Serum Fatty Acid Proportions Are Associated with Development of Abnormal Glucose Metabolism in Male Japanese: Tokushima Cohort Study

Few prospective cohort studies have examined the association between serum fatty acid (FA) proportions and type 2 diabetes (T2D). In addition, the involvement of serum FAs in the development of early stage abnormality of glucose homeostasis remains unclear. The present study investigated the association between serum FA proportions or FA ratios, which reflect desaturase activity, and the incidence of early stage abnormal glucose metabolism before the actual onset of T2D. We here report a prospective occupational-based cohort study, which has been conducted since 2008 in Japan. A total of 396 male workers without abnormal glucose metabolism aged 20 to 60 years were followed-up prospectively (mean follow-up period: 5.9 years). Abnormal glucose metabolism was defined as either: 1) fasting plasma glucose ≥ 110 mg/dl, 2) HbA1c ≥ 6.0% or 3) medication for hyperglycemia. We evaluated serum FA proportions and the activities of ⊿5desaturase, ⊿6desaturase and ⊿9desaturase, which reflect desaturation of FAs estimated from the FA product-to-precursor ratios. In multivariate analysis after adjusting for age, BMI, smoking habit, alcohol intake, regular exercise, HDL cholesterol, triglycerides, family history of diabetes, and hypertension, the HR of developing abnormal glucose metabolism was 4.42 [95% CI: 1.81 to 10.76, P=0.001] in the highest quartile of baseline serum dihomo-γ-linolenic acid proportion, compared with the lowest quartile. In addition, the age-adjusted incidence and multivariate-adjusted HR of abnormal glucose metabolism also increased with increasing quartile of ⊿6desaturase (P for trend for both <0.01). Our findings suggest that increased serum dihomo-γ-linolenic acid proportion and enhanced activity of ⊿6desaturase are predictive markers for the development of early stage abnormal glucose metabolism in male Japanese. These results imply that altered FA metabolism may associate with early stage disorders of glucose metabolism. Disclosure A. Hata: None. N. Aki: None. T. Ichihara: None. A. Tamura: None. T. Minagawa: None. Y. Kuwamura: None. M. Funaki: Consultant; Self; Happy, Inc. Research Support; Self; Otsuka Holdings Co., Ltd. Funding Japan Ministry of Education, Culture, Sports, Science and Technology