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Weight Gain Inflates Diabetes Risk More in Veterans With Than Without HIV
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20th Conference on Retroviruses and Opportunistic Infections, March 3-6, 2013, Atlanta
Mark Mascolini
Gaining weight boosted the risk of a new diabetes diagnosis 60% more in HIV-positive than HIV-negative members of the Veterans Aging Cohort Study (VACS) [1]. But overall diabetes risk was much lower in HIV-positive than HIV-negative veterans.
A CDC study at this conference found a higher obesity prevalence in the general population than in people with HIV, though 45% of HIV-positive women under 40 years old were obese [2]. Obesity poses a risk of diabetes, heart disease, and other illnesses prevalent in people with HIV. Gaining weight is a frequent consequence of starting combination antiretroviral therapy (cART), but long-term implications of these gains remain poorly understood. To address these issues, US researchers conducted this study aimed at answering two questions: (1) Does diabetes risk associated with body mass index vary by HIV status? (2) Does diabetes risk associated with weight gain vary by HIV status?
The study involved VACS participants enrolled from 1999 through 2008 who had body mass index recorded at a baseline point and 1 year later, as well as a later blood glucose test. The researchers excluded people who already had diabetes. All HIV-positive people considered had yet to begin cART and had a viral load above 500 copies. The study baseline date was the day cART began for people with HIV and the day of the first available body mass index for people without HIV.
The researchers defined weight categories in the usual way: underweight meant a body mass index below 18.5 kg/m(2), normal weight was 18.5 to less than 25, overweight was 25 to less than 30, and obese was 30 or more. They defined incident (newly diagnosed) diabetes as hemoglobin A1c at or above 6.5%. The VACS team assessed weight gain (in 5-pound increments) 12 months after baseline as the primary predictor of diabetes. On average, follow-up continued for another 5 years.
The analysis included 2891 veterans with HIV and 7567 without HIV. More than 95% in both groups were men. Age averaged 48 in the HIV group and 50 in the HIV-negative group. The HIV group had a somewhat lower proportion of whites (35.9% versus 44.0%) and a higher proportion of blacks (55.4% versus 47.7%). The HIV and no-HIV groups had similar proportions of current smokers (35.5% and 32.7%) and former smokers (8.1% and 7.7%).
Compared with HIV-negative veterans, the HIV-positive group had higher proportions of underweight and normal-weight members (7.0% versus 1.6% and 55.1% versus 25.8%), and lower proportions of overweight and obese members (28.5% versus 36.2% and 9.5% versus 36.3%). At the 1-year follow-up point, HIV-positive people gained a median of 7 pounds (interquartile range [IQR] -3 to +19), while HIV-negative people gained a median of 1 pound (IQR -6 to +8). Compared with HIV-negative veterans, those with HIV were more likely to gain more than 5 pounds whether their baseline weight was normal (56% versus 36%) or overweight/obese (46% versus 34%).
Diabetes incidence in the first 12 months of follow-up was similar in HIV-positive and negative veterans or greater in HIV-negative veterans in the normal, overweight, and obese baseline groups, regardless of whether they gained 5 to 10, 10 to 20, or more than 20 pounds in the first year of follow-up (see Figure 2 in poster linked below).
Through 5.5 years of follow-up, diabetes developed in 267 of 2891 veterans with HIV (9.2%) and 1311 of 7567 veterans without HIV (17.3%). Diabetes incidence was substantially lower in the HIV-positive group: 17 versus 31 cases per 1000 person-years. But HIV-positive veterans had a greater diabetes risk with each 5 pounds gained than did HIV-negative veterans. For the HIV-positive group, every 5 pounds gained hoisted the diabetes risk 10% (hazard ratio [HR] 1.10, 95% confidence interval [CI] 1.07 to 1.13, P < 0.001). For the HIV-negative group, every 5 pounds gained boosted the diabetes risk 6% (HR 1.06, 95% CI 1.04 to 1.08, P < 0.001).
The researchers calculated that the diabetes risk associated with weight gain was 60% greater in HIV-positive veterans than in HIV-negative veterans (P = 0.02). This association held true after statistical adjustment for protease inhibitor use, and after exclusion of cohort members with HCV, exclusion of HIV-positive veterans not reaching an HIV load below 500 copies, exclusion of veterans underweight at baseline, and exclusion of veterans who lost weight.
In this analysis HIV infection lowered the diabetes risk about 25%, while older age, black race, and baseline overweight or obesity raised the risk of a diabetes diagnosis:
Multivariable risk of new diabetes diagnosis:
HIV infection: HR 0.74, 95% CI 0.63 to 0.88, P < 0.001
Black versus white race: HR 1.39, 95% CI 1.25 to 1.54, P < 0.001
Every 5 years of age: HR 1.12, 95% CI 1.09 to 1.15, P < 0.001
Overweight at baseline: HR 1.72, 95% CI 1.47 to 2.00, P < 0.001
Obese at baseline: HR 4.12, 95% CI 3.56 to 4.76, P < 0.001
Every 5 pounds gained in HIV-negative: HR 1.06, 95% CI 1.04 to 1.08, P < 0.001
Every 5 pounds gained in HIV-positive: HR 1.10, 95% CI 1.07 to 1.13, P < 0.001
The researchers noted that their analysis is limited by the paucity of obese HIV-positive veterans at baseline and the low proportion of women in the study (under 5%). Indeed, the study described in the final paragraph indicated that HIV-positive women run a higher diabetes risk than women without HIV.
The VACS teams concluded that HIV infection is associated with a decreased overall risk of diabetes (at least in men), but that HIV-positive people who gain weight may run a higher diabetes risk than HIV-negative people who gain weight. They suggested that HIV-positive people starting cART and not underweight should avoid gaining more than 10 pounds.
A recent study of HIV-positive and negative women in the Women's Interagency HIV Study (WIHS) found an 83% higher diabetes incidence in the HIV-positive group when the researchers defined diabetes as (1) taking an antidiabetes drug, (2) fasting glucose at or above 126 mg/dL confirmed by a second fasting glucose above that level, or (3) diabetes reported by the provider and confirmed by two fasting blood glucose levels at or above 126 mg/dL [3]. A 2005 study of HIV-positive and negative men in the Multicenter AIDS Cohort Study found a 4 times higher diabetes risk in the HIV group, but this study did not use hemoglobin A1c to define diabetes or confirm diabetes with a second fasting glucose [4].
References
1. Herrin M, Tate J, Freiberg M, et al. Risk of incident diabetes associated with weight gain after cART initiation. 20th Conference on Retroviruses and Opportunistic Infections. March 3-6, 2013. Atlanta. Abstract 804. http://www.retroconference.org/2013b/PDFs/804.pdf
2. Thompson-Paul A, Wei S, Mattson C, Skarbinski J. Prevalence of obesity in a nationally representative sample of HIV+ adults receiving medical care in the US: Medical Monitoring Project, 2009. 20th Conference on Retroviruses and Opportunistic Infections. March 3-6, 2013. Atlanta. Abstract 777.
3. Tien PC, Schneider MF, Cox C, et al. Association of HIV infection with incident diabetes mellitus: impact of using hemoglobin a1c as a criterion for diabetes. J Acquir Immune Defic Syndr. 2012;61:334-340.
4. Brown TT, Cole SR, Li X, et al. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch Intern Med. 2005;165:1179-1184.
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