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

  1. Stephane De Wit, MD, PHD1,
  2. Caroline A. Sabin, PHD2,
  3. Rainer Weber, MD3,
  4. Signe Westring Worm, MD4,
  5. Peter Reiss, MD, PHD5,
  6. Charles Cazanave, MD6,
  7. Wafaa El-Sadr, MD, MPH7,
  8. Antonella d'Arminio Monforte, MD, DMSC8,
  9. Eric Fontas, MD9,
  10. Matthew G. Law, PHD10,
  11. Nina Friis-Møller, MD, PHD4 and
  12. Andrew Phillips, PHD2
  1. 1Centre Hospitalier Universitaire Saint-Pierre, Brussels, Belgium
  2. 2Royal Free and University College, London, U.K
  3. 3University Hospital Zurich, Zurich, Switzerland
  4. 4University of Copenhagen, Copenhagen, Denmark
  5. 5Academic Medical Center, Amsterdam, the Netherlands
  6. 6Bordeaux 2 University, Bordeaux, France
  7. 7Columbia University, Harlem Hospital, New York, New York
  8. 8University of Milan, Milan, Italy
  9. 9Centre Hospitalier Universitaire Nice, Hôpital de l'Archet, Nice, France
  10. 10National Centre in HIV Epidemiology and Clinical Research, Sydney, Australia
  1. 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}


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.


  • Published ahead of print at on 11 February 2008. DOI: 10.2337/dc07-2013.

    Additional information for this article can be found in an online appendix at

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    See accompanying editorial, p. 1267.

    • Accepted February 4, 2008.
    • Received October 19, 2007.
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  1. Diabetes Care vol. 31 no. 6 1224-1229
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