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Sample records for adding insulin glargine

  1. Insulin glargine overdose

    Directory of Open Access Journals (Sweden)

    Fatma Sari Dogan

    2012-01-01

    Full Text Available Insulin glargine is a long acting novel recombinant human insulin analogue indicated to improve glycemic control, in adults and children with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. The time course of action of insulins including insulin glargine may vary between individuals and/or within the same individual. Insulin glargine is given as a 24-h dosing regimen and has no documented half-life or peak effect. Hypoglycemia is the most common adverse effect of insulin, including insulin glargine. As with all insulins, the timing of hypoglycemia may differ among various insulin formulations. We present a case of a 76-year-old male insulin-dependent diabetic patient with refractory hypoglycemia secondary to an intentional overdose of insulin glargine. We would like to highlight the necessity of prolonging IV glucose infusion, for a much longer period than expected from pharmacokinetic properties of these insulin analogues after intentional massive overdose.

  2. [Medication of the month. Insulin glargine (Lantus)].

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    Scheen, A J

    2004-02-01

    Insulin glargine (Lantus) is a human insulin analogue produced by recombinant DNA technology and recently launched by Aventis. Modification of the human insulin molecule at position A21 and at the C-terminus of the B-chain results in the formation of a stable compound that is soluble at pH 4.0, but forms amorphous microprecipitates in subcutaneous tissue (pH > 7,4) from which small amounts of insulin glargine are gradually released. The plasma concentration versus time profile of insulin glargine is therefore relatively constant over 24 hours as compared to conventional human insulins, especially NPH. This allows once-daily injection as basal insulin therapy, at any moment of the clock time (but if possible at the same time from day to day). Reproducibility of plasma insulin levels is also improved with insulin glargine as compared to human NPH insulin. Insulin glargine administration should be combined to rapid insulin injections, before each meal in order to control postprandial hyperglycaemia, or with oral antidiabetic agents in type 2 diabetes. The pharmacokinetic properties of insulin glargine allow an easier titration of basal insulin dose, which should facilitate adequate blood glucose control while decreasing the risk of hypoglycaemia, especially during night time. Insulin glargine use is safe with no increased antigenicity, immunogenicity or mitogenicity reactions as compared to human insulin. Optimal use of this new insulin analogue should be integrated in a global management of the diabetic patient as well as in a new culture of insulin therapy. PMID:15112902

  3. Le medicament du mois. Insuline glargine (Lantus).

    OpenAIRE

    Scheen, André

    2004-01-01

    Insulin glargine (Lantus) is a human insulin analogue produced by recombinant DNA technology and recently launched by Aventis. Modification of the human insulin molecule at position A21 and at the C-terminus of the B-chain results in the formation of a stable compound that is soluble at pH 4.0, but forms amorphous microprecipitates in subcutaneous tissue (pH > 7,4) from which small amounts of insulin glargine are gradually released. The plasma concentration versus time profile of insulin glar...

  4. Insulin glargine: pharmacokinetic and pharmacodynamic basis of clinical effect

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    Vadim Valeryevich Klimontov

    2014-10-01

    Full Text Available Glargine became the first long-acting insulin analogue. Glargine was designed to meet basal insulin requirements throughout the day with a single injection. Pharmacokinetics of insulin glargine is characterized by biotransformation into metabolites M1 and M2 that transforms the B chain of glargine so it is similar to the B chain of human insulin. Plasma concentrations of active M1 and M2 metabolites have no pronounced peaks during the day, resulting in lower glucose variability and hypoglycaemia risk when compared with NPH insulin. The metabolic activities of M1 and M2 metabolites are similar to the effect of glargine, whereas the mitogenic effects of these metabolites do not exceed the effect of human insulin. Insulin glargine shows a higher affinity for the insulin-like growth factor-1 (IGF-1 receptor when compared with human insulin. Glargine has no proliferative effect in vivo owing to its rapid conversion into metabolites. Pharmacokinetic and pharmacodynamic variability of glargine is comparable to other insulins. These characteristics are important for the clinical efficacy and safety of glargine.

  5. Insulin degludec versus insulin glargine in insulin-naive patients with type 2 diabetes

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    Zinman, Bernard; Philis-Tsimikas, Athena; Cariou, Bertrand;

    2012-01-01

    To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs).......To compare ultra-long-acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs)....

  6. Insulin Glargine: a review 8 years after its introduction.

    Science.gov (United States)

    Goykhman, Stanislav; Drincic, Andjela; Desmangles, Jean Claude; Rendell, Marc

    2009-03-01

    Insulin Glargine was the first long-acting insulin analog produced by recombinant DNA technology, approved for use by the US FDA in April 2000 and by the European Agency for the Evaluation of Medicinal Products in June, 2000. It has become the most widely used insulin in the USA owing to its long duration of action without a pronounced peak. The principal advantage of insulin Glargine over neutral protamine Hagedorn (NPH) insulin is in a lower frequency of hypoglycemic reactions, thus affording improved safety. It is used in both type 1 and type 2 diabetes, usually as a single daily dose. In type 2 patients, it is often the first insulin introduced as a single daily dose. Although insulin Glargine is typically administered as a single nighttime dose, it can be given in the morning or at any other time convenient for the patient. In labile type 1 diabetes, it is often most effective given as two daily injections. In obese, insulin-resistant patients, it may be best to administer insulin Glargine in two separate doses, owing to the high volumes of injected insulin required. Insulin Glargine does not treat postprandial hyperglycemia. It is necessary to supplement with short-acting insulin at mealtimes to control glucose surges after meals. Insulin Glargine is effective in hospitalized and postsurgical patients on account of its lack of pronounced insulin peaks and long duration of action. Although there is considerable use of Glargine in pregnant diabetic women, there is no definitive study to confirm its benefits. Insulin Glargine is thought to coprecipitate supplementary short-acting insulins when co-administered in the same syringe. Therefore, more injections are typically needed in the usual treatment regimen for insulin requiring diabetes. In many cases, constant basal insulin levels may be achieved with multiple overlapping doses of NPH insulin given together with short-acting insulin at mealtimes. Such a therapy may be less costly, but the major advantage of

  7. Cancer Incidence Among Those Initiating Insulin Therapy With Glargine Versus Human NPH Insulin

    OpenAIRE

    Stürmer, Til; Marquis, M. Alison; Zhou, Haibo; Meigs, James B; Lim, Soo; Blonde, Lawrence; MacDonald, Eileen; Wang, Ray; LaVange, Lisa M.; Pate, Virginia; Buse, John B.

    2013-01-01

    OBJECTIVE To add to the evidence on comparative long-term effects of insulin analog glargine versus human NPH insulin on the risk for cancer. RESEARCH DESIGN AND METHODS We identified cohorts of initiators of glargine and human NPH without an insulin prescription during the prior 19 months among patients covered by the Inovalon Medical Outcomes Research for Effectiveness and Economics Registry (MORE2 Registry) between January 2003 and December 2010. Patients were required to have a second pre...

  8. 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....

  9. Insulin glargine: an updated review of its use in the management of diabetes mellitus.

    Science.gov (United States)

    Dunn, Christopher J; Plosker, Greg L; Keating, Gillian M; McKeage, Kate; Scott, Lesley J

    2003-01-01

    Insulin glargine is a human insulin analogue prepared by recombinant DNA technology. Modification of the human insulin molecule at position A21 and at the C-terminus of the B-chain results in the formation of a stable compound that is soluble at pH 4.0, but forms amorphous microprecipitates in subcutaneous tissue from which small amounts of insulin glargine are gradually released. The plasma concentration versus time profile of insulin glargine is therefore relatively constant in relation to conventional human insulins, with no pronounced peak over 24 hours. This allows once-daily administration as basal therapy. Early randomised trials with insulin glargine generally showed greater reductions in fasting blood or plasma glucose levels and a reduced frequency of nocturnal hypoglycaemia relative to neutral protamine Hagedorn (NPH) insulin in patients with type 1 diabetes mellitus. In addition to this basal therapy, patients continued to use the regular mealtime insulin regimen to which they were accustomed. More recent data with insulin glargine have included evidence of improved glycaemic control, with improvements in satisfaction with treatment over NPH insulin. Furthermore, the time of day at which insulin glargine is injected has no clinically relevant effect on glycaemic control in these patients. There are also data from small, nonblind studies to suggest comparable glycaemic control with insulin glargine and continuous subcutaneous insulin infusion. Results from comparative studies and meta-analyses in individuals with type 2 diabetes show lower incidences of nocturnal hypoglycaemia with insulin glargine than with NPH insulin, with two studies showing a significantly greater improvement in glycosylated haemoglobin levels with insulin glargine than with NPH. Insulin glargine is well tolerated, and is not associated with greater immunogenicity or increases in bodyweight than NPH insulin. Long-term data show maintenance of glycaemic control with insulin glargine

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

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    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.

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

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    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.

  12. Treatment satisfaction and quality of life with insulin glargine plus insulin lispro compared with NPH insulin plus unmodified human insulin in people with Type 1 diabetes

    OpenAIRE

    Ashwell , SG; Stephens, JW; Witthaus, E; Home, PD; Bradley, Clare

    2008-01-01

    OBJECTIVE— The purpose of this study was to compare quality of life and treatment satisfaction using insulin glargine plus insulin lispro with that using NPH insulin plus unmodified human insulin in adults with type 1 diabetes managed with multiple injection regimens. RESEARCH DESIGN AND METHODS— As part of a 32-week, five-center, two-way crossover study in 56 individuals with type 1 diabetes randomized to evening insulin glargine plus mealtime insulin lispro or to NPH insulin (once or twi...

  13. Spotlight on insulin glargine in type 1 and 2 diabetes mellitus.

    Science.gov (United States)

    McKeage, Kate; Goa, Karen L

    2002-01-01

    Insulin glargine is a recombinant human insulin analog produced by DNA technology using a nonpathogenic strain of Escherichia coli. Two modifications of human insulin result in a stable molecule which is soluble in slightly acidic conditions (pH 4.0) and precipitates in the neutral pH of subcutaneous tissue. Because of these properties, absorption of insulin glargine is delayed and the analog provides a fairly constant, basal insulin supply without peaks in plasma insulin levels for approximately 24 hours, similar to that achieved by a continuous subcutaneous insulin infusion. Insulin glargine is indicated as a once daily subcutaneous injection to provide basal glycemic control in adults and children aged >6 years with type 1 diabetes mellitus and in adults with type 2 diabetes mellitus. Fasting plasma glucose and fasting blood glucose levels generally improved to a greater extent in patients with type 1 diabetes mellitus receiving insulin glargine than patients who administered Neutral Protamine Hagedorn (NPH) insulin. In patients with type 1 or 2 disease, glycosylated hemoglobin levels were slightly reduced and to a similar extent with insulin glargine and NPH insulin. Most clinical trials in patients with type 1 or 2 diabetes mellitus demonstrated a lower incidence of hypoglycemia, especially nocturnal hypoglycemia, with insulin glargine compared with NPH insulin. One of the most common adverse events with insulin glargine treatment was injection site pain which, in some studies, occurred more frequently than in patients receiving NPH insulin. In all cases the symptoms were mild and treatment discontinuation was not required. Otherwise, the drug is well tolerated and does not appear to be immunogenic. In conclusion, insulin glargine once a day provides basal control of glycemia for approximately 24 hours without inducing peaks in plasma insulin levels in patients with type 1 or 2 diabetes mellitus. In long-term, well designed trials insulin glargine once daily

  14. Hypersensitivity Reaction to Insulin Glargine and Insulin Detemir in a Pediatric Patient: A Case Report

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    Badik, Jennifer; Chen, Jimmy; Letvak, Kira; So, Tsz-Yin

    2016-01-01

    Allergy to human insulin or its analogs is rare, but it is still a significant issue in current diabetes care. Allergic reactions can range from localized injection site reactions to generalized anaphylaxis, and they can be caused by excipients or the insulin molecules themselves. We presented a case of a 14-year-old male patient with generalized allergic reactions to insulin glargine and insulin detemir. The patient was successfully managed by being switched to a continuous subcutaneous insu...

  15. 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

  16. A case of hypersensitivity to soluble and isophane insulins but not to insulin glargine.

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    Belhekar, Mahesh N; Pai, Sarayu; Tayade, Parimal; Dalwadi, Pradip; Munshi, Renuka; Varthakavi, Prema

    2015-01-01

    Insulin is an important agent for the treatment of diabetes mellitus (DM). Allergic reactions to insulin therapy, although rare, have been evident since animal insulin became available for the treatment of DM in 1922. Hypersensitivity to insulin has considerably been reduced with the introduction of human insulin produced by recombinant deoxyribonucleic acid technology. Here, we present a case of Type 2 DM who demonstrated immediate (Type 1) hypersensitivity reaction on the sites of subcutaneous injection of soluble and isophane insulin but insulin glargine was tolerated well and provided good glycemic control. PMID:25878390

  17. A case of hypersensitivity to soluble and isophane insulins but not to insulin glargine

    Directory of Open Access Journals (Sweden)

    Mahesh N Belhekar

    2015-01-01

    Full Text Available Insulin is an important agent for the treatment of diabetes mellitus (DM. Allergic reactions to insulin therapy, although rare, have been evident since animal insulin became available for the treatment of DM in 1922. Hypersensitivity to insulin has considerably been reduced with the introduction of human insulin produced by recombinant deoxyribonucleic acid technology. Here, we present a case of Type 2 DM who demonstrated immediate (Type 1 hypersensitivity reaction on the sites of subcutaneous injection of soluble and isophane insulin but insulin glargine was tolerated well and provided good glycemic control.

  18. [INSULIN GLARGINE 300 U/mL (TOUJEO®)].

    Science.gov (United States)

    Scheen, A J

    2016-02-01

    This article presents a new formulation of insulin glargine concentrated at 300 U/mL (Gla-300). It is commercialized under the trade name of Toujeo® in an optimized pre-filled SoloStar™ pen for the treatment of type 1 and type 2 diabetes in adults. Besides a threefold higher concentration compared to the classical insulin Lantus® (100 U/mL or Gla-100), both pharmacokinetic and pharmacodynamic profiles of Gla-300 are flatter and longer (more than 24 hours) and have a lesser intra-/inter-variability, which makes them more reproducible. Overall, Toujeo® offers the same hypoglycaemic efficacy and the same safety profile when compared with Lantus®. However, a lower risk of hypoglycaemia, especially at night, a slightly smaller weight gain and a better flexibility in the time of injection have been reported. The two insulin formulations are not bioequivalent and the daily insulin requirement is slightly higher with insulin Gla-300 than with insulin Gla-100. The shift from an already available basal insulin towards Toujeo® may require a dose adjustment and a reinforcement of blood glucose monitoring.

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

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    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.

  20. 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.

  1. Electronic medical record cancer incidence over six years comparing new users of glargine with new users of NPH insulin.

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    Soo Lim

    Full Text Available BACKGROUND: Recent studies suggested that insulin glargine use could be associated with increased risk of cancer. We compared the incidence of cancer in new users of glargine versus new users of NPH in a longitudinal clinical cohort with diabetes for up to 6 years. METHODS AND FINDINGS: From all patients who had been regularly followed at Massachusetts General Hospital from 1/01/2005 to 12/31/2010, 3,680 patients who had a medication record for glargine or NPH usage were obtained from the electronic medical record (EMR. From those we selected 539 new glargine users (age: 60.1±13.6 years, BMI: 32.7±7.5 kg/m2 and 343 new NPH users (61.5±14.1 years, 32.7±8.3 kg/m2 who had no prevalent cancer during 19 months prior to glargine or NPH initiation. All incident cancer cases were ascertained from the EMR requiring at least 2 ICD-9 codes within a 2 month period. Insulin exposure time and cumulative dose were validated. The statistical analysis compared the rates of cancer in new glargine vs. new NPH users while on treatment, adjusted for the propensity to receive one or the other insulin. There were 26 and 28 new cancer cases in new glargine and new NPH users for 1559 and 1126 person-years follow-up, respectively. There were no differences in the propensity-adjusted clinical characteristics between groups. The adjusted hazard ratio for the cancer incidence comparing glargine vs. NPH use was 0.65 (95% CI: 0.36-1.19. CONCLUSIONS: Insulin glargine is not associated with development of cancers when compared with NPH in this longitudinal and carefully retrieved EMR data.

  2. Insulin glargine and risk of cancer: a cohort study in the French National Healthcare Insurance Database

    OpenAIRE

    Blin, P.; Lassalle, R.; Dureau-Pournin, C.; Ambrosino, B.; Bernard, M. A.; Abouelfath, A.; Gin, H; Le Jeunne, C; Pariente, A.; Droz, C.; Moore, N

    2012-01-01

    Aims/hypothesis Using the Echantillon Généraliste de Bénéficiaires: random 1/97 permanent sample of the French national healthcare insurance system database (EGB), we investigated whether, as previously suspected, the risk of cancer in insulin glargine (A21Gly,B31Arg,B32Arg human insulin) users is higher than in human insulin users. The investigation period was from 1 January 2003 to 30 June 2010. Methods We used Cox proportional hazards time-dependent models that were stratified on propensit...

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

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    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.

  4. Insulin glargine in the management of diabetes mellitus: an evidence-based assessment of its clinical efficacy and economic value

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    Rhian Clissold

    2007-11-01

    Full Text Available Rhian Clissold1, Steve Clissold21Endocrinology Department, Frenchay Hospital, Bristol, UK; 2Content Ed Net Communications S.L., Madrid, SpainIntroduction: Diabetes is a chronic disease associated with high morbidity and mortality, which represents a major public health concern. Interventions that can enhance patient care and reduce clinic visits will not only relieve some of this burden, they will also improve patient QOL and wellbeing.Aims: This review assesses the evidence for the use of insulin glargine in type 1 and type 2 diabetes mellitus.Evidence review: Once-daily insulin glargine has a prolonged, peakless activity profile, making it a candidate as a long-acting (basal insulin. In combination with bolus insulin to cover prandial glucose surges, it facilitates a more physiologic approach to patient management. Evidence from large, randomized, controlled clinical trials in patients with type 1 diabetes has confirmed its effectiveness and tolerability relative to neutral protamine hagedorn (NPH insulin, with a tendency toward causing less hypoglycemia. In patients with type 2 diabetes requiring insulin therapy, once-daily insulin glargine has proven to be clinically superior to NPH insulin in terms of providing at least as effective glycemic control, but with significantly fewer episodes of nocturnal hypoglycemia. A variety of economic analyses have confirmed the cost effectiveness of insulin glargine in type 1 and type 2 diabetes and in particular it was shown to be significantly superior to NPH insulin.Clinical value: Insulin glargine has established itself as a first-line choice in patients with type 1 diabetes, including children (>6 years and adolescents, and is a recommended treatment option. In patients with type 2 diabetes it is clearly associated with less hypoglycemia than NPH insulin, and this may help overcome one of the major barriers to starting insulin therapy in this class of patient. Thus, insulin glargine is a valuable

  5. All-Cause and Cause-Specific Mortality among Users of Basal Insulins NPH, Detemir, and Glargine

    OpenAIRE

    Strandberg, Arto Y.; Hoti, Fabian J.; Strandberg, Timo E.; Christopher, Solomon; Haukka, Jari; Korhonen, Pasi

    2016-01-01

    Background Insulin therapy in type 2 diabetes may increase mortality and cancer incidence, but the impact of different types of basal insulins on these endpoints is unclear. Compared to the traditional NPH insulin, the newer, longer-acting insulin analogues detemir and glargine have shown benefits in randomized controlled trials. Whether these advantages translate into lower mortality among users in real life is unknown. Objective To estimate the differences in all-cause and cause-specific mo...

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

    Institute of Scientific and Technical Information of China (English)

    LIU Shan-ying; LIANG Ying; LIN Tian-xin; SU Fang; LIANG Wei-wen; Uwe Heemann; LI Yan

    2012-01-01

    Background 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.Methods 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.Results 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.Conclusion MEK1 inhibits while MEK2 contributes to normal and human insulin-and insulin glargine-induced human bladder cancer T24 cell proliferation.

  7. All-Cause and Cause-Specific Mortality among Users of Basal Insulins NPH, Detemir, and Glargine.

    Directory of Open Access Journals (Sweden)

    Arto Y Strandberg

    Full Text Available Insulin therapy in type 2 diabetes may increase mortality and cancer incidence, but the impact of different types of basal insulins on these endpoints is unclear. Compared to the traditional NPH insulin, the newer, longer-acting insulin analogues detemir and glargine have shown benefits in randomized controlled trials. Whether these advantages translate into lower mortality among users in real life is unknown.To estimate the differences in all-cause and cause-specific mortality rates between new users of basal insulins in a population-based study in Finland.23 751 individuals aged ≥40 with type 2 diabetes, who initiated basal insulin therapy in 2006-2009 were identified from national registers, with comprehensive data for mortality, causes of death, and background variables. Propensity score matching was performed on characteristics. Follow-up time was up to 4 years (median 1.7 years.2078 deaths incurred. With NPH as reference, the adjusted HRs for all-cause mortality were 0.39 (95% CI, 0.30-0.50 for detemir, and 0.55 (95% CI, 0.44-0.69 for glargine. As compared to glargine, the HR was 0.71 (95% CI, 0.54-0.93 among detemir users. Compared to NPH, the mortality risk for both cardiovascular causes as well as cancer were also significantly lower for glargine, and especially for detemir in adjusted analysis. Furthermore, the results were robust in various sensitivity analyses.In real clinical practice, mortality was substantially higher among users of NPH insulin as compared to insulins detemir or glargine. Considering the large number of patients who require insulin therapy, this difference in risk may have major clinical and public health implications. Due to limitations of the observational study design, further investigation using an interventional study design is warranted.

  8. Body Composition and Epicardial Fat in Type 2 Diabetes Patients Following Insulin Detemir Versus Insulin Glargine Initiation.

    Science.gov (United States)

    Elisha, B; Azar, M; Taleb, N; Bernard, S; Iacobellis, G; Rabasa-Lhoret, R

    2016-01-01

    The aim of the study was to compare body composition and epicardial fat thickness changes in insulin-naïve inadequately controlled patients with type 2 diabetes following basal insulin initiation with detemir vs. glargine. Six-month, open-label, interventional randomized pilot study was conducted. Dual-energy X-ray absorptiometry and echocardiography were used to estimate the body composition and epicardial fat thickness respectively. Thirty-six patients in the detemir group and 20 in the glargine group completed the study. Study groups baseline characteristics were comparable. At 6 months, for similar glycemic control, those on detemir significantly gained less total weight (0.6±2.5 vs. 4.2±4.1 kg, p=0.004), total fat mass (0.9±2.2 vs. 2.9±2.4 kg, p=0.02), and truncal fat mass (0.8±1.5 vs. 2.1±1.7 kg, p=0.02), with a loss in truncal lean mass (- 0.8±1.9 kg vs. 0.3±1.7 kg; p=0.02). EFT significantly decreased from baseline in both group (detemir - 1.7±0.52-mm, glargine - 1.1±1.6-mm; p<0.05, without significant difference inter-groups). Within the detemir group, epicardial fat thickness change correlated with truncal fat and total fat mass changes (r=0.65, p=0.06 and r=0.60, p=0.07). In conclusion, detemir resulted in less fat mass gain, a trend for a more pronounced epicardial fat thickness reduction when compared with glargine. PMID:26340704

  9. Disruption of KEX1 gene reduces the proteolytic degradation of secreted two-chain Insulin glargine in Pichia pastoris.

    Science.gov (United States)

    Sreenivas, Suma; Krishnaiah, Sateesh M; Shyam Mohan, Anil H; Mallikarjun, Niveditha; Govindappa, Nagaraja; Chatterjee, Amarnath; Sastry, Kedarnath N

    2016-02-01

    Insulin glargine is a slow acting analog of insulin used in diabetes therapy. It is produced by recombinant DNA technology in different hosts namely E. coli and Pichia pastoris. In our previous study, we have described the secretion of fully folded two-chain Insulin glargine into the medium by over-expression of Kex2 protease. The enhanced levels of the Kex2 protease was responsible for the processing of the glargine precursor with in the host. Apart from the two-chain glargine product we observed a small proportion of arginine clipped species. This might be due to the clipping of arginine present at the C-terminus of the B-chain as it is exposed upon Kex2 cleavage. The carboxypeptidase precursor Kex1 is known to be responsible for clipping of C-terminal lysine or arginine of the proteins or peptides. In order to address this issue we created a Kex1 knock out in the host using Cre/loxP mechanism of targeted gene deletion. When two-chain glargine was expressed in the Kex1 knock out host of P. pastoris GS115 the C-terminal clipped species reduced by ∼80%. This modification further improved the process by reducing the levels of product related impurities.

  10. Disruption of KEX1 gene reduces the proteolytic degradation of secreted two-chain Insulin glargine in Pichia pastoris.

    Science.gov (United States)

    Sreenivas, Suma; Krishnaiah, Sateesh M; Shyam Mohan, Anil H; Mallikarjun, Niveditha; Govindappa, Nagaraja; Chatterjee, Amarnath; Sastry, Kedarnath N

    2016-02-01

    Insulin glargine is a slow acting analog of insulin used in diabetes therapy. It is produced by recombinant DNA technology in different hosts namely E. coli and Pichia pastoris. In our previous study, we have described the secretion of fully folded two-chain Insulin glargine into the medium by over-expression of Kex2 protease. The enhanced levels of the Kex2 protease was responsible for the processing of the glargine precursor with in the host. Apart from the two-chain glargine product we observed a small proportion of arginine clipped species. This might be due to the clipping of arginine present at the C-terminus of the B-chain as it is exposed upon Kex2 cleavage. The carboxypeptidase precursor Kex1 is known to be responsible for clipping of C-terminal lysine or arginine of the proteins or peptides. In order to address this issue we created a Kex1 knock out in the host using Cre/loxP mechanism of targeted gene deletion. When two-chain glargine was expressed in the Kex1 knock out host of P. pastoris GS115 the C-terminal clipped species reduced by ∼80%. This modification further improved the process by reducing the levels of product related impurities. PMID:26470649

  11. 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

  12. 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.

  13. 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 di

  14. 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.

  15. Rationale, Design, and Baseline Data of the Insulin Glargine (Lantus) Versus Insulin Detemir (Levemir) Treat-To-Target (L2T3) Study: A Multinational, Randomized Noninferiority Trial of Basal Insulin Initiation in Type 2 Diabetes

    NARCIS (Netherlands)

    S.G.H.A. Swinnen; F.J. Snoek; M.P. Dain; J.H. DeVries; J.B.L. Hoekstra; F. Holleman

    2009-01-01

    Objective: To discuss the design and baseline data of the Lantus (R) (sanofi-aventis, Paris, France) versus Levemir (R) (Novo Nordisk A/S, Bagsvaerd, Denmark) Treat-To-Target (L2T3) study, a multinational, randomized comparison between the basal insulin analogs insulin glargine and insulin detemir.

  16. Health economic evaluations comparing insulin glargine with NPH insulin in patients with type 1 diabetes: a systematic review

    Directory of Open Access Journals (Sweden)

    Dippel Franz-Werner

    2011-10-01

    Full Text Available Abstract Background Compared to conventional human basal insulin (neutral protamine Hagedorn; NPH the long-acting analogue insulin glargine (GLA is associated with a number of advantages regarding metabolic control, hypoglycaemic events and convenience. However, the unit costs of GLA exceed those of NPH. This study aims to systematically review the economic evidence comparing GLA with NPH in basal-bolus treatment (intensified conventional therapy; ICT of type 1 diabetes in order to facilitate informed decision making in clinical practice and health policy. Methods A systematic literature search was performed for the period of January 1st 2000 to December 1st 2009 via Embase, Medline, the Cochrane Library, the databases GMS (German Medical Science and DAHTA (Deutsche Agentur für Health Technology Assessment, and the abstract books of relevant international scientific congresses. Retrieved studies were reviewed based on predefined inclusion criteria, methodological and quality aspects. In order to allow comparison between studies, currencies were converted using purchasing power parities (PPP. Results A total of 7 health economic evaluations from 4 different countries fulfilled the predefined criteria: 6 modelling studies, all of them cost-utility analyses, and one claims data analysis with a cost-minimisation design. One cost-utility analysis showed dominance of GLA over NPH. The other 5 cost-utility analyses resulted in additional costs per quality adjusted life year (QALY gained for GLA, ranging from € 3,859 to € 57,002 (incremental cost effectiveness ratio; ICER. The cost-minimisation analysis revealed lower annual diabetes-specific costs in favour of NPH from the perspective of the German Statutory Health Insurance (SHI. Conclusions The incremental cost-utility-ratios (ICER show favourable values for GLA with considerable variation. If a willingness-to-pay threshold of £ 30,000 (National Institute of Clinical Excellence, UK is adopted

  17. Real-world outcomes of US employees with type 2 diabetes mellitus treated with insulin glargine or neutral protamine Hagedorn insulin: a comparative retrospective database study

    OpenAIRE

    Wang, Li; Wei, Wenhui; Miao, Raymond; Xie, Lin; Baser, Onur

    2013-01-01

    Objectives To compare real-world outcomes of initiating insulin glargine (GLA) versus neutral protamine Hagedorn (NPH) insulin among employees with type 2 diabetes mellitus (T2DM) who had both employer-sponsored health insurance and short-tem-disability coverages. Design Retrospective cohort study. Setting MarketScan Commercial Claims and Encounters/Health and Productivity Management Databases 2003–2009. Participants Adult employees with T2DM who were previously treated with oral antidiabetic...

  18. Insulin

    Science.gov (United States)

    ... Short Acting Humulin N NPH Human Insulin (Human Insulin Isophane Suspension) Intermediate Acting Novolin N NPH Human Insulin (Human Insulin Isophane Suspension) Intermediate Acting Lantus Insulin Glargine Long Acting ...

  19. Comparison between the therapeutic effect of metformin, glimepiride and their combination as an add-on treatment to insulin glargine in uncontrolled patients with type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Cheol-Young Park

    Full Text Available To compare the commonly prescribed oral anti-diabetic drug (OAD combinations to use as an add-on therapy with insulin glargine in patients with uncontrolled type 2 diabetes despite submaximal doses of OADs.People with inadequately controlled type 2 diabetes (n = 99 were randomly assigned on a 1∶1∶1 basis to receive insulin glargin, with fixed doses of glimepiride, metformin, and glimepiride plus metformin. Outcomes assessed included HbA1c, the changes in fasting glucose levels, body weight, serum lipids values, insulin dose and symptomatic hypoglycemia.After 24 weeks, HbA1C levels improved from (mean ± SD 8.5±0.9% to 7.7±0.8% (69.0±10.0 mmol/mol to 60.8±8.6 mmol/mol with insulin glargine plus metformin, from 8.4±1.0% to 7.7±1.3% (68.8±10.6 mmol/mol to 61.1±14.4 mmol/mol with insulin glargine plus glimepiride and from 8.7±0.9% to 7.3±0.6% (71.7±9.8 mmol/mol to 56.2±6.7 mmol/mol with insulin glargine plus glimepirde plus metformin. The decrease in HbA1c was more pronounced with insulin glargine plus glimepiride plus metformin than with insulin glargine plus metformin (0.49% [CI, 0.16% to 0.82%]; P = 0.005 (5.10 mmol/mol [CI, 1.64 to 8.61]; P = 0.005 and insulin glargine plus glimepiride (0.59% [CI, 0.13% to 1.05%]; P = 0.012 (5.87 mmol/mol [CI, 1.10 to 10.64]; P = 0.012 (overall P = 0.02. Weight gain and the risk of hypoglycemia of any type did not significantly differ among the treatment groups.The combination therapy of metformin and glimepiride plus glargine insulin resulted in a significant improvement in overall glycemic control as compared with the other combinations.ClinicalTrials.gov, NCT00708578. The approval number of Kangbuk Samsung hospital's institutional review board (IRB: C0825.

  20. A case of hypersensitivity to soluble and isophane insulins but not to insulin glargine

    OpenAIRE

    Belhekar, Mahesh N; Sarayu Pai; Parimal Tayade; Pradip Dalwadi; Renuka Munshi; Prema Varthakavi

    2015-01-01

    Insulin is an important agent for the treatment of diabetes mellitus (DM). Allergic reactions to insulin therapy, although rare, have been evident since animal insulin became available for the treatment of DM in 1922. Hypersensitivity to insulin has considerably been reduced with the introduction of human insulin produced by recombinant deoxyribonucleic acid technology. Here, we present a case of Type 2 DM who demonstrated immediate (Type 1) hypersensitivity reaction on the sites of subcutane...

  1. 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

    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.......8 mg once daily (n = 232), liraglutide placebo (n = 115) and open-label insulin glargine (n = 234), all in combination with metformin (1 g twice daily) and glimepiride (4 mg once daily). Investigators, participants and study monitors were blinded to the treatment status of the liraglutide and placebo...

  2. 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

  3. One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial

    NARCIS (Netherlands)

    Bunck, M.C.M.; Diamant, M.; Corner, A.; Eliasson, B.; Malloy, J.L.; Shaginian, R.M.; Deng, W.; Kendall, D.M.; Taskinen, M.R.; Smith, U.; Yki-Jarvinen, H.; Heine, R.J.

    2009-01-01

    0.0001). beta-Cell function measures returned to pretreatment values in both groups after a 4-week off-drug period. A1C and body weight rose to pretreatment values 12 weeks after discontinuation of either exenatide or insulin glargine therapy. CONCLUSIONS: Exenatide significantly improves beta-cell

  4. 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

    2016-09-01

    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 < 180 mg/dl, n = 1), less tight (LT: 110-150 mg/dL, n = 5), and tight (T: 70-100 mg/dL, n = 5). During the next 30 days daily contacts were used to adapt the insulin dose. The majority of all patients (70%) achieved a stable insulin glargine dose within 5 ± 6 days after initiation of the dose 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

  5. Improving treatment satisfaction and other patient-reported outcomes in people with type 2 diabetes: the role of once-daily insulin glargine.

    Science.gov (United States)

    Bradley, C; Gilbride, C J B

    2008-07-01

    Insulin therapy becomes essential for many people with type 2 diabetes. After starting insulin, people with diabetes that is poorly controlled with oral agents typically report improved well-being and treatment satisfaction. However, healthcare professionals and people with type 2 diabetes are often reluctant to begin insulin treatment, citing concerns such as time/resources needed to educate patients, increased risks of hypoglycaemia and fear of injections, which lead them to focus on intensifying conventional oral therapy. Insulin glargine, which offers people with diabetes a once-a-day injection regimen with low risk of hypoglycaemia, is more likely to overcome such initial barriers than other more complex insulin regimens. Once-daily insulin glargine, in combination with modern glucose-dependent oral agents that do not need to be chased with food to prevent hypoglycaemia, does not require the fixed mealtimes and set amounts of carbohydrates necessary with twice-daily injection mixes and older sulphonylureas. We know that it is such dietary restrictions that cause the most damage to quality of life (QoL). To avoid damaging QoL unnecessarily and to ensure optimal satisfaction with treatment, it is important to evaluate the effects of treatment on QoL, treatment satisfaction and other patient-reported outcomes (PROs) using questionnaires validated for this purpose, such as the widely used Diabetes Treatment Satisfaction Questionnaire and the Audit of Diabetes-Dependent Quality of Life measure. A systematic electronic literature search identified reports of studies evaluating PROs associated with insulin glargine in comparison with other treatments. The studies show that insulin glargine is usually associated with greater improvements in treatment satisfaction and other PROs compared with intensifying oral therapy or alternative insulin regimens. PMID:18577157

  6. The cost-effectiveness of insulin glargine vs. neutral protamine Hagedorn insulin in type 2 diabetes: a focus on health economics.

    Science.gov (United States)

    Levin, P

    2008-07-01

    Diabetes mellitus is a major public health problem, in particular because of long-term complications affecting essential organs, such as the eyes and kidneys, which can lead to a reduction in life expectancy and high healthcare costs. The number of individuals with diabetes mellitus is projected to rise worldwide from 171 million people in 2000 to 366 million people in 2030. With the number of patients with diabetes continually growing, the burden of pressure on worldwide health systems is huge. Accordingly, regulatory and marketing approvals of new medicines are beginning to incorporate economic evaluation techniques to determine their cost-effectiveness. Overall, the studies included in this review show that the initiation of insulin glargine is cost-effective and is expected to lead to substantial improvements in both life years (LYs) and quality-adjusted LYs compared with neutral protamine Hagedorn insulin. PMID:18577158

  7. 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

    OpenAIRE

    Ruiter, Rikje; Visser, Loes; Coebergh, Jan Willem; Herk-Sukel, Myrthe; Haak, H.R.; Geelhoed-Duijvestijn, P.H.; Straus, Sabine; Herings, Ron; Stricker, Bruno

    2012-01-01

    Aims/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 cohort study. Methods Data for this study were obtained from dispensing records from community pharmacies individually linked to hospital discharge records from 2.5 million individuals in the Netherlands. In a...

  8. Enhancement in production of recombinant two-chain Insulin Glargine by over-expression of Kex2 protease in Pichia pastoris.

    Science.gov (United States)

    Sreenivas, Suma; Krishnaiah, Sateesh M; Govindappa, Nagaraja; Basavaraju, Yogesh; Kanojia, Komal; Mallikarjun, Niveditha; Natarajan, Jayaprakash; Chatterjee, Amarnath; Sastry, Kedarnath N

    2015-01-01

    Glargine is an analog of Insulin currently being produced by recombinant DNA technology using two different hosts namely Escherichia coli and Pichia pastoris. Production from E. coli involves the steps of extraction of inclusion bodies by cell lysis, refolding, proteolytic cleavage and purification. In P. pastoris, a single-chain precursor with appropriate disulfide bonding is secreted to the medium. Downstream processing currently involves use of trypsin which converts the precursor into two-chain final product. The use of trypsin in the process generates additional impurities due to presence of Lys and Arg residues in the Glargine molecule. In this study, we describe an alternate approach involving over-expression of endogenous Kex2 proprotein convertase, taking advantage of dibasic amino acid sequence (Arg-Arg) at the end of B-chain of Glargine. KEX2 gene over-expression in Pichia was accomplished by using promoters of varying strengths to ensure production of greater levels of fully functional two-chain Glargine product, confirmed by HPLC and mass analysis. In conclusion, this new production process involving Kex2 protease over-expression improves the downstream process efficiency, reduces the levels of impurities generated and decreases the use of raw materials. PMID:25239036

  9. 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

    NARCIS (Netherlands)

    T.R.S. Hajos; F. Pouwer; R. de Grooth; F. Holleman; J.W.R. Twisk; M. Diamant; F.J. Snoek

    2011-01-01

    Diabet. Med. 28, 1096-1102 (2011) ABSTRACT: 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 Typ

  10. Intensification of insulin therapy in patients with type 2 diabetes: a retrospective, non- interventional cohort study of patients treated with insulin glargine or biphasic human insulin in daily clinical practice

    Science.gov (United States)

    2013-01-01

    Background The aim of this study is to compare the efficacy of intensification of insulin treatment with insulin glargine and biphasic human insulin in patients with type 2 diabetes on concomitant therapy with oral antidiabetic drugs (OAD) in daily clinical practice. Methods A retrospective multicentre parallel two-arm study included 301 patients with type 2 diabetes already on treatment with biphasic human insulin twice daily (bd) in combination with OAD. Data were collected retrospectively from 142 patients who had been switched from biphasic human insulin to insulin glargine in a period of 6–12 months prior to their inclusion (active group) and compared to data collected retrospectively from 159 patients who continued treatment with biphasic human insulin bd for the same time period (control group). Our primary objective was to examine the efficacy of the two treatments, assessed as change in HbA1c. Secondary objectives were to examine for changes in fasting blood glucose (FBG), body weight, treatment with OAD or fast-acting insulin and safety, by assessing the frequency and severity of hypoglycaemic episodes. Results At the end of the study there was a significant reduction in HbA1c in both arms. The least squares (LS) mean [(95% confidence intervals (CI)] reduction in HbA1c was -1.13 (-0.96 to -1.30)% in the active and -0.59 (-0.41to -0.77)% in the control group [LS mean treatment difference 0.53 (0.31-0.76)%, p < 0.001]. Similarly, fasting blood glucose declined significantly in both arms. The LS mean decline in FBG was -47.02 (-37.89 to -56.14) mg/dl in the active and -19.73 (-11.57 to -27.89) mg/dl in the control group [LS mean treatment difference 27.85 (15.74-39.95) mg/dl, p < 0.001]. No significant difference in hypoglycaemic episodes and in body weight was found. In the active group, more patients received rapid-acting pre-meal insulin and used insulin secretagogues drugs. Conclusions Glargine alone or in combination with fast acting insulin

  11. 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

    Science.gov (United States)

    Varewijck, Aimee J.; Yki-Järvinen, Hannele; Schmidt, Ronald; Tennagels, Norbert; Janssen, Joseph A.M.J.L.

    2013-01-01

    We 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 long-term insulin therapy in type 2 diabetic patients; and 3) IR-A and IR-B activation in vitro induced by serum from patients treated with GLA or NPH insulin. A total of 104 patients (age 56.3 ± 0.8 years, BMI 31.4 ± 0.5 kg/m2, and A1C 9.1 ± 0.1% [mean ± SE]) were randomized to GLA or NPH insulin therapy for 36 weeks. Plasma concentrations of GLA, M1, and M2 were determined by liquid chromatography–tandem mass spectrometry assay. IR-A, IR-B, and IGF-IR autophosphorylation was induced by purified hormones or serum by kinase receptor activation assays. In vitro, M1 induced comparable IR-A, IR-B, and IGF-IR autophosphorylation (activation) as NPH insulin. After 36 weeks, M1 increased from undetectable (<0.2 ng/mL) to 1.5 ng/mL (0.9–2.1), while GLA and M2 remained undetectable. GLA dose correlated with M1 (r = 0.84; P < 0.001). Serum from patients treated with GLA or NPH insulin induced similar IR-A and IR-B activation. These data suggest that M1 rather than GLA mediates GLA effects and that compared with NPH insulin, GLA does not increase IGF-IR signaling during long-term insulin therapy in type 2 diabetes. PMID:23569175

  12. 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

    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...... group and 131 (69%) in the lispro group. In the glargine group, the fall in mean fasting blood glucose (-4.3 [SD 2.3] mmol/L vs -1.8 [2.3] mmol/L; p<0.0001) and nocturnal blood glucose (-3.3 [2.8] mmol/L vs -2.6 [2.9] mmol/L; p=0.0041) was better than it was in the insulin lispro group, whereas insulin...... lispro better controlled postprandial blood glucose throughout the day (p<0.0001). The incidence of hypoglycaemic events was less with insulin glargine than with lispro (5.2 [95% CI 1.9-8.9] vs 24.0 [21-28] events per patient per year; p<0.0001). Respective mean weight gains were 3.01 (SD 4.33) kg and 3...

  13. Sitagliptin/Metformin Versus Insulin Glargine Combined With Metformin in Obese Subjects With Newly Diagnosed Type 2 Diabetes.

    Science.gov (United States)

    Ji, Ming; Xia, Libin; Cao, Jingzhu; Zou, Dajin

    2016-03-01

    To compare the therapeutic effects of different regimens in Chinese obese type 2 diabetic mellitus (T2DM) patients. From October 2013 to July 2014, a total of 166 T2DM outpatients who attended the Shanghai Changhai Hospital and the Yijishan Hospital of Wannan Medical College were randomly assigned into an experimental sitagliptin/metformin combined with low caloric diet group (n = 115) and an insulin glargine combined with metformin control group (n = 51). Inclusion criteria were body mass index (BMI) ≥ 25 kg/m and diagnosed with T2DM with glycosylated hemoglobin (glycated hemoglobin A1C [HbA1c]) >9%. Main outcome parameters were fasting plasma glucose, postprandial plasma glucose, BMI, HbA1c, fasting C-peptide, 2-h postprandial C-peptide, triglyceride (TG), total cholesterol (TC), high-density cholesterol (HDL-C), and low-density cholesterol (LDL-C), which were determined by the 75 g steamed-bun meal tolerance test before and 4, 8, 12, and 24 weeks after the treatment started. Treatment costs and life quality were also assessed. BMI, HbA1C, TG, TC, and LDL were significantly more reduced (P 9%, oral sitagliptin/metformin combined with a low caloric diet effectively and economically maintained glycemic control and significantly improved life quality.

  14. The Evolution of Insulin Glargine and its Continuing Contribution to Diabetes Care

    OpenAIRE

    Hilgenfeld, Rolf; Seipke, Gerhard; Berchtold, Harald; Owens, David R.

    2014-01-01

    The epoch-making discovery of insulin heralded a new dawn in the management of diabetes. However, the earliest, unmodified soluble insulin preparations were limited by their short duration of action, necessitating multiple daily injections. Initial attempts to protract the duration of action of insulin involved the use of various additives, including vasoconstrictor substances, which met with limited success. The subsequent elucidation of the chemical and three-dimensional structure of insuli...

  15. Similar risk of exercise-related hypoglycaemia for insulin degludec to that for insulin glargine in patients with type 1 diabetes: a randomized cross-over trial.

    Science.gov (United States)

    Heise, T; Bain, S C; Bracken, R M; Zijlstra, E; Nosek, L; Stender-Petersen, K; Rabøl, R; Rowe, E; Haahr, H L

    2016-02-01

    We compared changes in blood glucose (BG) and risk of hypoglycaemia during and after exercise in 40 patients with type 1 diabetes (T1D) treated with insulin degludec (IDeg) or insulin glargine (IGlar) in a randomized, open-label, two-period, crossover trial. After individual titration and a steady-state period, patients performed 30 min of moderate-intensity cycle ergometer exercise (65% peak rate of oxygen uptake). BG, counter-regulatory hormones and hypoglycaemic episodes were measured frequently during and for 24 h after exercise. BG changes during exercise were similar with IDeg and IGlar [estimated treatment difference (ETD) for maximum BG decrease: 0.14 mmol/l; 95% confidence interval (CI) -0.15, 0.42; p = 0.34], as was mean BG (ETD -0.16 mmol/l; 95% CI -0.36, 0.05; p = 0.13). No hypoglycaemic episodes occurred during exercise. Post-exercise mean BG, counter-regulatory hormone response and number of hypoglycaemic episodes in 24 h after starting exercise were similar with IDeg (18 events in 13 patients) and IGlar (23 events in 15 patients). This clinical trial showed that, in patients with T1D treated with a basal-bolus regimen, the risk of hypoglycaemia induced by moderate-intensity exercise was low with IDeg and similar to that with IGlar. PMID:26450456

  16. 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

    Science.gov (United States)

    Kumar, Ajay; Franek, Edward; Wise, Jonathan; Niemeyer, Marcus; Mersebach, Henriette; Simó, Rafael

    2016-01-01

    Purpose 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. Methods 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. Results 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 administration of IDegAsp with the main meal of the day, tailored to the individual patient’s needs. Trial Registration ClinicalTrials.gov: NCT01045707 [core]) and NCT01169766 [ext] PMID:27760129

  17. Insulin Glargine Combined with Glimepiride for Treating Type 2 Diabetes in 55 Cases%甘精胰岛素联合格列美脲治疗2型糖尿病55例

    Institute of Scientific and Technical Information of China (English)

    吕敏

    2015-01-01

    Objective To analyze the efficacy of insulin glargine combined with glimepiride in treating type 2 diabetes. Methods 110 cases of patients with type 2 diabetes in the outpatient department from January 2013 to January 2015 were randomly divided into the combination group ( insulin glargine combined with glimepiride ) and insulin group ( insulin glargine only ) , 55 cases in each group. Results The fasting blood glucose ( FBG ) , postprandial 2 h plasma glucose ( 2 hPG ) , HbA1C in the combination group and in-sulin group after 12 weeks of treatment were significantly lower than before treatment ( P 0. 05 ) . Conclusion Compared with using insulin glargine alone, glargine combined with glimepiride has better control of blood sugar levels in type 2 diabetes, decrease the insulin dose and improve the islet cell function.%目的 观察甘精胰岛素联合格列美脲治疗2型糖尿病的疗效.方法 选取2013年1月至2015年1月门诊收治的2型糖尿病患者110例,随机分为联合组(甘精胰岛素联合格列美脲治疗)和胰岛素组(单用甘精胰岛素),各55例.结果 两组患者治疗12周后的空腹血糖(FBG)、餐后2 h血糖(2 hPG)、糖化血红蛋白( HbA1C )显著低于治疗前( P0. 05).结论 与单用甘精胰岛素相比,甘精胰岛素联合格列美脲能更好地控制2型糖尿病血糖水平,降低胰岛素使用剂量,改善胰岛细胞功能.

  18. Long-acting insulin analogues (insulin glargine or determir) and continuous subcutaneous insulin infusion in the treatment of type 1 diabetes mellitus in the paediatric population.

    Science.gov (United States)

    Barrio Castellanos, Raquel

    2005-12-01

    Despite many improvements in the treatment of type 1 diabetes mellitus (DM1), the non-physiological time-action profiles of conventional insulins remain a significant obstacle. In recent years, recombinant DNA technology has been used to design insulin molecules that overcome the limitations of regular and NPH insulin. The rapid insulin analogs used as prandial and the long-acting insulin analogs used as basal simulate physiological insulin profiles more closely than the older conventional insulins. The efficacy of insulin analogs now available for multiple daily injection (MDI) and continuous subcutaneous insulin infusion (CSII) therapy in DM1 has been established in pediatric patients. Insulin pumps have improved since they were first introduced. CSII therapy may provide an effective alternative for selected pediatric patients with DM1. In most studies at pediatric age, CSII therapy resulted in a improvement in HbA1c, a decreased rate of hypoglycemia without an abnormal increase in BMI, and without adversely affecting psychosocial outcomes in children and adolescents with DM1. PMID:16398447

  19. 甘精胰岛素联合格列美脲治疗2型糖尿病80例%Insulin Glargine Combined Glimepiride for Treating 80 Cases of Type 2 Diabetes Mellitus

    Institute of Scientific and Technical Information of China (English)

    傅海东

    2012-01-01

    Objective To explore the efficacy and safety of insulin glargine combined glimepiride in the treatment of type II diabetes meUitus (T2DM). Methods Eighty cases of T2DM with fasting blood glucose (FBG) ≥ 10 mmol/L in our hospital from October 2008 to September 2011 were treated with insulin glargine by subcutaneous injection before going to bed and oral glimepiride for 12 weeks. The dosage of insulin was adjusted according to FBG levels, the goals of treatment was 5. 5 mmol/L 0. 05). Conclusion Insulin glargine combined glimepiride is effective for treating T2DM with the low rate of hypoglycemia and good safety, which is the ideal treatment scheme of T2DM.%目的 探讨甘精胰岛素联合格列美脲治疗2型糖尿病的疗效和安全性.方法 选择医院2008年10月至2011年9月收治的80例2型糖尿病患者[空腹血糖(FBG)不低于10 mmol/L],给予睡前皮下注射甘精胰岛素联合口服格列美脲治疗12周,根据FBG水平调整胰岛素用量,治疗目标为5.5 mmol/L0.05).结论 甘精胰岛素联合格列美脲治疗2型糖尿病的疗效好,低血糖发生率低,安全性好,是治疗2型糖尿病的理想方案.

  20. Insulin glargine combined with glimepiride in treatment of elderly patients with diabetes clinical effectiveness evaluation%甘精胰岛素联合格列美脲治疗老年糖尿病临床效果初评

    Institute of Scientific and Technical Information of China (English)

    周英; 吴强

    2015-01-01

    目的:对甘精胰岛素联合格列美脲治疗老年糖尿病临床效果进行评估.方法 :选取我院2013年至2014年收治的90例老年糖尿病患者作为本次研究的对象 ,随机分成观察和对照组各45 例.对照组采用鱼精蛋白锌胰岛素(N P H )联合格列美脲治疗法 ;观察组采用甘精胰岛素联合格列美脲治疗法.结果 :两组患者治疗后各项指标均有所改善.结论 :甘精胰岛素联合格列美脲治疗老年糖尿病有显著效果.%Objective:the clinical effect of diabetes on insulin glargine combined with glimepiride treatment is evaluated .Methods :90 cases of elderly patients with diabetes in our hospital from 2013 to 2014 were as the research object ,randomly divided into observation and control group with 45 cases in each group .Patients in control group were treated with protamine zinc insulin (NPH) combined with glimepiride therapy ;the observation group treated with insulin glargine combined with glimepiride therapy .Results :the two groups of patients after treatment ,the indexes were improved .Conclu-sion:insulin glargine combined with glimepiridein treatment of elderly patients with diabetes have a significant effect .

