Physical exercise for people with cirrhosis.

BACKGROUND: Loss of muscle mass and muscle weakness are common complications to cirrhosis and are associated with increased morbidity and mortality. Therefore, physical exercise may benefit people with cirrhosis. OBJECTIVES: To assess the beneficial and harmful effects of physical exercise versus sham exercise or no exercise for people with cirrhosis. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Embase Ovid, and three other databases, including manual searches through reference lists, abstracts, and presentations at conferences and meetings, Google Scholar, and online trial registers in February 2018. SELECTION CRITERIA: We included randomised clinical trials regardless of publication status or language. Inclusion criteria were cirrhosis irrespective of the aetiology or stage. Interventions were physical exercise compared with sham exercise or no intervention. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data. We undertook meta-analyses and presented results using risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, both with 95% confidence intervals (CI) and I2 values as markers of imprecision and heterogeneity. We assessed bias control using the Cochrane Hepato-Biliary Group domains and determined the credibility of the evidence using GRADE. MAIN RESULTS: We included six randomised clinical trials with 173 participants. All participants had Child-Pugh stage A or B cirrhosis. The intervention groups participated in eight to 14 weeks of physical exercise (aerobic: three trials; resistance: one trial; or aerobic plus resistance training: two trials). Control groups underwent sham exercise (supervised relaxation: one trial) or no intervention (five trials). None of the 89 participants allocated to exercise versus two of 84 participants in the control group died (RR 0.19, 95% CI 0.01 to 3.73; moderate-quality evidence). The cause of death was acute-on-chronic liver disease for both participants. Nine participants in the exercise group and 13 in the control group experienced serious adverse events (RR 0.61, 95% CI 0.19 to 1.94; low-quality evidence).Physical exercise showed no beneficial or detrimental effect on health-related quality of life assessed by the Chronic Liver Disease Questionnaire (MD 0.11, 95% CI -0.44 to 0.67; low-quality evidence). Likewise, physical exercise had no clear effect on physical fitness measured by peak exercise oxygen uptake (MD 0.3 mL/kg/minute, 95 % CI -2.74 to 3.35; low-quality evidence) and Six-Minute Walk Test (MD 56.06 min, 95% CI -9.14 to 121.26; very low-quality evidence). Physical exercise showed no clear effect on mid-thigh circumference (MD 1.76 cm, 95% CI -0.26 to 3.77; low-quality evidence), but showed an increase in mid-arm circumference (MD 2.61 cm, 95% CI 0.36 to 4.85; low-quality evidence). AUTHORS' CONCLUSIONS: We found no clear beneficial or harmful effect of physical exercise on mortality, morbidity, or health-related quality of life. Further evidence is needed to evaluate the beneficial and harmful effects of physical exercise on clinical outcomes.

Effect of semaglutide 2.4 mg once weekly on 10-year type 2 diabetes risk in adults with overweight or obesity.

OBJECTIVE: In the Semaglutide Treatment Effect in People with obesity (STEP) trials, once-weekly subcutaneous semaglutide 2.4 mg plus lifestyle intervention reduced body weight and improved cardiometabolic parameters in adults with obesity (or overweight with weight-related comorbidities). Effects on the risk of developing type 2 diabetes (T2D) require investigation. METHODS: STEP 1 (68 weeks) and 5 (104 weeks) randomized participants to semaglutide 2.4 mg or placebo. STEP 4 included a 20-week semaglutide run-in followed by randomization to 48 weeks of continued semaglutide or withdrawal (placebo). Ten-year T2D risk scores were calculated post hoc using Cardiometabolic Disease Staging. RESULTS: In STEP 1 (N = 1583), relative risk score reductions were greater with semaglutide versus placebo (semaglutide: -61.1%; placebo: -12.9%; p < 0.0001). These reductions were maintained to week 104 in STEP 5 (N = 295; semaglutide: -60.0%; placebo: 3.5%; p < 0.0001). Risk scores during the STEP 4 run-in period (N = 776) were reduced from 20.6% to 11.1% and further to 7.7% at week 68 with continued semaglutide, increasing to 15.4% with withdrawal (relative risk score change: semaglutide: -32.1%; placebo: +40.6%; p < 0.0001). Risk score reductions mirrored weight loss. CONCLUSIONS: Cardiometabolic Disease Staging risk assessment suggests that once-weekly semaglutide 2.4 mg may substantially lower 10-year T2D risk in people with overweight or obesity.

Plasma YKL-40 during pregnancy and gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is characterised by hyperglycaemia during pregnancy. The clinical circumstances involved in the development of GDM leaves the patient at a high risk of the subsequent development of type 2 diabetes. Plasma levels of the inflammation marker YKL-40 are elevated in type 2 diabetes and correlate with fasting plasma glucose levels and insulin resistance in patients with type 2 diabetes. With the present study we aimed to determine if pregnancy (and associated insulin resistance) with or without GDM affects plasma YKL-40 levels. Plasma from women diagnosed with GDM and healthy normal glucose-tolerant pregnant women (non-GDM) was obtained at the third trimester of pregnancy and again 3-4 months following delivery, and levels of YKL-40 and interleukin 6 (IL-6; known to regulate YKL-40) were measured. Plasma YKL-40 levels were similarly low during pregnancy in both groups and increased significantly after delivery, but remained lower in the GDM group compared with the non-GDM group postpartum. In contrast, plasma IL-6 levels were not affected by pregnancy or diagnosis of GDM, Nevertheless, YKL-40 levels were associated with IL-6 levels in the non-GDM group (but not in the GDM group). Pregnancy seems to be associated with a temporary reduction in circulating YKL-40, which increases after delivery, but to a much lesser extent in women with GDM than in non-GDM women.