Oral Presentation Australian & New Zealand Obesity Society 2016 Annual Scientific Meeting

Insulin-sensitive overweight/obese individuals remain as insulin sensitive and normotensive as lean subjects over 6 years (#41)

Alice Tang 1 2 3 , Katherine T Tonks 1 2 3 , Leonie K Heilbronn 4 , Nicholas A Pocock 1 3 5 6 , Lesley V Campbell 1 2 3 , David E James 7 , Donald J Chisholm 1 2 3 , Jerry R Greenfield* 1 2 3 , Dorit Samocha-Bonet* (Equal contributors) 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 Adelaide, Adelaide, SA, Australia
  5. Bone Densitometry, St Vincent's Clinic, Darlinghurst, NSW, Australia
  6. Nuclear Medicine, St Vincent's Hospital, Darlinghurst, NSW, Australia
  7. Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia

BACKGROUND: While obesity is a strong risk-factor for insulin-resistance, some obese individuals are as insulin-sensitive as lean individuals. However, whether insulin-sensitive obesity is an enduring phenotype remains unknown.

METHODS: Subjects were studied at the Garvan1,2  (2007-2010) using hyperinsulinaemic-euglycaemic clamps and DXA to measure insulin resistance and body composition, respectively (n=101, ‘baseline studies’). Participants were categorised as lean (BMI<25kg/m2), overweight/obese insulin-sensitive or overweight/obese insulin-resistant (Obsen or Obres; above or below median glucose infusion rate, respectively). Subjects were followed up after 6±1yr. Fifty-nine individuals had their weight, systolic (SBP) and diastolic blood pressure (DBP) measured; a sub-cohort agreed to participate in repeat clamp and DXA studies (n=42).

RESULTS: Average age at follow-up was 60±11yr. Insulin sensitivity (P=0.43), BMI (P=0.53) and body fat mass (P=0.10) did not change significantly over time in this cohort. Despite this, visceral abdominal fat (P=0.004), SBP (P=0.002) and DBP (P<0.001) increased, without a difference between groups (Pinteraction≥0.34). At baseline, insulin sensitivity was 90±40% and 40±10%, relative to lean, in Obsen (P=0.62) and Obres (P<0.001), respectively. This finding persisted at follow-up (78±31%, P=0.46; and 44±15%, P<0.001, in Obsen and Obres relative to lean, respectively).  At baseline, SBP (120±10mmHg) and DBP (76±7mmHg) measured in Obsen were not statistically different to lean (114±14mmHg, P=0.09; and 71±9mmHg, P=0.051, respectively), but were markedly lower than Obres (136±19mmHg, P=0.01; and 86±9mmHg, P<0.001, respectively). This pattern also persisted at follow-up where Obsen had similar SBP (126±19mmHg) and DBP (79±10mmHg) to lean (124±21mmHg, P=0.97; and 79±14mmHg, P=0.99, respectively), but values were lower than Obres (143±17mmHg, P=0.02; and 91±12mmHg, P=0.01, respectively).

CONCLUSION: We observed that in Obsen, relative normotension and insulin sensitivity was preserved over 6 years, suggesting a phenotype distinct from Obres. These findings may partly explain relative protection from cardiovascular disease observed in Obsen relative to Obres in longitudinal studies.

  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.