OBJECTIVE: Obesity and aging increase the risk of type 2 diabetes (T2D). We evaluated whether weight loss therapy improves pancreatic endocrine function and insulin sensitivity in obese older adults. METHODS AND PROCEDURES: Twenty-four obese (BMI 38 +/- 2 kg/m2) older (age 70 +/- 2 years) adults completed a 6-month randomized, controlled trial. Participants were randomized to diet and exercise (treatment group) or no therapy (control group). beta-Cell function (assessed using the c-peptide minimal model), alpha-cell function (assessed by the glucagon response to an oral glucose load), insulin sensitivity (assessed using the glucose minimal model), and insulin clearance rate were evaluated using a 5-h modified oral glucose tolerance test. RESULTS: Body weight decreased in the treatment group, but did not change in the control group (-9 +/- 1% versus 0 +/- 1%; p < 0.001). Insulin sensitivity doubled in the treatment group and did not change in the control group (116 +/- 49% versus -11 +/- 13%; p < 0.05). Even though indices of beta-cell responsivity to glucose did not change (p > 0.05), the disposition index (DI), which adjusts beta-cell insulin response to changes in insulin sensitivity, improved in the treatment group compared with the control group (100 +/- 47% versus -22 +/- 9%; p < 0.05). The glucagon response decreased in the treatment but not in the control group (-5 +/- 2% versus 4 +/- 4%; p < 0.05). Insulin secretion rate did not change (p > 0.05), but insulin clearance rate increased (51 +/- 25%; p < 0.05), resulting in lower plasma insulin concentrations. DISCUSSION: Weight loss therapy concomitantly improves beta-cell function, lowers plasma glucagon concentrations, and improves insulin action in obese older adults. These metabolic effects are likely to reduce the risk of developing T2D in this population.

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