Significant elevation of serum dipeptidyl peptidase-4 activity in young-adult type 1 diabetes

Abstract

AimsCurrently, inhibition of dipeptidyl peptidase-4 (DPP-4) is widely used in the treatment of type 2 diabetes. Application of this strategy is awaited as a new therapeutic approach for type 1 diabetes, but the scientific basis is still lacking. This report describes the evaluation of serum DPP-4 activity in type 1 diabetes compared with control subjects, and assessment of relationships between DPP-4 activity and diabetic complication markers and metabolic variables in type 1 diabetes. MethodsWe examined serum DPP-4 activity in Japanese young-adult type 1 diabetes (n=76, females 69.7%, age 30.9±6.2 years, duration of diabetes 16.5±11.1 years; mean±SD) and healthy controls (n=22). Association of the enzymatic activity with diabetic micro- and macro- vascular complication markers and clinical parameters was also assessed. ResultsSubjects with type 1 diabetes displayed significantly higher serum DPP-4 activity than healthy controls (relative value, control: 1.00±0.28, T1D, 1.29±0.38; p=0.0011) independent of other clinical parameters. In type 1 diabetes, DPP-4 activity was positively correlated with duration of diabetes (r=0.248, p=0.031), while not correlated with HbA1c level. In univariate correlation analysis of diabetic complication markers and other metabolic parameters, coefficient of variation of R-R intervals (CVR-R) and gamma (γ)-glutamyltransferase (GGT) levels were correlated with DPP-4 activity. GGT was extracted as an independent variable of DPP-4 activity in multivariate analysis (β=0.213, p=0.035). ConclusionsSerum DPP-4 activity is significantly elevated in Japanese type 1 diabetes, suggesting pathophysiological significance of the enzyme in type 1 diabetes.