timothy W.; Templeton, Matthew R.; Lockhart, Kelly E.

    2018-01-01

    The ADS Team has been working on a new system architecture and user interface named “ADS Bumblebee” since 2015. The new system presents many advantages over the traditional ADS interface and search engine (“ADS Classic”). A new, state of the art search engine features a number of new capabilities such as full-text search, advanced citation queries, filtering of results and scalable analytics for any search results. Its services are built on a cloud computing platform which can be easily scaled to match user demand. The Bumblebee user interface is a rich javascript application which leverages the features of the search engine and integrates a number of additional visualizations such as co-author and co-citation networks which provide a hierarchical view of research groups and research topics, respectively. Displays of paper analytics provide views of the basic article metrics (citations, reads, and age). All visualizations are interactive and provide ways to further refine search results. This new search system, which has been in beta for the past three years, has now matured to the point that it provides feature and content parity with ADS Classic, and has become the recommended way to access ADS content and services. Following a successful transition to Bumblebee, the use of ADS Classic will be discouraged starting in 2018 and phased out in 2019. You can access our new interface at https://ui.adsabs.harvard.edu

  5. Stimulatory effect of insulin on glucose uptake by muscle involves the central nervous system in insulin-sensitive mice

    NARCIS (Netherlands)

    Coomans, C.P.; Biermasz, N.R.; Geerling, J.J.; Guigas, B.; Rensen, P.C.N.; Havekes, L.M.; Romijn, J.A.

    2011-01-01

    OBJECTIVE - Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin-stimulated

  6. Insulin resistance vs. hyperinsulinemia in hypertension: insulin regulation of Ca2+ transport and Ca(2+)-regulation of insulin sensitivity.

    Science.gov (United States)

    Zemel, M B

    1995-06-01

    Hypertension in obesity and insulin resistance has been attributed to insulin stimulation of sympathetic neural output and renal sodium retention. However, recent data demonstrates a significant vasodilatory effect of insulin and suggests that vascular smooth muscle resistance to this action may instead be the cause of hypertension in insulin resistance. This concept is supported by the observation that pharmacological amplification of peripheral insulin sensitivity results in reduced arterial pressure. Insulin attenuates vasoconstrictor responses to pressor agonists and accelerates vascular smooth muscle relaxation, while these effects are blunted in obesity and insulin resistance. Insulin regulation of vasoconstriction and vascular relaxation appears to be secondary to regulation of intracellular Ca2+ ([Ca2+]i), as insulin attenuates both voltage- and receptor-mediated Ca2+ influx and stimulates both the transcription and activity of Ca(2+)-ATPase in vascular smooth muscle cells. Further, these effects are also blunted in insulin resistance. Although [Ca2+]i plays a poorly understood role in insulin signalling, increases beyond an optimal range results in impaired insulin sensitivity, possibly by Ca(2+)-inhibition of insulin-induced dephosphorylation of insulin-sensitive substrates. Consistent with this concept, ectopic overexpression of the agouti gene in the viable yellow (Avy) mouse results in increased skeletal myocyte [Ca2+]i. Accordingly, increased [Ca2+]i in primary insulin target tissues appears to result in peripheral insulin resistance which then results in aberrant regulation of vascular smooth muscle [Ca2+]i and increases in arterial pressure.

  7. Ad skepticisms: Antecedents and consequences

    Directory of Open Access Journals (Sweden)

    Rafique Ahmed

    2016-11-01

    Full Text Available Engaging customer is the burning issue for companies especially the service sector, either online or offline. Minimizing the customer disengagement is the same like reducing dissatisfaction or churn. Customer disengagement may be caused by many factors, ad skepticism is one of them; ad skepticism has two main antecedents personality variable and consumption/influencing varia-bles. This research explores the relationship of ad skepticism with customer disengagement through personality variables which are cynicism, reactance and self-esteem. The unit of analysis is the telecom and banking industry of Pakistan which is foreseeing an era of virtual currency and both are customer oriented industries. Only offline disengagement is researched and data is collected from the Business centers of telecom and banking branches dealing with virtual curren-cy in Pakistan. Hypothetical model is given after digging the relevant literature; model is tested through confirmatory factor analysis and structural equation modeling. Eight hypotheses were purposed from the connections of model, all hypotheses are accepted except the cynicism posi-tive effect on social ad skepticism. This can be due to commonality of social and charity in Paki-stani society, Muslims consider charity as a pious act and they do not think for cynic behavior in charity or social related works. The results manifest that customers in telecom industry are hav-ing ad skepticism and that is becoming the cause of their disengagement. Further, social ad skep-ticism has more impact on the customer disengagement than the general ad skepticism. While the reactance has more effect on general ad skepticism than other antecedents and cynicism has the lowest impact on social ad skepticism than other antecedents.

  8. [Insulin edema in hepatic glycogenosis].

    Science.gov (United States)

    Mahévas, T; Gobert, D; Gatfossé, M; Mekinian, A; Fain, O

    2017-03-01

    Hepatic glycogenosis is a rare syndrome, which includes poorly controlled diabetes mellitus, hepatomegaly, delayed puberty, and growth delay. Insulin edema is sometimes associated. An 18-year-old woman presented with diffuse edema, hepatomegaly, amenorrhea, uncontrolled diabetes, and elevated transaminases and cholestasis. Hepatic ultrasonography and abdominal computed tomographic scan confirmed the hepatomegaly. The liver biopsy showed a massive glycogenosis and the diagnosis of hepatic glycogenosis was confirmed. Too large doses of insulin were responsible of diffuse edema. Diabetes equilibration and diminution of insulin intakes allow correction of this disorder. Excess of insulin can lead to excessive hepatic glycogen storage by activation of glycogenosis enzymes. Biological manifestations consist on elevated liver enzymes and hyperlactatemia. There is a link between administration of high dose of insulin and edema. Hepatic glycogenosis should be suspected when diabetes is uncontrolled and be considered as a differential diagnosis of steatosis. It may be associated and revealed by insulin edema directly related to excessive insulin intakes. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  9. Isolation and amino acid sequences of squirrel monkey (Saimiri sciurea) insulin and glucagon

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Jinghua (Veterans Administration Medical Center, Bronx, NY (United States)); Eng, J.; Yalow, R.S. (Veterans Administration Medical Center, Bronx, NY (United States) City Univ. of New York, NY (United States))

    1990-12-01

    It was reported two decades ago that insulin was not detectable in the glucose-stimulated state in Saimiri sciurea, the New World squirrel monkey, by a radioimmunoassay system developed with guinea pig anti-pork insulin antibody and labeled park insulin. With the same system, reasonable levels were observed in rhesus monkeys and chimpanzees. This suggested that New World monkeys, like the New World hystricomorph rodents such as the guinea pig and the coypu, might have insulins whose sequences differ markedly from those of Old World mammals. In this report the authors describe the purification and amino acid sequences of squirrel monkey insulin and glucagon. They demonstrate that the substitutions at B29, B27, A2, A4, and A17 of squirrel monkey insulin are identical with those previously found in another New World primate, the owl monkey (Aotus trivirgatus). The immunologic cross-reactivity of this insulin in their immunoassay system is only a few percent of that of human insulin. It appears that the peptides of the New World monkeys have diverged less from those of the Old World mammals than have those of the New World hystricomorph rodents. The striking improvements in peptide purification and sequencing have the potential for adding new information concerning the evolutionary divergence of species.

