Erythrocyte membrane acetylcholinesterase in type 1 (insulin-dependent) diabetes mellitus.
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ABSTRACT:
SUBMITTER: Suhail M
PROVIDER: S-EPMC1138601 | biostudies-other | 1989 May
REPOSITORIES: biostudies-other
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Project description:BackgroundChronically elevated blood glucose levels are associated with significant morbidity and mortality. Many diabetes patients will eventually require insulin treatment to maintain good glycaemic control. There are still uncertainties about the optimal insulin treatment regimens for type 2 diabetes, but the long-acting insulin analogues seem beneficial. Several reviews have compared either insulin detemir or insulin glargine to NPH insulin, but research directly comparing both insulin analogues is limited.ObjectivesTo assess the effects of insulin detemir and insulin glargine compared with each other in the treatment of type 2 diabetes mellitus.Search strategyWe searched MEDLINE, EMBASE, The Cochrane Library, online registries of ongoing trials and abstract books. Date of last search was January 2011.Selection criteriaAll randomised controlled trials comparing insulin detemir with insulin glargine with a duration of 12 weeks or longer were included.Data collection and analysisTwo authors independently selected the studies and extracted the data. Pooling of studies by means of random-effects meta-analysis was performed.Main resultsThis review examined four trials lasting 24 to 52 weeks involving 2250 people randomised to either insulin detemir or glargine. Overall, risk of bias of the evaluated studies was high. Insulin glargine was dosed once-daily in the evening. Insulin detemir was initiated once-daily in the evening with the option of an additional dose in the morning in three studies and initiated twice-daily in one study. Of randomised patients 13.6% to 57.2% were injecting insulin detemir twice-daily at the end of trial.Glycaemic control, measured by glycosylated haemoglobin A1c (HbA1c) and HbA1c equal to or less than 7% with or without hypoglycaemia, did not differ statistically significantly between treatment groups.The results showed no significant differences in overall, nocturnal and severe hypoglycaemia between treatment groups.Insulin detemir was associated with less weight gain. Treatment with insulin glargine resulted in a lower daily basal insulin dose and a lower number of injection site reactions.There was no significant difference in the variability of FPG or glucose values in 24-hour profiles between treatment groups. It was not possible to draw conclusions on quality of life, costs or mortality. Only one trial reported results on health-related quality of life and showed no significant differences between treatment groups.Authors' conclusionsOur analyses suggest that there is no clinically relevant difference in efficacy or safety between insulin detemir and insulin glargine for targeting hyperglycaemia. However, to achieve the same glycaemic control insulin detemir was often injected twice-daily in a higher dose but with less weight gain, while insulin glargine was injected once-daily, with somewhat fewer injection site reactions.
| S-EPMC6486036 | biostudies-literature
Project description:Background: The prevalence of type 2 diabetes has increased dramatically in recent decades. Increasing brown adipose tissue (BAT) mass and activity has recently emerged as an interesting approach to not only increase energy expenditure, but also improve glucose homeostasis. BAT can be recruited by prolonged cold exposure in lean, healthy humans. Here, we tested whether cold acclimation could have therapeutic value for patients with type 2 diabetes by improving insulin sensitivity. Methods: Eight type 2 diabetic patients (age 59.3±5.8 years, BMI 29.8±3.2 kg/m2) followed a cold acclimation protocol, consisting of intermittent cold exposure (6 hours/day, 14-14.5 °C) for 12 consecutive days. Before and after cold acclimation, cold-induced BAT activity was assessed by [18F]FDG-PET/CT scanning, insulin sensitivity at thermoneutrality by a hyperinsulinemic-euglycemic clamp, and muscle and WAT biopsies were taken. Results: Cold-induced BAT activity was low, but increased in all patients upon cold acclimation (SUV from 0.40±0.29 to 0.63±0.78, p<0.05). Interestingly, insulin sensitivity showed a very pronounced 40% increase upon cold acclimation (glucose rate of disappearance from 14.9±4.1 to 20.5±6.9 μmol kg-1 min-1, p<0.05). A 40% increase in insulin sensitivity cannot be explained by BAT glucose uptake, in fact basal skeletal muscle GLUT4 content and translocation was markedly increased after cold acclimation, without effects on insulin signaling or AMPk activation. Conclusions: Regular mild cold exposure has marked effects on insulin sensitivity, which are accompanied by small increases in BAT activity and more pronounced effects on skeletal muscle. These data suggest a novel therapeutic option for the treatment of type 2 diabetes.
