HIV-infected men using antiretroviral therapy have higher rates of hyperglycaemia (high blood glucose) and diabetes compared with HIV-negative men, according to an American study presented on February 10th at the Eleventh Conference on Retroviruses and Opportunistic Infections in San Francisco.
Abnormalities in glucose metabolism (insulin resistance, hyperglycaemia, and diabetes mellitus) are a concern because persistently high blood glucose is associated with an increased risk of cardiovascular disease. Previous research has shown that insulin resistance and hyperglycaemia are common in people with HIV, but the risk of frank diabetes in this group is unclear, as is the association between blood glucose abnormalities and the use of highly active antiretroviral therapy (HAART). A higher prevalance of diabetes has been reported in HIV-positive women taking HAART, but this is the first study to report on incidence in men.
Researchers analysed the prevalence and incidence of blood glucose abnormalities in men enrolled in the Multicenter AIDS Cohort Study (MACS), an ongoing prospective study of HIV infection in homosexual and bisexual men in Baltimore, Chicago, Los Angeles, and Pittsburgh. MACS enrolled 5622 men (about 85% Caucasian) between April 1984 and September 1991. This study used data collected from April 1999 (when fasting serum glucose was first measured) through to March 2003.
Fasting hyperglycaemia was defined as having a fasting serum glucose level of at least 110 mg/dL, while diabetes was defined as a fasting serum glucose of 126 mg/dL or higher. Men who used antidiabetes medications or had a self-reported diagnosis of diabetes were classified as diabetic.
The prevalence analysis included 1278 men (710 HIV-negative, 130 HIV-positive not taking HAART, and 438 HIV-positive on HAART). The men in all three groups were similar, with a mean age of about 48 and a body mass index (BMI) of about 26. (A BMI of 25-29.9 is considered overweight, while a BMI of 30 or higher is considered obese.)
After adjusting for age and BMI (both of which are associated with increased risk of blood glucose abnormalities), the diabetes prevalence rate in the HIV-positive men not taking HAART was 2.11 times higher, and the rate in the HIV-positive men on HAART was 5.36 times higher, than the prevalence rate in the HIV-negative men.
All participants who had a fasting glucose greater than 105 mg/dL, or were taking antidiabetes medications, or had a history of diabetes, or had less than two available fasting serum glucose measurements, were then excluded. The remaining 765 men were included in the incidence analysis. Of these, 407 were HIV-negative, 86 were HIV-positive not taking HAART, and 272 were HIV-positive on HAART.
During the follow-up period, 104 total new cases of hyperglycaemia were seen. Forty-three HIV-negative men (10.5%) developed hyperglycaemia, yielding an incidence rate of 5.7 cases per 100 person-years (PY). Hyperglycaemia occurred in eight (9.3%) of the HIV-positive men not taking HAART (3.8/100 PY) and 53 (19.5%) of the HIV-positive men on HAART (9.1/100 PY). After adjusting for age and BMI, the HIV-positive men on HAART were more than twice as likely to develop hyperglycaemia compared with HIV-negative men (rate ratio=2.16).
New cases of diabetes occurred in 12 (2.9%) of the HIV-negative men (1.5/100 PY), four (4.7%) of the HIV-positive men not taking HAART (1.8/100 PY), and 30 (11%) of the HIV-positive men on HAART (4.9/100 PY). Again, after adjusting for age and BMI, the risk of diabetes was more than four times as high among the HIV-positive men on HAART compared with the HIV-negative men (rate ratio=4.37).
Looking at different antiretroviral drugs, the researchers found that men using regimens containing any protease inhibitor, d4T, or efavirenz were all at increased risk for incident hyperglycaemia compared with the HIV-negative men (rate ratios=2.38, 2.77, and 3.16, respectively). But no specific drug was associated with a significantly increased risk compared with HAART in general.
Stratifying by immune status, the researchers determined that men with nadir (lowest ever) CD4 counts of 100 cells/mm3 or less were 2.84 times as likely as HIV-negative men to develop hyperglycaemia, while men with CD4 nadirs of 300 cells/mm3 or higher had just 1.39 times the risk of uninfected men.
The researchers concluded that the risk of prevalent and incident fasting hyperglycaemia was 2-3 times greater, and the risk of prevalent and incident diabetes was 4-5 times greater, in HIV-positive men on HAART compared with HIV-negative men. Use of antiretroviral therapy was associated with a significantly increased risk of hyperglycaemia, but other factors - such as HIV disease severity and CD4 count - may also play an important role in the pathogenesis of blood glucose abnormalities in people with HIV.
Reference
Brown T et al. Prevalence and incidence of pre-diabetes and diabetes in the Multicenter AIDS Cohort Study. Eleventh Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 73, 2004.
Further information on this website
Diabetes risk increased threefold in HIV-positive women treated with PI - news story March 2003.
Multiple risk factors found for diabetes in HIV-positive HAART patients - news story April 2003