Saeko Osawa1, Dan Kawamori2, Naoto Katakami3, Mitsuyoshi Takahara4, Fumie Sakamoto1, Takashi Katsura1, Tetsuyuki Yasuda5, Hideaki Kaneto6, Munehide Matsuhisa7, Taka-Aki Matsuoka1, Iichiro Shimomura1. 1. Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan. 2. Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan; Medical Education Center, Faculty of Medicine, Osaka University, Osaka, Japan. Electronic address: kawamorid@endmet.med.osaka-u.ac.jp. 3. Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Metabolism and Atherosclerosis, Graduate School of Medicine, Osaka University, Osaka, Japan. 4. Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Diabetes Care Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan. 5. Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Internal Medicine, Osaka Police Hospital, Osaka, Japan. 6. Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Okayama, Japan. 7. Diabetes Therapeutics and Research Center, Tokushima University, Tokushima, Japan.
Abstract
AIMS: Currently, 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. METHODS: We 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. RESULTS: Subjects 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). CONCLUSIONS: Serum DPP-4 activity is significantly elevated in Japanese type 1 diabetes, suggesting pathophysiological significance of the enzyme in type 1 diabetes.
AIMS: Currently, 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. METHODS: We 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. RESULTS: Subjects 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). CONCLUSIONS: Serum DPP-4 activity is significantly elevated in Japanese type 1 diabetes, suggesting pathophysiological significance of the enzyme in type 1 diabetes.