Emerging insights into the roles of ANGPTL8 beyond glucose and lipid metabolism.

Angiopoietin-like protein 8 (ANGPTL8) is a secreted protein predominantly expressed in liver and adipose tissue. ANGPTL8 modulates the clearance of triglycerides (TGs) by suppressing the activity of lipoprotein lipase (LPL) within the plasma. Previous studies found that circulating ANGPTL8 levels were significantly increased in metabolic disorder-related diseases, such as type 2 diabetes mellitus (T2DM), obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD). Whether ANGPTL8 has a direct pathogenic role in these diseases remains to be determined. In this review, we summarize the emerging roles of ANGPTL8 in the regulation of inflammation, tumours, circulatory system-related diseases, and ectopic lipid deposition, which may provide new insights into the diverse functions of ANGPTL8 in various diseases beyond its well-established functions in glucose and lipid metabolism.

Uric acid lowering improves insulin sensitivity and lowers blood pressure: a meta-analysis of randomized parallel-controlled clinical trials.

OBJECTIVES: This meta-analysis aimed to investigate whether uric acid lowering treatment can improve ß-cell function and insulin sensitivity. METHODS: PubMed, Cochrane Library, EMBASE and China Biology Medicine were searched up to March 1, 2020. Randomized controlled clinical trials of urate lowering therapy in hyperuricemia patients were included in meta-analysis. Effect size was estimated as mean difference with 95% confidence interval (CI). RESULTS: Our search yielded 7 eligible trials with 503 participants. This meta-analysis showed that uric acid-lowering therapy decreased fasting insulin -1.43 µIU/ml (weighted mean differences (WMD, 95% CI -2.78 to -0.09), homeostasis model assessment of insulin resistance -0.65 (WMD, 95% CI -1.05 to -0.24), systolic blood pressure -2.45 mm Hg (WMD, 95%CI -4.57 to -0.33) and diastolic blood pressure -3.41 mm Hg (WMD, 95%CI -3.87 to -2.95). However, the treatment had no significant effect on fasting plasma glucose (WMD -0.19 mmol/L, 95%CI -0.42 to 0.05), homeostasis model assessment of ß-cell function index (WMD -0.02, 95%CI -0.28 to 0.24), total cholesterol (WMD 0.18 mg/dl; 95%CI, -1.39 to 1.75) and triglyceride (WMD 3.15 mg/dl, 95% CI -9.83 to 16.14). CONCLUSION: Uric acid-lowering therapies might improve insulin sensitivity and lower blood pressure, but had no significant effect on HOMA-ß and serum lipids.

Association between weight cycling and risk of developing diabetes in adults: A systematic review and meta-analysis.

AIMS/INTRODUCTION: In this meta-analysis, we aimed to explore the association between bodyweight cycling (weight fluctuation) and the risk of developing diabetes. MATERIALS AND METHODS: We analyzed data from eligible cohort studies that assessed the association between weight cycling in adults and the risk of developing diabetes from online databases PubMed, Cochrane Library and EMBASE databases (1966 to April 2020). We pooled data using relative risks (RRs) with a random effects model. RESULTS: A total of 14 studies involving 253,766 participants, including 8,904 diabetes events, were included. One study included eight independent reports, resulting in 21 reports in 14 studies. Summary analysis showed that individuals who suffered weight cycling had a higher risk of diabetes (RR 1.23. 95% confidence interval 1.07-1.41; P = 0.003). However, the association between weight cycling and the risk of developing diabetes was not observed in obese participants (body mass index ≥30 kg/m2 ; P = 0.08). CONCLUSIONS: The present meta-analysis showed that weight cycling was a strong independent predictor of new-onset diabetes. Future studies are required to detect the causal links between weight cycling and the risk of developing diabetes.

Body-Weight Fluctuation Was Associated With Increased Risk for Cardiovascular Disease, All-Cause and Cardiovascular Mortality: A Systematic Review and Meta-Analysis.

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.

Associations of hyperuricemia, gout, and UA-lowering therapy with the risk of fractures: A meta-analysis of observational studies.

OBJECTIVE: A systematic review and meta-analysis were conducted to investigate the associations of hyperuricemia, gout, and uric acid (UA)-lowering therapy with the risk of fractures. METHODS: Electronic searches on PubMed, the Cochrane Library, and Embase were conducted from inception to January 2, 2019. Observational studies assessing the effects of hyperuricemia, gout, and UA-lowering therapy on fractures were included in the meta-analysis. Summary risk estimates with 95% confidence intervals (CI) were calculated by a random-effects model. RESULTS: A total of 14 eligible studies with 909 803 participants and 64 047 incident fractures were included. The results suggested that hyperuricemia and gout are not associated with any type of fracture (relative risk [RR], 0.98, 95% CI 0.85-1.11; P = 0.71) or osteoporotic fractures (RR, 1.02, 95% CI 0.90-1.14; P = 0.79). Further analysis indicated that hyperuricemia is associated with a lower risk of fractures (RR, 0.80, 95% CI 0.66-0.96; P = 0.02) but not with osteoporotic fractures (RR, 0.84, 95% CI 0.68-1.03; P = 0.10). However, gout is associated with an increased risk of fractures (RR, 1.17, 95% CI 1.04-1.31; P = 0.007) as well as osteoporotic fractures (RR, 1.13, 95% CI 1.00-1.26; P = 0.045). Furthermore, no significant association of UA-lowering therapy with the risk of fractures was found compared with the placebo (RR, 0.88, 95% CI 0.76-1.03; P = 0.11). Evidence supporting a non-linear association between serum UA levels and fractures was found (P < 0.001 for non-linearity), which revealed a U-shaped curve. CONCLUSION: Our meta-analysis revealed that hyperuricemia was associated with lower risk for any type fracture but not associated with osteoporotic fractures; however, gout was associated with an increased risk of any type fracture as well as osteoporotic fractures. Notably, a U-shaped relationship may exist between the serum UA level and fractures. The associations observed in our study may be due to reasons other than causality.