Impaired glucose tolerance, beta cell function and lipid metabolism in HIV patients under treatment with protease inhibitors.
OBJECTIVE
To evaluate metabolic abnormalities, beta-cell function, lipid profile and vascular risk factors in HIV patients on protease inhibitors (PI).


METHODS
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.


CONCLUSIONS
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.
Department of Medicine, Hannover Medical School, Germany. behrens.georg@mh-hannover.de
G
G
Behrens
A
A
Dejam
H
H
Schmidt
H J
HJ
Balks
G
G
Brabant
T
T
Körner
M
M
Stoll
R E
RE
Schmidt
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D003327:Coronary Disease / Q000209:etiology; D003430:Cross-Sectional Studies; D048909:Diabetes Complications; D005260:Female; D018149:Glucose Intolerance / Q000139:chemically induced*; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D006946:Hyperinsulinism; D006949:Hyperlipidemias / Q000139:chemically induced; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
D019380:Anti-HIV Agents; D001786:Blood Glucose; D017320:HIV Protease Inhibitors; D007328:Insulin; D008074:Lipoproteins