Diabetes and dyslipidaemia are associated with oxidative stress independently of inflammation in long-term antiretroviral-treated HIV-infected patients - 24/03/19

Doi : 10.1016/j.diabet.2019.02.008

J.-P. Bastard ^a, C. Couffignal ^b, S. Fellahi ^a, J.-M. Bard ^c, F. Mentre ^b, D. Salmon ^d, C. Katlama ^e, F. Raffi ^f,^{^{1
These authors contributed equally to the study.}}, C. Leport ^b,^{^{1
These authors contributed equally to the study.}}, J. Capeau ^a,^⁎
ANRS CO, APROCO-COPILOTE Cohort study group
^a Faculty of medicine, Sorbonne université, inserm UMR_S938, ICAN, AP–HP, hôpital Tenon, 27, rue Chaligny, 75571 Paris cedex 12, Paris, France
^b Université Paris Diderot, Sorbonne Paris Cité, inserm UMR_S1137, COREB APHP, 16, rue Henri-Huchard, 75890 Paris cedex 18, France
^c UFR des sciences pharmaceutiques et biologiques, MMS - EA 2160, IUML FR3473 CNRS, Nantes and institut de cancérologie de l’Ouest, 4, rue Bras France, BP61112, 44035 Nantes cedex 1, France
^d Service des maladies infectieuses et tropicales, hôpital Cochin, AP–HP, 27, rue du Faubourg Saint-Jacques, 75014 Paris, France
^e Service de maladies infectieuses et tropicales hôpital Pitié-Salpêtrière, AP–HP, Sorbonne Universités, UPMC Université Paris-6, inserm UMR_S1136 IPLESP, 47–83, boulevard de l'Hôpital, 75013 Paris, France
^f Service des maladies infectieuses et tropicales, inserm CIC 1413, CHU de Nantes, 1, place Alexis-Ricordeau, 44000 Nantes, France

^⁎Corresponding author at: Faculty of medicine Saint-Antoine site, 27, rue Chaligny 75571 Paris cedex 12, France.Faculty of medicine Saint-Antoine site27, rue ChalignyParis cedex 1275571France

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Sunday 24 March 2019
Cet article a été publié dans un numéro de la revue, cliquez ici pour y accéder

Abstract

Aim

Ageing HIV-infected patients controlled by antiretroviral therapy (ART) frequently present age-related comorbidities, such as cardiovascular (CV) events, diabetes, dyslipidaemia, hypertension and chronic kidney disease (CKD). The prevalence of these comorbidities was evaluated in a cohort of long-term-monitored ART-controlled HIV-infected patients, then followed by a search into whether oxidative stress, like inflammation, might be associated with metabolic parameters and/or comorbidities.

Methods

Included were 352 long-term ART patients who started with protease inhibitors (PIs) in 1997–1999. They were evaluated at their final visit, 11 years later, for previous CV events, prevalence of diabetes, LDL-related and atherogenic (high TG/HDL) dyslipidaemias, hypertension and CKD. Also measured were circulating biomarkers to explore oxidative stress (Lp-PLA2, oxLDL, oxLDL/LDL ratio, paraoxonase and arylesterase activities), inflammation/immune activation (hsCRP, hsIL-6, D dimer, soluble CD14, β2 microglobulin, cystatin C), adipokines and insulin resistance. Levels were compared in patients with and without each comorbidity or condition using non-parametric correlation tests and multivariate adjusted analyses.

Results

At the final visit, 81.5% of patients were male and were aged (median, IQR) 49 years (45–56); BMI was 23.0 kg/m² (21.1–25.4), CD4+ lymphocytes were 620 cells/mm³ (453–790) and 91.5% had undetectable HIV-1 viral loads. The prevalence of diabetes was 11%, and LDL-related dyslipidaemia 28%, atherogenic dyslipidaemia 9%, hypertension 28%, CKD 9% and previous CV events 9%. Diabetes and atherogenic dyslipidaemia were associated with increased oxidative stress and independently with inflammation. LDL-related dyslipidaemia and impaired fasting glucose were associated with increased oxidative stress. No association of these biomarkers was detected with hypertension, CKD and previous CV events.

Conclusion

In long-term-treated HIV-infected patients with frequent comorbid conditions, oxidative stress could be contributing to diabetes and LDL-related and atherogenic dyslipidaemias independently of inflammation.

Le texte complet de cet article est disponible en PDF.

Keywords : Diabetes, Dyslipidaemia, HIV-infected patients, Oxidative stress, Inflammation