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.
Behrens
G
G
Department of Medicine, Hannover Medical School, Germany. behrens.georg@mh-hannover.de
Dejam
A
A
Schmidt
H
H
Balks
H J
HJ
Brabant
G
G
Körner
T
T
Stoll
M
M
Schmidt
R E
RE
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