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Glucose Metabolism Disorders, HIV and Antiretroviral Therapy among Tanzanian Adults

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      Abstract

      IntroductionMillions of HIV-infected Africans are living longer due to long-term antiretroviral therapy (ART), yet little is known about glucose metabolism disorders in this group. We aimed to compare the prevalence of glucose metabolism disorders among HIV-infected adults on long-term ART to ART-naïve adults and HIV-negative controls, hypothesizing that the odds of glucose metabolism disorders would be 2-fold greater even after adjusting for possible confounders.MethodsIn this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years) attending an HIV clinic in Tanzania were enrolled in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naïve, and 150 HIV-infected on ART for ≥ 2 years. The primary outcome was the prevalence of glucose metabolism disorders as determined by oral glucose tolerance testing. We compared glucose metabolism disorder prevalence between each HIV group vs. the control group by Fisher’s exact test and used multivariable logistic regression to determine factors associated with glucose metabolism disorders.ResultsHIV-infected adults on ART had a higher prevalence of glucose metabolism disorders (49/150 (32.7%) vs.11/153 (7.2%), p<0.001) and frank diabetes mellitus (27/150 (18.0%) vs. 8/153 (5.2%), p = 0.001) than HIV-negative adults, which remained highly significant even after adjusting for age, gender, adiposity and socioeconomic status (OR = 5.72 (2.78–11.77), p<0.001). Glucose metabolism disorders were significantly associated with higher CD4+ T-cell counts. Awareness of diabetes mellitus was <25%.ConclusionsHIV-infected adults on long-term ART had 5-fold greater odds of glucose metabolism disorders than HIV-negative controls but were rarely aware of their diagnosis. Intensive glucose metabolism disorder screening and education are needed in HIV clinics in sub-Saharan Africa. Further research should determine how glucose metabolism disorders might be related to immune reconstitution.

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        Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study.

        The risk of diabetes mellitus (DM) in human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART) has not been well defined. We conducted an analysis in the Multicenter AIDS Cohort Study to determine the prevalence and incidence of DM in this cohort of HIV-infected and HIV-seronegative men. Prevalence analysis included 1278 men (710 HIV seronegative and 568 HIV infected, 411 receiving HAART) with fasting glucose concentration determinations at baseline. Incidence analysis included 680 of these 1278 men who at the baseline visit had a fasting glucose concentration of 98 mg/dL (5.4 mmol/L) or less, no self-reported history of DM, and no self-reported use of antidiabetic medication. Diabetes mellitus was defined as a fasting glucose concentration of 126 mg/dL (7 mmol/L) or higher, self-reported diagnosis of DM, or self-reported use of antidiabetic medication. Fifty-seven (14%) of the 411 HIV-infected men using HAART at the baseline visit had prevalent DM compared with 33 (5%) of the 711 HIV-seronegative men (prevalence ratio = 4.6; 95% confidence interval, 3.0-7.1, adjusted for age and body mass index [calculated as weight in kilograms divided by the square of height in meters]). The rate of incident DM was 4.7 cases per 100 person-years among HIV-infected men using HAART compared with 1.4 cases per 100 person-years among HIV-seronegative men (rate ratio = 4.11; 95% confidence interval, 1.85-9.16, adjusted for age and body mass index), during the 4-year observation period, based on a median follow-up of 2.3 years. The incidence of DM in HIV-infected men with HAART exposure was greater than 4 times that of HIV-seronegative men, representing a risk that is higher than previous estimates.
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          Diagnosis, prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidaemia, and diabetes mellitus: a cohort study.

          The prevalence and severity of lipodystrophy syndrome with long-term therapy for HIV-1 infection that includes a protease inhibitor is unknown. We studied the natural course of the syndrome to develop diagnostic criteria and identifying markers that predict its severity. We assessed 113 patients who were receiving HIV-1 protease inhibitors (mean 21 months) and 45 HIV-1-infected patients (28 with follow-up) never treated with a protease inhibitor. Lipodystrophy was assessed by questionnaire (including patients' rating of severity), physical examination, and dual-energy x-ray absorptiometry. Body composition and fasting lipid and glycaemic variables were compared with data obtained 8 months previously. Oral glucose tolerance was investigated. There was 98% concordance between patients' reports of the presence or absence of lipodystrophy (reported by 83% of protease-inhibitor recipients and 4% of treatment-naïve patients; p=0.0001) and physical examination. Patients' ratings of lipodystrophy were significantly associated with declining total body fat (p=0.02). Lower body fat was independently associated with longer duration of protease-inhibitor therapy and lower bodyweight before therapy, and more severe lipodystrophy was associated with higher previous (p < 0.03) and current (p < or = 0.01) triglyceride and C-peptide concentrations, and less peripheral and greater central fat (p=0.005 and 0.09, respectively). Body fat declined a mean 1.2 kg over 8 months in protease-inhibitor recipients (p=0.05). The prevalence of hyperlipidaemia remained stable over time (74% of treated patients vs 28% of naïve patients; p=0.0001). Impaired glucose tolerance occurred in 16% of protease-inhibitor recipients and diabetes mellitus in 7%; in all but three patients these abnormalities were detected on 2 h post-glucose load values. Diagnosis and rating severity of lipodystrophy is aided by the combination of physical examination, patient's rating, and measurement of body fat, fasting triglycerides, and C-peptide. Weight before therapy, fasting triglyceride, and C-peptide concentrations early in therapy, and therapy duration seem to predict lipodystrophy severity. Lipodystrophy was common and progressive after almost 2 years of protease inhibitor therapy, but was not usually severe. Hyperlipidaemia and impaired glucose tolerance were also common.
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            Author and article information

            Affiliations
            [1 ]Department of Internal Medicine, Catholic University of Health and Allied Sciences, Mwanza, Tanzania
            [2 ]Department of Internal Medicine, Bugando Medical Centre, Mwanza, Tanzania
            [3 ]Center for Global Health, Weill Cornell Medical College, New York, United States of America
            [4 ]Weill Cornell Medical College in Qatar, Doha, Qatar
            FIOCRUZ, BRAZIL
            Author notes

            Competing Interests: The authors have declared that no competing interests exist.

            Conceived and designed the experiments: EM SK JK JD DF RP. Performed the experiments: EM RP. Analyzed the data: EM LS AS LO RP. Contributed reagents/materials/analysis tools: EM JD DF RP. Wrote the paper: EM LS JK AS LO JD DF RP.

            Contributors
            Role: Editor
            Journal
            PLoS One
            PLoS ONE
            plos
            plosone
            PLoS ONE
            Public Library of Science (San Francisco, CA USA )
            1932-6203
            19 August 2015
            2015
            : 10
            : 8
            26287742
            4545793
            10.1371/journal.pone.0134410
            PONE-D-15-14418
            (Editor)

            This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

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            Funding
            This study was supported by grants from the National Institutes of Health Fogarty Foundation (TW000018) and the National Institute of Allergy and Infectious Diseases (K24 AI098627). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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            Research Article
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            Due to ethical restrictions related to protecting patient confidentiality, all relevant data is available upon request from the Corresponding Author.

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