5th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 8–11 July 2003, Le Meridien Montparnasse, Paris, France

LIPOLYSIS DIMINISHES AND GLUCOSE METABOLISM IMPROVES MODESTLY, BUT FAT DISTRIBUTION REMAINS UNCHANGED IN SEVERE LIPODYSTROPHIC HIV-1 INFECTED PATIENTS 96 WEEKS FOLLOWING PROTEASE INHIBITOR WITHDRAWAL

Antiviral Therapy 2003; 8:L9 (abstract 8)

M van der Valk¹, G Allick², GJ Weverling³, JA Romijn⁴, MT Ackermans⁵, JMA Lange^1,6, BLF van Eck-Smit⁷, C van Kuijk⁸, E Endert⁵, HP Sauerwein² and P Reiss^6
1International Antiviral Therapy Evaluation Centre, University of Amsterdam, Amsterdam, the Netherlands; ²Department of Endocrinology and Metabolism, University of Amsterdam, Amsterdam, the Netherlands; ³Clinical Epidemiology and Biostatistics, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; ⁴Department of Endocrinology, Leiden University Medical Centre, Leiden, the Netherlands; ⁵Department of Clinical Chemistry, Laboratory of Endocrinology and Radiochemistry, University of Amsterdam, Amsterdam, the Netherlands; ⁶Department of Infectious Diseases, Tropical Medicine and AIDS, University of Amsterdam, Amsterdam, the Netherlands; ⁷Nuclear Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; and ⁸Radiology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands

INTRODUCTION: Treatment for HIV is complicated by lipodystrophy syndrome, which is associated with insulin resistance and an increased rate of lipolysis. In eight HIV-1-infected men with severe lipodystrophy, we studied the effects of 96 weeks of protease inhibitor (PI) withdrawal on insulin sensitivity and lipolysis using a hyperinsulinaemic euglycaemic clamp (insulin ~200 pmol/l). Fat distribution was assessed using dual-energy X-ray absorptiometry (DEXA) and single slice computerized tomography (CT) scan. Glucose metabolism and lipolysis were assessed by tracer dilution employing [6,6-²H₂] glucose and [²H₅] glycerol, respectively. Data are expressed as mean ±standard deviation (sd) or 95% confidence interval (CI), where appropriate.

RESULTS: The fasting total glucose production decreased from 16.1 ±2.5 µmol/kg/min at study entry by 1.1 (–2.1 to –0.1) to 15.0 ±1.6 µmol/kg/min after PI withdrawal. During fasting, the glucose oxidation expressed as percent of total glucose disposal increased from 30.5 ±10.4% at study entry by 18.4 (4.7–32)% to 48.8 ±15.6%. During insulin infusion, endogenous glucose production and total glucose disposal did not change significantly as a result of protease inhibitor (PI) withdrawal. However, glucose oxidation expressed as percent of total glucose disposal increased from 36.8 ±12.7% at study entry by 11.6 (1.5–21.7)% to 48.4 ±8.7% after PI withdrawal. With respect to lipolysis, fasting glycerol turnover decreased from 2.6 ±0.6 µmol/kg/min at study entry by 0.8 (–1.4 to –0.3) to 1.8 ±0.3 µmol/kg/min after PI withdrawal. Glycerol turnover during insulin infusion decreased from 1.8 ±0.6 µmol/kg/min at study entry by 0.6 (–1.2 to –0.1) to 1.2 ±0.5 µmol/kg/min. No significant changes were noted in fat distribution assessed both by DEXA and CT-scan.

CONCLUSIONS: Ninety-six weeks of PI withdrawal in severe lipodystrophic HIV-1 infected patients resulted in a significant decrease in lipolysis and improvement in glucose oxidation. During fasting, but not during insulin-stimulation, glucose production was modestly reduced, while insulin-stimulated glucose disposal and fat distribution had not improved. Taken together, our data suggest that mechanisms additional to inhibition of GLUT-4 activity are responsible for the changes in glucose metabolism seen in HIV-infected patients with established lipodystrophy.

Presenting author: M van der Valk

2003-07-08
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