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

Both insulin resistance and relative β-cell insensitivity are characteristics of HIV-associated glucose intolerance

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

KE Yarasheski¹, E Breda², M Hoffman¹, S Claxton¹, J Schulte¹, K Mondi¹, P Tebas¹, C Cobelle² and WG Powderly^1
1Washington University Medical School, St Louis, Mo., USA; and ²University of Padova, Padua, Italy

BACKGROUND AND OBJECTIVES: We examined the metabolic mechanisms that contribute to HIV-associated impaired glucose tolerance (GT) using the insulin-modified (0.02 U/kg over 5 min) intravenous 6,6-d₂-glucose tolerance test (300 mg/kg; iv GTI) with minimal modelling.

METHODS: We evaluated insulin sensitivity, β-cell sensitivity to glucose and hepatic insulin extraction in 12 HIV-infected men [42±9 years (mean±sD); bodymass index (BMI)=28±4 kg/m²; VL=4.4±2.5×10⁴ copies/ml; CD4=534±98 copies/µl]; four with normal GT (NGT), six with impaired GT (IGT) and two with NIDDM. Results from the HIV-infected men were also compared (ANOVA) to those from seven healthy young (25±4 year; BMI=27±2 kg/m²) and nine healthy older (69±5 year; BMI=28±3 kg/m²) men.

RESULTS: Insulin sensitivity (10⁴ min^-1 per µU/ml) was lower in the IGT+NIDDM HIV-infected men (1.0±0.8) than the NGT (6.9±0.4), young (6.2±3.9) and older men (4.6±2.3; P<0.0007), and was inversely correlated with exposure time (weeks) to protease inhibitors and nucleoside reverse transcriptase inhibitors (r²=0.3; P<0.04). Baseline insulin secretion rate normalized to fasting glucose concentration (10⁹ min^-1) was higher in the IGT+NIDDM HIV-infected men (14.3±3.3) than in the NGT (5.9±2.7), young (4.9±1.4) and older men (6.2±1.3; P<0.0001). β-cell sensitivity to glucose did not differ among groups during the initial portion of the ivGTI (first phase), while it was higher in IGT+NIDDM (17.8±9.6 10⁹ min^-1) than in NGT (8.1±4.2), young (9.9±4.3) and older men (11.4±5.2; P=0.052) during the latter portion of the ivGTI (second phase). β-cell sensitivity to glucose in IGT +NIDDM HIV-infected men was not adequate to compensate for their degree of insulin resistance, in either the basal, first or second phases, as reflected by significantly lower disposition indices (β-cell sensitivity &time; insulin sensitivity) when compared with NGT, young and older men. Baseline hepatic insulin extraction (%) was lower in both the NGT (40±30) and the IGT+NIDDM HIV-infected men (52±18) than in the young (67±10) and older men (75±7; P=0.002).

CONCLUSIONS: HIV-associated glucose intolerance is characterized by: (a) insulin resistance (b) insufficient β-cell insulin secretion given the fasting and ivGTI glucose levels and the degree of insulin resistance (that is, relative insulin deficiency) (c) a greater exposure to antiretroviral medications, and (d) an impaired ability of the liver to extract insulin.

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