2268-PUB: Relationship between Serum Free Fatty Acid and Proinsulin Concentrations

Abstract

Background: The causes of pancreatic beta-cell dysfunction include glucose toxicity and lipotoxicity. Basic research has suggested that free fatty acids (FFAs) damage pancreatic beta-cells. However, the relationship between FFAs and pancreatic beta-cell dysfunction has not been clarified in humans. Therefore, we investigated the relationship between the serum concentrations of FFA and proinsulin (PI), a marker of pancreatic beta-cell dysfunction, in a general Japanese population. Methods: This was a cross-sectional study of 489 people (226 men, 263 women; age 35-79 years) from a rural community in Hokkaido, Japan who were not taking diabetic medication and who provided fasting blood samples. Serum PI was measured by a radioimmunoassay, and was compared among quartiles defined with respect to FFA concentration. Because the serum FFA and PI levels showed skewed distributions, univariable and multivariable regression analyses were performed after logarithmic transformation. Results: PI, age, body mass index, and fasting blood glucose and insulin were positively associated with serum FFA quartile: for PI, median (first quartile, third quartile): Q1 8.1 (6.0, 11.7), Q2 8.5 (6.9, 13.1), Q3 9.2 (6.7, 14.5), and Q4 11.2 (7.6, 16.7); p<0.01. Univariable regression analysis showed that ln(FFA) was positively associated with ln(PI) (partial regression coefficient: 0.19, 95% confidence interval (CI): 0.07, 0.31, p<0.01). This positive association remained after adjustment for age and sex (partial regression coefficient: 0.19, 95% CI: 0.07, 0.31, p<0.01), and also after adjustment for age, sex, and HbA1c (partial regression coefficient: 0.12, 95% CI: 0.01, 0.23, p<0.05). Conclusion: Serum FFA was positively associated with PI in a general Japanese population. Thus, FFA may play a role in pancreatic beta-cell dysfunction. Disclosure K. Chiba: None. A. Nakamura: None. H. Miyoshi: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Novo Nordisk Inc., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd. Speaker’s Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., MDS CO. LTD., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd. Other Relationship; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd. S. Ukawa: None. K. Nakamura: None. T. Nakagawa: None. Y. Terauchi: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Novo Nordisk A/S, Sanofi. Consultant; Self; Astellas Pharma Inc. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker’s Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo, Eli Lilly Japan K.K., Kowa Company, Ltd., Medscape, Medtronic, Merck Sharp & Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. A. Tamakoshi: None. T. Atsumi: Consultant; Self; Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., GlaxoSmithKline plc., Pfizer Inc., UCB Japan Co. Ltd. Speaker’s Bureau; Self; AbbVie Inc., Alexion Pharmaceuticals, Inc., Astellas Pharma Inc., Bristol-Myers Squibb, Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo, Eisai Co., Ltd., Eli Lilly Japan K.K., Gilead Sciences, Inc., Mitsubishi Tanabe Pharma Corporation, Otsuka Pharmaceutical Co., Ltd., Pfizer Inc., Takeda Pharmaceutical Company Limited, UCB Japan Co. Ltd.