  1. 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.

  2. 格列美脲联合甘精胰岛素治疗2型糖尿病的疗效%Efficacy of glimepiride in combination with insulin glargine in treating type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    公永明; 赵敏

    2011-01-01

    Objective; To observe the efficacy of glimepiride + insulin glargine in type 2 diabetes patients with secondary failure to sulfonylurea (SFS). Methods; Patients treated with glimepiride in combination with injection of insulin glargine (n =24) or Humulin 30R (n =30). The blood glucose, glycated hemoglobin (HbAlc) and serum C peptide were measured and compared at 12 weeks after treatment. Results; Both blood glucose and HbAlc were decreased (P<0.01 or <0. 05), and C peptide increased (P <0.05) after the two treatments. Conclusions; Treatment with glimepiride plus insulin glargine has satisfactory effect and may improve β cell function in patients with type 2 diabetes.%目的:观察磺脲类药物继发性失效者联合甘精胰岛素治疗2型糖尿病的疗效及胰岛β细胞功能变化.方法:对磺脲类药物继发性失效患者改用格列美脲,睡前分别注射甘精胰岛素(甘精组,24例)、优泌林30R(优泌林组,30例),12周后比较两组血糖、糖化血红蛋白(HbA1c)以及血清C肽的变化.结果:两组血糖和HbA1c均有下降(P<0.01或P<0.05),治疗后C肽升高(P<0.05).结论:联合甘精胰岛素治疗2型糖尿病有较好疗效,并有可能改善β细胞的功能.

  3. 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

  4. Effect of Insulin Analogues on Insulin/IGF1 Hybrid Receptors: Increased Activation by Glargine but Not by Its Metabolites M1 and M2

    OpenAIRE

    Cécile Pierre-Eugene; Patrick Pagesy; Tuyet Thu Nguyen; Marion Neuillé; Georg Tschank; Norbert Tennagels; Cornelia Hampe; Tarik Issad

    2012-01-01

    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 presenc...

  5. 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

  6. Observe the use of insulin glargine in diabetic stroke rehabilitation%甘精胰岛素在糖尿病脑卒中康复的应用观察

    Institute of Scientific and Technical Information of China (English)

    李锐莉; 李莲花; 兰倩

    2014-01-01

    目的:观察甘精胰岛素联合口服降糖药物在2型糖尿病脑卒中康复治疗中的疗效。方法将2型糖尿病脑卒中患者80例随机分为试验组和对照组,每组40例,2组均行常规康复治疗。试验组给予入院后胰岛素的强化治疗,7 d~10 d后甘精胰岛素联合一种降糖药物降血糖,对照组给予常规口服药物降血糖。观察2组患者治疗后4周、8周神经功能评分,比较患者康复治疗疗效。结果试验组康复效果优于对照组,尤以治疗后8周效果显著。结论甘精胰岛素在糖尿病脑卒中康复治疗中具有良好作用,值得推广。%Objective Clinical observation of insulin glargine combined with oral hypoglycemic drugsin type2 diabetes, stroke rehabilitation. Methods 80 cases of type 2 diabeticpatients with stroke,randomly divided into experimental group,control group.40 patients in each group,two groups were given conventional rehabilitation therapy. The experimental group received intensive therapy of insulinafter admission ,7-10 days after insulin glargine combined with a hypoglycemic drug reducing blood sugar.The control group was given conventional oral hypoglycemicdrugs. The two groups were observed respectively after treatment 4 weeks,8 weeks,the use of neural function score,compared with the effect of rehabilitation therapy. Results The effect of experimental group is better than the control group. Conclusion insulin glargine have a good effect on stroke rehabilitation in the treatment of diabetes.

  7. 30 cases of metformin combined with insulin glargine in the treatment of type 2 diabetes mellitus curative effect analysis%30例二甲双胍联合甘精胰岛素治疗2型糖尿病疗效分析

    Institute of Scientific and Technical Information of China (English)

    杨丽明

    2012-01-01

    Objective To observe the effect of metformin combined with insulin glargine in the treatment of type 2 diabetes mellitus. Methods 30 cases of type 2 diabetes mellitus patients with metformin combined with insulin glargine in the treatment curative effect analysis. Results the fasting plasma glucose and glycosylated hemoglobin decreased significantly, no hypoglycemia, weight index declined. Conclusion metformin combined with insulin glargine in the treatment of type 2 diabetes mellitus patients with medicine, from the good, safe, effective, feasible.%目的观察二甲双胍联合甘精胰岛素治疗2型糖尿病的疗效。方法对30例2型糖尿病患者经二甲双胍联合甘精胰岛素治疗疗效进行临床分析。结果空腹血糖及糖化血红蛋白明显下降,无低血糖发生,体重指数有所下降。结论二甲双胍联合甘精胰岛素治疗2型糖尿病,患者医从性好,安全、有效,具有可行性。

  8. The therapeutic effect of insulin glargine versu NPH insulin as add-on therapy to previous acarbose or metformin in senile obese type 2 diabetics%加用甘精胰岛素对老年肥胖2型糖尿病口服降糖药控制不佳患者的疗效

    Institute of Scientific and Technical Information of China (English)

    王宾; 胡桂荣; 何丽; 孟红旗; 党静; 谢淑薏

    2012-01-01

    Objective To study the effectiveness and safety of insulin glargine versus isophane insulin as add-on therapy to previous OHA in senile obese type 2 diabetic patients who failed to control their blood glucose with oral hypoglycemic agents (OHA). Methods Sixty-one patients who failed to control their blood glucose with OHA were randomized into insulin glargine group and isophane insulin group. They were administered previous acarbose and/or metformin tablet and insulin glargine or isophand insulin as add-on therapy. The observation lasted for 12 weeks. Result (1) Both groups showed significant difference in HbAic FPG, and 2 hPG compared with before treatment, and in HbA1c and 2 hPG between the two groups (all P0. 05). (2) The BMI of the insulin glargine group was reduced by 2. 7 kg/m2 compared with before treatment) while that of the isophand insulin group was basically unchanged compared with before treatment (3) The 45. 2% of patients with insulin glargine treatment and the 73. 3% of patients with isophand insulin treatment had symptomatic hypoglycemia, and the difference was statistically significant (P<0. 05). (4) At the end of treatment, the dosa of insulin glargine group and isophand insulin group was (18. 7±3. 5) U/d and (26. 0±3. 7) U/d respectively, and the difference was statistically significant (P<0. 05). Conclusion The combination of insulin glargine with acarbose and/or metfonnin is effective in controlling the blood glucose, decreasing the incidence of hypoglycemia,and controlling the body weight of senile obese type 2 diabetic patients.%目的 研究口服降糖药控制不佳的老年肥胖T2DM患者加用甘精胰岛素或中效胰岛素联合应用治疗的有效性和安全性. 方法 将口服降糖药控制不佳的老年肥胖T2DM患者61例随机分为甘精胰岛素组和中效胰岛素组,治疗期内阿卡波糖和(或)二甲双胍剂量不变,分别加用甘精胰岛素或中效胰岛素每晚睡前注射1次联合治疗,进行12

  9. 甘精胰岛素联合格列美脲片治疗2型糖尿病的疗效观察%Efficacy of insulin glargine plus glimepiride for type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    谢彬; 熊晓清; 冉建民

    2010-01-01

    Objective To investigate the efficacy and safety of insulin glargine plus glimepiride in the treatment of type 2 diabetic patients. Methods Sixty patients poorly responsive to oral sulfonylureas were randomly assigned to receive oral glimepiride plus injections of either insulin glargine (GL group, 30 patients) or neural protamine hagedorn (NPH group, 30 patients) for 12 weeks. Levels of fasting blood glucose and C-peptide, postprandial blood glucose and C-peptide, and HbAlc were detected 12 weeks after treatment. Results The fasting and postprandial blood glucose levels were significantly decreased. The incidence of hypoglycemia was lower in GL group than in NPH group (P<0.05) and C-peptide level was markedly higher. Conclusions Combination therapy with insulin glargine and glimepiride for type 2 diabetes is safe, effective, simple, and feasible. It can reduce the incidence of hypoglycemia and improve pancreatic function.%目的 探讨甘精胰岛素联用格列美脲片治疗磺脲类药物继发性失效的2型糖尿病患者的疗效及安全性.方法 60例口服磺脲类降糖药血糖控制不理想的2型糖尿病患者随机分为甘精胰岛素治疗组(GL组)和中性鱼精蛋白锌胰岛素(NPH)组,予睡前皮下注射胰岛素联合口服格列美脲治疗12周,观察12周前后空腹血糖、餐后2h血糖、糖化血红蛋白、空腹C肽、餐后C肽的变化.结果 GL组治疗后FPG(6.3±1.4)mmol/L,2hPG(8.7±1.4)mmol/L,HbAlc(6.7±0.61%;NPH组治疗后FPG(6.4±1.0)mol/L,2hPG(8.8 4±1.2)mmol/L,HbAlc(6.6±0.7)%,较治疗前差异有极显著性(P<0.01);但GL组的低血糖事件明显少于NPH组(P<0.05).且GL组治疗后C肽水平明显升高.结论 甘精胰岛素联用格列美脲片治疗2型糖尿病的方案安全有效,简便易行,能减少低血糖事件的发生,且可能改善胰岛功能.

  10. Clinical effect of insulin glargine and insulin aspart on poorly controlled patients with type 2 diabetes mellitus%甘精胰岛素联合门冬胰岛素对血糖控制不佳的2型糖尿病患者临床疗效分析

    Institute of Scientific and Technical Information of China (English)

    邬培红

    2013-01-01

    目的 探讨甘精胰岛素联合门冬胰岛素治疗血糖控制不佳的2型糖尿病(T2DM)患者的临床疗效.方法 将86例T2DM患者随机分为2组,每组43例.观察组给予甘精胰岛素联合门冬胰岛素,对照组给予精蛋白生物合成人胰岛素联合生物合成人胰岛素.比较治疗3个月后2组空腹血糖(FPG)、餐后2h血糖(2 hPG)、糖化血红蛋白(HbAlc)水平的变化,以及血糖达标时间、体质量增加量、胰岛素日用量、血糖日波动量及低血糖发生率的差异.结果 观察组FPG、2hPG、HbAlc水平的改善幅度大于对照组;观察组血糖达标时间、体质量增加量、血糖日波动量及低血糖发生率均显著小于对照组.结论 对于血糖控制不佳的T2DM患者,甘精胰岛素与门冬胰岛素联合应用可理想控制血糖,减少体质量增加量,降低低血糖发生率,是安全而有效的胰岛素强化治疗方案.%Objective To explore the clinical effects of insulin glargine and insulin aspart on poorly controlled patients with type 2 diabetes mellitus (T2DM). Methods Eighty - six patients with T2DM were randomly divided into two groups, 43 cases in each group. The observation group received insulin glargine and insulin aspart, while the control group received biosynthetic human insulin and isophane protamine biosynthetic human insulin. After 3 - month treatment, the changes of fasting plasma glucose (FPG), plasma glucose 2 h after meals (2 hPG) and glycosylated hemoglobin (HbAlc) as well as the differences of target - hitting time of blood glucose, body mass increment, daily dosage of insulin, daily fluctuation quantity of insulin and hypoglycemic incidence in both groups were compared. Results The improved degrees of FPG, 2 hPG and HbAlc in the observation group were higher than that in the control group. The target - hitting time of blood glucose, body mass increment, daily dosage of insulin and hypoglycemic incidence in the observation group were

  11. One-year sustained glycaemic control and less hypoglycaemia with new insulin glargine 300 U/ml compared with 100 U/ml in people with type 2 diabetes using basal plus meal-time insulin: the EDITION 1 12-month randomized trial, including 6-month extension

    Science.gov (United States)

    Riddle, M C; Yki-Järvinen, H; Bolli, G B; Ziemen, M; Muehlen-Bartmer, I; Cissokho, S; Home, P D

    2015-01-01

    Aims To evaluate the maintenance of efficacy and safety of insulin glargine 300 U/ml (Gla-300) versus glargine 100 U/ml (Gla-100) in people with type 2 diabetes mellitus (T2DM) using basal plus meal-time insulin for 12 months in the EDITION 1 trial. Methods EDITION 1 was a multicentre, randomized, open-label, two-arm, phase IIIa study. Participants completing the initial 6-month treatment period continued to receive Gla-300 or Gla-100, as previously randomized, once daily for a further 6-month open-label extension phase. Changes in glycated haemoglobin (HbA1c) and fasting plasma glucose concentrations, insulin dose, hypoglycaemic events and body weight were assessed. Results Of 807 participants enrolled in the initial phase, 89% (359/404) assigned to Gla-300 and 88% (355/403) assigned to Gla-100 completed 12 months. Glycaemic control was sustained in both groups (mean HbA1c: Gla-300, 7.24%; Gla-100, 7.42%), with more sustained HbA1c reduction for Gla-300 at 12 months: least squares mean difference Gla-300 vs Gla-100: HbA1c −0.17 [95% confidence interval (CI) −0.30 to −0.05]%. The mean daily basal insulin dose at 12 months was 1.03 U/kg for Gla-300 and 0.90 U/kg for Gla-100. Lower percentages of participants had ≥1 confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemic event with Gla-300 than Gla-100 at any time of day [24 h; 86 vs 92%; relative risk 0.94 (95% CI 0.89–0.99)] and during the night [54 vs 65%; relative risk 0.84 (95% CI 0.75–0.94)], while the annualized rates of such hypoglycaemic events were similar. No between-treatment differences in adverse events were apparent. Conclusion During 12 months of treatment of T2DM requiring basal and meal-time insulin, glycaemic control was better sustained and fewer individuals reported hypoglycaemia with Gla-300 than with Gla-100. The mean basal insulin dose was higher with Gla-300 compared with Gla-100, but total numbers of hypoglycaemic events and overall tolerability did not differ between

  12. 加用甘精胰岛素或中效胰岛素的2型糖尿病患者血糖波动的比较%Comparison of the excursion of blood glucose in type 2 diabetes injected glargine and human isophane insulin

    Institute of Scientific and Technical Information of China (English)

    曾龙驿; 穆攀伟; 张国超; 陈燕铭; 傅静奕; 王曼曼

    2009-01-01

    目的 比较空腹血糖控制不佳的2型糖尿病患者加用甘精胰岛素(glargine)或中效胰岛素治疗对血糖波动的影响.方法 30例口服抗糖尿病药治疗的2型糖尿病患者(空腹血糖>9.0 mmoL/L,HbA1C> 8.5%),按1:1随机分成两组,分别加用甘精胰岛素(来得时(R))或中效胰岛素(诺和灵(R)N)联合治疗.以空腹指尖毛细血管血糖0.05).结论 空腹血糖控制不佳的2型糖尿病患者加用甘精胰岛素比加用中效胰岛素治疗更有利于血糖的平稳,且不增加低血糖的风险.%Objective To compare the excursion of blood glucose (BG) in the type 2 diabetes mellitus treated with oral antidiabetic drugs (OADs) plus glargine or human isophane insulin (HII). Methods A 1 : 1 randomization schedule assigned 30 type 2 diabetics inadequately controlled on OADs (fasting BG>9.0 mmol/L and HbA1C > 8.5%) to 2 groups additionally treated with glargine or HII. The insulin dose was titrated to achieve fasting capillary BG<6.0 mmol/L. Montoring BG with continuous glucose monitoring system, then the standard deviation of BG (SDBG), maximal excursion of BG (LAGE) and coefficient of variation (CV) of fasting plasma glucose (FPG) were calculated. Results SDBG (1.49±0.35 vs 1.73±0.46), LAGE (3.23±0.76 vs 3.73± 1.00) and CV-FPG (17.26±2.24 vs 20.33±3.21) were lower in glargine group than those in HII group (P< 0.05). No difference could be found in hypoglycaemia between two groups. Conclusion OADs plus glargine could make blood glucose more stable than OADs plus HII without increasing the incidence of hypoglycaemia.

  13. Clinical Observation of Therapeutic Efficiency of Insulin Glargine Combined with Oral Hypoglycemic Agents in Elderly Patients with Type 2 Diabetes%甘精胰岛素联合口服降糖药治疗2型糖尿病临床观察

    Institute of Scientific and Technical Information of China (English)

    何启胜

    2011-01-01

    目的 观察甘精胰岛素联合口服降糖药物治疗2型糖尿病的临床疗效和安全性.方法 选择口服降糖药物血糖控制不佳的56例老年2型糖尿病患者,随机分为加用甘精胰岛素治疗组和低精蛋白锌胰岛素组两组,观察治疗前和治疗24周后各组的FBG、P2hBG、HbA1c和BMI的变化.同时对两种方案的安全性进行比较.结果 治疗24周后甘精胰岛素组与低精蛋白锌胰岛素组均能降低FBG、P2hBG、HbAlc,且疗效相当,组内治疗前后比较差异无统计学意义,而BMI均没有明显变化.但甘精胰岛素组的严重低血糖发生率明显低于低精蛋白锌胰岛素组.结论 甘精胰岛素组与低精蛋白锌胰岛素组在降低血糖方面的疗效相当,但甘精胰岛素组比低精蛋白锌胰岛素组治疗安全性高.%Objective To evaluate the clinical observation of therapeutic efficiency and safty of insulin glargine combined with oral hypoglycemic agents in elderly patients with type 2 diabetes. Methods Fifty six elderly patients with type 2 diabetes and poorly glycemic control by oral medication were randomly divided into two groups: insulin glargine( + ) group and isophane insu-lin( + ) group. FBG,P2hBG,HbAlc and BMI in each group were measured before and after 24 weeks of treatment,and the adverse effect were also recorded. Results HbAlc,FBG and P2hBG of the two groups were declined obviously after 24 weeks of treatment,and the therapeutic equivalence between the two groups. No significant change of BMI in the two groups. But the incidence of severe hypoglycemia in the insulin glargine group was lower than that in the isophane insulin group. Conclusion The therapeutic equivalence of insulin glargine and isophane insulin in decreasing the blood sugar was observed,but the security in insulin glargine group was higher than that in the low protamine zinc insulin group.

  14. Concentrated insulins: the new basal insulins

    Directory of Open Access Journals (Sweden)

    Lamos EM

    2016-03-01

    Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

  15. Molecular Characterisation of Long-Acting Insulin Analogues in Comparison with Human Insulin, IGF-1 and Insulin X10

    OpenAIRE

    Bo F Hansen; Glendorf, Tine; Hegelund, Anne C.; Lundby, Anders; Lützen, Anne; Slaaby, Rita; Stidsen, Carsten Enggaard

    2012-01-01

    Aims/Hypothesis There is controversy with respect to molecular characteristics of insulin analogues. We report a series of experiments forming a comprehensive characterisation of the long acting insulin analogues, glargine and detemir, in comparison with human insulin, IGF-1, and the super-mitogenic insulin, X10. Methods We measured binding of ligands to membrane-bound and solubilised receptors, receptor activation and mitogenicity in a number of cell types. Results Detemir and glargine each ...

  16. Analysis of 40 cases with the effect of insulin glargine combined with glimepiride therapy in patients with type 2 diabetes mellitus%格列美脲与甘精胰岛素联合用药治疗2型糖尿病40例效果分析

    Institute of Scientific and Technical Information of China (English)

    古丽巴合提·黑莎依

    2015-01-01

    Objective: To explore the effect of insulin glargine combined with glimepiride and therapy in patients with type 2 diabetes. Methods: from 2013 June to 2014 June in our hospital in patients with type 2 diabetes of randomly selected 40 cases as the object of study, 40 patients were treated with insulin glargine and glimepiride combined medication treatment for patients with fasting blood glucose, postprandial 2H blood glucose, glycated hemoglobin, low blood sugar and weight index. Results: the patients after treatment, fasting blood glucose, postprandial 2H blood glucose, hypoglycemia to descend obviously, compared with before treatment, the difference has statistical significance of data (P0.05). Conclusion: insulin glargine combined with glimepiride and medication is significantly effective in treating type 2 diabetes mellitus, can effectively improve the patients with fasting blood glucose, postprandial 2H blood glucose, low glycemic index, is a safe and effective method, is worthy of promotion and application.%目的:探讨格列美脲与甘精胰岛素联合用药治疗2型糖尿病的疗效。方法从2013年6月至2014年6月我院收治的2型糖尿病患者中随机性抽取40例作为研究对象,40例患者均给予格列美脲与甘精胰岛素联合用药治疗,对于患者空腹血糖、餐后2h 血糖、糖化红蛋白、低血糖以及体重指标。结果患者治疗后空腹血糖、餐后2h 血糖、低血糖以均有明显下降,与治疗前比较,数据差异具有统计学意义(P0.05)。结论格列美脲与甘精胰岛素联合用药治疗2型糖尿病疗效显著,可以有效改善患者空腹血糖、餐后2h 血糖、低血糖指标,是一种安全有效的治疗方法,值得临床推广和应用。

  17. Insulin Glargine (rDNA origin) Injection

    Science.gov (United States)

    ... cloudy, or contains solid particles, or if the expiration date on the bottle has passed.Do not ... body wheezing difficulty breathing or swallowing shortness of breath fast pulse sweating swelling of the eyes, face, ...

  18. Clinical Research on Elderly Patients with Type 2 Diabetes Complicated by Medical Critical Illness Treated by Insulin Glargine%甘精胰岛素治疗老年2型糖尿病合并内科危重患者的临床研究

    Institute of Scientific and Technical Information of China (English)

    王晓飞

    2014-01-01

    Objective To investigate and analyze the clinical effect of insulin glargine on elderly patients with type 2 diabetes complicated by medical critical illness. Methods For patients in the control group, human insulin isophane was given to them and short-acting insulin was also given to the patients who were able to eat before meals for controlling the blood glucose concentration within the range of 5.0~8.0 mmol/L. And insulin glargine was given to the patients in the experimental group on the basis of the treatment given to the control group. Results The average blood glucose concentration of the experimental group and the control group 1, 3, 5d after treatment was (12.1±5.1) mmol/L, (7.6±1.2) mmol/L, (5.5±0.9) mmol/L;(13.4±5.7) mmol/L, (10.8±2.0) mmol/L, (6.6 ±1.0) mmol/L, respectively. Conclusion For elderly patients with type 2 diabetes complicated by medical critical illness in clinical practice, insulin glargine can effectively control the blood glucose level, alleviate the pain, improve the treatment effect, promote the rehabilitation of the patients and enhance the quality of life of the patients.%目的:探讨对老年2型糖尿病合并内科危重疾病患者采用甘精胰岛素治疗,探讨和分析其治疗的临床效果。方法选取该院2011年1月—2013年7月期间收治的110例老年2型糖尿病合并内科危重疾病患者。对照组:对患者采用中性低精蛋白锌人胰岛素进行治疗,可进食的患者,餐前给患者追加短效胰岛素,将患者的血糖浓度控制在5.0~8.0 mmol/L 范围内;试验组:在对照组治疗基础上,对患者采用甘精胰岛素治疗。结果经过治疗后,试验组和对照组在1、3、5d的平均血糖浓度分别为(12.1±5.1)mmol/L、(7.6±1.2)mmol/L、(5.5±0.9)mmol/L;(13.4±5.7)mmol/L、(10.8±2.0)mmol/L、(6.6±1.0)mmol/L;结论在临床上,对老年2型糖尿病合并内科危重疾病患者采用甘精胰岛素进行治疗,有效地控制患者的

  19. 甘精胰岛素佐治老年2型糖尿病肾病的临床价值分析%Clinical value analysis of insulin glargine treatment for elderly patients with type 2 diabetes complicated with nephropathy

    Institute of Scientific and Technical Information of China (English)

    李晓红

    2013-01-01

    Objective To investigate the clinical value of insulin glargine treatment for elderly patients with type 2 diabetes complicated with nephropathy. Methods 80 cases of elderly patients with type 2 diabetes complicated with nephropathy admitted to our hospital from May 2010 to May 2011 were randomly divided into two groups, control group( n =40 )and treatment group( n =40 ). The control group was given isophane protamine biosynthetic human insulin and repaglinide, the treatment group was given insulin glargine and repaglinide. The clinical efficacy, blood glucose and renal function of the two groups were observed and compared. Results The total effective rate of treatment group was significantly higher than that of control group( 92. 50% vs. 75. 00% , P < 0. 05 ); the incidence of hypoglycemia/ nocturnal hypoglycemia of treatment group was significantly lower than that of control group( P < 0. 05 ); the level of fasting plasma glucose,2-hour postprandial plasma glucose,glycated hemoglobin Alc of the treatment group after treatment were significantly less than those of control group( P < 0. 05 ); the level of blood urea nitrogen, serum creatinine, 24-hour urine protein of treatment group after treatment were significantly improved than those of control group( P < 0. 05 ). Conclusion The clinical application of insulin glargine for the elderly patients with type 2 diabetic nephropathy can significantly control the blood glucose and improve the patient's renal function.%目的 探讨甘精胰岛素佐治老年2型糖尿病肾病的临床价值.方法 将2010年5月至2011年5月我院诊治的80例糖尿病肾病患者随机分成2组:对照组40例,采用精蛋白生物合成人胰岛素+瑞格列奈治疗;试验组40例,采用甘精胰岛素+瑞格列奈治疗.观察比较两组的临床疗效、血糖水平和肾功能水平的变化情况.结果 试验组的总有效率显著高于对照组(92.50% vs.75.00%,P<0.05),试验组的低血糖/夜间低血糖的不良反

  20. 预混胰岛素治疗的2型糖尿病患者转为甘精胰岛素联合口服药的疗效分析%Analysis of the effect of premixed insulin converted to glargine combined with oral medicine for the treatment of patients with type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    陈云华

    2015-01-01

    目的:探讨预混胰岛素治疗的2型糖尿病患者转为甘精胰岛素联合口服药的临床疗效。方法:将2型糖尿病患者144例随机平分为两组,观察组停用预混胰岛采用甘精胰岛素联合口服降糖药进行治疗,对照组采用预混胰岛素联合口服降糖药进行治疗。观察并比较两组患者FBG(空腹血糖)、HbA1c(糖化血红蛋白)、2 hPG(餐后2 h血糖)及治疗期间患者BMI(体重指数)、低血糖发生次数。结果:两组治疗后FBG、HbA1c、2 hPG等各项指标均下降,下降幅度观察组明显优于对照组;观察组治疗过程中患者BMI无明显变化,而对照组BMI明显上升,且对照组低血糖发生次数明显多于观察组,P<0.05,差异有统计学意义。结论:预混胰岛素治疗效果欠佳的2型糖尿病患者采用甘精胰岛素联合口服降糖药进行治疗,可有效改善患者的FBG、HbA1c水平,降低低血糖风险,且患者体重不会增加。%Objective:To investigate the clinical effect of premixed insulin converted to glargine combined with oral medicine for the treatment of patients with type 2 diabetes mellitus.Methods:144 patients with type 2 diabetes mellitus were randomly divided into the two groups on average.Patients in the observation group deactivated the premixed insulin therapy,and they were treated by the combination of glargine and oral hypoglycemic agents.Patients in the control group were treated by the combination of premixed insulin and oral hypoglycemic agents.We observed and compared the FBG(fasting blood glucose),HbA1c(glycosylated hemoglobin),2 hPG(2 h postprandial blood sugar)and BMI(body mass index),the number of occurrences of hypoglycemia during treatment.Results:The indicators of FBG,HbA1c,2 hPG were all decreased of the two groups after treatment,and the decline of the observation group was significantly better than the control group.Patients in the observation group had no significant change in BMI

  1. 甘精胰岛素与格列本脲治疗初诊2型糖尿病的疗效对比%Comparison on the clinical effects of insulin glargine and glimepiride for newly diagnosed type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    班安然

    2013-01-01

    Objective To compare the therapeutic effects and safety of insulin glargine and glimepiride in the treatment of newly diagnosed type 2 diabetes mellitus (T2DM). Methods Sixty T2DM patients were randomly divided into 3 groups, 20 cases in each group. Group A was administered insulin glargine combined with metformin, group B glimepiride combined with metformin and group C Isophane Protamine Biosynthetic Human Insulin Injection (pre - mix 30R). Before and after treatment, the levels of fasting plasma glucose (FPG), 2 h postprandial plasma glucose (2 hPG), glycosylated hemoglobin (HbAlc) and postprandial C peptide after meals in the patients of 3 groups as well as hypoglycemia incidences of groups A and B were compared. Results The improved condition of each index in group A was markedly superior to those in groups B and C. The improved conditions of group B showed the tendency of preceding group C, but there was no statistical significance among each indexes except for HbAlc. The hypoglycemia incidences of group A in both previous and later 6 weeks showed the tendency of being inferior to group B, but the difference showed no statistical significance. Conclusion Insulin glargine combined with metformin in the treatment of T2DM, can significantly reduce the blood sugar and ameliorate glycometabolism, with a low incidence of hypoglycemia, high safety and superior to glimepiride combined with metformin, so it is worthy of clinical promotion.%目的 比较甘精胰岛素与格列本脲对初诊2型糖尿病(T2DM)的疗效及安全性.方法 将60例T2DM患者随机分为3组,每组20例.A组给予甘精胰岛素联合二甲双胍,B组给予格列本脲联合二甲双胍,C组给予精蛋白生物合成人胰岛素注射液(预混30R).比较3组患者治疗前后空腹血糖(FPG)、餐后2h血糖(2hPG)、糖化血红蛋白(HbAlc)、餐后C肽水平变化,以及A、B组低血糖发生率.结果 A组各指标改善情况均显著优于B、C组,B组各指标改善情况有

  2. 甘精胰岛素和人胰岛素对人乳腺癌MDA-MB-231细胞的增殖作用%Effect of insulin glargine and human insulin on proliferation f a human breast cancer cell line MDA-MB-231

    Institute of Scientific and Technical Information of China (English)

    刘珊英; 李焱; 潘秋辉; 魏菁; 梁颖; 傅玉如; 梁蔚文; 林天歆

    2010-01-01

    目的 探讨甘精胰岛素(insulin glargine)和人胰岛素(human insulin)对人乳腺癌细胞株MDA-MB-231增殖的影响及细胞外信号调节激酶(ERK)的调节作用.方法 使用不同浓度的甘精胰岛素和人胰岛素刺激人乳腺癌MDA-MB-231细胞株,检测不同时间段的细胞增殖作用,探讨抑制ERK1/2激活对细胞增殖的影响.使用cell counting kit-8(CCK-8)试剂检测细胞增殖,流式细胞术检测细胞周期分布.结果 甘精胰岛素和人胰岛素在1、10、100 IU·L-1刺激MDA-MB-231细胞96 h后均可轻度促进MDA-MB-231细胞增殖,相同条件下甘精胰岛素和人胰岛素的促增殖效应无差异.甘精胰岛素与人胰岛素以10 IU·L-1分别刺激48、72、96 h后两药均诱导细胞增殖,比较两种药物间增殖效应的差异无统计学意义.甘精胰岛素和人胰岛素均使S+G2/M期细胞比例增加,但两处理组间差异无显著性.ERK1/2抑制剂PD98059可抑制MDA-MB-231细胞增殖;但PD98059不影响甘精胰岛素和人胰岛素对MDA-MB-231细胞增殖的促进作用.结论 甘精胰岛素和人胰岛素对人乳腺癌细胞株MDA-MB-231增殖有类似的轻度促进作用,该作用不依赖于ERK的激活.

  3. Clinical Observation of 105 Cases with Insulin Glargine Plus Oral Hypoglycemic Drugs for Treating Type 2 Diabetes%甘精胰岛素加口服降糖药治疗2型糖尿病105例临床观察

    Institute of Scientific and Technical Information of China (English)

    刘红丽; 王叶菊

    2011-01-01

    Objective To observe the therapeutic efficacy and safety of insulin glargine plus acarbose on patients with type 2 diabetes with poor efficacy of premixed human insulin in converted. Methods To se-lect105 patients with type 2 diabetic in Hanzhong Central Hospital from 2008 June to 2010 June inpatient, previous use of premixed human insulin 30R, poor glycemic control or hypoglycemia has emerged frequently, conversion of insulin glargine plus acarbose treatment. After 12 weeks,fasting blood glucose( FBG ),2-hour plasma glucose( 2hPG ),hemoglobin A1C( HbAlC )and recorded the incidence rate of hypoglycemia, changes in body mass and insulin dose were observed. Results In98 cases,fasting blood glucose,2-hour plasma glucose, hemoglobin A1C compliance rate was respectively 92% ,87% ,83% ,the incidence of hypoglycemia significantly decreased, insulin dose was reduced, the body mass was not significant changes. Conclusion For patients with poor effect of premixed human insulin in treatment of poor patients," 2 back 1" treatment strategy to provide better glycemic control, and reduce the rate of hypoglycemia.%目的 观察预混人胰岛素疗效不佳的2型糖尿病患者转换甘精胰岛素加阿卡波糖治疗后的疗效及安全性.方法 选取汉中市中心医院2008年6月至2010年6月住院的2型糖尿病患者105例,既往使用预混人胰岛素30R,血糖控制不佳或频繁出现低血糖者,转换甘精胰岛素加阿卡波糖治疗.12周后观察空腹血糖、餐后2 h血糖、糖化血红蛋白,并记录低血糖发生次数、体质量变化及胰岛素剂量.结果 98例患者空腹、餐后2 h血糖、糖化血红蛋白达标率分别是92%、87%、83%,低血糖发生率明显降低,胰岛素剂量较前减少,体质量无明显变化.结论 对于预混人胰岛素治疗欠佳的患者,"2退1"的治疗策略能提供更佳的血糖控制,并减少低血糖的发生率.

  4. 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

  5. Clinical effect of glimepiride combined insulin glargine or neutral protamine hagedorn on type 2 diabetes mel itus%格列美脲联用甘精胰岛素或中性鱼精蛋白锌胰岛素治疗2型糖尿病的临床对比观察

    Institute of Scientific and Technical Information of China (English)

    贾维敏; 黄慧华

    2013-01-01

    0bjective:To compare the clinical therapeutic effects of glimepiride combined with insulin glargine (IG) or neutral protamine hagedorn (NPH) respectively on type 2 diabetes mel itus (T2DM) patients.Methods:Ninety-sixes patients of T2DM in plasma glucose poorly control ed with treatment of glimepiride combined with IG(IG group, 45 cases)or NPH (NPH group, 41 cases).The changes of plasma glucose levels before and after the treatment were compared and evaluated between IG group and NPH group.Results:By 24 weeks,the mean value of plasma glucose levels in IG group and NPH group decreased (PO.05).Compared with NPH group, the numbers of incidence of hypoglycemia decreased significantly in IG group (P0.05),但IG组低血糖发生率显著低于NPH组(P <0.05)。结论格列美脲联用IG或NPH可很好控制T2DM患者血糖,两者疗效相似,但格列美脲联用IG治疗T2DM更为安全、有效。

  6. 甘精胰岛素联合口服药物治疗2型糖尿病的疗效及安全性分析%Analysis of Efficacy and Safety of the Treatment of Insulin Glargine Combined with Oral Hypoglycemic Drugs for Type 2 Diabetic Patients

    Institute of Scientific and Technical Information of China (English)

    李敬华; 刘丽楠; 王素莉; 关树梅; 候雯莉

    2011-01-01

    Objective Evaluation of the efficacy end safety of the treatment insulin glargine combined with OADs for type 2 diabetic patients with poor glycemic control using premixed insulin therapy. Methods 50 cases of type 2 diabetic patients were randomly divided into treatment group (convert premixed insulin into insulin glargine plus OADs) (n= 30) and control group (continue to use the premixed insulin plus OADs) (n= 20), all groups were adjusted the dosage of insulin and OADs based on the levels of blood glucose. After 12 weeks the index of FBG、2hPG、HbA1c、BMI and the incidence of hypoglycemia during the test were compared in two groups. Results Compared with those before treatment, HbA1c、FBG、2hPG of the two groups have declined (P all < 0.01); the treatment group has no significant change in BMI (P >0.05). Compared with the control group, FBG、lunch 2hPG and HbA1c of the treatment group is lower (P all<0.01); BMI of treatment group is lower (P< 0.01); the incidence of hypoglycemia during the test of the treatment group is lower(P< 0.01). Conclusion The treatment of insulin glargine combined OADs for poor glycemic control in type 2 diabetic patients using premixed insulin,can significantly improve the levels of FBG and HbA1c, do not increase body weight, be simple, and can greatly reduce the risk of hypoglycemia.%目的 评价甘精胰岛素联合口服降糖药物(oral hypoglycemic drugs,OADs)治疗方案对使用预混胰岛素血糖控制欠佳的2型糖尿病患者的疗效及安全性.方法 预混胰岛素30/70单独或联合使用OADs血糖控制不良的2型糖尿病患者50例,随机分为治疗组(停用预混胰岛素,改为皮下注射甘精胰岛素联合OADs) (n= 30)和对照组(继续使用预混胰岛素早晚餐前皮下注射联合OADs)(n=20),各组均依据血糖监测水平调整胰岛素及OADs用量.12周后对比两组患者空腹血糖(fasting blood glucose,FBG)、三餐后2h血糖(2-hour postprandial blood glucose,2hPG

  7. 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.

  8. 老年2型糖尿病内科危重患者应用甘精胰岛素治疗的临床分析%Clinical Analysis the Severe Patients With Agedness Type 2 Diabetes Application for Insulin Glargine in Medicine

    Institute of Scientific and Technical Information of China (English)

    邢丽英; 姜丽萍

    2015-01-01

    Objective To explore the application in elderly patients with type 2 diabetes mellitus and medical critically ill the clinical effect of insulin therapy.Methods Selected 98 cases of elderly patients with type 2 diabetes mellitus and medical critically ill in our hospital as the object, were randomly divided into the control group and the treatment group, each group had 49 cases.The control group received neutral isophane human insulin therapy, the treatment group on the basis of received insulin glargine in the control group, compared clinical effect of two groups. Results The treatment group at 1 days, section 3 days, 5 days average blood glucose concentration was less than that in the control group,P<0.05, was difference had statistically significance. the treatment a few days rest and treatment comparison average blood glucose concentration after 7 dsys,P>0.05, was no difference had statistically significance.Conclusion Elderly patients with type 2 diabetes mellitus and internal critical application of insulin treatment, can well control blood sugar levels and improve the treatment effect.%目的 探讨老年2型糖尿病内科危重患者应用甘精胰岛素治疗的临床效果.方法 将我院收治的98例老年2型糖尿病合并内科危重患者作为研究对象,随机分为对照组与治疗组,各49例,对照组给予中性低精蛋白锌人胰岛素治疗,治疗组在对照组基础上应用甘精胰岛素治疗,对比两组患者的临床效果.结果 治疗组在第1 d、第3 d、第5 d的平均血糖浓度要少于对照组,P<0.05,差异具有统计学意义;其余治疗天数与治疗7 d后平均血糖浓度对比,P>0.05,差异不具有统计学意义.结论 老年2型糖尿病合并内科危重患者应用甘精胰岛素治疗,能够较好地控制血糖水平,改善治疗效果.

  9. 甘精胰岛素治疗2型糖尿病合并慢性肾脏疾病患者的临床观察%Clinical Observation of Patients with Type 2 Diabetes and Chronic Kidney Disease Treated by Insulin Glargine

    Institute of Scientific and Technical Information of China (English)

    彭耀尧

    2014-01-01

    目的:探讨对2型糖尿病合并慢性肾脏疾病患者采用甘精胰岛素治疗,探讨和分析其治疗的临床效果。方法将该院2012年10月—2013年12月期间所收治的55例2型糖尿病合并慢性肾脏疾病患者,按照随机数字表法分组为观察组(30例)和对照组(25例);治疗前,观察组和对照组患者24 h内的血糖平均浓度分别为(13.7±5.7)mmol/L、(13.4±6.0)mmol/L;对照组:采用中性低精蛋白锌人胰岛素进行治疗,可进食的患者,餐前追加短效胰岛素,将血糖浓度控制在5.0~8.0 mmol/L范围内;观察组:在对照组治疗基础上采用甘精胰岛素治疗。结果经过治疗后,观察组和对照组在1、3、5d的平均血糖浓度分别为(11.9±4.8)mmol/L、(7.4±1.3)mmol/L、(5.6±0.7)mmol/L;(13.5±5.6)mmol/L、(10.7±1.9)mmol/L、(6.5±0.8)mmol/L(P0.05)。结论在临床上,对2型糖尿病合并慢性肾脏疾病患者采用甘精胰岛素进行治疗,有效地控制患者的血糖水平,减轻患者痛苦,改善其临床症状,提高患者生活质量。%Objective To study and analyze the clinical effect of insulin glargine in the treatment of type 2 diabetes complicated by chronic kidney disease. Methods 55 patients with type 2 diabetes complicated by chronic kidney disease admitted in our hos-pital were grouped into the observation group (30 cases) and control group (25 cases) according to the random number table. Before treatment, the average blood glucose concentration within 24h of the observation group and the control group was(13.7±5.7)mmol/L, (13.4 ±6.0)mmol/L, respectively. For patients in the control group, human insulin isophane was given to them for treatment, and short-acting insulin was also given to the patients who were able to eat before meals for controlling the blood glucose concentration within the range of 5.0~8.0 mmol/L. And for patients in the observation group, insulin glargine was given to them on the basis of the

  10. 甘精胰岛素联合阿卡波糖对2型糖尿病患者血糖达标率及胰岛β细胞功能的影响%The effect of insulin glargine combined with carbose on blood glucose attaining standardand pancreatic β cell function of type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    包灵敏; 刘存安

    2013-01-01

    Objective To explore the effect of insulin glargine combined with carbose onblood glucose attaining standard and pancreatic β cell function of type 2 diabetic patients.Methods 70 type 2 diabetic patients were divided into observation group and control group.All the patients got fundamental treatment as diet control and physical exercise.Patients of observing group got extra treatment as using insulin glargine combined with carbose,while patients of control group got extra treatment as using premixed insulin 30R(isophane protamine biosynthetic human insulin),all the treatment lasted for 8 weeks.Results 8 weeks after treatment,the rate of reaching standard of FBG and 2h postprandial plasma glucose and glycosylated hemoglobin (95.0%,85.0% and 77.5%) of observing group were significantly higher than those of control group (77.5%,62.5% and 55.0%) (x2 =5.16,5.23 and 4.53,all P <0.05).The levels of FCP and PCP increased significantly in both groups than that of before treatment (t =2.43,2.32,2.28,2.19,all P < 0.05),and the change of observation group was more obviously than that of control group (t =2.17,2.13,all P < 0.05).The occurrence rate of hypoglycemia of observation group was significantly lower than that of control group(x2 =4.11,P <0.05).Conclusion Treating diabetic patient by insulin glargine combined with acarbose has high safety,and helps to reach the standard of FBG and glycosylated hemoglobin,reduce the incurrence rate of hypoglycemia,protect and improve the function of pancreatic 3 cell,and postpone the beginning and progress of complication.%目的 探讨甘精胰岛素联合阿卡波糖对2型糖尿病患者血糖达标率及胰岛β细胞功能的影响.方法 选择2型糖尿病患者70例,按就诊病历号顺序随机分为观察组与对照组.两组患者均予以饮食控制和体育锻炼等基础治疗.观察组在此基础上予以甘精胰岛素联合阿卡波糖治疗,对照组在此基础上予以精蛋白生物合成人

  11. 2型糖尿病从预混胰岛素转换为甘精胰岛素联合口服降糖药物治疗的观察性研究%Study of treatment switching from premixed insulin to glargine combined with oral antidiabetic drugs of patients with type 2 diabetic

    Institute of Scientific and Technical Information of China (English)

    杨艳; 李蓬秋; 包明晶; 刘丽梅; 张学军; 鲜杨; 吴冀川; 张磊; 朱显军

    2014-01-01

    目的 观察2型糖尿病患者从预混胰岛素转换为甘精胰岛素联合口服降糖药物(OADs)治疗的效果、安全性和患者的满意度.方法 采用自身前后对照研究,选择2型糖尿病患者,接受预混胰岛素治疗至少3个月,联合/或未联合OADs治疗,且糖化血红蛋白(HbA1c)≤10.0%的2型糖尿病患者43例,基于患者和医师的考虑,将预混胰岛素转换为甘精胰岛素联合OADs治疗,由医师根据血糖调整胰岛素和OADs的剂量,随访16周,目标空腹血糖≤5.6 mmol/L.结果 共36例患者完成全部随访观察,治疗16周后空腹血糖、餐后2h血糖、HbA1c均与治疗前相当(P均>0.05),而胰岛素用量明显减少[(23.8±6.0)、(9.6±4.0) U/d,t=13.59,P<0.01],体质量指数较治疗前明显下降[(24.4±2.9)、(23.8±2.8)kg/m2,t=3.25,P<0.05];随访期间36例入组患者中15例患者共发生低血糖30次,低血糖发生率41.7%(15/36),均无需他人帮助,少量进食后缓解,无重度低血糖发生,无患者因低血糖反应而退出本研究;36例患者转换前治疗总体满意率为36.1% (13/36),转换后为72.2%(26/36),转换后总体满意度明显高于转换前(x2=6.26,P<O.05).结论 HbA1c≤7.0%时将预混胰岛素转换为甘精胰岛素联合OADs治疗能有效控制血糖,且胰岛素用量及注射次数减少,患者体质量减轻,治疗满意度高.%Objective To evaluation the efficacy,safety and treatment satisfaction of glargine plus oral medications(OADs) switching from premixed insulin on patients with type 2 diabetic.Methods Forty-three patients with type 2 diabetes were enrolled into our study.All patients were treated with twice-daily premixed insulin therapy for at least 3 months with or without OADs and their glycosylated haemoglobin(HbA1c) were less than 10.0%.The aim of OADs treatment was FBG ≤ 5.6 mmol/L Results Thirty-six cases were performed a 16 weeks follow-up and no one lost.After 4 months OADs treatment,the levels of fasting

  12. Insulin analogs and cancer

    Directory of Open Access Journals (Sweden)

    Laura eSciacca

    2012-02-01

    Full Text Available Today, insulin analogs are used in millions of diabetic patients. Insulin analogs have been developed to achieve more physiological insulin replacement in terms of time course of the effect. Modifications in the amino acid sequence of the insulin molecule change the pharmacokinetics and pharmacodynamics of the analogs in respect to human insulin. However, these changes can also modify the molecular and biological effects of the analogs. The rapid-acting insulin analogs, lispro, aspart and glulisine, have a rapid onset and shorter duration of action. The long-acting insulin analogs glargine and detemir have a protracted duration of action and a relatively smooth serum concentration profile. Insulin and its analogs may function as growth factors and therefore have a theoretical potential to promote tumor proliferation. A major question is whether analogs have an increased mitogenic activity in respect to insulin. These ligands can promote cell proliferation through many mechanisms like the prolonged stimulation of the insulin receptor, stimulation of the IGF-1 receptor (IGF-1R, prevalent activation of the ERK rather than the AKT intracellular post-receptor pathways. Studies on in vitro models indicate that short-acting analogs elicit molecular and biological effects that are similar to those of insulin. In contrast, long-acting analogs behave differently. Although not all data are homogeneous, both glargine and detemir have been found to have a decreased binding to IR but an increased binding to IGF-1R, a prevalent activation of the ERK pathway, and an increased mitogenic effect in respect to insulin. Recent retrospective epidemiological clinical studies have suggested that treatment with long-acting analogs (specifically glargine may increase the relative risk for cancer. Results are controversial and methodologically weak. Therefore prospective clinical studies are needed to evaluate the possible tumor growth-promoting effects of these insulin

  13. Clinical curative effect and safety analysis of insulin glargine and acarbose treatment in elderly diabetes patients%甘精胰岛素联用阿卡波糖治疗老年糖尿病患者的临床疗效及安全性评价

    Institute of Scientific and Technical Information of China (English)

    王筱景; 阮凌燕; 周小爱

    2014-01-01

    目的:评价甘精胰岛素联用阿卡波糖治疗老年糖尿病患者的临床疗效及安全性。方法老年糖尿病患者120例随机分为治疗组和对照组,各60例。治疗组用甘精胰岛素联合阿卡波糖,对照组用精蛋白生物合成人胰岛素注射液联合阿卡波糖,胰岛素始剂量为0.15 U・ kg-1,根据血糖水平调整胰岛素用量及口服药物用量,随访观察3个月。监测患者血糖水平,并记录不良事件;随访记录2组患者的血糖达标时间和每日胰岛素总量,计算日平均血糖,检测患者治疗后的糖化血红蛋白水平和空腹 C 肽值。结果治疗3个月后,患者的糖化血红蛋白、空腹血糖及日平均血糖水平较治疗前均降低(P <0.05),其中,治疗组的日平均血糖水平显著低于对照组(P <0.05)。治疗组的血糖达标时间和胰岛素日用量均少于对照组(P 均<0.05),治疗后空腹 C 肽含量明显高于对照组(P <0.05)。治疗组的不良反应发生率低于对照组(P <0.05)。结论甘精胰岛素联用阿卡波糖治疗老年糖尿病患者具有良好疗效,能快速、安全、有效地控制患者血糖。%Objective To study the clinical curative effect and safety analysis of insulin glargine with acarbose treatment in elderly patients with diabetes.Methods A total of 120 cases of elderly patients with diabetes were randomly divided into two groups.The 60 patients of treat-ment group were treated with insulin glargine and acarbose combination , and the 60 patients of the control group were treated with isophane prota -mine biosynthetic human insulin injection and acarbose combination .The patient monitored blood glucose levels and recorded adverse events .The therapeutic time and the daily amount of insulin were recorded of two groups of patients.The average daily blood sugar were calculated and the HbA1c and fasting c -peptide values were detected at 3 months

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

    OpenAIRE

    Werner Haim; Chantelau Ernst A

    2011-01-01

    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 retrie...

