Poster Presentation 4th Metabolic Diseases; Breakthrough Discoveries in Diabetes & Obesity Meeting 2024

Mechanisms of hyperinsulinemia in healthy young adults with normal glucose tolerance (#110)

Vicky Kuriel 1 , Giang Dao 2 , Timothy Connor 2 , Greg M Kowalski 2 , Andrew C Betik 3 , Clinton R Bruce 1 , Chris S Shaw 1
  1. Faculty of Health, School of Exercise and Nutrition Science (IPAN), Deakin University, Geelong, Victoria, Australia
  2. Faculty of Medicine, Deakin University, Geelong, Victoria, Australia
  3. Faculty of Health, School of Exercise and Nutrition Science (IPAN), Deakin University, Burwood, Victoria, Australia

Hyperinsulinemia (HI) often occurs concurrently with obesity and insulin resistance. However, the precise role of HI in the trajectory of metabolic disease from a healthy state is unclear. HI can manifest in both the fasted and postprandial state, yet little is known about these different phenotypes. We explored mechanisms of fasting and postprandial HI in young non-obese individuals with normal glucose tolerance.  

We screened 147 volunteers (78 females; 69 males, age: 25.2±5.1y, BMI: 23.8±2.4kg/m2) via a 2h OGTT. Predetermined cut-offs relating to the 90th percentile of fasting and postprandial insulin were used to classify individuals as i) normal fasting and postprandial insulin (n=81), ii) normal fasting insulin with isolated postprandial hyperinsulinemia (IPH, n=26) or iii) fasting and postprandial hyperinsulinemia (HI, n=32). Mechanisms of hyperinsulinemia were examined in a subset of individuals from each group (n=40) via a graded glucose infusion (GGI). Glucose was infused for 1h at rates of 1, 4 and 8 mg/kg/min to achieve physiological increments in glucose and insulin.

BMI was not different between groups, but body fat percentage was significantly higher in both IPH and HI compared to the normal group (P<0.01). Blood glucose increased ~5-10% above basal during the 1 mg/kg/min stage and increased by ~50% and ~100% during the 4 mg/kg/min and 8 mg/kg/min stages respectively. There were no differences in blood glucose between groups during the GGI (P>0.05). Insulin concentrations increased ~1.4-fold, ~3-fold and ~10-fold above basal during each stage of the GGI.  Insulin concentrations at molar increments of plasma glucose ranging from 5-12 mM were obtained, with IPH having ~25% higher insulin response compared to the normal group, while the insulin response in HI was ~2-fold greater than the normal group.

Individuals with HI and IPH are characterised by increased adiposity and exhibit exaggerated insulin responses across the physiological range of hyperglycemia. Future work is ongoing to determine beta-cell sensitivity, insulin clearance and potential role of incretin hormones to HI.