BACKGROUND: While obesity is a strong risk factor for insulin resistance, some obese subjects are as insulin-sensitive as lean individuals. Whether insulin sensitivity in obesity is an enduring phenotype and the metabolic factors that predict insulin sensitivity over time remain unknown.
METHODS: Individuals studied at the Clinical Research Facility at the Garvan Institute1,2 between 2007-2010 using hyperinsulinaemic-euglycaemic clamps and dual-energy X-ray absorptiometry (DXA) to measure insulin resistance and body fat content, respectively (n=101, ‘baseline studies’) were recalled for a follow-up study after 6±1 years. Fifty nine individuals had their weight and blood pressure (BP) measured; a sub-cohort agreed to participate in a repeat clamp and DXA (n=42). Participants were categorised at baseline into lean (body mass index [BMI]<25 kg/m2) and overweight/obese (BMI≥25 kg/m2) insulin-sensitive (Obsen) and insulin-resistant (Obres) (based on clamp glucose infusion rate [GIR], above or below median, respectively).
RESULTS: Average age at follow-up was 60±11y. BMI (P=0.53), fat mass (P=0.10) and GIR (P=0.43) did not change significantly over 6y. However, systolic BP (P=0.002), diastolic BP (P<0.001) and visceral abdominal fat (VAT, P=0.004) increased in all groups, without a significant difference between groups (Pinteraction≥0.34).
At baseline, relative to lean subjects, insulin sensitivity was 90±40% and 40±10% in Obsen (P=0.62) and Obres (P<0.001), respectively. This pattern was maintained at follow up (78±31%, P=0.46; and 44±15%, P<0.001, in Obsen and Obres relative to lean, respectively). Using multiple linear regression, baseline GIR explained 60% of the variability in follow-up GIR (VAT and systolic BP were not retained in the model [P≥0.14]).
CONCLUSION: Overweight/obese insulin-sensitive individuals remain as insulin-sensitive as lean individuals at 6 years of follow up. Although BMI and fat mass were stable over time, increases in visceral adiposity may predispose to an overall worsening of metabolic health.