title: The association between impaired proinsulin processing and type 2 diabetes mellitus in non-obese Japanese individuals.
abstract: We aimed to examine the association between impaired proinsulin processing in pancreatic beta cells and type 2 diabetes mellitus in non-obese Japanese patients. Participants were divided into groups for normal glucose tolerance, prediabetes, and type 2 diabetes based on the oral glucose tolerance test (OGTT). Activities of prohormone convertase (PC) 1/3 and PC2 in fasting states were estimated. Multiple regression analysis was undertaken to ascertain if alteration of the activities of these enzymes contributes to the development of impaired glucose tolerance by comparison with HOMA-β and the oral disposition index (DI(O)). Overall, 452 subjects were included. PC1/3 activity tended to decrease in type 2 diabetes compared with normal glucose tolerance. PC2 activity showed no difference among the three groups. Decreased estimated PC1/3 activity was significantly associated with type 2 diabetes after adjustment for sex, age, creatinine, triglycerides, HOMA-β and DI(O). Odds ratios (95% CI) of PC1/3, HOMA-β, and DI(O) were 2.16 (1.12-4.19), 3.44 (1.82-6.52) and 14.60 (7.87-27.11), respectively. Furthermore, decreased PC1/3(≤1.7) combined with decreased HOMA-β (≤30) had a sensitivity of 73% and specificity of 62%. Decreased PC1/3 activity may be a useful measurement of beta-cell function alongside decreased HOMA-β or DI(O). A combined decrease in estimated fasting PC1/3 activity and HOMA-β measurement led to suspicion of type 2 diabetes in the non-obese Japanese population studied.
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Tokyo 181-8611, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Katsuta
authors.forename: Sachihiko
authors.initials: S
authors.lastname: Ozawa
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kazuto
authors.initials: K
authors.lastname: Takahashi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sumitani
authors.forename: Susumu
authors.initials: S
authors.lastname: Nishida
authors.forename: Takuma
authors.initials: T
authors.lastname: Kondo
authors.forename: Toshio
authors.initials: T
authors.lastname: Hosaka
authors.forename: Kouichi
authors.initials: K
authors.lastname: Inukai
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishida
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000208:ethnology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000208:ethnology; D007527:Isoenzymes / Q000378:metabolism; D007564:Japan; D008297:Male; D008875:Middle Aged; D011384:Proinsulin / Q000097:blood / Q000378:metabolism*; D043484:Proprotein Convertases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D007328:Insulin; D007527:Isoenzymes; C070703:proinsulin, des(31,32)-; D011384:Proinsulin; D043484:Proprotein Convertases