Relationship of Insulin Dynamics to Body Composition and Resting Energy Expenditure following Weight Loss

OBJECTIVE: To examine associations of baseline insulin dynamics with changes in body composition and resting energy expenditure (REE) following weight loss. METHODS: Twenty-one participants with overweight or obesity achieved 10-15% weight loss and then received 3 weight-loss maintenance diets (high-carbohydrate, moderate-carbohydrate, low-carbohydrate) in random order, each for 4 weeks. Body composition was measured at baseline and after weight loss. Insulin 30 minutes after glucose consumption (insulin-30; insulin response), C-peptide deconvolution analysis, HOMA, hepatic insulin sensitivity (IS), and REE were assessed at baseline and after each maintenance diet. RESULTS: Insulin-30, but not maximal insulin secretion, hepatic IS or HOMA, predicted changes in fat mass (standardized β=0.385, 1.7 kg difference between 10(th)-90(th) centile of insulin-30, P=0.04) after weight loss. Insulin-30 (β=−0.341, −312 kcal/d, P=0.008), maximal insulin secretion (β=−0.216, −95 kcal/d, P=0.0002), HOMA (β=−0.394,−350 kcal/d, P=0.002) and hepatic IS (β=0.217, 225 kcal/d, P=0.0003) predicted change in REE during weight-loss maintenance, independent of changes in body composition. The inverse relationship between insulin-30 and REE was substantially attenuated when the low-carbohydrate diet was consumed first. CONCLUSIONS: These findings distinguish a novel phenotype, characterized by high insulin response, at risk for weight regain, and identify a dietary approach to ameliorate this risk.