Weight Loss Improves β-Cell Function in People with Severe Obesity and Impaired Fasting Glucose: A Window of Opportunity

BACKGROUND: In people with obesity, beta-cell function may adapt to insulin resistance. We describe beta-cell function in people with severe obesity and normal fasting glucose (NFG), impaired fasting glucose (IFG), and type 2 diabetes (T2DM), as assessed before, 3 to 6 months after, and 2 years after medical weight loss to describe its effects on insulin sensitivity, insulin secretion, and beta-cell function. METHODS: Fifty-eight participants with body mass index (BMI) >/= 35 kg/m2 (14 with NFG, 24 with IFG, and 20 with T2DM) and 13 normal weight participants with NFG underwent mixed meal tolerance tests to estimate insulin sensitivity (S[I]), insulin secretion (Phi), and beta-cell function assessed as model-based Phi adjusted for S(I). All 58 obese participants were restudied at 3 to 6 months and 27 were restudied at 2 years. RESULTS: At 3 to 6 months, after a 20-kg weight loss and a decrease in BMI of 6 kg/m2, S(I) improved in all obese participants, Phi decreased in obese participants with NFG and IFG and tended to decrease in obese participants with T2DM, and beta-cell function improved in obese participants with NFG and tended to improve in obese participants with IFG. At 2 years, beta-cell function deteriorated in participants with NFG and T2DM but remained significantly better in participants with IFG compared to baseline. CONCLUSIONS: Short-term weight loss improves beta-cell function in participants with NFG and IFG, but beta-cell function tends to deteriorate over 2 years. In participants with IFG, weight loss improves longer-term beta-cell function relative to baseline and likely relative to no intervention, suggesting that obese people with IFG are a subpopulation whose beta-cell function is most likely to benefit from weight loss.