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      Effects of Omega-3 Fatty Acid Supplementation on Diabetic Nephropathy Progression in Patients with Diabetes and Hypertriglyceridemia

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          Abstract

          Beneficial effects of omega-3 fatty acid (O3FA) supplementation in a wide range of disease condition have been well studied. However, there is limited information regarding the effects of O3FAs on chronic kidney disease (CKD), especially in diabetic nephropathy (DN) with hypertriglyceridemia. We investigate whether O3FA supplementation could help maintain renal function in patients with diabetes and hypertriglyceridemia. Total 344 type 2 diabetic patients with a history of O3FA supplementation for managing hypertriglyceridemia were included. Reduction in urine albumin to creatinine ratio (ACR) and glomerular filtrate rate (GFR) were examined. Subgroup analyses were stratified according to the daily O3FA doses. Serum total cholesterol, triglyceride, and urine ACR significantly reduced after O3FA supplementation. Overall, 172 (50.0%) patients did not experience renal function loss, and 125 (36.3%) patients had a GFR with a positive slope. The patients treated with O3FAs at 4g/day showed greater maintenance in renal function than those treated with lower dosages (p < 0.001). This dose dependent effect remains significant after adjustment for multiple variables. O3FA supplementation in diabetic patients with hypertriglyceridemia shows benefits of reducing albuminuria and maintaining renal function. The effects are dependent on the dose of daily O3FA supplementation.

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          Diabetic nephropathy: diagnosis, prevention, and treatment.

          Jorge Gross, Mirela de Azevedo, Sandra P Silveiro … (2005)
          Diabetic nephropathy is the leading cause of kidney disease in patients starting renal replacement therapy and affects approximately 40% of type 1 and type 2 diabetic patients. It increases the risk of death, mainly from cardiovascular causes, and is defined by increased urinary albumin excretion (UAE) in the absence of other renal diseases. Diabetic nephropathy is categorized into stages: microalbuminuria (UAE >20 microg/min and or =200 microg/min). Hyperglycemia, increased blood pressure levels, and genetic predisposition are the main risk factors for the development of diabetic nephropathy. Elevated serum lipids, smoking habits, and the amount and origin of dietary protein also seem to play a role as risk factors. Screening for microalbuminuria should be performed yearly, starting 5 years after diagnosis in type 1 diabetes or earlier in the presence of puberty or poor metabolic control. In patients with type 2 diabetes, screening should be performed at diagnosis and yearly thereafter. Patients with micro- and macroalbuminuria should undergo an evaluation regarding the presence of comorbid associations, especially retinopathy and macrovascular disease. Achieving the best metabolic control (A1c 1.0 g/24 h and increased serum creatinine), using drugs with blockade effect on the renin-angiotensin-aldosterone system, and treating dyslipidemia (LDL cholesterol <100 mg/dl) are effective strategies for preventing the development of microalbuminuria, in delaying the progression to more advanced stages of nephropathy and in reducing cardiovascular mortality in patients with type 1 and type 2 diabetes.
          Article 0 comments Cited 266 times – based on 0 reviews     Review now
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            N-3 polyunsaturated fatty acids in coronary heart disease: a meta-analysis of randomized controlled trials.

            Heiner C Bucher, Peter Hengstler, Christian Schindler … (2002)
            Observational studies have shown an inconsistent association between n-3 polyunsaturated fatty acids and the risk of coronary heart disease. We investigated the effects of dietary and non-dietary (supplemental) intake of n-3 polyunsaturated fatty acids on coronary heart disease. We searched the literature to identify randomized controlled trials that compared dietary or non-dietary intake of n-3 polyunsaturated fatty acids with a control diet or placebo in patients with coronary heart disease. Studies had to have at least 6 months of follow-up data, and to have reported clinical endpoint data. We identified 11 trials, published between 1966 and 1999, which included 7951 patients in the intervention and 7855 patients in the control groups. The risk ratio of nonfatal myocardial infarction in patients who were on n-3 polyunsaturated fatty acid-enriched diets compared with control diets or placebo was 0.8 (95% confidence interval [CI]: 0.5 to 1.2, P = 0.16; Breslow-Day test for heterogeneity, P = 0.01), and the risk ratio of fatal myocardial infarction was 0.7 (95% CI: 0.6 to 0.8, P 0.20). In 5 trials, sudden death was associated with a risk ratio of 0.7 (95% CI: 0.6 to 0.9, P 0.20), whereas the risk ratio of overall mortality was 0.8 (95% CI: 0.7 to 0.9, P 0.20). There was no difference in summary estimates between dietary and non-dietary interventions of n-3 polyunsaturated fatty acids for all endpoints. This meta-analysis suggests that dietary and non-dietary intake of n-3 polyunsaturated fatty acids reduces overall mortality, mortality due to myocardial infarction, and sudden death in patients with coronary heart disease.
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              Does fish oil lower blood pressure? A meta-analysis of controlled trials.

