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1 Division of Musculoskeletal Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
2 Program In Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
* To whom correspondence should be addressed. E-mail: mtorriani{at}hms.harvard.edu.
The HIV-lipodystrophy syndrome is characterized by abnormalities of lipid metabolism, glucose homeostasis and fat distribution. Overaccumulation of intra-muscular lipid may contribute to insulin resistance in this population. We examined 63 men: HIV-positive with lipodystrophy (n=22), HIV-positive without lipodystrophy (n=20), and age- and body mass indexmatched HIV-negative controls (n=21). Single slice computed tomography (CT) was used to determine psoas muscle attenuation and visceral fat area. Plasma free fatty acids (FFA), lipid profile, and markers of glucose homeostasis were measured. Muscle attenuation was significantly decreased in subjects with lipodystrophy [median (inter-quartile range), 55.0 (51.0- 58.3)] compared to subjects without lipodystrophy [57.0 (55.0-59.0); P=0.05] and HIV-negative controls [59.5 (57.3-64.8); P<0.01]. Among HIV-infected subjects, muscle attenuation correlated significantly with FFA (r=-0.38; P=0.02), visceral fat (r=-0.49; P=0.002), glucose (r=-0.38; P=0.02) and insulin (r=-0.60; P=0.0001) response to 75-g OGTT. In forward stepwise regression analysis with psoas attenuation as the dependent variable, visceral fat (P=0.02) and FFA (P <0.05), but neither BMI, subcutaneous fat nor antiretroviral use, were strong independent predictors of muscle attenuation (r2=0.39 for model). Muscle attenuation (P=0.02) and visceral fat (P=0.02), but not BMI, subcutaneous fat, FFA, or antiretroviral use, were strong independent predictors of insulin response (area under the curve) to glucose challenge (r2=0.47 for model). These data demonstrate that decreased psoas muscle attenuation due to intra-muscular fat accumulation may contribute significantly to hyperinsulinemia and insulin resistance in HIVlipodystrophy patients. Further studies are needed to assess the mechanisms and consequences of intra-muscular lipid accumulation in HIV-infected patients.
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