Determinants of Insulin-Sensitive Obesity — ASN Events
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Determinants of Insulin-Sensitive Obesity (#110)

Daniel LT Chen 1 , DoritDorit Samocha-Bonet 1 , Rachael Brown 2 , Carsten Liess 3 , Michael Trenell 4 , Brad Milner 5 , Vaughan Macefield 2 , Donald Chisholm 1 , Jerry Greenfield 1
  1. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  2. Integrative Physiology School of Medicine, University of Western Sydney, Sydney, Australia
  3. Philips Healthcare, Hamburg, Germany
  4. MoveLab, Newcastle University, Newcastle, United Kingdom
  5. Medical Imaging, St Vincent's Hospital, Sydney, New South Wales, Australia

Background: While insulin resistance and obesity coexist, 30% of obese individuals remain insulin-sensitive. Most previous studies classified obese individuals as obese insulin-sensitive (Obsen) and obese insulin-resistant (Obres) using surrogate measures, rather than the gold standard hyperinsulinaemic-euglycaemic clamp. Our study examined the metabolic characteristics of insulin-sensitive obesity.


Methods: Sixty-four obese subjects aged 50±11 years were studied. Anthropometric and clinical metabolic data were measured. The hyperinsulinaemic-euglycaemic clamp (80 mU/m2/min) was used to stratify subjects. Subjects in the top tertile of glucose infusion rate (GIR) were deemed Obsen; the bottom two tertiles were Obres. Body composition and visceral/liver fat were measured by DXA and MRI, respectively. Tungsten microelectrodes were inserted percutaneously into the common peroneal nerve at the fibular head to measure muscle sympathetic nervous activity (MSNA).


Results: Age (P=0.97) and Body Mass Index (35.3±4.1 vs. 36.9±4.9 kg/m2, P=0.23) were similar in Obsen and Obres. By definition, insulin sensitivity was higher in Obsen than Obres (120±24 vs. 76±21 µmol/min/kgFFM). Obsen had lower HbA1c (5.2±0.2 vs. 5.6±0.3 %; P<0.01) and lower systolic (120±10 vs. 127±13 mmHg, P=0.04) and diastolic (79±8 vs. 84±9 mmHg; p=0.04) blood pressure. Despite similar subcutaneous fat (514±140 vs. 510±132 cm2; P=0.91), Obsen had lower visceral (213±50 vs 289±82 cm2, P<0.001) and liver (5.4±4.8 vs 17.1±11.8%, P<0.001) fat. Obsen men, but not women, had lower resting MSNA than Obres men (23.3±8.9 vs 37.6±10.5 burst/min; P=0.01). MSNA was significantly associated with visceral fat (r=0.30, p=0.05).


Conclusions: Compared to Obres, Obsen adults have lower glycaemia, lower blood pressure, less visceral and liver fat and lower basal MSNA. Whether lower liver lipid is a determinant of the Obsen phenotype or, rather, a consequence of hyperinsulinaemia is yet to be determined. Future studies will examine whether reduced activation of the sympathetic nervous system by insulin contributes to lower visceral fat deposition in Obsen.

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