430-P: Plasma Delta-5 Desaturase Index Is Associated with Arterial Stiffness in Type 2 Diabetes

Abstract

Decreased plasma n-3 polyunsaturated fatty acid (PUFA) levels or n-3/n-6 PUFA ratio is well known to be associated with the risk of cardiovascular diseases. The n-6 arachidonic acid (AA) to dihomo-γ-linolenic acid (DGLA) ratio in plasma, an indirect measure of delta-5 desaturase activity (D5D index), has been reported to be associated with insulin resistance, diabetes, and cardiovascular diseases. In this cross-sectional study, we investigated the association between plasma D5D index and arterial stiffness in patients with type 2 diabetes (T2D). This study included 382 patients with T2D and 118 healthy controls. Fasting plasma AA, DGLA, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) levels were measured by capillary gas chromatography. Arterial stiffness was assessed by measuring the heart-femoral pulse wave velocity (PWV). In patients with T2D, plasma AA levels (138.1 vs. 101.8 μg/mL, p<0.001) and plasma D5D index (5.85 vs. 4.49, p<0.001) were higher than the controls, while plasma DGLA levels were comparable to the controls (23.8 vs. 22.3 μg/mL, p=0.073). Patients with T2D had greater PWV than the controls (1141 vs. 935 cm/s, p<0.001). In the total population, the presence of T2D was independently associated with increased D5D index after adjusting for age, sex, and other metabolic parameters (β=0.311, p<0.001). Multivariate analysis in patients with T2D showed that D5D index was an independent determinant of PWV after adjusting for age, sex, (EPA+DHA)/AA ratio, and other cardiovascular risk factors (β=0.108, p=0.009). On the other hand, no significant association was found between D5D index and PWV in the controls. These data indicate that plasma n-6 AA/DGLA ratio, an estimate of D5D activity, is increased in patients with T2D and is associated with increased PWV, independently of classical cardiovascular risk factors and n-3 PUFAs. This study suggests that abnormal n-6 PUFA metabolism plays a role in advanced arterial stiffness in T2D. Disclosure T. Morioka: Research Support; Self; Eli Lilly and Company, Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Sanofi K.K., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Roche Diagnostics K.K., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Other Relationship; Self; Ono Pharmaceutical Co., Ltd. M. Emoto: Research Support; Self; Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. Speaker's Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama Pharmaceutical CO., Ltd., Takeda Pharmaceutical Company Limited. Y. Kakutani: None. Y. Yamazaki: None. K. Mori: Speaker's Bureau; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd. S. Fukumoto: Research Support; Self; Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Kowa Pharmaceutical Europe Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Novo Nordisk Inc., Sanofi K.K. A. Shioi: None. T. Shoji: Research Support; Self; Bayer Yakuhin, Ltd., Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd. Speaker's Bureau; Self; Kissei Pharmaceutical Co., Ltd., Kowa, Kyowa Hakko Kirin Co., Ltd. M. Inaba: None.