title: Significant elevation of serum dipeptidyl peptidase-4 activity in young-adult type 1 diabetes.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Saeko
authors.initials: S
authors.lastname: Osawa
authors.affiliation: 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.
authors.forename: Dan
authors.initials: D
authors.lastname: Kawamori
authors.affiliation: 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.
authors.forename: Naoto
authors.initials: N
authors.lastname: Katakami
authors.affiliation: 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.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Takahara
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Fumie
authors.initials: F
authors.lastname: Sakamoto
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Katsura
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan; Department of Internal Medicine, Osaka Police Hospital, Osaka, Japan.
authors.forename: Tetsuyuki
authors.initials: T
authors.lastname: Yasuda
authors.affiliation: Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Okayama, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneto
authors.affiliation: Diabetes Therapeutics and Research Center, Tokushima University, Tokushima, Japan.
authors.forename: Munehide
authors.initials: M
authors.lastname: Matsuhisa
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Taka-Aki
authors.initials: TA
authors.lastname: Matsuoka
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan.
authors.forename: Iichiro
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications; D018819:Dipeptidyl Peptidase 4 / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018819:Dipeptidyl Peptidase 4
keywords: Complications; DPP-4; Liver function; Type 1 diabetes