  15. 糖尿病及长效胰岛素类似物是否增加病人罹患肿瘤的风险?——1例糖尿病合并胰腺癌患者的循证治疗%Does Diabetes and Long-acting Insulin Glargine Increase the Risk of Malignancies: An Evidence-based Treatment for a Diabetic Patient Accompanied with Pancreatic Cancer

    Institute of Scientific and Technical Information of China (English)

    孙倩倩; 王双; 郑玉霞; 廖再波

    2011-01-01

    Objective Through studying a diabetic patient accompanied with pancreatic cancer by means of evidence-based clinical practice, to find out the relationship between diabetes mellitus and cancer and whether the longacting insulin glargine increases the risk of cancer or not, which is regarded as a disputable hot issue at present.Methods Such databases as The Cochrane Library (Issue 3, 2010), OVID-EBM Reviews (1991 to Sept.2010), MEDLINE (1950 to Sept.2010) and CNKI (2000 to Sept.2010) were retrieved to collect high quality clinical evidence, and the best therapy was formulated in accordance with the willingness of patients themselves.Results Eight randomized controlled trials (RCTs), four meta-analyses and one RCT meta-analysis were included.The evidence indicated that: a) Diabetes mellitus was kind of related to the occurrence of malignancies; b) There was no evidence at present showing the relationship between long-acting insulin glargine and cancer; c) Strictly controlling of blood sugar did not increase the risk of tumorigenesis, but hyperglycemia causing cancer was proofless; and d) Whether the diabetic patient with cancer should stop taking long-acting insulin glargine or not should require suggestions from specialists rather than patients themselves.Conclusion No evidence at present shows that tumorigenesis is related to diabetes mellitus, long-acting insulin glargine and strict controlling of blood sugar.It is necessary to require more evidence to decide whether the therapy should be adjusted or not for the diabetic patient with cancer who is in the process of glargine therapy.%目的 糖尿病与肿瘤的关系以及长效胰岛素类似物是否致癌是目前颇有争议的热点问题,结合1例糖尿病合并胰腺癌患者的病情,用循证临床实践的方法,对糖尿病与肿瘤的关系及长效胰岛素类似物是否致癌进行讨论.方法 计算机检索Cochrane图书馆(2010年第3期)、OVID-EBM Reviews (1991~2010.9),MEDLINE(1950~2010

  16. Rapid Acting Insulin Use and Persistence among Elderly Type 2 Diabetes Patients Adding RAI to Oral Antidiabetes Drug Regimens

    Science.gov (United States)

    Zhou, Steve; Fan, Tao

    2016-01-01

    We examined the real-world utilization and persistence of rapid acting insulin (RAI) in elderly patients with type 2 diabetes who added RAI to their drug (OAD) regimen. Insulin-naïve patients aged ≥65 years, with ≥1 OAD prescription during the baseline period, who were continuously enrolled in the US Humana Medicare Advantage insurance plan for 18 months and initiated RAI were included. Among patients with ≥2 RAI prescriptions (RAIp), persistence during the 12-month follow-up was assessed. Multivariate logistic regression analyses identified factors affecting RAI use and persistence. Of 3734 patients adding RAI to their OAD regimen, 2334 (62.5%) had a RAIp during follow-up. Factors associated with RAIp included using ≤2 OADs; cognitive impairment, basal insulin use during follow-up; and higher RAI out-of-pocket costs ($36 to <$56 versus $0 to $6.30). Patients were less likely to persist with RAI when on ≤2 OADs versus ≥3 OADs and when having higher RAI out-of-pocket costs ($36 to <$56 versus $0 to $6.30) and more likely to persist when they had cognitive impairment and basal insulin use during follow-up. Real-world persistence of RAI in insulin-naïve elderly patients with type 2 diabetes was very poor when RAI was added to an OAD regimen. PMID:27761472

  17. Insulin, insulin analogues and diabetic retinopathy.

    Science.gov (United States)

    Chantelau, Ernst; Kimmerle, Renate; Meyer-Schwickerath, Rolf

    2008-02-01

    Insulin is absolutely vital for living beings. It is not only involved in metabolism, but also in the regulation of growth factors, e.g. IGF-1. In this review we address the role insulin has in the natural evolution of diabetic retinopathy. On the one hand, chronic deficiency of insulin and IGF-1 at the retina is thought to cause capillary degeneration, with subsequent ischaemia. On the other hand, acute abundance of (exogenously administered) insulin and IGF-1 enhances ischaemia-induced VEGF expression. A critical ratio of tissue VEGF-susceptibility: VEGF-availability triggers vascular proliferation (i.e. of micro-aneurysms and/or abnormal vessels). The patent-protected insulin analogues Lispro, Glulisine, Aspart, Glargine and Detemir are artificial insulin derivatives with altered biological responses compared to natural insulin (e.g. divergent insulin and /or IGF-1 receptor-binding characteristics, signalling patterns, and mitogenicity). Their safety profiles concerning diabetic retinopathy remain to be established by randomised controlled trials. Anecdotal reports and circumstantial evidence suggest that Lispro and Glargine might worsen diabetic retinopathy.

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

    NARCIS (Netherlands)

    E.M. Heintjes (Edith); T.L. Thomsen (Trine Lyager); F.J.A. Penning-Van Beest (Fernie); T.E. Christensen (Torsten); R.M.C. Herings (Ron)

    2010-01-01

    textabstractIntroduction: 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. Methods: Insulin-naïve patients with T2D, st

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

    OpenAIRE

    Ahmann, Andrew

    2015-01-01

    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 ...

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

    Science.gov (United States)

    Lowndes, Joshua; Sinnett, Stephanie S.; Rippe, James M.

    2015-01-01

    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 0.05). 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. PMID:26512691

  1. Insulin Analogs Versus Human Insulin in the Treatment of Patients With Diabetic Ketoacidosis

    Science.gov (United States)

    Umpierrez, Guillermo E.; Jones, Sidney; Smiley, Dawn; Mulligan, Patrick; Keyler, Trevor; Temponi, Angel; Semakula, Crispin; Umpierrez, Denise; Peng, Limin; Cerón, Miguel; Robalino, Gonzalo

    2009-01-01

    OBJECTIVE To compare the safety and efficacy of insulin analogs and human insulins both during acute intravenous treatment and during the transition to subcutaneous insulin in patients with diabetic ketoacidosis (DKA). RESEARCH DESIGN AND METHODS In a controlled multicenter and open-label trial, we randomly assigned patients with DKA to receive intravenous treatment with regular or glulisine insulin until resolution of DKA. After resolution of ketoacidosis, patients treated with intravenous regular insulin were transitioned to subcutaneous NPH and regular insulin twice daily (n = 34). Patients treated with intravenous glulisine insulin were transitioned to subcutaneous glargine once daily and glulisine before meals (n = 34). RESULTS There were no differences in the mean duration of treatment or in the amount of insulin infusion until resolution of DKA between intravenous treatment with regular and glulisine insulin. After transition to subcutaneous insulin, there were no differences in mean daily blood glucose levels, but patients treated with NPH and regular insulin had a higher rate of hypoglycemia (blood glucose <70 mg/dl). Fourteen patients (41%) treated with NPH and regular insulin had 26 episodes of hypoglycemia and 5 patients (15%) in the glargine and glulisine group had 8 episodes of hypoglycemia (P = 0.03). CONCLUSIONS Regular and glulisine insulin are equally effective during the acute treatment of DKA. A transition to subcutaneous glargine and glulisine after resolution of DKA resulted in similar glycemic control but in a lower rate of hypoglycemia than with NPH and regular insulin. Thus, a basal bolus regimen with glargine and glulisine is safer and should be preferred over NPH and regular insulin after the resolution of DKA. PMID:19366972

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

    NARCIS (Netherlands)

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

    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

  4. 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.

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

    Science.gov (United States)

    Arif, Idam; Nasir, Zulfa

    2015-09-01

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

  6. Streptozotocin Intracerebroventricular-Induced Neurotoxicity and Brain Insulin Resistance: a Therapeutic Intervention for Treatment of Sporadic Alzheimer's Disease (sAD)-Like Pathology.

    Science.gov (United States)

    Kamat, Pradip K; Kalani, Anuradha; Rai, Shivika; Tota, Santosh Kumar; Kumar, Ashok; Ahmad, Abdullah S

    2016-09-01

    Alzheimer's disease (AD) is a neurodegenerative disorder that is remarkably characterized by pathological hallmarks which include amyloid plaques, neurofibrillary tangles, neuronal loss, and progressive cognitive loss. Several well-known genetic mutations which are being used for the development of a transgenic model of AD lead to an early onset familial AD (fAD)-like condition. However, these settings are only reasons for a small percentage of the total AD cases. The large majorities of AD cases are considered as a sporadic in origin and are less influenced by a single mutation of a gene. The etiology of sporadic Alzheimer's disease (sAD) remains unclear, but numerous risk factors have been identified that increase the chance of developing AD. Among these risk factors are insulin desensitization/resistance state, oxidative stress, neuroinflammation, synapse dysfunction, tau hyperphosphorylation, and deposition of Aβ in the brain. Subsequently, these risk factors lead to development of sAD. However, the underlying molecular mechanism is not so clear. Streptozotocin (STZ) produces similar characteristic pathology of sAD such as altered glucose metabolism, insulin signaling, synaptic dysfunction, protein kinases such as protein kinase B/C, glycogen synthase-3β (GSK-3β) activation, tau hyperphosphorylation, Aβ deposition, and neuronal apoptosis. Further, STZ also leads to inhibition of Akt/PKB, insulin receptor (IR) signaling molecule, and insulin resistance in brain. These alterations mediated by STZ can be used to explore the underlying molecular and pathophysiological mechanism of AD (especially sAD) and their therapeutic intervention for drug development against AD pathology. PMID:26298663

  7. Functional Evaluation of the Reusable JuniorSTAR® Half-Unit Insulin Pen

    OpenAIRE

    Klonoff, David; Nayberg, Irina; Rabbone, Ivana; Domenger, Catherine; Stauder, Udo; Oualali, Hamid; Danne, Thomas

    2015-01-01

    Background: The functional performance of the JuniorSTAR® (Sanofi, Paris, France) half-unit insulin pen was evaluated through a series of specific objective tests to assess the dose accuracy, pen weight, injection force, and dialing torque. Method: Pens (n = 60) were tested under standard atmospheric conditions with 3 different types of insulins manufactured by Sanofi (insulin glargine, insulin glulisine, and biphasic insulin isophane). The dose accuracy was tested according to the ISO 11608-...

  8. 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.

  9. 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.

  10. 甘精胰岛素联合二甲双胍治疗对新诊断2型糖尿病伴非酒精性脂肪肝病患者血糖和胰岛β细胞功能的影响%Influence of insulin glargine combined with metformin therapy on glycemic control and pancreatic β-cell function in newly diagnosed pa-tients with type 2 diabetes mellitus companied with non-alcoholic fatty liver disease

    Institute of Scientific and Technical Information of China (English)

    张四青; 习燕华; 钟树妹; 郭经琴

    2015-01-01

    Objective To explore the influence of insulin glargine combined with metformin therapy on glycemic control and pancreatic β-cell function in newly diagnosed type 2 diabetes mellitus (T2DM) patients with non-alcoholic fatty liver disease (NAFLD). Methods 62 newly diagnosed T2DM patients with NAFLD from June 2012 December 2013 in our hospital were selected and randomly divided into the control group (30 cases) and the treatment group(32cases). The control group was given metformin plus glimepiride,the treatment group was given metformin plus insulin glargine. The levels of FBG,2 h PG,HbA1c,FINS and the index of β-cell function in two groups before and after treatment was compared. Results The level of FPG,2 h PG,HbA1c after 12 weeks of treatment was lower than that before treatment, with significant difference (P<0.05). The level of FINS,HOMA-βF,△I30/△G30 after 12 weeks of treatment was higher than that before treatment,with significant difference (P<0.05).The level of FINS,HOMA-βF,△I30/△G30 after treatment in the treatment group was higher than that in the control group after treatment,with significant difference (P<0.05). Conclu-sion Insulin glargine or glimepiride combined with metformin can effectively improve glycemic control and early phase insulin secretion in newly diagnosed T2DM patients with NAFLD,insulin glargine combined with metformin can more effectively improve early phase insulin secretion.%目的:探讨甘精胰岛素联合二甲双胍治疗对新诊断2型糖尿病(T2DM)伴非酒精性脂肪肝病(NAFLD)患者血糖和胰岛β细胞功能的影响。方法选取2012年6月~2013年12月在本院内分泌科门诊就诊的62例新诊断T2DM伴NAFLD患者作为研究对象,随机分为治疗组(32例)和对照组(30例)。对照组给予二甲双胍联合格列美脲片,治疗组给予二甲双胍联合甘精胰岛素。比较两组治疗前后的FBG、2 h PG、HbA1c、FINS水平和胰岛β细胞功能指数。结果两组治疗12

  11. Proliferative and signaling activities of insulin analogues in endometrial cancer cells.

    Science.gov (United States)

    Aizen, Daniel; Sarfstein, Rive; Bruchim, Ilan; Weinstein, Doron; Laron, Zvi; Werner, Haim

    2015-05-01

    Insulin analogues have been developed to achieve further improvement in the therapy of diabetes. However, modifications introduced into the insulin molecule may enhance their affinity for the insulin-like growth factor-1 receptor (IGF1R). Hyperinsulinemia has been identified as a risk factor for endometrial cancer. We hypothesized that insulin analogues may elicit atypical proliferative and signaling activities in endometrial cancer cells. Our results demonstrate that glargine, but not detemir, stimulated cell proliferation, displayed an anti-apoptotic effect, and had a positive effect on cell cycle progression in endometrial cancer cell lines ECC-1 and USPC-1. In addition, we showed that glargine and detemir induced dual activation of the insulin receptor (INSR) and IGF1R in both cell types. Furthermore, we showed that glargine elicited signaling events that are markedly different from those induced by insulin. In conclusion, our data support the concept that, although insulin analogues were designed to display insulin-like metabolic effects, glargine and, possibly, additional analogues exhibit IGF1-like activities and, accordingly, may function as IGF1 analogues. PMID:25697343

  12. [Insulin analogues: modifications in the structure, molecular and metabolic consequences].

    Science.gov (United States)

    de Luis, D A; Romero, E

    2013-01-01

    Recombinant DNA technology has provided insulin analogues for the treatment of diabetes mellitus, with an efficacy and safety that has improved the treatment of this disease. We briefly review the principal characteristics of the insulin analogues currently available. Both rapid-acting (lispro, aspart and glulisine) and long acting (glargine and determir) insulin analogues are included in this review. We describe the pharmacology of each insulin analogue, their differences with the human insulin, the administration, indication, efficacy and safety. In addition we discussed the main controversies of the use of these insulin analogues. In particular, those related with the risk of cancer and retinopathy, and their use in pregnant women. PMID:23517895

  13. Molecular Characterisation of Long-Acting Insulin Analogues in Comparison with Human Insulin, IGF-1 and Insulin X10

    Science.gov (United States)

    Hansen, Bo F.; Glendorf, Tine; Hegelund, Anne C.; Lundby, Anders; Lützen, Anne; Slaaby, Rita; Stidsen, Carsten Enggaard

    2012-01-01

    Aims/Hypothesis There is controversy with respect to molecular characteristics of insulin analogues. We report a series of experiments forming a comprehensive characterisation of the long acting insulin analogues, glargine and detemir, in comparison with human insulin, IGF-1, and the super-mitogenic insulin, X10. Methods We measured binding of ligands to membrane-bound and solubilised receptors, receptor activation and mitogenicity in a number of cell types. Results Detemir and glargine each displayed a balanced affinity for insulin receptor (IR) isoforms A and B. This was also true for X10, whereas IGF-1 had a higher affinity for IR-A than IR-B. X10 and glargine both exhibited a higher relative IGF-1R than IR binding affinity, whereas detemir displayed an IGF-1R:IR binding ratio of ≤1. Ligands with high relative IGF-1R affinity also had high affinity for IR/IGF-1R hybrid receptors. In general, the relative binding affinities of the analogues were reflected in their ability to phosphorylate the IR and IGF-1R. Detailed analysis revealed that X10, in contrast to the other ligands, seemed to evoke a preferential phosphorylation of juxtamembrane and kinase domain phosphorylation sites of the IR. Sustained phosphorylation was only observed from the IR after stimulation with X10, and after stimulation with IGF-1 from the IGF-1R. Both X10 and glargine showed an increased mitogenic potency compared to human insulin in cells expressing many IGF-1Rs, whereas only X10 showed increased mitogenicity in cells expressing many IRs. Conclusions Detailed analysis of receptor binding, activation and in vitro mitogenicity indicated no molecular safety concern with detemir. PMID:22590494

  14. Molecular characterisation of long-acting insulin analogues in comparison with human insulin, IGF-1 and insulin X10.

    Directory of Open Access Journals (Sweden)

    Bo F Hansen

    Full Text Available AIMS/HYPOTHESIS: There is controversy with respect to molecular characteristics of insulin analogues. We report a series of experiments forming a comprehensive characterisation of the long acting insulin analogues, glargine and detemir, in comparison with human insulin, IGF-1, and the super-mitogenic insulin, X10. METHODS: We measured binding of ligands to membrane-bound and solubilised receptors, receptor activation and mitogenicity in a number of cell types. RESULTS: Detemir and glargine each displayed a balanced affinity for insulin receptor (IR isoforms A and B. This was also true for X10, whereas IGF-1 had a higher affinity for IR-A than IR-B. X10 and glargine both exhibited a higher relative IGF-1R than IR binding affinity, whereas detemir displayed an IGF-1R:IR binding ratio of ≤ 1. Ligands with high relative IGF-1R affinity also had high affinity for IR/IGF-1R hybrid receptors. In general, the relative binding affinities of the analogues were reflected in their ability to phosphorylate the IR and IGF-1R. Detailed analysis revealed that X10, in contrast to the other ligands, seemed to evoke a preferential phosphorylation of juxtamembrane and kinase domain phosphorylation sites of the IR. Sustained phosphorylation was only observed from the IR after stimulation with X10, and after stimulation with IGF-1 from the IGF-1R. Both X10 and glargine showed an increased mitogenic potency compared to human insulin in cells expressing many IGF-1Rs, whereas only X10 showed increased mitogenicity in cells expressing many IRs. CONCLUSIONS: Detailed analysis of receptor binding, activation and in vitro mitogenicity indicated no molecular safety concern with detemir.

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

    Science.gov (United States)

    Owens, David R; Matfin, Glenn; Monnier, Louis

    2014-02-01

    Insulin remains the most effective and consistent means of controlling blood glucose levels in diabetes. Since 1946, neutral protamine Hagedorn (NPH) has been the predominant basal insulin in clinical use. However, absorption is variable due to the need for resuspension and the time-action profile (peak activity 4-6 h after subcutaneous administration) confers an increased propensity for between-meal and nocturnal hypoglycaemia. In the 1980s, recombinant DNA technology enabled modifications to the insulin molecule resulting in the soluble long-acting insulin analogues, glargine and detemir. Both exhibit a lower risk of hypoglycaemia compared with neutral protamine Hagedorn due to improved time-action profiles and reduced day-to-day glucose variability. Glargine is indicated for administration once daily and detemir once or twice daily. Degludec is the latest prolonged-acting insulin which forms long subcutaneous multi-hexamers that delay absorption. Recent phase III trials in type 1 and type 2 diabetes show that degludec was non-inferior to comparators (predominantly glargine) with a minimal although inconsistent reduction in overall hypoglycaemia and a small absolute difference in nocturnal hypoglycaemia. Newer developmental agents include LY2605541 and glargine U300. LY2605541 comprises insulin lispro combined with polyethylene glycol, thereby increasing its hydrodynamic size and retarding absorption from the subcutaneous tissue. Glargine U300 is a new formulation of glargine resulting in a flatter and more prolonged time-action profile than its predecessor. This article reviews recent advances in basal insulin analogues, including a critical appraisal of the degludec trials. PMID:24026961

  16. Drug: D03250 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D03250 Drug Insulin glargine (genetical recombination) (JAN); Insulin glargine (USA...llaneous 2492 Pancreatic hormones D03250 Insulin glargine (genetical recombinatio...ogues for injection, long-acting A10AE04 Insulin glargine D03250 Insulin glargine (genetical recombination) ...cose Regulators Insulins Insulin glargine D03250 Insulin glargine (genetical recombination) (JAN); Insulin g...7] Insulin glargine [ATC:A10AE04] D03250 Insulin glargine (genetical recombination) (JAN); Insulin glargine

  17. An update on the treatment of type 1 and type 2 diabetes mellitus: focus on insulin detemir, a long-acting human insulin analog

    Science.gov (United States)

    Raslova, Katarina

    2010-01-01

    Basal insulin analogs are used to minimize unpredictable processes of NPH insulin. Modification of the human insulin molecule results in a slower distribution to peripheral target tissues, a longer duration of action with stable concentrations and thus a lower rate of hypoglycemia. Insulin detemir is a basal insulin analog that provides effective therapeutic options for patients with type 1 and type 2 diabetes. For glycemic control, no significant differences were found in HbA1c levels compared with NPH and insulin glargine. It is comparable with insulin glargine in significantly reducing rates of all types of hypoglycemia. Clinical studies have demonstrated that detemir is responsible for significantly lower within-subject variability and no or less weight gain than NPH insulin and glargine. Recent pharmacodynamic studies have shown that detemir can be used once daily in many patients with diabetes. Together with patient-friendly injection devices and dose adjustments, it provides a treatment option with the potential to lower the key barriers of adherence to insulin therapy in type 2 diabetes. Recent guidelines for treatment of type 2 diabetes suggest starting intensive therapy of hyperglycemia at an early stage of diabetes and recommend therapeutic options that provide the possibility of reaching HbA1c goals individually, with a low risk of hypoglycemia or other adverse effects of treatment. The properties of insulin detemir match these requirements. PMID:20539842

  18. Cardiovascular effects of basal insulins

    Directory of Open Access Journals (Sweden)

    Mannucci E

    2015-07-01

    Full Text Available Edoardo Mannucci,1 Stefano Giannini,2 Ilaria Dicembrini1 1Diabetes Agency, Careggi Teaching Hospital, Florence, 2Section of Endocrinology, Department of Biomedical Clinical and Experimental Sciences, University of Florence and Careggi University Hospital, Florence, Italy Abstract: Basal insulin is an important component of treatment for both type 1 and type 2 diabetes. One of the principal aims of treatment in patients with diabetes is the prevention of diabetic complications, including cardiovascular disease. There is some evidence, although controversial, that attainment of good glycemic control reduces long-term cardiovascular risk in both type 1 and type 2 diabetes. The aim of this review is to provide an overview of the potential cardiovascular safety of the different available preparations of basal insulin. Current basal insulin (neutral protamine Hagedorn [NPH], or isophane and basal insulin analogs (glargine, detemir, and the more recent degludec differ essentially by various measures of pharmacokinetic and pharmacodynamic effects in the bloodstream, presence and persistence of peak action, and within-subject variability in the glucose-lowering response. The currently available data show that basal insulin analogs have a lower risk of hypoglycemia than NPH human insulin, in both type 1 and type 2 diabetes, then excluding additional harmful effects on the cardiovascular system mediated by activation of the adrenergic system. Given that no biological rationale for a possible difference in cardiovascular effect of basal insulins has been proposed so far, available meta-analyses of publicly disclosed randomized controlled trials do not show any signal of increased risk of major cardiovascular events between the different basal insulin analogs. However, the number of available cardiovascular events in these trials is very small, preventing any clear-cut conclusion. The results of an ongoing clinical trial comparing glargine and degludec with

  19. Evaluation of the incidence and risk of hypoglycemic coma associated with selection of basal insulin in the treatment of diabetes: a Finnish register linkage study†

    OpenAIRE

    Haukka, Jari; Hoti, Fabian; Erästö, Panu; Saukkonen, Tero; Mäkimattila, Sari; Korhonen, Pasi

    2013-01-01

    Objective Long-acting basal insulin analogs have demonstrated positive effects on the balance between effective glycemic control and risk of hypoglycemia versus neutral protamine Hagedorn (NPH) insulin in randomized controlled trials. Evidence of severe hypoglycemic risk with insulin detemir, insulin glargine, or NPH insulin is presented from a nationwide retrospective database study. Research design and methods Data from hospital and secondary healthcare visits due to hypoglycemic coma from ...

  20. 甘精胰岛素联合阿卡波糖与预混胰岛素治疗2型糖尿病的效果比较%Study on the effects of glargined with acarbose and isophane protamine biosynthetcic human insulin in patients with type 2 diabetic

    Institute of Scientific and Technical Information of China (English)

    李艳萍; 李红梅

    2009-01-01

    目的 比较甘精胰岛素(Glargine)联合阿卡波糖与预混胰岛素(精蛋白生物合成人胰岛素30R)治疗2型糖尿病的疗效及对血糖波动的影响.方法 将65例2型糖尿病随机分为A组采用甘精胰岛素联合阿卡波糖治疗,B组采用预混胰岛素每日2次皮下注射.以空腹血糖(mFBG)<7mmol/L为目标,并监测早餐后2h血糖(mFPIG),午餐后2h血糖(mFP2G)和晚餐后2h血糖(mFP3G)计算1d 4次血糖样本的标准差(SD),以及最高和最低血糖之差(△).观察两组的血糖波动、胰岛素日用量、低血糖发生率.结果 A组胰岛素日用量、低血糖发生率均低于B组(P<0.05),血糖波动小.结论 甘精胰岛素联合阿卡波糖治疗2型糖尿病比预混胰岛素更利于血糖的平稳,低血糖的发生率低,波动影响更小,患者依从性好.

  1. Human Insulin Does Not Increase Bladder Cancer Risk

    OpenAIRE

    Chin-Hsiao Tseng

    2014-01-01

    BACKGROUND: Whether human insulin can induce bladder cancer is rarely studied. METHODS: The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 785,234 patients with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Users of pioglitazone were excluded and the period since the initiation of insulin glargine (marketed after the ent...

  2. Starting Insulin in Type 2 Diabetes: Real-World Outcomes After the First 12 Months of Insulin Therapy in a New Zealand Cohort

    OpenAIRE

    Sehgal, Shekhar; Khanolkar, Manish

    2015-01-01

    Aims Currently, there is no consensus on which form of insulin to use when initiating insulin in type 2 diabetes (T2D). Our aim was to compare glycated hemoglobin (HbA1C) reduction, weight change and severe hypoglycemia rates during the first year after initiation of intermediate-acting insulin isophane, insulin glargine and pre-mixed insulin in patients with T2D. Methods Electronic clinical records of patients with T2D, starting insulin at a tertiary referral center in Auckland, New Zealand,...

  3. Cardiovascular effects of basal insulins.

    Science.gov (United States)

    Mannucci, Edoardo; Giannini, Stefano; Dicembrini, Ilaria

    2015-01-01

    Basal insulin is an important component of treatment for both type 1 and type 2 diabetes. One of the principal aims of treatment in patients with diabetes is the prevention of diabetic complications, including cardiovascular disease. There is some evidence, although controversial, that attainment of good glycemic control reduces long-term cardiovascular risk in both type 1 and type 2 diabetes. The aim of this review is to provide an overview of the potential cardiovascular safety of the different available preparations of basal insulin. Current basal insulin (neutral protamine Hagedorn [NPH], or isophane) and basal insulin analogs (glargine, detemir, and the more recent degludec) differ essentially by various measures of pharmacokinetic and pharmacodynamic effects in the bloodstream, presence and persistence of peak action, and within-subject variability in the glucose-lowering response. The currently available data show that basal insulin analogs have a lower risk of hypoglycemia than NPH human insulin, in both type 1 and type 2 diabetes, then excluding additional harmful effects on the cardiovascular system mediated by activation of the adrenergic system. Given that no biological rationale for a possible difference in cardiovascular effect of basal insulins has been proposed so far, available meta-analyses of publicly disclosed randomized controlled trials do not show any signal of increased risk of major cardiovascular events between the different basal insulin analogs. However, the number of available cardiovascular events in these trials is very small, preventing any clear-cut conclusion. The results of an ongoing clinical trial comparing glargine and degludec with regard to cardiovascular safety will provide definitive evidence. PMID:26203281

  4. 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 studies....... 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...... administered several times daily at mealtimes can improve glycaemic control without increasing the risk of hypoglycaemia. The fast-acting analogues are now also available as insulin mixed with NPH. Insulin glargine is a new long-acting insulin which is soluble and precipitates after injection, resulting...

  5. Insulin requirements in patients with diabetes and declining kidney function: differences between insulin analogues and human insulin?

    Science.gov (United States)

    Kulozik, Felix

    2013-01-01

    Objectives: In diabetic nephropathy the decline of renal function causes modifications of the insulin and carbohydrate metabolism resulting in changed insulin requirements. The aim of the present study was to identify potential differences in the requirements of human insulin and various insulin analogues in patients with type 1 diabetes mellitus and renal dysfunction. Methods: The insulin requirements of 346 patients with type 1 diabetes mellitus under everyday life circumstances were assessed in an observational study. Simultaneously, laboratory parameters were measured and the estimated glomerular filtration rate (eGFR) was calculated using the formula by Cockcroft–Gault. Medical history and concomitant medication were recorded. The insulin requirements of long- and short-acting insulin were tested for a relationship with the eGFR and laboratory parameters. Results: The dosage of long-acting human insulin did not show any relation to eGFR. In contrast, a strong positive relation between dosage and renal function was found for insulin glargine and insulin detemir. After classification according to renal function, the insulin dosage at eGFR less than 60 ml/min was 29.7% lower in glargine-treated and 27.3% lower in detemir-treated patients compared with eGFR greater than 90 ml/min. Considering the whole range of eGFR, short-acting human insulin did not show a relation with renal function. Only after classification according to renal function was a dose reduction found for human insulin at eGFR less than 60 ml/min. In contrast, requirements of insulin lispro were significantly related to eGFR over the whole range of eGFR. At eGFR less than 60 ml/min the insulin dosage was 32.6% lower than at eGFR greater than 90 ml/min. The requirements of insulin aspart did not show any association with the eGFR. Conclusions: Patients with type 1 diabetes mellitus show different insulin requirements according to the renal function depending on the applied insulin. This finding is

  6. Evaluation of the incidence and risk of hypoglycemic coma associated with selection of basal insulin in the treatment of diabetes: a Finnish register linkage study†

    Science.gov (United States)

    Haukka, Jari; Hoti, Fabian; Erästö, Panu; Saukkonen, Tero; Mäkimattila, Sari; Korhonen, Pasi

    2013-01-01

    Objective Long-acting basal insulin analogs have demonstrated positive effects on the balance between effective glycemic control and risk of hypoglycemia versus neutral protamine Hagedorn (NPH) insulin in randomized controlled trials. Evidence of severe hypoglycemic risk with insulin detemir, insulin glargine, or NPH insulin is presented from a nationwide retrospective database study. Research design and methods Data from hospital and secondary healthcare visits due to hypoglycemic coma from 75 682 insulin-naïve type 1 or 2 diabetes patients initiating therapy with NPH insulin, insulin glargine, or insulin detemir in Finland between 2000 and 2009 were analyzed. Incidence rates with 95% confidence intervals (CIs) were calculated using Poisson regression. Hazard ratios were estimated using Cox's regression with adjustments for relevant background variables. Results The adjusted risk of hospital/secondary healthcare visits due to the first severe hypoglycemic event was 21.7% (95% CI 9.6–32.1%, p < 0.001) lower for insulin detemir and 9.9% (95% CI 1.5–17.6%, p = 0.022) lower for insulin glargine versus NPH insulin. Risk of hypoglycemic coma recurrence was 36.3% (95% CI 8.9–55.5%, p = 0.014) lower for detemir and 9.5% but not significantly (95% CI −10.2 to 25.7%, p = 0.318) lower for glargine versus NPH insulin. Risk of all hypoglycemic coma events was 30.8% (95% CI 16.2–42.8%, p-value <0.001) lower for detemir and 15.6% (95% CI 5.1–25.0%, p-value 0.005) lower for glargine versus NPH. Insulin detemir had a significantly lower risk for first (13.1% lower [p = 0.034]), recurrent (29.6% lower [p = 0.021]), and all (17.9% lower [p = 0.016]) severe hypoglycemic events than insulin glargine. Conclusions There were considerable differences in risk of hospitalization or secondary healthcare visits due to hypoglycemic coma between basal insulin treatments in real-life clinical practice. PMID:24150837

  7. 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

  8. Insulin degludec. Uncertainty over cardiovascular harms.

    Science.gov (United States)

    2014-06-01

    Insulin isophane (NPH) is the standard long-acting human insulin for patients with type 1 and type 2 diabetes. Long-acting human insulin analogues are also available: insulin glargine and insulin detemir. Uncertainties remain concerning their long-term adverse effects. Insulin degludec (Tresiba, Novo Nordisk) is another long-acting human insulin analogue, also approved in the EU for patients with type 1 and type 2 diabetes. It was authorised at a concentration of 100 units per ml, like other insulins, and also at a concentration of 200 units per ml. There are no comparative data on insulin degludec 200 units per ml in patients using high doses of insulin. Insulin degludec has mainly been evaluated in ten randomised, unblinded, "non-inferiority" trials lasting 26 to 52 weeks, nine versus insulin glargine and one versus insulin detemir. Insulin degludec was administered at a fixed time each evening, or in either the morning or evening on alternate days, at varying intervals of 8 to 40 hours between doses. Efficacy in terms of HbA1c control was similar to that of the other insulin analogues administered once a day. The frequency of severe hypoglycaemia was similar in the groups treated with insulin degludec and those treated with the other insulins (10% to 12% among patients with type 1 diabetes and less than 5% in patients with type 2 diabetes). Deaths and other serious adverse events were similarly frequent in the different groups. A meta-analysis of clinical trials, carried out by the US Food and Drug Administration, suggested an increase of about 60% in the incidence of cardiovascular complications, based on a composite endpoint combining myocardial infarction, stroke and cardiovascular death. Other adverse effects observed in these trials were already known to occur with human insulin and its analogues, including weight gain, hypersensitivity reactions, reactions at the injection site, etc. The trials were too short in duration to assess long-term harms

  9. An update on the treatment of type 1 and type 2 diabetes mellitus: focus on insulin detemir, a long-acting human insulin analog

    Directory of Open Access Journals (Sweden)

    Katarina Raslova

    2010-05-01

    Full Text Available Katarina RaslovaMetabolic Center Ltd and Slovak Medical University, Bratislava, Slovak RepublicAbstract: Basal insulin analogs are used to minimize unpredictable processes of NPH insulin. Modification of the human insulin molecule results in a slower distribution to peripheral target tissues, a longer duration of action with stable concentrations and thus a lower rate of hypoglycemia. Insulin detemir is a basal insulin analog that provides effective therapeutic options for patients with type 1 and type 2 diabetes. For glycemic control, no significant differences were found in HbA1c levels compared with NPH and insulin glargine. It is comparable with insulin glargine in significantly reducing rates of all types of hypoglycemia. Clinical studies have demonstrated that detemir is responsible for significantly lower within-subject variability and no or less weight gain than NPH insulin and glargine. Recent pharmacodynamic studies have shown that detemir can be used once daily in many patients with diabetes. Together with patient-friendly injection devices and dose adjustments, it provides a treatment option with the potential to lower the key barriers of adherence to insulin therapy in type 2 diabetes. Recent guidelines for treatment of type 2 diabetes suggest starting intensive therapy of hyperglycemia at an early stage of diabetes and recommend therapeutic options that provide the possibility of reaching HbA1c goals individually, with a low risk of hypoglycemia or other adverse effects of treatment. The properties of insulin detemir match these requirements.Keywords: insulin analog, insulin detemir, diabetes mellitus, hypoglycemia, within-subject variability

  10. 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.

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

    Science.gov (United States)

    Werner, Haim; Chantelau, Ernst A

    2011-01-01

    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.

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

    Science.gov (United States)

    2011-01-01

    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. PMID:21714872

  13. Translating structure to clinical properties of an ideal basal insulin.

    Science.gov (United States)

    Unnikrishnan, A G; Bantwal, Ganapathi; Sahay, R K

    2014-01-01

    There is a need for ideal basal insulin which can overcome the unmet need of a truly once daily insulin, with a flat peakless profile. Useful for all types of patients Insulin degludec is next generation insulin with a unique mode of protraction of forming soluble multi-hexamers and slow continuous absorption giving it a flat profile compared to the existing basal insulin. In patients with type 1 diabetes or with type 2 diabetes, at steady-state, the mean terminal half-life of insulin degludec was 25 hours, i.e., approximately twice as long as for insulin glargine (half-life of 12.1 hours). In once-daily dosing regimen it reaches steady state after approximately 3 days. The duration of action of insulin degludec was estimated to be beyond 42 hours in euglycaemic clamp studies and this gives the unique opportunity of flexible time dosing which is not an available option with the existing basal insulin. The glucose-lowering effect is evenly distributed across a 24-hour dosing interval with insulin degludec having 4 times lower variability than insulin glargine. This is an important attribute given the narrow therapeutic window of insulin and the goal of achieving night time and inter-prandial glycaemic control without increasing the risk for hypoglycaemia, a goal that is challenging given the variability of absorption and lower PK half-lives of current basal insulin products. The combination of the ultra-long, flat and stable profile with an improved hour-to-hour and day-to-day variability could present an improved risk-benefit trade-off with the lower risk of hypoglycaemia, allowing for targeting improved levels of glycaemic control.

  14. Pregnancy and the long-acting insulin analogue: a case study.

    Science.gov (United States)

    Caronna, Silvana; Cioni, Federico; Dall'Aglio, Elisabetta; Arsenio, Leone

    2006-04-01

    R.S. is a 22 years old Caucasian woman suffering from obesity, hypertension and Type I Diabetes Mellitus since the age of 6 years. Type I DM treatment includes 3 insulin injections at meal time and one glargine injection at bedtime. The insulin therapy regimen was prolonged during pregnancy and continued after childbirth. Optimal glycemic compensations were monitored throughout the pregnancy using HbA1c variations and other standard controls included in the OBG routine protocols, all within normal values. The pregnancy ended at the 38th week of gestation with a caesarean birth, during which a 3,54 Kg healthy boy with an APGAR of 9 was born. Both the mother and the newborn resulted in perfect health conditions confirming that the possibility of using glargine insulin profiles during pregnancy in selected cases with close monitoring may exist.

  15. Can a new ultra-long-acting insulin analogue improve patient care? Investigating the potential role of insulin degludec.

    Science.gov (United States)

    Robinson, Jennifer D; Neumiller, Joshua J; Campbell, R Keith

    2012-12-24

    The basal-bolus concept of delivering insulin to diabetic patients makes physiological sense, as it mimics normal insulin release in people without diabetes. In line with this concept, a major effort put forth by insulin manufacturers has been to develop the ideal exogenous basal insulin product. The perfect basal insulin product would be injected into subcutaneous tissue without causing irritation, release insulin continuously at a constant rate for at least 24 hours, be stable, not contribute to weight gain, have a low risk of allergic reactions and, very importantly, minimize the risk of hypoglycaemia. While the perfect insulin has not yet been discovered, advancements are still being made. Insulin degludec is an ultra-long-acting basal insulin analogue that possesses a flat, stable glucose-lowering effect in patients with type 1 or type 2 diabetes mellitus. Insulin degludec achieves these pharmacokinetic properties by forming soluble multihexamers upon subcutaneous injection, resulting in the formation of a depot in the subcutaneous tissue that is slowly released and absorbed into circulation. Insulin degludec has been associated with slightly less weight gain and fewer nocturnal hypoglycaemic episodes when compared with insulin glargine in some, but not all, clinical studies. This article briefly reviews current evidence for the use of insulin degludec in patients with type 1 or type 2 diabetes mellitus and discusses the potential impact of this new basal insulin on clinical practice. PMID:23145524

  16. Combination therapy with insulin and oral agents: optimizing glycemic control in patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Yki-Järvinen, Hannele

    2002-01-01

    The United Kingdom Prospective Diabetes Study (UKPDS) showed that tight glycemic control with any of several therapeutic regimens has the potential to significantly reduce the risk for long-term microvascular complications of type 2 diabetes. An important question that remains to be answered is what is the best approach to optimizing glycemic control in patients with this disease. This article reviews results of studies in which insulin was used alone or in combination with oral antidiabetic agents for treatment of patients with type 2 diabetes. Analysis of comparative studies (13 in insulin-naive and 26 in previously insulin-treated patients) showed that combination therapy involving one to two insulin injections per day plus oral therapy is usually more effective than insulin monotherapy for achieving and maintaining glycemic control. Combination treatment for type 2 diabetes can be significantly improved by newly developed preparations that lack the major limitations of older products. Once-daily administration of isophane insulin (NPH insulin) is limited by a 15-18-h duration of action and a peak effect that occurs about 6 h after injection. Insulin glargine, a new insulin analogue developed using recombinant DNA technology, has a flat pharmacodynamic profile and a 24-h duration of action. Results from a recent comparative study indicate that insulin glargine plus oral therapy may provide better post-dinner glucose control as well as less symptomatic and nocturnal hypoglycemia than oral therapy combined with NPH insulin. The studies reviewed in the present article support the conclusion that combination therapy with insulin glargine combined with one or more oral antidiabetic agents may be the treatment of choice for achieving glycemic control in patients with type 2 diabetes. PMID:12324990

  17. 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

  18. Protamine-containing insulins are strong risk factors, and human insulin analogues are possible risk factors for insulin autoantibody: case-control study

    Directory of Open Access Journals (Sweden)

    Hiroyuki Kinoshita

    2013-01-01

    Full Text Available Insulin autoantibody is known to cause fluctuation of blood glucose. We examined whether medications for diabetes are risk factors for insulin autoantibody. Especially, we examined the associations between types of insulin and insulin autoantibody. We performed a case-control study. From April 2005 to March 2010, insulin autoantibody was measured 273 times in 217 patients in our hospital. Insulin autoantibody was positive (greater than 10% 53 times in 19 patients (case, and was negative 220 times in 198 patients (control. Oral hypoglycemic agents were not risk factors for insulin autoantibody; the odds ratio was 0.0. In contrast, insulin use was a significant risk factor for insulin autoantibody; the odds ratio (95% confidence interval was 56.3 (7.3-432.5. As for the types of insulin and insulin autoantibody, human insulins without protamine were not risk factors; the odds ratio was 0.0. For protamine-containing insulins, the odds ratio and adjusted odds ratio (adjusted by age, gender, and disease: type 1 diabetes mellitus, type 2 diabetes mellitus, and no diabetes were 35.3 (9.6-129.5 and 29.6 (7.6- 115.4, respectively. For Aspart-containing insulins, they were 6.2 (2.2-17.9 and 3.8 (1.2- 12.0, respectively. For Glargine, they were 3.2 (0.6-16.7 and 1.3 (0.2-8.3, respectively. To decrease the problem of insulin antibody, avoiding the use of protamine-containing insulins and avoiding the use of human insulin analogues might be preferable for the patients with diabetes.

  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. Successful desensitization with human insulin in a patient with an insulin allergy and hypersensitivity to protamine: a case report

    Directory of Open Access Journals (Sweden)

    Pföhler Claudia

    2008-08-01

    Full Text Available Abstract Introduction Insulin allergy may occur in patients treated with subcutaneous applications of insulin preparations. Besides additives in the insulin preparation such as protamine, cresol, and phenol, the insulin molecule itself may be the cause of the allergy. In the latter case, therapeutic options are rare. Case presentation A 68-year-old man with poorly controlled type 2 diabetes mellitus received different insulin preparations subcutaneously while on oral medication. Six to eight hours after each subcutaneous application, he developed pruritic plaques with a diameter of >15 cm at the injection sites that persisted for several days. Allergologic testing revealed positive reactions against every insulin preparation and against protamine. Investigation of serum samples demonstrated IgG antibodies against human and porcine insulin. We treated the patient with human insulin using an ultra-rush protocol beginning with 0.004 IU and a rapid augmentation in dose up to 5 IU. Therapy was accompanied by antihistamine therapy. Subsequent conversion to therapy with glargine insulin (6 IE twice daily was well-tolerated. Conclusion As reported in this case, desensitization with subcutaneously administered human insulin using an ultra-rush protocol in patients with an insulin allergy may present an easy form of therapy that is successful within a few days.

  1. A critical appraisal of the role of insulin analogues in the management of diabetes mellitus.

    Science.gov (United States)

    Oiknine, Ralph; Bernbaum, Marla; Mooradian, Arshag D

    2005-01-01

    Insulin is one of the oldest and best studied treatments for diabetes mellitus. Despite many improvements in the management of diabetes, the nonphysiological time-action profiles of conventional insulins remain a significant obstacle. However, the advent of recombinant DNA technology made it possible to overcome these limitations in the time-action profiles of conventional insulins. Used as prandial (e.g. insulin lispro or insulin aspart) and basal (e.g. insulin glargine) insulin, the analogues simulate physiological insulin profiles more closely than the older conventional insulins. If rapid-acting insulin analogues are used in the hospital, healthcare providers will need a new mind-set. Any error in coordination between timing of rapid-acting insulin administration and meal ingestion may result in hypoglycaemia. However, guidelines regarding in-hospital use of insulin analogues are few. The safety profile of insulin analogues is still not completely established in long-term clinical studies. Several studies have shown conflicting results with respect to the tumourigenic potential of this new class of agents. The clinical implications of these findings are not clear. Although novel insulin analogues are promising 'designer drugs' in our armamentarium to overcome some of the limitations of conventional insulin therapy, cost may be a limiting factor for some patients. PMID:15669878

  2. Review of insulin and its analogues in diabetes mellitus.

    Science.gov (United States)

    Mane, Krishnappa; Chaluvaraju, Kc; Niranjan, Ms; Zaranappa, Tr; Manjuthej, Tr

    2012-03-01

    Diabetes is a metabolic disorder where in human body does not produce or properly uses insulin, a hormone that is required to convert sugar, starches and other food into energy. Diabetes finally leads to more complications and to prevent these complications insulin and its analogues are used. After more than half a century of treating diabetics with animal insulin's, recombinant DNA technologies and advanced protein chemistry made human insulin preparations available in the early 1980s. As the next step, over the last decade, insulin analogues were constructed by changing the structure of the native protein with the goal of improving the therapeutic properties of it, because the pharmacokinetic characteristics of rapid, intermediate and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. The first clinically available insulin analogue, lispro, confirmed the hopes by showing that improved glycaemic control can be achieved without an increase in hypoglycaemic events. Two new insulin analogues, insulin glargine and insulin aspart, have recently been approved for clinical use in the United States and several other analogues are being intensively tested. PMID:24826038

  3. 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

    : A systematic literature search was performed on breast cell-line, animal and human studies using the key words 'insulin analogue' and 'breast neoplasia' in MEDLINE at PubMed, EMBASE, and ISI Web of Science databases. A quantitative and qualitative review was performed on the epidemiological data; due...... 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...... animal, 2 in vivo human and 29 epidemiological papers were included. Insulin AspB10 showed mitogenic properties in vitro and in animal studies. Glargine was the only clinically available insulin analogue for which an increased proliferative potential was found in breast cancer cell lines. However...

  4. Use of basal insulin and the associated clinical outcomes among elderly nursing home residents with type 2 diabetes mellitus: a retrospective chart review study

    Directory of Open Access Journals (Sweden)

    Davis KL

    2014-10-01

    Full Text Available Keith L Davis,1 Wenhui Wei,2 Juliana L Meyers,1 Brett S Kilpatrick,3 Naushira Pandya4 1RTI Health Solutions, Research Triangle Park, NC, USA; 2Sanofi US, Inc, Bridgewater, NJ, USA; 3AnalytiCare, LLC, Glenview, IL, USA; 4Nova Southeastern University College of Osteopathic Medicine, Fort Lauderdale, FL, USA Background: The management of type 2 diabetes mellitus in long-term care (LTC settings can be complex as a result of age-related complications. Despite guideline recommendations, sliding scale insulin remains commonplace in the LTC setting and data on basal insulin use are lacking.Methods: This retrospective study used medical chart data and the Minimum Data Set from elderly LTC facility patients who received basal insulin (insulin glargine, insulin detemir, or neutral protamine Hagedorn insulin for the treatment of diabetes, to investigate the practice patterns and associated clinical outcomes.Results: A total of 2,096 elderly, insulin-treated patients in LTC were identified, with 59.5% of them (N=1,247 receiving basal insulin. Of these, more than 50% of patients received sliding scale insulin in co-administration with basal insulin. Despite its ease of use, insulin pen use was very low, at 14.6%. Significant differences were observed between the basal insulin groups for glycated hemoglobin level and dosing frequency. Hypoglycemia was uncommon -17.2% of patients experienced at least one event, and there was no significant difference in the prevalence of hypoglycemia between the groups.Conclusion: These data suggest the underutilization of basal insulin in the LTC setting and worryingly high combinational use with sliding scale insulin. Differences in glycated hemoglobin and dosing frequencies between types of basal insulin warrant further comparative effectiveness studies. Keywords: long-term care, nursing homes, type 2 diabetes mellitus, insulin detemir, insulin glargine, NPH insulin

  5. Production and manufacturing of biosimilar insulins: implications for patients, physicians, and health care systems

    Directory of Open Access Journals (Sweden)

    Kuhlmann MK

    2014-11-01

    Full Text Available Martin K Kuhlmann,1 Andrea Schmidt2 1Department of Internal Medicine–Nephrology, Klinikum im Friedrichshain, Berlin, Germany; 2Sanofi, Frankfurt, Germany Abstract: More than 380 million people worldwide have diabetes, a disease that accounts for almost US$550 billion in global health care spending. The majority of patients with diabetes will require insulin replacement as part of their therapeutic regimen. In some countries, the approaching patent expiry dates for the long-acting insulin analog insulin glargine mean there is increasing interest in the potential of biosimilar insulins. However, the production and manufacturing of biosimilar insulins is a proprietary, complex, multistep process in which each stage can potentially introduce variability, possibly leading to adverse clinical and safety outcomes. Thus, marketing authorization in countries in which stringent regulatory requirements are in place requires manufacturers to demonstrate similarity in pharmacokinetic/pharmacodynamic properties, clinical efficacy, and adverse event and immunogenicity profiles, as well as provide proof of the quality of the production process between the biosimilar and the reference insulin product. A risk management plan and pharmacovigilance program may also be needed for the approval process. Regulatory guidelines for the introduction of biosimilar insulins differ between countries but are most developed for the European Union. As of the date of submission of this manuscript (April 30, 2014, no insulin or insulin analogs have received marketing authorization based on the European Union standards established for biosimilars; however, European Medicines Agency approval of a biosimilar glargine insulin is awaited for the end of 2014. In recent years several copies of the long-acting insulin glargine have been brought onto the market in countries such as India, the People’s Republic of China, Pakistan, Mexico, and Kenya without following a biosimilar

  6. 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...

  7. 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

    Luminal nutrients stimulate structural and functional regeneration in the intestine through mechanisms thought to involve insulin-like growth factor I (IGF-I) and glucagon-like peptide-2 (GLP-2). We investigated the relationship between IGF-I and GLP-2 responses and mucosal growth in rats fasted...

  8. Insulin resistance and Alzheimer’s disease

    OpenAIRE

    de la Monte, Suzanne M.

    2009-01-01

    Emerging data demonstrate pivotal roles for brain insulin resistance and insulin deficiency as mediators of cognitive impairment and neurodegeneration, particularly Alzheimer’s disease (AD). Insulin and insulin-like growth factors (IGFs) regulate neuronal survival, energy metabolism, and plasticity, which are required for learning and memory. Hence, endogenous brain-specific impairments in insulin and IGF signaling account for the majority of AD-associated abnormalities. However, a second maj...

  9. Insulin Secretagogues

    Science.gov (United States)

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

  10. Recombinant DNA technology in the treatment of diabetes: insulin analogs.

    Science.gov (United States)

    Vajo, Z; Fawcett, J; Duckworth, W C

    2001-10-01

    After more than half a century of treating diabetics with animal insulins, recombinant DNA technologies and advanced protein chemistry made human insulin preparations available in the early 1980s. As the next step, over the last decade, insulin analogs were constructed by changing the structure of the native protein with the goal of improving the therapeutic properties of it, because the pharmacokinetic characteristics of rapid-, intermediate-, and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. The first clinically available insulin analog, lispro, confirmed the hopes by showing that improved glycemic control can be achieved without an increase in hypoglycemic events. Two new insulin analogs, insulin glargine and insulin aspart, have recently been approved for clinical use in the United States, and several other analogs are being intensively tested. Thus, it appears that a rapid acceleration of basic and clinical research in this arena will be seen, which will have direct significance to both patients and their physicians. The introduction of new short-acting analogs and the development of the first truly long-acting analogs and the development of analogs with increased stability, less variability, and perhaps selective action, will help to develop more individualized treatment strategies targeted to specific patient characteristics and to achieve further improvements in glycemic control. Data on the currently available and tested analogs, as well as data on those currently being developed, are reviewed. PMID:11588149

  11. Insulin allergy treated with human insulin (recombinant DNA).

    Science.gov (United States)

    De Leeuw, I; Delvigne, C; Bekaert, J

    1982-01-01

    Two insulin-dependent diabetic subjects treated with pork and beef insulin during a period of 6 mo developed severe local reactions. Both patients had an important allergic history (asthma, urticaria, drug reactions, rhinitis). Skin-testing revealed type I allergy to beef and pork insulin. Specific IgE-insulin binding was demonstrated with both insulins. After negative skin testing with NPH Lilly human insulin (recombinant DNA), treatment was started with this compound and remained successful during a period of 6-9 mo. In one patient a local reaction occurred when regular human insulin (recombinant DNA) was added to NPH in order to obtain better control. Skin testing with regular human insulin was positive, but not with NPH human insulin alone. The mechanism of this phenomenon remains unsolved. PMID:6765530

  12. Insulin and Insulin Resistance

    OpenAIRE

    Wilcox, Gisela

    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, stru...

  13. 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.

