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Diabetes Care Publish Ahead of Print published online ahead of print February 11, 2008
DOI: 10.2337/dc07-2013
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Original Research

Incidence and risk factors for new onset diabetes mellitus in HIV infected patients: the D:A:D study

Stephane De Wit, M.D., Ph.D.1, Caroline A. Sabin, Ph.D.2, Rainer Weber, M.D.3, Signe Westring Worm4, Peter Reiss, M.D., Ph.D.5, Charles Cazanave, M.D.6, Wafaa El-Sadr, M.D., M.P.H.7, Antonella d'Arminio Monforte, M.D., D.M.Sc.8, Eric Fontas, M.D.9, Matthew G. Law, Ph.D.10, Nina Friis-Møller, M.D., Ph.D.4 and Jens D. Lundgren, M.D., D.M.Sc.4

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

stephane_dewit{at}stpierre-bru.be

ABSTRACT

Objective: To determine the incidence of Diabetes Mellitus (DM) among HIV patients in the D:A:D (Data Collection on Adverse Events of Anti-HIV Drugs) cohort, to identify demographic, HIV-related and combination antiretroviral therapy (cART)-related factors associated with the onset of DM, 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 patients; DM is a study endpoint. Poisson regression models assessed the relation between DM and exposure to cART after adjusting for known risk factors for DM, CD4 count, lipids and lipodystrophy.

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

Conclusion: Stavudine and zidovudine are significantly associated with DM after adjustment for risk factors for DM and lipids. Adjustment for lipodystrophy did not modify the relationship, suggesting the two thymidine analogues probably directly contribute to insulin resistance potentially through mitochondrial toxicity.


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