title: HIV-infected persons with type 2 diabetes show evidence of endothelial dysfunction and increased inflammation.
abstract: 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.
  
  
  
  Cross-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.
  
  
  
  The 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).
  
  
  
  Elevated 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.
authors.affiliation: Department of Infectious Diseases, Rigshospitalet, University Hospital of Copenhagen, opgang 86, 3 sal, Blegdamsvej 9, 2100 Kbh Ø, Copenhagen, Denmark.
authors.forename: Malene
authors.initials: M
authors.lastname: Hove-Skovsgaard
authors.affiliation: Department of Infectious Diseases, Rigshospitalet, University Hospital of Copenhagen, opgang 86, 3 sal, Blegdamsvej 9, 2100 Kbh Ø, Copenhagen, Denmark.
authors.forename: Julie Christine
authors.initials: JC
authors.lastname: Gaardbo
authors.affiliation: Department of Infectious Diseases, Hvidovre Hospital, University Hospital of Copenhagen, Copenhagen, Denmark.
authors.forename: Lilian
authors.initials: L
authors.lastname: Kolte
authors.affiliation: Centre of Inflammation and Metabolism, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.
authors.forename: Kamilla
authors.initials: K
authors.lastname: Winding
authors.affiliation: Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital Ulleval, Oslo, Norway.|Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ingebjørg
authors.initials: I
authors.lastname: Seljeflot
authors.affiliation: Department of Clinical Science, University of Bergen, N-5020, Bergen, Norway.
authors.forename: Asbjørn
authors.initials: A
authors.lastname: Svardal
authors.affiliation: Department of Clinical Science, University of Bergen, N-5020, Bergen, Norway.|Department of Heart Disease, Haukeland University Hospital, N-5021, Bergen, Norway.
authors.forename: Rolf Kristian
authors.initials: RK
authors.lastname: Berge
authors.affiliation: Department of Infectious Diseases, Rigshospitalet, University Hospital of Copenhagen, opgang 86, 3 sal, Blegdamsvej 9, 2100 Kbh Ø, Copenhagen, Denmark.
authors.forename: Jan
authors.initials: J
authors.lastname: Gerstoft
authors.affiliation: Department of Clinical Immunology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Ullum
authors.affiliation: Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Copenhagen, Norway.|Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.|Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway.|K.G. Jebsen Inflammatory Research Center, University of Oslo, Oslo, Norway.
authors.forename: Marius
authors.initials: M
authors.lastname: Trøseid
authors.affiliation: Department of Infectious Diseases, Rigshospitalet, University Hospital of Copenhagen, opgang 86, 3 sal, Blegdamsvej 9, 2100 Kbh Ø, Copenhagen, Denmark. sdn@dadlnet.dk.
authors.forename: Susanne Dam
authors.identifier: 0000-0001-6391-7455
authors.initials: SD
authors.lastname: Nielsen
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D008297:Male; D008744:Methylamines / Q000097:blood; D008875:Middle Aged; D012307:Risk Factors; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D008744:Methylamines; C018524:N,N-dimethylarginine; D001120:Arginine; C005855:trimethyloxamine
keywords: ADMA; HIV infection; Inflammation; TMAO; Type 2 diabetes