Oral glucose tolerance and insulin sensitivity are unaffected by either HIV status or the use of antiretroviral therapy, according to a US study conducted among overweight women and published in the May 1st edition of the Journal of Acquired Immune Deficiency Syndromes. The investigators, from the Women’s Interagency Study (WIHS), found that the body mass index (BMI) was the only variable associated with insulin resistance, prediabetes or diabetes in a total population of 258, including HIV-negative, HIV-positive, but HAART-naïve and HAART experienced overweight women.
The investigators note that their findings are in contrast to earlier studies which found an association between antiretroviral therapy and impaired glucose tolerance and urge that the results of their study should be treated with caution. Nevertheless, they conclude that routine oral glucose tolerance testing is not warranted in HIV-positive women unless they have specific risk factors for diabetes.
Soon after HAART became available, a number of metabolic abnormalities were noted in HIV-positive patients including insulin resistance, impaired glucose tolerance and type two diabetes, and data from large cohort studies suggest that as many as 60% of HIV-positive individuals taking HAART have impaired glucose tolerance or insulin resistance.
In an earlier analysis investigators from the WIHS found that HIV-positive women taking antiretroviral therapy had a three-fold increased risk of diabetes.
On the basis of this finding, and studies conducted in HIV-positive men, they hypothesised that diabetes would be more common in HIV-positive women compared to HIV-negative women matched according to BMI. They also predicted that insulin resistance determined by an oral glucose tolerance test would be greater in HIV-positive women than HIV-negative controls.
Investigators designed a cross-sectional study, during which HIV-positive women taking HAART, HIV-negative women naïve to antiretroviral therapy, and HIV negative women underwent 75g oral glucose tolerance testing. This was performed after an overnight fast. Blood glucose and insulin levels were obtained at the time of oral glucose tolerance testing, and then after 30, 60, 90 and 120 minutes.
A total of 258 women were included in the investigators’ analysis. The study population included 96 HIV-positive women taking HAART, 74 HIV-positive women who were not taking HAART, and 88 HIV-negative women. The HIV-negative women were significantly younger (p 2). There were no significant racial differences between HIV-positive and HIV-negative women, nor did the amount of exercise HIV-positive and HIV-negative women engage in differ. Furthermore, these variables did not differ between HIV-positive women taking HAART and HIV-positive women who were not.
Hepatitis C virus prevalence was similar across all three groups. Among the HIV-positive women, nadir CD4 cell count, but not current CD4 cell count, was lower amongst the women taking HAART (188 cells/mm3 versus 270 cells/mm3, p
In their preliminary analysis, the investigators found no relationship between any of the study variables other than BMI and prediabetes (p = 0.003) and diabetes (p = 0.007).
When the investigators adjusted the results of oral glucose tolerance testing for BMI, age, race and menopausal status, no significant differences were noted between HIV-positive and HIV-negative women, or between HIV-positive women taking HAART and those who were not.
Furthermore, no significant difference was observed in the prevalence of prediabetes (17% HIV-negative women, 18% HIV-positive women not taking HAART, 12% HIV-positive women taking HAART) using either fasting or two hour postglucose challenge levels. Nor were any differences noted in the prevalence of diabetes (10% HIV-negative women, 8% HIV-positive women not on HAART, 4% HIV-positive women taking HAART) using both fasting and two hour postgucose challenge levels.
In further analysis, using a logistic regression model, the only parameter that emerged for any glucose intolerance was BMI (p = 0.0002), even after adjustment. HIV infection and the use of HAART had no effect on diabetes status in this model.
An additional examination of data was then undertaken, looking at the relationship between BMI and HIV status and HAART use. Women were divided into one of three categories according to their BMI. However, in none of the categories was glucose intolerance found to be associated with either HIV status or use of anti-HIV therapy.
“In our study of 258 well-characterised HIV-infected women and their demographically matched, HIV-negative counterparts, no statistically significant association was observed between HIV serostatus or antiretroviral regimen and fasting blood sugar…or insulin…in response to a standard oral glucose tolerance test…insulin resistance…or frequency of diabetes of prediabetes”, write the investigators, who add “the only feature that emerged as significantly associated with diabetes and prediabetes was BMI.”
The investigators note that their findings stand in contrast to earlier studies. They suggest that this could be because of the differences in demographics, HIV disease status, and the duration of HAART use. They also urge that their findings should be treated with caution. They note “our study was powered to find a three-fold difference and it is possible that a smaller but still clinically significant effect may occur…both in vitro and in vivo data provide compelling evidence that antiretroviral therapy may be associated with rapid and clinically relevant insulin resistance and we share the concern regarding this growing evidence.”
Further research is encouraged by the investigators in studies which match HIV-positive individuals with demographically matched HIV-negative individuals.
The investigators recommend that physicians should be “cognizant of the potent effect of BMI on glucose regulation”. They conclude that routine oral glucose tolerance testing is of little value in HIV-positive women unless there are risks of glucose intolerance. HIV-positive women should be provided with information about lifestyle changes that can minimise the risk of glucose intolerance. They further conclude that “direct in vivo measures of insulin sensitivity and beta-cell fuction, couples with in vitro investigations studying the effect of HIV or its treatments, will be most illuminating.”
Danoff A et al. Oral glucose tolerance and insulin sensitivity are unaffected by HIV infection or antiretroviral therapy in overweight women. J Acquir Immune Defic Syndr 39 (1): 55 - 62, 2005.