  10. Insulin in human milk and the use of hormones in infant formulas.

    Science.gov (United States)

    Shamir, Raanan; Shehadeh, Naim

    2013-01-01

    Human milk contains a substantial number of hormones and growth factors. Studies in animal models show that some of these peptides (e.g. insulin, insulin-like growth factor 1, IGF-1, epidermal growth factors) have an effect on the small intestine after orogastric administration. Recently, two efforts were made to incorporate growth factors into infant formulas. One of these efforts included the incorporation of IGF-1, and the second is an ongoing effort to evaluate the safety and efficacy of incorporating insulin into infant formulas. The rational and current evidence for adding insulin to infant formulas (presence in human milk, effects of orally administrated insulin on gut maturation, intestinal permeability, systemic effects and preliminary encouraging results of supplementing insulin to a preterm infant formula) is detailed in this review. If the addition of insulin to preterm infant formulas indeed results in better growth and accelerated intestinal maturation, future studies will need to address the supplementation of insulin in term infants and assess the efficacy of such supplementation in enhancing gut maturation and prevention of later noncommunicable diseases such as allergy, autoimmune diseases and obesity. Copyright © 2013 Nestec Ltd., Vevey/S. Karger AG, Basel.

  11. Aβ-Induced Insulin Resistance and the Effects of Insulin on the Cholesterol Synthesis Pathway and Aβ Secretion in Neural Cells.

    Science.gov (United States)

    Najem, Dema; Bamji-Mirza, Michelle; Yang, Ze; Zhang, Wandong

    2016-06-01

    Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) toxicity, tau pathology, insulin resistance, neuroinflammation, and dysregulation of cholesterol homeostasis, all of which play roles in neurodegeneration. Insulin has polytrophic effects on neurons and may be at the center of these pathophysiological changes. In this study, we investigated possible relationships among insulin signaling and cholesterol biosynthesis, along with the effects of Aβ42 on these pathways in vitro. We found that neuroblastoma 2a (N2a) cells transfected with the human gene encoding amyloid-β protein precursor (AβPP) (N2a-AβPP) produced Aβ and exhibited insulin resistance by reduced p-Akt and a suppressed cholesterol-synthesis pathway following insulin treatment, and by increased phosphorylation of insulin receptor subunit-1 at serine 612 (p-IRS-S612) as compared to parental N2a cells. Treatment of human neuroblastoma SH-SY5Y cells with Aβ42 also increased p-IRS-S612, suggesting that Aβ42 is responsible for insulin resistance. The insulin resistance was alleviated when N2a-AβPP cells were treated with higher insulin concentrations. Insulin increased Aβ release from N2a-AβPP cells, by which it may promote Aβ clearance. Insulin increased cholesterol-synthesis gene expression in SH-SY5Y and N2a cells, including 24-dehydrocholesterol reductase (DHCR24) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR) through sterol-regulatory element-binding protein-2 (SREBP2). While Aβ42-treated SH-SY5Y cells exhibited increased HMGCR expression and c-Jun phosphorylation as pro-inflammatory responses, they also showed down-regulation of neuro-protective/anti-inflammatory DHCR24. These results suggest that Aβ42 may cause insulin resistance, activate JNK for c-Jun phosphorylation, and lead to dysregulation of cholesterol homeostasis, and that enhancing insulin signaling may relieve the insulin-resistant phenotype and the dysregulated cholesterol-synthesis pathway to promote A

  12. Engineering of insulin receptor isoform-selective insulin analogues

    National Research Council Canada - National Science Library

    Glendorf, Tine; Stidsen, Carsten E; Norrman, Mathias; Nishimura, Erica; Sørensen, Anders R; Kjeldsen, Thomas

    2011-01-01

    .... The aim of this study was to investigate the importance of the C-terminus of the B chain in IR isoform binding in order to explore the possibility of engineering tissue-specific/liver-specific insulin analogues...

  13. Insulin Resistance, Hyperglycemia, and Atherosclerosis

    Science.gov (United States)

    Bornfeldt, Karin E.; Tabas, Ira

    2011-01-01

    Progress in preventing atherosclerotic coronary artery disease (CAD) has been stalled by the epidemic of type 2 diabetes. Further advances in this area demand a thorough understanding of how two major features of type 2 diabetes, insulin resistance and hyperglycemia, impact atherosclerosis. Insulin resistance is associated with systemic CAD risk factors, but increasing evidence suggests that defective insulin signaling in atherosclerotic lesional cells also plays an important role. The role of hyperglycemia in CAD associated with type 2 diabetes is less clear. Understanding the mechanisms whereby type 2 diabetes exacerbates CAD offers hope for new therapeutic strategies to prevent and treat atherosclerotic vascular disease. PMID:22055501

  14. Autoantibodies to Insulin Receptor Spontaneously Develop as Anti-Idiotypes in Mice Immunized with Insulin

    Science.gov (United States)

    Shechter, Yoram; Maron, Ruth; Elias, Dana; Cohen, Irun R.

    1982-04-01

    Mice immunized with insulin developed antibodies to both insulin and the insulin receptor. The antibodies to insulin receptor displaced labeled insulin from insulin receptors and mimicked the actions of insulin in stimulating the oxidation of glucose and its incorporation into lipids, and in inhibiting lipolysis. The antibodies to insulin receptor could be blocked by or bound to the antibodies to insulin, and therefore were identified as anti-idiotypes. Thus, immunization against a hormone may activate spontaneously an idiotype-anti-idiotype network resulting in antibodies to the hormone receptor.

  15. Structural Perspectives of Insulin Receptor Isoform-Selective Insulin Analogs

    Czech Academy of Sciences Publication Activity Database

    Jiráček, Jiří; Žáková, Lenka

    2017-01-01

    Roč. 8, Jul 27 (2017), č. článku 167. ISSN 1664-2392 R&D Projects: GA ČR GA15-19018S Institutional support: RVO:61388963 Keywords : insulin receptor * insulin binding * analog * diabetes * glucose Subject RIV: CE - Biochemistry Impact factor: 3.675, year: 2016 http:// journal .frontiersin.org/article/10.3389/fendo.2017.00167/full

  16. Evaluation of insulin-like growth factor-1, total thyroxine, feline pancreas-specific lipase and urinary corticoid-to-creatinine ratio in cats with diabetes mellitus in Switzerland and the Netherlands.

