(01-10-07) Supplementary EPA Reduces Atherosclerosis Progression in Type 2 Diabetics

Major cardiovascular problems are responsible for about 80% of the mortality in people with diabetes mellitus (diabetes). Impaired circulation in the large and small blood vessels is a frequent diabetic complication. In the larger arteries, lipid deposits, blood clots and plaque impede blood flow, leading to cerebrovascular, peripheral artery and cardiovascular diseases. This pathology is known as macroangiopathy. Impaired circulation in the small blood vessels, microangiopathy, leads to kidney failure and diabetic retinopathy. Several causes of damaged blood vessels are specific to diabetes: for example, the formation of advanced glycation end-products and the desulfation of glycosaminoglycan. Other vascular problems include reduced nitric oxide production, increased oxidative stress, and endothelial inflammation. Because the consequences of these vascular complications are potentially fatal, there is considerable clinical emphasis on reducing these macro- and microangiopathies. It is believed that careful attention to controlling blood sugar and glycosylated hemoglobin is effective in counteracting diabetic microvascular damage. A more comprehensive approach to improving lifestyle, lipid profile and hypertension is required to reduce cardiovascular risks.

To control arterial disease and reduce the chance of thrombosis in diabetic patients, physicians often prescribe aspirin, which carries a risk of hemorrhage, gastrointestinal effects and lack of patient response. An additional therapeutic choice would be n-3 LC-PUFAs. These fatty acids suppress thromboxane production that promotes platelet aggregation and inflammatory responses. They could potentially improve blood flow and the angiopathies associated with diabetes. To find out if n-3 LC-PUFAs affected the progress of macroangiopathy, investigators at the Juntendo University School of Medicine in Tokyo conducted an open-label prospective trial in 81 diabetic Japanese patients and monitored the progression of atherosclerosis in the carotid artery.

Patients with type 2 diabetes, who did not have serious complications, such as renal, hepatic or overt cardiovascular disease, were recruited from the outpatient clinic. Their average age was 60. Patients were randomly divided into 2 groups, matched for age and gender after their first screening visit. Both groups received standard therapy and appropriate medications to control blood sugar, blood pressure and lipids. One group received 1.8 g/day of supplementary eicosapentaenoic acid (EPA), an n-3 LC-PUFA, provided as ethyl ester capsules. Participants received bilateral ultrasonography of their carotid arteries, with images taken in 3 different longitudinal projections. Scans of the common carotid artery, carotid bulb and internal carotid artery were used to calculate arterial intima-media thickness. These pictures permit measurement of arterial blockage and changes in the obstructions related to study interventions. The technique is commonly used to assess the progression of atherosclerosis.

Study participants also received measurements of their brachial ankle pressure and brachial-ankle pulse wave velocity (evaluations of blood flow) as well as clinical assessments of glycosylated hemoglobin, blood lipids and blood pressure. All measurements were performed at baseline and after 2 years, although patients were monitored every 3 months. Sixty patients completed the study. At baseline, the 2 groups were not significantly different in clinical assessments or carotid intima-media thickness.

After 2 years, the mean carotid intima-media thickness decreased 4.7% in the EPA group, but increased 2.4% in the control group (Figure 1), a difference that was statistically significant (P=0.03). The maximum intima-media thickness diminished by 11.8% in the EPA group compared with a decrease of 0.9% in the untreated patients P<0.001). Arterial stiffness, as reflected in the 2.3% decreased brachial-ankle pulse wave velocity measurements was reduced in patients consuming EPA, but worsened by 5.4% in the untreated patients. The difference in glycosylated hemoglobin between the 2 groups was not statistically significant. Within-group statistical analysis indicated that the changes in intima-media thickness in patients consuming EPA were statistically significant over the 2-year period. No other clinical parameters differed between the 2 groups. Considering the high fish consumption in Japan, more information on baseline and endpoint EPA status would have been useful. Use of a blinded placebo-controlled study design would have strengthened this study.

Nevertheless, these findings show that when EPA consumption increases, favorable changes in occur in diabetics that may retard atherosclerosis. The study also supports the limited number of studies in various patient populations reporting reduced progression of atherosclerotic plaque related to n-3 LC-PUFA intake or status. For example, women with coronary artery disease and the highest concentrations of phospholipid docosahexaenoic acid (DHA) had the least reduction in artery inner diameter compared with women with lower DHA concentrations. Progression of atherosclerotic lesions was slowed in monkeys consuming EPA and in postmenopausal diabetic women consuming 2 or more fish meals/week. These encouraging reports suggest that controlled trials of n-3 LC-PUFA supplementation in type 2 diabetic patients are much needed.
Mita T, Watada H, Ogihara T, Nomiyama T, Ogawa O, Kinoshita J, Shimizu T, Hirose T, Tanaka Y, Kawamori R. Eicosapentaenoic acid reduces the progression of carotid intima-media thickness in patients with type 2 diabetes.

Source: Atherosclerosis 2007;191:162-167. [PubMed]

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