Effects of a hypercaloric diet on β-cell responsivity in lean healthy men

Objective Insulin resistance and hyperinsulinaemia precede the onset of obesity-induced DM2. The early adaptation of the beta-cell during the initial phase of overfeeding and weight gain has only been partly elucidated. We studied the early changes in insulin clearance and beta-cell responsivity during a positive and negative energy balance in lean healthy men. Design We studied in nine healthy lean men [age, 37 (2743) years; BMI, 23.6 (20.625.6) kg/m2] insulin sensitivity, insulin clearance, insulin secretion and static and dynamic beta-cell responsivity at baseline and after the hypercaloric and subsequent hypocaloric diet. Results Participants gained 7 [5.17.6]% of their initial body weight on the hypercaloric diet. Compared to baseline, insulin sensitivity and insulin clearance decreased, while glucose-stimulated insulin secretion was higher. The GLP-1 response to oral glucose did not change. The dynamic beta-cell responsivity index increased but the basal and static responsivity indexes did not change. Total and static disposition indexes (DIs) in the hypercaloric state showed a trend towards a decrease. During the hypocaloric diet, insulin sensitivity, glucose-stimulated insulin secretion and insulin clearance returned to baseline. The responsivity and the DIs were not different in the hypocaloric phase compared to baseline. Conclusion A positive energy balance resulting in weight gain in lean men induces hyperinsulinaemia, which is explained by a combined effect on insulin clearance and insulin secretion. Increased insulin secretion was related to insulin resistance-induced higher glucose concentrations but also to increased dynamic beta-cell responsivity. Glucose sensitivity of the beta-cell did not change. These early adaptations are completely reversible during a negative energy balance after loss of the gained weight.