Prospective evaluation of the effect of initiating indinavir-based therapy on insulin sensitivity and B-cell function in HIV-infected patients.
OBJECTIVE
To determine whether initiation of antiretroviral therapy that includes the protease inhibitor indinavir causes insulin resistance or abnormal B-cell function in study subjects with HIV infection.


METHODS
Nonwasted, HIV-infected study subjects who did not have concurrent diabetes were prospectively evaluated by oral and intravenous glucose tolerance testing at baseline, at 2 weeks after starting indinavir monotherapy, and at another 6 weeks after initiating indinavir-based triple-therapy.


RESULTS
Mean CD4 count at entry was 282 cells/microl and median HIV RNA was 33,000 copies/ml; all experienced a virologic response. Fasting glucose increased from 83.2 +/- 3.7 mg/dl at baseline to 86.8 +/- 3.2 at week 2 and 91.7 +/- 3.5 at week 8 (p =.003). Insulin sensitivity by minimal model analysis decreased by 30.5% over 8 weeks, from 3.83 +/- 0.63 min-1 per microU/ml x 10-4 to 3.09 +/- 0.53 at week 2 and 2.66 +/- 0.35 at week 8 (p =.01). Insulin secretion by the acute insulin response to intravenous glucose did not change (baseline 822 +/- 283 microU/ml x min, week 8 880 +/- 289; p = 0.4), and the insulin response to oral glucose (30 minute insulin:glucose ratio) fell from 1.69 +/- 0.54 microU/ml per mg/dl at baseline to 1.18 +/- 0.34 at week 8 (p =.05).


CONCLUSIONS
During 8 weeks of indinavir-based therapy, fasting glucose increased and insulin sensitivity decreased, without a compensatory increase in insulin release. This combination of insulin resistance without augmented B-cell response may explain the hyperglycemia and other metabolic abnormalities seen in some protease inhibitor-treated patients.
Dubé
M P
MP
Department of Medicine, Division of Infectious Diseases, University of Southern California School of Medicine, Los Angeles, California, U.S.A. mpdube@iupui.edu
Edmondson-Melançon
H
H
Qian
D
D
Aqeel
R
R
Johnson
D
D
Buchanan
T A
TA
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology*; D001786:Blood Glucose / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D005951:Glucose Tolerance Test; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D015497:HIV-1; D006801:Humans; D019469:Indinavir / Q000009:adverse effects* / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use
D019380:Anti-HIV Agents; D001786:Blood Glucose; D007328:Insulin; D018894:Reverse Transcriptase Inhibitors; D019469:Indinavir