Prolonged time spent in sedentary behaviors (i.e., activities performed while sitting or reclining) has been consistently shown as an independent risk factor for increased cardiometabolic risk and all-cause mortality, whereas breaking up sedentary time is associated with improved cardiometabolic profile. However, there is still great controversy with the respect to what would be the optimal or minimum type, intensity, and frequency of physical activity necessary to revenue such positive outcomes in different populations. In this review, we aimed to discuss the available evidence from prospective experimental studies regarding the beneficial effects of breaking up prolonged sitting time on cardiometabolic risk factors, and the influence of intensity, frequency, and volume of the physical activity replacing sitting. A structured computer-based search on the electronic databases PUBMED and SCOPUS was independently conducted by two researchers. Only prospective intervention studies (controlled and uncontrolled) evaluating the effects of explicitly replacing sitting time with physical activity (including standing) on metabolic parameters as outcomes were included. Seventeen studies were included in the review. The currently available prospective experimental studies do advocate that breaking up sitting time and replacing it with light-intensity ambulatory physical activity and standing may be a stimulus sufficient enough to induce acute favorable changes in the postprandial metabolic parameters in physically inactive and type 2 diabetic subjects, whereas a higher intensity or volume seems to be more effective in rendering such positive outcomes in young habitually physically active subjects. Prospective experimental studies provide considerable evidence of the positive effects of breaking up prolonged time spent sitting on metabolic outcomes. However, it seems that the type, intensity, and frequency of physical activity necessary to effectively counteract the detrimental effects of prolonged sitting may differ according to the subjects' characteristics, especially with respect to the subjects' habitual physical activity level.

Importance It is unclear whether a lifestyle intervention can maintain glycemic control in patients with type 2 diabetes. Objective To test whether an intensive lifestyle intervention results in equivalent glycemic control compared with standard care and, secondarily, leads to a reduction in glucose-lowering medication in participants with type 2 diabetes. Design, Setting, and Participants Randomized, assessor-blinded, single-center study within Region Zealand and the Capital Region of Denmark (April 2015-August 2016). Ninety-eight adult participants with non–insulin-dependent type 2 diabetes who were diagnosed for less than 10 years were included. Participants were randomly assigned (2:1; stratified by sex) to the lifestyle group (n = 64) or the standard care group (n = 34). Interventions All participants received standard care with individual counseling and standardized, blinded, target-driven medical therapy. Additionally, the lifestyle intervention included 5 to 6 weekly aerobic training sessions (duration 30-60 minutes), of which 2 to 3 sessions were combined with resistance training. The lifestyle participants received dietary plans aiming for a body mass index of 25 or less. Participants were followed up for 12 months. Main Outcomes and Measures Primary outcome was change in hemoglobin A_1c(HbA_1c) from baseline to 12-month follow-up, and equivalence was prespecified by a CI margin of ±0.4% based on the intention-to-treat population. Superiority analysis was performed on the secondary outcome reductions in glucose-lowering medication. Results Among 98 randomized participants (mean age, 54.6 years [SD, 8.9]; women, 47 [48%]; mean baseline HbA_1c, 6.7%), 93 participants completed the trial. From baseline to 12-month follow-up, the mean HbA_1clevel changed from 6.65% to 6.34% in the lifestyle group and from 6.74% to 6.66% in the standard care group (mean between-group difference in change of −0.26% [95% CI, −0.52% to −0.01%]), not meeting the criteria for equivalence (P = .15). Reduction in glucose-lowering medications occurred in 47 participants (73.5%) in the lifestyle group and 9 participants (26.4%) in the standard care group (difference, 47.1 percentage points [95% CI, 28.6-65.3]). There were 32 adverse events (most commonly musculoskeletal pain or discomfort and mild hypoglycemia) in the lifestyle group and 5 in the standard care group. Conclusions and Relevance Among adults with type 2 diabetes diagnosed for less than 10 years, a lifestyle intervention compared with standard care resulted in a change in glycemic control that did not reach the criterion for equivalence, but was in a direction consistent with benefit. Further research is needed to assess superiority, as well as generalizability and durability of findings. Trial Registration clinicaltrials.gov Identifier:NCT02417012

Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.

Objectives: To systematically review and analyse studies of high amounts of physical activity and mortality risk in the general population. Eligibility criteria: Inclusion 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 sources: Systematic searches were conducted in Embase and Pubmed from database inception to 2 March 2019. Risk of bias: The quality of the studies was assessed with the Newcastle–Ottawa scale. Included studies: From 31 368 studies identified, 48 were included. Two authors independently extracted outcome estimates and assessed study quality. Synthesis of results: We 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 evidence: The 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. Interpretation: Compared 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. Registration: PROSPERO CRD42017055727.