              M C Morris, F Sacks, B Rosner (1993)
              In a meta-analysis of 31 placebo-controlled trials on 1356 subjects, we examined the effect of omega-3 fatty acids in fish oil on blood pressure by grouping studies that were similar in fish oil dose, length of treatment, health of the subjects, or study design. The mean reduction in blood pressure caused by fish oil for the 31 studies was -3.0/-1.5 mm Hg (95% confidence intervals: systolic blood pressure: -4.5, -1.5; diastolic blood pressure: -2.2, -0.8). There was a statistically significant dose-response effect when studies were grouped by omega-3 fatty acid dose: -1.3/-0.7 mm Hg at doses < or = 3 g/d, -2.9/-1.6 mm Hg at 3.3 to 7 g/d, and -8.1/-5.8 mm Hg at 15 g/d. Both eicosapentaenoic acid and docosahexaenoic acid were significantly related to blood pressure response. There was no effect on blood pressure in eight studies of "healthy" persons (mean reduction, -0.4/-0.7 mm Hg) at an overall mean dose of 4.2 g omega-3 fatty acids/d. By contrast, there was a significant effect of -3.4/-2.0 mm Hg in the group of hypertensive studies with a mean fish oil dose of 5.6 g/d and on systolic blood pressure only in six studies of hypercholesterolemic patients (-4.4/-1.1 mm Hg) with a mean dose of 4.0 g/d. A nonsignificant decrease in blood pressure was observed in four studies of patients with atherosclerotic cardiovascular disease (-6.3/-2.9 mm Hg). Variations in the length of treatment (from 3 to 24 weeks), type of placebo, and study design (crossover or parallel groups) did not appear to account for inconsistent findings among studies. There is a dose-response effect of fish oil on blood pressure of -0.66/-0.35 mm Hg/g omega-3 fatty acids. The hypotensive effect may be strongest in hypertensive subjects and those with clinical atherosclerotic disease or hypercholesterolemia.
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                Author and article information

                Contributors
                Wolf-Hagen Schunck: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 2 May 2016
                Publication date Collection: 2016
                Volume: 11
                Issue: 5
                Electronic Location Identifier: e0154683
                Affiliations
                [1 ]Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
                [2 ]Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
                [3 ]Institute of Endocrine Research, Yonsei University College of Medicine, Seoul, Korea
                [4 ]Division of Nephrology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
                [5 ]Graduate school, Yonsei University College of Medicine, Seoul, Korea
                Max Delbrueck Center for Molecular Medicine, GERMANY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: EH YY ESK. Performed the experiments: EH YY ESK. Analyzed the data: EH YY GK YL HJW. Contributed reagents/materials/analysis tools: BWL BSC BSK ESK. Wrote the paper: EH YY ESK.

                Author information
                http://orcid.org/0000-0002-0364-4675
                Article
                Publisher ID: PONE-D-15-47927
                DOI: 10.1371/journal.pone.0154683
                PMC ID: 4852914
                PubMed ID: 27135947
                SO-VID: 6217e874-8cf0-4645-bb21-970aa6d24ed5
                Copyright © © 2016 Han et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 2 November 2015
                Date accepted : 18 April 2016
                Page count
                Figures: 0, Tables: 4, Pages: 11
                Funding
                The authors have no support or funding to report.
                Categories
                Subject: Research Article
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Renal Physiology
                Subject: Glomerular Filtration Rate
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Renal Physiology
                Subject: Glomerular Filtration Rate
                Subject: Medicine and Health Sciences
                Subject: Endocrinology
                Subject: Endocrine Disorders
                Subject: Diabetes Mellitus
                Subject: Medicine and Health Sciences
                Subject: Metabolic Disorders
                Subject: Diabetes Mellitus
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Body Fluids
                Subject: Urine
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Body Fluids
                Subject: Urine
                Subject: Biology and Life Sciences
                Subject: Physiology
                Subject: Body Fluids
                Subject: Urine
                Subject: Medicine and Health Sciences
                Subject: Physiology
                Subject: Body Fluids
                Subject: Urine
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Lipids
                Subject: Cholesterol
                Subject: Biology and Life Sciences
                Subject: Anatomy
                Subject: Renal System
                Subject: Medicine and Health Sciences
                Subject: Anatomy
                Subject: Renal System
                Subject: Medicine and Health Sciences
                Subject: Vascular Medicine
                Subject: Blood Pressure
                Subject: Medicine and Health Sciences
                Subject: Pharmacology
                Subject: Drugs
                Subject: Statins
                Subject: Medicine and Health Sciences
                Subject: Nephrology
                Subject: Chronic Kidney Disease
                Custom metadata
                Data Availability All relevant data are within the paper and its Supporting Information files.

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