  14. A New Choice for Combination Therapy with Insulin:Adding SGLT-2 Inhibitors to Basal Insulin%胰岛素联合治疗的新选择--基础胰岛素+SGLT-2抑制剂

    Institute of Scientific and Technical Information of China (English)

    郭琳; 李强

    2016-01-01

    Mechanism complementary, simple and effective treatment is important for decreasing the blood glucose level of type 2 diabetes patient. Aglycone SGLT2 inhibitors with competitive combined glucose transporters, effectively restrain the activity of renal proximal convoluted tubules SGLT-2, reduce renal tubular epithelial cells reabsorption of glucose, increase the excretion of urine glucose, thereby reducing the blood sugar level. Because the mechanism is not dependent on insulin secretion and insulin action of unique mechanism of action of SGLT2 inhibitor is especially suitable for as a choice for insulin combined treatment drugs. This paper reviews the basic evidence for insulin combined SGLT-2 inhibitor treatment in the following respects:starting time, patients and safety, to point out the combination therapy in the treatment of type 2 diabetes will have good application prospects.%机制互补且简单有效的治疗方案更利于2型糖尿病患者的血糖管理。S G LT-2抑制剂的糖苷配基通过与葡萄糖竞争性结合转运蛋白,有效抑制肾脏近曲小管S G LT-2的活性,减少肾小管上皮细胞对葡萄糖的重吸收,使尿葡萄糖排泄增加,从而降低血糖水平。由于其不依赖于胰岛素分泌和胰岛素作用的独特的作用机制,SGLT-2抑制剂特别适合作为胰岛素联合治疗的选择药物。本文综述了基础胰岛素联合SGLT-2抑制剂治疗的循证证据、起始时机、适应人群和安全性,指出这种联合治疗在2型糖尿病的治疗中将拥有良好的应用前景。

  15. The efficacy and safety of liraglutide added to metformin in patients with diabetes: a meta-analysis of randomized controlled trials

    Science.gov (United States)

    Gu, Jianqiu; Meng, Xin; Guo, Yan; Wang, Lei; Zheng, Hongzhi; Liu, Yixuan; Wu, Bingshu; Wang, Difei

    2016-09-01

    Liraglutide, a glucagon-like peptide (GLP-1) receptor agonist, has showed favorable effects in the glycaemic control and weight reduction in patients with type 2 diabetes mellitus (T2DM). The meta-analysis was to compare the efficacy and safety of liraglutide added to metformin with other treatments in patients with T2DM. A systematic literature search on PubMed, Embase, Web of Science and the Cochrane library databases were performed. Eligible studies were randomized controlled trials (RCTs) of patients with T2DM who received the combination treatment of liraglutide and metformin. Pooled estimates were performed using a fixed-effects model or random-effects model. A total of nine RCTs met the inclusion criteria. Compared with control (placebo, sitagliptin, glimepiride, dulaglutide, insulin glargine, and NPH), liraglutide in combination with metformin resulted in significant reductions in HbA1c, bodyweight, FPG, and PPG, and similar reductions in SBP, and DBP. Moreover, liraglutide combined with metformin did not increase the risk of hypoglycemia, but induced a higher incidence of gastrointestinal disorders. In conclusion, this meta-analysis confirmed the use of liraglutide as add-on to metformin appeared to be effective and safe for patients with T2DM. However, considering the potential limitations in this study, more large-scale, well-conducted RCTs are needed to identify our findings.

  16. The efficacy and safety of liraglutide added to metformin in patients with diabetes: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Gu, Jianqiu; Meng, Xin; Guo, Yan; Wang, Lei; Zheng, Hongzhi; Liu, Yixuan; Wu, Bingshu; Wang, Difei

    2016-01-01

    Liraglutide, a glucagon-like peptide (GLP-1) receptor agonist, has showed favorable effects in the glycaemic control and weight reduction in patients with type 2 diabetes mellitus (T2DM). The meta-analysis was to compare the efficacy and safety of liraglutide added to metformin with other treatments in patients with T2DM. A systematic literature search on PubMed, Embase, Web of Science and the Cochrane library databases were performed. Eligible studies were randomized controlled trials (RCTs) of patients with T2DM who received the combination treatment of liraglutide and metformin. Pooled estimates were performed using a fixed-effects model or random-effects model. A total of nine RCTs met the inclusion criteria. Compared with control (placebo, sitagliptin, glimepiride, dulaglutide, insulin glargine, and NPH), liraglutide in combination with metformin resulted in significant reductions in HbA1c, bodyweight, FPG, and PPG, and similar reductions in SBP, and DBP. Moreover, liraglutide combined with metformin did not increase the risk of hypoglycemia, but induced a higher incidence of gastrointestinal disorders. In conclusion, this meta-analysis confirmed the use of liraglutide as add-on to metformin appeared to be effective and safe for patients with T2DM. However, considering the potential limitations in this study, more large-scale, well-conducted RCTs are needed to identify our findings. PMID:27600499

  17. 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

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

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    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.

  19. Insulin Test

    Science.gov (United States)

    ... especially as a result of taking non-human (animal or synthetic) insulin, these can interfere with insulin testing. In this case, a C-peptide may be performed as an alternative way to evaluate insulin production. Note also that ...

  20. The role of insulin analogues in the current treatment of diabetes mellitus

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    Mitrović Milena

    2006-01-01

    Full Text Available Introduction. Ever since insulin was discovered by Banting and Best in 1921, all further researches in this field had been conducted with one goal: to find new insulin molecules which would provide better glycemic control with fewer side effects i.e. to mimic endogenous physiological insulin secretion. Normal insulin secretion. In healthy individuals, endogenous insulin secretion can be classified as basal (which provides basal glucose homeostasis and stimulated (as a response to a meal. Conventional insulin preparations - human insulin, have time-action profiles that cannot fully imitate endogenous insulin secretion, thus leading to postprandial hyperglicemia and high glycemic oscilations during the day. Rapid-acting analogues. Rapid acting analogues should have a time-action profile with onset of less than one hour, duration less than four hours, hypoglycemic potency equal or greater than that of human insulin, and similar effects in all patients. Two rapid action analouges, lispro and aspart are available. Basal insulin analogues. The ideal basal insulin should provide slow and constant absorption, long half-life that would provide once daily dosing (or every other day, and peakless effect. Insulin glargine led to solubility at pH 4 and to slow absorption in neutral pH environment. Insulin detemir is a soluble insulin analogue with neutral pH and affinity to bind to serum albumin, thus gaining prolonged action. Mitogenic influence. The mitogenic influence of insulin is due to the affinity to bind to IGF-1 receptors. Following two-year administration of glargine in mice and rats, systemic carcinogenic potential was not found, though there were reports of hepatocellular carcinomas, which are frequently found in these animals. Conclusion. In the last two decades, many trials have shown that unsatisfactory glycemic control leads to chronic complications in both types of diabetes. Using basal glucose level, postprandial glycemy and HbA1c as

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

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    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.

  2. Pharmacokinetics and pharmacodynamics of insulin analogs in special populations with type 2 diabetes mellitus

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    Morello CM

    2011-12-01

    Full Text Available Candis M Morello1,21Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 2School of Pharmacy, University of California San Francisco, Veterans Affairs San Diego Healthcare System, San Diego, CA, USAIntroduction: The goal of insulin therapy in patients with either type 1 diabetes mellitus (T1DM or type 2 diabetes mellitus (T2DM is to match as closely as possible normal physiologic insulin secretion to control fasting and postprandial plasma glucose. Modifications of the insulin molecule have resulted in two long-acting insulin analogs (glargine and detemir and three rapid-acting insulins (aspart, lispro, and glulisine with improved pharmacokinetic/pharmacodynamic (PK/PD profiles. These agents can be used together in basal-bolus therapy to more closely mimic physiologic insulin secretion patterns.Methods: This study reviews effects of the multiple demographic and clinical parameters in the insulin analogs glargine, detemir, lispro, aspart, and glulisine in patients with T2DM. A search was conducted on PubMed for each major topic considered (effects of injection site, age, race/ethnicity, obesity, renal or hepatic dysfunction, pregnancy, exercise, drug interactions using the topic words and name of each type of insulin analog. Information was also obtained from the prescribing information for each insulin analog.Results: The PK/PD profiles for insulin analogs may be influenced by many variables including age, weight, and hepatic and renal function. However, these variables do not have equivalent effects on all long-acting or rapid-acting insulin analogs.Conclusion: Rapid-acting and long-acting insulin analogs represent major advances in treatment for patients with T2DM who require insulin therapy. However, there are potentially important PK and PD differences between the two long-acting agents and among the three rapid-acting insulin analogs, which should be considered when designing treatment regimens for

  3. Effecttivity and safety of glargine treatment on perioperative patients with type 2 diabetes%甘精胰岛素用于2型糖尿病患者围手术期的疗效及安全性评价

    Institute of Scientific and Technical Information of China (English)

    熊燕; 赖晓阳; 张美英

    2011-01-01

    Objective To observe the clinical effectivity and safety of Glargine treatment in perioperative patient with type 2 diabetes. Methods 60 T2DM patients scheduled for surgery were divided into glargine insulin group (Gla, n=30) and MDI group (Humulin N, n=30). The Dosage was adjusted according to a blood glucose fluctuations to compare the effect and safety between the two groups. Results The levels of blood glucose in the two groups were reduced after treatments (P<0. 01) and there is no significant difference in hypoglycemic effect between the two groups (P>0. 05). But the blood glucose fluctuation was smaller in Gla group than in MDI group and the glucose target arrival time was shorter in Gla group than in MDI group (P<0. 01). The insulin dosage, the incidences of hypoglycemia and wound infection and delayed healing rate were less in Gla group than in MDI group (P<0. 05). Conclusions Glargine treatment can effectively, rapidly and savely control the blood glucose and is especially suitable for the perioperative patient requiring a sufficient basal insulin.%目的 观察2型糖尿病(T2DM)患者围手术期甘精胰岛素治疗的临床疗效及安全性.方法 将60例拟行手术治疗的T2DM患者分为甘精胰岛素治疗组(Gla组,30例)及分次皮下注射胰岛素组(MDI组,30例),控制围手术期血糖.根据血糖监测结果调整药物剂量,比较2组患者降糖疗效及安全性.结果 两组均可有效降低血糖(P0.05).但Gla组血糖波动更小,达到良好血糖控制的所需时间明显缩短(P<0.01);Gla组胰岛素用量、低血糖发生率、切口感染或延迟愈合率均少于MDI组(P<0.05).结论 甘精胰岛素治疗能有效、安全、平稳、迅速地控制血糖,尤其适用于需要更有效补充基础胰岛素治疗阶段的糖尿病围手术期患者,值得临床推广运用.

  4. 甘精胰岛素及格列美脲对新诊断2型糖尿病患者血糖波动的影响%Effect of glargine combined with glimepiride on blood glucose variability in newly diagnosed type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)

    余维巍; 李彩萍

    2012-01-01

    Objective To explore the effect of glargine combined with glimepiride on blood glucose variability irt newly diagnosed type 2 diabetic patients with HbA1c>9%. Methods Forty-six patients were randomized into two groups and treated with glargine plus glimepiride versus insulin aspart 30 respectively for 12 weeks. The daily blood glucose level was measured with the continuous glucose monitoring system and compared before and after intensive therapy between two groups. Results The blood glucose levels in both groups were well controlled. However, there was a more stable blood glucose profile, less hypoglycemia, and smaller insulin dosage in the group treated with glargine + glimepiride than in insulin aspart 30 group (P9%.%目的 探讨甘精胰岛素联合格列美脲及诺和锐30对HbA1c>9%的新诊断T2DM患者血糖波动的影响. 方法 将46例新诊断的T2DM患者随机分为甘精胰岛素联合格列美脲(IG)组与诺和锐30(AS30)组.IG组予以睡前皮下注射甘精胰岛素联合口服格列美脲治疗12周;AS30组予以诺和锐30于早晚餐时皮下注射12周,对比两组治疗前后血糖谱的变化. 结果 IG组与AS30组血糖均得到效控制,但IG组血糖波动小、低血糖事件发生率低、胰岛素用量少(P<0.05). 结论 甘精胰岛素联合格列美脲对HbA1c>9%的新诊断T2DM患者是一种更为安全、方便的治疗方案.

  5. 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

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

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    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.

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

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    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.

  8. Quantitation of Insulin Analogues in Serum Using Immunoaffinity Extraction, Liquid Chromatography, and Tandem Mass Spectrometry.

    Science.gov (United States)

    Van Der Gugten, J Grace; Wong, Sophia; Holmes, Daniel T

    2016-01-01

    Insulin analysis is used in combination with glucose, C-peptide, beta-hydroxybutyrate, and proinsulin determination for the investigation of adult hypoglycemia. The most common cause is the administration of too much insulin or insulin secretagogue to a diabetic patient or inadequate caloric intake after administration of either. Occasionally there is a question as to whether hypoglycemia has been caused by an exogenous insulin-whether by accident, intent, or even malicious intent. While traditionally this was confirmed by a low or undetectable C-peptide in a hypoglycemic specimen, this finding is not entirely specific and would also be expected in the context of impaired counter-regulatory response, fatty acid oxidation defects, and liver failure-though beta-hydroxybutyrate levels can lend diagnostic clarity. For this reason, insulin is often requested. However, popular automated chemiluminescent immunoassays for insulin have distinctly heterogeneous performance in detecting analogue synthetic insulins with cross-reactivities ranging from near 0 % to greater than 100 %. The ability to detect synthetic insulins is vendor-specific and varies between insulin products. Liquid Chromatography and Tandem Mass Spectrometry (LC-MS/MS) offers a means to circumvent these analytical issues and both quantify synthetic insulins and identify the specific type. We present an immunoaffinity extraction and LC-MS/MS method capable of independent identification and quantitation of native sequence insulins (endogenous, Insulin Regular, Insulin NPH), and analogues Glargine, Lispro, Detemir, and Aspart with an analytical sensitivity for endogenous insulin of between 1 and 2 μU/mL in patient serum samples.

  9. Insulin Injection

    Science.gov (United States)

    ... or buttocks. Do not inject insulin into muscles, scars, or moles. Use a different site for each ... you are using insulin.Alcohol may cause a decrease in blood sugar. Ask your doctor about the ...

  10. [Insulin therapy for type 1 diabetes mellitus: past and present].

    Science.gov (United States)

    Pires, Antonio Carlos; Chacra, Antonio Roberto

    2008-03-01

    The discovery of insulin can be considered the milestone of diabetes mellitus history and a great achievement for its treatment. The first insulin available was the regular. Afterwards, Hagedorn added the protamine to the insulin, thus, creating the NPH insulin. In the 1950s an insulin free of protamine was synthesized: the lente insulin. With the advent of molecular biology, synthetic human insulin was synthesized using recombinant DNA technology. Most recently several types of insulin analogues were available, providing the patients with better metabolic control. Type 1 diabetes mellitus treatment includes plain substitution and individualization for short-acting plus long-acting insulin according to the physician's assistance, besides regular practice of physical activities and diet orientations. In type 1 diabetes mellitus the insulin of low variability is the best choice since basal/bolus insulin therapy or continuous subcutaneous insulin infusion pump can mimetize the physiological release of insulin by beta cells. PMID:18438537

  11. Biphasic Insulin Aspart 30/70: Pharmacokinetics and Pharmacodynamics Compared With Once-Daily Biphasic Human Insulin and Basal-Bolus Therapy

    Science.gov (United States)

    Heise, Tim; Heinemann, Lutz; Hövelmann, Ulrike; Brauns, Bianca; Nosek, Leszek; Haahr, Hanne L.; Olsen, Klaus J.

    2009-01-01

    OBJECTIVE Pharmacological profiles of biphasic insulin aspart 30/70 (BIAsp 30) once daily (OD), twice daily (b.i.d.), and three times daily (t.i.d.) were compared with other insulin regimens in two crossover glucose clamp studies of insulin-treated type 2 diabetic patients. RESEARCH DESIGNS AND METHODS Study 1 consisted of BIAsp 30 OD, b.i.d., and t.i.d. versus biphasic human insulin 30/70 (BHI 30), OD (n = 24). Study 2 examined BIAsp 30 t.i.d. versus basal-bolus therapy (insulin glargine OD plus insulin glulisine t.i.d.) (n = 24). Pharmacokinetics/pharmacodynamics (PK/PD) were investigated over 24 h. RESULTS Study 1: PK and PD were markedly different between BIAsp 30 OD and BHI 30 OD: the maximum insulin concentration and glucose infusion rate (GIR) were higher for BIAsp 30; time to maximum metabolism was 1.7 h sooner for BIAsp 30. Study 2: both regimens showed three distinct prandial-related GIR peaks. GIR 24-h area under the curve for BIAsp t.i.d. was higher than for basal-bolus therapy: 2,585.2 vs. 2,289.2 mg/kg. CONCLUSIONS BIAsp had pharmacological advantages over BHI. BIAsp t.i.d. had a similar PD profile to basal-bolus therapy. PMID:19487640

  12. Oral Insulin

    OpenAIRE

    Kalra Sanjay; Kalra Bharti; Agrawal Navneet

    2010-01-01

    Abstract Oral insulin is an exciting area of research and development in the field of diabetology. This brief review covers the various approaches used in the development of oral insulin, and highlights some of the recent data related to novel oral insulin preparation.

  13. Insulin resistance and hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Manuel Romero-Gómez

    2006-01-01

    Insulin resistance is the major feature of the metabolic syndrome and depends on insulin secretion and insulin sensitivity. In chronic hepatitis C, insulin resistance and type 2 diabetes mellitus are more often seen than in healthy controls or chronic hepatitis B patients.Hepatitis C virus (HCV) infection promotes insulin resistance, mainly by increased TNF production together with enhancement of suppressor of cytokine (SOC-3); both events block PI3K and Akt phosphorylation. Two types of insulin resistance could be found in chronic hepatitis C patients: "viral" and "metabolic" insulin resistance. Insulin resistance in chronic hepatitis C is relevant because it promotes steatosis and fibrosis. The mechanisms by which insulin resistance promotes fibrosis progression include: (1) steatosis, (2) hyperleptinemia, (3) increased TNF production, (4) impaired expression of PPARy receptors. Lastly, insulin resistance has been found as a common denominator in patients difficult-to-treat like cirrhotics, overweight, HIV coinfected and Afro-American.Insulin resistance together with fibrosis and genotype has been found to be independently associated with impaired response rate to peginterferon plus ribavirin.Indeed, in genotype 1, the sustained response rate was twice (60%) in patients with HOMA ≤ 2 than patients with HOMA > 2. In experiments carried out on Huh-7cells transfected by full length HCVRNA, interferon alpha blocks HCV replication. However, when insulin (at doses of 128 μU/mL, similar that seen in the hyperinsulinemic state) was added to interferon, the ability to block HCV replication disappeared, and the PKR synthesis was abolished. In summary, hepatitis C promotes insulin resistance and insulin resistance induces interferon resistance,steatosis and fibrosis progression.

  14. 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.

  15. Comparison of efficacy and safety of two starting insulin regimens in non-Asian, Asian Indian, and East Asian patients with type 2 diabetes: a post hoc analysis of the PARADIGM study

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    Ji L

    2016-08-01

    Full Text Available Linong Ji,1 Kyung Wan Min,2 Juliana Oliveira,3 Thomas Lew,4 Ran Duan3 1Department of Endocrinology, Peking University People's Hospital, Beijing, People's Republic of China; 2Department of Endocrinology, Eulji Hospital, Seoul, Republic of Korea; 3Eli Lilly and Company, Indianapolis, IN, USA; 4Eli Lilly and Company, Taipei, Songshan District, Taiwan Objective: The objective of this study was to explore the efficacy and safety of insulin lispro mix 25 (25% insulin lispro and 75% insulin lispro protamine suspension [LM25] or insulin glargine plus insulin lispro (G+L in insulin-naïve patients with type 2 diabetes from different racial/ethnic groups. Methods: Three subgroups from the PARADIGM study were analyzed post hoc: non-Asian (n=130, Asian Indian (n=106, and East Asian (n=89. Results: All subgroups recorded glycated hemoglobin (HbA1c reductions: non-Asian (LM25, -2.07%; G+L, -2.05%, Asian Indian (LM25, -1.75%; G+L, -1.60%, and East Asian (LM25, -2.03%; G+L, -1.76%; end point HbA1c values were higher in Asian Indians and East Asians than in non-Asians. Fewer Asian Indians (LM25, 43.2%; G+L, 29.2% and East Asians (LM25, 37.5%; G+L, 36.1% reached HbA1c ,7% versus non-Asians (LM25, 51.7%; G+L, 48.1%; differences were not significant (P=0.12 and P=0.06, respectively. The mean total daily insulin dose (U/kg for non-Asians was 0.67 (LM25 and 0.61 (G+L, for Asian Indians was 0.91 (LM25 and 0.90 (G+L, and for East Asians was 0.53 (LM25 and 0.59 (G+L. The ratio of mealtime to total insulin dose in the G+L arm for non-Asians was 0.19±0.23, for Asian Indians was 0.33±0.25, and for East Asians was 0.34±0.27. Overall incidence (% of hypoglycemia in non-Asians was 94.1 (LM25 and 91.8 (G+L, in Asian Indians was 90.4 (LM25 and 88.5 (G+L, and in East Asians was 69.8 (LM25 and 77.3 (G+L. Conclusion: Asian Indians showed least improvement in glycemic HbA1c reduction despite greater insulin use. East Asians and non-Asians achieved similar HbA1c reduction in the

  16. Human insulin does not increase bladder cancer risk.

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    Chin-Hsiao Tseng

    Full Text Available BACKGROUND: Whether human insulin can induce bladder cancer is rarely studied. METHODS: The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 785,234 patients with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Users of pioglitazone were excluded and the period since the initiation of insulin glargine (marketed after the entry date in Taiwan was not included in the calculation of follow-up. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, duration of therapy and cumulative dose were calculated and the hazard ratios were estimated by Cox regression. RESULTS: There were 87,940 ever-users and 697,294 never-users, with respective numbers of incident bladder cancer of 454 (0.52% and 3,330 (0.48%, and respective incidence of 120.49 and 94.74 per 100,000 person-years. The overall hazard ratios (95% confidence intervals indicated a significant association with insulin in the age-sex-adjusted models [1.238 (1.122-1.366], but not in the model adjusted for all covariates [1.063 (0.951-1.187]. There was also a significant trend for the hazard ratios for the different categories of the dose-response parameters in the age-sex-adjusted models, which became insignificant when all covariates were adjusted. CONCLUSIONS: This study relieves the concern of a bladder cancer risk associated with human insulin. Appropriate adjustment for confounders is important in the evaluation of cancer risk associated with a medication.

  17. Human Insulin Does Not Increase Bladder Cancer Risk

    Science.gov (United States)

    Tseng, Chin-Hsiao

    2014-01-01

    Background Whether human insulin can induce bladder cancer is rarely studied. Methods The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 785,234 patients with type 2 diabetes were followed up for bladder cancer incidence until the end of 2009. Users of pioglitazone were excluded and the period since the initiation of insulin glargine (marketed after the entry date in Taiwan) was not included in the calculation of follow-up. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, duration of therapy and cumulative dose) were calculated and the hazard ratios were estimated by Cox regression. Results There were 87,940 ever-users and 697,294 never-users, with respective numbers of incident bladder cancer of 454 (0.52%) and 3,330 (0.48%), and respective incidence of 120.49 and 94.74 per 100,000 person-years. The overall hazard ratios (95% confidence intervals) indicated a significant association with insulin in the age-sex-adjusted models [1.238 (1.122–1.366)], but not in the model adjusted for all covariates [1.063 (0.951–1.187)]. There was also a significant trend for the hazard ratios for the different categories of the dose-response parameters in the age-sex-adjusted models, which became insignificant when all covariates were adjusted. Conclusions This study relieves the concern of a bladder cancer risk associated with human insulin. Appropriate adjustment for confounders is important in the evaluation of cancer risk associated with a medication. PMID:24466131

  18. Comparison of efficacy and safety of two starting insulin regimens in non-Asian, Asian Indian, and East Asian patients with type 2 diabetes: a post hoc analysis of the PARADIGM study

    Science.gov (United States)

    Ji, Linong; Min, Kyung Wan; Oliveira, Juliana; Lew, Thomas; Duan, Ran

    2016-01-01

    Objective The objective of this study was to explore the efficacy and safety of insulin lispro mix 25 (25% insulin lispro and 75% insulin lispro protamine suspension [LM25]) or insulin glargine plus insulin lispro (G+L) in insulin-naïve patients with type 2 diabetes from different racial/ethnic groups. Methods Three subgroups from the PARADIGM study were analyzed post hoc: non-Asian (n=130), Asian Indian (n=106), and East Asian (n=89). Results All subgroups recorded glycated hemoglobin (HbA1c) reductions: non-Asian (LM25, −2.07%; G+L, −2.05%), Asian Indian (LM25, −1.75%; G+L, −1.60%), and East Asian (LM25, −2.03%; G+L, −1.76%); end point HbA1c values were higher in Asian Indians and East Asians than in non-Asians. Fewer Asian Indians (LM25, 43.2%; G+L, 29.2%) and East Asians (LM25, 37.5%; G+L, 36.1%) reached HbA1c <7% versus non-Asians (LM25, 51.7%; G+L, 48.1%); differences were not significant (P=0.12 and P=0.06, respectively). The mean total daily insulin dose (U/kg) for non-Asians was 0.67 (LM25) and 0.61 (G+L), for Asian Indians was 0.91 (LM25) and 0.90 (G+L), and for East Asians was 0.53 (LM25) and 0.59 (G+L). The ratio of mealtime to total insulin dose in the G+L arm for non-Asians was 0.19±0.23, for Asian Indians was 0.33±0.25, and for East Asians was 0.34±0.27. Overall incidence (%) of hypoglycemia in non-Asians was 94.1 (LM25) and 91.8 (G+L), in Asian Indians was 90.4 (LM25) and 88.5 (G+L), and in East Asians was 69.8 (LM25) and 77.3 (G+L). Conclusion Asian Indians showed least improvement in glycemic HbA1c reduction despite greater insulin use. East Asians and non-Asians achieved similar HbA1c reduction in the LM25 arm with a lower rate of hypoglycemia. Asians required more mealtime insulin coverage than non-Asians. This study added important insight into the effect of ethnicity on insulin treatment outcomes in patients with type 2 diabetes.

  19. Hairy AdS Solitons

    CERN Document Server

    Anabalon, Andres; Choque, David

    2016-01-01

    We construct exact hairy AdS soliton solutions in Einstein-dilaton gravity theory. We discuss the role of these solutions for the existence of first order phase transitions for planar hairy black holes within these theories.

  20. Newer insulin analogues and inhaled insulin

    OpenAIRE

    Girish C; Manikandan S; Jayanthi M

    2006-01-01

    Diabetes is a metabolic disease with high prevalence worldwide. Exogenous insulin is used in the management of this condition. The development of human insulin has provided tighter control of glycaemia in diabetic patients. Insulin analogues like insulin lispro and aspart were developed to closely match its profile with physiological secretion. The newer additions to this armamentarium are insulin glulisine, insulin detemir and albulin.Insulin glulisine is a short acting analogue with a rapid...

  1. 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

  2. Glycemic Effects of Once-a-Day Rapid-Acting Insulin Analogue Addition on a Basal Insulin Analogue in Korean Subjects with Poorly Controlled Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Eun Yeong Choe

    2012-06-01

    Full Text Available BackgroundThe present study investigates the efficacy in glycemic control by adding once-a-day glulisine to glargine as a basal plus regimen and factors influencing glycemic control with the basal plus regimen in Korean subjects with type 2 diabetes.MethodsIn the present retrospective study, subjects previously treated with the basal plus regimens for at least 6 months were reviewed. Changes in glycemic profiles and clinical parameters were evaluated.ResultsA total of 87 subjects were ultimately enrolled in this study. At baseline, mean glycated hemoglobin (A1c and glycated albumin were 8.5% (8.0% to 9.6% and 25.2±7.6%, respectively. After treatment with the basal plus regimen, patients had significant reductions of A1c at 6 months (0.8±0.1%, P<0.001 and their postprandial glucose levels were decreased by 48.7±10.3 mg/dL (P<0.001. Multiple logistic regression showed old age (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.02 to 1.55, high initial A1c (OR, 22.21; 95% CI, 2.44 to 201.78, and lower amounts of glargine (OR, 0.85; 95% CI, 0.76 to 0.99, and glimepiride (OR, 0.23; 95% CI, 0.06 to 0.93 at baseline were independently associated with good responders whose A1c reduction was more than 0.5%.ConclusionThe authors suggest a basal plus regimen may be effective in reducing glucose levels of subjects with old age, high initial A1c, and patients on low doses of glimepiride and glargine. Despite the use of high doses of hypoglycemic agents, elderly patients with poorly-controlled diabetes are preferred for early initiation of the basal plus regimen.

  3. 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

  4. 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.

    Science.gov (United States)

    Rojas, Joselyn; Villalobos, Marjorie; Martínez, María Sofía; Chávez-Castillo, Mervin; Torres, Wheeler; Mejías, José Carlos; Miquilena, Edgar; Bermúdez, Valmore

    2014-01-01

    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. PMID:25548690

  5. 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.

  6. Added Sugars

    Science.gov (United States)

    ... Restaurant Deciphering the Menu Ordering Your Meal Eating Fast Food Dining Out Tips by Cuisine Physical Activity Fitness ... Learn more about reading food labels . Limit your consumption of foods with high amounts of added sugars, ...

  7. 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.

  8. Wormholes in AdS

    OpenAIRE

    Maldacena, Juan; Maoz, Liat

    2004-01-01

    We construct a few Euclidean supergravity solutions with multiple boundaries. We consider examples where the corresponding boundary field theory is well defined on each boundary. We point out that these configurations are puzzling from the AdS/CFT point of view. A proper understanding of the AdS/CFT dictionary for these cases might yield some information about the physics of closed universes.

  9. 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

  10. 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

    Institute of Scientific and Technical Information of China (English)

    Gang Wu; Dong-Liang Liu; Xiang-Jun Li; Xiao-Yun Fan

    2016-01-01

    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 micro-inflammatory 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.

  11. Clinical comparative study of three kinds of insulin application schemes in the treatment of patients with type 2 diabetes for poor glycemic control by oral hypoglycemic drugs%三种胰岛素应用方案治疗口服降糖药物血糖控制不佳2型糖尿病临床对比研究

    Institute of Scientific and Technical Information of China (English)

    刘咏梅

    2016-01-01

    Objective:To investigate the clinical effects and safety differences of three kinds of insulin application schemes in the treatment of pa-tients with type 2 diabetes for poor glycemic control by oral hypoglycemic drugs including neutral protamine zinc insulin ,insulin glargine and insulin detemir .Methods :150 patients with type 2 diabetes for poor glycemic control by oral hypoglycemic drugs were chosen in our hospital in the period from March 2012 to June 2015 and randomly divided into 3 groups including A group (50 patients) with neutral protamine zinc insulin ,B group (50 pa-tients) with insulin glargine and C group (50patients) with insulin detemir ;and the blood glucose index level before and after treatment ,insulin dosage and the incidence of hypoglycemia of 3 groups were compared .Results:The blood glucose index level after treatment of 3 groups was significantly lower than before treatment(P0 .05) .The insulin dosage of A group was significantly fewer than B group and C group(P0 .05);A 组患者胰岛素用量显著多于B组、C组 ,差异有统计学意义(P<0 .05);A 组患者低血糖发生率显著高于B组、C组 ,差异有统计学意义(P<0 .05).结论:三种胰岛素应用方案治疗口服降糖药物血糖控制不佳2 型糖尿病临床疗效接近 ,但甘精胰岛素和地特胰岛素应用可有效减少胰岛素用量 ,降低低血糖发生风险.

  12. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... Disease Organizations (PDF, 293 KB). Alternate Language URL Insulin Resistance and Prediabetes Page Content On this page: ... Nutrition Points to Remember Clinical Trials What is insulin? Insulin is a hormone made in the pancreas, ...

  13. Increased skeletal muscle capillarization enhances insulin sensitivity.

    Science.gov (United States)

    Akerstrom, Thorbjorn; Laub, Lasse; Vedel, Kenneth; Brand, Christian Lehn; Pedersen, Bente Klarlund; Lindqvist, Anna Kaufmann; Wojtaszewski, Jørgen F P; Hellsten, Ylva

    2014-12-15

    Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. Therefore, we investigated whether increased skeletal muscle capillarization increases insulin sensitivity. Skeletal muscle-specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist prazosin to the drinking water of Sprague-Dawley rats (n = 33), whereas 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-wk 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 insulin sensitivity increased by ∼24%, and insulin-stimulated skeletal muscle 2-deoxy-[(3)H]glucose disposal increased by ∼30% concomitant with an ∼20% increase in skeletal muscle capillarization. Adipose tissue insulin sensitivity was not affected by the treatment. Insulin-stimulated muscle glucose uptake was enhanced independent of improvements in skeletal muscle insulin signaling to glucose uptake and glycogen synthesis, suggesting that the improvement in insulin-stimulated muscle glucose uptake could be due to improved diffusion conditions for glucose in the muscle. The prazosin treatment did not affect the rats on any other parameters measured. We conclude that an increase in skeletal muscle capillarization is associated with increased insulin sensitivity. These data point toward the importance of increasing skeletal muscle capillarization for prevention or treatment of type 2 diabetes. PMID:25352432

  14. Relationship Between Plasma Insulin Level and Apolipoprotein E Gene Polymorphysm in Alzheimer′s Disease

    Institute of Scientific and Technical Information of China (English)

    Luo Zhuming; Yuan Qiang

    2000-01-01

    Objective: To study relationship between plasma insulin level and apolipoprotein E Gene polymorphysm in Alzheimcr′s Disease. Background: Recent researches have shown that there was a close relationship between ApoE- ε 4 allele and AD. Because of the discovery of hyperinsulineamia in AD patients, the study of insulin on the pathogenesis of AD become a hot point of AD reseearch. Methods: We apply PCR-RFLP to the ApoE genotype study of 45 AD paticnts and 32 normal controls. At the same time, plasma insulin and glucose level was measured in the abovc objects. Results and Discussion: The frequency of ApoE- ε 4 in AD (32.2%) is much higher than in controls (10.9%). On the contrary, the frequency of ApeE- ε 4 is relatively lower in AD than in thc controls. The resistence of hyperinsulineamia in AD. Insulin sensitivity decreased in AD. Conclusion: When gene dose of ApoE- ε 4 increases, the prcvalance of AD increase, while the on-set ages of AD decrease (P<0.05). These findings indicatc that AD patients may have insulin resistance anbd insulin probably play a role in AD pathogenesis. In addition, the s 4 homozygote AD patients seem to have loweer plasma insulin level that the non- ε 4 homozygote AD patients (P<0.05). But this situation need to be replicated in studies of larger sample.

  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. PMID:25219675

  16. Insulin Resistance and Hyperinsulinemia

    OpenAIRE

    Kim, Sun H.; Reaven, Gerald M

    2008-01-01

    OBJECTIVE—Recently, it has been suggested that insulin resistance and hyperinsulinemia can exist in isolation and have differential impacts on cardiovascular disease (CVD). To evaluate this suggestion, we assessed the degree of discordance between insulin sensitivity and insulin response in a healthy, nondiabetic population. RESEARCH DESIGN AND METHODS—Insulin sensitivity was quantified by determining the steady-state plasma glucose (SSPG) concentration during an insulin suppression test in 4...

  17. Autoantibodies against human insulin.

    OpenAIRE

    Wilkin, T J; Nicholson, S.

    1984-01-01

    Sera from 680 non-diabetic subjects with suspected autoimmune disease were screened for 13 different antibodies. Of the 582 sera found to contain these antibodies, nine bound insulin in an IgG specific enzyme linked immunosorbent assay (micro ELISA). Four of the sera bound human, porcine, and bovine insulins and five bound exclusively human insulin. "Cold" human, porcine, and bovine insulins each displaced, in a dose dependent manner, the four sera which bound all three insulins, but only hum...

  18. NEWER STRATEGIES FOR INSULIN DELIVERY

    OpenAIRE

    Singh Nisha; Lokwani Priyanka; Kaushik Avinash Yogendraji; Sharma Ritu

    2011-01-01

    Insulin is a proteinaceous hormone produced in the islets of Langerhans in the pancreas and used as a treatment in the diabetes mellitus. Successful oral insulin delivery involves overcoming the enzymatic and physical barriers and taking steps to conserve bioactivity during formulation processing. Newer strategies for insulin delivery include insulin pen injector, Refillable insulin injection pen, Insulin Syringe, Transfersome and Implantable insulin pumps.

  19. Insulin pumps.

    Science.gov (United States)

    Pickup, J

    2011-02-01

    The last year has seen a continued uptake of insulin pump therapy in most countries. The USA is still a leader in pump use, with probably some 40% of type 1 diabetic patients on continuous subcutaneous insulin infusion (CSII), but the large variation in usage within Europe remains, with relatively high use (> 15%) in, for example, Norway, Austria, Germany and Sweden and low use (companies or funding from national health services, the availability of sufficient diabetes nurse educators and dietitians trained in pump procedures, and clear referral pathways for the pump candidate from general practitioner or general hospital to specialist pump centre. There are now several comprehensive national guidelines on CSII use (see ATTD Yearbook 2009) but more work needs to be done in unifying uptake and ensuring all those who can benefit do so. Technology developments recently include increasing use of pumps with continuous glucose monitoring (CGM) connectivity (see elsewhere in this volume) and the emergence of numerous manufacturers developing so-called 'patch pumps', often for the type 2 diabetes market. Interestingly, the evidence base for CSII in this group is not well established, and for this reason the selected papers on CSII in this section include several in this area. The use of CSII in diabetic pregnancy is a long-established practice, in spite of the lack of evidence that it is superior to multiple daily injections (MDI), and few randomised controlled trials have been done in recent years. Several papers in this field this year continue the debate about the usefulness of CSII in diabetic pregnancy and are reviewed here. It is pleasing to see more research on the psychosocial aspects of CSII during the year, both from the point of view of how psychological beliefs influence outcomes on CSII (is there a type of patient who does particularly well or poorly on CSII?) and how CSII affects psychological factors like mood, behaviour and quality of life. Quality of

  20. Estradiol Binds to Insulin and Insulin Receptor Decreasing Insulin Binding in vitro

    OpenAIRE

    RobertRoot-Bernstein

    2014-01-01

    Rationale: Insulin resistance associated with hyperestrogenemias occurs in gestational diabetes mellitus, polycystic ovary syndrome, ovarian hyperstimulation syndrome, estrogen therapies, metabolic syndrome and obesity. The mechanism by which insulin and estrogen interact is unknown. We hypothesize that estrogen binds directly to insulin and the insulin receptor producing insulin resistance. Objectives: To determine the binding constants of steroid hormones to insulin, the insulin recepto...

  1. Intranasal insulin therapy

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, S; Hvidberg, A;

    1995-01-01

    To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more...... quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

  2. 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...

  3. Generalised insulin oedema after intensification of treatment with insulin analogues

    OpenAIRE

    Adamo, Luigi; Thoelke, Mark

    2013-01-01

    We report a case of generalised insulin oedema after intensification of treatment with genetically modified insulin. This is the first case of generalised oedema in response to treatment with insulin analogues in a patient not insulin naive.

  4. Human insulin genome sequence map, biochemical structure of insulin for recombinant DNA insulin.

    Science.gov (United States)

    Chakraborty, Chiranjib; Mungantiwar, Ashish A

    2003-08-01

    Insulin is a essential molecule for type I diabetes that is marketed by very few companies. It is the first molecule, which was made by recombinant technology; but the commercialization process is very difficult. Knowledge about biochemical structure of insulin and human insulin genome sequence map is pivotal to large scale manufacturing of recombinant DNA Insulin. This paper reviews human insulin genome sequence map, the amino acid sequence of porcine insulin, crystal structure of porcine insulin, insulin monomer, aggregation surfaces of insulin, conformational variation in the insulin monomer, insulin X-ray structures for recombinant DNA technology in the synthesis of human insulin in Escherichia coli. PMID:12769691

  5. Monoclonal antibodies to the insulin receptor mimic metabolic effects of insulin but do not stimulate receptor autophosphorylation in transfected NIH 3T3 fibroblasts

    International Nuclear Information System (INIS)

    The metabolic actions of insulin and anti-insulin receptor monoclonal antibodies were compared with their effects on insulin receptor phosphorylation in mouse NIH 3T3 fibroblasts transfected with human insulin receptor cDNA. In serum-starved NIH 3T3 HIR3.5 cells, uptake of 2-deoxy-[3H]glucose was stimulated up to 2-fold after 30 min with insulin, with a half-maximal effect at 0.1 nM insulin. Incorporation of [3H]thymidine was stimulated ∼ 12-fold after a 16-hr preincubation with insulin, with a half-maximal effect at 2 nM insulin. Phosphorylation of insulin receptor β-subunit in cells prelabeled with [32P]phosphate was increased 10- to 20-fold within 5 min of adding insulin. Monoclonal antibodies reacting with four different epitopes on the insulin receptor mimicked the effect of insulin on 2-deoxyglucose uptake. These antibodies also stimulated thymidine incorporation, although the maximum stimulation was only ∼ 30% that of insulin. It is concluded that the insulin-like metabolic effects of antibodies involve a mechanism of receptor activation that is independent of autophosphorylation and hence that receptor autophosphorylation is not an essential step in triggering at least some events in the insulin signaling pathway

  6. Insulin Attenuates Beta-Amyloid-Associated Insulin/Akt/EAAT Signaling Perturbations in Human Astrocytes.

    Science.gov (United States)

    Han, Xiaojuan; Yang, Liling; Du, Heng; Sun, Qinjian; Wang, Xiang; Cong, Lin; Liu, Xiaohui; Yin, Ling; Li, Shan; Du, Yifeng

    2016-08-01

    The excitatory amino acid transporters 1 and 2 (EAAT1 and EAAT2), mostly located on astrocytes, are the main mediators for glutamate clearance in humans. Malfunctions of these transporters may lead to excessive glutamate accumulation and subsequent excitotoxicity to neurons, which has been implicated in many kinds of neurodegenerative disorders including Alzheimer's disease (AD). Yet, the specific mechanism of the glutamate system dysregulation remains vague. To explore whether the insulin/protein kinase B (Akt)/EAAT signaling in human astrocytes could be disturbed by beta-amyloid protein (Aβ) and be protected by insulin, we incubated HA-1800 cells with varying concentrations of Aβ1-42 oligomers and insulin. Then the alterations of several key substrates in this signal transduction pathway were determined. Our results showed that expressions of insulin receptor, phospho-insulin receptor, phospho-protein kinase B, phospho-mammalian target of rapamycin, and EAAT1 and EAAT2 were decreased by the Aβ1-42 oligomers in a dose-dependent manner (p  0.05), and the mRNA levels of EAAT1 and EAAT2 were also unchanged (p > 0.05). Taken together, this study indicates that Aβ1-42 oligomers could cause disturbances in insulin/Akt/EAAT signaling in astrocytes, which might be responsible for AD onset and progression. Additionally, insulin can exert protective functions to the brain by modulating protein modifications or expressions. PMID:26358886

  7. Giving an insulin injection

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000660.htm Giving an insulin injection To use the sharing features on this ... and syringes. Filling the Syringe - One Type of Insulin Wash your hands with soap and water. Dry ...

  8. Insulin Lispro Injection

    Science.gov (United States)

    ... not use any type of insulin after the expiration date printed on the bottle has passed.Insulin ... sweating weakness muscle cramps abnormal heartbeat shortness of breath large weight gain in a short period of ...

  9. Online Ad Assignment with an Ad Exchange

    OpenAIRE

    Dvořák, Wolfgang; Henzinger, Monika

    2016-01-01

    Ad exchanges are becoming an increasingly popular way to sell advertisement slots on the internet. An ad exchange is basically a spot market for ad impressions. A publisher who has already signed contracts reserving advertisement impressions on his pages can choose between assigning a new ad impression for a new page view to a contracted advertiser or to sell it at an ad exchange. This leads to an online revenue maximization problem for the publisher. Given a new impression to sell decide whe...

  10. The Insulin Pump

    OpenAIRE

    Toews, C. J.

    1985-01-01

    Subcutaneous continuous insulin infusion systems deliver insulin at a basal rate designed to keep blood glucose levels normal in the non-fed state. Additional insulin is delivered at meal time. Pumps can provide near optimal control of blood glucose concentrations in selected, highly motivated patients. The pump provides better diabetic control than once daily insulin injections, although several daily injections can provide comparable control. Optimal control with the pump causes some short-...

  11. Glycosphingolipids and insulin resistance

    NARCIS (Netherlands)

    M. Langeveld; J.F.M.G. Aerts

    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 sphingol

  12. Insulin and the Lung

    DEFF Research Database (Denmark)

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

    2013-01-01

    , molecular understanding is necessary. Insulin resistance is a strong, independent risk factor for asthma development, but it is unknown whether a direct effect of insulin on the lung is involved. This review summarizes current knowledge regarding the effect of insulin on cellular components of the lung...... 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...

  13. Insulin enhances glucose-stimulated insulin secretion in healthy humans

    OpenAIRE

    Bouche, Clara; Lopez, Ximena; Fleischman, Amy; Cypess, Aaron M.; O'Shea, Sheila; Stefanovski, Darko; Bergman, Richard N.; Rogatsky, Eduard; Stein, Daniel T.; Kahn, C. Ronald; Kulkarni, Rohit N.; Goldfine, Allison B.

    2010-01-01

    Islet β-cells express both insulin receptors and insulin-signaling proteins. Recent evidence from rodents in vivo and from islets isolated from rodents or humans suggests that the insulin signaling pathway is physiologically important for glucose sensing. We evaluated whether insulin regulates β-cell function in healthy humans in vivo. Glucose-induced insulin secretion was assessed in healthy humans following 4-h saline (low insulin/sham clamp) or isoglycemic-hyperinsulinemic (high insulin) c...

  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. Magnetite nanoparticle interactions with insulin amyloid fibrils

    Science.gov (United States)

    Chen, Yun-Wen; Chang, Chiung-Wen; Hung, Huey-Shan; Kung, Mei-Lang; Yeh, Bi-Wen; Hsieh, Shuchen

    2016-10-01

    Accumulation of amyloid fibrils is one of the likely key factors leading to the development of Alzheimer’s disease and other amyloidosis associated diseases. Magnetic nanoparticles (NPs) have been developed as promising medical materials for many medical applications. In this study, we have explored the effects of Fe3O4 NPs on the fibrillogenesis process of insulin fibrils. When Fe3O4 NPs were co-incubated with insulin, Fe3O4 NPs had no effect on the structural transformation into amyloid-like fibrils but had higher affinity toward insulin fibrils. We demonstrated that the zeta potential of insulin fibrils and Fe3O4 NPs were both positive, suggesting the binding forces between Fe3O4 NPs and insulin fibrils were van der Waals forces but not surface charge. Moreover, a different amount of Fe3O4 NPs added had no effect on secondary structural changes of insulin fibrils. These results propose the potential use of Fe3O4 NPs as therapeutic agents against diseases related to protein aggregation or contrast agents for magnetic resonance imaging.

  16. Polarised black holes in AdS

    Science.gov (United States)

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

    2016-06-01

    We consider solutions in Einstein-Maxwell theory with a negative cosmological constant that asymptote to global AdS 4 with conformal boundary {S}2× {{{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 Hawking-Page phase transition. The AdS soliton dominates the low temperature phase and the black hole the high temperature phase, with a critical temperature that decreases as the external electric field increases. Finally, we consider the simple case of a free charged scalar field on {S}2× {{{R}}}t with conformal coupling. For a field in the SU(N ) adjoint representation we compare the phase diagram with the above gravitational system.

  17. Estradiol Binds to Insulin and Insulin Receptor Decreasing Insulin Binding in vitro

    Directory of Open Access Journals (Sweden)

    Robert eRoot-Bernstein

    2014-07-01

    Full Text Available Rationale: Insulin resistance associated with hyperestrogenemias occurs in gestational diabetes mellitus, polycystic ovary syndrome, ovarian hyperstimulation syndrome, estrogen therapies, metabolic syndrome and obesity. The mechanism by which insulin and estrogen interact is unknown. We hypothesize that estrogen binds directly to insulin and the insulin receptor producing insulin resistance.Objectives: To determine the binding constants of steroid hormones to insulin, the insulin receptor, and insulin-like peptides derived from the insulin receptor; and to investigate the effect of estrogens on the binding of insulin to its receptor.Methods: Ultraviolet spectroscopy, capillary electrophoresis and NMR demonstrated estrogen binding to insulin and its receptor. Horse-radish peroxidase-linked insulin was used in an ELISA-like procedure to measure the effect of estradiol on binding of insulin to its receptor. Measurements: Binding constants for estrogens to insulin and the insulin receptor were determined by concentration-dependent spectral shifts. The effect of estradiol on insulin-HRP binding to its receptor was determined by shifts in the insulin binding curve. Main Results: Estradiol bound to insulin with a Kd of 12 x 10-9 M and to the insulin receptor with a Kd of 24 x 10-9 M, while other hormones had significantly less affinity. 200 nM estradiol shifted the binding curve of insulin to its receptor 0.8 log units to the right. Conclusions: Estradiol concentrations in many hyperestrogenemic syndromes are sufficient to interfere with insulin binding to its receptor producing significant insulin resistance.

  18. Rat liver insulin receptor

    International Nuclear Information System (INIS)

    Using insulin affinity chromatography, the authors have isolated highly purified insulin receptor from rat liver. When evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions, the rat liver receptor contained the M/sub r/ 125,000 α-subunit, the M/sub r/ 90,000 β-subunit, and varying proportions of the M/sub r/ 45,000 β'-subunit. The specific insulin binding of the purified receptor was 25-30 μg of 125I-insulin/mg of protein, and the receptor underwent insulin-dependent autophosphorylation. Rat liver and human placental receptors differ from each other in several functional aspects: (1) the adsorption-desorption behavior from four insulin affinity columns indicated that the rat liver receptor binds less firmly to immobilized ligands; (2) the 125I-insulin binding affinity of the rat liver receptor is lower than that of the placental receptor; (3) partial reduction of the rat liver receptor with dithiothreitol increases its insulin binding affinity whereas the binding affinity of the placental receptor is unchanged; (4) at optimal insulin concentration, rat liver receptor autophosphorylation is stimulated 25-50-fold whereas the placental receptor is stimulated only 4-6-fold. Conversion of the β-subunit to β' by proteolysis is a major problem that occurs during exposure of the receptor to the pH 5.0 buffer used to elute the insulin affinity column. Proteolytic destruction and the accompanying loss of insulin-dependent autophosphorylation can be substantially reduced by proteolysis inhibitors. In summary, rat liver and human placental receptors differ functionally in both α- and β-subunits. Insulin binding to the α-subunit of the purified rat liver receptor communicates a signal that activates the β-subunit; however, major proteolytic destruction of the β-subunit does not affect insulin binding to the α-subunit

  19. Concentrated insulins: the new basal insulins

    OpenAIRE

    Lamos EM; Younk LM; Davis SN

    2016-01-01

    Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with in...

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

    OpenAIRE

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

    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 s...

  1. Allergy reactions to insulin: effects of continuous subcutaneous insulin infusion and insulin analogues.

    OpenAIRE

    RADERMECKER, Régis; Scheen, André

    2007-01-01

    The purification of animal insulin preparations and the use of human recombinant insulin have markedly reduced the incidence but not completely suppressed the occurrence of insulin allergy manifestations. Advances in technologies concerning the mode of delivery of insulin, i.e. continuous subcutaneous insulin infusion (CSII), and the use of insulin analogues, resulting from the alteration in the amino acid sequence of the native insulin molecule, may influence the immunogenicity and antigenic...

  2. 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.

  3. Polarised Black Holes in AdS

    CERN Document Server

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

    2015-01-01

    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...

  4. 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...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...... was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS...

  5. 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...... 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......-called counter-regulatory hormones tend to increase plasma glucose by increasing hepatic glucose production and adipose tissue lipolysis. If the pre-exercise plasma insulin level is high, hypoglycaemia may develop during exercise whereas hyperglycaemia and ketosis may develop if pre-exercise plasma insulin...

  6. Classifying insulin regimens

    DEFF Research Database (Denmark)

    Neu, A; Lange, K; Barrett, T;

    2015-01-01

    Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1...... diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin...... variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides...

  7. 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...

  8. Etiopathogenesis of insulin autoimmunity.

    OpenAIRE

    Åke Lenmark; Moustakas, Antonis K; Papadopoulos, George K; Norio Kanatsuna

    2012-01-01

    Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (pro)insulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and ...

  9. Landmarks in Insulin Research

    OpenAIRE

    Ward, Colin W.; Lawrence, Michael C.

    2011-01-01

    Ever since the discovery of insulin and its role in the regulation of glucose uptake and utilization, there has been great interest in insulin, its structure and the way in which it interacts with its receptor and effects signal transduction. As the 90th anniversary of the discovery of insulin approaches, it is timely to provide an overview of the landmark discoveries relating to the structure and function of this remarkable molecule and its receptor.

