In adults with obesity, fasting hyperinsulinaemia is frequently observed and has been linked to diabetes progression, but the determinants of this response remain incompletely defined. In Diabetologia, findings are reported from an analysis of the European Group for the Study of Insulin Resistance-Relationship between Insulin Sensitivity and Cardiovascular Disease cohort (EGIR-RISC) examining how adiposity relates to insulin secretion and beta cell function.

The study analysed data from 1,250 healthy participants aged 30 to 60 years, including 547 men and 703 women, followed for 3.5 years. Assessments included body composition, insulin secretion, beta cell function modelling from an oral glucose tolerance test (OGTT), and clamp-derived insulin sensitivity. Endogenous glucose production (EGP) was measured in a subset of 368 participants. Multivariable regression models evaluated the associations between adiposity indices and fasting insulin secretion.

Across the full spectrum of body mass index (BMI) and waist-to-hip ratio (WHR) values, fasting insulin secretion increased in a continuous manner and was more pronounced in men. Among adiposity measures, fat mass (standardised beta coefficient, 0.27; p<0.0001) and waist circumference (standardised beta coefficient, 0.21; p<0.0001) showed the strongest associations. Insulin secretion increased 2.4-fold across BMI deciles and was linked to hyperglycaemia and an increase in insulin secretion rate at 5 mmol/L glucose.

Weight gain during follow-up was associated with increases in fasting insulin secretion and fasting glucose, whereas weight loss was associated with reductions in both. Subset analyses showed a rightward shift in the dose-response curve for EGP across fat mass quintiles, despite preserved hepatic insulin response. These findings indicate that body mass–related insulin hypersecretion is continuous, sex-dependent, and only partly explained by conventional metabolic factors.