Increased Plasma DPP4 Activity Is an Independent Predictor of the Onset of Metabolic Syndrome in Chinese over 4 Years: Result from the China National Diabetes and Metabolic Disorders Study

Abstract

AimsTo determine whether fasting plasma Dipeptidyl Peptidase 4 (DPP4) activity and active Glucagon-Like Peptide-1 (GLP-1) were predictive of the onset of metabolic syndrome.MethodsA prospective cohort study was conducted of 2042 adults (863 men and 1,179 women) aged 18-70 years without metabolic syndrome examined in 2007(baseline) and 2011(follow-up). Baseline plasma DPP4 activity was determined as the rate of cleavage of 7-amino-4- methylcoumarin (AMC) from the synthetic substrate H-glycyl-prolyl-AMC and active GLP-1 was determined by enzymoimmunoassay.ResultsDuring an average of 4 years of follow-up, 131 men (15.2%) and 174 women (14.8%) developed metabolic syndrome. In multiple linear regression analysis, baseline DPP4 activity was an independent predictor of an increase in insulin resistance over a 4-year period (P<0.01). In multivariable-adjusted models, the odds ratio (OR) for incident metabolic syndrome comparing the highest with the lowest quartiles of DPP4 activity and active GLP-1 were 2.82, 0.45 for men and 2.48, 0.36 for women respectively. Furthermore, plasma DPP4 activity significantly improved the area under the ROC curve for predicting new-onset metabolic syndrome based on information from metabolic syndrome components (Both P<0.01).ConclusionsDPP4 activity is an important predictor of the onset of insulin resistance and metabolic syndrome in apparently healthy Chinese men and women. This finding may have important implications for understanding the aetiology of metabolic syndrome.Trial Registration#TR-CCH-Chi CTR-CCH-00000361

Circulating dipeptidyl peptidase-4 activity is associated with insulin resistance in type 1 diabetic patients

“…Following the data interpretation in the light of indexes of kidney function, DPP4 serum activity remained independently associated with lower insulin sensitivity. In support to our study results, Yang et al (2014) [28] have recently demonstrated that DPP4 activity is significantly higher in healthy subjects with higher blood pressure and insulin resistance determinated by HOMA-IR index in apparently healthy Chinese man and woman. Recent experimental and clinical studies suggest that DPP4 inhibition reduces blood pressure [29] although the underlying mechanism remains poorly understood.…”

Increased plasma dipeptidyl peptidase-4 activities are associated with high prevalence of subclinical atherosclerosis in Chinese patients with newly diagnosed type 2 diabetes: A cross-sectional study

“…Subjects were instructed to maintain their usual physical activity and diet for at least three days before undergoing an oral glucose tolerance test (OGTT). After an overnight fast of ≥10 h, venous blood samples were collected to measure HbA1c, fasting plasma glucose (FPG), fasting insulin, blood lipids Plasma glucose levels, insulin, TC, TG, HDL-C, LDL-C, IL-6, hs-CRP, M6P-R, nitrotyrosine, and 8-iso-PGF2a and c-IMT were measured as previously described [5,6,9,20]. B-mode ultrasonography of the common carotid artery (CCA) was performed using an ultrasound machine (Toshiba; Toshiba Medical Systems, Tokyo, Japan).Each subject was examined in the supine position, with the head elevated ≤45° and a side tilt of 30° to the right and then the same to the left.…”

“…Recent studies have demonstrated that DPP4 is also a newly identified adipokine that has been shown to contribute to hyperglycemia, insulin resistance, dislipidemia, oxidative stress and inflammation [4][5][6][7][8][9][10], all which have been suggested to be involved in the pathogenesis of subclinical atherosclerosis [11,12]. More importantly, a recent in vitro study proved that soluble DPP4 directly activated the MAPK and NF-κB signaling cascade involving PAR2 and resulting in the induction of inflammation and proliferation of human vascular smooth muscle cells (hVSMC), all direct effects of sDPP4 on signaling, proliferation and inflammation could completely be prevented by DPP4 inhibition [13].…”

Increased plasma DPP4 activity predicts new-onset hypertension in Chinese over a 4-year period: possible associations with inflammation and oxidative stress

“…20 The human IGF-2R enzyme-linked immunosorbent assay (ELISA) kit (Ever Systems Biology Laboratory Inc., Los Angeles, CA, USA) and human IL-6 ELISA Kit (R&D Systems, Minneapolis, MN, USA) were used in this study to determine serum IGF-II/M6P-R and IL-6 according to the manufacturer's protocols. Hs-CRP was measured by immunoturbidimetric assay (Roche Diagnostics, Indianapolis, IN, USA).…”