2015-07-05 | GSE67297 | GEO
Project description:Background: The prevalence of type 2 diabetes has increased dramatically in recent decades. Increasing brown adipose tissue (BAT) mass and activity has recently emerged as an interesting approach to not only increase energy expenditure, but also improve glucose homeostasis. BAT can be recruited by prolonged cold exposure in lean, healthy humans. Here, we tested whether cold acclimation could have therapeutic value for patients with type 2 diabetes by improving insulin sensitivity. Methods: Eight type 2 diabetic patients (age 59.3±5.8 years, BMI 29.8±3.2 kg/m2) followed a cold acclimation protocol, consisting of intermittent cold exposure (6 hours/day, 14-14.5 °C) for 12 consecutive days. Before and after cold acclimation, cold-induced BAT activity was assessed by [18F]FDG-PET/CT scanning, insulin sensitivity at thermoneutrality by a hyperinsulinemic-euglycemic clamp, and muscle and WAT biopsies were taken. Results: Cold-induced BAT activity was low, but increased in all patients upon cold acclimation (SUV from 0.40±0.29 to 0.63±0.78, p<0.05). Interestingly, insulin sensitivity showed a very pronounced 40% increase upon cold acclimation (glucose rate of disappearance from 14.9±4.1 to 20.5±6.9 μmol kg-1 min-1, p<0.05). A 40% increase in insulin sensitivity cannot be explained by BAT glucose uptake, in fact basal skeletal muscle GLUT4 content and translocation was markedly increased after cold acclimation, without effects on insulin signaling or AMPk activation. Conclusions: Regular mild cold exposure has marked effects on insulin sensitivity, which are accompanied by small increases in BAT activity and more pronounced effects on skeletal muscle. These data suggest a novel therapeutic option for the treatment of type 2 diabetes. Microarray analysis was performed on abdominal subcutaneous white adipose tissue samples from human type 2 diabetic patients before, and after 10 days of cold acclimation. A total of 14 samples, from 7 subjects, were used for the microarray analysis.
2015-07-05 | E-GEOD-67297 | biostudies-arrayexpress
Project description:The prevalence of microalbuminuria was assessed in 50 patients of non-insulin dependent diabetes mellitus. The mean age of patients was 52.1 ± 11.6 years and the duration of diabetes was 8.3 ± 6.8 years. Twenty (40%) patients had microalbuminuria. Microalbuminuria was more common in patients with a longer duration of diabetes (more than 5 years), a poor glycaemic control, and higher systolic blood pressure.
| S-EPMC5530379 | biostudies-other
Project description:Abstract This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of ultra‐long acting insulin compared with long‐acting insulin in patients with T1DM.
| S-EPMC6513582 | biostudies-literature
Project description:Insulin-degrading enzyme (IDE) selectively degrades peptides, such as insulin, amylin, and amyloid β (Aβ) that form toxic aggregates, to maintain proteostasis. IDE defects are linked to the development of type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD). Structural and biochemical analyses revealed the molecular basis for IDE-mediated destruction of amyloidogenic peptides and this information has been exploited to develop promising inhibitors of IDE to improve glucose homeostasis. However, the inhibition of IDE can also lead to glucose intolerance. In this review, I focus on recent advances regarding our understanding of the structure and function of IDE and the discovery of IDE inhibitors, as well as challenges in developing IDE-based therapy for human diseases, particularly T2DM.
| S-EPMC4698235 | biostudies-literature
Project description:OBJECTIVE:To review published clinical studies on the efficacy and safety of new insulin glargine 300 units/mL (Gla-300), a new long-acting insulin analog, for the treatment of type 1 and type 2 diabetes mellitus (T1DM, T2DM). MATERIALS AND METHODS:Data sources comprised primary research articles on Gla-300, including pharmacodynamic, pharmacokinetic, and clinical studies. RESULTS:In pharmacodynamic and pharmacokinetic studies, Gla-300 showed a flatter time-action profile and longer duration of action than Gla-100. Noninferiority of Gla-300 versus Gla-100 for lowering of glycated hemoglobin was demonstrated in Phase III clinical studies covering a range of T1DM and T2DM patient populations. Over 6-12 months of follow-up, Gla-300 consistently showed comparable glycemic efficacy with less hypoglycemia vs Gla-100, even during the first 8 weeks of treatment. Although titrated insulin doses were 11%-17% higher with Gla-300 vs Gla-100, changes in body weight were similar or favored Gla-300. CONCLUSION:Clinical studies provide evidence that the pharmacodynamic and pharmacokinetic properties of Gla-300 may translate into clinical benefits in both T1DM and T2DM. Gla-300 may provide a new option for people initiating basal insulin, those requiring higher basal insulin doses, those with T1DM, and those who may be at increased risk for hypoglycemia, such as people with chronic kidney disease, the elderly, and those with cardiovascular comorbidities.
