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AIDS Res Hum Retroviruses. 2018 Jun;34(6):536-543. doi: 10.1089/AID.2017.0314. Epub 2018 May 2.

Lower Concentrations of Circulating Medium and Long-Chain Acylcarnitines Characterize Insulin Resistance in Persons with HIV.

Author information

1
1 Department of Medicine, Vanderbilt University Medical Center , Nashville, Tennessee.
2
2 Department of Biostatistics, Vanderbilt University Medical Center , Nashville, Tennessee.
3
3 Sanford Burnham Prebys Metabolomics Core at the Southeast Center for Integrated Metabolomics, University of Florida , Gainesville, Florida.
4
4 Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center , Nashville, Tennessee.
5
5 Division of Infectious Diseases, Vanderbilt University Medical Center , Nashville, Tennessee.

Abstract

In human immunodeficiency virus (HIV)-negative individuals, a plasma metabolite profile, characterized by higher levels of branched-chain amino acids (BCAA), aromatic amino acids, and C3/C5 acylcarnitines, is associated with insulin resistance and increased risk of diabetes. We sought to characterize the metabolite profile accompanying insulin resistance in HIV-positive persons to assess whether the same or different bioenergetics pathways might be implicated. We performed an observational cohort study of 70 nondiabetic, HIV-positive individuals (50% with body mass index ≥30 kg/m2) on efavirenz, tenofovir, and emtricitabine with suppressed HIV-1 RNA levels (<50 copies/mL) for at least 2 years and a CD4+ count over 350 cells/μL. We measured fasting insulin resistance using the homeostatic model assessment 2, plasma free fatty acids (FFA) using gas chromatography, and amino acids, acylcarnitines, and organic acids using liquid chromatography/mass spectrometry. We assessed the relationship of plasma metabolites with insulin resistance using multivariable linear regression. The median age was 45 years, median CD4+ count was 701 cells/μL, and median hemoglobin A1c was 5.2%. Insulin resistance was associated with higher plasma C3 acylcarnitines (p = .01), but not BCAA or C5 acylcarnitines. However, insulin resistance was associated with lower plasma levels of C18, C16, C12, and C2 acylcarnitines (p ≤ .03 for all), and lower C18 and C16 acylcarnitine:FFA ratios (p = .002, and p = .03, respectively). In HIV-positive persons, lower levels of plasma acylcarnitines, including the C2 product of complete fatty acid oxidation, are a more prominent feature of insulin resistance than changes in BCAA, suggesting impaired fatty acid uptake and/or mitochondrial oxidation is a central aspect of glucose intolerance in this population.

KEYWORDS:

HIV; diabetes mellitus; insulin resistance; lipid metabolism; metabolomics

PMID:
29607651
PMCID:
PMC5994672
[Available on 2019-06-01]
DOI:
10.1089/AID.2017.0314

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