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ImportanceThe efficacy and safety of time-restricted eating (TRE) on nonalcoholic fatty liver disease (NAFLD) remain uncertain.ObjectiveTo compare the effects of TRE vs daily calorie restriction (DCR) on intrahepatic triglyceride (IHTG) content and metabolic risk factors among patients with obesity and NAFLD.Design, Setting, and ParticipantsThis 12-month randomized clinical trial including participants with obesity and NAFLD was conducted at the Nanfang Hospital in Guangzhou, China, between April 9, 2019, and August 28, 2021.InterventionsParticipants with obesity and NAFLD were randomly assigned to TRE (eating only between 8:00 am and 4:00 pm) or DCR (habitual meal timing). All participants were instructed to maintain a diet of 1500 to 1800 kcal/d for men and 1200 to 1500 kcal/d for women for 12 months.Main Outcomes and MeasuresThe primary outcome was change in IHTG content measured by magnetic resonance imaging; secondary outcomes were changes in body weight, waist circumference, body fat, and metabolic risk factors. Intention-to-treat analysis was used.ResultsA total of 88 eligible patients with obesity and NAFLD (mean [SD] age, 32.0 [9.5] years; 49 men [56%]; and mean [SD] body mass index, 32.2 [3.3]) were randomly assigned to the TRE (n = 45) or DCR (n = 43) group. The IHTG content was reduced by 8.3% (95% CI, −10.0% to −6.6%) in the TRE group and 8.1% (95% CI, −9.8% to −6.4%) in the DCR group at the 6-month assessment. The IHTG content was reduced by 6.9% (95% CI, −8.8% to −5.1%) in the TRE group and 7.9% (95% CI, −9.7% to −6.2%) in the DCR group at the 12-month assessment. Changes in IHTG content were comparable between the 2 groups at 6 months (percentage point difference: −0.2; 95% CI, −2.7 to 2.2; P = .86) and 12 months (percentage point difference: 1.0; 95% CI, −1.6 to 3.5; P = .45). In addition, liver stiffness, body weight, and metabolic risk factors were significantly and comparably reduced in both groups.Conclusions and RelevanceAmong adults with obesity and NAFLD, TRE did not produce additional benefits for reducing IHTG content, body fat, and metabolic risk factors compared with DCR. These findings support the importance of caloric intake restriction when adhering to a regimen of TRE for the management of NAFLD.Trial RegistrationClinicalTrials.gov Identifiers: NCT03786523 and NCT04988230

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Diabetic cardiomyopathy is characterized by diabetes‐induced myocardial abnormalities, accompanied by inflammatory response and alterations in inflammation‐related signalling pathways. Kirenol, isolated from Herba Siegesbeckiae, has potent anti‐inflammatory properties. In this study, we aimed to investigate the cardioprotective effect of kirenol against DCM and underlying the potential mechanisms in a type 2 diabetes mellitus model. Kirenol treatment significantly decreased high glucose‐induced cardiofibroblasts proliferation and increased the cardiomyocytes viability, prevented the loss of mitochondrial membrane potential and further attenuated cardiomyocytes apoptosis, accompanied by a reduction in apoptosis‐related protein expression. Kirenol gavage could affect the expression of pro‐inflammatory cytokines in a dose‐dependent manner but not lower lipid profiles, and only decrease fasting plasma glucose, fasting plasma insulin and mean HbA1c levels in high‐dose kirenol‐treated group at some time‐points. Left ventricular dysfunction, hypertrophy, fibrosis and cell apoptosis, as structural and functional abnormalities, were ameliorated by kirenol administration. Moreover, in diabetic hearts, oral kirenol significantly attenuated activation of mitogen‐activated protein kinase subfamily and nuclear translocation of NF‐κB and Smad2/3 and decreased phosphorylation of IκBα and both fibrosis‐related and apoptosis‐related proteins. In an Electrophoretic mobility shift assay, the binding activities of NF‐κB, Smad3/4, SP1 and AP‐1 in the nucleus of diabetic myocardium were significantly down‐regulated by kirenol treatment. Additionally, high dose significantly enhanced myocardial Akt phosphorylation without intraperitoneal injection of insulin. Kirenol may have potent cardioprotective effects on treating for the established diabetic cardiomyopathy, which involves the inhibition of inflammation and fibrosis‐related signalling pathways and is independent of lowering hyperglycaemia, hyperinsulinemia and lipid profiles.

OBJECTIVE To examine the associations of circulating 25-hydroxyvitamin D (25[OH]D) concentrations with cardiovascular disease (CVD) and all-cause mortality in individuals with prediabetes and diabetes from the large population-based UK Biobank cohort study. RESEARCH DESIGN AND METHODS A total of 67,789 individuals diagnosed with prediabetes and 24,311 with diabetes who had no CVD or cancer at baseline were included in the current study. Serum 25(OH)D concentrations were measured at baseline. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs for cardiovascular outcomes and mortality after 10–14 years. RESULTS After multivariable adjustment, higher serum 25(OH)D levels were significantly and nonlinearly associated with lower risk of cardiovascular outcomes and all-cause mortality among participants with prediabetes and diabetes (all P nonlinearity < 0.05). Compared with those in the lowest category of 25(OH)D levels (<25 nmol/L), participants with prediabetes in the highest category of 25(OH)D levels (≥75 nmol/L) had a significant association with lower risk of cardiovascular events (HR 0.78; 95% CI 0.71–0.86), coronary heart disease (CHD) (HR 0.79; 95% CI 0.71–0.89), heart failure (HR 0.66; 95% CI 0.54–0.81), stroke (HR 0.75; 95% CI 0.61–0.93), CVD mortality (HR 0.43; 95% CI 0.32–0.59), and all-cause mortality (HR 0.66; 95% CI 0.58–0.75). Likewise, these associations with cardiovascular events, CHD, heart failure, CVD mortality, and all-cause mortality were observed among participants with diabetes, except for stroke. CONCLUSIONS These findings highlight the importance of monitoring and correcting vitamin D deficiency in the prevention of CVD and mortality among adults with prediabetes and diabetes.