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Factors associated with the development of diabetes mellitus in HIV-infected patients on antiretroviral therapy: a case-control study
  The incidence of diabetes mellitus (DM) in HIV-infected patients receiving antiretroviral therapy (ART) ranges from 1 to 7%, with a greater incidence of glucose intolerance. Although the development of DM has been associated with highly active antiretroviral therapy (HAART), other factors might influence its appearance in these patients.
In order to identify factors associated with the development of DM in HIV-infected patients on HAART, we undertook a 1 : 1 outpatient case-control study. The cases were HIV patients being followed from January 1997 to December 2001 who developed DM after starting ART. Each case was matched for age ( 5 years), sex and body mass index (BMI; 2.5 kg/m2) with one HIV patient without DM being followed in the same clinic. These controls were selected prospectively from January 2002 to April 2002. A family history (first-degree relatives) of DM, BMI at the start of follow-up for HIV infection, HIV risk factors, the use of ART, and the type and duration of medication were analysed. Laboratory measurements were performed in the fasting state at the time of inclusion in the study. All the cases had normal fasting glycaemia before initiating ART. DM and dyslipemias were diagnosed according to international criteria, and obesity was defined as a BMI above 27.3 kg/m2. Self-perceived lipodystrophy was defined according to the patient's report of body habit changes, confirmed by physical examination. The [chi]2 and Fisher's exact tests were used to analyse categorical variables, the Student t-test for continuous variables with a normal distribution and the Mann-Whitney U test for variables without a normal distribution. Multivariate analysis was performed by multiple conditional logistic regression. Statistical analyses were performed using SPSS 8.0.
Among 846 HIV patients in follow-up, 745 were receiving ART, 71 of whom (9.5%) had glucose intolerance and 34 DM (4.5%). Two of the latter were excluded as no matched controls could be found. The cases had a greater incidence of a family history of DM, of previous obesity, and of lipodystrophy. Although HAART use was similar in both groups, the time on protease inhibitors (PI) was greater in the cases; plasma triglyceride levels were also higher in cases. Multivariate analysis showed that only obesity at the start of the follow-up for HIV infection, the duration of treatment with PI, and the presence of lipodystrophy were associated with the development of DM.
The few studies of the effects of HIV infection on glucose metabolism reported in the pre-HAART era provided varying results. A more recent study showed that HIV infection itself can lead to glucose metabolism disorders. Soon after the incorporation of PI into daily clinical practice, cases of hyperglycaemia and DM associated with ART were reported, with the estimated prevalence of DM being 1-7%. The mechanism by which ART induces these metabolic disorders has not been fully determined, but characteristics of PI-associated DM suggest a similar pathogenesis to that of type 2 DM. The results of our study suggest a multifactorial aetiology of DM in HIV patients on ART. Obesity at the start of follow-up for HIV infection, time on PI, and the presence of lipodystrophy were the factors with the greatest association with DM. Although previous clinical studies have shown an obvious relation between PI and the development of DM, current data suggest that high plasma glucose levels or increased insulin resistance may be a consequence of either the HIV infection itself, or of the use of PI or nucleoside reverse transcriptase inhibitors, or of lipodystrophy, or else depend on such personal factors as age or BMI. In our study, these personal factors, well-known risk factors for DM, are eliminated from consideration as the cases were paired with controls for age, sex, and BMI. Even so, those patients with DM had a greater BMI at the start of follow-up for HIV infection, so that this could be considered a predictive factor for developing DM. A family history of DM was more common in our cases than the controls, but it was not significant in the multivariate analysis. The time of exposure to ART, mainly PI, was associated with the development of DM. There was also a strong association between lipodystrophy and DM, as reported by others, which supports the idea of insulin resistance being the pathogenic mechanism of the glucose disorders in these patients.
In conclusion, our results suggest a multifactorial aetiology of DM in patients with HIV infection. The coincidence of personal and genetic factors with other HIV-associated factors appear to contribute to the appearance of DM. All patients starting ART should thus undergo a baseline evaluation and a routine follow-up of glucose metabolism, taking special note of those who, because of their family or personal history, are predisposed to DM.
AIDS 2003; 17(6):933-935
Rosario Palacios; Jesus Santos; Josefa Ruiz; Mercedes Gonzalez; Manuel Marquez. Infectious Diseases Unit, Internal Medicine Service, Virgen de la Victoria Hospital, Campus Teatinus s/n, 29010 Malaga, Spain.
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