    Science.gov (United States)

    Schaefer, Sandra; Kooistra, Hans S; Riond, Barbara; Suchodolski, Jan S; Steiner, Jörg M; Prins, Marrit; Zini, Eric; Reusch, Claudia E

    2017-08-01

    Objectives The aim of the study was to evaluate circulating insulin-like growth factor-1 (IGF-1), feline pancreas-specific lipase (fPLI) and total thyroxine (TT4) concentrations and urinary corticoid-to-creatinine ratio (UCCR) as indicators for the prevalence of acromegaly, pancreatitis, hyperthyroidism and hypercortisolism in cats with diabetes mellitus. Methods Blood and urine samples were collected from diabetic cats treated in primary care clinics in Switzerland and the Netherlands. Standardised questionnaires and physical examination forms provided clinical information from owners and veterinarians. Laboratory testing included serum biochemistry profile analysis and measurement of circulating fructosamine, IGF-1, fPLI, and TT4 concentrations and UCCR. CT of the pituitary gland was performed using a multidetector computed tomography scanner. Results Blood samples were available from 215 cats and urine samples were collected at home from 117 cats. Age ranged from 2-18 years (median 12 years) and body weight from 2.7-12.3 kg (median 5.5 kg). Sixty-five percent of the cats were castrated male and 35% were female (33% spayed); 82% were domestic shorthair cats. Eighty percent of cats received a porcine insulin zinc suspension, 19.5% insulin glargine and 0.5% a human neutral protamine hagedorn insulin. Thirty-six of 202 (17.8%) cats had IGF-1 concentrations >1000 ng/ml. Serum fPLI, and TT4 concentrations and UCCR were increased in 86/196 (43.9%), 9/201 (4.5%) and 18/117 cats (15.3%), respectively. Prevalence did not differ between countries. Conclusions Hyperthyroidism is rare, whereas increased fPLI concentration, possibly reflecting pancreatitis, is common in diabetic cats. The high UCCR may reflect activation of the hypothalamus-pituitary-adrenal axis, which also occurs in diabetic humans. The percentage of cats with increased IGF-1 was high but lower than reported in recent studies.

  17. Cinnamon extract improves insulin sensitivity in the brain and lowers liver fat in mouse models of obesity.

    Directory of Open Access Journals (Sweden)

    Tina Sartorius

    Full Text Available OBJECTIVES: Treatment of diabetic subjects with cinnamon demonstrated an improvement in blood glucose concentrations and insulin sensitivity but the underlying mechanisms remained unclear. This work intends to elucidate the impact of cinnamon effects on the brain by using isolated astrocytes, and an obese and diabetic mouse model. METHODS: Cinnamon components (eugenol, cinnamaldehyde were added to astrocytes and liver cells to measure insulin signaling and glycogen synthesis. Ob/ob mice were supplemented with extract from cinnamomum zeylanicum for 6 weeks and cortical brain activity, locomotion and energy expenditure were evaluated. Insulin action was determined in brain and liver tissues. RESULTS: Treatment of primary astrocytes with eugenol promoted glycogen synthesis, whereas the effect of cinnamaldehyde was attenuated. In terms of brain function in vivo, cinnamon extract improved insulin sensitivity and brain activity in ob/ob mice, and the insulin-stimulated locomotor activity was improved. In addition, fasting blood glucose levels and glucose tolerance were greatly improved in ob/ob mice due to cinnamon extracts, while insulin secretion was unaltered. This corresponded with lower triglyceride and increased liver glycogen content and improved insulin action in liver tissues. In vitro, Fao cells exposed to cinnamon exhibited no change in insulin action. CONCLUSIONS: Together, cinnamon extract improved insulin action in the brain as well as brain activity and locomotion. This specific effect may represent an important central feature of cinnamon in improving insulin action in the brain, and mediates metabolic alterations in the periphery to decrease liver fat and improve glucose homeostasis.

  18. Cinnamon Extract Improves Insulin Sensitivity in the Brain and Lowers Liver Fat in Mouse Models of Obesity

    Science.gov (United States)

    Sartorius, Tina; Peter, Andreas; Schulz, Nadja; Drescher, Andrea; Bergheim, Ina; Machann, Jürgen; Schick, Fritz; Siegel-Axel, Dorothea; Schürmann, Annette; Weigert, Cora; Häring, Hans-Ulrich; Hennige, Anita M.

    2014-01-01

    Objectives Treatment of diabetic subjects with cinnamon demonstrated an improvement in blood glucose concentrations and insulin sensitivity but the underlying mechanisms remained unclear. This work intends to elucidate the impact of cinnamon effects on the brain by using isolated astrocytes, and an obese and diabetic mouse model. Methods Cinnamon components (eugenol, cinnamaldehyde) were added to astrocytes and liver cells to measure insulin signaling and glycogen synthesis. Ob/ob mice were supplemented with extract from cinnamomum zeylanicum for 6 weeks and cortical brain activity, locomotion and energy expenditure were evaluated. Insulin action was determined in brain and liver tissues. Results Treatment of primary astrocytes with eugenol promoted glycogen synthesis, whereas the effect of cinnamaldehyde was attenuated. In terms of brain function in vivo, cinnamon extract improved insulin sensitivity and brain activity in ob/ob mice, and the insulin-stimulated locomotor activity was improved. In addition, fasting blood glucose levels and glucose tolerance were greatly improved in ob/ob mice due to cinnamon extracts, while insulin secretion was unaltered. This corresponded with lower triglyceride and increased liver glycogen content and improved insulin action in liver tissues. In vitro, Fao cells exposed to cinnamon exhibited no change in insulin action. Conclusions Together, cinnamon extract improved insulin action in the brain as well as brain activity and locomotion. This specific effect may represent an important central feature of cinnamon in improving insulin action in the brain, and mediates metabolic alterations in the periphery to decrease liver fat and improve glucose homeostasis. PMID:24643026

  19. Cinnamon extract improves insulin sensitivity in the brain and lowers liver fat in mouse models of obesity.

    Science.gov (United States)

    Sartorius, Tina; Peter, Andreas; Schulz, Nadja; Drescher, Andrea; Bergheim, Ina; Machann, Jürgen; Schick, Fritz; Siegel-Axel, Dorothea; Schürmann, Annette; Weigert, Cora; Häring, Hans-Ulrich; Hennige, Anita M

    2014-01-01

    Treatment of diabetic subjects with cinnamon demonstrated an improvement in blood glucose concentrations and insulin sensitivity but the underlying mechanisms remained unclear. This work intends to elucidate the impact of cinnamon effects on the brain by using isolated astrocytes, and an obese and diabetic mouse model. Cinnamon components (eugenol, cinnamaldehyde) were added to astrocytes and liver cells to measure insulin signaling and glycogen synthesis. Ob/ob mice were supplemented with extract from cinnamomum zeylanicum for 6 weeks and cortical brain activity, locomotion and energy expenditure were evaluated. Insulin action was determined in brain and liver tissues. Treatment of primary astrocytes with eugenol promoted glycogen synthesis, whereas the effect of cinnamaldehyde was attenuated. In terms of brain function in vivo, cinnamon extract improved insulin sensitivity and brain activity in ob/ob mice, and the insulin-stimulated locomotor activity was improved. In addition, fasting blood glucose levels and glucose tolerance were greatly improved in ob/ob mice due to cinnamon extracts, while insulin secretion was unaltered. This corresponded with lower triglyceride and increased liver glycogen content and improved insulin action in liver tissues. In vitro, Fao cells exposed to cinnamon exhibited no change in insulin action. Together, cinnamon extract improved insulin action in the brain as well as brain activity and locomotion. This specific effect may represent an important central feature of cinnamon in improving insulin action in the brain, and mediates metabolic alterations in the periphery to decrease liver fat and improve glucose homeostasis.

