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      Beneficial Effects of Omega-3 Fatty Acids on Low Density Lipoprotein Particle Size in Patients with Type 2 Diabetes Already under Statin Therapy

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          Abstract

          Beyond statin therapy for reducing low density lipoprotein cholesterol (LDL-C), additional therapeutic strategies are required to achieve more optimal reduction in cardiovascular risk among diabetic patients with dyslipidemia. To evaluate the effects and the safety of combined treatment with omega-3 fatty acids and statin in dyslipidemic patients with type 2 diabetes, we conducted a randomized, open-label study in Korea. Patients with persistent hypertriglyceridemia (≥200 mg/dL) while taking statin for at least 6 weeks were eligible. Fifty-one patients were randomized to receive either omega-3 fatty acid 4, 2 g, or no drug for 8 weeks while continuing statin therapy. After 8 weeks of treatment, the mean percentage change of low density lipoprotein (LDL) particle size and triglyceride (TG) level was greater in patients who were prescribed 4 g of omega-3 fatty acid with statin than in patients receiving statin monotherapy (2.8%±3.1% vs. 2.3%±3.6%, P=0.024; -41.0%±24.1% vs. -24.2%±31.9%, P=0.049). Coadministration of omega-3 fatty acids with statin increased LDL particle size and decreased TG level in dyslipidemic patients with type 2 diabetes. The therapy was well tolerated without significant adverse effects.

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          Most cited references11

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          Lipoprotein management in patients with cardiometabolic risk: consensus statement from the American Diabetes Association and the American College of Cardiology Foundation.

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            The forgotten majority: unfinished business in cardiovascular risk reduction.

            Despite meaningful progress in the identification of risk factors and the development of highly effective clinical tools, deaths from cardiovascular disease continue to increase worldwide. Sparked by an obesity epidemic, the metabolic syndrome and the rising incidence of type 2 diabetes have led to an upsurge of cardiovascular risk. Although pharmacologic treatments with the statin class of drugs have reduced cholesterol levels and lowered mortality rates, several large controlled clinical trials, including the Scandinavian Simvastatin Survival Study, the Cholesterol and Recurrent Events trial, the Air Force/Texas Coronary Atherosclerosis Prevention studies, and Long-term Intervention with Pravastatin in Ischemic Disease study, have indicated that cardiovascular events continue to occur in two thirds of all patients. Follow-up studies, such as the Heart Protection Study and the Pravastatin or Atorvastatin Evaluation and Infection Therapy/Thrombolysis In Myocardial Infarction-22 trials, reinforced these earlier results. Although therapy with gemfibrozil, a fibric acid derivative, showed reduced occurrence of cardiovascular events in the Helsinki Heart Study and the Veterans Affairs HDL Intervention Trial, results of other studies, e.g., the Bezafibrate Intervention Program and the Diabetes Atherosclerosis Intervention study, showed less encouraging results. Although lifestyle modifications, such as improved diet and increased exercise levels, benefit general health and the metabolic syndrome and insulin resistance in particular, most people continue to resist changes in their daily routines. Thus, physicians must continue to educate their patients regarding an optimal balance of drug therapy and personal behavior.
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              Ratio of triglycerides to HDL cholesterol is an indicator of LDL particle size in patients with type 2 diabetes and normal HDL cholesterol levels.

              In patients with type 2 diabetes, a normal HDL cholesterol level does not rule out that LDL particles may be small. Although techniques for analyzing LDL subfractions are not likely to be used in clinical practice, a prediction of LDL size based on a regular lipid profile may be useful for assessment of cardiovascular risk. Sixty patients with type 2 diabetes with acceptable glycemic control and an HDL cholesterol level > or = 1 mmol/l were recruited after cessation of lipid-altering treatments. LDL size was determined by 2-20% PAGE; patients having small LDL (n = 30) were compared with those having intermediate or large LDL (n = 30). Clinical characteristics, pharmacological therapies, lifestyle, and prevalence of diabetes-related complications were similar in both patient groups. LDL size correlated negatively with plasma triglycerides (TGs) (R2 = 0.52) and positively with HDL cholesterol (R2 = 0.14). However, an inverse correlation between the TG-to-HDL cholesterol molar ratio and LDL size was even stronger (R2 = 0.59). The ratio was > 1.33 in 90% of the patients with small LDL particles (95% CI 79.3-100) and 16.5% of those with larger LDL particles. A cutoff point of 1.33 for the TG-to-HDL cholesterol ratio distinguishes between patients having small LDL values better than TG cutoff of 1.70 and 1.45 mmol/l. The TG-to-HDL cholesterol ratio may be related to the processes involved in LDL size pathophysiology and relevant with regard to the risk of clinical vascular disease. It may be suitable for the selection of patients needing an earlier and aggressive treatment of lipid abnormalities.
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                Author and article information

                Journal
                Diabetes Metab J
                Diabetes Metab J
                DMJ
                Diabetes & Metabolism Journal
                Korean Diabetes Association
                2233-6079
                2233-6087
                June 2013
                14 June 2013
                : 37
                : 3
                : 207-211
                Affiliations
                [1 ]Department of Endocrinology, Gwangmyeong Sung Ae Hospital, Gwangmyeong, Korea.
                [2 ]Department of Endocrinology, Good Morning Hospital, Pyeongtaek, Korea.
                [3 ]Division of Endocrinology, Institute of Endocrine Research, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
                [4 ]Department of Endocrinology and Metabolism, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
                [5 ]Department of Endocrinology and Metabolism, National Health Insurance Cooperation Ilsan Hospital, Goyang, Korea.
                [6 ]Dr.Cho's Internal Medicine Clinic, Seoul, Korea.
                [7 ]Department of Endocrinology and Metabolism, CHA Bundang Medical Center, CHA University, Seongnam, Korea.
                Author notes
                Corresponding author: Seok Won Park. Department of Endocrinology and Metabolism, CHA Bundang Medical Center, CHA University, 59 Yatap-ro, Bundang-gu, Seongnam 463-712, Korea. spark@ 123456cha.ac.kr
                Corresponding author: Eun Jig Lee. Division of Endocrinology, Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, Korea. ejlee423@ 123456yuhs.ac
                Article
                10.4093/dmj.2013.37.3.207
                3689018
                23807924
                af4e98ce-0054-48ec-822a-b9b19f0d4566
                Copyright © 2013 Korean Diabetes Association

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 26 May 2012
                : 18 February 2013
                Categories
                Brief Report
                Clinical Care/Education

                Endocrinology & Diabetes
                diabetes mellitus, type 2,dyslipidemia,fatty acids, omega-3,hypertriglyceridemia,low density lipoprotein particle

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