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

AIDS. 1999 Jul 9;13(10):F63-70. doi: 10.1097/00002030-199907090-00001.


Objectives: To evaluate metabolic abnormalities, beta-cell function, lipid profile and vascular risk factors in HIV patients on protease inhibitors (PI).

Design: Prospective cross-sectional study.

Methods: Thirty-eight HIV-1-infected patients receiving at least one PI were 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 assessment of apolipoproteins including lipoprotein (a). Fibrinogen, homocysteine, and anticardiolipin antibodies were also assessed.

Results: Twenty-seven (71%) of the PI-treated group had detectable hyperlipidaemia. Isolated hypertriglyceridaemia was present in 12 patients (44%), two (7%) of them had type V and 10 (37%) subjects had type IV hyperlipidaemia (Frederickson classification). Type IIb hyperlipidaemia defined as an increase of both very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) was found in 10 (36%) subjects, and five (18%) patients presented with isolated hypercholesterolaemia (type IIa). PI treatment was associated 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. Eighteen (46%) patients on PI had impaired oral glucose tolerance and five (13%) had diabetes. Although four (24%) of the PI-naive patients were glucose intolerant, none had diabetes. Fasting concentrations and secretion response of insulin, proinsulin, and C-peptide to glucose ingestion was significantly 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 impaired glucose tolerance, hyperproinsulinaemia as an indicator for beta-cell dysfunction, and lipid abnormalities proved to be significant risk factors for coronary heart disease. Moreover, PI may have an impact on the processing of proinsulin to insulin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use
  • Blood Glucose / metabolism
  • Coronary Disease / etiology
  • Cross-Sectional Studies
  • Diabetes Complications
  • Female
  • Glucose Intolerance / chemically induced*
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / metabolism
  • HIV Protease Inhibitors / adverse effects*
  • HIV Protease Inhibitors / therapeutic use
  • Humans
  • Hyperinsulinism
  • Hyperlipidemias / chemically induced
  • Insulin / metabolism
  • Islets of Langerhans / metabolism*
  • Lipid Metabolism*
  • Lipoproteins / blood
  • Male
  • Middle Aged
  • Prospective Studies
  • Risk Factors


  • Anti-HIV Agents
  • Blood Glucose
  • HIV Protease Inhibitors
  • Insulin
  • Lipoproteins