| S-EPMC5501629 | biostudies-literature
Project description:IntroductionTo estimate the cost-effectiveness of insulin degludec (IDeg) versus insulin glargine U100 (IGlar U100) and new-to-market basal insulin analogues in patients with diabetes in order to aid decision-making in a complex basal insulin market.MethodsA simple, short-term model was used to evaluate the costs and effects of treatment with IDeg versus IGlar U100 over a 12-month period in patients with type 1 (T1DM) and type 2 diabetes (T2DM) from the perspective of the UK National Health Service. New-to-market basal insulin analogues were evaluated in scenario analyses.ResultsIDeg is dominant (more effective and less costly) versus IGlar U100 in patients with T1DM and patients with T2DM on a basal-only therapy regimen (T2DMBOT), and is cost-effective versus IGlar U100 in patients with T2DM on a basal-bolus regimen (T2DMB/B). In T1DM, lower costs are primarily driven by lower insulin costs, as a result of a lower daily dose of IDeg. In T2DMBOT, lower overall costs with IDeg are driven by lower costs of severe hypoglycaemic events due to the significant reduction in number of events with IDeg versus IGlar U100. Improvements in clinical outcomes in all three patient groups are a result of the reduced incidence of hypoglycaemic events. Sensitivity analyses demonstrate that the results are robust. Scenario analyses versus two new-to-market basal insulin analogues indicate that in patients with T1DM and T2DMBOT, IDeg is likely to be highly cost-effective versus IGlar biosimilar Abasaglar® and dominant versus IGlar U300 (Toujeo®). In T2DMB/B, IDeg is likely to be cost-effective versus both comparators, with incremental cost-effectiveness ratios (ICERs) below the accepted threshold.ConclusionIDeg is a cost-effective alternative to IGlar U100 for patients with diabetes in the UK, and it also likely to be cost-effective versus two new-to-market basal insulin analogues.
| S-EPMC5380498 | biostudies-literature
Project description:BackgroundLipohypertrophy (LH) of subcutaneous tissue is an insulin-induced complication occurring in patients with diabetes. We aimed to define the prevalence of LH and identify its risk factors in type 1 diabetes (T1DM) patients treated with continuous subcutaneous insulin infusion (CSII).Materials and methodsThe study included 79 consecutive CSII-treated T1DM patients. The diagnose of LH was based on ultrasonography (US) as a reference method, physical examination was also performed. Clinical characteristics were available from the medical records.ResultsThe median age of patients was 28 years (interquartile range [IQR], 24-30.5) with a body mass index (BMI) of 24.5 ± 3.5 kg/m2, HbA1c 7.1% (IQR, 6.7-8.1), T1DM duration 15 (9-20) years, and CSII use duration of 8 year (IQR, 5-11). LH was detected by US in 75 (94.9%) patients. This value was much higher than this obtained by visual assessment (n = 39, 49.4%) or palpation (n = 59, 74.7%). In univariate analyses, the following risk factors for occurrence of 5 and more LH lesions were identified: the ratio of insulin dose to body mass exceeding 0.7 IU/kg (OR, 3.69; 95% CI, 1.43-10.01) and the total daily insulin dose (OR, 1.05; 95% CI, 1.02-1.09). A higher dose of insulin per kg remained a significant risk factor of LH amount in multivariate analysis.ConclusionThis selected T1DM cohort treated with CSII had a very high prevalence of LH. US assessment should be considered as a reference method for LH screening in T1DM patients. The identified risk factors for the number of LH lesions were related to insulin dosing.
| S-EPMC8803446 | biostudies-literature
Project description:Diabetes Mellitus Type 1 miRnome
| PRJEB51173 | ENA