4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 22-25 September 2002, San Diego, CA, USA

ADIPONECTIN, LEPTIN AND SOLUBLE TNF RECEPTORS CIRCULATING LEVELS ARE RELATED TO INSULIN RESISTANCE AND CARDIOVASCULAR RISK FACTORS IN HIV PATIENTS UNDER ANTIRETROVIRAL TREATMENT

Antiviral Therapy 2002; 7:L24 (abstract 33)

C Vigouroux¹, M Maachi¹, T-H Nguyen², Y Salhi², S Coussieu³, S Gharakhanian², T Funahashi⁴, Y Matsuzawa⁴, I Shimomura⁴, W Rozenbaum², J Capeau¹ and J-P Bastard^1
1INSERM: U-402 and Biochemistry department, Tenon hospital, Paris, France; ²Infectious diseases department, Rothschild and Tenon hospitals, France; ³Hôtel-Dieu hospital, Paris, France; ⁴University of Osaka, Japan

OBJECTIVES: Altered endocrine function of the adipose tissue could be a major determinant of the lipodystophy and metabolic alterations observed in patients under antiretroviral treatment. We analysed the relations between adiponectin, leptin, IL-6, TNFα and soluble TNFα receptors circulating concentrations and the metabolic parameters in patients with different lipodystrophic phenotypes.

METHODS: We studied 132 male patients under protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors with a body mass index (BMI) <27. We quantified fasting plasma levels of adipocytokines, sTNFαRI and RII, high sensitivity C-reactive protein (hs-CRP), triglycerides, cholesterol, B and A1 apolipoproteins, fasted and 2 h-post glucose loading glycaemia and insulinaemia. We assessed insulin sensitivity by the quantitative insulin sensitivity check index (QUICKI).

RESULTS: We found a positive correlation between QUICKI and adiponectin which remained significant after adjustment for BMI and waist-to-hip ratio and an inverse correlation between QUICKI and both leptin and IL-6 but not TNFα levels. Adiponectin, but not leptin, was negatively correlated with all the metabolic parameters and the cardiovascular risk markers, hs-CRP and the apolipoproteins B/A1 ratio. We used the adiponectin/leptin ratio (A/L) to get rid of the effect of body fat mass on these parameters. A/L was negatively correlated with insulin resistance, metabolic parameters and cardiovascular risk markers while sTNFαRI was positively correlated. Patients were classified in four groups: no lipodystrophy (NL), lipohypertrophy (LH), lipoatrophy (LA) and mixed lipodystrophy (ML). When compared to the NL group, the ML group was the most insulin resistant and presented an alteration of all the metabolic parameters; interestingly, leptin and adiponectin levels were respectively increased and decreased. The LA group was characterized by a longer duration of infection and PI treatment. We found higher IL-6, TNFα and sTNFαRI and RII levels than in the NL group, but leptin, adiponectin and metabolic parameters were not different and QUICKI only mildly decreased.

CONCLUSIONS: These results suggest that adiponectin and the TNFα system are involved in the insulin resistance and metabolic alterations present in patients under ART. We propose that A/L and sTNFαRI could be good indicators of insulin sensitivity and cardiovascular risk in these patients. Patients with lipoatrophy could be evolving from the mixed syndrome but, interestingly, appear metabolically less affected.

Presenting author: J-P Bastard

2002-09-22
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