3rd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 23-26 October 2001, Athens, Greece

Increased rates of lipolysis among HIV-infected men with and without fat redistribution

Antiviral Therapy 2001; 6(Suppl. 4):6 (abstract no. 7)

C Hadigan¹, S Borgonha², J Rabe¹, V Young² and S Grinspoon^1
1Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA; and ²Clinical Research Center, Massachusetts Institute ofTechnology, Cambridge, Mass., USA

BACKGROUND: HIV lipodystrophy is associated with fat redistribution, dyslipidemia and insulin resistance, however, the mechanism of insulin resistance remains unknown.

OBJECTIVE: We hypothesized that HIV-infected subjects with fat redistribution have increased rates of lipolysis and increased circulating free fatty acid (FFA) levels that contribute to insulin resistance.

METHODS: Stable isotope infusions of glycerol and palmitate were completed following an overnight fast and an oral glucose challenge to assess rates of lipolysis and FFA flux in HIV-infected men (n=19) with and without fat redistribution and healthy age- and bodymass index (BMI)-matched controls (n=8).

RESULTS: Rates of lipolysis were significantly increased among HIV-infected subjects (Ra glycerol, fasting: 4.1±0.2 versus 3.3±0.2 µmol/kg/min in controls, P=0.02 and post glucose: 4.8±0.3 versus 3.5±0.4 µmol/kg/min, P=0.02). Although there was no difference in FFA flux as measured by palmitate, total FFA levels after glucose challenge were increased among HIV-infected subjects and positively associated with abdominal visceral adipose tissue area (among HIV subjects r=0.58, P=0.01). In contrast, fasting total FFA levels were inversely associated with subcutaneous fat area. Among HIV-infected subjects, use of stavudine (P=0.006) and the rate of lipolysis (that is, Ra glycerol, P=0.03) were strong positive predictors of insulin resistance as measured by HOMA-IR, controlling for effects of age, BMI, waist-to-hip ratio and protease inhibitor exposure.

CONCLUSIONS: These data demonstrate increased rates of lipolysis and increased total FFA levels in association with fat redistribution in HIV-infected subjects and suggest that increased lipolysis contributes to insulin resistance in this patient population.

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