Endocrine Abstracts

Background: Plasma insulin concentrations reflect the balance between insulin section and clearance. Reduced insulin clearance is a common feature of obesity and contributes to hyperinsulinemia, a cardiometabolic disease (CMD) risk factor. Although there are sex-related differences in CMD risk, it remains unclear if sex differences in fasting and postprandial insulin kinetics exist under physiological conditions.

Aim: To investigate whether there are sex differences in fasting and postprandial insulin kinetics and their relationship to CMD risk factors.

Methods: Following an overnight fast, 19 male (51 ± 5yr, 28.3 ± 3.7 kg/m²) and 20 female (53 ± 6yr, 26.3 ± 3.9 kg/m²) individuals underwent a 4h mixed-meal feeding study. Intrahepatic triglyceride content (IHTG%) was quantified by MRI/S. Plasma metabolites, pancreatic islet hormones, and the contribution of gluconeogenesis to fasting plasma glucose were assessed. Prehepatic insulin secretion and clearance mathematically modelled and CMD risk was approximated using plasma low-density-lipoprotein (LDL) cholesterol.

Results: Compared to age and BMI matched females, males had a greater (p<0.01) waist-hip ratio, IHTG%, HOMA-IR and fasting LDL-cholesterol. Despite this, males and females had similar postprandial increases in plasma insulin, which corresponded to similarly increased insulin secretion rate (ISR; males:142±68 pmol/min/m², females:126±75 pmol/min/m²) and decreased insulin clearance rate (ICR; males:1.26±0.46 L/min/m², females:1.42±0.63 L/min/m²). Fasting and postprandial glycaemia, and fasting glucose derived from gluconeogenesis did not differ between sexes. A stepwise linear regression model revealed sex was the only significant predictor for the variance in LDL-cholesterol (p=0.01; adj. R²=0.14) in our cohort. A partial correlation showed that when controlling for sex, time-averaged ICR and ISR were not correlated with LDl.

Conclusion: Although males display markers of increased insulin resistance compared to females, postprandial glycaemic control and insulin kinetics were comparable. Our findings suggest that differences in CMD risk in age- and BMI-matched males and females are not explained by postprandial insulin kinetics.