Abstract
Objective: This study aimed to quantify the association of essential and other plasma fatty acids biomarkers with macrovascular disease, microvascular disease and death in individuals with type 2 diabetes. Design and method: A case cohort study (N = 3,576), including 654 macrovascular events, 341 microvascular events and 631 deaths during 5 years of median follow-up was undertaken in participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study. The fatty acids measured from baseline plasma samples, by proton nuclear magnetic resonance (NMR) analysis, were omega-3, docosahexaenoic acid (DHA), omega-6, linoleic acid (LA), polyunsaturated (PUFA), monounsaturated (MUFA) and saturated fatty acids (SFA). Hazard ratios (HRs) were modelled per standard deviation higher percentage fatty acid. C-statistics and net reclassification improvement were used to test the added value of fatty acids for risk prediction. Results: After adjustment for traditional cardiovascular risk factors, an inverse association was observed for omega-3 fatty acids and DHA (HR [95%CI]: 0.87 [0.80, 0.95] and 0.88 [0.81, 0.96], respectively per 1SD higher percentage) with the risk of macrovascular events, and for omega-3 fatty acids (HR [95%CI]: 0.91 [0.84, 0.99] per 1SD higher percentage) with death. Such associations were also evident when investigating absolute levels of fatty acids. There were no statistically significant associations between any fatty acids and microvascular disease after adjustment. However, there was limited improvement in predictive ability of models when any fatty acid was added. Conclusions: Plasma omega-3 fatty acids and DHA were found to be inversely associated with macrovascular disease, whilst omega-3 fatty acids was also inversely associated with death. These results provide additional support for regular consumption of food rich in omega-3 fatty acids in type 2 diabetes.
Highlights
Type 2 diabetes is associated with a substantial risk of macrovascular disease, including coronary and cerebrovascular diseases; microvascular disease, including kidney disease and retinopathy; and premature death [1]
Similar findings were observed in the absolute fatty acid levels, for most fatty acids considered in this study, where the mean levels were significantly higher in participants who were free from major macrovascular events and alive at the end of the study
A Presented for the multiple-adjusted model with traditional cardiovascular disease (CVD) risk factors; the difference in the C statistic given the addition of each fatty acid is presented as a difference with 95% CI of the difference b Adjusted for age, sex, region, randomised treatment, history of macrovascular disease, duration of diabetes, current smoking status, systolic BP, BMI, urinary albumin/creatinine ratio, eGFR, HbA1c, HDL-cholesterol, triacylglycerols, and use of aspirin or other antiplatelet agents, statins or other lipid-lowering agents, β-blockers, and ACE inhibitors or angiotensin receptor blockers stronger associations with cardiovascular death and non-fatal stroke
Summary
Type 2 diabetes is associated with a substantial risk of macrovascular disease, including coronary and cerebrovascular diseases; microvascular disease, including kidney disease and retinopathy; and premature death [1]. The recent Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) observed pronounced protective effects of high-dose (4 g/day) supplementation with n-3 fatty acids against cardiovascular outcomes among individuals with established CVD or with diabetes and other risk factors [7]. Based upon these results, the recent scientific statement from the American Heart Association (AHA) recommends the prescription of n-3 fatty acids, whether EPA+DHA or EPA only, at a dose of 4 g/day as an effective and safe treatment for reducing triacylglycerols among individuals with hypertriglyceridaemia [8]
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