Abstract
OBJECTIVE: To assess effects of increasing omega-3, omega-6, and total polyunsaturated fatty acids (PUFA) on diabetes diagnosis and glucose metabolism. DESIGN: Systematic review and meta-analyses. DATA SOURCES: Medline, Embase, Cochrane CENTRAL, WHO International Clinical Trials Registry Platform, Clinicaltrials.gov, and trials in relevant systematic reviews. ELIGIBILITY CRITERIA: Randomised controlled trials of at least 24 weeks’ duration assessing effects of increasing α-linolenic acid, long chain omega-3, omega-6, or total PUFA, which collected data on diabetes diagnoses, fasting glucose or insulin, glycated haemoglobin (HbA1c), and/or homoeostatic model assessment for insulin resistance (HOMA-IR). DATA SYNTHESIS: Statistical analysis included random effects meta-analyses using relative risk and mean difference, and sensitivity analyses. Funnel plots were examined and subgrouping assessed effects of intervention type, replacement, baseline risk of diabetes and use of antidiabetes drugs, trial duration, and dose. Risk of bias was assessed with the Cochrane tool and quality of evidence with GRADE. RESULTS: 83 randomised controlled trials (mainly assessing effects of supplementary long chain omega-3) were included; 10 were at low summary risk of bias. Long chain omega-3 had little or no effect on likelihood of diagnosis of diabetes (relative risk 1.00, 95% confidence interval 0.85 to 1.17; 58 643 participants, 3.7% developed diabetes) or measures of glucose metabolism (HbA1c mean difference -0.02%, 95% confidence interval -0.07% to 0.04%; plasma glucose 0.04, 0.02 to 0.07, mmol/L; fasting insulin 1.02, -4.34 to 6.37, pmol/L; HOMA-IR 0.06, -0.21 to 0.33). A suggestion of negative outcomes was observed when dose of supplemental long chain omega-3 was above 4.4 g/d. Effects of α-linolenic acid, omega-6, and total PUFA on diagnosis of diabetes were unclear (as the evidence was of very low quality), but little or no effect on measures of glucose metabolism was seen, except that increasing α-linolenic acid may increase fasting insulin (by about 7%). No evidence was found that the omega-3/omega-6 ratio is important for diabetes or glucose metabolism. CONCLUSIONS: This is the most extensive systematic review of trials to date to assess effects of polyunsaturated fats on newly diagnosed diabetes and glucose metabolism, including previously unpublished data following contact with authors. Evidence suggests that increasing omega-3, omega-6, or total PUFA has little or no effect on prevention and treatment of type 2 diabetes mellitus.
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Key Points
This review found that long chain omega-3 fats seem to have little or no effect on type 2 diabetes or measures of glucose metabolism including insulin resistance (measured using HOMA-IR), glycated haemoglobin (HbA1c), fasting glucose, or insulin. Although effects of α-linolenic acid, omega-6, and total PUFA on diagnosis of diabetes were unclear (as the evidence was of very low quality), little or no effect on measures of glucose metabolism, except that increasing α-linolenic acid may increase fasting insulin (low quality evidence) was found. No evidence that the omega-3/omega-6 ratio is important to type 2 diabetes mellitus or glucose metabolism was shown.
Strengths of this review include its large size (including 81 trials, with more than 95 000 randomised participants with and without diabetes, from around the world), and searching of multiple databases. Creation of a dataset of randomised controlled trials regardless of outcomes and contacting authors to request relevant data allowed inclusion of data that would otherwise have been missed or remained unpublished (particularly for diagnosis of diabetes in populations not at high risk) and also allowed us to identify the extent and sometimes the import of missing data.
Weaknesses of the review include limited data on effects of increasing α-linolenic acid, omega-6, and total PUFA, as well as potentially serious risk of bias in many included trials. The review did not find evidence of the importance of the omega-3/omega-6 ratio, but limiting to trials comparing increased omega-3 fats with increased omega-6 limits the quantity of data (reducing our power to see any effect) and the quality (only one of the included trials was at low summary risk of bias) of the available information. Additionally, doses of omega-6 were often small, so the review could be missing important effects of the ratio.
Further randomised controlled trials of effects of α-linolenic acid, omega-6, oily fish, and total PUFA with rigorous methods (larger sample sizes, adequate and well reported allocation concealment and blinding, at least 12 months’ duration) on diagnosis of diabetes and measures of glucose metabolism would be helpful. Increasing long chain omega-3 had little or no effect on likelihood of diagnosis of diabetes or on glucose metabolism, with no difference by duration, baseline glucose metabolism, or nutrients replaced.There was a suggestion that high dose supplementation (>4.4 g/d) with long chain omega-3 may worsen glucose metabolism. Increasing α-linolenic acid, omega-6, and total polyunsaturated fatty acids had little or no effect on glucose metabolism, except that increasing α-linolenic acid may increase fasting insulin by about 7%.