Severe insulin resistance contrasting with mild anthropometric changes in the adipose tissue of HIV-infected children with lipohypertrophy

BACKGROUND: The HIV-associated lipodystrophic syndrome (HIV-LDS) combines redistribution of fat mass with insulin resistance and hyperlipidemia. We have previously reported that HIV-LDS prevails in children in a comparable pattern as in adults. The metabolic activity itself of the lipodystrophic adipose tissue in HIV infection has been poorly studied. AIM AND METHODS: To assess in situ the insulin sensitivity of the lipohypertrophic subcutaneous abdominal adipose tissue using the microdialysis technique in HIV-infected children. Insulin sensitivity, assessed by the inhibition of glycerol release, was measured in the abdominal subcutaneous adipose tissue during a standard oral glucose tolerance test (OGTT) in six HIV-infected children under multi-therapy with abdominal lipohypertrophy (supra-iliac skinfold thickness >97th percentile) (HIV/LH+), in six obese children (obese group) and in eight HIV-infected children without lipodystrophy (HIV/LH-). RESULTS: Glucose tolerance was normal in all subjects. Mean insulin areas under the curve (IAUC) were significantly higher in the obese and HIV/LH+ groups than in HIV/LH- (8769+/-5429, 8161+/-4552 and 3618+/-2222 mU min l-1, respectively; P=0.04 for the three groups comparison by the Kruskal-Wallis test), reflecting insulin resistance in the two former groups independent of a significant difference in percentage fat mass (37.2+/-4.7, 22.8+/-10.9 and 20.77.1%, respectively; P= 0.006). The crude inhibition of glycerol release, expressed as the relative change in dialysate glycerol concentration between baseline and 120 min, was not statistically different between the three groups (14% in obese, -3814% in HIV/LH+ and -5117% in HIV/LH- groups; P=0.3). The inhibition of glycerol release with respect to the circulating insulin level (expressed by IAUC) was similar in HIV/LH+ and obese groups (-6+/-5x10-3 and -7+/-5x10-3 l mU-1 min-1, respectively, P=0.4 for two-groups comparison by the U-Mann-Whitney test) and four-fold less than in the HIV/LH- group (-24+/-25x10-3 l mU-1 min-1; P=0.02). CONCLUSION: These data argue in favor of insulin resistance in the adipose tissue of lipohypertrophies associated with HIV infection.