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


Correspondence: Myrte Brands, Department of Endocrinology and Metabolism, Academic Medical Center, F5-162, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. Tel.: +31 20 5666071; Fax: +31 20 6917682; E-mail:



Insulin resistance and hyperinsulinaemia precede the onset of obesity-induced DM2. The early adaptation of the β-cell during the initial phase of overfeeding and weight gain has only been partly elucidated. We studied the early changes in insulin clearance and β-cell responsivity during a positive and negative energy balance in lean healthy men.


We studied in nine healthy lean men [age, 37 (27–43) years; BMI, 23·6 (20·6–25·6) kg/m2] insulin sensitivity, insulin clearance, insulin secretion and static and dynamic β-cell responsivity at baseline and after the hypercaloric and subsequent hypocaloric diet.


Participants gained 7 [5·1–7·6]% 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 β-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.


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 β-cell responsivity. Glucose sensitivity of the β-cell did not change. These early adaptations are completely reversible during a negative energy balance after loss of the gained weight.