  10. Ad Hoc网络%Ad Hoc Network

    Institute of Scientific and Technical Information of China (English)

    王海涛

    2005-01-01

    首先介绍了Ad Hoc网络的基本概念、技术特点以及关键技术等,然后较为全面地归纳了Ad Hoc网络的典型应用,最后讨论了Ad Hoc网络的发展趋势和有待解决的问题.

  11. Human ultralente insulin.

    OpenAIRE

    Holman, R R; Steemson, J; Darling, P; Reeves, W G; Turner, R.C.

    1984-01-01

    The greater solubility of human insulin and its possible faster action have led to doubts about whether a sufficiently long acting formulation could be produced to provide a basal supply for diabetics. In a double blind crossover study in 18 diabetics human ultralente insulin was as effective as beef ultralente insulin in controlling basal plasma glucose concentrations (median 5.7 mmol/l (103 mg/100 ml) with human and 6.3 mmol/l (114 mg/100 ml) with beef ultralente insulin respectively). Ther...

  12. Baby Skyrmions in AdS

    OpenAIRE

    Elliot-Ripley, Matthew; Winyard, Thomas

    2015-01-01

    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...

  13. Binding of insulin to rat pancreatic islets: comparison between pancreatic human insulin and biosynthetic human insulin

    Energy Technology Data Exchange (ETDEWEB)

    Verspohl, E.J.; Ammon, H.P.

    Human pancreatic insulin, biosynthetic human insulin (BHI), and pork insulin were compared in terms of their binding characteristics to insulin receptors on rat pancreatic islets. There was no difference in binding or on biologic effect, i.e., ability to inhibit insulin secretion.

  14. Alternative Devices for Taking Insulin

    Science.gov (United States)

    ... KB). Alternate Language URL Alternative Devices for Taking Insulin Page Content On this page: What alternative devices ... the skin. [ Top ] What alternative devices for taking insulin are available? Insulin pens provide a convenient, easy- ...

  15. Eternal Black Holes in AdS

    OpenAIRE

    Maldacena, Juan M.

    2001-01-01

    We propose a dual non-perturbative description for maximally extended Schwarzschild Anti-de-Sitter spacetimes. The description involves two copies of the conformal field theory associated to the AdS spacetime and an initial entangled state. In this context we also discuss a version of the information loss paradox and its resolution.

  16. Current status of AdS instability

    CERN Document Server

    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].

  17. 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.

  18. Preformed Seeds Modulate Native Insulin Aggregation Kinetics.

    Science.gov (United States)

    Dutta, Colina; Yang, Mu; Long, Fei; Shahbazian-Yassar, Reza; Tiwari, Ashutosh

    2015-12-10

    Insulin aggregates under storage conditions via disulfide interchange reaction. It is also known to form aggregates at the site of repeated injections in diabetes patients, leading to injection amyloidosis. This has fueled research in pharmaceutical and biotechnology industry as well as in academia to understand factors that modulate insulin stability and aggregation. The main aim of this study is to understand the factors that modulate aggregation propensity of insulin under conditions close to physiological and measure effect of "seeds" on aggregation kinetics. We explored the aggregation kinetics of insulin at pH 7.2 and 37 °C in the presence of disulfide-reducing agent dithiothreitol (DTT), using spectroscopy (UV-visible, fluorescence, and Fourier transform infrared spectroscopy) and microscopy (scanning electron microscopy, atomic force microscopy) techniques. We prepared insulin "seeds" by incubating disulfide-reduced insulin at pH 7.2 and 37 °C for varying lengths of time (10 min to 12 h). These seeds were added to the native protein and nucleation-dependent aggregation kinetics was measured. Aggregation kinetics was fastest in the presence of 10 min seeds suggesting they were nascent. Interestingly, intermediate seeds (30 min to 4 h incubation) resulted in formation of transient fibrils in 4 h that converted to amorphous aggregates upon longer incubation of 24 h. Overall, the results show that insulin under disulfide reducing conditions at pH and temperature close to physiological favors amorphous aggregate formation and seed "maturity" plays an important role in nucleation dependent aggregation kinetics.

  19. Labile disulfide bonds in human placental insulin receptor.

    OpenAIRE

    Finn, F. M.; Ridge, K D; HOFMANN, K

    1990-01-01

    The disulfide crosslinking pattern of human placental insulin receptor was investigated using selective reduction with tributylphosphine followed by alkylation with N-[3H]ethylmaleimide. Insulin receptor contains a single sulfhydryl group in each beta subunit whose alkylation with N-[3H]ethylmaleimide inhibits receptor autophosphorylation. Alkylation is partially inhibited by ATP or the nonhydrolyzable substrate analog adenosine 5'-[beta,gamma-imido]triphosphate when the nucleotides are added...

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

    Directory of Open Access Journals (Sweden)

    Radhika H Muzumdar

    Full Text Available BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

  1. Relationship of Insulin Sensitivity, Insulin Secretion, and Adiposity With Insulin Clearance in a Multiethnic Population

    OpenAIRE

    Lorenzo, Carlos; Hanley, Anthony J.G.; Wagenknecht, Lynne E; Rewers, Marian J.; Stefanovski, Darko; Goodarzi, Mark O.; Haffner, Steven M

    2012-01-01

    OBJECTIVE We aimed to examine insulin clearance, a compensatory mechanism to changes in insulin sensitivity, across sex, race/ethnicity populations, and varying states of glucose tolerance. RESEARCH DESIGN AND METHODS We measured insulin sensitivity index (S I), acute insulin response (AIR), and metabolic clearance rate of insulin (MCRI) by the frequently sampled intravenous glucose tolerance test in 1,295 participants in the Insulin Resistance Atherosclerosis Study. RESULTS MCRI was positive...

  2. Superradiant instability in AdS

    CERN Document Server

    Ganchev, Bogdan

    2016-01-01

    The phenomenon of superradiance in the context of asymptotically global AdS spacetimes is investigated with particular accent on its effect on the stability of the systems under consideration. To this end, the concept of an asymptotically AdS spacetime is explained, together with its implications on the boundary conditions at $\\mathcal{I}$, as well as the Newman-Penrose-Teukolsky formalism, whereby the Teukolsky master equation in a most general form for Kerr-AdS is given. Furthermore, work done in the cases of RN-AdS and Kerr-AdS is laid out in a concise manner, putting emphasis on the important steps taken in determining the endpoint of the superradiant instability in the two configurations. For the former this turns out to be a black hole with reduced charge and a static charged scalar condensate around it, whereas for the latter two of the more probable outcomes are presented, both of which imply a violation of one of the cosmic censorships.

  3. 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

  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

    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

  5. Instability corners in AdS space

    CERN Document Server

    Dimitrakopoulos, Fotios V; Lippert, Matthew; Yang, I-Sheng

    2014-01-01

    We investigate whether arbitrarily small perturbations in global AdS space are generically unstable and collapse into black holes on the time scale set by gravitational interactions. We argue that current evidence, combined with our analysis, strongly suggests that a set of nonzero measure in the space of initial conditions does not collapse on this time scale. On the other hand, existing results do not provide an equally strong indication whether the unstable solutions also form a set of nonzero measure. We perform an analysis in position space to address this puzzle, and our formalism allows us to directly address the vanishing-amplitude limit. We show that gravitational self-interaction leads to tidal deformations which are equally likely to focus or defocus energy, and we sketch the phase diagram accordingly. We also clarify the connection between gravitational evolution in global AdS and holographic thermalization.

  6. Baby Skyrmions in AdS

    CERN Document Server

    Elliot-Ripley, Matthew

    2015-01-01

    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.

  7. Indirect comparison of lixisenatide versus neutral protamine Hagedorn insulin as add-on to metformin and sulphonylurea in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Fournier, Marie

    2014-10-01

    Full Text Available [english] Objective: There is currently a lack of evidence from direct comparisons of treatment outcomes with lixisenatide versus neutral protamine Hagedorn (NPH-insulin in type 2 diabetes mellitus (T2DM patients with suboptimal glycaemic control with oral antidiabetic drugs (OADs. Hence, the current analysis indirectly compared available evidence on the risk of hypoglycaemia and weight change between lixisenatide and NPH-insulin based on randomized controlled trial (RCT data with exenatide, insulin glargine and placebo as common references. Methods: A systematic search of PubMed, Embase, the Cochrane database and clinical registries identified English- and German-language articles published from January 1980 to October 2012 reporting data from RCTs. Only publications of trials that reported outcomes from 24 to 30 weeks comparing glucagon-like peptide-1 receptor agonists or basal insulin versus another antidiabetic agent or placebo were included. Hypoglycaemia, patients at glycated haemoglobin (HbA target and discontinuations due to adverse events (AEs were treated as binary variables, with risk ratios and odds ratios (ORs calculated. HbA and body weight were treated as continuous variables with difference in mean change from baseline (MD calculated. Meta-analyses were performed with random effects models and indirect comparisons were performed according to Bucher’s method.Results: Seven RCTs (n=3,301 patients comparing the efficacy and safety of lixisenatide, exenatide, insulin glargine and NPH-insulin with different antidiabetic treatments in adult patients with T2DM were included in the final analysis. In the adjusted indirect comparison, there was a significant difference in symptomatic hypoglycaemia (OR = 0.38; 95% CI = [0.17, 0.85] and in confirmed hypoglycaemia (OR = 0.46; 95% CI = [0.22, 0.96] favouring lixisenatide over NPH-insulin and comparable changes in HbA from baseline (MD = 0.07%; 95% CI = [–0.26%, 0.41%]. In contrast to NPH-insulin

  8. Effect of insulin and metformin on methylation and glycolipid metabolism of peroxisome proliferator-activated receptor γcoactivator-1A of rat offspring with gestational diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Ai-Qin Song; Li-Rong Sun; Yan-Xia Zhao; Yan-Hua Gao; Lei Chen

    2016-01-01

    Objective: To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A (PPARGC1A) ofrat offspring with gestational diabetes mellitus (GDM). Methods: A total of 45 pregnant rats received the intraperitoneal injection of streptozotocin to establish the pregnant rat model of GDM. A total of 21 pregnant rats with GDM were randomly divided into three groups, with 7 rats in each group, namely the insulin group, metformin group and control group. Rats in the insulin group received the abdominal subcutaneous injection of 1 mL/kg recombinant insulin glargine at 18: 00 every day. Rats in the metformin group received the intragastric infusion of metformin hydrochloride at 18: 00 every day, with the first dose of 300 mg/kg. The doses of two groups were adjusted every 3 d to maintain the blood glucose level at 2.65-7.62 mmol/L. Rats in the control group received the intragastric infusion of 1 mL normal saline at 18:00 every day. After the natural delivery of pregnant rats, 10 offspring rats were randomly selected from each group. At birth, 4 wk and 8 wk after the birth of offspring rats, the weight of offspring rats was measured. The blood glucose level of offspring rats was measured at 4 wk and 8 wk, while the level of serum insulin, triglyceride and leptin was measured at 8 wk.Results: The weight of offspring rats at birth in the insulin group and metformin group was significantly lower than the one in the control group (P0.05). The fasting blood glucose and random blood glucose in the insulin group and metformin group at 4 wk and 8 wk were all significantly lower than ones in the control group (P0.05). The expression of PPARGC1A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1A was significantly lower than the one in the control group (P0.05). Insulin and leptin at 8 wk in the insulin group and metformin group were

  9. 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.)

  10. Insulin Resistance and Hypertension

    Institute of Scientific and Technical Information of China (English)

    张建华; 张春秀

    2002-01-01

    Summary: The insulin sensitivity in hypertensive patients with normal glucose tolerance (NGT),impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM) and the insulin resistance(IR) under the disorder of glucose metabolism and hypertension were studied. By glucose toler-ance test and insulin release test, insulin sensitivity index (ISI) and the ratio of area under glucosetolerance curve (AUCG) to area under insulin release curve (AUC1) were calculated and analyzed.The results showed that ISI was decreased to varying degrees in the patients with hypertension,the mildest in the group of NGT with hypertension, followed by the group of IGT without hyper-tension, the group of IGT with hypertension and DM (P=0). There was very significant differ-ence in the ratio of AUCG/AUC1 between the hypertensive patients with NGT and controls (P=0). It was concluded that a significant IR existed during the development of IGT both in hyperten-sion and nonhypertension. The increase of total insulin secretion (AUC1) was associated with non-hypertension simultaneously. IR of the hypertensive patients even existed in NGT and was wors-ened with the deterioration of glucose metabolism disorder, but the AUC1 in the HT groupchanged slightly. A relative deficiency of insulin secretion or dysfunction of β-cell of islet existed inIGT and DM of the hypertensive patients.

  11. Efficacy and safety comparison between liraglutide as add-on therapy to insulin and insulin dose-increase in Chinese subjects with poorly controlled type 2 diabetes and abdominal obesity

    Directory of Open Access Journals (Sweden)

    Li Chun-jun

    2012-11-01

    Full Text Available Abstract Objective To assess the efficacy and safety of adding liraglutide to established insulin therapy in poorly controlled Chinese subjects with type 2 diabetes and abdominal obesity compared with increasing insulin dose. Methods A 12-week, randomized, parallel-group study was carried out. A total of 84 patients completed the trial who had been randomly assigned to either the liraglutide-added group or the insulin-increasing group while continuing current insulin based treatment. Insulin dose was reduced by 0-30% upon the initiation of liraglutide. Insulin doses were subsequently adjusted to optimized glycemic control. Glycosylated hemoglobin (HbA1c values, blood glucose, total daily insulin dose, body weight, waist circumference, and the number of hypoglycemic events and adverse events were evaluated. Results At the end of study, the mean reduction in HbA1c between the liraglutide-added group and the insulin-increasing group was not significantly different (1.9% vs. 1.77%, p>0.05. However, the percentage of subjects reaching the composite endpoint of HbA1c ≤ 7.0% with no weight gain and no hypoglycemia, was significantly higher in the liraglutide-added group than in the insulin-increasing group (67% vs. 19%, p2, p Conclusions Addition of liraglutide to abdominally obese, insulin-treated patients led to improvement in glycemic control similar to that achieved by increasing insulin dosage, but with a lower daily dose of insulin and fewer hypoglycemic events. Adding liraglutide to insulin also induced a significant reduction in body weight and waist circumference. Liraglutide combined with insulin may be the best treatment option for poorly controlled type 2 diabetes and abdominal obesity.

  12. A superactive insulin: [B10-aspartic acid]insulin(human).

    OpenAIRE

    Schwartz, G P; Burke, G. T.; Katsoyannis, P G

    1987-01-01

    The genetic basis for a case of familial hyperproinsulinemia has been elucidated recently. It involves a single point mutation in the proinsulin gene resulting in the substitution of aspartic acid for histidine-10 of the B chain of insulin. We have synthesized a human insulin analogue, [AspB10]insulin, corresponding to the mutant proinsulin and evaluated its biological activity. [AspB10]Insulin displayed a binding affinity to insulin receptors in rat liver plasma membranes that was 534 +/- 14...

  13. Insulin glulisine: insulin receptor signaling characteristics in vivo.

    Science.gov (United States)

    Hennige, Anita M; Lehmann, Rainer; Weigert, Cora; Moeschel, Klaus; Schäuble, Myriam; Metzinger, Elisabeth; Lammers, Reiner; Häring, Hans-Ulrich

    2005-02-01

    In recent years, recombinant DNA technology has been used to design insulin molecules that overcome the limitations of regular insulin in mealtime supplementation. However, safety issues have been raised with these alternatives, as the alteration of the three-dimensional structure may alter the interaction with the insulin and/or IGF-I receptors and therefore lead to the activation of alternate metabolic as well as mitogenic signaling pathways. It is therefore essential to carefully study acute and long-term effects in a preclinical state, as insulin therapy is meant to be a lifelong treatment. In this study, we determined in vivo the insulin receptor signaling characteristics activated by insulin glulisine (Lys(B3), Glu(B29)) at the level of insulin receptor phosphorylation, insulin receptor substrate phosphorylation, and downstream signaling elements such as phosphatidylinositol (PI) 3-kinase, AKT, and mitogen-activated protein kinase. C57BL/6 mice were injected with insulin glulisine or regular insulin and Western blot analysis was performed for liver and muscle tissue. The extent and time course of insulin receptor phosphorylation and activation of downstream signaling elements after insulin glulisine treatment was similar to that of human regular insulin in vivo. Moreover, insulin signaling in hypothalamic tissue determined by PI 3-kinase activity was comparable. Therefore, insulin glulisine may be a useful tool for diabetes treatment. PMID:15677493

  14. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    Samir Bhattacharya; Debleena Dey; Sib Sankar Roy

    2007-03-01

    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, leading to a reduced amount of IR protein in insulin target cells. PDK1-independent phosphorylation of PKCε causes this reduction in insulin receptor gene expression. One of the pathways through which fatty acid can induce insulin resistance in insulin target cells is suggested by these studies. We provide an overview of this important area, emphasizing the current status.

  15. Refined Holographic Entanglement Entropy for the AdS Solitons and AdS black Holes

    CERN Document Server

    Ishihara, Masafumi; Ning, Bo

    2012-01-01

    We consider the refinement of the holographic entanglement entropy on a disk region for the holographic dual theories to the AdS solitons and AdS black holes, including the corrected ones by the Gauss-Bonnet term. The AdS soliton is dual to a gapped system with an IR fixed-point. The refinement is obtained by extracting the UV-independent piece of the holographic entanglement entropy. We then study the renormalization group (RG) flow of the refinement by tuning the linear size of the chosen disk region. Our main results are (i) the RG flow of the refinement decreases monotonically for most of the cases; (ii) there is no topological entanglement entropy for AdS$_5$ soliton even with Gauss-Bonnet correction; (iii) for the AdS black holes, the refinement obeys the volume law at IR regime, and the transition between UV and IR regimes is a smooth crossover; however, the crossover will turn into phase transition by the Gauss-Bonnet correction; (iv) for the AdS solitons, there are discontinuous phase transitions bet...

  16. Refined holographic entanglement entropy for the AdS solitons and AdS black holes

    International Nuclear Information System (INIS)

    We consider the refinement of the holographic entanglement entropy for the holographic dual theories to the AdS solitons and AdS black holes, including the corrected ones by the Gauss–Bonnet term. The refinement is obtained by extracting the UV-independent piece of the holographic entanglement entropy, the so-called renormalized entanglement entropy which is independent of the choices of UV cutoff. Our main results are: (i) the renormalized entanglement entropies of the AdSd+1 soliton for d=4,5 are neither monotonically decreasing along the RG flow nor positive-definite, especially around the deconfinement/confinement phase transition; (ii) there is no topological entanglement entropy for AdS5 soliton even with Gauss–Bonnet correction; (iii) for the AdS black holes, the renormalized entanglement entropy obeys an expected volume law at IR regime, and the transition between UV and IR regimes is a smooth crossover even with Gauss–Bonnet correction; (iv) based on AdS/MERA conjecture, we postulate that the IR fixed-point state for the non-extremal AdS soliton is a trivial product state

  17. 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...

  18. Effect of berberine chloride on expression of insulin degrading enzyme in rat models with AD%小檗碱对阿尔茨海默病大鼠模型胰岛素降解酶表达的影响

    Institute of Scientific and Technical Information of China (English)

    朱飞奇; 马英; 孙永安; 褚文政; 钱采韵

    2010-01-01

    目的 研究小檗碱对AD大鼠模型胰岛素降解酶(IDE)表达的影响.方法 18只SD大鼠采用完全随机数字表法分为正常组、模型组和小檗碱组,每组6只.正常组不做任何处理,模型组及小檗碱组大鼠通过双侧海马立体定向注射凝聚态Aβ1-40(5 μg)建立AD模型.小檗碱组造模后灌胃给予盐酸小檗碱50mg/kg,1次/d,共14d.采用实时荧光定量PCR法和Western blotting法观察小檗碱对IDE表达的影响.结果 小檗碱组大鼠IDE mRNA的相对拷贝数(45.70±12.80)较正常组(23.40±11.30)及模型组(34.20±6.70)明显增加,小檗碱组大鼠海马IDE蛋白相对表达量(0.61±0.05)较正常组(0.23±0.03)及模型组(0.46±0.07)明显增加,差异均有统计学意义(P<0.05).结论 大鼠海马立体定向注射凝聚态Aβ1-40可以导致海马部位IDE表达增加,小檗碱可以通过促进IDE的表达而促进Aβ的清除.%Objective To explore the effect of berberine chloride on the expression of insulin degrading enzyme (IDE) in the rat models with Alzheimer's disease (AD). Methods Eighteen adult male SD rats, weighting 220-250 g, were randomly divided into normal control group, Aβ1-40 group and Aβ40+berberine chloride group (n=6). The rat models with AD were established by stereotactically injecting condensed Aβ1-40 (5 μg) into the bilateral hippocampus of rats. The rats in the Aβ1-40+berberine chloride group were given berberine chloride (50 mg/kg) by intragastric administration once daily for 14 d. The expressions of IDE were assayed by real time polymerase chain reaction (real-time PCR) and Western blotting. Results The relative quantity of mRNA expression of IDE was (34.2±6.7) in the Aβ1-40+berberine group, which was significantly increased as compared with that in the Aβ1-40 group (45.7±12.8) and normal control group (23.4±11.3, P<0.05). The relative quantity of protein expression of IDE was (0.61 ±0.05) in the Aββ1-40+berberine group, which was significantly

  19. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... Research Training & Career Development Grant programs for students, postdocs, and faculty Research at NIDDK Labs, faculty, and ... it for energy. Insulin's Role in Blood Glucose Control When blood glucose levels rise after a meal, ...

  20. Insulin Human Inhalation

    Science.gov (United States)

    ... control pills); oral medications for diabetes such as pioglitazone (Actos, in Actoplus Met, in Duetact, in Oseni) or ... or lower legs sudden weight gain extreme drowsiness confusion dizziness Insulin inhalation may increase the risk that ...

  1. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... use it for energy. Insulin's Role in Blood Glucose Control When blood glucose levels rise after a meal, ... also helps a person lose weight control blood glucose levels control blood pressure control cholesterol levels People in the ...

  2. 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...

  3. Insulin Augmentation of Glucose-Stimulated Insulin Secretion Is Impaired in Insulin-Resistant Humans

    OpenAIRE

    Halperin, Florencia; Lopez, Ximena; Manning, Raquel; Kahn, C. Ronald; Kulkarni, Rohit Narayan; Goldfine, Allison Braunwald

    2012-01-01

    Type 2 diabetes (T2D) is characterized by insulin resistance and pancreatic β-cell dysfunction, the latter possibly caused by a defect in insulin signaling in β-cells. We hypothesized that insulin’s effect to potentiate glucose-stimulated insulin secretion (GSIS) would be diminished in insulin-resistant persons. To evaluate the effect of insulin to modulate GSIS in insulin-resistant compared with insulin-sensitive subjects, 10 participants with impaired glucose tolerance (IGT), 11 with T2D, a...

  4. Winding Strings in AdS_3

    CERN Document Server

    Minces, P; Minces, Pablo; Nunez, Carmen

    2006-01-01

    Correlation functions of one-unit spectral flowed states in string theory on AdS_3 are considered. We present a formalism which allows to explicitly find the modified Knizhnik-Zamolodchikov and null vector equations to be satisfied by amplitudes of states in w=1 sectors. We give a precise prescription to solve this system of linear differential equations in cases that are relevant to obtain three and four point functions involving spectral flowed string states. We specifically compute three point functions with two and three one-unit spectral flowed operators and also discuss four point functions.

  5. Inhaled insulin: overview of a novel route of insulin administration

    Directory of Open Access Journals (Sweden)

    Lucy D Mastrandrea

    2010-01-01

    Full Text Available Lucy D MastrandreaDepartment of Pediatrics, School of Medicine and Biochemical Sciences, University at Buffalo, Buffalo, NY, USAAbstract: Diabetes is a chronic disease characterized by inadequate insulin secretion with resulting hyperglycemia. Diabetes complications include both microvascular and macrovascular disease, both of which are affected by optimal diabetes control. Many individuals with diabetes rely on subcutaneous insulin administration by injection or continuous infusion to control glucose levels. Novel routes of insulin administration are an area of interest in the diabetes field, given that insulin injection therapy is burdensome for many patients. This review will discuss pulmonary delivery of insulin via inhalation. The safety of inhaled insulin as well as the efficacy in comparison to subcutaneous insulin in the various populations with diabetes are covered. In addition, the experience and pitfalls that face the development and marketing of inhaled insulin are discussed.Keywords: glycemic control, hemoglobin A1c, inhalation, insulin, type 1 diabetes, type 2 diabetes

  6. Etiopathogenesis of Insulin Autoimmunity

    Directory of Open Access Journals (Sweden)

    Norio Kanatsuna

    2012-01-01

    Full Text Available Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (proinsulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and -DQ8 is reviewed and illustrated by molecular modeling. The importance of the cellular immune reaction involving cytotoxic CD8-positive T cells to kill beta cells through Class I MHC is discussed along with speculations of the possible role of B lymphocytes in presenting the proinsulin autoantigen over and over again through insulin-carrying insulin autoantibodies. In contrast to autoantibodies against other islet autoantigens such as GAD65, IA-2, and ZnT8 transporters, it has not been possible yet to standardize the insulin autoantibody test. As islet autoantibodies predict type 1 diabetes, it is imperative to clarify the mechanisms of insulin autoimmunity.

  7. Conformational Dynamics of Insulin

    Directory of Open Access Journals (Sweden)

    Qing-xin eHua

    2011-10-01

    Full Text Available We have exploited a prandial insulin analogue (insulin lispro, the active component of Humalog®; Eli Lilly and Co. to elucidate the underlying structure and dynamics of insulin as a monomer in solution. Whereas NMR-based modeling recapitulates structural relationships of insulin crystals (T-state protomers, dynamic anomalies are revealed by amide-proton exchange kinetics in D2O. Surprisingly, the majority of hydrogen bonds observed in crystal structures are only transiently maintained in solution, including key T-state-specific inter-chain contacts. Long-lived hydrogen bonds (as defined by global exchange kinetics exist only at a subset of four -helical sites (two per chain flanking an internal disulfide bridge (cystine A20-B19; these sites map within the proposed folding nucleus of proinsulin. The anomalous flexibility of insulin otherwise spans its active surface and may facilitate receptor binding. Because conformational fluctuations promote the degradation of pharmaceutical formulations, we envisage that dynamic re-engineering of insulin may enable design of ultra-stable formulations for humanitarian use in the developing world.

  8. Insulin degludec and insulin aspart: novel insulins for the management of diabetes mellitus

    OpenAIRE

    Atkin, Stephen; Javed, Zeeshan; Fulcher, Gregory

    2015-01-01

    Patients with type 2 diabetes mellitus require insulin as disease progresses to attain or maintain glycaemic targets. Basal insulin is commonly prescribed initially, alone or with one or more rapid-acting prandial insulin doses, to limit mealtime glucose excursions (a basal–bolus regimen). Both patients and physicians must balance the advantages of improved glycaemic control with the risk of hypoglycaemia and increasing regimen complexity. The rapid-acting insulin analogues (insulin aspart, i...

  9. 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.

  10. 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

  11. Value Adding Management

    DEFF Research Database (Denmark)

    Jensen, Per Anker; Katchamart, Akarapong

    2011-01-01

    Purpose: To investigate how Facilities Management (FM) can add value and develop a management concept that can assist facilities managers in implementing value adding strategies and practices. Theory: The study is based on the management model for FM included in the European FM standards, recent...... theories on added value of FM and real estate and the related concept of Value Management from building projects. The study is related to the EuroFM research group on The Added Value of FM. Design/methodology/approach: The study outlines a preliminary theoretical based management concept, which...... the relevance of the basic concept and provides an important example of how Value Adding Management can be implemented and added value measured. Originality/value: The study develops a concept of Value Adding Management, which is new in FM literature. It is expected to increase the awareness of the impacts...

  12. Insulin Resistance and Risk of Cardiovascular Disease in Postmenopausal Women

    DEFF Research Database (Denmark)

    Schmiegelow, Michelle D; Hedlin, Haley; Stefanick, Marcia L;

    2015-01-01

    studies with no history of CVD, atrial fibrillation, or diabetes mellitus at baseline (1993-1998). We assessed the prognostic value of adding fasting serum insulin, HOMA-IR (homeostasis model assessment-insulin resistance), serum-triglyceride-to-serum-high-density lipoprotein-cholesterol ratio TG....../HDL-C, or impaired fasting glucose (serum glucose ≥110 mg/dL) to traditional risk factors in separate Cox multivariable analyses and assessed risk discrimination and reclassification. The study end point was major CVD events (nonfatal and fatal coronary heart disease and ischemic stroke) within 10 years, which.......98-1.15); for TG/HDL-C, 1.11 (CI, 0.99-1.25); and for glucose, 1.20 (CI, 0.96-1.50). Insulin resistance measures did not improve CVD risk discrimination and reclassification. CONCLUSIONS: Measures of insulin resistance were no longer associated with CVD risk after adjustment for high-density lipoprotein-cholesterol...

  13. AdS3: the NHEK generation

    Science.gov (United States)

    Bena, Iosif; Heurtier, Lucien; Puhm, Andrea

    2016-05-01

    It was argued in [1] that the five-dimensional near-horizon extremal Kerr (NHEK) geometry can be embedded in String Theory as the infrared region of an infinite family of non-supersymmetric geometries that have D1, D5, momentum and KK monopole charges. We show that there exists a method to embed these geometries into asymptotically- {AdS}_3× {S}^3/{{Z}}_N solutions, and hence to obtain infinite families of flows whose infrared is NHEK. This indicates that the CFT dual to the NHEK geometry is the IR fixed point of a Renormalization Group flow from a known local UV CFT and opens the door to its explicit construction.

  14. 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.

  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. Analog insulin detemir for patients with type 1 and type 2 diabetes: a review

    Directory of Open Access Journals (Sweden)

    Gregory E Peterson

    2009-05-01

    Full Text Available Gregory E PetersonDepartment of Internal Medicine, Des Moines University, USAObjective: To review insulin detemir for clinical use to better manage patients with type 1 and type 2 diabetes.Methods: A MEDLINE search, in English, from June 30, 2006 to December 1, 2008, using the terms “insulin analogs,” “insulin detemir” and “long-acting insulin analog.”Results: Insulin detemir improves glycemic control, based on HbA1C reduction and fasting glucose levels, without increasing the risk of hypoglycemia and weight gain. Insulin detemir has lower glycemic variability, with less intra-subject variability in blood glucose levels in patients with type 1 and type 2 diabetes, without increasing the risk of hypoglycemia. When added to oral anti-diabetes agents (OADs in type 2 diabetes, insulin detemir demonstrates superiority to other basal insulin options.Conclusion: Insulin detemir appears to provide better glycemic control with a lower risk of hypoglycemia and less weight gain in the treatment of patients with type 1 and type 2 diabetes.Keywords: type 1 diabetes, type 2 diabetes, insulin analogs, insulin detemir

  17. Insulin receptor activation in the nucleus accumbens reflects nutritive value of a recently ingested meal.

    Science.gov (United States)

    Woods, C A; Guttman, Z R; Huang, D; Kolaric, R A; Rabinowitsch, A I; Jones, K T; Cabeza de Vaca, S; Sclafani, A; Carr, K D

    2016-05-15

    With respect to feeding, insulin is typically thought of as a satiety hormone, acting in the hypothalamus to limit ingestive behavior. However, accumulating evidence suggests that insulin also has the ability to alter dopamine release in the striatum and influence food preferences. With increased access to high calorie foods, Western societies have a high prevalence of obesity, accompanied by insulin insensitivity. Little is known about how insulin is trafficked into the brain following food consumption and whether insulin insensitivity in the periphery is mirrored in the central nervous system. We investigated insulin receptor activation in the ventral striatum of rats receiving water or 16% glucose either orally or intragastrically. We also investigated whether glucose-induced insulin receptor activation was altered in food-restricted (FR) or diet-induced obesity (OB) rat models. Lastly, we examined whether insulin plays a significant role in flavor-nutrient preference learning. Glucose intake stimulated a rapid increase in insulin receptor activity in the ventral striatum of FR and ad libitum (AL) fed rats, but not OB rats. Similarly, both AL and FR, but not OB rats demonstrated significant flavor-nutrient preferences. However AL rats receiving brief inhibition of insulin activity during conditioning failed to acquire a significant flavor-nutrient preference. These findings suggest that impaired insulin receptor activation in the ventral striatum may result in inaccurate valuation of nutritive foods, which could lead to overconsumption of food or the selection of foods that don't accurately meet the body's current physiological needs. PMID:26988281

  18. 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....

  19. 3种新型长效胰岛素类似物%Three novel long acting human insulin analogs produced

    Institute of Scientific and Technical Information of China (English)

    赵腾; 肖拥军; 曹春来; 彭韪

    2013-01-01

    The basal secretion of insulin is continuous low secretion. Regular human insulin secretion, the normal physiological insulin in diabetic patients can't rebuild a higher incidence of hypoglycemia, its clinical application. With the development of genetic engineering technology, the long-acting insulin analogues can simulate normal human insulin secretion after the injection for a small amount of release. Insulin glargine, detemir and degludec are all of human insulin analogs produced, although they are by changing the isoelectric point of insulin or increasing analogs molecular weight, to break down and absorption and extend the duration of action and simulate normal human insulin secretion, but having different molecular structure, long acting mechanisms, artworks and different clinical effects.%胰岛素的基础分泌是指其少量持续的分泌.常规人胰岛素由于不能很好地在糖尿病患者中重建正常生理性胰岛素分泌,低血糖发生率较高,影响了其临床应用.随着基因工程技术的发展,一批新出现的长效胰岛素类似物可以模拟正常人胰岛素的基础分泌,在注射后持续少量的释放.而目前3种新型的长效胰岛素类似物:甘精胰岛素、地特胰岛素和德谷胰岛素,虽然都通过改变胰岛素的等电点或增加类似物分子量的方法,使其分解、吸收及作用时间延长,更好地模拟正常人胰岛素的基础分泌,但其在分子结构、长效机制、生产工艺和临床使用上又有诸多不同.

  20. 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. PMID:27074369

  1. Consumption of a High-Fat Diet Induces Central Insulin Resistance Independent of Adiposity

    OpenAIRE

    Clegg, Deborah J.; Gotoh, Koro; Kemp, Christopher; Wortman, Matthew D.; Benoit, Stephen C.; Brown, Lynda M.; D’Alessio, David; Tso, Patrick; Seeley, Randy J.; Woods, Stephen C

    2011-01-01

    Plasma insulin enters the CNS where it interacts with insulin receptors in areas that are related to energy homeostasis and elicits a decrease of food intake and body weight. Here, we demonstrate that consumption of a high-fat (HF) diet impairs the central actions of insulin. Male Long-Evans rats were given chronic (70-day) or acute (3-day) ad libitum access to HF, low-fat (LF), or chow diets. Insulin administered into the 3rd-cerebral ventricle (i3vt) decreased food intake and body weight of...

  2. Ovarian tumors secreting insulin.

    Science.gov (United States)

    Battocchio, Marialberta; Zatelli, Maria Chiara; Chiarelli, Silvia; Trento, Mariangela; Ambrosio, Maria Rosaria; Pasquali, Claudio; De Carlo, Eugenio; Dassie, Francesca; Mioni, Roberto; Rebellato, Andrea; Fallo, Francesco; Degli Uberti, Ettore; Martini, Chiara; Vettor, Roberto; Maffei, Pietro

    2015-08-01

    Combined ovarian germ cell and neuroendocrine tumors are rare. Only few cases of hyperinsulinism due to ovarian ectopic secretion have been hypothesized in the literature. An ovarian tumor was diagnosed in a 76-year-old woman, referred to our department for recurrent hypoglycemia with hyperinsulinism. In vivo tests, in particular fasting test, rapid calcium infusion test, and Octreotide test were performed. Ectopic hyperinsulinemic hypoglycemia was demonstrated in vivo and hypoglycemia disappeared after hysteroadnexectomy. Histological exam revealed an ovarian germ cell tumor with neuroendocrine and Yolk sac differentiation, while immunostaining showed insulin positivity in neuroendocrine cells. A cell culture was obtained by tumoral cells, testing Everolimus, and Pasireotide. Insulin was detected in cell culture medium and Everolimus and Pasireotide demonstrated their potentiality in reducing insulin secretion, more than controlling cell viability. Nine cases of hyperinsulinism due to ovarian ectopic secretion reported in literature have been reviewed. These data confirm the ovarian tissue potentiality to induce hyperinsulinemic hypoglycemic syndrome after neoplastic transformation. PMID:25896552

  3. Insulin C-peptide test

    Science.gov (United States)

    C-peptide ... the test depends on the reason for the C-peptide measurement. Ask your health care provider if ... C-peptide is measured to tell the difference between insulin the body produces and insulin someone injects ...

  4. Adipokines and Hepatic Insulin Resistance

    OpenAIRE

    Yu Li; Lin Ding; Waseem Hassan; Daoud Abdelkader; Jing Shang

    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, clarificatio...

  5. Adenoviral vector-mediated insulin gene transfer in the mouse pancreas corrects streptozotocin-induced hyperglycemia.

    Science.gov (United States)

    Shifrin, A L; Auricchio, A; Yu, Q C; Wilson, J; Raper, S E

    2001-10-01

    Therapy for type 1 diabetes consists of tight blood glucose (BG) control to minimize complications. Current treatment relies on multiple insulin injections or an insulin pump placement, beta-cell or whole pancreas transplantation. All approaches have significant limitations and have led to the realization that novel treatment strategies are needed. Pancreatic acinar cells have features that make them a good target for insulin gene transfer. They are not subject to autoimmune attack, a problem with pancreas or islets transplantation, they are avidly transduced by recombinant adenoviral vectors, and capable of exporting a variety of peptides into the portal circulation. Recombinant adenoviral vectors were engineered to express either wild-type or furin-modified human insulin cDNA (AdCMVhInsM). Immunodeficient mice were made diabetic with streptozotocin and injected intrapancreatically with the vectors. BG and blood insulin levels have normalized after administration of AdCMVhInsM. Immunohistochemistry and electron microscopy showed the presence of insulin in acinar cells throughout the pancreas and localization of insulin molecules to acinar cell vesicles. The data clearly establish a relationship between intrapancreatic vector administration, decreased BG and elevated blood insulin levels. The findings support the use of pancreatic acinar cells to express and secrete insulin into the blood stream. PMID:11593361

  6. Cinnamon, glucose and insulin sensitivity

    Science.gov (United States)

    Compounds found in cinnamon not only improve the function of insulin but also function as antioxidants and may be anti-inflammatory. This is very important since insulin function, antioxidant status, and inflammatory response are closely linked; with decreased insulin sensitivity there is also decr...

  7. ADS National Programmes: India

    International Nuclear Information System (INIS)

    Initial preliminary studies in India on ADS concepts were aimed toward applications such as, one way coupled booster reactor concept, thorium burner concept, enhancement of breeding rate of thorium– fueled fast reactors, and to incinerate Pu and minor actinides discharged from heavy water and fast reactors. These studies led to a roadmap on development of ADS subsystems in India, which was chalked out initially in June 2001. It was realized in these studies that the most challenging subsystem in terms of technology development and capital investment for ADS in India would be the high intensity proton accelerator, and that it must be accomplished in phased manner. Of the two alternative accelerator types, viz. the cyclotron and linear accelerator (linac), it is concluded that only linac would provide the necessary intense beam current for ADS applications. The energy amplifier (EA) scheme, with lead (45.5%) bismuth (55.5%) eutectic (LBE) as target & coolant, which was proposed in the early nineties would be one of the desired configurations of ADS for Indian applications. Additionally, subcritical reactor core of Indian Advanced Heavy Water Reactor (AHWR), with advantages of its low fission power density, and neutron economy is also a candidate among various ADS reactor configurations. These options of ADS configurations for thorium utilization are based on the neutronic properties of 233U isotope as fissile fuel, which are more or less similar in thermal and in moderately fast neutron spectra

  8. 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.

  9. Generation-dependent effect of PAMAM dendrimers on human insulin fibrillation and thermal stability.

    Science.gov (United States)

    Nowacka, Olga; Milowska, Katarzyna; Belica-Pacha, Sylwia; Palecz, Bartlomiej; Šipošová, Katarina; Gazova, Zuzana; Bryszewska, Maria

    2016-01-01

    We have studied the effect of polyamidoamine (PAMAM) dendrimers of various generations on the thermal stability and fibrillation of human insulin. Thermostability of human insulin used differential scanning calorimetry (DSC), which showed two phase-transitions for insulin at 60 and 82°C. After adding dendrimers at 0.6 μmol/l, the first peaks disappeared and the second peaks were higher. We posited that, in the presence of dendrimers, the dimers in the solution were transformed into hexamers. The effect of dendrimers on insulin fibrillation was monitored by measuring ThT fluorescence, and visualization of insulin fibrils by transmission electron microscopy (TEM) and atomic force microscopy (AFM). The effect of PAMAM dendrimers on insulin fibrillation was strongly dependent on the dendrimers generation and dendrimer:protein ratio. PMID:26598047

  10. Insulin Degludec, The New Generation Basal Insulin or Just another Basal Insulin?

    OpenAIRE

    Sami N. Nasrallah; L. Raymond Reynolds

    2012-01-01

    The advances in recombinant DNA technology have led to an improvement in the properties of currently available long-acting insulin analogs. Insulin degludec, a new generation ultra-long-acting basal insulin, currently in phase 3 clinical trials, has a promising future in clinical use. When compared to its rival basal insulin analogs, a longer duration of action and lower incidence of hypoglycemic events in both type 1 and type 2 diabetic patients has been demonstrated.1,2 Its unique mechanism...

  11. New Insulin Delivery Recommendations.

    Science.gov (United States)

    Frid, Anders H; Kreugel, Gillian; Grassi, Giorgio; Halimi, Serge; Hicks, Debbie; Hirsch, Laurence J; Smith, Mike J; Wellhoener, Regine; Bode, Bruce W; Hirsch, Irl B; Kalra, Sanjay; Ji, Linong; Strauss, Kenneth W

    2016-09-01

    Many primary care professionals manage injection or infusion therapies in patients with diabetes. Few published guidelines have been available to help such professionals and their patients manage these therapies. Herein, we present new, practical, and comprehensive recommendations for diabetes injections and infusions. These recommendations were informed by a large international survey of current practice and were written and vetted by 183 diabetes experts from 54 countries at the Forum for Injection Technique and Therapy: Expert Recommendations (FITTER) workshop held in Rome, Italy, in 2015. Recommendations are organized around the themes of anatomy, physiology, pathology, psychology, and technology. Key among the recommendations are that the shortest needles (currently the 4-mm pen and 6-mm syringe needles) are safe, effective, and less painful and should be the first-line choice in all patient categories; intramuscular injections should be avoided, especially with long-acting insulins, because severe hypoglycemia may result; lipohypertrophy is a frequent complication of therapy that distorts insulin absorption, and, therefore, injections and infusions should not be given into these lesions and correct site rotation will help prevent them; effective long-term therapy with insulin is critically dependent on addressing psychological hurdles upstream, even before insulin has been started; inappropriate disposal of used sharps poses a risk of infection with blood-borne pathogens; and mitigation is possible with proper training, effective disposal strategies, and the use of safety devices. Adherence to these new recommendations should lead to more effective therapies, improved outcomes, and lower costs for patients with diabetes.

  12. 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...

  13. To observe and compare the effect of glycemic control in intensively treated adult subject with type 2 diabetes using insulin analogs and gene recombine human insulin%胰岛素类似物和重组人胰岛素强化治疗糖尿病观察

    Institute of Scientific and Technical Information of China (English)

    鲜杨; 李蓬秋; 陈树; 张学军; 吴冀川; 包明晶; 杨艳; 张磊; 朱显军

    2009-01-01

    Objective The study was designed to evaluate the clinical effectiveness and safety of glycose control using insulin analogs or gene recombine human insulin intensively treated adult subject with type 2 diabetes inadequately controlled with oral antidiabetes drugs. Methods This was 9 months open label randomized control trial involving 45 type 2 diabetes that needed using insulin assigned into two groups either using insulin analogs group or gene recombine human insulin group. Rapid-act insu-lin analogs lispro insulin or human regular insulin before each med plus long-act insulin analogs glargine or NPH insulin at bed-time was given subcutaneous injection quartic week respectively. Patients monitor blood glucose week by themselves, A1C was de-termine quarterly. Results Baseline A1C, diabetes duration and demography was similar in two groups. Mean A1C was significant-ly decreased insulin analogs group (-2.89±0.054)% ; recombine human insulin group (-2.32±0.052)% (P<0.05). Insulin analogs group showed superiority in A1C improvement (-0.57% ;P<0.01). A significantly higher number of subjects achieved Alc≤6.5% (52.17%vs 27.27%) and within target range was higher in the insulin analogs group(73.91% vs 45.45% ). Insulin does was similar, body weight was not significant differences between the two groups. Above target range glycemia were lower in the insulin analogs group. Nocturnal and severe hypoglycemia were lower in the insulin analogs group. Conclusion Our result shows that improved glycemic control can be gained and maintained over 9 months in patients with type 2 diabeties by using insulin analogs with no differece in dose and weight gain.%目的 比较胰岛素类似物和重组人胰岛素治疗成人2型糖尿病的疗效和安全性.方法 45例T2DM患者,分别给予超短效胰岛素类似物加长效胰岛素类似物或基因重组正规人胰岛素加精蛋白锌胰岛素强化治疗9个月,比较A1C、平均PG的达标率、低血糖和严重低血糖

  14. Coopetitive Ad Auctions

    OpenAIRE

    Hoy, Darrell; Jain, Kamal; Wilkens, Christopher A.

    2012-01-01

    A single advertisement often benefits many parties, for example, an ad for a Samsung laptop benefits Microsoft. We study this phenomenon in search advertising auctions and show that standard solutions, including the status quo ignorance of mutual benefit and a benefit-aware Vickrey-Clarke-Groves mechanism, perform poorly. In contrast, we show that an appropriate first-price auction has nice equilibria in a single-slot ad auction --- all equilibria that satisfy a natural cooperative envy-freen...

  15. Insulin gene mutations and diabetes

    OpenAIRE

    Nishi, Masahiro; Nanjo, Kishio

    2011-01-01

    Abstract Some mutations of the insulin gene cause hyperinsulinemia or hyperproinsulinemia. Replacement of biologically important amino acid leads to defective receptor binding, longer half‐life and hyperinsulinemia. Three mutant insulins have been identified: (i) insulin Chicago (F49L or PheB25Leu); (ii) insulin Los Angeles (F48S or PheB24Ser); (iii) and insulin Wakayama (V92L or ValA3Leu). Replacement of amino acid is necessary for proinsulin processing results in hyperproinsulinemia. Four t...

  16. AdS_3: the NHEK generation

    CERN Document Server

    Bena, Iosif; Puhm, Andrea

    2015-01-01

    It was argued in arXiv:1203.4227 that the five-dimensional near-horizon extremal Kerr (NHEK) geometry can be embedded in String Theory as the infrared region of an infinite family of non-supersymmetric geometries that have D1, D5, momentum and KK monopole charges. We show that there exists a method to embed these geometries into asymptotically-AdS_3 x S^3/Z_N solutions, and hence to obtain infinite families of flows whose infrared is NHEK. This indicates that the CFT dual to the NHEK geometry is the IR fixed point of a Renormalization Group flow from a known local UV CFT and opens the door to its explicit construction.

  17. 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

  18. Insulin degludec for diabetes mellitus.

    Science.gov (United States)

    2013-07-01

    Over the last few years there has been a steady increase in the number of prescriptions dispensed in primary care for intermediate and long-acting insulin analogues and a reduction in prescriptions for biphasic isophane insulin. For example, in England, the volume of intermediate and long-acting insulin analogues in general practice has risen from approximately 650,000 prescriptions per quarter in 2007 to over 850,000 per quarter in 2012.(1) ▾Insulin degludec (Tresiba, Novo Nordisk) is a new long acting basal insulin analogue for the management of diabetes mellitus in adults.(2) Two strengths of insulin degludec (100 units/mL and 200 units/mL) were launched in the UK in February 2013. Here we discuss evidence for the effectiveness and safety of insulin degludec. PMID:23842634

  19. Superactive insulin: [B10-aspartic acid]insulin(human)

    International Nuclear Information System (INIS)

    The genetic basis for a case of familial hyperproinsulinemia has been elucidated recently. It involves a single point mutation in the proinsulin gene resulting in the substitution of aspartic acid for histidine-10 of the B chain of insulin. The authors have synthesized a human insulin analogue, [Asp/sup B10/] insulin, corresponding to the mutant proinsulin and evaluated its biological activity. [Asp/sup B10/] Insulin displayed a binding affinity to insulin receptors in rat liver plasma membranes that was 534 +- 146% relative to the natural hormone. In lipogenesis assays, the synthetic analogue exhibited a potency that was 435 +- 144% relative to insulin, which is statistically not different from its binding affinity. Reversed-phase HPLC indicated that the synthetic analogue is more apolar than natural insulin. They suggest that the observed properties reflect changes in the conformation of the analogue relative to natural insulin, which results in a stronger interaction with the insulin receptor. Thus, a single substitution of an amino acid residue of human insulin has resulted in a superactive hormone

  20. Superactive insulin: (B10-aspartic acid)insulin(human)

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, G.P.; Burke, G.T.; Katsoyannis, P.G.

    1987-09-01

    The genetic basis for a case of familial hyperproinsulinemia has been elucidated recently. It involves a single point mutation in the proinsulin gene resulting in the substitution of aspartic acid for histidine-10 of the B chain of insulin. The authors have synthesized a human insulin analogue, (Asp/sup B10/) insulin, corresponding to the mutant proinsulin and evaluated its biological activity. (Asp/sup B10/) Insulin displayed a binding affinity to insulin receptors in rat liver plasma membranes that was 534 +- 146% relative to the natural hormone. In lipogenesis assays, the synthetic analogue exhibited a potency that was 435 +- 144% relative to insulin, which is statistically not different from its binding affinity. Reversed-phase HPLC indicated that the synthetic analogue is more apolar than natural insulin. They suggest that the observed properties reflect changes in the conformation of the analogue relative to natural insulin, which results in a stronger interaction with the insulin receptor. Thus, a single substitution of an amino acid residue of human insulin has resulted in a superactive hormone.

  1. 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.

  2. Euglycemic Infusion of Insulin Detemir Compared With Human Insulin Appears to Increase Direct Current Brain Potential Response and Reduces Food Intake While Inducing Similar Systemic Effects

    Science.gov (United States)

    Hallschmid, Manfred; Jauch-Chara, Kamila; Korn, Oliver; Mölle, Matthias; Rasch, Björn; Born, Jan; Schultes, Bernd; Kern, Werner

    2010-01-01

    OBJECTIVE In the treatment of diabetic patients, the long-acting insulin analog insulin detemir is less prone to induce weight gain than other insulin formulations. Assuming that because of its pharmacologic properties, detemir displays stronger central nervous anorexigenic efficacy than human insulin, we compared acute effects of human insulin and detemir on electroencephalography (EEG) measures and food intake. RESEARCH DESIGN AND METHODS Frontocortical EEG direct current (DC) potentials were recorded in 15 healthy men during two hyperinsulinemic-euglycemic clamps that included an insulin bolus injection (human insulin, 17.75 mU/kg body wt; detemir, 90 mU/kg body wt) followed by a steady 90-min infusion (1.0 vs. 2.0 mU · kg−1 · min−1). A higher dosage was chosen for detemir to compensate for its delay in impact relative to human insulin and to elicit similar systemic effects. At 20 min after infusion, subjects were allowed to eat ad libitum from a test buffet. RESULTS Mean glucose infusions to maintain euglycemia (P > 0.93) and blood glucose concentrations (P > 0.34) did not differ between conditions. Detemir infusion induced a negative DC-potential shift, averaging −372.2 μV from 21 to 90 min that was not observed during human insulin infusion (146.5 μV, P = 0.02). Detemir, in comparison with human insulin, reduced subsequent food intake by 303 kcal (1,257 vs. 1,560, P < 0.04). CONCLUSIONS While inducing comparable peripheral effects, detemir exerts stronger acute effects on brain functions than human insulin and triggers a relative decrease in food consumption, suggesting an enhanced anorexigenic impact of detemir compared with human insulin on central nervous networks that control nutrient uptake. PMID:20068139

  3. Serological analysis of human IgG and IgE anti-insulin antibodies by solid-phase radioimmunoassays

    International Nuclear Information System (INIS)

    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

  4. Prevention of insulin resistance with Hibiscus sabdariffa Linn. extract in high-fructose fed rat

    OpenAIRE

    Trinovita Andraini; Sophie Yolanda

    2015-01-01

    Background: Dyslipidemia and stress oxidative play an important role as the cause of insulin resistance. One herb that has potent antioxidant effect and may improve dyslipidemia is Hibiscus sabdariffa Linn. The aim of this study was to evaluate the effect of Hibiscus sabdariffa Linn. extract on fasting blood glucose level, fasting blood insulin level, and insulin resistance index (HOMA-IR) in high-fructose fed rat.Methods: This was an experimental study in 25 Sprague-Dawley rats which were ad...

