Incidence and risk factors for new-onset diabetes in HIV-infected patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study.
OBJECTIVE
The aims of this study were to determine the incidence of diabetes among HIV-infected patients in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort, to identify demographic, HIV-related, and combination antiretroviral therapy (cART)-related factors associated with the onset of diabetes, and to identify possible mechanisms for any relationships found.


METHODS
D:A:D is a prospective observational study of 33,389 HIV-infected patients; diabetes is a study end point. Poisson regression models were used to assess the relation between diabetes and exposure to cART after adjusting for known risk factors for diabetes, CD4 count, lipids, and lipodystrophy.


RESULTS
Over 130,151 person-years of follow-up (PYFU), diabetes was diagnosed in 744 patients (incidence rate of 5.72 per 1,000 PYFU [95% CI 5.31-6.13]). The incidence of diabetes increased with cumulative exposure to cART, an association that remained significant after adjustment for potential risk factors for diabetes. The strongest relationship with diabetes was exposure to stavudine; exposures to zidovudine and didanosine were also associated with an increased risk of diabetes. Time-updated measurements of total cholesterol, HDL cholesterol, and triglycerides were all associated with diabetes. Adjusting for each of these variables separately reduced the relationship between cART and diabetes slightly. Although lipodystrophy was significantly associated with diabetes, adjustment for this did not modify the relationship between cART and diabetes.


CONCLUSIONS
Stavudine and zidovudine are significantly associated with diabetes after adjustment for risk factors for diabetes and lipids. Adjustment for lipodystrophy did not modify the relationship, suggesting that the two thymidine analogs probably directly contribute to insulin resistance, potentially through mitochondrial toxicity.
De Wit
Stephane
S
Centre Hospitalier Universitaire Saint-Pierre, Brussels, Belgium. stephane_dewit@stpierre-bru.be
Sabin
Caroline A
CA
Weber
Rainer
R
Worm
Signe Westring
SW
Reiss
Peter
P
Cazanave
Charles
C
El-Sadr
Wafaa
W
Monforte
Antonella d'Arminio
Ad
Fontas
Eric
E
Law
Matthew G
MG
Friis-Møller
Nina
N
Phillips
Andrew
A
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000453:epidemiology*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D015994:Incidence; D008297:Male; D015999:Multivariate Analysis; D011446:Prospective Studies; D012307:Risk Factors
D019380:Anti-HIV Agents