The latest finding of the DAD study (Data Collection on Adverse Events of Anti-HIV Drugs) links stavudine (d4T) to an increased risk of developing diabetes. Other NRTIs - zidovudine (AZT) and didanosine (ddI) - have also been implicated, but to a lesser degree. Interestingly, the PI, ritonavir, and the NNRTI, nevirapine, are associated with a reduced risk in developing the disease.
The findings come out of observing 33,389 people with HIV over time. Of the 744 participants who have developed diabetes since joining the study, a significant proportion were on treatments and particularly stavudine.
Though the study did not establish causality, the authors concluded, "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." http://care.diabetesjournals.org/cgi/content/short/31/6/1224