  5. ADS National Programmes: Italy

    International Nuclear Information System (INIS)

    Following a preliminary design developed in 1998, based on the Energy Amplifier concept proposed by CERN, a first configuration of a lead-bismuth Eutectic cooled Experimental ADS (LBE-XADS) was worked out in the period 1999–2001, under the aegis of MURST, by a group of Italian organizations led by Ansado Nucleare, with the aim of assessing the feasibility of a small sized (80 MWth) ADS. At the end of 1997 a joint effort of ENEA (National Agency for New Technology, Energy and the Environment) and INFN (National Institute for Nuclear Physics) led to the approval of a national programme by MURST (Minister for University and Scientific and Technological Research) named TRASCO (TRAsmutazione SCOrie) aiming at the study of physics and technologies needed to design an ADS for radioactive waste transmutation. The programme consisted of research subprogrammes on accelerator, neutronics, thermalhydraulics analysis, beam window technology, and material technology and compatibility with Pb and Pb-Bi. At now, most of the activities in support to the ADS development carried out at national level are part of EU-funded Projects. These activities are complemented by the programme agreement (AdP -Accordo di programma), signed between ENEA and the Ministry of Economic Development, which provides in general a range of activities aimed at the development of sustainable nuclear fission systems. Several universities and the national industry are involved, besides ENEA, in the activities

  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. ADS National Programmes: China

    International Nuclear Information System (INIS)

    In China the conceptual study of an ADS concept which lasted for about five years ended in 1999. As one project of the National Basic Research Programme of China (973 Programme) in energy domain, which is sponsored by the China Ministry of Science and Technology (MOST), a five year programme of fundamental research of ADS physics and related technology was launched in 2000 and passed national review at the end of 2005. From 2007, another five year 973 Programme Key Technology Research of Accelerator Driven Subcritical System for Nuclear waste Transmutation started. The research activities were focused on HPPA physics and technology, reactor physics of external source driven subcritical assembly, nuclear data base and material study. For HPPA, a high current injector consisting of an ECR ion source, LEBT and an RFQ accelerating structure of 3.5 MeV has been built and were being improved. In reactor physics study, a series of neutron multiplication experimental study has been carrying out. The VENUS I facility has been constructed as the basic experimental platform for neutronics study in ADS blanket. VENUS I a zero power subcritical neutron multiplying assembly driven by external neutron produced by a pulsed neutron generator or 252Cf neutron source. The theoretical, experimental and simulation studies on nuclear data, material properties and nuclear fuel circulation related to ADS are carried out in order to provide the database for ADS system analysis. China Institute of Atomic Energy (CIAE), Institute of High Energy Physics (IHEP) and other Chinese institutes carried out the MOST project together. Besides CIAE, China Academy of Science (CAS) pays more and more attention to Advanced Nuclear Fuel Cycles (ANFC). A large programme of ANFC, including ADS and Th based nuclear fuel cycle, has been launched by CAS

  8. Insulin receptor in Drosophila melanogaster

    Energy Technology Data Exchange (ETDEWEB)

    Petruzzelli, L.; Herrera, R.; Rosen, O.

    1986-05-01

    A specific, high affinity insulin receptor is present in both adult Drosophila and in Drosophila embryos. Wheat germ lectin-enriched extracts of detergent-solubilized membranes from embryos and adults bind insulin with a K/sub d/ of 15 nM. Binding is specific for insulin; micromolar concentrations of proinsulin, IGFI, and IGFII are required to displace bound /sup 125/I-insulin. Insulin-dependent protein tyrosine kinase activity appears during embryogenesis. It is evident between 6 and 12 hours of development, peaks between 12 and 18 hours and falls in the adult. During 0-6 hours of embryogenesis, and in the adult, a specific protein band (Mr = 135,000) is crosslinked to /sup 125/I-insulin. During 6-12 and 12-18 hours of embryogenesis stages in which insulin-dependent protein tyrosine kinase is high, an additional band (Mr = 100,000) becomes crosslinked to /sup 125/I-insulin. Isolation and DNA sequence analysis of genomic clones encoding the Drosophila insulin receptor will be presented as will the characterization of insulin receptor mRNA's during development.

  9. Insulin receptor in Drosophila melanogaster

    International Nuclear Information System (INIS)

    A specific, high affinity insulin receptor is present in both adult Drosophila and in Drosophila embryos. Wheat germ lectin-enriched extracts of detergent-solubilized membranes from embryos and adults bind insulin with a K/sub d/ of 15 nM. Binding is specific for insulin; micromolar concentrations of proinsulin, IGFI, and IGFII are required to displace bound 125I-insulin. Insulin-dependent protein tyrosine kinase activity appears during embryogenesis. It is evident between 6 and 12 hours of development, peaks between 12 and 18 hours and falls in the adult. During 0-6 hours of embryogenesis, and in the adult, a specific protein band (Mr = 135,000) is crosslinked to 125I-insulin. During 6-12 and 12-18 hours of embryogenesis stages in which insulin-dependent protein tyrosine kinase is high, an additional band (Mr = 100,000) becomes crosslinked to 125I-insulin. Isolation and DNA sequence analysis of genomic clones encoding the Drosophila insulin receptor will be presented as will the characterization of insulin receptor mRNA's during development

  10. 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

  11. Insulin and insulin mutants stimulate glucose uptake in rat adipocytes

    Institute of Scientific and Technical Information of China (English)

    姚矢音; 张新堂; 许英镐; 张信娜; 朱尚权

    1999-01-01

    A simple method to determine the in vitro biological activity of insulin by measuring glucose uptake in the rat adipocytes is presented here. In the presence of insulin, the glucose uptake is 5-6 times more than the basal control. And the uptake of D-[3-3H]-glucose is linear as the logarithm of insulin concentration from 0.2 μg/L to 1.0 μg/L. Glucose and 3-O-methyl-glucose inhibit D-[3-3H]-glucose uptake into adipocytes. By this method, the in vitro biological activity of [B2-Lys]-insulin and [B3-Lys]-insulin was measured to be 61.6% and 154% respectively, relative to that of insulin.

  12. 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

  13. Eating ad Libitum

    DEFF Research Database (Denmark)

    Hillersdal, Line

    in the context of the 'ad libitum meal'. The analytical interest is thus what kind of eaters and bodies are enacted in the meal test and what ideas of prevention and treatment are embedded in their standards. Drawing from ongoing empirical work among Danish obesity researchers performing scientific meal tests I...... ask what make up food stuff and eaters in the meal tests? More specifically I explore a scientific testing of changes in taste preferences before and after weight-loss surgery using an ad libitum buffet with a selection of different foods and another testing the effect of exercise on appetite also...

  14. 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

    2015-01-01

    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 GL

  15. Alternate Phosphorylation/O-GlcNAc Modification on Human Insulin IRSs: A Road towards Impaired Insulin Signaling in Alzheimer and Diabetes

    Science.gov (United States)

    Jahangir, Zainab; Ahmad, Waqar; Shabbiri, Khadija

    2014-01-01

    Impaired insulin signaling has been thought of as important step in both Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). Posttranslational modifications (PTMs) regulate functions and interaction of insulin with insulin receptors substrates (IRSs) and activate insulin signaling downstream pathways via autophosphorylation on several tyrosine (TYR) residues on IRSs. Two important insulin receptor substrates 1 and 2 are widely expressed in human, and alternative phosphorylation on their serine (Ser) and threonine (Thr) residues has been known to block the Tyr phosphorylation of IRSs, thus inhibiting insulin signaling and promoting insulin resistance. Like phosphorylation, O-glycosylation modification is important PTM and inhibits phosphorylation on same or neighboring Ser/Thr residues, often called Yin Yang sites. Both IRS-1 and IRS-2 have been shown to be O-glycosylated; however exact sites are not determined yet. In this study, by using neuronal network based prediction methods, we found more than 50 Ser/Thr residues that have potential to be O-glycosylated and may act as possible sites as well. Moreover, alternative phosphorylation and O-glycosylation on IRS-1 Ser-312, 984, 1037, and 1101 may act as possible therapeutic targets to minimize the risk of AD and T2DM. PMID:25580119

  16. Alternate Phosphorylation/O-GlcNAc Modification on Human Insulin IRSs: A Road towards Impaired Insulin Signaling in Alzheimer and Diabetes

    Directory of Open Access Journals (Sweden)

    Zainab Jahangir

    2014-01-01

    Full Text Available Impaired insulin signaling has been thought of as important step in both Alzheimer’s disease (AD and type 2 diabetes mellitus (T2DM. Posttranslational modifications (PTMs regulate functions and interaction of insulin with insulin receptors substrates (IRSs and activate insulin signaling downstream pathways via autophosphorylation on several tyrosine (TYR residues on IRSs. Two important insulin receptor substrates 1 and 2 are widely expressed in human, and alternative phosphorylation on their serine (Ser and threonine (Thr residues has been known to block the Tyr phosphorylation of IRSs, thus inhibiting insulin signaling and promoting insulin resistance. Like phosphorylation, O-glycosylation modification is important PTM and inhibits phosphorylation on same or neighboring Ser/Thr residues, often called Yin Yang sites. Both IRS-1 and IRS-2 have been shown to be O-glycosylated; however exact sites are not determined yet. In this study, by using neuronal network based prediction methods, we found more than 50 Ser/Thr residues that have potential to be O-glycosylated and may act as possible sites as well. Moreover, alternative phosphorylation and O-glycosylation on IRS-1 Ser-312, 984, 1037, and 1101 may act as possible therapeutic targets to minimize the risk of AD and T2DM.

  17. ADS National Programmes: Belgium

    International Nuclear Information System (INIS)

    The Belgian activities in the field of Accelerator Driven Systems (ADS) are mainly related to the MYRRHA project development. MYRRHA is an accelerator driven, multi purpose fast neutron spectrum facility for R&D, cooled by a lead-bismuth eutectic. SCK•CEN has started the MYRRHA project as a national programme with several national & international bilateral collaboration agreements; the project has now evolved as an European integrated project in the frame of the IPEUROTRANS (European Commission, Sixth Framework Programme). The MYRRHA ‘Draft-2’ predesign file (completed in the early 2005) has been proposed to the partners as a basis for the XT-ADS machine. After a detailed investigation of potential alternatives, the MYRRHA concept (for the subcritical core, the primary coolant system, the accommodation of experimental rigs, the reactor vessel and the spallation target) has been kept with some modifications to achieve the XT-ADS objectives. The most recent version of the XT-ADS design was presented in the 2007 TWG meeting

  18. Insulin Degludec, The New Generation Basal Insulin or Just another Basal Insulin?

    Science.gov (United States)

    Nasrallah, Sami N; Reynolds, L Raymond

    2012-01-01

    The advances in recombinant DNA technology have led to an improvement in the properties of currently available long-acting insulin analogs. Insulin degludec, a new generation ultra-long-acting basal insulin, currently in phase 3 clinical trials, has a promising future in clinical use. When compared to its rival basal insulin analogs, a longer duration of action and lower incidence of hypoglycemic events in both type 1 and type 2 diabetic patients has been demonstrated.1,2 Its unique mechanism of action is based on multihexamer formation after subcutaneous injection. This reportedly allows for less pharmacodynamic variability and within-subject variability than currently available insulin analogs, and a duration of action that is over 24 hours.3 The lack of proof of carcinogenicity with insulin degludec is yet another factor that would be taken into consideration when choosing the optimal basal insulin for a diabetic individual.4 A formulation of insulin degludec with insulin aspart, Insulin degludec 70%/aspart 30%, may permit improved flexibly of dosing without compromising glycemic control or safety.5. PMID:22879797

  19. Extrapancreatic insulin effect of glibenclamide.

    Science.gov (United States)

    Mulder, H; Schopman, W; van der Lely, A J

    1991-01-01

    In eight patients with uncomplicated non insulin dependent diabetes mellitus, serum insulin levels, serum C-peptide levels and blood glucose levels were measured before and after oral administration of glibenclamide 0.1 mg/kg body weight and a test meal, or after a test meal alone. The rise in serum insulin levels persisted longer after glibenclamide. The initial rise in serum insulin was of the same magnitude in both situations, as was the rise in serum C-peptide levels during the entire 5 h study. It is concluded that glibenclamide is able to maintain a more prolonged increase in serum insulin levels by inhibiting the degradation of insulin in the vascular endothelial cells of the liver. The inhibition contributes to the blood glucose lowering effect of glibenclamide. PMID:1904820

  20. 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...

  1. Insulin Neuroprotection and the Mechanisms

    Institute of Scientific and Technical Information of China (English)

    Li-Yun Yu; Yu Pei

    2015-01-01

    Objective:To analyze the mechanism of neuroprotection of insulin and which blood glucose range was benefit for insulin exerting neuroprotective action.Data Sources:The study is based on the data from PubMed.Study Selection:Articles were selected with the search terms "insulin","blood glucose","neuroprotection","brain","glycogen","cerebral ischemia","neuronal necrosis","glutamate","γ-aminobutyric acid".Results:Insulin has neuroprotection.The mechanisms include the regulation of neurotransmitter,promoting glycogen synthesis,and inhibition of neuronal necrosis and apoptosis.Insulin could play its role in neuroprotection by avoiding hypoglycemia and hyperglycemia.Conclusions:Intermittent and long-term infusion insulin may be a benefit for patients with ischemic brain damage at blood glucose 6-9 mmol/L.

  2. D-branes in Lorentzian AdS(3)

    CERN Document Server

    Israel, D

    2005-01-01

    We study the exact construction of D-branes in Lorentzian AdS(3). We start by defining a family of conformal field theories that gives a natural Euclidean version of the SL(2,R) CFT and does not correspond to H(3)+, the analytic continuation of AdS(3). We argue that one can recuperate the exact CFT results of Lorentzian AdS(3), upon an analytic continuation in the moduli space of these conformal field theories. Then we construct exact boundary states for various symmetric and symmetry-breaking D-branes in AdS(3).

  3. Localization on $AdS_2\\times S^1$

    CERN Document Server

    David, Justin R; Gupta, Rajesh Kumar; Narain, Kumar

    2016-01-01

    Conformal symmetry relates the metric on $AdS_2 \\times S^{1}$ to that of $S^3$. This implies that under a suitable choice of boundary conditions for fields on $AdS_2$ the partition function of conformal field theories on these spaces must agree which makes $AdS_2 \\times S^{1}$ a good testing ground to study localization on non-compact spaces. We study supersymmetry on $AdS_2\\times S^1$ and determine the localizing Lagrangian for ${\\cal N}=2$ supersymmetric Chern-Simons theory on $AdS_2\\times S^1$. We evaluate the partition function of ${\\cal N}=2$ supersymmetric Chern-Simons theory on $AdS_2 \\times S^1$ using localization, where the radius of $S^1$ is $q$ times that of $AdS_2$. With boundary conditions on $AdS_2\\times S^1$ which ensure that all the physical fields are normalizable and lie in the space of square integrable wave functions in $AdS_2$, the result for the partition function precisely agrees with that of the theory on the $q$-fold covering of $S^3$.

  4. Nutritional Modulation of Insulin Resistance

    OpenAIRE

    Weickert, Martin O.

    2012-01-01

    Insulin resistance has been proposed as the strongest single predictor for the development of Type 2 Diabetes (T2DM). Chronic oversupply of energy from food, together with inadequate physical activity, have been recognized as the most relevant factors leading to overweight, abdominal adiposity, insulin resistance, and finally T2DM. Conversely, energy reduced diets almost invariably to facilitate weight loss and reduce abdominal fat mass and insulin resistance. However, sustained weight loss i...

  5. Protein Crystal Recombinant Human Insulin

    Science.gov (United States)

    1994-01-01

    The comparison of protein crystal, Recombiant Human Insulin; space-grown (left) and earth-grown (right). On STS-60, Spacehab II indicated that space-grown crystals are larger and of greater optical clarity than their earth-grown counterparts. Recombiant Human Insulin facilitates the incorporation of glucose into cells. In diabetics, there is either a decrease in or complete lack of insulin, thereby leading to several harmful complications. Principal Investigator is Larry DeLucas.

  6. Cell factories for insulin production

    OpenAIRE

    Baeshen, Nabih A.; Baeshen, Mohammed N; Sheikh, Abdullah; Bora, Roop S; Mohamed Morsi M. Ahmed; Ramadan, Hassan A I; Saini, Kulvinder Singh; Redwan, Elrashdy M.

    2014-01-01

    The rapid increase in the number of diabetic patients globally and exploration of alternate insulin delivery methods such as inhalation or oral route that rely on higher doses, is bound to escalate the demand for recombinant insulin in near future. Current manufacturing technologies would be unable to meet the growing demand of affordable insulin due to limitation in production capacity and high production cost. Manufacturing of therapeutic recombinant proteins require an appropriate host org...

  7. Diabetic lipohypertrophy delays insulin absorption.

    Science.gov (United States)

    Young, R J; Hannan, W J; Frier, B M; Steel, J M; Duncan, L J

    1984-01-01

    The effect of lipohypertrophy at injection sites on insulin absorption has been studied in 12 insulin-dependent diabetic patients. The clearance of 125I-insulin from sites with lipohypertrophy was significantly slower than from complementary nonhypertrophied sites (% clearance in 3 h, 43.8 +/- 3.5 +/- SEM) control; 35.3 +/- 3.9 lipohypertrophy, P less than 0.05). The degree of the effect was variable but sufficient in several patients to be of clinical importance. Injection-site lipohypertrophy is another factor that modifies the absorption of subcutaneously injected insulin.

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

    Science.gov (United States)

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

    2010-01-01

    Insulin resistance has been found to be an independent factor predicting sustained response to peginterferon plus ribavirin in patients with chronic hepatitis C. Insulin resistance seems to be involved in decreased sensitivity to interferon and could block interferon intracellular signaling. Insulin resistance promotes steatosis and fibrosis progression, induces pro-inflammatory cytokine secretion and increases adipose tissue, decreasing interferon availability. Moreover, suppressor of cytokines 3 and protein tyrosine-phosphatase seems to be able to block interferon and insulin signaling, building a feed-forward loop. Insulin resistance can be treated with exercise, diet or through the use of drugs that improve insulin sensitivity, like biguanides or glitazones. A recent controlled, randomized, double-blind clinical trial (TRIC-1) examined the effect of adding metformin to standard therapy in the treatment of hepatitis C. This study demonstrated that women infected with hepatitis C virus genotype 1 and HOMA >2 treated with metformin showed a greater drop in viral load during the first 12 weeks and a doubled sustained viral response in comparison with females receiving placebo. Pioglitazone has been used in previous nonresponders and naïve patients with disappointing results in two pilot trials. The mechanisms by which the virus promotes insulin resistance seems to be genotype-dependent and could explain, at least in part, the discrepancies between insulin sensitizers. Insulin resistance is a new target in the challenging management of chronic hepatitis C. PMID:20460925

  9. Glucose-responsive artificial promoter-mediated insulin gene transfer improves glucose control in diabetic mice

    Institute of Scientific and Technical Information of China (English)

    Jaeseok Han; Eung-Hwi Kim; Woohyuk Choi; Hee-Sook Jun

    2012-01-01

    AIM:To investigate the effect of insulin gene therapy using a glucose-responsive synthetic promoter in type 2 diabetic obese mice.METHODS:We employed a recently developed novel insulin gene therapy strategy using a synthetic promoter that regulates insulin gene expression in the liver in response to blood glucose level changes.We intravenously administered a recombinant adenovirus expressing furin-cleavable rat insulin under the control of the synthetic promoter (rAd-SP-rINSfur) into diabetic Leprdb/db mice.A recombinant adenovirus expressing β-galactosidase under the cytomegalovirus promoter was used as a control (rAd-CMV-βgal).Blood glucose levels and body weights were monitored for 50 d.Glucose and insulin tolerance tests were performed.Immunohistochemical staining was performed to investigate islet morphology and insulin content.RESULTS:Administration of rAd-SP-rINSfur lowered blood glucose levels and normoglycemia was maintained for 50 d,whereas the rAd-CMV-βgal control virus-injected mice remained hyperglycemic.Glucose tolerance tests showed that rAd-SP-rINSfur-treated mice cleared exogenous glucose from the blood more efficiently than control virus-injected mice at 4 wk [area under the curve (AUC):21 508.80 ± 2248.18 vs 62 640.00 ± 5014.28,P < 0.01] and at 6 wk (AUC:29 956.60 ± 1757.33 vs 60 016.60 ± 3794.47,P < 0.01).In addition,insulin sensitivity was also significantly improved in mice treated with rAd-SP-rINSfur compared with rAd-CMV-βgal-treated mice (AUC:9150.17±1007.78 vs 11 994.20 ± 474.40,P < 0.05).The islets from rAd-SP-rINSfur-injected mice appeared to be smaller and to contain a higher concentration of insulin than those from rAd-CMV-βgal-injected mice.CONCLUSION:Based on these results,we suggest that insulin gene therapy might be one therapeutic option for remission of type 2 diabetes.

  10. Management job ads

    DEFF Research Database (Denmark)

    Holmgreen, Lise-Lotte

    2014-01-01

    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...... 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 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...

  11. Intranasal insulin therapy: the clinical realities

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, Sten; Hvidberg, A;

    1995-01-01

    quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

  12. ADS National Programmes: France

    International Nuclear Information System (INIS)

    Studies related to nuclear reactors and radioactive waste started at the French National Centre for Scientific research, CNRS, as a result of the French law on radioactive waste that was published in 1991. They were initially organized around the programme PACE (Physique pour l’Aval du Cycle Electronucléaire = physics of the back end of the nuclear fuel cycle), which became PACEN (Physique pour l’Aval du Cycle et production d’Energie Nucléaire = Physics of the back end of the nuclear fuel cycle and production of nuclear energy) in 2006. Research on accelerator driven systems was from the beginning part of this programme. This research is mainly funded by the National Institute for Nuclear end Particle Physics (IN2P3) of CNRS and within the EURATOM European programmes (FP5, 6 and 7). The programme took place in several stages, and covered various scientific fields, benefitting from expertise of CNRS in the field. More specifically, it aimed and still aims to: – Test and verify the feasibility and design of the ADS concept, in terms of neutronics, physics of materials, design of the accelerator and tests of its prototypical components that have been built (or are at present under construction); – Measure and-or improve nuclear data related to radioactive waste transmutation. Today, most of the activities in support to ADS development carried out by CNRS focus on accelerator developments, GUINEVERE (Generator of Uninterrupted Intense NEutron at the lead VEnus REactor) experiment, ADS core studies, deployment scenarios and nuclear data measurements. The CEA R&D programmes on ADS are mainly focused on the European project EUROTRANS of the 6th Framework programme (2005–2010) and continued in the FREYA project of the 7th Framework Programme

  13. Adding linear orders

    CERN Document Server

    Shelah, Saharon

    2011-01-01

    We address the following question: Can we expand an NIP theory by adding a linear order such that the expansion is still NIP? Easily, if acl(A)=A for all A, then this is true. Otherwise, we give counterexamples. More precisely, there is a totally categorical theory for which every expansion by a linear order has IP. There is also an \\omega-stable NDOP theory for which every expansion by a linear order interprets bounded arithmetic.

  14. Human insulin prepared by recombinant DNA techniques and native human insulin interact identically with insulin receptors.

    OpenAIRE

    Keefer, L M; Piron, M A; DE MEYTS, P.

    1981-01-01

    Human insulin synthesized from A and B chains separately produced in Escherichia coli from cloned synthetic genes (prepared by the Eli Lilly Research Laboratories, Indianapolis, IN) was characterized by examining its interaction with human cultured lymphocytes, human circulating erythrocytes in vitro, and isolated rat fat cells. The binding behavior of the biosynthetic insulin with human cells was indistinguishable from that of native human or porcine insulins, with respect to affinity, assoc...

  15. Monoclonal antibodies to the human insulin receptor block insulin binding and inhibit insulin action.

    OpenAIRE

    Roth, R A; Cassell, D J; Wong, K. Y.; Maddux, B A; Goldfine, I D

    1982-01-01

    Antibodies to the insulin receptor were prepared in BALB/c mice by immunization with IM-9 human lymphocytes, a cell type that has a large number of plasma membrane insulin receptors. The spleens of these mice were then removed, and their lymphocytes were fused to a mouse myeloma cell line, FO cells. After screening over 1,200 resulting hybrids, one stable hybrid was obtained that produced IgG1 antibodies directed towards the insulin receptor. This antibody blocked 125I-labeled insulin binding...

  16. AdS 3-manifolds and Higgs bundles

    DEFF Research Database (Denmark)

    Alessandrini, Daniele; Li, Qiongling

    2015-01-01

    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 the volumes. We also find...

  17. 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.

  18. The effects of GLP-1 analogues in obese, insulin-using type 2 diabetes in relation to eating behaviour

    OpenAIRE

    de Boer, Stefanie Amarens; Lefrandt, Joop Daniel; Petersen, Japke Frida; Boersma, Hendrikus Hessel; Mulder, Douwe Johannes; Hoogenberg, Klaas

    2015-01-01

    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 GLP-1 RA treatment on body weight, glycaemic control and total daily insulin dose in obese, insulin-using type 2 diabetes patients after 2 years follow-up in a real life setting and to explore a poss...

  19. Insulin resistance and progression to type 1 diabetes in the European Nicotinamide Diabetes Intervention Trial (ENDIT)

    DEFF Research Database (Denmark)

    Bingley, Polly J; Mahon, Jeffrey L; Gale, Edwin A M;

    2008-01-01

    OBJECTIVE: Insulin resistance can modulate progression to type 1 diabetes in individuals with ongoing islet autoimmunity. We wanted to see whether measures of insulin resistance improved risk assessment in islet cell antibody (ICA)-positive relatives when added to other immune and metabolic markers......-up was 4.21 years, and 105 individuals developed diabetes. Oral and intravenous glucose tolerance tests were performed at baseline; antibodies to GAD, IA-2, and insulin were determined by radioimmunoassay; and insulin resistance was estimated by homeostasis model assessment. Risk was assessed by Cox...... glucose tolerance test (P insulin resistance (HOMA2-IR) achieved only borderline significance (P = 0.06). HOMA2-IR was an independent determinant in participants with loss of FPIR (P = 0...

  20. Neuronal LRP1 Regulates Glucose Metabolism and Insulin Signaling in the Brain

    OpenAIRE

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

    2015-01-01

    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 durin...

  1. Evaporation of large black holes in AdS

    International Nuclear Information System (INIS)

    The AdS/CFT correspondence offers a new perspective on the long-standing black hole information paradox. However, to be able to use the available gauge/gravity machinery one is forced to consider so-called 'large' black holes in AdS, and these objects are thermodynamically stable - they do not evaporate. We describe a simple toy model that allows large AdS black holes to decay, by coupling the emitted radiation to an external scalar field propagating in an auxiliary space. This effectively changes the properties of the boundary of AdS, making it partly absorbing. We demonstrate that the evaporation process never ceases by explicitly presenting (a) the transmission coefficient for a wave scattering from the bulk into auxiliary space and (b) the greybody factor for a black 3-brane in an AdS background. Therefore, the model provides an interesting framework to address the information paradox using AdS/CFT techniques.

  2. Insulin Signaling and Heart Failure.

    Science.gov (United States)

    Riehle, Christian; Abel, E Dale

    2016-04-01

    Heart failure is associated with generalized insulin resistance. Moreover, insulin-resistant states such as type 2 diabetes mellitus and obesity increases the risk of heart failure even after adjusting for traditional risk factors. Insulin resistance or type 2 diabetes mellitus 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 box O 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.

  3. [Local lipohypertrophy in insulin treatment].

    Science.gov (United States)

    Herold, D A; Albrecht, G

    1993-01-01

    Local lipoatrophy and lipohypertrophy at injection sites are well known side effects of treatment with insulin. Conditions favouring these local complications are created when repeated or continuous injections are given into the same areas. We report on a 27-year-old female patient who suffered from persistent local swellings after use of an external pump which continuously injected human insulin via indwelling cannulas.

  4. Extrapancreatic insulin effect of glibenclamide

    NARCIS (Netherlands)

    H.W. Mulder (H. W.); W. Schopman Sr. (W.); A-J. van der Lely (Aart-Jan)

    1991-01-01

    textabstractIn eight patients with uncomplicated non insulin dependent diabetes mellitus, serum insulin levels, serum C-peptide levels and blood glucose levels were measured before and after oral administration of glibenclamide 0.1 mg/kg body weight and a test meal, or after a test meal alone. The r

  5. The effect of Ad

    Institute of Scientific and Technical Information of China (English)

    李小艳

    2010-01-01

    There is the trend that now people appreciate those who are slim and regard slim even thin people beautiful. The thinner a person is, the more beautiful. Women, born to pursuit beauty, try various means to follow the trend. We all watch TV, and find a lot of advertisements on diet. The effect of them is tremendous. We all know the fact that it is not at all the better mouse trap will catch mouse. The sales methods are more important. If an advertisement is very interesting and seemingly effective, people will be lured by the ad and then try some of the products.

  6. Insulin secretion and signaling in response to dietary restriction and subsequent re-alimentation in cattle.

    Science.gov (United States)

    Keogh, Kate; Kenny, David A; Kelly, Alan K; Waters, Sinéad M

    2015-08-01

    The objectives of this study were to examine systemic insulin response to a glucose tolerance test (GTT) and transcript abundance of genes of the insulin signaling pathway in skeletal muscle, during both dietary restriction and re-alimentation-induced compensatory growth. Holstein Friesian bulls were blocked to one of two groups: 1) restricted feed allowance for 125 days (period 1) (RES, n = 15) followed by ad libitum feeding for 55 days (period 2) or 2) ad libitum access to feed throughout (periods 1 and 2) (ADLIB, n = 15). On days 90 and 36 of periods 1 and 2, respectively, a GTT was performed. M. longissimus dorsi biopsies were harvested from all bulls on days 120 and 15 of periods 1 and 2, respectively, and RNA-Seq analysis was performed. RES displayed a lower growth rate during period 1 (RES: 0.6 kg/day, ADLIB: 1.9 kg/day; P alimentation (RES: 2.5 kg/day, ADLIB: 1.4 kg/day; P alimentation (P > 0.05). Genes differentially expressed in the insulin signaling pathway suggested a greater sensitivity to insulin in skeletal muscle, with pleiotropic effects of insulin signaling interrupted during dietary restriction. Collectively, these results indicate increased sensitivity to glucose clearance and skeletal muscle insulin signaling during dietary restriction; however, no overall role for insulin was apparent in expressing compensatory growth. PMID:26015430

  7. Randall-Sundrum with AdS(7)

    CERN Document Server

    Bao, R; Bao, Ruoyu; Lykken, Joseph

    2005-01-01

    In the same sense that AdS_5 warped geometries arise naturally from Type IIB string theory with stacks of D3 branes, AdS_7 warped geometries arise naturally from M theory with stacks of M5 branes. We compactify two spatial dimensions of AdS_7 to get AdS_5 x \\Sigma^2, where \\Sigma^2 is e.g. a torus T^2 or a sphere S^2. The metric for \\Sigma inherits the same warp factor as appears in the AdS_5. Bulk fields generically have both Kaluza-Klein and winding modes associated with \\Sigma. In the effective 5d action these will contribute exotic new excitations. We analyze the 5d spectrum in detail for the case of a bulk scalar or a graviton in AdS_5 x T^2, in a setup which mimics the first Randall-Sundrum model. The results display several novel features, some of which might be observed in experiments at the LHC. For example, we obtain TeV scale string winding states without lowering the string scale. This is due to the double warping which is a generic feature of winding states along compactified AdS directions. Expe...

  8. 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. PMID:27440831

  9. 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.

  10. Dirac operator on fuzzy AdS2

    International Nuclear Information System (INIS)

    In this article we construct the chirality and Dirac operators on fuzzy AdS2. We also derive the discrete spectrum of the Dirac operator which is important in the study of the spectral triple associated to AdS2. It is shown that the degeneracy of the spectrum present in the commutative AdS2 is lifted in the noncommutative case. The way we construct the chirality operator is suggestive of how to introduce the projector operators of the corresponding projective modules on this space. (author)

  11. Dirac Operator on Noncommutative AdS_2

    CERN Document Server

    Fakhri, H

    2003-01-01

    In this article we construct the chirality and Dirac operators on noncommutative AdS_2. We also derive the discrete spectrum of the Dirac operator which is important in the study of the spectral triple associated with AdS_2. It is shown that the degeneracy of the spectrum present in the commutative AdS_2 is lifted in the noncommutative case. The way we construct the chirality operator is suggestive of how to introduce the projector operators of the corresponding projective modules on this space.

  12. Dirac operator on fuzzy AdS2

    Science.gov (United States)

    Fakhri, Hossein; Imaanpur, Ali

    2003-03-01

    In this article we construct the chirality and Dirac operators on noncommutative AdS2. We also derive the discrete spectrum of the Dirac operator which is important in the study of the spectral triple associated to AdS2. It is shown that the degeneracy of the spectrum present in the commutative AdS2 is lifted in the noncommutative case. The way we construct the chirality operator is suggestive of how to introduce the projector operators of the corresponding projective modules on this space.

  13. Dirac Operator on Fuzzy AdS_2

    OpenAIRE

    H. Fakhri; Imaanpur, A.

    2003-01-01

    In this article we construct the chirality and Dirac operators on noncommutative AdS_2. We also derive the discrete spectrum of the Dirac operator which is important in the study of the spectral triple associated with AdS_2. It is shown that the degeneracy of the spectrum present in the commutative AdS_2 is lifted in the noncommutative case. The way we construct the chirality operator is suggestive of how to introduce the projector operators of the corresponding projective modules on this space.

  14. Radius-dependent gauge unification in AdS5

    OpenAIRE

    Choi, Kiwoon; Kim, Hyung Do; Kim, Ian-Woo

    2002-01-01

    We examine the relation of the 4-dimensional low energy coupling of bulk gauge boson in a slice of AdS5 to the 5-dimensional fundamental couplings as a function of the orbifold radius R. This allows us to address the gauge coupling unification in AdS5 by means of the radius running as well as the conventional momentum running. We then compute the radius dependence of 1-loop low energy couplings in generic AdS5 theory with 4-dimensional supersymmetry, and discuss the low energy predictions whe...

  15. Towards integrability for AdS3/CFT2

    CERN Document Server

    Sfondrini, Alessandro

    2014-01-01

    We review the recent progress towards applying worldsheet integrability techniques to the $AdS_3/CFT_2$ correspondence to find its all-loop S matrix and Bethe-Yang equations. We study in full detail the massive sector of $AdS_3\\times S^3\\times T^4$ superstrings supported by pure Ramond-Ramond (RR) fluxes. The extension of this machinery to accommodate massless modes, to the $AdS_3\\times S^3\\times S^3\\times S^1$ pure-RR background and to backgrounds supported by mixed background fluxes is also reviewed. While the results discussed here were found elsewhere, our exposition is original.

  16. The Role of Insulin, Insulin Growth Factor, and Insulin-Degrading Enzyme in Brain Aging and Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Claude Messier

    2005-01-01

    Full Text Available Most brain insulin comes from the pancreas and is taken up by the brain by what appears to be a receptor-based carrier. Type 2 diabetes animal models associated with insulin resistance show reduced insulin brain uptake and content. Recent data point to changes in the insulin receptor cascade in obesity-related insulin resistance, suggesting that brain insulin receptors also become less sensitive to insulin, which could reduce synaptic plasticity. Insulin transport to the brain is reduced in aging and in some animal models of type 2 diabetes; brain insulin resistance may be present as well. Studies examining the effect of the hyperinsulinic clamp or intranasal insulin on cognitive function have found a small but consistent improvement in memory and changes in brain neuroelectric parameters in evoked brain potentials consistent with improved attention or memory processing. These effects appear to be due to raised brain insulin levels. Peripheral levels of Insulin Growth Factor-I (IGF-I are associated with glucose regulation and influence glucose disposal. There is some indication that reduced sensitivity to insulin or IGF-I in the brain, as observed in aging, obesity, and diabetes, decreases the clearance of Aβ amyloid. Such a decrease involves the insulin receptor cascade and can also increase amyloid toxicity. Insulin and IGF-I may modulate brain levels of insulin degrading enzyme, which would also lead to an accumulation of Aβ amyloid.

  17. Optimizing the insulin therapy in patients with T2DM: More safety and efficiency%优化胰岛素治疗让2型糖尿病患者更安全获益

    Institute of Scientific and Technical Information of China (English)

    彭永德

    2012-01-01

    2009年美国糖尿病学会(ADA)和欧洲糖尿病研究学会(EASD)关于T2DM治疗的共识,及2007年中国糖尿病治疗指南均指出,生活方式干预和优化口服降糖药(OAD)控制血糖不佳时,应首选基础胰岛素治疗.但在临床实践中,预混胰岛素联合1~2种OADs治疗方案占目前胰岛素治疗的主导地位.研究显示,既往预混胰岛素控制不佳的患者转换成甘精胰岛素加OADs继续治疗时,血糖进一步改善.转换治疗后注射次数少,使用简便,同时体重无增加,因此患者满意度明显提高.%The consensus of 2009 ADA/EASD and 2007 Chinese Diabetes Society recommend that type 2 diabetes patients should initiate basal insulin therapy when life-style intervention and metformin combination therapy is failure. But in clinical practice, twice daily premix insulin combined with 1 ~ 2 OADs treatment is the leading regimen. Studies showed that type 2 diabetic patients previously uncontrolled by premix insulin, switching to glargine insulin plus OADs regimen can lead to further-controlled blood glucose, with less frequency of injection, being easier to use, less weight gain, and better treatment satisfaction of patients.

  18. Conical singularities in AdS space time

    International Nuclear Information System (INIS)

    Full text: In recent years, the study of conformal gauge theories from 10-D has been motivated by the AdSd+1/CFTd correspondence, first conjectured by J. Maldacena. The aim of this work is to consider the d = 4 case by analysing the configuration of the N coincident D3 branes. In this context, the work shows that there is a duality between type IIB string theory in AdS5 x S5 and N = 4 SU(N) Super Yang-Mills Theory in the IR. The AdS5/CFT4 correspondence brought also new approaches to the strong coupling problem in QCD. Nowadays, there is a whole line of works that focus on the low dimensional correspondence AdS4/CFT3, like the application to graphene and topological insulators, and the AdS3/CFT2 correspondence, related with the entanglement entropy. In this work, we consider the vortex configuration solution to the AdS4 and AdS3 space-time. The most important motivation is to discuss the boundary theory resulting from these solutions. We have examined a straightforward approach to a holographic computation of the graphene and entanglement entropy in the presence of the conical singularity. After this analysis, we consider the scalar field in the bulk in the presence of this metrics and work out the compactification modes. Taking the holographic point of view, we study and discuss the resulting Green function. (author)

  19. 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. PMID:24107496

  20. 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.

  1. Isolation and amino acid sequences of squirrel monkey (Saimiri sciurea) insulin and glucagon

    International Nuclear Information System (INIS)

    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

  2. Measurement of insulin in human sera using a new RIA kit. 1

    International Nuclear Information System (INIS)

    A sensitive and versatile radioimmunoassay (RIA) for insulin was established using human insulin standard, a specific guinea pig anti-insulin antiserum and rabbit anti-guinea pig serum. Radioiodination was performed according to a modified chloramine T method. Tracer preparations were used for as long as 6 weeks after iodination. The standard curve ranges from 0.044 to 1.2 nmol/l. The intra-assay coefficient of variation (CV) was 3-5% and the inter-assay CV was 6-9% in the optimal range between 0.4 and 0.9 nmol/l. The average recovery of human insulin added to plasma or serum samples was 100.2 ± 2.0% (n = 38) and 100.1 ± 1.9% (n = 42), respectively. In addition to human insulin, procine, canine, rabbit and bovine insulin can also be determined but not rat or mouse insulin. The cross-reactivity of the antiserum with porcine proinsulin was found to be 40 % on the molar basis. The range of mean fasting plasma insulin concentrations in healthy subjects and under various pathological conditions were estimated. (author)

  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. 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.

  5. ADS National Programmes: Netherlands

    International Nuclear Information System (INIS)

    The ADS related activities within the Netherlands are concentrated at NRG. From 2000 to 2006, NRG supported SCK•CEN in their development of MYRRHA. The support was mainly devoted to Computational Fluid Dynamics (CFD) simulations for the windowless target option. This collaboration was prolonged within the framework of the EU FP6 EUROTRANS project. Eventually this lead to a solution strategy for the hydraulic (without heat transfer) evaluation of a windowless target with one free surface using an Eulerian-Eulerian modeling approach. As a second free surface was added to the target design later, this approach would need to be revisited. The developed approach was applied to an assess the feasibility of a three feeder windowless target design. This preliminary assessment confirmed that there were no serious show stoppers for a three feeder design. Another study undertaken using related to the windowless target was a preliminary assessment of the risk of lead-bismuth splashing in case of a sudden heat deposition by the beam, e.g. at beam startup or beam interuptions. Within the framework of the EU FP7 CDT project, a window target is currently being assessed thermalhydraulicly in collaboration with SCK•CEN. Within the EU FP5 ASCHLIM project, the state of the art with regard to turbulence modelling for CFD approaches was determined. It was concluded that accurate simulation of heat transport in HLM was not feasible, especially in natural or mixed convection regimes. Within the EU FP7 THINS project this issue is currently being treated. NRG assists the commercial CFD code vendor CD adapco in implementing and testing a promising, academically tested, algebraic heat flux model

  6. Dressing phases of AdS3/CFT2

    CERN Document Server

    Borsato, Riccardo; Sfondrini, Alessandro; Stefanski, Bogdan; Torrielli, Alessandro

    2013-01-01

    We determine the all-loop dressing phases of the AdS3/CFT2 integrable system related to type IIB string theory on AdS3 x S3 x 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 appearing in AdS5/CFT4 and AdS4/CFT3. In the strongly-coupled regime, their leading order reduces to the universal Arutyunov-Frolov-Staudacher phase as expected. We also compute their sub-leading order and compare it with recent one-loop perturbative results, and co

  7. Dressing phases of AdS3/CFT2

    Science.gov (United States)

    Borsato, Riccardo; Ohlsson Sax, Olof; Sfondrini, Alessandro; Stefański, Bogdan, Jr.; Torrielli, Alessandro

    2013-09-01

    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 appearing in AdS5/CFT4 and AdS4/CFT3. In the strongly coupled regime, their leading order reduces to the universal Arutyunov-Frolov-Staudacher phase as expected. We also compute their subleading order and compare it with recent one-loop perturbative results and comment on their weak-coupling expansion.

  8. Differential interaction of Apolipoprotein-E isoforms with insulin receptors modulates brain insulin signaling in mutant human amyloid precursor protein transgenic mice.

    Science.gov (United States)

    Chan, Elizabeth S; Chen, Christopher; Cole, Gregory M; Wong, Boon-Seng

    2015-09-08

    It is unclear how human apolipoprotein E4 (ApoE4) increases the risk for Alzheimer's disease (AD). Although Aβ levels can lead to insulin signaling impairment, these experiments were done in the absence of human ApoE. To examine ApoE role, we crossed the human ApoE-targeted replacement mice with mutant human amyloid precursor protein (APP) mice. In 26 week old mice with lower Aβ levels, the expression and phosphorylation of insulin signaling proteins remained comparable among APP, ApoE3xAPP and ApoE4xAPP mouse brains. When the mice aged to 78 weeks, these proteins were markedly reduced in APP and ApoE4xAPP mouse brains. While Aβ can bind to insulin receptor, how ApoE isoforms modulate this interaction remains unknown. Here, we showed that ApoE3 had greater association with insulin receptor as compared to ApoE4, regardless of Aβ42 concentration. In contrast, ApoE4 bound more Aβ42 with increasing peptide levels. Using primary hippocampal neurons, we showed that ApoE3 and ApoE4 neurons are equally sensitive to physiological levels of insulin. However, in the presence of Aβ42, insulin failed to elicit a downstream response only in ApoE4 hippocampal neurons. Taken together, our data show that ApoE genotypes can modulate this Aβ-mediated insulin signaling impairment.

  9. Influence of insulin antibodies on pharmacokinetics and bioavailability of recombinant human and highly purified beef insulins in insulin dependent diabetics.

    OpenAIRE

    Gray, R S; Cowan, P.; Di Mario, U.; Elton, R A; Clarke, B F; Duncan, L J

    1985-01-01

    Sixteen insulin dependent diabetics of long standing, with undetectable fasting plasma C peptide concentrations, and eight non-diabetic controls were each infused intravenously with biosynthetic human and highly purified beef insulin (1 mU/kg/min) while euglycaemia was maintained by a Biostator. No difference was observed between the two insulins in respect of insulin pharmacokinetics or biological action. The diabetics showed appreciable insulin resistance, manifested by a 40% reduction in t...

  10. Chaos and hydrodynamics near AdS$_2$

    CERN Document Server

    Jensen, Kristan

    2016-01-01

    We revisit AdS$_2$ holography with the Sachdev-Ye-Kitaev models in mind. Our main result is to rewrite a generic theory of gravity near an AdS$_2$ throat as a novel hydrodynamics coupled to the correlation functions of a conformal quantum mechanics. This gives a prescription for the computation of $n$-point functions in the dual quantum mechanics. We thereby find that the dual is maximally chaotic.

  11. Continuation versus discontinuation of insulin secretagogues when initiating insulin in type 2 diabetes

    NARCIS (Netherlands)

    S.G. Swinnen; M.P. Dain; D. Mauricio; J.H. Devries; J.B. Hoekstra; F. Holleman

    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 di

  12. Alternative routes of insulin delivery

    Institute of Scientific and Technical Information of China (English)

    Ranjith K. Krishnankutty; Aju Mathew; Saikiran K. Sedimbi; Shrikumar Suryanarayan; Carani B. Sanjeevi

    2009-01-01

    Parenteral route of insulin administration has been the mode of treatment for all Type 1 diabetics and Type 2 diabetics with complications. Patient compliance has really been a major concern for this route of administration. Several alternative routes of administration are under consideration for effective glycemic control, including oral, inhaled, buccal, nasal, and patch routes. One of the approaches involving inhaled insulin has now reached the market. Several other candidates may reach the market in the near future, the promising one being oral insulin.

  13. New ways of insulin delivery.

    Science.gov (United States)

    Heinemann, L

    2010-02-01

    When Exubera (EXU), the first inhaled insulin formulation to make it through the clinical development process, was introduced to the market some years ago it was hoped that this would be the first in a series of novel insulin formulations applied by this route. In addition, it was hoped that inhaled insulin would pave the way for other alternative routes of insulin administration (ARIA), i.e. oral insulin, nasal insulin or transdermal insulin to mention only some of the different attempts that have been studied in the last 90 years. The failure of EXU, i.e. its withdrawal from the market due to insufficient market success, was followed by the cessation of nearly all other attempts to develop inhaled insulin formulations. Currently there is only one company (MannKind) which moves sturdily ahead with their Technosphere insulin. This company has submitted an NDA for their product recently and hopes to bring it to the market by the end of 2010 or early 2011. Even if the product is able to pass the approval hurdles in the USA and Europe, this does not guarantee that it will become a market success. Many diabetologists were sceptical about the need/advantages of inhaled insulin/EXU from the start and the introduction of this product has raised even more scepticism. Reports about 'side effects' (development of lung cancer in patients treated with EXU) of inhaled insulin are also not helpful, even if the causality of the appearance of cancer with this type of insulin therapy is not proven. One of the very negative consequences of stopping EXU are the huge financial losses to Pfizer. The managers in charge in other pharmaceutical companies and also most venture capitalists are reluctant to invest in ARIA nowadays. This in turn means that many of the small companies that try to develop new forms of insulin administration have issues when they try to find a big brother and/or sufficient financial support. Clearly the economic crisis has further aggravated this issue. One can

  14. Cutaneous allergy to human (recombinant DNA) insulin.

    Science.gov (United States)

    Grammer, L C; Metzger, B E; Patterson, R

    1984-03-16

    p6 report two cases of cutaneous allergy to human (recombinant DNA) insulin. Each patient had a history of systemic allergic reactions to porcine insulin and was at least as reactive to human as to porcine insulin by end-point cutaneous titration. Both patients' insulin allergy was managed with animal insulins and both have done well. Our experience with these two patients indicates that human insulin (rDNA) should not be expected to be efficacious in all patients with systemic allergy to insulin. PMID:6366262

  15. Inhaled insulin: overview of a novel route of insulin administration

    OpenAIRE

    Lucy D Mastrandrea

    2010-01-01

    Lucy D MastrandreaDepartment of Pediatrics, School of Medicine and Biochemical Sciences, University at Buffalo, Buffalo, NY, USAAbstract: Diabetes is a chronic disease characterized by inadequate insulin secretion with resulting hyperglycemia. Diabetes complications include both microvascular and macrovascular disease, both of which are affected by optimal diabetes control. Many individuals with diabetes rely on subcutaneous insulin administration by injection or continuous infusion to contro...

  16. Fatty acid-induced insulin resistance

    DEFF Research Database (Denmark)

    Le Marchand-Brustel, Y; Gual, P; Grémeaux, T;

    2003-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterized by a decrease in the insulin effect on glucose transport in muscle and adipose tissue. Tyrosine phosphorylation of IRS-1 (insulin receptor...... substrate 1) and its binding to PI 3-kinase (phosphoinositide 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Various studies have implicated lipids as a cause of insulin resistance in muscle. Elevated plasma fatty acid concentrations...... are associated with reduced insulin-stimulated glucose transport activity as a consequence of altered insulin signalling through PI 3-kinase. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine phosphorylation, PI 3-kinase activity and glucose...

  17. Discrimination in Online Ad Delivery

    OpenAIRE

    Sweeney, Latanya

    2013-01-01

    A Google search for a person's name, such as "Trevon Jones", may yield a personalized ad for public records about Trevon that may be neutral, such as "Looking for Trevon Jones?", or may be suggestive of an arrest record, such as "Trevon Jones, Arrested?". This writing investigates the delivery of these kinds of ads by Google AdSense using a sample of racially associated names and finds statistically significant discrimination in ad delivery based on searches of 2184 racially associated person...

  18. ADS National Programmes: Germany

    International Nuclear Information System (INIS)

    The German R&D programme for ADS development is related to the partitioning and transmutation of spent fuel. This programme is implemented mainly by the three national research centres belonging to the Helmholtz Association, i.e. Karlsruhe Institute of Technology (KIT), Forschungszentrum Jülich (FZJ) in cooperation with the Technical University of Aachen (RWTH Aachen) and the Helmholtz Zentrum Dresden Rossendorf (HZDR). The main purpose of this R&D programme is the prospect to manage the high level radioactive waste such as to reduce the burden on a final repository. P&T does not eliminate the need for a final repository whatever the strategy, but it allows the reduction of the radio-toxicity associated with radioactive waste, the increase of the repository capacity as a consequence of the reduction of masses to be stored and their associated residual heat load. Different fuel cycle scenarios to implement P&T can be envisaged. These scenarios have been evaluated to identify the impact of P&T on the characteristics, number and deployment pace of the installations of the fuel cycle (reprocessing, fuel fabrication, storage etc). Almost all activities conducted in the R&D programme are embedded in European and international projects and initiatives. In the following more details on the relevant components of the R&D programme are summarized

  19. Complexity Growth for AdS Black Holes

    CERN Document Server

    Cai, Rong-Gen; Wang, Shao-Jiang; Yang, Run-Qiu; Peng, Rong-Hui

    2016-01-01

    We further investigate the Complexity-Action (CA) duality conjecture for stationary anti de-Sitter (AdS) black holes and derive some exact results for the growth rate of action within Wheeler-DeWitt (WDW) patch at late time approximation, which is dual to the growth rate of quantum complexity of holographic state. Based on the results from the general $D$-dimensional Reissner-Nordstr\\"{o}m (RN)-AdS black hole, rotating/charged Ba\\~{n}ados-Teitelboim-Zanelli (BTZ) black hole, Kerr-AdS black hole and charged Gauss-Bonnet-AdS black hole, we present a new complexity bound but leave unchanged the conjecture that the stationary AdS black hole in Einstein gravity is the fastest computer in nature.

