Omega-3, omega-6 and total dietary polyunsaturated fat for prevention and treatment of type 2 diabetes mellitus: systematic review & meta-analysis of randomised controlled trials

Objective: To assess effects of increasing omega-3, omega-6 and total polyunsaturated fatty acid (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 (RCTs) of ≥24 weeks duration assessing effects of increasing alpha-linolenic acid (ALA), long-chain omega-3 (LCn3), omega-6 or total polyunsaturated fats (PUFA), that collected data on diabetes diagnoses, fasting glucose or insulin, glycated haemoglobin (HbA1c) and/or homeostatic model assessment for insulin resistance (HOMA-IR). Data Synthesis Statistical analysis included random-effects meta-analyses using relative risk (RR) and mean difference (MD), and sensitivity analyses. Funnel plots were examined and subgrouping assessed effects of intervention type, replacement, baseline diabetes risk and use of diabetic medications, trial duration and dose. Risk of bias was assessed using the Cochrane tool, quality of evidence using GRADE. Results: 83 RCTs (mainly assessing effects of supplementary LCn3) were included, ten were at low summary risk of bias. LCn3 had little or no effect on likelihood of diabetes diagnosis (RR 1.00, 95% CI 0.85 to 1.17, 58643 participants, 3.7% developed diabetes) or measures of glucose metabolism (HbA1c MD -0.02%, -0.07 to 0.04; plasma glucose MD 0.04mmol/L, 95% CI 0.02 to 0.07; fasting insulin MD 1.02 pmol/L, 95% CI -4.34 to 6.37; HOMA-IR MD 0.06, 95% CI -0.21 to 0.33). There was a suggestion of negative outcomes when supplemental LCn3 dose was >4.4g/d. While effects of ALA, omega-6 and total PUFA on diabetes diagnosis were unclear (as the evidence was of very low-quality), we found little or no effect on measures of glucose metabolism, except that increasing ALA may increase fasting insulin (by ~7%). We found no evidence 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date to assess effects of polyunsaturated fats on newly diagnosed diabetes and glucose metabolism, including previously unpublished data following author contact. 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.  Systematic Review Registration: PROSPERO registry no. CRD42017064110