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4th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV22-25 September 2002, San Diego, CA, USA |
INSULIN SENSITIVITY, SERUM LIPIDS AND ABDOMINAL ADIPOSE TISSUE DISTRIBUTION IN PROTEASE INHIBITOR-TREATED AND PROTEASE INHIBITOR-NAÏVE HIV-INFECTED CHILDREN
Antiviral Therapy 2002; 7:L5 (abstract 8)
A Bitnun1, E Sochett2, P Babyn3, C Arneson1, S Holowka3, J Forbes4, S Read1, and SM King1
1Division of Infectious Diseases, The Hospital for Sick Children, University of Toronto, Ontario;
2Division of Endocrinology and Diabetes, The Hospital for Sick Children, University of Toronto, Ontario;
3Department of Radiology, The Hospital for Sick Children, University of Toronto, Ontario;
4Department of Pediatrics, University of British Columbia, Vancouver;
OBJECTIVES: The purpose of this ongoing study is to determine the extent and severity of abnormalities of glucose homeostasis, serum lipids and abdominal adipose tissue distribution in HIV-infected children, and to investigate the role of the protease inhibitors (PIs) in the development of these abnormalities.
METHODS: Patients were recruited from consenting PI-treated and PI-naïve HIV-infected children 3-18 years of age. Serum glucose, insulin, proinsulin, C-peptide, triglycerides and total HDL and LDL cholesterol were measured in the fasting state. Insulin sensitivity was assessed using the insulin-modified frequent sampling intravenous glucose tolerance test and abdominal adipose tissue distribution using single slice computed tomography at the umbilical level.
RESULTS: Thirty-three PI-treated children (mean duration 26 months, range 8-59 months) and 15 PI-naïve children were included. The mean age, viral load and CD4 count were 9.1 ±4.3 years, 10,527 ±27,985 copies/ml and 962 ±611 cells/µl for PI-treated, and 8.7 ±3.6 years, 19,231 ±8,123 copies/ml and 704 ±363 cells/µl for PI-naïve subjects, respectively. The mean insulin sensitivity index for PI-treated and PI-naïve children was 1.03 ±1.06×10-4 [pmol/l]-1min-1 and 1.77 ±2.15×10-4 [pmol/l]-1min-1, respectively. Independent predictors of insulin sensitivity included age (P=0.0002), HIV immunological category (P=0.0186), PI therapy (P=0.0333) and stavudine exposure (P=0.0764). Subgroup analysis demonstrated that PI therapy was significantly associated with insulin sensitivity in pubertal (P=0.0163), but not in prepubertal subjects (P=0.41). There were no significant differences between PI-treated and PI-naïve children with respect to serum glucose, insulin or C-peptide or abdominal adipose tissue distribution. The increase in visceral/subcutaneous adipose tissue ratio associated with age was significant in PI-treated (P=0.0086) but not in PI-naïve children (P=0.44). The mean total cholesterol, LDL cholesterol and triglycerides were 5.30 ±1.53, 3.40 ±1.36 and 1.81 ±1.32 mmol/l in PI-treated children, and 3.93 ±0.76, 2.34 ±0.70 and 1.08 ±0.52 mmol/l in PI-naïve children, respectively (P<0.01 for all).
CONCLUSIONS: In HIV-infected children, PI therapy is associated with hypercholesterolemia, hypertriglyceridemia and a modest decline in insulin sensitivity, but not with fasting hyperinsulinemia or an increase in the proportion of adipose tissue in the visceral compartment. Insulin sensitivity and abdominal adipose tissue distribution are more strongly related to age and/or Tanner stage than to PI therapy. PI therapy is an important predictor of reduced insulin sensitivity in pubertal but not prepubertal children.
Presenting author: A Bitnun
2002-09-22
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