Aims/hypothesis The study aimed to quantitatively summarise the dose–response relationships between cardiorespiratory fitness and muscular strength on the one hand and risk of type 2 diabetes on the other and estimate the hypothetical benefits associated with population-wide changes in the distribution of fitness. Methods We performed a systematic review with meta-analysis. The PubMed and EMBASE electronic databases were searched from inception dates to 12 December 2018 for cohort studies examining the association of cardiorespiratory fitness or muscular strength with risk of incident type 2 diabetes in adults. The quality of included studies was evaluated using the Newcastle–Ottawa Scale. Results Twenty-two studies of cardiorespiratory fitness and 13 studies of muscular strength were included in the systematic review with both exposures having ten estimates available for the primary adiposity- or body size-controlled meta-analysis. In random-effects meta-analysis including 40,286 incident cases of type 2 diabetes in 1,601,490 participants, each 1 metabolic equivalent (MET) higher cardiorespiratory fitness was associated with an 8% (95% CI 6%, 10%) lower RR of type 2 diabetes. The association was linear throughout the examined spectrum of cardiorespiratory fitness. In 39,233 cases and 1,713,468 participants each 1 SD higher muscular strength was associated with a 13% (95% CI 6%, 19%) lower RR of type 2 diabetes. We estimated that 4% to 21% of new annual cases of type 2 diabetes among 45–64-year-olds could be prevented by feasible and plausible population cardiorespiratory fitness changes. Conclusions/interpretation Relatively small increments in cardiorespiratory fitness and muscle strength were associated with clinically meaningful reductions in type 2 diabetes risk with indication of a linear dose–response relationship for cardiorespiratory fitness. Registration: PROSPERO (CRD42017064526). Electronic supplementary material The online version of this article (10.1007/s00125-019-4867-4) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

ObjectivesTo systematically review and analyse studies of high amounts of physical activity and mortality risk in the general population.Eligibility criteriaInclusion criteria related to follow-up (minimum 2 years), outcome (mortality from all causes, cancer, cardiovascular disease (CVD) or coronary heart disease), exposure (eg, a category of >1000 metabolic equivalent of task (MET) min/week), study design (prospective cohort, nested case control or case-cohort) and reports of cases and person years of exposure categories.Information sourcesSystematic searches were conducted in Embase and Pubmed from database inception to 2 March 2019.Risk of biasThe quality of the studies was assessed with the Newcastle–Ottawa scale.Included studiesFrom 31 368 studies identified, 48 were included. Two authors independently extracted outcome estimates and assessed study quality.Synthesis of resultsWe estimated hazard ratios (HRs) using random effect restricted cubic spline dose–response meta-analyses. Compared with the recommended level of physical activity (750 MET min/week), mortality risk was lower at physical activity levels exceeding the recommendations, at least until 5000 MET min/week for all cause mortality (HR=0.86, 95% CI 0.78 to 0.94) and for CVD mortality (HR=0.73, 95% CI 0.56 to 0.95).Strengths and limitations of evidenceThe strengths of this study include the detailed dose–response analyses, inclusion of 48 studies and examination of sources of heterogeneity. The limitations include the observational nature of the included studies and the inaccurate estimations of amount of physical activity.InterpretationCompared with the recommended level, mortality risk was lower at physical activity levels well above the recommended target range. Further, there was no threshold beyond which lifespan was compromised.RegistrationPROSPERO CRD42017055727.

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