Impaired glucose tolerance, beta cell function and lipid metabolism in HIVpatients under treatment with protease inhibitors

Objectives: To evaluate metabolic abnormalities, beta-cell function, lipid profile and vascular risk factors in HIV patients on protease inhibitors (P I). Design: Prospective cross-sectional study. Methods: Thirty-eight HIV-1-infected patients receiving at least one PI wer e compared with 17 PI-naive HIV patients in an oral glucose tolerance test (OGTT). Serum glucose, insulin, proinsulin, and C-peptide were determined. The fasting lipid pattern was analysed using electrophoresis and the assess ment of apolipoproteins including lipoprotein (a). Fibrinogen, homocysteine , and anticardiolipin antibodies were also assessed. Results: Twenty-seven (71%) of the PI-treated group had detectable hyperlip idaemia. Isolated hypertriglyceridaemia was present in 12 patients (44%), t wo (7%) of them had type V and 10 (37%) subjects had type IV hyperlipidaemi a (Frederickson classification). Type IIb hyperlipidaemia defined as an inc rease of both very-low-density lipoproteins (VLDL) and low-density lipoprot eins (LDL) was found in 10 (36%) subjects, and five (18%) patients presente d with isolated hypercholesterolaemia (type IIa). PI treatment was associat ed with significant higher fasting cholesterol, triglycerides, LDL and VLDL levels. Apolipoprotein B and E concentrations were significantly increased in patients receiving PI. Elevated concentrations of lipoprotein (a) (> 30 mg/dl) were detected in six (16%) of the hyperlipidaemic patients on PI. E ighteen (46%) patients on PI had impaired oral glucose tolerance and five ( 13%) had diabetes. Although four (24%) of the PI-naive patients were glucos e intolerant, none had diabetes. Fasting concentrations and secretion respo nse of insulin, proinsulin, and C-peptide to glucose ingestion was signific antly increased in the PI-treated group suggesting a beta-cell dysfunction in addition to peripheral insulin resistance. Beta-cell abnormalities were associated with the abnormal lipid pattern and PI treatment. Conclusion: Combination drug regimens including PI are accompanied by impai red glucose tolerance, hyperproinsulinaemia as an indicator for beta-cell d ysfunction, and lipid abnormalities proved to be significant risk factors f or coronary heart disease. Moreover, PI may have an impact on the processin g of proinsulin to insulin. (C) 1999 Lippincott Williams & Wilkins.