Background: In nonalcoholic fatty liver disease (NAFLD), increased alanine aminotransferase (ALT) concentrations are considered to be a consequence of hepatocyte damage. We performed a prospective study to examine the association between ALT within its reference interval and risk for subsequent development of NAFLD. Methods: The study cohort comprised 5237 healthy men without diagnosed NAFLD and without increases of either ALT (≥35 U/L) or γ-glutamyltransferase (GGT; ≥40 U/L) above the reference intervals. We assessed alcohol intake via self-reporting (questionnaire) and performed biochemical tests for liver and metabolic function and abdominal ultrasonography. We used the Cox proportional hazards model to calculate the adjusted hazard ratios (aHRs) in the model for NAFLD. Results: During 13 276.6 person-years of follow-up over a 4-year period, 984 new incident cases of NAFLD developed. We adjusted for age, weight change, body mass index, glucose, blood pressure, triglycerides, HDL cholesterol, smoking, alcohol consumption, regular exercise, homeostasis model assessment of insulin resistance, C-reactive protein, and incident diabetes. Compared with an ALT concentration of <16 U/L, aHR values (95% confidence intervals) for ALT concentrations were 1.53 (1.18–1.98), 1.66 (1.29–2.13), 1.62 (1.26–2.08), and 2.21 (1.73–2.81) for ALT concentrations of 16–18, 19–21, 22–25, and 26–34 U/L, respectively. This relationship remained significant even among normal-weight participants who were still within the reference interval of ALT and GGT at all follow-up examinations. Conclusions: In apparently healthy, nondiabetic Korean men, increased ALT concentration, even within the reference interval, was an independent predictor of incident NAFLD.

Objective—: Short and long sleep duration are associated with increased risk of clinical cardiovascular events, but the association between sleep duration and subclinical cardiovascular disease is not well established. We examined the association between sleep duration and sleep quality with coronary artery calcification (CAC) and with brachial–ankle pulse wave velocity (PWV) in a large sample of young and middle-aged asymptomatic adults. Approach and Results—: We conducted a cross-sectional study of adult men and women who underwent a health checkup examination, including assessment of sleep duration and quality and coupled with either CAC (n=29 203) or brachial–ankle PWV (n=18 106). The multivariate-adjusted CAC score ratios (95% confidence interval) comparing sleep durations of ≤5, 6, 8, and ≥9 hours with 7 hours of sleep were 1.50 (1.17–1.93), 1.34 (1.10–1.63), 1.37 (0.99–1.89), and 1.72 (0.90–3.28), respectively ( P for quadratic trend=0.002). The corresponding average differences in brachial–ankle PWV were 6.7 (0.75–12.6), 2.9 (−1.7 to 7.4), 10.5 (4.5–16.5), and 9.6 (−0.7 to 19.8) cm/s, respectively ( P for quadratic trend=0.019). Poor subjective sleep quality was associated with CAC in women but not in men, whereas the association between poor subjective sleep quality and brachial–ankle PWV was stronger in men than in women. Conclusions—: In this large study of apparently healthy men and women, extreme sleep duration and poor subjective sleep quality were associated with increased prevalence of CAC and higher PWV. Our results underscore the importance of an adequate quantity and quality of sleep to maintain cardiovascular health.

A few epidemiological data are available assessing the associations of intakes of sodium (Na) and potassium (K) with non-alcoholic fatty liver disease (NAFLD). We aimed to examine the associations of dietary intake of Na and K with the prevalence of ultrasound-diagnosed NAFLD. We performed a cross-sectional study of 100 177 participants (46 596 men and 53 581 women) who underwent a health screening examination and completed a FFQ at the Kangbuk Samsung Hospital Total Healthcare Centers, South Korea, between 2011 and 2013. NAFLD was defined by ultrasonographic detection of fatty liver in the absence of excessive alcohol intake or other known causes of liver disease. The proportion of NAFLD was 35·6 % for men and 9·8 % for women. Increasing prevalence of NAFLD was observed with increasing Na intake. The multivariable-adjusted prevalence ratios (PR) of NAFLD comparing the highest with the lowest quintile of energy-adjusted Na intake were 1·25 (95 % CI 1·18, 1·32; P_trend<0·001) in men and 1·32 (95 % CI 1·18, 1·47; P_trend <0·001) in women. However, when we additionally adjusted for body fat percentage, the association became attenuated; the corresponding PR of NAFLD were 1·15 (95 % CI 1·09, 1·21) in men and 1·06 (95 % CI 0·95, 1·17) in women. No inverse association was observed for energy-adjusted K intake. Our findings suggest that higher Na intake is associated with a greater prevalence of NAFLD in young and middle-aged asymptomatic adults, which might be partly mediated by adiposity.

Objectives: We performed a prospective study to determine whether weight gain predicts future ultrasonographically detected fatty liver (USFL) in a lean adult population. Methods: Among 15 347 Korean male workers, aged 30–59 years, who participated in a health check-up programme in 2002, a USFL-free cohort of 4246 non-diabetic men was followed until September 2007. Alcohol consumption was assessed by a questionnaire. Weight change for each subject was calculated as the difference between baseline and subsequent measurements. Biochemical tests for liver and metabolic function were done. The primary outcome was ultrasound-diagnosed fatty liver. A standard Cox proportional hazards model and time-dependent Cox model were performed. Results: During 16 829.7 person-years of follow-up, 622 participants developed USFL. After adjusting for age, the period from visit 1 to visit 2, BMI, HDL-C, triglyceride, uric acid, alanine aminotransferase, and HOMA-IR, the risk for USFL increased with increasing quartiles of weight change (p for trend <0.001). This association remained significant when weight change and covariates, except age and the period from visit 1 to visit 2, were modelled as time-dependent variables. Subjects in the fourth quartile (weight gain ⩾2.3 kg) were at significantly elevated risk for USFL (adjusted hazard ratio (aHR), 1.26; 95% CI, 1.01 to 1.58). These associations did not change, even in normal weight men with a baseline BMI between 18.5 and 22.9 kg/m ² (n = 2186). Conclusion: Weight gain per se appears to increase the risk for developing USFL. Thus, avoiding weight gain, even among lean adult individuals, can be helpful in preventing this disease.