A low ratio of serum eicosapentaenoic acid to arachidonic acid (EPA/AA) has been reported to correlate with coronary heart disease (1–3), and no previous studies have investigated serum polyunsaturated fatty acid (PUFA) levels exclusively in patients with diabetes, in whom atherosclerotic diseases are commonly found. We therefore examined the association between serum EPA/AA ratio and the prevalence of diabetic angiopathies in patients with type 2 diabetes.
The serum levels of EPA and AA were determined in 744 Japanese patients with type 2 diabetes (aged 67 ± 12 years, 60% males, duration of diabetes 13 ± 11 years, estimated glomerular filtration rate [eGFR] 78 ± 32 mL/min/1.73 m2, serum EPA 79.6 ± 52.6 μg/mL, serum AA 189.5 ± 55.0 μg/mL) and in 285 age- and sex-matched subjects without diabetes between October and December 2012. Individuals taking EPA capsules were excluded from the study.
The serum EPA/AA ratio was not significantly different between the diabetic (mean ± SD 0.45 ± 0.31, median 0.37) and nondiabetic (0.48 ± 0.31, 0.39) groups. The EPA/AA ratio correlated significantly with age in both the diabetic (r = 0.25, P < 0.01) and the nondiabetic (r = 0.26, P < 0.01) groups. A logistic regression analysis demonstrated that a lower EPA/AA ratio was associated with an eGFR <60 mL/min/1.73 m2 (odds ratio 0.43 [95% CI 0.19–0.92], P = 0.04), coronary heart disease (0.43 [0.20–0.88], P = 0.03), and peripheral arterial disease (0.17 [0.03–0.70], P = 0.03) in diabetic patients when the EPA/AA ratio and known risk factors such as age, sex, smoking history, BMI, hypertension, and dyslipidemia were used as independent variables. Although the EPA/AA ratio was not significantly different between subjects with an eGFR ≥60 mL/min/1.73 m2 and those with an eGFR <60 mL/min/1.73 m2 among the total sample, the EPA/AA ratio was significantly lower in subjects with an eGFR <60 mL/min/1.73 m2 (0.45 ± 0.25) than in those with an eGFR ≥60 mL/min/1.73 m2 (0.56 ± 0.38) in the subgroup aged ≥75 years (Fig. 1A). The EPA/AA ratio was also significantly lower in subjects with coronary heart disease (0.44 ± 0.23) than in those without (0.57 ± 0.38) in the subgroup aged ≥75 years (Fig. 1B).
Serum EPA/AA ratios between diabetic subjects with an eGFR ≥60 mL/min/1.73 m2 and those with an eGFR <60 mL/min/1.73 m2 among age-groups (A) and between diabetic subjects with and without coronary heart disease among age-groups (B). *P = 0.04 vs. subjects with an eGFR ≥60 mL/min/1.73 m2, **P < 0.01 vs. subjects without coronary heart disease (Wilcoxon signed rank test).
Serum EPA/AA ratios between diabetic subjects with an eGFR ≥60 mL/min/1.73 m2 and those with an eGFR <60 mL/min/1.73 m2 among age-groups (A) and between diabetic subjects with and without coronary heart disease among age-groups (B). *P = 0.04 vs. subjects with an eGFR ≥60 mL/min/1.73 m2, **P < 0.01 vs. subjects without coronary heart disease (Wilcoxon signed rank test).
Several studies have demonstrated that the consumption of fish oil containing n-3 PUFAs reduces the risk of cardiovascular events and mortality (4,5). We found that a lower serum EPA/AA ratio is associated with coronary heart disease and renal impairment in the older patients with diabetes. Earlier intervention with EPA might be desirable in younger diabetic patients with lower EPA/AA levels if the administration of EPA is effective for preventing vascular events. Because the EPA/AA ratio was positively associated with age, it might be necessary to make separate reference values for different age-groups.
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Acknowledgments.
The authors thank Tomoko Koyanagi (Secretarial Section, Edogawa Hospital) for valuable help in the data collection. The authors also thank SRL Inc. for the information about the measurement of PUFA concentration.
Duality of Interest. No potential conflicts of interest relevant to this article were reported.
Author Contributions. H.I. collected and analyzed data and wrote the manuscript. H.O. collected data, contributed to the discussion, and reviewed and edited the manuscript. T.C., T.O., M.S., S.N., S.A., M.M., and M.T. collected data. M.A. collected data and contributed to the discussion. H.I. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
