Diabetes and HIV

[Guest guest]

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.

De Wit S, Sabin CA, Weber R, Worm SW, Reiss P, Cazanave C, El-Sadr W,

Monforte A, Fontas E, Law MG, Friis-Møller N, A;Data

Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study.

Centre Hospitalier Universitaire Saint-Pierre, Brussels, Belgium.

stephane_dewit@...

Diabetes Care. 2008 Jun;31(6):1224-9. Epub 2008 Feb 11.

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.

RESEARCH DESIGN AND 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.

CONCLUSION: 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.