PSUN137 Suppression of endogenous insulin secretion during euglycemic hyperinsulinemia – effects of obesity

Hyperinsulinemia is strongly linked with excessive body fat. However, with the exception of plasma glucose concentrations, the other factors regulating insulin secretion are under-studied. We examined the effects of hyperinsulinemia itself on beta cell insulin secretion during exogenous insulin and glucose infusions in adults with insulin-resistant upper body (UBO), insulin-sensitive lower body obesity (LBO) and non-obese controls. Data from the euglycemic, hyperinsulinemic clamp studies of 33 volunteers (9 controls, 5 LBO, 19 UBO) was analyzed; basal and insulin-suppressed (residual) insulin secretion rates were determined using deconvolution of C-peptide concentrations. Obesity phenotype was determined using waist: hip ratio and body composition was assessed with dual-energy X-ray absorptiometry and abdominal computed tomography. Plasma insulin concentrations were log transformed to achieve a normal distribution before statistical analysis. The plasma glucose concentration change during the clamp was 0.3 (SD: 3) mg/dl, and similar among groups (p=0.7). Median, achieved serum insulin concentrations was 66 (IQR: 45-105) mIU/mL, and greater in participants with obesity. Fasting insulin secretion rates were 0.093 (SD: 0.029), 0.158 (SD: 0.036), and 0.216 (0.078) nmol/min in controls, LBO and UBO, respectively (UBO p<0.001 vs. other groups). Insulin secretion was suppressed by 28% during hyperinsulinemia with no between group differences (p= 0.69). The ratios of insulin secretion rate (from C-peptide deconvolution) to serum insulin concentration (nmol/min per mIU/mL) was 0.058 (SD: 0.015) in controls, 0.090 (SD: 0.016) in LBO and 0.111 (SD: 0.039) in UBO (UBO vs. other groups P = 0.001). The ratio of insulin secretion rates to plasma insulin concentrations was correlated with BMI (r=0.69, P <0.001). We conclude that adults with obesity have greater residual insulin secretion during an exogenous insulin infusion and that this is related to upper body fat distribution. However, because the proportional suppression of endogenous insulin secretion is similar in these groups, this could indicate the primary abnormality is fasting insulin secretion. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.