  20. ADS/CFT and QCD

    Energy Technology Data Exchange (ETDEWEB)

    Brodsky, Stanley J.; /SLAC; de Teramond, Guy F.; /Costa Rica U. /SLAC

    2007-02-21

    The AdS/CFT correspondence between string theory in AdS space and conformal .eld theories in physical spacetime leads to an analytic, semi-classical model for strongly-coupled QCD which has scale invariance and dimensional counting at short distances and color confinement at large distances. Although QCD is not conformally invariant, one can nevertheless use the mathematical representation of the conformal group in five-dimensional anti-de Sitter space to construct a first approximation to the theory. The AdS/CFT correspondence also provides insights into the inherently non-perturbative aspects of QCD, such as the orbital and radial spectra of hadrons and the form of hadronic wavefunctions. In particular, we show that there is an exact correspondence between the fifth-dimensional coordinate of AdS space z and a specific impact variable {zeta} which measures the separation of the quark and gluonic constituents within the hadron in ordinary space-time. This connection allows one to compute the analytic form of the frame-independent light-front wavefunctions, the fundamental entities which encode hadron properties and allow the computation of decay constants, form factors, and other exclusive scattering amplitudes. New relativistic lightfront equations in ordinary space-time are found which reproduce the results obtained using the 5-dimensional theory. The effective light-front equations possess remarkable algebraic structures and integrability properties. Since they are complete and orthonormal, the AdS/CFT model wavefunctions can also be used as a basis for the diagonalization of the full light-front QCD Hamiltonian, thus systematically improving the AdS/CFT approximation.

  1. Continuation versus discontinuation of insulin secretagogues when initiating insulin in type 2 diabetes

    NARCIS (Netherlands)

    Swinnen, S. G.; Dain, M.-P.; Mauricio, D.; DeVries, J. H.; Hoekstra, J. B.; Holleman, F.

    2010-01-01

    We compared the combined use of basal insulin, metformin and insulin secretagogues with a combination of basal insulin and metformin in patients with type 2 diabetes starting basal insulin analogue therapy. This analysis was part of a 24-week trial, in which 964 insulin-naive patients with type 2

  2. Effect of insulin glargine and n-3FA on carotid intima-media thickness in people with dysglycemia at high risk for cardiovascular events: the glucose reduction and atherosclerosis continuing evaluation study (ORIGIN-GRACE)

    National Research Council Canada - National Science Library

    Lonn, Eva M; Bosch, Jackie; Diaz, Rafael; Lopez-Jaramillo, Patricio; Ramachandran, Ambady; Hâncu, Nicolae; Hanefeld, Markolf; Krum, Henry; Ryden, Lars; Smith, Sandra; McQueen, Matthew J; Dyal, Leanne; Yusuf, Salim; Gerstein, Hertzel C

    2013-01-01

    ... (CIMT). We enrolled 1,184 people with cardiovascular (CV) disease and/or CV risk factors plus impaired fasting glucose, impaired glucose tolerance, or early type 2 diabetes in a randomized multicenter 2...

  3. Maximal temperature of a gas in AdS spacetime

    Science.gov (United States)

    Dai, De-Chang; Stojkovic, Dejan

    2017-04-01

    Assuming only statistical mechanics and general relativity, we calculate the maximal temperature of gas of particles placed in anti-de Sitter (AdS) spacetime. If two particles with a given center of mass energy come close enough, according to classical gravity, they will form a black hole. We focus only on the black holes with a Hawking temperature lower than the environment, because they do not disappear. The number density of such black holes grows with the temperature in the system. At a certain finite temperature, the thermodynamical system will be dominated by black holes. This critical temperature is lower than the Planck temperature for the values of the AdS vacuum energy density below the Planck density. This result might be interesting from the AdS/CFT correspondence point of view, since it is different from the Hawking-Page phase transition, and it is not immediately clear what effect dynamically limits the maximal temperature of the thermal state on the CFT side of the correspondence.

  4. Short-Term Moderate Sleep Restriction Decreases Insulin Sensitivity in Young Healthy Adults

    Science.gov (United States)

    Wang, Xuewen; Greer, Julian; Porter, Ryan R.; Kaur, Kamaljeet; Youngstedt, Shawn D.

    2017-01-01

    Context and Purpose The literature suggests that severe sleep loss of more than a few hours a night decreases glucose tolerance and insulin sensitivity. The aim of this study was to determine whether moderate sleep restriction had similar effects. Methods Fifteen healthy non-obese (BMI=24.5±3.4 kg/m2) young adults (20.6±1.3 years) completed two 2-hour oral glucose tolerance tests (OGTT): one was after 3 days of time-in-bed restriction by 1–3 hours each night, and the other was after 3 days of ad libitum sleep. Glucose and insulin concentrations during OGTT, and fasting glucagon and cortisol concentrations were determined. The homeostasis model of insulin resistance (HOMA-IR), Matsuda index, and the quantitative insulin sensitivity check index (QUICKI) were calculated. Results The total time-in-bed during the sleep restriction and the ad libitum phase was 5.98±0.76 and 7.98±0.54 hours/day, and total sleep time was 5.16±0.49 and 6.65±0.64 hours/day, respectively. Glucose concentrations before and 30, 60, 90, and 120 minutes following consumption of glucose and area under the curve were not different for the two OGTT (p > 0.10 for all). Insulin concentration at fasting and area under the curve during the OGTT were significantly higher (p = 0.034 and 0.038, respectively) following restricted sleep than following ad libitum sleep. Fasting glucagon concentration was also higher (p = 0.003). The HOMA-IR, Matsuda index, and QUICKI all suggested decreased insulin sensitivity following restricted sleep. Conclusion Short-term moderate sleep restriction reduced insulin sensitivity compared to ad libitum sleep in this group of healthy young adults. PMID:28819636

  5. New ways of insulin delivery.

    Science.gov (United States)

