Abstract
Accumulating evidence suggests obese women maintain higher insulin sensitivity than obese men, but factors underlying this sex difference in insulin resistance remain unclear. We recently developed a semi-automated method for quantifying visceral and hepatic fat using advanced chemical shift-encoded magnetic resonance imaging (MRI). Using this method, we explored whether sex differences in ectopic fat accumulation may contribute to differences in insulin resistance. Twenty-one obese women (32 ± 6 year, 34.5 ± 3.1 kg/m2, 43.1 ± 5.5 kg fat mass (FM)) and a well-matched cohort of fifteen obese men (29 ± 6 year, 34.5 ± 3.3 kg/m2, 42.0 ± 7.8 kg FM) underwent an MRI scan during which 5mm axial slices were acquired from the abdominal region. Using 3D Slicer software, visceral fat area was quantified on three axial slices from the L2-L3 vertebrae region and averaged. Hepatic fat was quantified as the average percentage fat from three axial slices of the liver. On a separate day, subjects underwent a hyperinsulinemic-euglycemic clamp to quantify insulin sensitivity. Compared with men, women had lower hepatic (4.2 ± 5.5 vs. 13.1 ± 9.7%, p<0.001) and visceral (114 ± 49 vs. 201 ± 87 cm2, p<0.001) fat, which corresponded with higher insulin sensitivity (Glucose infusion rate during clamp [GIR]: 514 ± 330 vs. 263 ± 134 umol/kgFFM/SSI/min, p<0.05). To further examine the relationship between ectopic lipid accumulation and insulin resistance, we stratified subjects into tertiles by hepatic fat content (n=12 per group). Interestingly, nearly all subjects in the lowest tertile for hepatic fat (1.1 ± 0.6%) were women, and when compared to the highest hepatic fat tertile (17.7 ± 8.2%), they also had lower visceral fat (101 ± 61 vs. 214 ± 83 cm2, p<0.001) and importantly, were also more insulin sensitive (GIR: 626 ± 350 vs. 279 ± 238 umol/kgFFM/SSI/min, p<0.05). Our findings suggest lower ectopic fat deposition may help explain the lower degree of insulin resistance in obese women compared with men. Disclosure J.B. Gillen: None. B.J. Ryan: None. R.A. Gioscia-Ryan: None. A. Ludzki: None. T.L. Chenevert: None. J.F. Horowitz: None.
Published Version
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