Background: The aim of this study was to evaluate associations between body-weight fluctuation and risk of mortality and cardiovascular diseases (CVD).Methods: PubMed, EMBASE databases and Cochrane Library were searched for cohort studies published up to May 20, 2019, reporting on associations of body-weight fluctuation and mortality from all causes, CVD and cancer, as well as morbidity of CVD and hypertension. Summary relative risks (RRs) were estimated using a random-effects model.Results: Twenty-five eligible publications from 23 studies with 441,199 participants were included. Body-weight fluctuation was associated with increased risk for all-cause mortality (RR, 1.41; 95% confidence interval (CI): 1.27–1.57), CVD mortality (RR, 1.36; 95% CI 1.22–1.52), and morbidity of CVD (RR, 1.49, 95% CI 1.26–1.76) and hypertension (RR, 1.35, 95% CI 1.14–1.61). However, there was no significant association between weight fluctuation and cancer mortality (RR, 1.01; 95% CI 0.90–1.13). No evidence of publication bias was observed (all P > 0.05) except for studies on all-cause mortality (Egger's test, P = 0.001; Begg's test, P = 0.014).Conclusions: Body-weight fluctuation was associated with higher mortality due to all causes and CVD and a higher morbidity of CVD and hypertension.

BackgroundIncretin-based agents, including dipeptidyl peptidase-4 inhibitors (DPP-4Is) and glucagon-like peptide-1 agonists (GLP-1As), work via GLP-1 receptor for hyperglycemic control directly or indirectly, but have different effect on cardiovascular (CV) outcomes. The present study is to evaluate and compare effects of incretin-based agents on CV and pancreatic outcomes in patients with type 2 diabetes mellitus (T2DM) and high CV risk.MethodsSix prospective randomized controlled trials (EXMAINE, SAVOR-TIMI53, TECOS, ELIXA, LEADER and SUSTAIN-6), which included three trials for DPP-4Is and three trials for GLP-1As, with 55,248 participants were selected to assess the effect of different categories of incretin-based agents on death, CV outcomes (CV mortality, major adverse CV events, nonfatal myocardial infarction, nonfatal stroke, heart failure hospitalization), pancreatic events (acute pancreatitis and pancreatic cancer) as well as on hypoglycemia.ResultsWhen we evaluated the combined effect of six trials, the results suggested that incretin-based treatment had no significant effect on overall risks of CV and pancreatic outcomes compared with placebo. However, GLP-1As reduced all-cause death (RR = 0.90, 95% CI 0.82–0.98) and CV mortality (RR = 0.84, 95% CI 0.73–0.97), whereas DPP-4Is had no significant effect on CV outcomes but elevated the risk for acute pancreatitis (OR = 1.76, 95% CI 1.14–2.72) and hypoglycemia (both any and severe hypoglycemia), while GLP-1As lowered the risk of severe hypoglycemia.ConclusionsGLP-1As decreased risks of all-cause and CV mortality and severe hypoglycemia, whereas DPP-4Is had no effect on CV outcomes but increased risks in acute pancreatitis and hypoglycemia.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-017-0512-z) contains supplementary material, which is available to authorized users.

Betatrophin is regarded as a liver-produced hormone induced by insulin resistance (IR). However, it remains largely unknown how IR regulates betatrophin expression. To study whether IR could regulate betatrophin expression and the corresponding molecular mechanisms, betatrophin levels were examined in 6 in vitro IR models which were established using human hepatocytes L02 with different agents, including tumor necrosis factor-α, interleukin-1β, dexamethasone, palmitate, high glucose and insulin and betatrophin levels were elevated only in the insulin group. These results suggest that it is insulin, not IR that promotes betatrophin expression. In the meantime, PI3K/Akt pathway was activated by insulin and suppressed by above agents that caused IR. Insulin-upregulated betatrophin expression was suppressed by PI3K/Akt inhibitors and IR, suggesting that insulin upregulates and IR decreases betatrophin production through PI3K/Akt pathway. Consistently, the treatment of insulin in mice dose-dependently upregulated betatrophin levels, and the administration of metformin in IR mice also stimulated betatrophin production since published study showed metformin improved PI3K/Akt pathway and IR. In humans, compared with those without insulin treatment, serum betatrophin levels were increased in type 2 diabetic patients with insulin treatment. In conclusion, insulin stimulates betatrophin secretion through PI3K/Akt pathway and IR may play an opposite role.