Childhood Predictors of Adult Acute Insulin Response and Insulin Action

Abstract

Objective: Because declines in acute insulin response (AIR) and insulin action (M) predict development of type 2 diabetes, we sought to determine childhood factors that predict M and AIR using longitudinal data from young Pima Indian adults with normal glucose regulation.

Research Design and Methods: Predictors of adult M, measured by the euglycemic-hyperinsulinemic clamp, and AIR, measured after a 25g glucose bolus, were assessed in 76 individuals from a set of childhood data (BMI, systolic (SBP) and diastolic blood pressure, cholesterol, fasting and 2 hour insulin and glucose levels during an oral glucose tolerance test).

Results: After adjustment for sex, adult percent body fat, adult and childhood age, childhood BMI and SBP were negative and independent predictors of adult M. A 5 kg/m² increase in childhood BMI was associated with an 7.4% decrease in adult M (95% CI -12.7%, −1.8%, p=0.01) and a 10 mmHg increase in childhood SBP with a 5.0% decrease in adult M (95% CI −8.4%, −1.4%, p=0.007). After a similar adjustment with M as an additional covariate, childhood 2 hour insulin was a positive predictor of adult AIR such that a 25% increase predicted a 7.3% increase in adult AIR (95% CI 1.5%, 13.5%, p=0.014).

Conclusions: Childhood insulin response during an oral glucose challenge predicts adult AIR indicating β-cell capacity may be set early in life. Childhood measures related to adiposity predict adult insulin action which may reflect common underlying mechanisms that may be amenable to modification through programs targeting prevention or treatment of childhood obesity.