Affiliation:
1. Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases , Phoenix, AZ 85014 , USA
Abstract
Abstract
Context
Insulin secretion and sensitivity regulate glycemia, with inadequately compensated deficiencies leading to diabetes.
Objective
We investigated effects of weight loss, an intensive lifestyle intervention (ILS), and metformin on the relationship between insulin secretion and sensitivity using repository data from 2931 participants in the Diabetes Prevention Program clinical trial in adults at high risk of developing type 2 diabetes.
Methods
Insulin secretion and sensitivity were estimated from insulin and glucose concentrations in fasting and 30-minute postload serum samples at baseline and 1, 2, and 3 years after randomization, during the active intervention phase. The nonlinear relationship of secretion and sensitivity was evaluated by standardized major axis regression to account for variability in both variables. Insulin secretory demand and compensatory insulin secretion were characterized by distances along and away from the regression line, respectively.
Results
ILS and metformin decreased secretory demand while increasing compensatory insulin secretion, with greater effects of ILS. Improvements were directly related to weight loss; decreased weight significantly reduced secretory demand (b=−0.144 SD; 95% CI (−0.162, −0.125)/5 kg loss) and increased compensatory insulin secretion (b = 0.287 SD, 95% CI (0.261, 0.314)/5 kg loss). In time-dependent hazard models, increasing compensatory insulin secretion (hazard ratio [HR] = 0.166 per baseline SD, 95% CI 0.133, 0.206) and weight loss (HR = 0.710 per 5 kg loss, 95% CI 0.613, 0.819) predicted lower diabetes risk.
Conclusion
Diabetes risk reduction was directly related to the amount of weight loss, an effect mediated by lowered insulin secretory demand (due to increased insulin sensitivity) coupled with improved compensatory insulin secretion.
Funder
NIDDK
National Institutes of Health
Subject
Biochemistry (medical),Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献