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  18th CROI
Conference on Retroviruses
and Opportunistic Infections
Boston, MA
February 27 - March 2, 2011
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Vitamin D3 Supplements May Thwart Diabetes Emergence in People With HIV
  18th Conference on Retroviruses and Opportunistic Infections, February 27-March 2, 2011, Boston
Mark Mascolini
Vitamin D-deficient HIV-positive people who took D3 supplements had a lower incidence of diabetes than D-deficient HIV-positive people who did not take supplements, according to results of a retrospective cohort analysis in Italy [1]. Although taking D supplements independently lowered the risk of a new diabetes diagnosis, deficiency rates remained similar in those who took supplements and those who did not. So the role of vitamin D supplementation in preventing diabetes remains unclear in this study.
Low vitamin D has been linked to insulin resistance and type 2 diabetes mellitus in the general population. Researchers at the University of Modena and Reggio Emilia recently reported an association between vitamin D and type 2 diabetes in a cross-sectional study of HIV-positive people attending a metabolic clinic [2]. After statistical adjustment for vitamin D supplementation, gender, age, body mass index, and hepatitis C virus (HCV) coinfection, vitamin D deficiency (25(OH)D under 20 ng/mL) almost doubled the risk of type 2 diabetes mellitus (adjusted odds ratio 1.85, 95% confidence interval [CI] 1.03 to 3.32, P = 0.038).
For the supplementation study, the same investigators focused on 1574 people who entered the metabolic clinic without type 2 diabetes and had at least one follow-up visit. The researchers recorded a diagnosis of diabetes if fasting glucose rose to 126 mg/dL or higher after the first visit or if the primary care physician began treatment for diabetes. Clinic patients were advised to begin vitamin D supplementation if their 25(OH)D level lay below 30 ng/mL. People who reported taking the recommended 30,000 IU of vitamin D monthly were considered supplementers.
Most study participants (65%) were men, median age was 44 years (interquartile range [IQR] 40 to 48), median CD4 count was 509 (IQR 367 to 687), and 61% had an undetectable viral load. The median vitamin D level was 17 ng/mL (IQR 10.5 to 26.2), 1272 people (81%) had vitamin D deficiency, and 232 people (15%) took vitamin D supplements. Follow-up lasted a median of 2.4 years.
People who took supplements were slightly but significantly older (median 45 versus 44 years, P = 0.010), included a lower proportion of smokers (38% versus 45%, P = 0.006), and had lower levels of insulin (11.3 versus 13.6 microUI,mL, P < 0.001), insulin resistance by HOMA-IR (2.48 versus 3.01, P = 0.002), and vitamin D (15.0 versus 17.4 ng/mL, P = 0.004). The supplement group had higher total cholesterol (196 versus 184 mg/dL, P < 0.001), low-density lipoprotein cholesterol (122.5 versus 112 mg/dL, P < 0.001), and parathyroid hormone (62 versus 58 pg/mL, P = 0.046).
An initial multivariate model considered age, gender, nadir and current CD4 count, undetectable viral load, baseline vitamin D, vitamin D supplementation, HOMA-IR, body mass index, girth, and triglycerides. In this analysis vitamin D supplementation independently lowered the risk of incident diabetes mellitus 83% (hazard ratio [HR] 0.17, 95% CI 0.04 to 0.72, P = 0.012). Age, baseline vitamin D, and baseline HOMA-IR were also independently associated with incident diabetes.
In a second multivariate model that also considered HCV antibody status and cumulative antiretroviral exposure, vitamin D supplementation lowered the risk of diabetes 87% (HR 0.13, 95% CI 0.02 to 0.98, P = 0.048), HCV antibody positivity doubled the risk (HR 2.05, 95% CI 1.05 to 3.99, P = 0.036), and age and HOMA-IR remained independently associated with diabetes.
But how supplementation may have lowered diabetes risk in this analysis remains unclear because taking vitamin D did not raise concentrations of 25(OH)D into the normal range. Equivalent proportions of supplementers and nonsupplementers remained D deficient in winter and summer (78% to 85%). In addition, the last available vitamin D level after supplementation was not associated with a lower diabetes risk in univariate analysis.
The researchers proposed that 30,000 IU of vitamin D3 monthly may be too little to normalize D levels in this population. They noted that their liberal definition of newly diagnosed diabetes may have led to an overestimate in incidence. These investigators called for placebo-controlled trials to test the value of supplementing vitamin D in people with HIV, and results of two such trials were unveiled at this meeting (and are reported separately by NATAP). One found that 12 weeks of vitamin D supplementation in D-deficient adults with HIV did not improve endothelial function [3]. The other found that vitamin D3 supplementation by 18-to-24-year-olds appeared to offset the negative impact of tenofovir on parathyroid hormone, which stimulates production of vitamin D and thus enhances absorption of calcium from the small intestine [4].

1. Guaraldi G, Zona S, Orlando G, et al. Vitamin D3 supplementation decreases the risk of diabetes mellitus among patients with HIV infection. 18th Conference on Retroviruses and Opportunistic Infections. February 27-March 2, 2011. Boston. Abstract 827.
2. Szep Z, Guaraldi G, Shah SS, et al. Vitamin D deficiency is associated with type 2 diabetes mellitus in HIV infection. AIDS. 2011;25:525-529.
3. Longenecker C, Hileman C, Carman T, et al. Vitamin D supplementation and endothelial function among vitamin D-deficient HIV-infected persons: a randomized placebo-controlled trial. 18th Conference on Retroviruses and Opportunistic Infections. February 27-March 2, 2011. Boston. Abstract 829.
4. Havens P, Hazra R, Stephensen C, et al. Vitamin D3 supplementation decreases PTH in HIV-infected youth being treated with TDF-containing combination ART: a randomized, double-blind, placebo-controlled multicenter trial: Adolescent Trials Network Study 063. 18th Conference on Retroviruses and Opportunistic Infections. February 27-March 2, 2011. Boston. Abstract 80.