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Correction for Dagogo-Jack, Diabetes Care 31 (6) 1267-1268.
Published online February 11, 2008
Diabetes Care 31:1224-1229, 2008
DOI: 10.2337/dc07-2013
© 2008 by the American Diabetes Association
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Cardiovascular and Metabolic Risk
Original Research

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

Stephane De Wit, MD, PHD1, Caroline A. Sabin, PHD2, Rainer Weber, MD3, Signe Westring Worm, MD4, Peter Reiss, MD, PHD5, Charles Cazanave, MD6, Wafaa El-Sadr, MD, MPH7, Antonella d'Arminio Monforte, MD, DMSC8, Eric Fontas, MD9, Matthew G. Law, PHD10, Nina Friis-Møller, MD, PHD4 and Andrew Phillips, PHD2

1 Centre Hospitalier Universitaire Saint-Pierre, Brussels, Belgium
2 Royal Free and University College, London, U.K
3 University Hospital Zurich, Zurich, Switzerland
4 University of Copenhagen, Copenhagen, Denmark
5 Academic Medical Center, Amsterdam, the Netherlands
6 Bordeaux 2 University, Bordeaux, France
7 Columbia University, Harlem Hospital, New York, New York
8 University of Milan, Milan, Italy
9 Centre Hospitalier Universitaire Nice, Hôpital de l'Archet, Nice, France
10 National Centre in HIV Epidemiology and Clinical Research, Sydney, Australia

Corresponding author: Stéphane De Wit, MD, PhD, Department of Infectious Diseases, St. Pierre University Hospital, 322, rue Haute, B-1000 Brussels, Belgium. E-mail: stephane_dewit{at}stpierre-bru.be

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.

Abbreviations: cART, combination antiretroviral therapy • CVD, cardiovascular disease • D:A:D, Data Collection on Adverse Events of Anti-HIV Drugs • MACS, Multicenter AIDS Cohort Study • NNRTI, nonnucleoside reverse transcriptase inhibitor • NRTI, nucleoside reverse transcriptase inhibitor • PYFU, person-years of follow-up • RR, relative risk


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