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
Aims To 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. Methods A 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. Results During 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). Conclusions DPP4 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
References
[1]
von Bibra H, Sutton MSJ (2010) Diastolic dysfunction in diabetes and the metabolic syndrome: promising potential for diagnosis and prognosis. Diabetologia 53: 1033–1045. doi: 10.1007/s00125-010-1682-3
[2]
Sattar N, McConnachie A, Shaper AG, Blauw GJ, Buckley BM, et al. (2008) Can metabolic syndrome usefully predict cardiovascular disease and diabetes? Outcome data from two prospective studies. The Lancet 371: 1927–1935. doi: 10.1016/s0140-6736(08)60602-9
[3]
Wellen KE, Hotamisligil GS (2005) Inflammation, stress, and diabetes. Journal of Clinical Investigation 115: 1111–1119. doi: 10.1172/jci25102
[4]
Sell H, Dietze-Schroeder D, Eckel J (2006) The adipocyte–myocyte axis in insulin resistance. Trends in Endocrinology & Metabolism 17: 416–422. doi: 10.1016/j.tem.2006.10.010
[5]
Matteucci E, Giampietro O (2009) Dipeptidyl peptidase-4 (CD26): knowing the function before inhibiting the enzyme. Current medicinal chemistry 16: 2943–2951. doi: 10.2174/092986709788803114
[6]
Lamers D, Famulla S, Wronkowitz N, Hartwig S, Lehr S, et al. (2011) Dipeptidyl peptidase 4 is a novel adipokine potentially linking obesity to the metabolic syndrome. Diabetes 60: 1917–1925. doi: 10.2337/db10-1707
[7]
Cordero OJ, Salgado FJ, Nogueira M (2009) On the origin of serum CD26 and its altered concentration in cancer patients. Cancer immunology, immunotherapy 58: 1723–1747. doi: 10.1007/s00262-009-0728-1
[8]
Yang W, Lu J, Weng J, Jia W, Ji L, et al. (2010) Prevalence of diabetes among men and women in China. New England Journal of Medicine 362: 1090–1101. doi: 10.1056/nejmoa0908292
[9]
Luepker R, Evans A, McKeigue P, Reddy K (2004) Cardiovascular Survey Methods World Health Organization. Geneva, Switzerland.
[10]
Kirino Y, Sei M, Kawazoe K, Minakuchi K, Sato Y (2011) Plasma dipeptidyl peptidase 4 activity correlates with body mass index and the plasma adiponectin concentration in healthy young people. Endocrine journal 59: 949–953. doi: 10.1507/endocrj.ej12-0158
[11]
Li L, El-Kholy W, Rhodes C, Brubaker P (2005) Glucagon-like peptide-1 protects beta cells from cytokine-induced apoptosis and necrosis: role of protein kinase B. Diabetologia. 48: 1339–1349. doi: 10.1007/s00125-005-1787-2
[12]
Zhang J, Tokui Y, Yamagata K, Kozawa J, Sayama K, et al. (2007) Continuous stimulation of human glucagon-like peptide-1 (7–36) amide in a mouse model (NOD) delays onset of autoimmune type 1 diabetes. Diabetologia 50: 1900–1909. doi: 10.1007/s00125-007-0737-6
[13]
?rskov C, Wettergren A, Holst JJ (1993) Biological effects and metabolic rates of glucagonlike peptide-1 7–36 amide and glucagonlike peptide-1 7–37 in healthy subjects are indistinguishable. Diabetes 42: 658–661. doi: 10.2337/diabetes.42.5.658