  20. Constructing the AdS dual of a Fermi liquid: AdS Black holes with Dirac hair

    CERN Document Server

    \\vCubrović, Mihailo; Schalm, Koenraad

    2010-01-01

    We provide new evidence that the holographic dual to a strongly coupled charged Fermi Liquid has a non-zero fermion density in the bulk. We show that the pole-strength of the stable quasiparticle characterizing the Fermi surface is encoded in the spatially averaged AdS probability density of a single normalizable fermion wavefunction in AdS. Recalling Migdal's theorem which relates the pole strength to the Fermi-Dirac characteristic discontinuity in the number density at $\\ome_F$, we conclude that the AdS dual of a Fermi liquid is described by occupied on-shell fermionic modes in AdS. Encoding the occupied levels in the total probability density of the fermion field directly, we show that an AdS Reissner-Nordstr\\"{o}m black hole in a theory with charged fermions has a critical temperature, at which the system undergoes a first-order transition to a black hole with a non-vanishing profile for the bulk fermion field. Thermodynamics and spectral analysis confirm that the solution with non-zero AdS fermion-profil...

  1. 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...

  2. Insulin Signaling and Glucose Uptake in the Soleus Muscle of 30-Month-Old Rats After Calorie Restriction With or Without Acute Exercise.

    Science.gov (United States)

    Wang, Haiyan; Sharma, Naveen; Arias, Edward B; Cartee, Gregory D

    2016-03-01

    Exercise and calorie restriction (CR) can each improve insulin sensitivity in older individuals, but benefits of combining these treatments on skeletal muscle insulin signaling and glucose uptake are poorly understood, especially in predominantly slow-twitch muscles (eg, soleus). Accordingly, our purpose was to determine independent and combined effects of prior acute exercise and CR (beginning at 14 weeks old) on insulin signaling and glucose uptake in insulin-stimulated soleus muscles of 30-month-old rats. CR alone (but not exercise alone) versus ad libitum sedentary controls induced greater insulin-stimulated glucose uptake. There was a main effect of diet (CR > ad libitum) for insulin-stimulated Akt(Ser473) and Akt(Thr308) phosphorylation. CR alone versus ad libitum sedentary increased Akt substrate of 160 kDa (AS160) Ser(588) phosphorylation and TBC1D1 Thr(596), but not AS160 Thr(642) phosphorylation or abundance of GLUT4, GLUT1, or hexokinase II proteins. Combined CR and exercise versus CR alone did not further increase insulin-stimulated glucose uptake although phosphorylation of Akt(Ser473), Akt(Thr308), TBC1D1(Thr596), and AMPK(Thr172) for the combined group exceeded values for CR and/or exercise alone. These results revealed that although the soleus was highly responsive to a CR-induced enhancement of insulin-stimulated glucose uptake, the exercise protocol did not elevate insulin-stimulated glucose uptake, either alone or when combined with CR.

  3. Alteration of mTOR signaling occurs early in the progression of Alzheimer disease (AD): analysis of brain from subjects with pre-clinical AD, amnestic mild cognitive impairment and late-stage AD.

    Science.gov (United States)

    Tramutola, Antonella; Triplett, Judy C; Di Domenico, Fabio; Niedowicz, Dana M; Murphy, Michael P; Coccia, Raffaella; Perluigi, Marzia; Butterfield, D Allan

    2015-06-01

    The clinical symptoms of Alzheimer disease (AD) include a gradual memory loss and subsequent dementia, and neuropathological deposition of senile plaques and neurofibrillary tangles. At the molecular level, AD subjects present overt amyloid β (Aβ) production and tau hyperphosphorylation. Aβ species have been proposed to overactivate the phosphoinositide3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) axis, which plays a central role in proteostasis. The current study investigated the status of the PI3K/Akt/mTOR pathway in post-mortem tissue from the inferior parietal lobule (IPL) at three different stages of AD: late AD, amnestic mild cognitive impairment (MCI) and pre-clinical AD (PCAD). Our findings suggest that the alteration of mTOR signaling and autophagy occurs at early stages of AD. We found a significant increase in Aβ (1-42) levels, associated with reduction in autophagy (Beclin-1 and LC-3) observed in PCAD, MCI, and AD subjects. Related to the autophagy impairment, we found a hyperactivation of PI3K/Akt/mTOR pathway in IPL of MCI and AD subjects, but not in PCAD, along with a significant decrease in phosphatase and tensin homolog. An increase in two mTOR downstream targets, p70S6K and 4EBP1, occurred in AD and MCI subjects. Both AD and MCI subjects showed increased, insulin receptor substrate 1, a candidate biomarker of brain insulin resistance, and GSK-3β, a kinase targeting tau phosphorylation. Nevertheless, tau phosphorylation was increased in the clinical groups. The results hint at a link between Aβ and the PI3K/Akt/mTOR axis and provide further insights into the relationship between AD pathology and insulin resistance. In addition, we speculate that the alteration of mTOR signaling in the IPL of AD and MCI subjects, but not in PCAD, is due to the lack of substantial increase in oxidative stress. The figure represents the three different stages of Alzheimer Disease: Preclinical Alzheimer Disease (PCAD), Mild cognitive impairment (MCI

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

    OpenAIRE

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

    2010-01-01

    Objective: To describe insulin persistence among patients with type 2 diabetes initiating insulin therapy with basal insulin or insulin mixtures and determine factors associated with nonpersistence. Research design and methods: The Thomson Reuters MarketScan® databases were used to retrospectively analyze insulin-naïve patients with type 2 diabetes by initiating insulin therapy. Insulin use was described using a variety of measures. The persistence to insulin was described using both a gap-ba...

  5. Diabetes due to secretion of a structurally abnormal insulin (insulin Wakayama). Clinical and functional characteristics of [LeuA3] insulin.

    OpenAIRE

    Nanjo, K; Sanke, T; Miyano, M; Okai, K.; Sowa, R; Kondo, M.; Nishimura, S; Iwo, K; Miyamura, K; Given, B D

    1986-01-01

    We have identified a non-insulin-dependent diabetic patient with fasting hyperinsulinemia (90 microU/ml), an elevated insulin:C-peptide molar ratio (1.68; normal, 0.05-0.20), normal insulin counterregulatory hormone levels, and an adequate response to exogenously administered insulin. Insulin-binding antibodies were absent from serum, erythrocyte insulin receptor binding was normal, and greater than 90% of circulating immunoreactive insulin coeluted with 125I-labeled insulin on gel filtration...

  6. Glucose Intolerance, Insulin Resistance and Alzheimer’s Disease Pathology in the Baltimore Longitudinal Study of Aging

    Science.gov (United States)

    Thambisetty, M.; Metter, E.J.; Yang, A.; Dolan, H.; Marano, C.; Zonderman, A.B.; Troncoso, J.; Zhou, Y; Wong, D.F.; Ferrucci, L.; Egan, J.M.; Resnick, S.M.; OBrien, R.

    2014-01-01

    Objective To investigate associations between serial measures of glucose intolerance and insulin resistance with in vivo amyloid burden, measured with 11C-PiB, and Alzheimer’s disease (AD) pathology at autopsy in a prospective cohort from the Baltimore Longitudinal Study of Aging. Methods Brain CERAD and Braak scores were correlated with measures of hyperglycemia, hyperinsulinemia, glucose intolerance and insulin resistance in 197 participants who had come to autopsy and had two or more oral glucose tolerance tests (OGTT) during life. Glucose intolerance was measured by fasting and 120-minute post-load glucose values. Insulin resistance was measured by fasting and 120-minute post-load serum insulin values and the ratio of serum glucose to insulin at baseline and following a glucose load. In addition, the same measures of glucose intolerance and insulin resistance were correlated with brain 11C-PiB retention in 53 living subjects. Results There were no significant correlations between measures of brain AD pathology or 11C-PiB derived amyloid load and either glucose intolerance or insulin resistance in subjects who had a mean of 6.4 ± 3.2 (S.D.) OGTT evaluations over 22.1 ± 8.0 (S.D.) years of follow-up. Thirty subjects with frank diabetes on medication also had AD pathology scores that were similar to the cohort as a whole. Conclusions In this prospective cohort with multiple assessments of glucose intolerance and insulin resistance, measures of glucose and insulin homeostasis were not associated with AD pathology. PMID:23897112

  7. 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.

  8. Different views of AEGIS / AD-6 Experiment (AD facility) AD-6

    CERN Multimedia

    Maximilien Brice

    2012-01-01

    Different views of AEGIS / AD-6 Experiment (AD facility) in July of 2012. The visible parts are the positron accumulator (blue structures on top of of the antiproton extraction line) and the 5T magnet which traps the antiprotons.

  9. Global geometric properties of AdS space and the AdS/CFT correspondence

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The Poisson kernels and relations between them for a massive scalar field in a unit ball Bn with Hua's metric and conformal flat metric are obtained by describing the Bn as a submanifold of an (n+1)-dimensional embedding space. Global geometric properties of the AdS space are discussed. We show that the(n+1)-dimensional AdS space AdSn+1 is isomorphic to RP1×Bn and boundary of the AdS is isomorphic to RP1×Sn-1. Bulk-boundary propagator and the AdS/CFT like correspondence are demonstrated based on these global geometric properties of the RP1×Bn.

  10. AdS-Carroll Branes

    CERN Document Server

    Clark, T E

    2016-01-01

    Coset methods are used to determine the action of a co-dimension one brane (domain wall) embedded in (d+1)-dimensional AdS space in the Carroll limit in which the speed of light goes to zero. The action is invariant under the non-linearly realized symmetries of the AdS-Carroll spacetime. The Nambu-Goldstone field exhibits a static spatial distribution for the brane with a time varying momentum density related to the brane's spatial shape as well as the AdS-C geometry. The AdS-C vector field dual theory is obtained.

  11. Improved postprandial glycaemic control with insulin Aspart in type 2 diabetic patients treated with insulin

    DEFF Research Database (Denmark)

    Rosenfalck, A M; Thorsby, P; Kjems, L;

    2000-01-01

    The effect on postprandial blood glucose control of an immediately pre-meal injection of the rapid acting insulin analogue Aspart (IAsp) was compared with that of human insulin Actrapid injected immediately or 30 minutes before a test meal in insulin-treated type 2 diabetic patients with residual...... that the improved glucose control previously demonstrated with insulin Aspart compared to human insulin in healthy subjects and type 1 diabetic patients also applies to insulin-treated type 2 diabetic patients....

  12. Exercise modulates postreceptor insulin signaling and glucose transport in muscle-specific insulin receptor knockout mice

    OpenAIRE

    Wojtaszewski, Jørgen F. P.; Higaki, Yasuki; Hirshman, Michael F.; Michael, M. Dodson; Dufresne, Scott D.; Kahn, C. Ronald; Goodyear, Laurie J.

    1999-01-01

    Physical exercise promotes glucose uptake into skeletal muscle and makes the working muscles more sensitive to insulin. To understand the role of insulin receptor (IR) signaling in these responses, we studied the effects of exercise and insulin on skeletal muscle glucose metabolism and insulin signaling in mice lacking insulin receptors specifically in muscle. Muscle-specific insulin receptor knockout (MIRKO) mice had normal resting 2-deoxy-glucose (2DG) uptake in soleus muscles but had no si...

  13. Multicenter clinical study on the efficacy and safety of inhalable insulin aerosol in the treatment of type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    LIAO Zhi-hong; WENG Jian-ping; CHEN Ying-li; LI Fang-ping; YAN Xiang; LU Hai; YAN Li; ZHOU Zhi-guang; ZHU Da-long; JI Li-nong

    2008-01-01

    Background A new inhalable insulin aerosoI(Inh-Ins)was developed in China.The aim of this multicenter clinical study was to evaluate the efficacy and safety of this new Inh-Ins as a treatment of type 2 diabetes.Regular porcine insulin(RI)was used as a control.Methods This study is a prospective,randomized,open-label,parallel-group multicenter clinical trial in which 253 qualified patients with type 2 diabetes received the insulin Glargine daily at bedtime plus either a pre-meal Inh-Ins or a pre-meal subcutaneous RI for 12 weeks.HbA1c,fasting plasma glucose(FPG),the 1-hour-postprandial blood glucose(1hPBG)and the 2-hour-postprandial blood glucose(2hPBG)were measured.Events were monitored for adverse effects.Results After 12 weeks,the HbA1c decreased significantly from baseline in both treatment groups,with no significant difference between the two regimens.In the Inh-Ins group,FPG,both 1hPBG and 2hPBG significantly declined from baseline after the 8th-and 12th-weeks of treatment.The reduced values of FPG or 1hPBG between the two groups showed a more significant hypoglycemic effect with the Inh-Ins than the RI.After 12 weeks,the pulmonary carbon monoxide diffusing capacity(DLco)was significantly lower in Inh-Ins group than in the RI.The main side effects of Inh-Ins were coughing,excessive sputum,and hypoglycemia.Conclusions Inh-Ins was effective in decreasing HbA1c like the RI.It was better in lowering the FPG and the 1hPBG than the RI.Its main side effects were coughing,excessive sputum,and hypoglycemia.Also,Inh-Ins slightly impaired DLco.

  14. Peripheral insulin sensitivity as modified by diet and exercise training.

    Science.gov (United States)

    Grimditch, G K; Barnard, R J; Hendricks, L; Weitzman, D

    1988-07-01

    To determine which component of a high-fat sucrose diet (HFS) caused insulin resistance and whether exercise training or fiber could prevent it, six dietary treatments were tested in rats: low-fat complex carbohydrate (LFCC); high-fat complex carbohydrate (HFCC); low-fat sucrose (LFS); high-fat sucrose (HFS); HFS plus fiber (HFS + F); and HFS plus exercise training (HFS + EX). After 10 wk rats were subjected to an intravenous glucose-tolerance test. The HFS and HFS + F groups developed glucose intolerance, as indicated by significantly greater areas under their glucose curves compared with the LFCC group's areas. The LFS, HFS, HFS + F, and HFS + EX groups developed insulin resistance, as indicated by significantly greater areas under their insulin curves compared with the LFCC and HFCC groups' areas. Either the presence of sucrose or the absence of complex carbohydrates, not high fat, was responsible for the insulin resistance and it was not improved by adding fiber to the diet or by exercise training.

  15. 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.

  16. 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.

  17. Defective insulin response of cyclic adenosine monophosphate-dependent protein kinase in insulin-resistant humans.

    OpenAIRE

    Kida, Y; Nyomba, B L; Bogardus, C; Mott, D M

    1991-01-01

    Insulin-stimulated glycogen synthase activity in human muscle correlates with insulin-mediated glucose disposal and is reduced in insulin-resistant subjects. Inhibition of the cyclic AMP-dependent protein kinase (A-kinase) is considered as a possible mechanism of insulin action for glycogen synthase activation. In this study, we investigated the time course of insulin action on human muscle A-kinase activity during a 2-h insulin infusion in 13 insulin-sensitive (group S) and 7 insulin-resista...

  18. Human insulin and porcine insulin in the treatment of diabetic children: comparison of metabolic control and insulin antibody production.

    OpenAIRE

    Mann, N P; Johnston, D I; Reeves, W G; Murphy, M A

    1983-01-01

    Semisynthetic human insulin and highly purified porcine insulin were compared in a double blind crossover study in 21 diabetic children. Glycosylated haemoglobin values at the end of four month treatment periods were higher after treatment with human insulin than after treatment with porcine insulin (mean 15.7% (SD 2.3%) v 14.2% (2.3%); p less than 0.01). Higher fasting blood glucose concentrations occurred during treatment with human insulin than with porcine insulin (mean 12.0 (SD 2.1) v 11...

  19. Intranasal insulin therapy: the clinical realities

    DEFF Research Database (Denmark)

    Hilsted, J; Madsbad, Sten; Hvidberg, A;

    1995-01-01

    To evaluate metabolic control and safety parameters (hypoglycaemia frequency and nasal mucosa physiology), 31 insulin-dependent diabetic patients were treated with intranasal insulin at mealtimes for 1 month and with subcutaneous fast-acting insulin at meals for another month in an open, crossover...... randomized trial. During both treatment periods the patients were treated with intermediate-acting insulin at bedtime. Six of the patients were withdrawn from the study during intranasal insulin therapy due to metabolic dysregulation. Serum insulin concentrations increased more rapidly and decreased more...... quickly during intranasal as compared with subcutaneous insulin administration. Metabolic control deteriorated, as assessed by haemoglobin A1c concentrations, slightly but significantly after intranasal as compared with subcutaneous insulin therapy. The bioavailability of intranasally applied insulin...

  20. Bioavailability and variability of biphasic insulin mixtures

    DEFF Research Database (Denmark)

    Søeborg, Tue; Rasmussen, Christian Hove; Mosekilde, Erik;

    2012-01-01

    Absorption of subcutaneously administered insulin is associated with considerable variability. Some of this variability was quantitatively explained for both soluble insulin and insulin suspensions in a recent contribution to this journal (Søeborg et al., 2009). In the present article......, the absorption kinetics for mixtures of insulins is described. This requires that the bioavailability of the different insulins is considered. A short review of insulin bioavailability and a description of the subcutaneous depot thus precede the presentation of possible mechanisms associated with subcutaneous...... insulin degradation. Soluble insulins are assumed to be degraded enzymatically in the subcutaneous tissue. Suspended insulin crystals form condensed heaps that are assumed to be degraded from their surface by invading macrophages. It is demonstrated how the shape of the heaps affects the absorption...

  1. Protein engineering of insulin: Two novel fast-acting insulins [B16Ala]insulin and [B26Ala]insulin

    Institute of Scientific and Technical Information of China (English)

    ZHANG; Zhou; (张舟); TANG; Yuehua; (唐月华); YAO; Shiyin; (姚矢音); ZHU; Shangquan; (朱尚权); FENG; Youmin; (冯佑民)

    2003-01-01

    Blood glucose lowering assay proved that [B16Ala]insulin and [B26Ala]insulin exhibit potency of acute blood glucose lowering in normal pigs, which demonstrates that they are fast- acting insulin. Single-chain precursor of [B16Ala]insulin and [B26Ala]insulin is [B16Ala]PIP and [B26Ala]PIP, respectively, which are suitable for gene expression. Secretory expression level of the precursors in methylotrophic yeast Pichia pastoris was quite high, 650 mg/L and 130 mg/L, respectively. In vivo biological assay showed that the two fast-acting insulins have full or nearly full biological activity. So both [B16Ala]insulin and [B26Ala]insulin can be well developed as fast-acting insulin for clinic use.

  2. Human insulin: DNA technology's first drug.

    Science.gov (United States)

    The, M J

    1989-11-01

    The history, biologic activity, and immunogenicity of human insulin are described. Recombinant human insulin first entered clinical trials in humans in 1980. At that time, the A and B chains of the insulin molecule were produced separately and then combined by chemical techniques. Since 1986, a different recombinant process has been used. The human genetic coding for proinsulin is inserted into Escherichia coli cells, which are then grown by fermentation to produce proinsulin. The connecting peptide is cleaved enzymatically from proinsulin to produce human insulin. Studies indicate that there are no important differences between pork insulin and human insulin in terms of therapeutic efficacy and disposition after intravenous administration. Recombinant human insulin has a faster onset of action and lower immunogenicity than pork or beef insulin. Diabetic patients may have an improvement in glucose concentrations when their therapy is switched from animal-source insulin to human insulin. Such a change usually requires a dosage adjustment, which must be determined by a physician. Pharmacists are responsible for educating patients concerning all insulin products and for preventing patients from interchanging insulin products. The availability of human insulin as the first pharmaceutical product manufactured through recombinant DNA technology, however, has had little effect on the pharmacist's role in the care of such patients. The production of human insulin through recombinant DNA technology represents an important advance in the treatment of patients with diabetes. PMID:2690608

  3. Treatment of insulin resistance in uremia.

    Science.gov (United States)

    Stefanović, V; Nesić, V; Stojimirović, B

    2003-02-01

    Insulin resistance is a characteristic feature of uremia. As long as the hyperinsulinemia adequate to overcome the insulin resistance, glucose tolerance remains normal. In patients destined to develop type 2 diabetes, the beta cell compensatory response declines, and relative, or absolute, insulin deficiency develops. At this point glucose intolerance and eventually frank type 2 diabetes occur. Insulin resistance and concomitant hyperinsulinemia are present irrespective of the type of renal disease. Several studies have confirmed that hemodialysis (HD) treatment significantly improves insulin resistance. Both CAPD and CCPD are shown to improve insulin resistance in uremic patients. Comparing the effect of PD and HD treatment, it was found that the CCPD group has significantly higher insulin sensitivity than the HD group with the CAPD group similar to HD. Treatment of calcium and phosphate disturbances, including vitamin D therapy, significantly reduces insulin resistance in uremia. Treatment with recombinant human erythropoietin (EPO) is an efficient way to increase hematocrit, to reverse cardiovascular problems and to improve insulin sensitivity. Angiotensin-converting enzyme inhibitors have been shown to improve insulin resistance, hyperinsulinemia and glucose intolerance in uremic patients. Thiazolidinediones (TZDs), the new insulin-sensitizing drugs, provide the proof that pharmacologic treatment of insulin resistance can be of enormous clinical benefit. The great potential of insulin resistance therapy illuminated by the TZDs will continue to catalyze research in this area directed toward the discovery of new insulin-sensitizing agents that work through other mechanisms. PMID:12653342

  4. Entanglement entropy for free scalar fields in AdS

    CERN Document Server

    Sugishita, Sotaro

    2016-01-01

    We compute entanglement entropy for free massive scalar fields in anti-de Sitter (AdS) space. The entangling surface is a minimal surface whose boundary is a sphere at the boundary of AdS. The entropy can be evaluated from the thermal free energy of the fields on a topological black hole by using the replica method. In odd-dimensional AdS, exact expressions of the Renyi entropy S_n are obtained for arbitrary n. We also evaluate 1-loop corrections coming from the scalar fields to holographic entanglement entropy. Applying the results, we compute the leading difference of entanglement entropy between two holographic CFTs related by a renormalization group flow triggered by a double trace deformation. The difference is proportional to the shift of a central charge under the flow.

  5. Detailed ultraviolet asymptotics for AdS scalar field perturbations

    CERN Document Server

    Evnin, Oleg

    2016-01-01

    We present a range of methods suitable for accurate evaluation of the leading asymptotics for integrals of products of Jacobi polynomials in limits when the degrees of some or all polynomials inside the integral become large. The structures in question have recently emerged in the context of effective descriptions of small amplitude perturbations in anti-de Sitter (AdS) spacetime. The limit of high degree polynomials corresponds in this situation to effective interactions involving extreme short-wavelength modes, whose dynamics is crucial for the turbulent instabilities that determine the ultimate fate of small AdS perturbations. We explicitly apply the relevant asymptotic techniques to the case of a self-interacting probe scalar field in AdS and extract a detailed form of the leading large degree behavior, including closed form analytic expressions for the numerical coefficients appearing in the asymptotics.

  6. Asymptotically AdS spacetimes with a timelike Kasner singularity

    Science.gov (United States)

    Ren, Jie

    2016-07-01

    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.

  7. Microstates at the boundary of AdS

    CERN Document Server

    Mathur, Samir D

    2011-01-01

    The bound states of the D1D5 brane system have a known gravitational description: flat asymptotics, an anti-de Sitter region, and a 'cap' ending the AdS region. We construct perturbations that correspond to the action of chiral algebra generators on Ramond ground states of D1D5 branes. Abstract arguments in the literature suggest that the perturbation should be pure gauge in the AdS region; our perturbation indeed has this structure, with the nontrivial deformation of the geometry occurring at the 'neck' between the AdS region and asymptotic infinity. This 'non-gauge' deformation is needed to provide the nonzero energy and momentum carried by the perturbation. We also suggest implications this structure may have for the majority of microstates which live at the cap.

  8. Null warped AdS in higher spin gravity

    CERN Document Server

    Breunhoelder, Veronika; Grumiller, Daniel; Prohazka, Stefan

    2015-01-01

    We equip three-dimensional spin-3 gravity in the principal embedding with a new set of boundary conditions that we call "asymptotically null warped AdS". We find a chiral copy of the Polyakov-Bershadsky algebra as asymptotic symmetry algebra, reminiscent of the situation in topologically massive gravity with strict null warped AdS boundary conditions. We prove the invertibility of the map between zuvielbein and metric variables and construct a global gauge transformation to half of AdS spin-3 gravity in the diagonal embedding. This explains why the theory is chiral and why the Polyakov-Bershadsky algebra arises. We then introduce chemical potentials, derive the entropy, free energy, and the holographic response functions, and conclude with a discussion.

  9. New massive gravity and AdS(4) counterterms.

    Science.gov (United States)

    Jatkar, Dileep P; Sinha, Aninda

    2011-04-29

    We show that the recently proposed Dirac-Born-Infeld extension of new massive gravity emerges naturally as a counterterm in four-dimensional anti-de Sitter space (AdS(4)). The resulting on-shell Euclidean action is independent of the cutoff at zero temperature. We also find that the same choice of counterterm gives the usual area law for the AdS(4) Schwarzschild black hole entropy in a cutoff-independent manner. The parameter values of the resulting counterterm action correspond to a c=0 theory in the context of the duality between AdS(3) gravity and two-dimensional conformal field theory. We rewrite this theory in terms of the gauge field that is used to recast 3D gravity as a Chern-Simons theory. PMID:21635026

  10. Towards integrability for AdS3/CFT2

    International Nuclear Information System (INIS)

    We review the recent progress towards applying worldsheet integrability techniques to the AdS3/CFT2 correspondence to find its all-loop S matrix and Bethe–Yang equations. We study in full detail the massive sector of AdS3×S3×T4 superstrings supported by pure Ramond–Ramond (RR) fluxes. The extension of this machinery to accommodate massless modes, to the AdS3×S3×S3×S1 pure-RR background and to backgrounds supported by mixed background fluxes is also reviewed. While the results discussed here were found elsewhere, our presentation sometimes deviates from the one found in the original literature in an effort to be pedagogical and self-contained. (topical review)

  11. Identification of phageotope of rat liver insulin receptor

    International Nuclear Information System (INIS)

    Introduction: Insulin receptor; a kind of growth factors overexpressed on hepatocellular carcinoma (HCC) cells, mediated HCC cells proliferation. The present study is to looking for' the inhibitors of the insulin receptor to suppress minor growth or to getting potent ligands targeted to HCC via affinity selection of a cyclic phage random peptide library (C7C NEB) displayed on bacteriophage M13. Methods: 17.7u of rat insulin receptor(SIGMA) immobilized on a 60 x 15mm polystyrene plate(Becton Dickinson) by incubating overnight at 4 degree C. After blocking and washing of the receptor coated plates 2 x 1011 virons of C7C phage library were added to the plate and the dish was incubated 40min at room temperature. Washed the dish with TBST and collected the phages attacked to the insulin receptors immobilized on the dish with 0.2M glycine-HCl. Positive phage clones were amplified with 200 μl ER2738 in 20ml LB-Medium in a 250 ml Erlenmeyer flask. The IC 50 ratio of the selected clones compared to the phage library mixture binding to insulin receptors was determined with a set of phages in ELISA assay. DNA sequencing of 10 positive clones were performed after three rounds of biopanning and the amino acid sequences of the fused peptides were deduced. Results: The IC50 of a positive phage clone after three rounds of biopanning was 1.23 x 108 virions, and that of the phage library mixture was 2.16 x 1010 (The ratio of the IC50 is 1: 172.4). Six peptides have a common sequence XXSXGYX via DNA sequencing. Another four peptide sequences are not similar to the motif. Corresponding peptides TK1 was synthesized according to the common sequence and the selected peptide. The TK1 partly inhibited the insulin binding to insulin receptor in three times of detection. Conclusion: A synthesized peptide TK1 with a common sequence XXSXGYX, shows special affinity to insulin receptor, was obtained via affinity selected from the C7C peptide library. It could be a potent suppressing agent and

  12. Logarithmic conformal field theories and AdS correspondence

    OpenAIRE

    Khorrami, A. M. Ghezelbash. M.; Aghamohammadi, A

    1998-01-01

    We generalize the Maldacena correspondence to the logarithmic conformal field theories. We study the correspondence between field theories in (d+1)-dimensional AdS space and the d-dimensional logarithmic conformal field theories in the boundary of $AdS_{d+1}$. Using this correspondence, we get the n-point functions of the corresponding logarithmic conformal field theory in d-dimensions.

  13. Metabolic flexibility and insulin resistance.

    Science.gov (United States)

    Galgani, Jose E; Moro, Cedric; Ravussin, Eric

    2008-11-01

    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" is mostly the consequence of impaired cellular glucose uptake. Indeed, after controlling for insulin-stimulated glucose disposal rate (amount of glucose available for oxidation), metabolic flexibility is not altered in obesity regardless of the presence of type 2 diabetes. To understand how intramyocellular lipids accumulate and cause insulin resistance, the assessment of metabolic flexibility to high-fat diets is more relevant than metabolic flexibility during a hyperinsulinemic clamp. An impaired capacity to upregulate muscle lipid oxidation in the face of high lipid supply may lead to increased muscle fat accumulation and insulin resistance. Surprisingly, very few studies have investigated the response to high-fat diets. In this review, we discuss the role of glucose disposal rate, adipose tissue lipid storage, and mitochondrial function on metabolic flexibility. Additionally, we emphasize the bias of using the change in respiratory quotient to calculate metabolic flexibility and propose novel approaches to assess metabolic flexibility. On the basis of current evidence, one cannot conclude that impaired metabolic flexibility is responsible for the accumulation of intramyocellular lipid and insulin resistance. We propose to study metabolic flexibility in response to high-fat diets in individuals having contrasting degree of insulin sensitivity and/or mitochondrial characteristics. PMID:18765680

  14. Phases of Global AdS Black Holes

    CERN Document Server

    Basu, Pallab; Subramanian, P N Bala

    2016-01-01

    We study the phases of gravity coupled to a charged scalar and gauge field in an asymptotically Anti-de Sitter spacetime ($AdS_4$) in the grand canonical ensemble. For the conformally coupled scalar, an intricate phase diagram is charted out between the four relevant solutions: global AdS, boson star, Reissner-Nordstrom black hole and the hairy black hole. The nature of the phase diagram undergoes qualitative changes as the charge of the scalar is changed, which we discuss. We also discuss the new features that arise in the extremal limit.

  15. Phases of global AdS black holes

    Science.gov (United States)

    Basu, Pallab; Krishnan, Chethan; Subramanian, P. N. Bala

    2016-06-01

    We study the phases of gravity coupled to a charged scalar and gauge field in an asymptotically Anti-de Sitter spacetime ( AdS 4) in the grand canonical ensemble. For the conformally coupled scalar, an intricate phase diagram is charted out between the four relevant solutions: global AdS, boson star, Reissner-Nordstrom black hole and the hairy black hole. The nature of the phase diagram undergoes qualitative changes as the charge of the scalar is changed, which we discuss. We also discuss the new features that arise in the extremal limit.

  16. Mixed-symmetry fields in AdS(5), conformal fields, and AdS/CFT

    CERN Document Server

    Metsaev, R R

    2014-01-01

    Mixed-symmetry arbitrary spin massive, massless, and self-dual massive fields in AdS(5) are studied. Light-cone gauge actions for such fields leading to decoupled equations of motion are constructed. Light-cone gauge formulation of mixed-symmetry anomalous conformal currents and shadows in 4d flat space is also developed. AdS/CFT correspondence for normalizable and non-normalizable modes of mixed-symmetry AdS fields and the respective boundary mixed-symmetry anomalous conformal currents and shadows is studied. We demonstrate that the light-cone gauge action for massive mixed-symmetry AdS field evaluated on solution of the Dirichlet problem amounts to the light-cone gauge 2-point vertex of mixed-symmetry anomalous shadow. Also we show that UV divergence of the action for mixed-symmetry massive AdS field with some particular value of mass parameter evaluated on the Dirichlet problem amounts to the action of long mixed-symmetry conformal field, while UV divergence of the action for mixed-symmetry massless AdS fi...

  17. Patient self-monitoring of blood glucose and refinements of conventional insulin treatment.

    Science.gov (United States)

    Tattersall, R; Gale, E

    1981-01-01

    The compelling evidence that blood glucose control will slow or prevent microvascular complications has stimulated research to find better ways of managing insulin-dependent diabetes. The excellent results obtained with "open loop" insulin infusion systems suggest that the relative failure of conventional treatment is the result of (1) a lack of appropriate feedback to the patient and (2) the use of insulin regimens which do not mimic physiologic insulinemia, particularly in the basal state. Doctors regard blood glucose measurements as an essential part of diabetic management and extension of this technology to patients has added a new dimension, particularly in the assessment of control. Nevertheless, home blood-glucose monitoring will not necessarily improve diabetic control; the best results have been obtained when it has been offered as part of a package deal which includes more investment of time and interest by patients and doctor together with joint discussions of problems and changes in treatment. The biggest problem with conventional twice daily insulin regimens is to sustain constant basal insulin levels during the night. Attempts to obtain fasting normoglycemia with an injection before supper often result in nocturnal hyperinsulinemia and hypoglycemia. This can usually be resolved by changing to a three times daily regimen with an extra injection of NPH insulin at bedtime. Three times daily insulin injections with feedback from home blood-glucose monitoring give as good blood glucose control as infusion systems and are cheaper and more acceptable to patients. PMID:7006390

  18. Surface engineering of silica nanoparticles for oral insulin delivery: characterization and cell toxicity studies.

    Science.gov (United States)

    Andreani, Tatiana; Kiill, Charlene P; de Souza, Ana Luiza R; Fangueiro, Joana F; Fernandes, Lisete; Doktorovová, Slavomira; Santos, Dario L; Garcia, Maria L; Gremião, Maria Palmira D; Souto, Eliana B; Silva, Amélia M

    2014-11-01

    The present work aimed at studying the interaction between insulin and SiNP surfaced with mucoadhesive polymers (chitosan, sodium alginate or polyethylene glycol) and the evaluation of their biocompatibility with HepG2 and Caco-2 cell lines, which mimic in vivo the target of insulin-loaded nanoparticles upon oral administration. Thus, a systematic physicochemical study of the surface-modified insulin-silica nanoparticles (Ins-SiNP) using mucoadhesive polymers has been described. The surfacing of nanoparticle involved the coating of silica nanoparticles (SiNP) with different mucoadhesive polymers, to achieve high contact between the systems and the gut mucosa to enhance the oral insulin bioavailability. SiNP were prepared by a modified Stöber method at room temperature via hydrolysis and condensation of tetraethyl orthosilicate (TEOS). Interaction between insulin and nanoparticles was assessed by differential scanning calorimetry (DSC), X-ray and Fourier-transform infrared (FTIR) studies. The high efficiency of nanoparticles' coating resulted in more stable system. FTIR spectra of insulin-loaded nanoparticles showed amide absorption bands which are characteristic of α-helix content. In general, all developed nanoparticles demonstrated high biocompatible, at the tested concentrations (50-500 μg/mL), revealing no or low toxicity in the two human cancer cell lines (HepG2 and Caco-2). In conclusion, the developed insulin-loaded SiNP surfaced with mucoadhesive polymers demonstrated its added value for oral administration of proteins. PMID:25466464

  19. Compact AdS space, Brane geometry and the AdS/CFT correspondence

    CERN Document Server

    Boschi-Filho, H; Boschi-Filho, Henrique; Braga, Nelson R. F.

    2002-01-01

    The AdS/CFT correspondence can be realized in spaces that are globally different but share the same asymptotic behavior. Two known cases are: a compact AdS space and the space generated by a large number of coincident branes. We discuss the physical consistency, in the sense of the Cauchy problem, of these two formulations. We show that the role of the boundary in the compact AdS space is equivalent to that of the flat asymptotic region in the brane space. We also show, by introducing a second coordinate chart for the pure AdS space, that a point at its spatial infinity corresponds to a horizon in the brane system.

  20. Insulin resistance: β-arrestin development

    Institute of Scientific and Technical Information of China (English)

    Joseph T Rodgers; Pere Puigserver

    2009-01-01

    @@ Insulin resistance is simply the in-ability of insulin to elicit a physiologic response. While insulin resistance is most commonly associated with the pathogenesis of metabolic disorders such as type II diabetes and obesity, it is also a predisposing factor to a number of other diseases such as cancer and car-diovascular disease . There are just as many theories as to the cause of insulin resistance as there are insulin signal-ing molecules and it is very unclear as to which are the actual molecular mechanisms of insulin resistance in diseased states.

  1. Clinical use of the co-formulation of insulin degludec and insulin aspart

    DEFF Research Database (Denmark)

    Kumar, A; Awata, T; Bain, S C;

    2016-01-01

    AIMS: To provide a review of the available data and practical use of insulin degludec with insulin aspart (IDegAsp). Premixed insulins provide basal and prandial glucose control; however, they have an intermediate-acting prandial insulin component and do not provide as effective basal coverage...... as true long-acting insulins, owing to the physicochemical incompatibility of their individual components, coupled with the inflexibility of adjustment. The molecular structure of the co-formulation of IDegAsp, a novel insulin preparation, allows these two molecules to coexist without affecting...... (HbA1c ) to current modern insulins, but with lower risk of nocturnal hypoglycaemia. In prior insulin users, glycaemic control was achieved with lower or equal insulin doses vs. other basal+meal-time or premix insulin regimens. In insulin-naïve patients with T2DM, IDegAsp can be started once or twice...

  2. Insulin-regulated Srebp-1c and Pck1 mRNA expression in primary hepatocytes from zucker fatty but not lean rats is affected by feeding conditions.

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    Full Text Available Insulin regulates the transcription of genes for hepatic glucose and lipid metabolism. We hypothesized that this action may be impaired in hepatocytes from insulin resistant animals. Primary hepatocytes from insulin sensitive Zucker lean (ZL and insulin resistant Zucker fatty (ZF rats in ad libitum or after an overnight fasting were isolated, cultured and treated with insulin and other compounds for analysis of gene expression using real-time PCR. The mRNA levels of one insulin-induced (Srebp-1c and one insulin-suppressed (Pck1 genes in response to insulin, glucagon, and compactin treatments in hepatocytes from ad libitum ZL and ZF rats were analyzed. Additionally, the effects of insulin and T1317 on their levels in hepatocytes from ad libitum or fasted ZL or ZF rats were compared. The mRNA levels of Srebp-1c, Fas, and Scd1, but not that of Insr, Gck and Pck1, were higher in freshly isolated hepatocytes from ad libitum ZF than that from ZL rats. These patterns of Srebp-1c and Pck1 mRNA levels remained in primary hepatocyte cultured in vitro. Insulin's ability to regulate Srebp-1c and Pck1 expression was diminished in hepatocytes from ad libitum ZF, but not ZL rats. Glucagon or compactin suppressed Srebp-1c mRNA expression in lean, but not fatty hepatocytes. However, glucagon induced Pck1 mRNA expression similarly in hepatocytes from ad libitum ZL and ZF rats. Insulin caused the same dose-dependent increase of Akt phosphorylation in hepatocytes from ad libitum ZL and ZF rats. It synergized with T1317 to induce Srebp-1c, and suppressed Pck1 mRNA levels in hepatocytes from fasted, but not that from ad libitum ZF rats. We demonstrated that insulin was unable to regulate its downstream genes' mRNA expression in hepatocytes from ad libitum ZF rats. This impairment can be partially restored in hepatocytes from ZF rats after an overnight fasting, a phenomenon that deserves further investigation.

  3. Insulin and insulin-like growth factor receptors and responses

    International Nuclear Information System (INIS)

    Insulin is a member of a family of structurally related hormones with diverse physiological functions. In humans, the best-characterized members of this family include insulin, insulin-like growth factor (IGF)-I, and IGF-II. Each of these three polypeptide hormones has its own distinct receptor. The structures of each of these receptors have now been deduced from analyses of isolated cDNA clones. To study further the responses mediated through these three different receptors, the authors have been studying cells expressing the proteins encoded by these three cDNAs. The isolated cDNAs have been transfected into Chinese hamster ovary (CHO) cells, and the resulting transfected cell lines have been characterized as to the ligand-binding activities and signal-transducing activities of the expressed proteins

  4. Patient Perspectives on Biosimilar Insulin.

    Science.gov (United States)

    Wilkins, Alasdair R; Venkat, Manu V; Brown, Adam S; Dong, Jessica P; Ran, Nina A; Hirsch, James S; Close, Kelly L

    2014-01-01

    Given that a new wave of biosimilar insulins will likely enter the market in coming years, it is important to understand patient perspectives on these biosimilars. A survey (N = 3214) conducted by the market research company dQ&A, which maintains a 10 000-patient panel of people with type 1 or type 2 diabetes in roughly equal measure, investigated these perspectives. The survey asked whether patients would switch to a hypothetical less expensive biosimilar insulin that was approved by their provider. Approximately 66% of respondents reported that they would "definitely" or "likely" use a biosimilar insulin, while 17% reported that they were "unlikely" to use or would "definitely not use" such a product. Type 2 diabetes patients demonstrated slightly more willingness to use biosimilars than type 1 diabetes patients. Common patient concerns included whether biosimilars would be as effective as reference products (~650 respondents), whether side effect profiles would deviate from those of reference products (~220 respondents), and the design of the delivery device (~50 respondents). While cost savings associated with biosimilar insulins could increase patient uptake, especially among patients without health insurance (some recent estimates suggest that biosimilars will come at a substantial discount), patients may still need assurance that a cheaper price tag is not necessarily associated with substandard quality. Overall, the dQ&A survey indicates that the majority of patients are willing to consider biosimilar insulins, but manufacturers will need to work proactively to address and assuage patient concerns regarding efficacy, safety, drug administration, and other factors. PMID:24876533

  5. Oral insulin--a perspective.

    Science.gov (United States)

    Raj, N K Kavitha; Sharma, Chandra P

    2003-01-01

    Diabetes mellitus is generally controlled quite well with the administration of oral medications or by the use of insulin injections. The current practice is the use of one or more doses, intermediate or long acting insulin per day. Oral insulin is a promising yet experimental method providing tight glycemic control for patients with diabetes. A biologically adhesive delivery systems offer important advantage over conventional drug delivery systems. The engineered polymer microspheres made of erodable polymer display strong adhesive interactions with gastrointestinal mucus and cellular lining can traverse both the mucosal epithelium and the follicle associated epithelium covering the lymphoid tissue of Peyer's patches. Alginate, a natural polymer recovered from seaweed is being developed as a nanoparticle for the delivery of insulin without being destroyed in the stomach. Alginate is in fact finding application in biotechnology industry as thickening agent, a gelling agent and a colloid stabilizer. Alginate has in addition, several other properties that have enabled it to be used as a matrix for entrapment and for the delivery of a variety of proteins such as insulin and cells. These properties include: a relatively inert aqueous environment within the matrix; a mild room temperature encapsulation process free of organic solvents; a high gel porosity which allows for high diffusion rates of macromolecules; the ability to control this porosity with simple coating procedures and dissolution and biodegradation of the system under normal physiological conditions.

  6. 门冬胰岛素与生物合成人胰岛素治疗新诊断Ⅱ型糖尿病的对照研究%Comparative study on clinical therapeutic effect of insulin aspart and biosynthetic human insulin in the treatment of newly diagnosed type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    陈中英

    2012-01-01

    Objective To compare the clinical efficacy between insulin aspart and biosynthetic human insulin in the treatment of newly diagnosed type 2 diabetes. Methods Ninety-six newly diagnosed type 2 diabetic patients were randomly divided into insulin aspart group (treatment group, n=48) and biosynthetic human insulin group (control group, n =48). The patients received subcutaneous injection of insulin aspart or biosynthetic human insulin before daily meals, and they were treated with insulin glargine at the bedtime. The blood sugar levels, incidence of hypo-glycemic episodes and the dosage of insulin were compared between the two groups. Results After administration of the drugs, the blood sugar levels were significantly reduced, and the blood sugar levels was lower in insulin aspart group than in the control group. The incidence of hypoglycemia in the treatment group was lower than in the control group, and the difference was statistically significant. The dosage of insulin showed no significant difference in the two groups. Conclusion Insulin aspart was better in the control of blood sugar levels and more effective in the treatment of patients with type 2 diabetes.%目的 比较门冬胰岛素与生物合成人胰岛素治疗新诊断Ⅱ型糖尿病的临床疗效.方法 将新诊断的96例Ⅱ型糖尿病患者随机均分为2组,分别为门冬胰岛素(治疗)组和生物合成人胰岛素(对照)组.患者分别在每日餐前给予皮下注射门冬胰岛素和生物合成人胰岛素,且均每晚定时皮下注射一次甘精胰岛素.比较2组患者血糖、低血糖事件、胰岛素用量的差异.结果 用药后2组餐前及餐后的血糖含量均明显降低,且门冬胰岛素组餐前、餐后血糖均低于生物合成人胰岛素组;门冬胰岛素组患者低血糖发生次数低于生物合成人胰岛素组,差异有统计学意义;但2组胰岛素用量无显著差异.结论 门冬胰岛素能够更好地控制Ⅱ型糖尿病的血糖,对Ⅱ

  7. BRST Quantization of String Theory in AdS(3)

    CERN Document Server

    Pakman, A

    2003-01-01

    We study the BRST quantization of bosonic and NSR strings propagating in AdS(3) x N backgrounds. The no-ghost theorem is proved using the Frenkel-Garland-Zuckerman method. Regular and spectrally-flowed representations of affine SL(2,R) appear on an equal footing. Possible generalizations to related curved backgrounds are discussed.

  8. 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 li

  9. 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.

  10. Penrose inequality for asymptotically AdS spaces

    Energy Technology Data Exchange (ETDEWEB)

    Itkin, Igor [Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University, Tel-Aviv 69978 (Israel); Oz, Yaron, E-mail: yaronoz@post.tau.ac.il [Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University, Tel-Aviv 69978 (Israel)

    2012-02-28

    In general relativity, the Penrose inequality relates the mass and the entropy associated with a gravitational background. If the inequality is violated by an initial Cauchy data, it suggests a creation of a naked singularity, thus providing means to consider the cosmic censorship hypothesis. We propose a general form of Penrose inequality for asymptotically locally AdS spaces.

  11. 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.

  12. Predicting AD conversion: comparison between prodromal AD guidelines and computer assisted PredictAD tool.

    Directory of Open Access Journals (Sweden)

    Yawu Liu

    Full Text Available 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 and CSF biomarkers.Altogether 391 MCI cases (158 AD converters were selected from the ADNI cohort. All the cases had baseline cognitive tests, MRI and/or CSF levels of Aβ1-42 and Tau. Using baseline data, the status of MCI patients (AD or MCI three years later was predicted using current diagnostic research guidelines and the PredictAD software tool designed for supporting clinical diagnostics. The data used were 1 clinical criteria for episodic memory loss of the hippocampal type, 2 visual MTA, 3 positive CSF markers, 4 their combinations, and 5 when the PredictAD tool was applied, automatically computed MRI measures were used instead of the visual MTA results. The accuracies of diagnosis were evaluated with the diagnosis made 3 years later.The PredictAD tool achieved the overall accuracy of 72% (sensitivity 73%, specificity 71% in predicting the AD diagnosis. The corresponding number for a clinician's prediction with the assistance of the PredictAD tool was 71% (sensitivity 75%, specificity 68%. Diagnosis with the PredictAD tool was significantly better than diagnosis by biomarkers alone or the combinations of clinical diagnosis of hippocampal pattern for the memory loss and biomarkers (p≤0.037.With the assistance of PredictAD tool, the clinician can predict AD conversion more accurately than the current diagnostic criteria.

  13. Coset construction of AdS particle dynamics

    CERN Document Server

    Heinze, Martin; Megrelidze, Luka

    2016-01-01

    We analyze dynamics of the AdS$_{N+1}$ particle realized on the coset SO$(2,N)/$SO$(1,N)$. Hamiltonian reduction provides the physical phase space in terms of the coadjoint orbit obtained by boosting a timelike element of ${\\frak so}(2,N)$. We show equivalence of this approach to geometric quantization and to the SO$(N)$ covariant oscillator description, for which the boost generators entail a complicated operator ordering. As an alternative scheme, we introduce dual oscillator variables and derive their algebra at the classical and the quantum level. This simplifies the calculations of the commutators for the boost generators and leads to unitary irreducible representations of ${\\frak so}(2,N)$ for all admissible values of the mass parameter. We furthermore discuss a SO$(N)$ covariant supersymmetric extensions of the oscillator quantization, with its realization for superparticles in AdS$_2$ and AdS$_3$ given by recent works.

  14. Entanglement temperature and perturbed AdS3 geometry

    Science.gov (United States)

    Levine, G. C.; Caravan, B.

    2016-06-01

    Generalizing the first law of thermodynamics, the increase in entropy density δ S (x ) of a conformal field theory (CFT) is proportional to the increase in energy density, δ E (x ) , of a subsystem divided by a spatially dependent entanglement temperature, TE(x ) , a fixed parameter determined by the geometry of the subsystem, crossing over to thermodynamic temperature at high temperatures. In this paper we derive a generalization of the thermodynamic Clausius relation, showing that deformations of the CFT by marginal operators are associated with spatial temperature variations, δ TE(x ) , and spatial energy correlations play the role of specific heat. Using AdS/CFT duality we develop a relationship between a perturbation in the local entanglement temperature of the CFT and the perturbation of the bulk AdS metric. In two dimensions, we demonstrate a method through which direct diagonalizations of the boundary quantum theory may be used to construct geometric perturbations of AdS3 .

  15. AdS5 backgrounds with 24 supersymmetries

    Science.gov (United States)

    Beck, S.; Gutowski, J.; Papadopoulos, G.

    2016-06-01

    We prove a non-existence theorem for smooth AdS 5 solutions with connected, compact without boundary internal space that preserve strictly 24 supersymmetries. In particular, we show that D = 11 supergravity does not admit such solutions, and that all such solutions of IIB supergravity are locally isometric to the AdS 5 × S 5 maximally supersymmetric background. Furthermore, we prove that (massive) IIA supergravity also does not admit such solutions, provided that the homogeneity conjecture for massive IIA supergravity is valid. In the context of AdS/CFT these results imply that if gravitational duals for strictly mathcal{N}=3 superconformal theories in 4-dimensions exist, they are either singular or their internal spaces are not compact.

  16. AdS5 Backgrounds with 24 Supersymmetries

    CERN Document Server

    Beck, S W; Papadopoulos, G

    2016-01-01

    We prove a non-existence theorem for smooth AdS5 solutions with connected, compact without boundary internal space that preserve strictly 24 supersymmetries. In particular, we show that D=11 supergravity does not admit such solutions, and that all such solutions of IIB supergravity are locally isometric to the AdS_5 * S^5 maximally supersymmetric background. Furthermore, we prove that (massive) IIA supergravity also does not admit such solutions, provided that the homogeneity conjecture for massive IIA supergravity is valid. In the context of AdS/CFT these results imply that if strictly N=3 superconformal theories in 4-dimensions exist, their gravitational dual backgrounds are either singular or their internal spaces are not compact.

  17. Microvascular Recruitment in Insulin Resistance

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker

    the resonating sound from the microbubbles in the systemic circulation were recorded for determination of microvascular recruitment in designated muscle segments. Results showed that microvascular recruitment increased with insulin stimulation by ~30% in rats and ~40% in humans (study I). Furthermore......, it was observed that muscle contractions increased muscle perfusion rapidly by 3-4 fold and by 1-2 fold compared to basal and insulin, respectively, in both rat and human skeletal muscle (study I). The real-time contrast-enhanced ultrasound method was applied to investigate the vaso-active effect of the incretin...... hormone glucagon-like-peptide-1 (GLP-1) in the microcirculation. Glucagon-like-peptide-1 analogs are drugs used for treatments of insulin resistance and type 2 diabetes but the vascular effects of GLP-1 in vivo are elusive. Here it was shown that GLP-1 rapidly increased the microvascular recruitment...

