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

doi:10.2337/dc07-2013

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. (stephane_dewit{at}stpierre-bru.be)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

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.