HIV-infected persons with type 2 diabetes show evidence of endothelial dysfunction and increased inflammation

Malene Hove-Skovsgaard,Julie Christine Gaardbo,Kamilla Winding,Asbjørn Svardal,Jan Gerstoft,Rolf Kristian Berge,Lilian Kolte,Marius Trøseid,Susanne Dam Nielsen,Ingebjørg Seljeflot,Henrik Ullum

doi:10.1186/s12879-017-2334-8

Abstract

BackgroundIncreased incidence of cardiovascular diseases (CVD) in both HIV infection and type 2 diabetes (T2D) compared to the general population has been described. Little is known about the combined effect of HIV infection and T2D on inflammation and endothelial function, both of which may contribute to elevated risk of CVD.MethodsCross-sectional study including 50 HIV-infected persons on combination anti-retroviral therapy (cART), with HIV RNA <200 copies/mL (n = 25 with T2D (HIV + T2D+), n = 25 without T2D (HIV + T2D-)) and 50 uninfected persons (n = 22 with T2D (HIV-T2D+) and n = 28 without T2D (HIV-T2D-)). Groups were matched on age and sex.High sensitive C-reactive protein (hsCRP) was used to determine inflammation (cut-off 3 mg/L). The marker of endothelial dysfunction asymmetric dimethylarginine (ADMA) was measured using high performance liquid chromatography. Trimethylamine-N-oxide (TMAO), a microbiota-dependent, pro-atherogenic marker was measured using stable isotope dilution LC/MS/MS.ResultsThe percentage of HIV + T2D+, HIV + T2D-, HIV-T2D+, and HIV-T2D- with hsCRP above cut-off was 50%, 19%, 47%, and 11%, respectively. HIV + T2D+ had elevated ADMA (0.67 μM (0.63-0.72) compared to HIV + T2D- (0.60 μM (0.57-0.64) p = 0.017), HIV-T2D+ (0.57 μM (0.51-63) p = 0.008), and HIV-T2D- (0.55 μM (0.52-0.58) p < 0.001). No differences in TMAO between groups were found. However, a positive correlation between ADMA and TMAO was found in the total population (rs = 0.32, p = 0.001), which was mainly driven by a close correlation in HIV + T2D+ (rs = 0.63, p = 0.001).ConclusionElevated inflammation and evidence of endothelial dysfunction was found in HIV-infected persons with T2D. The effect on inflammation was mainly driven by T2D, while both HIV infection and T2D may contribute to endothelial dysfunction. Whether gut microbiota is a contributing factor to this remains to be determined.

Highlights

Increased incidence of cardiovascular diseases (CVD) in both Human immunodeficiency virus (HIV) infection and type 2 diabetes (T2D) compared to the general population has been described
Higher asymmetric dimethylarginine (ADMA) and lower Larginine/ADMA ratio was found in HIV + T2D+ compared to all three control groups indicating endothelial dysfunction
We found that 50% of HIV + T2D+ had High sensitive C-reactive protein (hsCRP) above 3 mg/L indicating an increased risk of CVD [26]

Summary

Introduction

Increased incidence of cardiovascular diseases (CVD) in both HIV infection and type 2 diabetes (T2D) compared to the general population has been described. Little is known about the combined effect of HIV infection and T2D on inflammation and endothelial function, both of which may contribute to elevated risk of CVD. Introduction of combination anti-retroviral therapy (cART) has increased life expectancy for HIV-infected persons. New challenges are emerging, and incidence of cardiovascular disease (CVD) is increased in HIV-infected persons compared to the general. Type 2 diabetes (T2D) is characterized by chronic inflammation and endothelial dysfunction [3], and T2D is an independent risk factor for CVD in the general population as well as in the HIV-infected population [3, 4]. L-arginine/ADMA ratio is important since ADMA, by a competitive reversible blocking of NO-production from L-arginine, affects endothelial function [13, 14]

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