    Heinemann, L

    2011-02-01

    The predominant number of papers published from the middle of 2009 to the middle of 2010 about alternative routes of insulin administration (ARIA) were still about inhaled insulin. Long-term experience with Exubera was the topic of a number of publications that are also of relevance for inhaled insulin in general. The clinical trials performed with AIR insulin by Eli Lilly were published in a supplement issue of one diabetes technology journal and most of these will be presented. A number of other publications (also one in a high ranked journal) about their inhaled insulin were from another company: MannKind. The driving force behind Technosphere insulin (TI) - which is the only one still in clinical development - is Al Mann; he has put a lot of his personal fortune in this development. We will know the opinion of the regulatory authorities about TI in the near future; however, I am personally relatively confident that the Food and Drug Administration will provide TI with market approval. The more critical question for me is: will diabetologists and patients jump on this product once it becomes commercially available? Will it become a commercial success? In view of many negative feelings in the scientific community about inhaled insulin, it might be of help that MannKind publish their studies with TI systematically. Acknowledging being a believer in this route of insulin administration myself, one has to state that Exubera and AIR insulin had not offered profound advantages in terms of pharmacokinetic (PK) and pharmacodynamic (PD) properties in comparison with subcutaneously (SC) applied regular human insulin (RHI) and rapid-acting insulin analogues. The time-action profiles of these inhaled insulins were more or less comparable with that of rapid-acting insulin analogues. This is clearly different with TI which exhibits a strong metabolic effect shortly after application and a rapid decline in the metabolic effect thereafter; probably the duration of action is

  6. Insulin resistance as a key link for the increased risk of cognitive impairment in the metabolic syndrome.

    Science.gov (United States)

    Kim, Bhumsoo; Feldman, Eva L

    2015-03-13

    Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors that includes obesity, diabetes, and dyslipidemia. Accumulating evidence implies that MetS contributes to the development and progression of Alzheimer's disease (AD); however, the factors connecting this association have not been determined. Insulin resistance (IR) is at the core of MetS and likely represent the key link between MetS and AD. In the central nervous system, insulin plays key roles in learning and memory, and AD patients exhibit impaired insulin signaling that is similar to that observed in MetS. As we face an alarming increase in obesity and T2D in all age groups, understanding the relationship between MetS and AD is vital for the identification of potential therapeutic targets. Recently, several diabetes therapies that enhance insulin signaling are being tested for a potential therapeutic benefit in AD and dementia. In this review, we will discuss MetS as a risk factor for AD, focusing on IR and the recent progress and future directions of insulin-based therapies.

  7. Insulin receptor signaling in cones

    National Research Council Canada - National Science Library

    Rajala, Ammaji; Dighe, Radhika; Agbaga, Martin-Paul; Anderson, Robert E; Rajala, Raju V S

    2013-01-01

    .... To date there are no studies on the insulin receptor signaling in cones; however, mRNA levels of IR signaling proteins are significantly higher in cone-dominant neural retina leucine zipper (Nrl...

  8. Metabolic flexibility and insulin resistance

    OpenAIRE

    Galgani, Jose E.; Moro, Cedric; Ravussin, Eric

    2008-01-01

    Metabolic flexibility is the capacity for the organism to adapt fuel oxidation to fuel availability. The inability to modify fuel oxidation in response to changes in nutrient availability has been implicated in the accumulation of intramyocellular lipid and insulin resistance. The metabolic flexibility assessed by the ability to switch from fat to carbohydrate oxidation is usually impaired during a hyperinsulinemic clamp in insulin-resistant subjects; however, this “metabolic inflexibility” i...

  9. [Insulin secretion: mechanisms of regulation].

    Science.gov (United States)

    Radosavljević, Tatjana; Todorović, Vera; Sikić, Branka

    2004-01-01

    REGULATION OF INSULIN SECRETION: Beta cells are unique endocrine cells. They respond positively, in terms of insulin secretion, not only to changes in the extracellular glucose concentration, but also to activators of the phospholipase C (cholecystokinin or acetylcholine), and to activators of adenylate cyclase (glucagon, glucagon-like peptide-1, or gastric inhibitory polypeptide). Major messengers which mediate glucose action for insulin release are Ca2+, adenosine triphosphate (ATP) and diacylglycerol (DAG). MAJOR PATHWAYS OF INSULIN RELEASE STIMULATION: There are four major pathways involved in stimulation of insulin release. The first pathway is KATP channel-dependent pathway in which increased blood glucose concentrations and increased b-cell metabolism result in a change in intracellular ATP/ADP ratio. This is a contributory factor in closure of ATP-dependent K+ channels, depolarization of b-cell membrane, in increased voltage-dependent L-type Ca2+ channel activity. Increased Ca2+ influx results in increased intracellular Ca2+ and stimulated insulin release. KATP channel-independent pathway augments Ca(2+) -stimulated insulin secretion of KATP channel-dependent pathway. Major potentiation of release results from hormonal and peptidergic activation of receptors linked to adenylyl cyclase. Adenylyl cyclase activity is stimulated by hormones such as vasoactive intestinal peptide (VIP), glucagon-like peptide-1 (GLP-1), and so on. These hormones, acting via G protein, stimulate adenylyl cyclase, thus causing a rise in cyclic adenosine monophosphate (cAMP) and activation of protein kinase A (PKA). Increased activity of PKA results in potentiation of insulin secretion.

  10. Fermionic currents in AdS spacetime with compact dimensions

    Science.gov (United States)

    Bellucci, S.; Saharian, A. A.; Vardanyan, V.

    2017-09-01

    We derive a closed expression for the vacuum expectation value (VEV) of the fermionic current density in a (D +1 )-dimensional locally AdS spacetime with an arbitrary number of toroidally compactified Poincaré spatial dimensions and in the presence of a constant gauge field. The latter can be formally interpreted in terms of a magnetic flux treading the compact dimensions. In the compact subspace, the field operator obeys quasiperiodicity conditions with arbitrary phases. The VEV of the charge density is zero and the current density has nonzero components along the compact dimensions only. They are periodic functions of the magnetic flux with the period equal to the flux quantum and tend to zero on the AdS boundary. Near the horizon, the effect of the background gravitational field is small and the leading term in the corresponding asymptotic expansion coincides with the VEV for a massless field in the locally Minkowski bulk. Unlike the Minkowskian case, in the system consisting of an equal number of fermionic and scalar degrees of freedom, with same masses, charges and phases in the periodicity conditions, the total current density does not vanish. In these systems, the leading divergences in the scalar and fermionic contributions on the horizon are canceled and, as a consequence of that, the charge flux, integrated over the coordinate perpendicular to the AdS boundary, becomes finite. We show that in odd spacetime dimensions the fermionic fields realizing two inequivalent representations of the Clifford algebra and having equal phases in the periodicity conditions give the same contribution to the VEV of the current density. Combining the contributions from these fields, the current density in odd-dimensional C -,P - and T -symmetric models are obtained. As an application, we consider the ground state current density in curved carbon nanotubes described in terms of a (2 +1 )-dimensional effective Dirac model.

