Objective: Hyperglycemia, insulin resistance, dislipidemia, oxidative stress and inflammation are well-documented risk factors for subclinical atherosclerosis. Dipeptidyl peptidase-4(DPP4) is a newly identified adipokine related to these risk factors. Hence, we aimed to investigate the association between plasma DPP4 activities and subclinical atherosclerosis in type 2 diabetes.
Methods: A total of 985 newly diagnosed type 2 diabetic subjects were studied. Plasma DPP4 activity, mannose 6-phosphate receptor (M6P-R), oxidative stress parameters, inflammatory markers and common carotid artery Intima-Media Thickness (c-IMT) were measured in all participants.
Results: Participants in the highest quartile of DPP4 activity had higher HbA1c, homeostatic model assessment of insulin resistance(HOMA-IR), triglyceride, low-density lipoprotein cholesterol(LDL-C), oxidized LDL, nitrotyrosine, 8-iso-PGF2a, interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), M6P-R, c-IMT compared with participants in the lowest quartile (all P < 0.001). DPP4 activities were associated positively with HbA1c, HOMA-IR, triglyceride, LDL-C, oxidized LDL, nitrotyrosine, 8-iso-PGF2a, IL-6, hs-CRP, M6P-R and c-IMT (all P < 0.05). The ORs for insulin resistance, dislipidemia, oxidative stress and inflammation were higher with increasing DPP4 quartiles (P < 0.001 for trend). In the highest DPP4 quartile, subclinical atherosclerosis risk was significantly higher (OR 4.97; 95% CI 3.03-8.17) than in the lowest quartile. This association remained strong (2.17; 1.21-3.89) after further controlling for HbA1c, HOMA-IR, triglyceride, oxidized LDL, nitrotyrosine, and IL-6.
Conclusions: This study shows that increased DPP4 activities are positively and independently associated with subclinical atherosclerosis in type 2 diabetes. Our findings suggest of potential role of DPP4 in the pathogenesis of subclinical atherosclerosis and in the prevention and management of this disease.
Keywords: Atherosclerosis; DPP4 activity; Dislipidemia; Inflammation; Insulin resistance; Oxidative stress.
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