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

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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-017-2334-8) contains supplementary material, which is available to authorized users.

Impact of HIV and Type 2 diabetes on Gut Microbiota Diversity, Tryptophan Catabolism and Endothelial Dysfunction

“…The total study cohort consisted of 100 participants in a cross-sectional study 10 . Gut microbiota samples were available from 84 participants who were included in the present study: 21 HIV-infected individuals with T2D (HIV+T2D), 23 HIV-infected without T2D (HIV only), 16 individuals with T2D without HIV (T2D only) and 24 individuals without HIV and T2D (denoted controls).…”

“…Asymmetric dimethylarginine (ADMA) is a well-established biomarker for nitric oxide (NO)-dependent endothelial dysfunction in both HIV and T2D 7 – 9 . We have recently shown an additive effect of HIV and T2D on endothelial dysfunction as measured by ADMA 10 . Previous works have suggested a potential role of inflammation in this patient group, with low levels of IL-10 production in HIV-infected with diabetes 11 , and soluble TNFR1 predicting incident diabetes in HIV-infected on ART 12 , but the potential triggers remain unknown.…”

Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target

“…In humans, patients with type 2 diabetes and chronic kidney disease have a higher proportion of TMA-producing microbiota and found a positive correlation between TMAO and some biomarkers of inflammation and endothelial dysfunction [ 60 ]. Nevertheless, other reports showed a positive correlation between TMAO and ADMA (endothelial dysfunction biomarker) only in patients with HIV and type 2 diabetes, but found no correlation with high sensitivity C-reactive protein (hsCRP), which is an inflammatory biomarker [ 61 ].…”

Uremic Toxin–Targeting as a Therapeutic Strategy for Preventing Cardiorenal Syndrome

“…The TMAO level positively correlates with serum ADMA levels in clinical research as well. 65 Taken together, TMAO is likely involved in ADMA production, but, further studies are necessary to elucidate the crosstalk between TMAO and ADMA.…”