Association between Erythrocyte n-3 Polyunsaturated Fatty Acid and the Risk of Type 2 Diabetes Mellitus: Case-Control Study in Korea

Abstract

The incidence of type 2 diabetes mellitus is increased and a dietary habit, especially fish intake has been suggested to associate with the decreased risk of type 2 diabetes mellitus. However, the association between blood levels of n-3 polyunsaturated fatty acids (PUFA) as a biomarker of fish intake and the risk of type 2 diabetes mellitus is unclear. Blood levels of n-3 PUFA were higher in patients with than without type 2 diabetes mellitus in Australian, whereas lower in the patients with than without type 2 diabetes mellitus in Chinese. Studies showed that the risk of type 2 diabetes mellitus was negatively associated with activity of delta-5 desaturase (D5D; 20:4n6/20:3n6), but positively with activities of delta-6 desaturase (D6D; 18:3n6/18:2n6) and stearoyl coenzyme A desaturase (SCD or delta-9 desaturase; 18:1n9/18:0). Thus, n-3 PUFA may play an important role in fatty acid metabolism by affecting activities of desaturases. In the present study, we investigated the hypothesis that the risk of type 2 diabetes mellitus was negatively associated with erythrocyte levels of n-3 PUFA and activity of D5D, while positively associated with activities of D6D and SCD in Korean. Cases (n=130) were consisted of patients diagnosed with type 2 diabetes mellitus defined by fasting glucose levels ≥ 126 mg/dL and confirmed by medical personals. On the other hands, controls (n=260) were age-matched healthy subjects without history of type 2 diabetes mellitus. Erythrocyte levels of 18:0, n-3 PUFA, eicosapentaenoic acid (EPA, 20:5n3), 22:5n3, docosahexaenoic acid (DHA, 22:6n3), Omega-3 Index (the sum of EPA and DHA), and 20:4n6 were significantly lower in cases than controls. However, erythrocyte levels of monounsaturated fatty acids (MUFA), 18:1n9, 18:2n6, 18:3n6, n-6/n-3 PUFA ratio, trans fatty acids (TFA), and activities of D6D and SCD were significantly higher in cases than controls. Linear regression analysis showed that the risk of type 2 diabetes mellitus was positively associated with erythrocyte levels of 16:0, MUFA, 18:1n9, 18:3n3, 18:2n6, 18:3n6, TFA, n-6/n-3 PUFA ratio, and activities of D6D and SCD, but negatively associated with erythrocyte levels of 18:0, PUFA, n-3 PUFA, 22:5n3, DHA, Omega-3 Index, and 20:4n6 after adjusting for confounding factors. In addition, levels of glucose were positively correlated with erythrocyte levels of 14:0, 18:1n9, 18:2n6 and, SCD activity, while negatively correlated with erythrocyte level of 16:1n7 in cases and controls. Levels of HbA1c were positively correlated with erythrocyte levels of 16:0, MUFA, 18:1n9, n-6/n-3 PUFA ratio, TFA, and activities of D5D and SCD, while negatively correlated with erythrocyte levels of 18:0 and DHA in cases and controls. In conclusion, erythrocyte levels of n-3 PUFA and Omega-3 Index were negatively associated with the risk of type 2 diabetes mellitus, while activities of D6D and SCD were positively associated with the risk of type 2 diabetes mellitus in Korean. Clinical trials are necessary to confirm whether n-3 PUFA could prevent type 2 diabetes mellitus in Korean.