  11. New Features in ADS Labs

    Science.gov (United States)

    Accomazzi, Alberto; Kurtz, M. J.; Henneken, E. A.; Grant, C. S.; Thompson, D.; Di Milia, G.; Luker, J.; Murray, S. S.

    2013-01-01

    The NASA Astrophysics Data System (ADS) has been working hard on updating its services and interfaces to better support our community's research needs. ADS Labs is a new interface built on the old tried-and-true ADS Abstract Databases, so all of ADS's content is available through it. In this presentation we highlight the new features that have been developed in ADS Labs over the last year: new recommendations, metrics, a citation tool and enhanced fulltext search. ADS Labs has long been providing article-level recommendations based on keyword similarity, co-readership and co-citation analysis of its corpus. We have now introduced personal recommendations, which provide a list of articles to be considered based on a individual user's readership history. A new metrics interface provides a summary of the basic impact indicators for a list of records. These include the total and normalized number of papers, citations, reads, and downloads. Also included are some of the popular indices such as the h, g and i10 index. The citation helper tool allows one to submit a set of records and obtain a list of top 10 papers which cite and/or are cited by papers in the original list (but which are not in it). The process closely resembles the network approach of establishing "friends of friends" via an analysis of the citation network. The full-text search service now covers more than 2.5 million documents, including all the major astronomy journals, as well as physics journals published by Springer, Elsevier, the American Physical Society, the American Geophysical Union, and all of the arXiv eprints. The full-text search interface interface allows users and librarians to dig deep and find words or phrases in the body of the indexed articles. ADS Labs is available at http://adslabs.org

  12. Entanglement entropy and duality in AdS4

    Directory of Open Access Journals (Sweden)

    Ioannis Bakas

    2015-07-01

    Full Text Available Small variations of the entanglement entropy δS and the expectation value of the modular Hamiltonian δE are computed holographically for circular entangling curves in the boundary of AdS4, using gravitational perturbations with general boundary conditions in spherical coordinates. Agreement with the first law of thermodynamics, δS=δE, requires that the line element of the entangling curve remains constant. In this context, we also find a manifestation of electric–magnetic duality for the entanglement entropy and the corresponding modular Hamiltonian, following from the holographic energy–momentum/Cotton tensor duality.

  13. Fermionic continuous spin gauge field in (AdS space

    Directory of Open Access Journals (Sweden)

    R.R. Metsaev

    2017-10-01

    Full Text Available Fermionic continuous spin field propagating in (AdS space–time is studied. Gauge invariant Lagrangian formulation for such fermionic field is developed. Lagrangian of the fermionic continuous spin field is constructed in terms of triple gamma-traceless tensor–spinor Dirac fields, while gauge symmetries are realized by using gamma-traceless gauge transformation parameters. It is demonstrated that partition function of fermionic continuous spin field is equal to one. Modified de Donder gauge condition that considerably simplifies analysis of equations of motion is found. Decoupling limits leading to arbitrary spin massless, partial-massless, and massive fermionic fields are studied.

  14. Insulin Resistance, Obesity and Lipotoxicity.

    Science.gov (United States)

    Yazıcı, Dilek; Sezer, Havva

    2017-01-01

    Lipotoxicity , originally used to describe the destructive effects of excess fat accumulation on glucose metabolism, causes functional impairments in several metabolic pathways, both in adipose tissue and peripheral organs, like liver, heart, pancreas and muscle. Lipotoxicity has roles in insulin resistance and pancreatic beta cell dysfunction. Increased circulating levels of lipids and the metabolic alterations in fatty acid utilization and intracellular signaling, have been related to insulin resistance in muscle and liver. Different pathways, like novel protein kinase c pathways and the JNK-1 pathway are involved as the mechanisms of how lipotoxicity leads to insulin resistance in nonadipose tissue organs, such as liver and muscle. Mitochondrial dysfunction plays a role in the pathogenesis of insulin resistance. Endoplasmic reticulum stress, through mainly increased oxidative stress, also plays important role in the etiology of insulin resistance, especially seen in non-alcoholic fatty liver disease. Visceral adiposity and insulin resistance both increase the cardiometabolic risk and lipotoxicity seems to play a crucial role in the pathophysiology of these associations.

  15. Insulin therapy in special conditions

    Directory of Open Access Journals (Sweden)

    León E Litwak

    2017-10-01

    Full Text Available Hyperglycemia during hospitalization is a common condition associated with poor prognosis. To date, insulin is the best strategy to treat hyperglycemia in these patients. An adequate glycemic control is associated with better clinical results. Nevertheless, glycemic goals are still controversial due to the increase of hypoglycemia and other adverse events. Diabetes mellitus is still the main cause of chronic renal failure in our country and its treatment deserves a special analysis considering that insulin pharmacokinetics is altered. Recommendations in this setting are based in expert panel opinions, focusing mainly in intermediate or long acting insulins combined with regular insulin and/or rapid acting analogues. During pregnancy, NPH and regular insulin are safe and effective. It is worth mentioning that the development of new long and rapid acting molecules yielded lower glycemic variability, better post-prandial control and less hypoglycemia. The aim of this study is to provide a review of the proper use of insulin in these special conditions.

  16. Cotransplantation of adipose tissue-derived insulin-secreting mesenchymal stem cells and hematopoietic stem cells: a novel therapy for insulin-dependent diabetes mellitus.

    Science.gov (United States)

    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.

  17. Cotransplantation of Adipose Tissue-Derived Insulin-Secreting Mesenchymal Stem Cells and Hematopoietic Stem Cells: A Novel Therapy for Insulin-Dependent Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    A. V. Vanikar

    2010-01-01

    Full Text Available 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: 2.1×103/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: 28.1×103/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.

  18. Intrahippocampal Administration of Amyloid-β1–42 Oligomers Acutely Impairs Spatial Working Memory, Insulin Signaling, and Hippocampal Metabolism

    Science.gov (United States)

    Pearson-Leary, Jiah; McNay, Ewan C.

    2017-01-01

    Increasing evidence suggests that abnormal brain accumulation of amyloid-β1–42 (Aβ1–42) oligomers plays a causal role in Alzheimer’s disease (AD), and in particular may cause the cognitive deficits that are the hallmark of AD. In vitro, Aβ1–42 oligomers impair insulin signaling and suppress neural functioning. We previously showed that endogenous insulin signaling is an obligatory component of normal hippocampal function, and that disrupting this signaling led to a rapid impairment of spatial working memory, while delivery of exogenous insulin to the hippocampus enhanced both memory and metabolism; diet-induced insulin resistance both impaired spatial memory and prevented insulin from increasing metabolism or cognitive function. Hence, we tested the hypothesis that Aβ1–42 oligomers could acutely impair hippocampal metabolic and cognitive processes in vivo in the rat. Our findings support this hypothesis: Aβ1–42 oligomers impaired spontaneous alternation behavior while preventing the task-associated dip in hippocampal ECF glucose observed in control animals. In addition, Aβ1–42 oligomers decreased plasma membrane translocation of the insulin-sensitive glucose transporter 4 (GluT4), and impaired insulin signaling as measured by phosphorylation of Akt. These data show in vivo that Aβ1–42 oligomers can rapidly impair hippocampal cognitive and metabolic processes, and provide support for the hypothesis that elevated Aβ1–42 leads to cognitive impairment via interference with hippocampal insulin signaling. PMID:22430529

  19. Intrahippocampal administration of amyloid-β(1-42) oligomers acutely impairs spatial working memory, insulin signaling, and hippocampal metabolism.