  18. Quantification of adipose tissue insulin sensitivity

    DEFF Research Database (Denmark)

    Søndergaard, Esben; Jensen, Michael D

    2016-01-01

    In metabolically healthy humans, adipose tissue is exquisitely sensitive to insulin. Similar to muscle and liver, adipose tissue lipolysis is insulin resistant in adults with central obesity and type 2 diabetes. Perhaps uniquely, however, insulin resistance in adipose tissue may directly contribute...... to development of insulin resistance in muscle and liver because of the increased delivery of free fatty acids to those tissues. It has been hypothesized that insulin adipose tissue resistance may precede other metabolic defects in obesity and type 2 diabetes. Therefore, precise and reproducible...... quantification of adipose tissue insulin sensitivity, in vivo, in humans, is an important measure. Unfortunately, no consensus exists on how to determine adipose tissue insulin sensitivity. We review the methods available to quantitate adipose tissue insulin sensitivity and will discuss their strengths and...

  19. Quantification of adipose tissue insulin sensitivity.

    Science.gov (United States)

    Søndergaard, Esben; Jensen, Michael D

    2016-06-01

    In metabolically healthy humans, adipose tissue is exquisitely sensitive to insulin. Similar to muscle and liver, adipose tissue lipolysis is insulin resistant in adults with central obesity and type 2 diabetes. Perhaps uniquely, however, insulin resistance in adipose tissue may directly contribute to development of insulin resistance in muscle and liver because of the increased delivery of free fatty acids to those tissues. It has been hypothesized that insulin adipose tissue resistance may precede other metabolic defects in obesity and type 2 diabetes. Therefore, precise and reproducible quantification of adipose tissue insulin sensitivity, in vivo, in humans, is an important measure. Unfortunately, no consensus exists on how to determine adipose tissue insulin sensitivity. We review the methods available to quantitate adipose tissue insulin sensitivity and will discuss their strengths and weaknesses.

  20. Insulin requirements in type 1 diabetic pregnancy

    DEFF Research Database (Denmark)

    Callesen, Nicoline; Ringholm, Lene; Stage, Edna;

    2012-01-01

    To evaluate the insulin requirements in women with type 1 diabetes during twin pregnancy compared with singleton pregnancy.......To evaluate the insulin requirements in women with type 1 diabetes during twin pregnancy compared with singleton pregnancy....

  1. Insulin Aspart (rDNA Origin) Injection

    Science.gov (United States)

    ... not use any type of insulin after the expiration date printed on the bottle has passed.Insulin ... or itching over the whole body shortness of breath wheezing dizziness blurred vision fast heartbeat sweating weakness ...

  2. The impact of calcineurin inhibitors on insulin sensitivity and insulin secretion

    DEFF Research Database (Denmark)

    Øzbay, Aygen; Møller, N; Juhl, C;

    2012-01-01

    pulsatile insulin secretion were not significantly affected by the drugs. CONCLUSION: In conclusion, 8-10 days of treatment with cyclosporine and tacrolimus impairs insulin sensitivity to a similar degree in haemodialysis patients, while acute insulin responses and pulsatile insulin secretion remain...

  3. Aminoacid polymorphisms of insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Almind, K; Bjørbaek, C; Vestergaard, H;

    1993-01-01

    Since relative or absolute insulin deficiency and insulin insensitivity are involved in the aetiology of non-insulin-dependent diabetes mellitus (NIDDM), we examined whether patients with NIDDM exhibit genetic variability in the coding region of insulin receptor substrate-1 (IRS-1), a candidate...

  4. Early Clinical Detection of Pharmacologic Response in Insulin Action in a Nondiabetic Insulin-Resistant Population

    Directory of Open Access Journals (Sweden)

    Sudha S. Shankar, MD

    2015-12-01

    Conclusions: Significant changes in insulin action across multiple insulin-sensitive tissues can be detected within 2 weeks of initiation of insulin-sensitizing therapy with pioglitazone in obese patients with nondiabetic insulin resistance. ClinicalTrials.gov identifier: NCT01115712.

  5. Comparison of metformin and insulin versus insulin alone for type 2 diabetes

    DEFF Research Database (Denmark)

    Hemmingsen, Bianca; Christensen, Louise Lundby; Wetterslev, Jørn;

    2012-01-01

    To compare the benefits and harms of metformin and insulin versus insulin alone as reported in randomised clinical trials of patients with type 2 diabetes.......To compare the benefits and harms of metformin and insulin versus insulin alone as reported in randomised clinical trials of patients with type 2 diabetes....

  6. Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation

    OpenAIRE

    DU, XUELIANG; Edelstein, Diane; Obici, Silvana; Higham, Ninon; Zou, Ming-Hui; Brownlee, Michael

    2006-01-01

    Insulin resistance markedly increases cardiovascular disease risk in people with normal glucose tolerance, even after adjustment for known risk factors such as LDL, triglycerides, HDL, and systolic blood pressure. In this report, we show that increased oxidation of FFAs in aortic endothelial cells without added insulin causes increased production of superoxide by the mitochondrial electron transport chain. FFA-induced overproduction of superoxide activated a variety of proinflammatory signals...

  7. 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

  8. Serum Insulin, Proinsulin and Proinsulin/Insulin Ratio in Type 2 Diabetic Patients: As an Index of β-Cell Function or Insulin Resistance

    OpenAIRE

    Kim, Nan Hee; Kim, Dong Lim; Choi, Kyung Mook; Baik, Sei Hyun; Choi, Dong Seop

    2000-01-01

    Background Although insulin resistance and decreased insulin secretion are characteristics of established type 2 DM, which of these metabolic abnormalities is the primary determinant of type 2 DM is controversial. It is also not well known how insulin resistance and beta cell dysfunction influence serum insulin, proinsulin, proinsulin/insulin ratio in type 2 DM. Methods We compared serum insulin, proinsulin and proinsulin/insulin ratio in type 2 diabetic patients and control subjects. We also...

  9. High levels of dietary stearate promote adiposity and deteriorate hepatic insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Havekes Louis M

    2010-03-01

    Full Text Available Abstract Background Relatively little is known about the role of specific saturated fatty acids in the development of high fat diet induced obesity and insulin resistance. Here, we have studied the effect of stearate in high fat diets (45% energy as fat on whole body energy metabolism and tissue specific insulin sensitivity. Methods C57Bl/6 mice were fed a low stearate diet based on palm oil or one of two stearate rich diets, one diet based on lard and one diet based on palm oil supplemented with tristearin (to the stearate level of the lard based diet, for a period of 5 weeks. Ad libitum fed Oxidative metabolism was assessed by indirect calorimetry at week 5. Changes in body mass and composition was assessed by DEXA scan analysis. Tissue specific insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp analysis and Western blot at the end of week 5. Results Indirect calorimetry analysis revealed that high levels of dietary stearate resulted in lower caloric energy expenditure characterized by lower oxidation of fatty acids. In agreement with this metabolic phenotype, mice on the stearate rich diets gained more adipose tissue mass. Whole body and tissue specific insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp and analysis of insulin induced PKBser473 phosphorylation. Whole body insulin sensitivity was decreased by all high fat diets. However, while insulin-stimulated glucose uptake by peripheral tissues was impaired by all high fat diets, hepatic insulin sensitivity was affected only by the stearate rich diets. This tissue-specific pattern of reduced insulin sensitivity was confirmed by similar impairment in insulin-induced phosphorylation of PKBser473 in both liver and skeletal muscle. Conclusion In C57Bl/6 mice, 5 weeks of a high fat diet rich in stearate induces a metabolic state favoring low oxidative metabolism, increased adiposity and whole body insulin resistance characterized by severe hepatic insulin

  10. Safety and Efficacy of Modern Insulin Analogues

    OpenAIRE

    Hye Jin Yoo; Keun Yong Park; Kang Seo Park; Kyu Jeung Ahn; Kyung Wan Min; Jeong Hyun Park; Sang Ah Chang; Bong Soo Cha; Dong-Jun Kim; Yong Seong Kim; Tae Keun Oh; Suk Chon; Il Seong Nam-Goong; Mi Jin Kim; Hye-Soon Kim

    2013-01-01

    Background A1chieve® was a noninterventional study evaluating the clinical safety and efficacy of biphasic insulin aspart 30, insulin detemir, and insulin aspart. Methods Korean type 2 diabetes patients who have not been treated with the study insulin or have started it within 4 weeks before enrollment were eligible for the study. The patient selection and the choice of regimen were at the discretion of the physician. The safety and efficacy information was collected from the subjects at base...

  11. Role of Mitochondrial Dysfunction in Insulin Resistance

    OpenAIRE

    Kim, Jeong-a; Wei, Yongzhong; Sowers, James R.

    2008-01-01

    Insulin resistance is characteristic of obesity, type 2 diabetes, and components of the cardiometabolic syndrome, including hypertension and dyslipidemia, that collectively contribute to a substantial risk for cardiovascular disease. Metabolic actions of insulin in classic insulin target tissues (eg, skeletal muscle, fat, and liver), as well as actions in nonclassic targets (eg, cardiovascular tissue), help to explain why insulin resistance and metabolic dysregulation are central in the patho...

  12. Insulin Pump Safety Meeting: Summary Report

    OpenAIRE

    Klonoff, David C; Reyes, Juliet S.

    2009-01-01

    Diabetes Technology Society convened a panel of insulin pump experts in Bethesda, Maryland, on November 12, 2008, at the request of the Food and Drug Administration. The group consisted of physicians, nurses, diabetes educators, and engineers from across the United States. The panel members (1) discussed safety features of insulin pump therapy and (2) recommended adjustments to current insulin pump design and use to enhance overall safety. Software and hardware features of insulin pumps were ...

  13. Self-dual warped AdS3 black holes

    Science.gov (United States)

    Chen, Bin; Ning, Bo

    2010-12-01

    We study a new class of solutions of three-dimensional topological massive gravity. These solutions can be taken as nonextremal black holes, with their extremal counterparts being discrete quotients of spacelike warped AdS3 along the U(1)L isometry. We study the thermodynamics of these black holes and show that the first law is satisfied. We also show that for consistent boundary conditions, the asymptotic symmetry generators form only one copy of the Virasoro algebra with central charge cL=(4νℓ)/(G(ν2+3)), with which the Cardy formula reproduces the black hole entropy. We compute the real-time correlators of scalar perturbations and find a perfect match with the dual conformal field theory (CFT) predictions. Our study provides a novel example of warped AdS/CFT correspondence: the self-dual warped AdS3 black hole is dual to a CFT with nonvanishing left central charge. Moreover, our investigation suggests that the quantum topological massive gravity asymptotic to the same spacelike warped AdS3 in different consistent ways may be dual to different two-dimensional CFTs.

  14. 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....

  15. Synergistic Effect of Insulin on in vitro Development of Immature Bovine Oocytes

    Directory of Open Access Journals (Sweden)

    Mojtaba Dashtizad

    2010-01-01

    Full Text Available Problem statement: Development of efficient culture system to support embryonic development would be valuable when quality of produced embryos was important. However, the rate of bovine embryo production in vitro was still lower than expected. Present study, including of three experiments, was carried out to investigate the effect of insulin on nuclear maturation and subsequent development of immature bovine oocytes and in vitro fertilized embryos. Approach: Grade one cumulus-oocyte-complexes harvested from slaughterhouse ovaries were selected and randomly allocated in each treatment groups. In experiment 1, in vitro maturation medium (Hepes-buffered medium 199 + fetal calf serum + gonadotrophins + antibiotics supplemented with 0 (control, 1, 10, 20 and 100 µg mL-1 of insulin. In experiment 2, to eliminate the effect of serum and hormones, Hepesbuffered medium 199 was supplemented with 1 mg mL-1 polyvinyl alcohols (PVA and same levels of insulin. In experiment 3, the effect of insulin on bovine in vitro embryo development was assessed. Presumptive zygotes were randomly cultured in synthetic oviductal fluid added with 0 (control, 1, 10, 20 and 100 ìg mL-1 of insulin. Results: In experiment 1, nuclear maturation and embryo development rates were significantly higher in 1 and 10 µg mL-1 compared with other groups (P-1 insulin. The only treatment resulted in higher hatchability was 10 ìg mL-1 insulin (17.1±2.34% compared with control (11.34±3.94. In experiment 3, cleavage and morula rates were significantly greater in 1 and 10 µg mL-1 insulin compared with other groups; although the highest rates resulted by using 10 µg mL-1. Conclusion: Obtained results show that inclusion of 10 µg mL-1 insulin in maturation and culture medium exerted beneficial effects on nuclear maturation of bovine oocytes and in vitro embryo development till morula stage.

  16. The Effect of Different Doses of Vitamin D Supplementation on Insulin Resistance in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Rastegar Hoseini

    2016-04-01

    Full Text Available Background and Aim: Type 2 diabetes mellitus (T2DM and vitamin D deficiency are both too common during menopause. Since the effect of different doses of vitamin D supplements on blood sugar, insulin concentration  and insulin resistance are unknown, the present study aimed at investigating the effects of different doses of the vitamin D supplements on visceral fat, blood sugar, insulin concentration,  and insulin resistance in ovariectomized rats. Materials and Methods: In this randomized experimental study, 32 female Wistar rats were divided into 4 equal groups  as follows: three groups . that received vitamin D supplements (high, moderate, and low dose and one control group. After 8 weeks of different doses of vitamin D supplementation plasma concentration of glucose, insulin and HOMA-IR were measured  in the three groups. The obtained data  was statistically analyzed by means of dependent t-test and ANOVA . at the significance level of P<0.05. Results: After a period of eight-week  intervention, body weight, BMI, waist circumference, visceral fat, insulin, blood glucose and HOMA-IR at high, moderate, and low doses of vitamin D supplementation were significantly lower than those in the control group (P<0.05. High dose of vitamin D compared with moderate and low doses significantly caused reduction in insulin, blood glucose, and HOMA-IR (P<0.001 for all three variables. Conclusion: The findings of the current study showed that a high dose of vitamin D causes significant improvements in FPG, insulin, and insulin resistance  evaluated by HOMA-IR. It was also found that adding vitamin D supplements can improve glucose control in menopause model of rats.

  17. Imaging dynamic insulin release using a fluorescent zinc indicator for monitoring induced exocytotic release (ZIMIR).

    Science.gov (United States)

    Li, Daliang; Chen, Shiuhwei; Bellomo, Elisa A; Tarasov, Andrei I; Kaut, Callan; Rutter, Guy A; Li, Wen-hong

    2011-12-27

    Current methods of monitoring insulin secretion lack the required spatial and temporal resolution to adequately map the dynamics of exocytosis of native insulin granules in intact cell populations in three dimensions. Exploiting the fact that insulin granules contain a high level of Zn(2+), and that Zn(2+) is coreleased with insulin during secretion, we have developed a fluorescent, cell surface-targeted zinc indicator for monitoring induced exocytotic release (ZIMIR). ZIMIR displayed a robust fluorescence enhancement on Zn(2+) chelation and bound Zn(2+) with high selectivity against Ca(2+) and Mg(2+). When added to cultured β cells or intact pancreatic islets at low micromolar concentrations, ZIMIR labeled cells rapidly, noninvasively, and stably, and it reliably reported changes in Zn(2+) concentration near the sites of granule fusion with high sensitivity that correlated well with membrane capacitance measurement. Fluorescence imaging of ZIMIR-labeled β cells followed the dynamics of exocytotic activity at subcellular resolution, even when using simple epifluorescence microscopy, and located the chief sites of insulin release to intercellular junctions. Moreover, ZIMIR imaging of intact rat islets revealed that Zn(2+)/insulin release occurred largely in small groups of adjacent β cells, with each forming a "secretory unit." Concurrent imaging of ZIMIR and Fura-2 showed that the amplitude of cytosolic Ca(2+) elevation did not necessarily correlate with insulin secretion activity, suggesting that events downstream of Ca(2+) signaling underlie the cell-cell heterogeneity in insulin release. In addition to studying stimulation-secretion coupling in cells with Zn(2+)-containing granules, ZIMIR may find applications in β-cell engineering and screening for molecules regulating insulin secretion on high-throughput platforms. PMID:22160693

  18. Redox regulation of insulin degradation by insulin-degrading enzyme.

    Directory of Open Access Journals (Sweden)

    Crystal M Cordes

    Full Text Available Insulin-degrading enzyme (IDE is a thiol sensitive peptidase that degrades insulin and amyloid β, and has been linked to type 2 diabetes mellitus and Alzheimer's disease. We examined the thiol sensitivity of IDE using S-nitrosoglutathione, reduced glutathione, and oxidized glutathione to distinguish the effects of nitric oxide from that of the redox state. The in vitro activity of IDE was studied using either partially purified cytosolic enzyme from male Sprague-Dawley rats, or purified rat recombinant enzyme. We confirm that nitric oxide inhibits the degrading activity of IDE, and that it affects proteasome activity through this interaction with IDE, but does not affect the proteasome directly. Oxidized glutathione inhibits IDE through glutathionylation, which was reversible by dithiothreitol but not by ascorbic acid. Reduced glutathione had no effect on IDE, but reacted with partially degraded insulin to disrupt its disulfide bonds and accelerate its breakdown to trichloroacetic acid soluble fragments. Our results demonstrate the sensitivity of insulin degradation by IDE to the redox environment and suggest another mechanism by which the cell's oxidation state may contribute to the development of, and the link between, type 2 diabetes and Alzheimer's disease.

  19. Novel covalently linked insulin dimer engineered to investigate the function of insulin dimerization

    DEFF Research Database (Denmark)

    Vinther, Tine N.; Norrman, Mathias; Strauss, Holger M.;

    2012-01-01

    An ingenious system evolved to facilitate insulin binding to the insulin receptor as a monomer and at the same time ensure sufficient stability of insulin during storage. Insulin dimer is the cornerstone of this system. Insulin dimer is relatively weak, which ensures dissociation into monomers...... in the circulation, and it is stabilized by hexamer formation in the presence of zinc ions during storage in the pancreatic ß-cell. Due to the transient nature of insulin dimer, direct investigation of this important form is inherently difficult. To address the relationship between insulin oligomerization...... and insulin stability and function, we engineered a covalently linked insulin dimer in which two monomers were linked by a disulfide bond. The structure of this covalent dimer was identical to the self-association dimer of human insulin. Importantly, this covalent dimer was capable of further oligomerization...

  20. Vitamin A and feeding statuses modulate the insulin-regulated gene expression in Zucker lean and fatty primary rat hepatocytes.

    Directory of Open Access Journals (Sweden)

    Wei Chen

    Full Text Available Unattended hepatic insulin resistance predisposes individuals to dyslipidemia, type 2 diabetes and many other metabolic complications. The mechanism of hepatic insulin resistance at the gene expression level remains unrevealed. To examine the effects of vitamin A (VA, total energy intake and feeding conditions on the insulin-regulated gene expression in primary hepatocytes of Zucker lean (ZL and fatty (ZF rats, we analyze the expression levels of hepatic model genes in response to the treatments of insulin and retinoic acid (RA. We report that the insulin- and RA-regulated glucokinase, sterol regulatory element-binding protein-1c and cytosolic form of phosphoenolpyruvate carboxykinase expressions are impaired in hepatocytes of ZF rats fed chow or a VA sufficient (VAS diet ad libitum. The impairments are partially corrected when ZF rats are fed a VA deficient (VAD diet ad libitum or pair-fed a VAS diet to the intake of their VAD counterparts in non-fasting conditions. Interestingly in the pair-fed ZL and ZF rats, transient overeating on the last day of pair-feeding regimen changes the expression levels of some VA catabolic genes, and impairs the insulin- and RA-regulated gene expression in hepatocytes. These results demonstrate that VA and feeding statuses modulate the hepatic insulin sensitivity at the gene expression level.

  1. Kolmogorov-Zakharov spectrum in AdS gravitational collapse.

    Science.gov (United States)

    de Oliveira, H P; Pando Zayas, Leopoldo A; Rodrigues, E L

    2013-08-01

    We study black hole formation during the gravitational collapse of a massless scalar field in asymptotically D-dimensional anti-de Sitter AdS(D) spacetimes for D = 4, 5. We conclude that spherically symmetric gravitational collapse in asymptotically AdS spaces is turbulent and characterized by a Kolmogorov-Zakharov spectrum. Namely, we find that after an initial period of weakly nonlinear evolution, there is a regime where the power spectrum of the Ricci scalar evolves as ω(-s) with the frequency, ω, and s ≈ 1.7 ± 0.1.

  2. Technology of Ad hoc Networks%Ad hoc技术

    Institute of Scientific and Technical Information of China (English)

    曹常义

    2002-01-01

    Ad hoc技术是从无线移动Ad hoc网络(WMANET)抽象出来的一个一般性概念,该项技术所标称的是自组识、多跳的一个临时分布式系统,是一种网络构架技术.它要面临多项难题.本文就是从OSI模型的角度把Ad hoc技术分层介绍,最后给出了一种WMANET应用方案.

  3. Insulin sensitivity : modulation by the brain

    NARCIS (Netherlands)

    Coomans, Claudia Pascalle

    2012-01-01

    The studies in this thesis contribute to the understanding of the role of the brain in insulin sensitivity. We demonstrate that disturbances in circadian rhythm resulting in alterations in SCN output, can contribute to the development of insulin resistance. We also shown that insulin-stimulated gluc

  4. Insulin: pancreatic secretion and adipocyte regulation.

    Science.gov (United States)

    Baumgard, L H; Hausman, G J; Sanz Fernandez, M V

    2016-01-01

    Insulin is the primary acute anabolic coordinator of nutrient partitioning. Hyperglycemia is the main stimulant of insulin secretion, but other nutrients such as specific amino acids, fatty acids, and ketoacids can potentiate pancreatic insulin release. Incretins are intestinal hormones with insulinotropic activity and are secreted in response to food ingestion, thus integrating diet chemical composition with the regulation of insulin release. In addition, prolactin is required for proper islet development, and it stimulates β-cell proliferation. Counterintuitively, bacterial components appear to signal insulin secretion. In vivo lipopolysaccharide infusion acutely increases circulating insulin, which is paradoxical as endotoxemia is a potent catabolic condition. Insulin is a potent anabolic orchestrator of nutrient partitioning, and this is particularly true in adipocytes. Insulin dictates lipid accretion in a dose-dependent manner during preadipocyte development in adipose tissue-derived stromal vascular cell culture. However, in vivo studies focused on insulin's role in regulating adipose tissue metabolism from growing, and market weight pigs are sometimes inconsistent, and this variability appears to be animal, age and depot dependent. Additionally, porcine adipose tissue synthesizes and secretes a number of adipokines (leptin, adiponectin, and so forth) that directly or indirectly influence insulin action. Therefore, because insulin has an enormous impact on agriculturally important phenotypes, it is critical to have a better understanding of how insulin homeostasis is governed.

  5. 21 CFR 522.1160 - Insulin.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Insulin. 522.1160 Section 522.1160 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1160 Insulin. (a) Specifications—(1) Each milliliter (mL) of porcine insulin zinc suspension contains 40 international units...

  6. [A21-Asparaginimide] insulin. Saponification of insulin hexamethyl ester, I.

    Science.gov (United States)

    Gattner, H G; Schmitt, E W

    1977-01-01

    [Asn A21]Insulin is formed as the main product during alkaline saponification of insulin hexamethyl ester. Purification was achieved by gel chromatography followed by ion-exchange chromatography on carboxymethyl cellulose at pH 4 or by preparative isoelectric focusing in a granulated gel over a narrow pH range. Two main products could be isolated. One of them showed the electrophoretic behaviour of insulin (A), whilst the other corresponded to insulin with a blocked carboxyl function (B). Incubation of this product B with carboxypeptidase A liberated only the C-terminal alanine of the B-chain, but not the asparagine of the C-terminus of the A-chain. Chymotryptic digestion of the isolated S-sulfonate A-chain derivative (C) followed by high-voltage electrophoresis confirmed that the carboxyl function of asparagine A21 was blocked. In order to determine the free carboxyl functions of the A-chain derivative C, it was coupled with glycine methyl ester yielding D. Amino acid analysis of the chymotryptic peptides of D showed that the carboxyl functions of glutamic acid A4 and A17 had been free prior to coupling. The amino acid analysis of the enzymatic hydrolysate (subtilisin, aminopeptidase M) of the A-chain derivative C showed an additional peak with an elution position identical to the model compound aminosuccinimide. The biological activity of the [Asm A21[insulin was found to be about 40% in the fat cell test and 13.2 units/mg measured by the mouse convulsion method.

  7. Interstitial insulin concentrations determine glucose uptake rates but not insulin resistance in lean and obese men.

    OpenAIRE

    Castillo, C.; Bogardus, C; Bergman, R.; Thuillez, P; Lillioja, S

    1994-01-01

    Insulin action and obesity are both correlated with the density of muscle capillary supply in humans. Since the altered muscle anatomy in the obese might affect interstitial insulin concentrations and reduce insulin action, we have cannulated peripheral lymphatic vessels in lean and obese males, and compared peripheral lymph insulin concentrations with whole body glucose uptake during a euglycemic, hyperinsulinemic clamp. Lymph insulin concentrations in the lower limb averaged only 34% of art...

  8. Clinical application of insulin pumps in the management of insulin dependent diabetes.

    OpenAIRE

    Greene, S.A.; Smith, M. A.; Baum, J D

    1983-01-01

    Seven volunteers aged 12.0 to 17.9 years participated in a trial to compare conventional insulin treatment with continuous open loop (pump) insulin infusion. After 6 weeks of conventional treatment followed by 6 weeks of insulin pump treatment, 4 children chose to manage their diabetes permanently by means of the insulin pump. The mean blood glucose concentration (based on home blood glucose monitoring) while on conventional insulin treatment showed no appreciable change during the 6 weeks' t...

  9. Insulin signal transduction in skeletal muscle : special consideration for insulin resistance and diabetes

    OpenAIRE

    Song, Xiao Mei

    2000-01-01

    This dissertation work is focused on the insulin-signal-transduction pathways to glucose transport in skeletal muscle from animal models of NIDDM. The overall objective is to determine the effectiveness of different pharmacological treatments to improve insulin action in skeletal muscle. Muscle-fiber-type-specific differences in insulin signal transduction was first considered. We noted increased insulin action on insulin signaling events including; IR, IRS- 1, IRS-2, PI...

  10. Subetta increases phosphorylation of insulin receptor β-subunit alone and in the presence of insulin

    OpenAIRE

    Gorbunov, E A; Nicoll, J; Kachaeva, E. V.; Tarasov, S A; Epstein, O. I.

    2015-01-01

    It has been previously shown that Subetta (a drug containing released-active forms of antibodies to the insulin receptor β-subunit and antibodies to endothelial nitric oxide synthase) stimulated insulin-induced adiponectin production by mature human adipocytes in the absence of insulin. Therefore, it was assumed that Subetta could activate the insulin receptor. To confirm this hypothesis, the capacity of Subetta to activate the insulin receptor in mature human adipocytes in the absence or pre...

  11. Universal isolation in the AdS landscape

    CERN Document Server

    Danielsson, U H; Vargas, S C

    2016-01-01

    We study the universal conditions for quantum non-perturbative stability against bubble nucleation for pertubatively stable AdS vacua based on positive energy theorems. We also compare our analysis with the pre-existing ones in the literature carried out within the thin-wall approximation. The aforementioned criterion is then tested in two explicit examples describing massive type IIA string theory compactified on $S^3$ and $S^3\\,\\times\\,S^3$, respectively. The AdS landscape of both classes of compactifications is known to consist of a set of isolated points. The main result is that all critical points respecting the Breitenlohner-Freedaman (BF) bound also turn out be stable at a non-perturbative level. Finally, we speculate on the possible universal features that may be extracted from the above specific examples.

  12. Thermodynamics of Einstein-Proca AdS Black Holes

    CERN Document Server

    Liu, Hai-Shan; Pope, C N

    2014-01-01

    We study static spherically-symmetric solutions of the Einstein-Proca equations in the presence of a negative cosmological constant. We show that the theory admits solutions describing both black holes and also solitons in an asymptotically AdS background. Interesting subtleties can arise in the computation of the mass of the solutions and also in the derivation of the first law of thermodynamics. We make use of holographic renormalisation in order to calculate the mass, even in cases where the solutions have a rather slow approach to the asymptotic AdS geometry. By using the procedure developed by Wald, we derive the first law of thermodynamics for the black hole and soliton solutions. This includes a non-trivial contribution associated with the Proca "charge." The solutions cannot be found analytically, and so we make use of numerical integration techniques to demonstrate their existence.

  13. AdS nonlinear instability: moving beyond spherical symmetry

    CERN Document Server

    Dias, Oscar J C

    2016-01-01

    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 [1,2]. We give evidence that the gravitational sector of perturbations behaves differently from the scalar one studied in [2]. In contrast with [2], 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 in [2]. Moreover, if the seed has two normal modes, more than one resonance can be generated at third order, unlike the spherical collapse of [2]. 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.

  14. Perturbative entanglement thermodynamics for AdS spacetime: Renormalization

    CERN Document Server

    Mishra, Rohit

    2015-01-01

    We study the effect of charged excitations in the AdS spacetime on the first law of entanglement thermodynamics. It is found that `boosted' AdS black holes give rise to a more general form of first law which includes chemical potential and charge density. To obtain this result we have to resort to a second order perturbative calculation of entanglement entropy for small size subsystems. At first order the form of entanglement law remains unchanged even in the presence of charged excitations. But the thermodynamic quantities have to be appropriately `renormalized' at the second order due to the corrections. We work in the perturbative regime where $T_{thermal}\\ll T_E$.

  15. Smoothed Transitions in Higher Spin AdS Gravity

    CERN Document Server

    Banerjee, Shamik; Hellerman, Simeon; Hijano, Eliot; Lepage-Jutier, Arnaud; Maloney, Alexander; Shenker, Stephen

    2012-01-01

    We consider CFTs conjectured to be dual to higher spin theories of gravity in AdS_3 and AdS_4. Two dimensional CFTs with W_N symmetry are considered in the lambda=0 (k --> infinity) limit, where they are conjectured to be described by continuous orbifolds. The torus partition function is computed, using reasonable assumptions, and equals that of a free field theory. We find no phase transition at temperatures of order one; the usual Hawking-Page phase transition is removed by the highly degenerate light states associated with conical defect states in the bulk. Three dimensional Chern-Simons-matter CFTs with vector-like matter are considered on T^3, where the dynamics is described by an effective theory for the eigenvalues of the holonomies. Likewise, we find no evidence for a Hawking-Page phase transition at large level k.

  16. Ambitwistors, oscillators and massless fields on $AdS_5$

    CERN Document Server

    Uvarov, D V

    2016-01-01

    Positive energy unitary irreducible representations of $SU(2,2)$ can be constructed with the aid of bosonic oscillators in (anti)fundamental representation of $SU(2)_L\\times SU(2)_R$ that are closely related to Penrose twistors. Starting with the correspondence between the doubleton representations, homogeneous functions on projective twistor space and on-shell $SL(2,\\mathbb C)$ generalized Weyl curvature spinors and their low-spin counterparts, we study in the similar way the correspondence between the massless representations, homogeneous functions on ambitwistor space and, via the Penrose transform, with the gauge fields on Minkowski boundary of $AdS_5$. The possibilities of reconstructing massless fields on $AdS_5$ and some applications are also discussed.

  17. 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.

  18. Semiclassical Virasoro Blocks from AdS$_3$ Gravity

    CERN Document Server

    Hijano, Eliot; Perlmutter, Eric; Snively, River

    2015-01-01

    We present a unified framework for the holographic computation of Virasoro conformal blocks at large central charge. In particular, we provide bulk constructions that correctly reproduce all semiclassical Virasoro blocks that are known explicitly from conformal field theory computations. The results revolve around the use of geodesic Witten diagrams, recently introduced in arXiv:1508.00501, evaluated in locally AdS$_3$ geometries generated by backreaction of heavy operators. We also provide an alternative computation of the heavy-light semiclassical block -- in which two external operators become parametrically heavy -- as a certain scattering process involving higher spin gauge fields in AdS$_3$; this approach highlights the chiral nature of Virasoro blocks. These techniques may be systematically extended to compute corrections to these blocks and to interpolate amongst the different semiclassical regimes.

  19. Semiclassical Virasoro blocks from AdS3 gravity

    Science.gov (United States)

    Hijano, Eliot; Kraus, Per; Perlmutter, Eric; Snively, River

    2015-12-01

    We present a unified framework for the holographic computation of Virasoro conformal blocks at large central charge. In particular, we provide bulk constructions that correctly reproduce all semiclassical Virasoro blocks that are known explicitly from conformal field theory computations. The results revolve around the use of geodesic Witten diagrams, recently introduced in [1], evaluated in locally AdS3 geometries generated by backreaction of heavy operators. We also provide an alternative computation of the heavy-light semiclassical block — in which two external operators become parametrically heavy — as a certain scattering process involving higher spin gauge fields in AdS3; this approach highlights the chiral nature of Virasoro blocks. These techniques may be systematically extended to compute corrections to these blocks and to interpolate amongst the different semiclassical regimes.

  20. Relationship between plasma analytes and SPARE-AD defined brain atrophy patterns in ADNI.

    Directory of Open Access Journals (Sweden)

    Jon B Toledo

    Full Text Available Different inflammatory and metabolic pathways have been associated with Alzheimeŕs disease (AD. However, only recently multi-analyte panels to study a large number of molecules in well characterized cohorts have been made available. These panels could help identify molecules that point to the affected pathways. We studied the relationship between a panel of plasma biomarkers (Human DiscoveryMAP and presence of AD-like brain atrophy patterns defined by a previously published index (SPARE-AD at baseline in subjects of the ADNI cohort. 818 subjects had MRI-derived SPARE-AD scores, of these subjects 69% had plasma biomarkers and 51% had CSF tau and Aβ measurements. Significant analyte-SPARE-AD and analytes correlations were studied in adjusted models. Plasma cortisol and chromogranin A showed a significant association that did not remain significant in the CSF signature adjusted model. Plasma macrophage inhibitory protein-1α and insulin-like growth factor binding protein 2 showed a significant association with brain atrophy in the adjusted model. Cortisol levels showed an inverse association with tests measuring processing speed. Our results indicate that stress and insulin responses and cytokines associated with recruitment of inflammatory cells in MCI-AD are associated with its characteristic AD-like brain atrophy pattern and correlate with clinical changes or CSF biomarkers.

  1. High fasting serum insulin level due to autoantibody interference in insulin immunoassay discloses autoimmune insulin syndrome: a case report.

    Science.gov (United States)

    Lamy, Pierre-Jean; Sault, Corinne; Renard, Eric

    2016-08-01

    Insulin-antibodies are a cause of misleading results in insulin immunoassays. They may also mediate deleterious blood glucose variations. A patient presented with overtiredness, recurrent episodes of sweating, dizziness and fainting fits. A fasting serum insulin assay performed on a Modular platform (Modular analytic E170, Roche Diagnostic, Meylan, France) showed a highly elevated value of 194.7 mIU/L, whereas on the same sample glucose and C-peptide levels were normal. Other immunometric insulin assays were performed, as well as antibodies anti-insulin radiobinding assay (RBA) and gel filtration chromatography (GFC). While complementary insulin assays yielded closer to normal fasting levels, the free insulin concentration assessed after PEG precipitation was 14.0 mIU/L and the RBA was positive. GFC revealed that most of the insulin was complexed with a 150 kDa molecule, corresponding to an immunoglobulin G (IgG). A high fasting serum insulin level in a patient with neuroglucopenic symptoms was related to a high insulin-antibody level, suggesting an insulin autoimmune syndrome. PMID:27492703

  2. Alday-Maldacena duality and AdS Plateau problem

    OpenAIRE

    Morozov, A.

    2008-01-01

    A short summary of approximate approach to the study of minimal surfaces in AdS, based on solving Nambu-Goto equations iteratively. Today, after partial denunciation of the BDS conjecture, this looks like the only constructive approach to understanding the ways of its possible modification and thus to saving the Alday-Maldacena duality. Numerous open technical problems are explicitly formulated throughout the text.

  3. One loop gauge couplings in AdS5

    OpenAIRE

    Choi, Kiwoon; Kim, Ian-Woo

    2002-01-01

    We calculate the full 1-loop corrections to the low energy coupling of bulk gauge boson in a slice of AdS5 which are induced by generic 5-dimensional scalar, Dirac fermion, and vector fields with arbitrary Z_2 times Z_2' orbifold boundary conditions. In supersymmetric limit, our results correctly reproduce the results obtained by an independent method based on 4-dimensional effective supergravity. This provides a nontrivial check of our results and assures the regularization scheme-independen...

  4. Universal Kounterterms in Lovelock AdS gravity

    OpenAIRE

    Kofinas, Georgios; Olea, Rodrigo

    2008-01-01

    We show the universal form of the boundary term (Kounterterm series) which regularizes the Euclidean action and background-independent definition of conserved quantities for any Lovelock gravity theory with AdS asymptotics (including Einstein-Hilbert and Einstein-Gauss-Bonnet). We discuss on the connection of this procedure to the existence of topological invariants and Chern-Simons forms in the corresponding dimensions.

  5. Mellin amplitudes for $AdS_5\\times S^5$

    CERN Document Server

    Rastelli, Leonardo

    2016-01-01

    We revisit the calculation of holographic correlation functions in IIB supergravity on $AdS_5\\times S^5$. Results for four-point functions simplify drastically when expressed in Mellin space. We conjecture a compact formula for the four-point functions of one-half BPS singe-trace operators of arbitrary weight. Our methods rely on general consistency conditions and eschew detailed knowledge of the supergravity effective action.

  6. N=2 supersymmetric sigma-models in AdS

    CERN Document Server

    Butter, Daniel

    2011-01-01

    We construct the most general N=2 supersymmetric nonlinear sigma-model in four-dimensional anti-de Sitter (AdS) space in terms of N=1 chiral superfields. The target space is shown to be a non-compact hyperkahler manifold restricted to possess a special Killing vector field. A remarkable property of the sigma-model constructed is that the algebra of OSp(2|4) transformations is closed off the mass shell.

  7. Mitochondrial efficiency and insulin resistance.

    Science.gov (United States)

    Crescenzo, Raffaella; Bianco, Francesca; Mazzoli, Arianna; Giacco, Antonia; Liverini, Giovanna; Iossa, Susanna

    2014-01-01

    Insulin resistance, "a relative impairment in the ability of insulin to exert its effects on glucose, protein and lipid metabolism in target tissues," has many detrimental effects on metabolism and is strongly correlated to deposition of lipids in non-adipose tissues. Mitochondria are the main cellular sites devoted to ATP production and fatty acid oxidation. Therefore, a role for mitochondrial dysfunction in the onset of skeletal muscle insulin resistance has been proposed and many studies have dealt with possible alteration in mitochondrial function in obesity and diabetes, both in humans and animal models. Data reporting evidence of mitochondrial dysfunction in type two diabetes mellitus are numerous, even though the issue that this reduced mitochondrial function is causal in the development of the disease is not yet solved, also because a variety of parameters have been used in the studies carried out on this subject. By assessing the alterations in mitochondrial efficiency as well as the impact of this parameter on metabolic homeostasis of skeletal muscle cells, we have obtained results that allow us to suggest that an increase in mitochondrial efficiency precedes and therefore can contribute to the development of high-fat-induced insulin resistance in skeletal muscle. PMID:25601841

  8. Nutritional Modulation of Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Martin O. Weickert

    2012-01-01

    Full Text Available Insulin resistance has been proposed as the strongest single predictor for the development of Type 2 Diabetes (T2DM. Chronic oversupply of energy from food, together with inadequate physical activity, have been recognized as the most relevant factors leading to overweight, abdominal adiposity, insulin resistance, and finally T2DM. Conversely, energy reduced diets almost invariably to facilitate weight loss and reduce abdominal fat mass and insulin resistance. However, sustained weight loss is generally difficult to achieve, and distinct metabolic characteristics in patients with T2DM further compromise success. Therefore, investigating the effects of modulating the macronutrient composition of isoenergetic diets is an interesting concept that may lead to additional important insights. Metabolic effects of various different dietary concepts and strategies have been claimed, but results from randomized controlled studies and particularly from longer-term-controlled interventions in humans are often lacking. However, some of these concepts are supported by recent research, at least in animal models and short-term studies in humans. This paper provides an update of the current literature regarding the role of nutrition in the modulation of insulin resistance, which includes the discussion of weight-loss-independent metabolic effects of commonly used dietary concepts.

  9. Obesity genes and insulin resistance

    Science.gov (United States)

    Belkina, Anna C.; Denis, Gerald V.

    2011-01-01

    Purpose of review The exploding prevalence of insulin resistance and Type 2 diabetes (T2D) linked to obesity has become an alarming public health concern. Worldwide, approximately 171 million people suffer from obesity-induced diabetes and public health authorities expect this situation to deteriorate rapidly. An interesting clinical population of ‘metabolically healthy but obese’ (MHO) cases is relatively protected from T2D and its associated cardiovascular risk. The molecular basis for this protection is not well understood but is likely to involve reduced inflammatory responses. The inflammatory cells and pathways that respond to overnutrition are the primary subject matter for this review. Recent findings The chance discovery of a genetic mutation in the Brd2 gene, which is located in the class II major histocompatibility complex and makes mice enormously fat but protects them from diabetes, offers revolutionary new insights into the cellular mechanisms that link obesity to insulin resistance and T2D. These Brd2-hypomorphic mice have reduced inflammation in fat that is normally associated with insulin resistance, and resemble MHO patients, suggesting novel therapeutic pathways for obese patients at risk for T2D. Summary Deeper understanding of the functional links between genes that control inflammatory responses to diet-induced obesity is crucial to the development of therapies for obese, insulin-resistant patients. PMID:20585247

  10. Continue subcutane insuline-infusie

    NARCIS (Netherlands)

    Ballegooie, Evert van

    1984-01-01

    In dit proefschrift worden de resultaten beschreven van een onderzoek naar: (1) de rol van bloedsuikerstrips en insuline-infusiepompjes bij de behandeling van diabetes mellitus; (2) de invloed van een verbetering van de diabetesregulatie op het verloop van de nefro-, neuro- en retinopathie en (3) de

  11. AdS sub 3 gravity and conformal field theories

    CERN Document Server

    Behrndt, K; Gaida, I

    1999-01-01

    We present a detailed analysis of AdS sub 3 gravity, the BTZ black hole and the associated conformal field theories (CFTs). In particular we focus on the non-extreme six-dimensional string solution with background metric AdS sub 3 x S sup 3 near the horizon. In addition we introduce momentum modes along the string, corresponding to a BTZ black hole, and a Taub-NUT soliton in the transverse Euclidean space. We show that the AdS sub 3 space-time of this configuration has the spatial geometry of an annulus with a Liouville model at the outer boundary and a two-dimensional black hole at the inner boundary. These CFTs provide the dynamical degrees of freedom of the three-dimensional effective model and, together with the CFT corresponding to S sup 3 , provide a statistical interpretation of the corresponding Bekenstein-Hawking entropy. We test the proposed exact black hole entropy, which should hold to all orders in alpha', by an independent field theoretical analysis including higher-order curvature corrections. ...

  12. SUSY properties of warped AdS$_3$

    CERN Document Server

    Jeong, Jaehoon; Yoshida, Kentaroh

    2014-01-01

    We examine supersymmetric properties of null-warped AdS$_3$, or alternatively Schrodinger geometries, dual to putative warped CFTs in two dimensions. We classify super Schrodinger subalgebras of the superalgebra psu(1, 1$|$2) $\\oplus$ psu(1, 1$|$2) , corresponding to the superconformal algebra of the AdS$_3 \\times$ S$^3$ geometry. We comment on geometric realisations and provide a string theory description with enhanced supersymmetry in terms of intersecting D3-branes. For type IIB supergravity solutions based on T$^{1,1}$, we consider the relationship between five-dimensional Schrodinger solutions and their three-dimensional null-warped counterparts, corresponding to R symmetry twists. Finally, we study a family of null-warped AdS$_3$ solutions in a setting where there is an ambiguity over the R symmetry and confirm that, for examples admitting a KK reduction to three dimensions, the minimisation of a real superpotential of the three-dimensional gauged supergravity captures the central charge and R symmetry.

  13. AdS Field Theory from Conformal Field Theory

    CERN Document Server

    Fitzpatrick, A Liam

    2012-01-01

    We provide necessary and sufficient conditions for a Conformal Field Theory to have a description in terms of a perturbative Effective Field Theory in AdS. The first two conditions are well-known: the existence of a perturbative `1/N' expansion and an approximate Fock space of states generated by a finite number of low-dimension operators. We add a third condition, that the Mellin amplitudes of the CFT correlators must be well-approximated by functions that are bounded by a polynomial at infinity in Mellin space, or in other words, that the Mellin amplitudes have an effective theory-type expansion. We explain the relationship between our conditions and unitarity, and provide an analogy with scattering amplitudes that becomes exact in the flat space limit of AdS. The analysis also yields a simple connection between conformal blocks and AdS diagrams, providing a new calculational tool very much in the spirit of the S-Matrix program. We also begin to explore the potential pathologies associated with higher spin ...

  14. N=2 AdS supergravity and supercurrents

    CERN Document Server

    Butter, Daniel

    2011-01-01

    We consider the minimal off-shell formulation for four-dimensional N=2 supergravity with a cosmological term, in which the second compensator is an improved tensor multiplet. We use it to derive a linearized supergravity action (and its dual versions) around the anti-de Sitter (AdS) background in terms of three N=2 off-shell multiplets: an unconstrained scalar superfield, vector and tensor multiplets. This allows us to deduce the structure of the supercurrent multiplet associated with those supersymmetric theories which naturally couple to the supergravity formulation chosen, with or without a cosmological term. Finally, our linearized N=2 AdS supergravity action is reduced to N=1 superspace. The result is a sum of two N=1 linearized actions describing (i) old minimal supergravity; and (ii) an off-shell massless gravitino multiplet. We also derive dual formulations for the massless N=1 gravitino multiplet in AdS. As a by-product of our consideration, we derive the consistent supergravity extension of the N=1 ...

  15. Correction of Diabetic Hyperglycemia and Amelioration of Metabolic Anomalies by Minicircle DNA Mediated Glucose-Dependent Hepatic Insulin Production.

    Directory of Open Access Journals (Sweden)

    Tausif Alam

    Full Text Available Type 1 diabetes mellitus (T1DM is caused by immune destruction of insulin-producing pancreatic β-cells. Commonly used insulin injection therapy does not provide a dynamic blood glucose control to prevent long-term systemic T1DM-associated damages. Donor shortage and the limited long-term success of islet transplants have stimulated the development of novel therapies for T1DM. Gene therapy-based glucose-regulated hepatic insulin production is a promising strategy to treat T1DM. We have developed gene constructs which cause glucose-concentration-dependent human insulin production in liver cells. A novel set of human insulin expression constructs containing a combination of elements to improve gene transcription, mRNA processing, and translation efficiency were generated as minicircle DNA preparations that lack bacterial and viral DNA. Hepatocytes transduced with the new constructs, ex vivo, produced large amounts of glucose-inducible human insulin. In vivo, insulin minicircle DNA (TA1m treated streptozotocin (STZ-diabetic rats demonstrated euglycemia when fasted or fed, ad libitum. Weight loss due to uncontrolled hyperglycemia was reversed in insulin gene treated diabetic rats to normal rate of weight gain, lasting ∼1 month. Intraperitoneal glucose tolerance test (IPGT demonstrated in vivo glucose-responsive changes in insulin levels to correct hyperglycemia within 45 minutes. A single TA1m treatment raised serum albumin levels in diabetic rats to normal and significantly reduced hypertriglyceridemia and hypercholesterolemia. Elevated serum levels of aspartate transaminase, alanine aminotransferase, and alkaline phosphatase were restored to normal or greatly reduced in treated rats, indicating normalization of liver function. Non-viral insulin minicircle DNA-based TA1m mediated glucose-dependent insulin production in liver may represent a safe and promising approach to treat T1DM.

  16. Increased skeletal muscle capillarization enhances insulin sensitivity

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Laub, Lasse; Vedel, Kenneth;

    2014-01-01

    Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. We therefore investigated whether increased skeletal muscle capillarization increases insulin sensitivity......-body insulin sensitivity increased by ~24% and insulin-stimulated skeletal muscle 2-deoxy-[(3)H]-Glucose disposal increased by ~30% concomitant with a ~20% increase in skeletal muscle capillarization. Adipose tissue insulin sensitivity was not affected by the treatment. Insulin-stimulated muscle glucose uptake...... the rats on any other parameters measured. We conclude that an increase in skeletal muscle capillarization is associated with increased insulin sensitivity. These data point towards the importance of increasing skeletal muscle capillarization for prevention or treatment of type 2 diabetes....

  17. Leptin therapy, insulin sensitivity, and glucose homeostasis

    Directory of Open Access Journals (Sweden)

    Gilberto Paz-Filho

    2012-01-01

    Full Text Available Glucose homeostasis is closely regulated not only by insulin, but also by leptin. Both hormones act centrally, regulating food intake and adiposity in humans. Leptin has several effects on the glucose-insulin homeostasis, some of which are independent of body weight and adiposity. Those effects of leptin are determined centrally in the hypothalamus and peripherally in the pancreas, muscles and liver. Leptin has beneficial effects on the glucose-insulin metabolism, by decreasing glycemia, insulinemia and insulin resistance. The understanding of the effects of leptin on the glucose-insulin homeostasis will lead to the development of leptin-based therapies against diabetes and other insulin resistance syndromes. In these review, we summarize the interactions between leptin and insulin, and their effects on the glucose metabolism.

  18. [Insulin-induced lipohypertrophy treated by liposuction].

    Science.gov (United States)

    Brun, A; Comparin, J-P; Voulliaume, D; Chekaroua, K; Foyatier, J-L; Perrot, P

    2007-06-01

    The incidence of insulin-dependent diabetes mellitus increase permanently, with early diagnosis. Insulin is the treatment of this pathology. Insulin therapy is associated with complication such as lipodystrophies at injection sites leading functional and aesthetics disorders (pain, reduction of treatment efficiency, haematomas and oedemas). Our report two cases to illustrate the effectiveness of the suction-assisted lipectomy (SAL) on these lipodystrophies. We present two cases of insulin dependent diabetics patients with lipodystrophies of thighs, abdomen, and shoulders treated by SAL. The various analyzed parameters are: aesthetic aspect, efficiency of insulin treatment, ease injection, and pain reduction. We observe a significant reduction of insulin dose necessary to obtain a normoglycemia half time. This treatment allow a better control of pain, control of haematomas and oedemas at the injection sites and an aesthetic improvement. The lipoaspiration is thus a simple and effective treatment of lipodystrophies due to insulin.

  19. Insulin-responsiveness of tumor growth.

    Science.gov (United States)

    Chantelau, Ernst

    2009-05-01

    In October 2008, the 2nd International Insulin & Cancer Workshop convened roughly 30 researchers from eight countries in Düsseldorf/Germany. At this meeting, which was industry-independent like the preceding one in 2007, the following issues were discussed a) association between certain cancers and endogenous insulin production in humans, b) growth-promoting effects of insulin in animal experiments, c) mitogenic and anti-apoptotic activity of pharmaceutic insulin and insulin analogues in in vitro experiments, d) potential mechanisms of insulin action on cell growth, mediated by IGF-1 receptor and insulin receptor signaling, and e) IGF-1 receptor targeting for inhibition of tumor growth. It was concluded that further research is necessary to elucidate the clinical effects of these observations, and their potential for human neoplastic disease and treatment.

  20. Pathogenesis of Insulin Resistance in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Muhammad A. Abdul-Ghani

    2010-01-01

    Full Text Available Insulin resistance in skeletal muscle is manifested by decreased insulin-stimulated glucose uptake and results from impaired insulin signaling and multiple post-receptor intracellular defects including impaired glucose transport, glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis. Insulin resistance is a core defect in type 2 diabetes, it is also associated with obesity and the metabolic syndrome. Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle. Recent studies have reported a mitochondrial defect in oxidative phosphorylation in skeletal muscle in variety of insulin resistant states. In this review, we summarize the cellular and molecular defects that contribute to the development of insulin resistance in skeletal muscle.