ObjectiveTo assess effects of increasing omega-3, omega-6, and total polyunsaturated fatty acids (PUFA) on diabetes diagnosis and glucose metabolism.DesignSystematic review and meta-analyses.Data sourcesMedline, Embase, Cochrane CENTRAL, WHO International Clinical Trials Registry Platform, Clinicaltrials.gov, and trials in relevant systematic reviews.Eligibility criteriaRandomised 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 synthesisStatistical 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.Results83 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.ConclusionsThis 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date to assess effects of polyunsaturated fats on newly diagnosed diabetes and glucose metabolism, including previously unpublished data following contact with authors.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.Systematic review registrationPROSPERO CRD42017064110.

Pseudomonas aeruginosa is an opportunistic pathogen that regularly causes nosocomial infections in hospitalized patients. The type VI secretion system (T6SS) is responsible for the secretion of numerous virulence effector proteins that can both interfere with competing microbes and manipulate host cells. Here, we report a detailed investigation of a P. aeruginosa H2-T6SS-dependent phospholipase effector, TplE, which acts as a trans-kingdom toxin. Delivery of TplE to the periplasmic space of rival bacteria leads to growth inhibition. Importantly, TplE, also contains a eukaryotic PGAP1-like domain, which targets the host ER apparatus, ultimately leading to disruption of the ER. TplE activity leads to the activation of the unfolded protein response (UPR) through the IRE1α-XBP1 pathway, enhancing autophagic flux. These findings indicate that this T6SS-delivered phospholipase effector is active against both prokaryotic and eukaryotic cellular targets, highlighting the T6SS as a versatile weapon in the Pseudomonas arsenal.

This is the most extensive systematic review of RCTs conducted to date to assess effects of increasing PUFA on cardiovascular disease, mortality, lipids or adiposity. Increasing PUFA intake probably slightly reduces risk of coronary heart disease and cardiovascular disease events, may slightly reduce risk of coronary heart disease mortality and stroke (though not ruling out harms), but has little or no effect on all-cause or cardiovascular disease mortality. The mechanism may be via lipid reduction, but increasing PUFA probably slightly increases weight.

The current evidence does not show a definite association between health literacy and medication adherence in older adults with cardiovascular disease or diabetes mellitus. In the absence of a definite link, efforts to develop interventions to improve health literacy would not necessarily improve adherence to cardiovascular medications. There is an urgent need for robust studies outside of the US, with wider, generalized recruitment of participants.