    Science.gov (United States)

    Pearson-Leary, Jiah; McNay, Ewan C

    2012-01-01

    Increasing evidence suggests that abnormal brain accumulation of amyloid-β(1-42) (Aβ(1-42)) oligomers plays a causal role in Alzheimer's disease (AD), and in particular may cause the cognitive deficits that are the hallmark of AD. In vitro, Aβ(1-42) oligomers impair insulin signaling and suppress neural functioning. We previously showed that endogenous insulin signaling is an obligatory component of normal hippocampal function, and that disrupting this signaling led to a rapid impairment of spatial working memory, while delivery of exogenous insulin to the hippocampus enhanced both memory and metabolism; diet-induced insulin resistance both impaired spatial memory and prevented insulin from increasing metabolism or cognitive function. Hence, we tested the hypothesis that Aβ(1-42) oligomers could acutely impair hippocampal metabolic and cognitive processes in vivo in the rat. Our findings support this hypothesis: Aβ(1-42) oligomers impaired spontaneous alternation behavior while preventing the task-associated dip in hippocampal ECF glucose observed in control animals. In addition, Aβ(1-42) oligomers decreased plasma membrane translocation of the insulin-sensitive glucose transporter 4 (GluT4), and impaired insulin signaling as measured by phosphorylation of Akt. These data show in vivo that Aβ(1-42) oligomers can rapidly impair hippocampal cognitive and metabolic processes, and provide support for the hypothesis that elevated Aβ(1-42) leads to cognitive impairment via interference with hippocampal insulin signaling.

  20. Introducing ADS 2.0

    Science.gov (United States)

    Accomazzi, Alberto; Kurtz, M. J.; Henneken, E. A.; Grant, C. S.; Thompson, D.; Luker, J.; Chyla, R.; Murray, S. S.

    2014-01-01

    In the spring of 1993, the Smithsonian/NASA Astrophysics Data System (ADS) first launched its bibliographic search system. It was known then as the ADS Abstract Service, a component of the larger Astrophysics Data System effort which had developed an interoperable data system now seen as a precursor of the Virtual Observatory. As a result of the massive technological and sociological changes in the field of scholarly communication, the ADS is now completing the most ambitious technological upgrade in its twenty-year history. Code-named ADS 2.0, the new system features: an IT platform built on web and digital library standards; a new, extensible, industrial strength search engine; a public API with various access control capabilities; a set of applications supporting search, export, visualization, analysis; a collaborative, open source development model; and enhanced indexing of content which includes the full-text of astronomy and physics publications. The changes in the ADS platform affect all aspects of the system and its operations, including: the process through which data and metadata are harvested, curated and indexed; the interface and paradigm used for searching the database; and the follow-up analysis capabilities available to the users. This poster describes the choices behind the technical overhaul of the system, the technology stack used, and the opportunities which the upgrade is providing us with, namely gains in productivity and enhancements in our system capabilities.

  1. AdS nonlinear instability: moving beyond spherical symmetry

    Science.gov (United States)

    Dias, Óscar J. C.; Santos, Jorge E.

    2016-12-01

    Anti-de Sitter (AdS) is conjectured to be nonlinear unstable to a weakly turbulent mechanism that develops a cascade towards high frequencies, leading to black hole formation (Dafermos and Holzegel 2006 Seminar at DAMTP (University of Cambridge) available at https://dpmms.cam.ac.uk/~md384/ADSinstability.pdf, Bizon and Rostworowski 2011 Phys. Rev. Lett. 107 031102). We give evidence that the gravitational sector of perturbations behaves differently from the scalar one studied by Bizon and Rostworowski. In contrast with Bizon and Rostworowski, we find that not all gravitational normal modes of AdS can be nonlinearly extended into periodic horizonless smooth solutions of the Einstein equation. In particular, we show that even seeds with a single normal mode can develop secular resonances, unlike the spherically symmetric scalar field collapse studied by Bizon and Rostworowski. Moreover, if the seed has two normal modes, more than one resonance can be generated at third order, unlike the spherical collapse of Bizon and Rostworowski. We also show that weak turbulent perturbative theory predicts the existence of direct and inverse cascades, with the former dominating the latter for equal energy two-mode seeds.

  2. AdS pure spinor superstring in constant backgrounds

    Energy Technology Data Exchange (ETDEWEB)

    Chandia, Osvaldo [Departamento de Ciencias, Facultad de Artes Liberales, Universidad Adolfo Ibáñez,Facultad de Ingeniería y Ciencias, Universidad Adolfo Ibáñez,Diagonal Las Torres 2640, Peñalolén, Santiago (Chile); Bevilaqua, L. Ibiapina [Escola de Ciências e Tecnologia, Universidade Federal do Rio Grande do Norte,Caixa Postal 1524, 59072-970, Natal, RN (Brazil); Vallilo, Brenno Carlini [Facultad de Ciencias Exactas, Departamento de Ciencias Físicas, Universidad Andres Bello,Republica 220, Santiago (Chile)

    2014-06-05

    In this paper we study the pure spinor formulation of the superstring in AdS{sub 5}×S{sup 5} around point particle solutions of the classical equations of motion. As a particular example we quantize the pure spinor string in the BMN background.

  3. Insulin in Central Nervous System: More than Just a Peripheral Hormone

    Directory of Open Access Journals (Sweden)

    Ana I. Duarte

    2012-01-01

    Full Text Available Insulin signaling in central nervous system (CNS has emerged as a novel field of research since decreased brain insulin levels and/or signaling were associated to impaired learning, memory, and age-related neurodegenerative diseases. Thus, besides its well-known role in longevity, insulin may constitute a promising therapy against diabetes- and age-related neurodegenerative disorders. More interestingly, insulin has been also faced as the potential missing link between diabetes and aging in CNS, with Alzheimer's disease (AD considered as the “brain-type diabetes.” In fact, brain insulin has been shown to regulate both peripheral and central glucose metabolism, neurotransmission, learning, and memory and to be neuroprotective. And a future challenge will be to unravel the complex interactions between aging and diabetes, which, we believe, will allow the development of efficient preventive and therapeutic strategies to overcome age-related diseases and to prolong human “healthy” longevity. Herewith, we aim to integrate the metabolic, neuromodulatory, and neuroprotective roles of insulin in two age-related pathologies: diabetes and AD, both in terms of intracellular signaling and potential therapeutic approach.

