Aims/hypothesis Muscle mass and strength may protect against type 2 diabetes as a sink for glucose disposal. In randomised controlled trials, resistance training improves glucose metabolism in people with the metabolic syndrome. Whether increasing muscle mass and strength protects against diabetes in the general population is unknown. We assessed the effect of markers of muscle mass and strength on diabetes and glycaemic traits using bi-directional Mendelian randomisation. Methods Inverse variance weighting estimates were obtained by applying genetic variants that predict male lean mass, female lean mass and grip strength, obtained from the UK Biobank GWAS, to the largest available case-control study of diabetes (DIAbetes Genetics Replication And Meta-analysis [DIAGRAM]; n = 74,124 cases and 824,006 controls) and to a study of glycaemic traits (Meta-Analyses of Glucose and Insulin-related traits Consortium [MAGIC]). Conversely, we also applied genetic variants that predict diabetes, HbA 1c , fasting glucose, fasting insulin and HOMA-B to UK Biobank summary statistics for genetic association with lean mass and grip strength. As sensitivity analyses we used weighted median, Mendelian randomisation (MR)-Egger and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and removed pleiotropic SNPs. Results Grip strength was not significantly associated with diabetes using inverse variance weighting (OR 0.72 per SD increase in grip strength, 95% CI 0.51, 1.01, p = 0.06) and including pleiotropic SNPs but was significantly associated with diabetes using MR-PRESSO (OR 0.77, 95% CI 0.62, 0.95, p = 0.02) after removing pleiotropic SNPs. Female lean mass was significantly associated with diabetes (OR 0.91, 95% CI 0.84, 0.99, p = 0.02) while male lean mass was not significant but directionally similar (OR 0.94, 95% CI 0.88, 1.01, p = 0.09). Conversely, diabetes was inversely and significantly associated with male lean mass (β −0.02 SD change in lean mass, 95% CI −0.04, −0.00, p = 0.04) and grip strength (β −0.01, 95% CI −0.02, −0.00, p = 0.01). Conclusions/interpretation Increased muscle mass and strength may be related to lower diabetes risk. Diabetes may also be associated with grip strength and lean mass. Muscle strength could warrant further investigation as a possible target of intervention for diabetes prevention.

Background Systemic inflammation has been suggested to be associated with Alzheimer’s-disease progression, although whether it is a cause or a downstream effect is still controversial. This study aims to assess the effect of systemic inflammatory regulators on Alzheimer’s disease within a bidirectional Mendelian-randomization design. Methods Genetic associations with Alzheimer’s disease were obtained from the largest and most up-to-date genome-wide association study (GWAS) (cases and proxy cases: 71 880; controls: 383 378) and with inflammatory regulators from two recent GWASs on the human proteome and cytokines. Estimates were obtained by inverse-variance weighting with sensitivity analyses using MR-Egger, weighted median and MR-PRESSO. Possible bias due to selective survival and competing risk was also considered. Results None of 41 systemic inflammatory regulators was associated with risk of Alzheimer’s disease with consistent results in validation analysis. Conversely, Alzheimer’s disease was suggestively associated with five systemic inflammatory regulators, i.e. basic fibroblast growth factor, granulocyte-colony-stimulating factor, interferon gamma, interleukin-13 and interleukin-7. Conclusion The systemic inflammatory regulators considered did not appear to be associated with the risk of Alzheimer’s disease. Conversely, specific systemic inflammatory regulators may be downstream effects of Alzheimer’s disease or consequences of common factors causing both inflammation and Alzheimer’s disease.

Food reformulation has been suggested to be one of the strategies to reduce population added sugar (AS) intake. This study aims to investigate the untested assumption that a reduction in AS through reformulation will result in a reduction in population intakes of AS and energy. Plausible dietary data from 4,140 respondents of an Australian national nutrition survey were used. Dietary modelling was performed at AS reductions of 10%, 15%, and 25% using four strategies: simple removal of AS or replacement with non-nutritive sweeteners (NNS), and replacement of AS with NNS and either: polyols, 50% fibres or 50% maltodextrin. Paired t-tests were conducted to compare the intake of energy, fat, and AS pre- and post-reformulation. The chosen reformulation strategies resulted in a projected reduction in AS and energy, with the greatest reduction found in 25% reformulation which was the highest level modelled. The overall projected mean (SD) reduction in energy and AS after 25% reformulation was 114 (92) kJ/day and 11.73 (7.52) g/day, p < 0.001. To conclude, product reformulation may be a potentially useful strategy for reducing AS intake. Although the magnitude of projected reduction was small at the individual level, the impact may be meaningful at a population level.

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