1497-P: Proinsulin as a Potential Marker of Early Pancreatic Beta-Cell Dysfunction

Abstract

Background: Previous studies have indicated that deterioration of pancreatic beta-cell function or mass becomes apparent before a diagnosis of type 2 diabetes and is part of the natural history of type 2 diabetes progression. Among several methods for estimating beta-cell function, assessment using parameters from fasting blood samples would be simple and clinically useful. The objective of this population-based study was to investigate associations between glucose tolerance and beta-cell function, as evaluated by five estimation methods, in Japanese participants. Methods: We analyzed data from the Dynamics of Lifestyle and Neighborhood Community on Health Study (DOSANCO Health Study). Study participants, aged between 35 and 79 years, provided fasting blood samples. A total of 489 participants (263 females) were divided into three groups: a normal glucose tolerance (NGT) group, a prediabetes (PDM) group, and a diabetes (DM) group. Beta-cell function was estimated by homeostasis model assessment of beta-cell function (HOMA-β%); proinsulin (PI); C-peptide index (CPI); ratio of PI to C-peptide (PI/CPR); and ratio of PI to insulin (PI/I). Results: In the crude analysis, PI and PI/CPR were significantly higher in the DM group than in the PDM and NGT groups, and these parameters were significantly higher in the PDM group than in the NGT group. Only PI were significantly increased in the PDM group compared with the NGT group after adjustment for age, sex and BMI [ln(proinsulin): PDM group: 2.38 (2.29, 2.47) pmol/L; NGT group: 2.17 (2.12, 2.22) pmol/L; P < 0.01]. In addition, PI levels were significantly and positively associated with HbA1c quartile in participants without diabetes. Conclusion: Our data demonstrated that fasting PI levels were increased in participants with PDM in a population-based study. Considering the potential deterioration of beta-cell function in PDM, PI could serve as a marker of early pancreatic beta-cell dysfunction. Disclosure A. Nakamura: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Ono Pharmaceutical Co., Ltd. H. Miyoshi: Research Support; Self; Astellas Pharma Inc., AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceutical Europe Co. Ltd., Mitsubishi Tanabe Pharma Corporation, MSD, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Eli Lilly and Company, Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceutical Europe Co. Ltd., Mitsubishi Tanabe Pharma Corporation, MSD, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. S. Ukawa: None. K. Nakamura: None. T. Nakagawa: None. Y. Terauchi: Advisory Panel; Self; AstraZeneca, Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Sanofi. Research Support; Self; Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Bayer Yakuhin, Ltd., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Shionogi & Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. A. Tamakoshi: None. T. Atsumi: Research Support; Self; Astellas Pharma Inc., Bayer Yakuhin, Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, Eisai Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; AbbVie Inc., Astellas Pharma Inc., Bristol-Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, Pfizer Inc., Takeda Pharmaceutical Company Limited, UCB, Inc. Funding Integration Research for Agriculture and Interdisciplinary Fields (14538261); Japan Society for the Promotion of Science (JP26670322)