  4. Insulin addition to swine semen diluted and cooled at 15 ºC

    Directory of Open Access Journals (Sweden)

    Evandro César Pereira Cunha

    2012-04-01

    Full Text Available The objective of this study was to evaluate the effect of adding different doses of insulin to swine semen processed and stored at 15 ºC. The experiment used sixteen ejaculates from four commercial breeding pigs, distributed in a randomized block design (ejaculate with split plot along time (0, 24, 48 and 72 hours of storage with four treatments (insulin levels - 0.0 4.0 8.0 and 12.0 IU per dose and 16 repetitions. The experimental unit was made of two insemination doses of 100 mL each, with 3×10(9 spermatozoids. Insulin used was NPH-human, added at the time of processing the doses. The addition of insulin did not affect motility, sperm viability, the percentage of abnormal cells, the osmotic resistance or the degradation rate of motility in 120 minutes. There was a linear decrease in semen quality over storage time, regardless of insulin levels. The addition of insulin at the mentioned concentrations does not influence the quality of insemination dose in pigs.

  5. A 2-year Trial of Intermittent Insulin Therapy versus Metformin for the Preservation of Beta-cell Function after Initial Short-term Intensive Insulin Induction in early Type 2 Diabetes.

    Science.gov (United States)

    Retnakaran, Ravi; Choi, Haysook; Ye, Chang; Kramer, Caroline K; Zinman, Bernard

    2018-01-27

    When administered in early type 2 diabetes (T2DM), short-term intensive insulin therapy (IIT) can improve reversible beta-cell dysfunction and induce subsequent remission of diabetes. However, this remission is ultimately temporary, as beta-cell function deteriorates over time after stopping IIT. Thus, to preserve beta-cell function, we hypothesized that "induction" IIT needs to be followed by a "maintenance therapy." In this context, we sought to evaluate the impact on beta-cell function over 2-years of two approaches to maintenance therapy: intermittent short-term IIT every 3-months versus daily metformin. In this trial, 24 adults with T2DM of 2.0±1.7 years duration and A1c 6.4±0.1% were randomized to 3-weeks of induction IIT (glargine, lispro) followed by either (i) repeat IIT for up to 2-weeks every 3-months or (ii) daily metformin. Participants underwent serial assessment of beta-cell function by Insulin Secretion-Sensitivity Index-2 (ISSI-2) on oral glucose tolerance test every 3-months. The primary outcome of baseline-adjusted ISSI-2 at 2-years was higher in the metformin arm compared to intermittent IIT (245.0±31.7 vs 142.2±18.4, p=0.008). Baseline-adjusted A1c at 2-years (secondary outcome) was lower in the metformin arm (6.0±0.2% vs 7.3±0.2%, p=0.0006). At study completion, 66.7% of participants randomized to metformin had A1c≤6.0% compared to 8.3% of those on intermittent IIT (p=0.009). There were no differences in insulin sensitivity. Following induction IIT, metformin was superior to intermittent IIT for maintaining beta-cell function and glycemic control over 2-years. The strategy of induction and maintenance therapy to preserve beta-cell function warrants exploration in early T2DM. This article is protected by copyright. All rights reserved.

  6. Numerical Simulations of Asymptotically AdS Spacetimes

    Science.gov (United States)

    Bantilan, Hans

    In this dissertation, we introduce a numerical scheme to construct asymptotically anti-de Sitter spacetimes with Lorentzian signature, focusing on cases that preserve five-dimensional axisymmetry. We study the field theories that are dual to these spacetimes by appealing to the AdS/CFT correspondence in the regime where the gravity dual is completely described by Einstein gravity. The numerical scheme is based on generalized harmonic evolution, and we begin by obtaining initial data defined on some Cauchy hypersurface. For the study described in this dissertation, we use a scalar field to source deviations from pure AdS5, and obtain data that correspond to highly deformed black holes. We evolve this initial data forward in time, and follow the subsequent ringdown. What is novel about this study is that the initial horizon geometry cannot be considered a small perturbation of the final static horizon, and hence we are probing an initial non-linear phase of the evolution of the bulk spacetime. On the boundary, we find that the dual CFT stress tensor behaves like that of a thermalized N = 4 SYM fluid. We find that the equation of state of this fluid is consistent with conformal invariance, and that its transport coefficients match those previously calculated for an N = 4 SYM fluid via holographic methods. Modulo a brief transient that is numerical in nature, this matching appears to hold from the initial time onwards. We transform these solutions computed in global AdS onto a Minkowski piece of the boundary, and examine the temperature of the corresponding fluid flows. Under this transformation, the spatial profile of temperature at the initial time resembles a Lorentz-flattened pancake centered at the origin of Minkowski space. By interpreting the direction along which the data is flattened as the beam-line direction, our initial data can be thought of as approximating a head-on heavy ion collision at its moment of impact.

  7. Smooth causal patches for AdS black holes

    Science.gov (United States)

    Raju, Suvrat

    2017-06-01

    We review the paradox of low energy excitations of a black hole in anti-de Sitter space (AdS). An appropriately chosen unitary operator in the boundary theory can create a locally strong excitation near the black hole horizon, whose global energy is small as a result of the gravitational redshift. The paradox is that this seems to violate a general rule of statistical mechanics, which states that an operator with energy parametrically smaller than k T cannot create a significant excitation in a thermal system. When we carefully examine the position dependence of the boundary unitary operator that produces the excitation and the bulk observable necessary to detect the anomalously large effect, we find that they do not both fit in a single causal patch. This follows from a remarkable property of position-space AdS correlators that we establish explicitly and resolves the paradox in a generic state of the system, since no combination of observers can both create the excitation and observe its effect. As a special case of our analysis, we show how this resolves the "Born rule" paradox of Marolf and Polchinski [J. High Energy Phys. 01 (2016) 008, 10.1007/JHEP01(2016)008] and we verify our solution using an independent calculation. We then consider boundary states that are finely tuned to display a spontaneous excitation outside the causal patch of the infalling observer, and we propose a version of causal patch complementarity in AdS/CFT that resolves the paradox for such states as well.

  8. Pioglitazone acutely reduces energy metabolism and insulin secretion in rats

    National Research Council Canada - National Science Library

    Lamontagne, Julien; Jalbert-Arsenault, Elise; Pepin, Emilie; Peyot, Marie-Line; Ruderman, Neil B; Nolan, Christopher J; Joly, Erik; Madiraju, S R Murthy; Poitout, Vincent; Prentki, Marc

    2013-01-01

    Our objective was to determine if the insulin-sensitizing drug pioglitazone acutely reduces insulin secretion and causes metabolic deceleration in vivo independently of change in insulin sensitivity...

  9. ADS-B in space

    DEFF Research Database (Denmark)

    Knudsen, Bjarke Gosvig; Jensen, Morten; Birklykke, Alex

    201