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Predictors of sustained drug-free diabetes remission over 48?weeks following short-term intensive insulin therapy in early type 2 diabetes.

ABSTRACT: In early type 2 diabetes (T2DM), short-term intensive insulin therapy (IIT) for 2-4?weeks can decrease insulin resistance, reduce glucagonemia, improve ?-cell function, and even induce a remission of diabetes that can last up to 1?year in some patients. However, little is known about the predictors of such a sustained remission.We evaluated data from the placebo arm of a double-blind randomized controlled trial in which patients with early T2DM (?7?years duration) underwent 4?weeks of IIT (basal detemir, bolus aspart), followed by placebo therapy for 48?weeks (n=25). Participants underwent an oral glucose tolerance test every 12?weeks, enabling serial assessment of insulin sensitivity, ?-cell response, and ?-cell function. Diabetes remission was defined as A1c<6.5% on no medication for T2DM.At 48?weeks post-IIT, 56% of the participants remained in remission. Comparison of remitters to non-remitters revealed no differences in waist, body mass index, insulin sensitivity (Matsuda index), or glucagon profile, either at baseline or over 48?weeks. Compared to non-remitters, the remission group had lower baseline A1c (p=0.006) and better baseline ?-cell function (Insulin Secretion-Sensitivity Index-2) (p=0.01) that was then sustained across 48?weeks post-IIT (p=0.006). On logistic regression analyses, however, shorter duration of diabetes supplanted baseline A1c (p=0.24) and ?-cell function (p=0.19) as an independent predictor of remission (p=0.04). In particular, diabetes duration <2?years predicted persistence of remission (p=0.006).The key determinant of the likelihood of inducing sustained drug-free diabetes remission with short-term IIT is early intervention, particularly within the first 2?years after diagnosis.ClinicalTrials.Gov NCT01270789; Post-results.

SUBMITTER: Kramer CK

PROVIDER: S-EPMC4985916 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Predictors of sustained drug-free diabetes remission over 48 weeks following short-term intensive insulin therapy in early type 2 diabetes.

Kramer Caroline K CK Zinman Bernard B Choi Haysook H Retnakaran Ravi R

BMJ open diabetes research & care 20160801 1

<h4>Objective</h4>In early type 2 diabetes (T2DM), short-term intensive insulin therapy (IIT) for 2-4 weeks can decrease insulin resistance, reduce glucagonemia, improve β-cell function, and even induce a remission of diabetes that can last up to 1 year in some patients. However, little is known about the predictors of such a sustained remission.<h4>Methods</h4>We evaluated data from the placebo arm of a double-blind randomized controlled trial in which patients with early T2DM (≤7 years duratio ...[more]

PMID: 27547422

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Project description:BackgroundThe Uganda Ministry of Health issued restrictive guidelines on the use of dolutegravir (DTG) in persons stratified to have a heightened risk of diabetes mellitus. This followed multiple reports of persons with HIV (PWH) presenting with accelerated hyperglycemia after a few weeks to months of exposure to DTG. Having demonstrated a low incidence of diabetes mellitus and improving blood glucose trajectories in a cohort of ART naïve Ugandan PWH on DTG, we sought to determine whether the observed improvement in blood glucose did not mask background compensated insulin resistance.MethodsIn this analysis, 63 patients underwent serial oral glucose tolerance tests over 48 weeks. Using fasting serum insulin and glucose, we calculated insulin resistance and pancreatic beta cell function by homeostatic modelling (HOMA IR and HOMA%β respectively). Absolute mean changes between baseline and post-baseline blood glucose, pancreatic beta cell function and insulin resistance were computed by subtracting each post-baseline value from the baseline value and compared using student t-test. Multiple linear regression models were used to determine the factors associated with changes in pancreatic beta cell function and insulin resistance.ResultsOf the 63 participants, 37 (58%) were female. Median age was 31 (IQR: 28-37). Despite a trend towards an initial increase in both HOMA IR and HOMA%β at 12 weeks followed by a decline through 36 weeks to 48 weeks, the HOMA IR and HOMA%β at 48 weeks were not significantly different from baseline i.e. (difference in mean HOMA IR from baseline: 0.14, 95%CI: -0.46, 0.733, p = 0.648) and (difference in mean HOMA %β from baseline: 6.7, 95%CI: -13.4, 26.8, p = 0.506) respectively.ConclusionWe demonstrated insignificant changes in both insulin resistance and pancreatic beta cell function in clinically stable young adult Ugandan PWH on dolutegravir for 48 weeks. We add to the body of evidence demonstrating glucose metabolic safety of dolutegravir in ART naïve patients. Ugandan guidelines should reconsider restricting DTG initiation in ART naive adults at high risk for diabetes.

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Predictors of sustained drug-free diabetes remission over 48?weeks following short-term intensive insulin therapy in early type 2 diabetes.

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Predictors of sustained drug-free diabetes remission over 48 weeks following short-term intensive insulin therapy in early type 2 diabetes.

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