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Superior Glucose Tolerance and Metabolomic Profiles, Independent of Adiposity, in HIV-Infected Women Compared With Men on Antiretroviral Therapy.

ABSTRACT: In epidemiologic studies, human immunodeficiency virus (HIV)-infected men on antiretroviral therapy (ART) are at higher risk of incident diabetes mellitus compared with women with similar treatment histories. We used metabolomics to determine whether a sex difference in plasma amino acids, acylcarnitines, and organic acids predictive of diabetes and impaired energy metabolism is present in HIV-infected persons on long-term ART.We enrolled 70 HIV-infected adults (43% women) on efavirenz, tenofovir, and emtricitabine (Atripla) with HIV-1 RNA <50?copies/mL for over 2 years. Half of the HIV-infected subjects were obese, and these were matched with 30 obese HIV-negative controls. All subjects had no history of diabetes, statin use, or heavy alcohol use. Fasting insulin sensitivity was measured using homeostatic model assessment 2 (HOMA2), and adipose tissue was measured using dual-energy x-ray absorptiometry (DEXA). Liquid chromatography/mass spectrometry was used to quantitate fasting plasma branched chain and aromatic amino acids predictive of incident diabetes, and C3 and C5 acylcarnitinines and organic acids indicative of impaired energy metabolism.HIV-infected women had more baseline risk factors for insulin resistance: women were older (46 vs 44 years) and had a longer ART duration (8.4 vs 5.1 years, P?

SUBMITTER: Koethe JR

PROVIDER: S-EPMC4902518 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Superior Glucose Tolerance and Metabolomic Profiles, Independent of Adiposity, in HIV-Infected Women Compared With Men on Antiretroviral Therapy.

Koethe John R JR Jenkins Cathy A CA Petucci Christopher C Culver Jeffrey J Shepherd Bryan E BE Sterling Timothy R TR

Medicine 20160501 19

In epidemiologic studies, human immunodeficiency virus (HIV)-infected men on antiretroviral therapy (ART) are at higher risk of incident diabetes mellitus compared with women with similar treatment histories. We used metabolomics to determine whether a sex difference in plasma amino acids, acylcarnitines, and organic acids predictive of diabetes and impaired energy metabolism is present in HIV-infected persons on long-term ART.We enrolled 70 HIV-infected adults (43% women) on efavirenz, tenofovi ...[more]

PMID: 27175676

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Project description:Background and Aims: Studies of both animals and humans show that a high intake of vitamin A is associated with a lower risk of dyslipidemia. However, an association of plasma retinol levels with dyslipidemia is unclear. Therefore, the aim of this study is to investigate an association between plasma retinol and dyslipidemia and to identify related metabolites and pathways in the general population. Methods: We included 250 participants aged 20-80 years from the Wellness Living Laboratory (WELL) China cohort. Associations between plasma retinol levels and dyslipidemia were analyzed using adjusted logistic models. Related metabolites were identified using ANCOVA, adjusted for the false discovery rate (FDR) and used for pathway analyses. Because there are sex differences in plasma retinol levels, all analyses were conducted separately by sex. Results: Plasma retinol was significantly higher in men than in women. A positive association between plasma retinol and dyslipidemia was found in both sexes. In men, the 2nd and 3rd tertiles showed significantly higher proportions of dyslipidemia than the 1st tertile (1st tertile vs. 2nd tertile: p = 0.026; 1st tertile vs. 3rd tertile: p = 0.003). In women, the 3rd tertile showed a significantly higher proportion of dyslipidemia than the 1st and 2nd tertile (3rd tertile vs. 1st tertile: p = 0.002, 3rd tertile vs. 2nd tertile: p = 0.002). Overall, 75 and 30 metabolites were significantly associated with retinol levels in men and women, respectively. According to these metabolites, lipid metabolic pathways, including glycerophospholipid, arachidonic acid, linoleic acid, alpha-linolenic acid, and glycosylphosphatidylinositol (GPI), as well as steroid hormone biosynthesis pathways were found to overlap across the sexes. These pathways showed that elevated retinol levels might be associated with hormone metabolism and inflammation status. Conclusions: We found a positive association between plasma retinol levels and dyslipidemia. Related metabolomic profiles and interrupted pathways showed that such an increase might be associated with steroid hormone synthesis and inflammation. In addition, large, population-based longitudinal studies and intervention studies are needed to confirm the role of retinol in lipid metabolism and the prevention of cardiovascular disease (CVD).

Project description:BackgroundAlthough intake of Hass avocado has been cross-sectionally linked to lower abdominal obesity, knowledge of the effects of avocado consumption on abdominal adiposity and glycemic outcomes remains limited.ObjectiveThe effects of avocado consumption on abdominal adiposity, insulin resistance, oral-glucose-tolerance test (OGTT), and estimated β-cell function were evaluated.MethodsA total of 105 adults aged 25-45 y (61% female) with BMI ≥25 kg/m2 were randomly assigned to an intervention (N = 53) that received a daily meal with 1 fresh Hass avocado or a control (N = 52) that received an isocaloric meal with similar ingredients without avocado for 12 wk. DXA was used to assess the primary outcomes of abdominal adiposity [visceral adipose tissue (VAT), subcutaneous abdominal adipose tissue (SAAT), and the ratio of VAT to SAAT (VS Ratio)]. Fasted glucose and insulin were used to assess the primary outcomes of insulin resistance (HOMA-IR), and insulin sensitivity (Matsuda index) and β-cell function (Insulinogenic index) were estimated using an OGTT. Changes between groups were compared using an ANCOVA. Secondary analyses were conducted based on sex.ResultsThe control group exhibited a greater reduction in SAAT [-54.5 ± 155.8 g (control) compared with 17.4 ± 155.1 g (treatment), P = 0.017] and increase in VS Ratio [0.007 ± 0.047 (control) compared with -0.011 ± 0.044 (treatment), P = 0.024]. Among females, the treatment group exhibited a greater reduction in VAT [1.6 ± 89.8 g (control) compared with -32.9 ± 81.6 g (treatment), P = 0.021] and VS Ratio [0.01 ± 0.05 (control) compared with -0.01 ± 0.03 (treatment), P = 0.001]. Among males, there was no significant difference between groups in changes in abdominal adiposity or glycemic outcomes.ConclusionsDaily consumption of 1 fresh Hass avocado changed abdominal adiposity distribution among females but did not facilitate improvements in peripheral insulin sensitivity or β-cell function among adults with overweight and obesity.This study was registered at clinicaltrials.gov as NCT02740439.

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Dataset Information

Superior Glucose Tolerance and Metabolomic Profiles, Independent of Adiposity, in HIV-Infected Women Compared With Men on Antiretroviral Therapy.

Publications

Superior Glucose Tolerance and Metabolomic Profiles, Independent of Adiposity, in HIV-Infected Women Compared With Men on Antiretroviral Therapy.

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