Dataset Information

Weight Loss, Lifestyle Intervention, and Metformin Affect Longitudinal Relationship of Insulin Secretion and Sensitivity.

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.

SUBMITTER: Vazquez Arreola E

PROVIDER: S-EPMC9923796 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Publications

Weight Loss, Lifestyle Intervention, and Metformin Affect Longitudinal Relationship of Insulin Secretion and Sensitivity.

Vazquez Arreola Elsa E Knowler William C WC Hanson Robert L RL

The Journal of clinical endocrinology and metabolism 20221101 11

<h4>Context</h4>Insulin secretion and sensitivity regulate glycemia, with inadequately compensated deficiencies leading to diabetes.<h4>Objective</h4>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.<h4>Methods</h4>Insulin secretion and sensi ...[more]

PMID: 36062951

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Project description:Dietary calorie restriction and exercise promote weight loss and may have additive effects for improving insulin sensitivity, independent of weight loss. It is not known if these effects are attributable to changes in circulating cytokines. We evaluated the hypothesis that modest, matched weight loss induced by calorie restriction and exercise have additive effects on circulating cytokines and these changes correlate with improvements in insulin sensitivity. Overweight and sedentary women and men (n = 52, 45-65 years) were randomized to undergo 7 % weight loss by using 3-6 months of calorie restriction, exercise, or a combination of both calorie restriction and exercise. Concentrations of cytokines and hormones were measured in fasting and oral glucose tolerance test blood samples. Insulin sensitivity was estimated based on oral glucose tolerance test for glucose and insulin. With all groups combined, fasting leptin (p < 0.0001) and high molecular weight adiponectin (p = 0.04) decreased and pentraxin-3 increased (p < 0.0001), in a manner that correlated with improvements in insulin sensitivity (all p ≤ 0.0002). These changes, combined with decreases in glucose-dependent insulinotropic polypeptide from the oral glucose tolerance test, explained 63 % of the variance (p < 0.0001) in insulin sensitivity improvements. Exercise and calorie restriction had additive effects on leptin, with a similar trend for high molecular weight adiponectin. Monocyte chemoattractant protein-1 and C-reactive protein concentrations did not change. Calorie restriction and exercise had opposite effects on soluble tumor necrosis factor receptor-1. Modest weight loss in overweight adults decreases serum leptin and high molecular weight adiponectin, and increases pentraxin-3 concentrations in a manner that correlates with increased insulin sensitivity. Exercise has additive effects to those induced by calorie restriction for reductions in leptin and possibly adiponectin. These changes may contribute to the additive effects of calorie restriction and exercise for improving insulin sensitivity.

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Dataset Information

Weight Loss, Lifestyle Intervention, and Metformin Affect Longitudinal Relationship of Insulin Secretion and Sensitivity.

Context

Objective

Methods

Results

Conclusion

Publications

Weight Loss, Lifestyle Intervention, and Metformin Affect Longitudinal Relationship of Insulin Secretion and Sensitivity.

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