Insulin-sensitive overweight/obese adults remain as insulin-sensitive as lean subjects over 6 years — ASN Events
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Insulin-sensitive overweight/obese adults remain as insulin-sensitive as lean subjects over 6 years (#182)

Alice Tang 1 2 3 , Katherine T Tonks 1 2 3 , Louise Purtell 3 , Jackson Blythe 1 3 , Matt Govendir 1 3 , Nathan A Johnson 4 , Nicholas A Pocock 1 3 5 6 , Lesley V Campbell 1 2 3 , Donald J Chisholm 1 2 3 , Jerry R Greenfield 1 2 3 , Dorit Samocha-Bonet 1 3
  1. The University of New South Wales, Kensington, NSW, Australia
  2. Endocrinology, St Vincent's Hospital, Darlinghurst, NSW, Australia
  3. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  4. The University of Sydney, Camperdown, NSW, Australia
  5. Bone Densitometry, St Vincent's Clinic, Darlinghurst, NSW, Australia
  6. Nuclear Medicine, St Vincent's Hospital, Darlinghurst, NSW, Australia

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.

  1. Samocha-Bonet D, Campbell LV, Viardot A, Freund J, Tam CS, Greenfield JR, Heilbronn LK. A family history of type 2 diabetes increases risk factors associated with overfeeding. Diabetologia 2010; 53(8): 1700-8.
  2. Tonks KT, Ng Y, Miller S, Coster ACF, Samocha-Bonet D, Iseli TJ, Xu A, Patrick E, Yang JYH, Junutula JR, Modrusan Z, Kolumam G, Stöckli J, Chisholm DJ, James DE, Greenfield JR. Impaired Akt phosphorylation in insulin-resistant human muscle is accompanied by selective and heterogeneous downstream defects. Diabetologia 2013; 56(4): 875-85.
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