Weight Change and the Development of Nonalcoholic Fatty Liver Disease in Metabolically Healthy Overweight Individuals.

INTRODUCTION: The study sought to investigate the effect of weight change on hepatic steatosis (HS) incidence with or without liver fibrosis in metabolically healthy overweight or obese individuals. METHODS: A cohort of 14,779 metabolically healthy men and women who were overweight or obese (body mass index ≥23 kg/m2) and free from HS and an intermediate or high probability of fibrosis at baseline were followed for a median of 5.2 years. Metabolic health was defined as freedom from the components of metabolic syndrome and a homeostatic model assessment of insulin resistance <2.5. Weight changes were calculated as differences from baseline at the next subsequent visit. The outcome was HS incidence, with or without liver fibrosis, as assessed by liver ultrasound and 2 noninvasive fibrosis scores. RESULTS: During 76,794.6 person-years of follow-up, 3539 cases of HS incidence were identified. The multivariable adjusted hazard ratios (95% confidence intervals) for HS incidence by weight change group, <-5.0%, -5.0%-1.0%, 1.0%-5.0%, and >5.0%, relative to the no weight change group (-0.9% to 0.9%) were 0.52 (0.44-0.60), 0.83 (0.75-0.92), 1.21 (1.10-1.33), and 1.51 (1.36-1.69), respectively. Clinically relevant weight loss of >5% was also associated with a lowered risk of HS with intermediate or high probability of advanced fibrosis. In mediation analyses, associations remained significant, although adjustment for metabolic risk factors was attenuating. DISCUSSION: Clinically relevant weight loss was associated with a reduced risk of developing nonalcoholic fatty liver disease with or without intermediate or high probability of advanced fibrosis in metabolically healthy overweight or obese individuals.

Association Between Frailty-Related Factors and Depression among Older Adults.

OBJECTIVES: We analyzed the association between individual frailty-related factors and depression in older adults. METHODS: A total of 796 older adults who underwent geriatric assessments were included in this cross-sectional study. The frailty-related factors studied were grip strength, physical activity, walking speed, weight loss, and recurrent falls. Depression was based on the Geriatric Depression Scale. RESULTS: After adjustment for covariates, recurrent falls were associated with depression in males (OR 3.84, 95% CI 1.30-11.35). Among females, weakest grip strength, slow walking speed, and weight loss were associated with depression (OR 2.61, 95% CI 1.52-4.49; OR 1.78, 95% CI 1.02-3.11; and OR 2.52, 95% CI 1.17-5.44, respectively). Having more frailty-related factors was also associated with higher odds of depression. CONCLUSIONS: The associations between individual frailty-related factors and depression differed among males and females. Further prospective studies on depression and individual frailty-related factors by sex may help elucidate specific targets to be prioritized for clinical assessment and intervention. CLINICAL IMPLICATIONS: Older adults affected by depression and frailty may present different clinical manifestations based on sex, and require different treatment approaches. Clinicians should assess both physical and psychological needs for integrated care in frail older adults.

Low Levels of Alcohol Consumption, Obesity, and Development of Fatty Liver With and Without Evidence of Advanced Fibrosis.

BACKGROUND AND AIMS: The effects of low-level alcohol consumption on fatty liver disease and the potential for effect modification by obesity is uncertain. We investigated associations among low-level alcohol consumption, obesity status, and the development of incident hepatic steatosis (HS), either with or without an increase in noninvasive liver fibrosis score category (from low to intermediate or high category). APPROACH AND RESULTS: A total of 190,048 adults without HS and a low probability of fibrosis with alcohol consumption less than 30 g/day (men) and less than 20 g/day (women) were followed for up to 15.7 years. Alcohol categories of no, light, and moderate consumption were defined as 0, 1-9.9, and 10-29.9 g/day (10-19.9 g/day for women), respectively. HS was diagnosed by ultrasonography, and the probability of fibrosis was estimated using the fibrosis-4 index (FIB-4). Parametric proportional hazards models were used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 43,466 participants developed HS, 2,983 of whom developed HS with an increase in FIB-4 index (to intermediate or high scores). Comparing light drinkers and moderate drinkers with nondrinkers, multivariable-adjusted HRs (95% CI) for incident HS were 0.93 (0.90-0.95) and 0.90 (0.87-0.92), respectively. In contrast, comparing light drinkers and moderate drinkers with nondrinkers, multivariable-adjusted HRs (95% CI) for developing HS plus intermediate/high FIB-4 were 1.15 (1.04-1.27) and 1.49 (1.33-1.66), respectively. The association between alcohol consumption categories and incident HS plus intermediate/high FIB-4 was observed in both nonobese and obese individuals, although the association was stronger in nonobese individuals (P for interaction by obesity = 0.017). CONCLUSIONS: Light/moderate alcohol consumption has differential effects on the development of different stages of fatty liver disease, which is modified by the presence of obesity.

'You gotta have something to chew on': perceptions of stress-induced eating and weight gain among office workers in South Korea.

OBJECTIVE: Job-related chronic stress has been discussed as a risk factor for weight change and metabolic disorders. The current study was conducted to understand the situations in which stress-induced eating occurs among office workers and how workers perceive stress to influence their daily eating practices and weight change. DESIGN: In-depth, one-on-one interviews were conducted with office workers. SETTING: Metropolitan areas in South Korea. PARTICIPANTS: Twenty-two office workers from thirteen companies participated in the study. RESULTS: Most participants mentioned that they often felt work-related stress and reported various levels of perceived stress, as measured with open-ended questions. The main sources of work stress were (i) the nature of job characteristics, (ii) performance evaluations and (iii) relationships within the organisation. Participants linked stress with increased food consumption and cravings for sweet, savoury and greasy foods. Many participants emphasised the links between multiple health behaviours and stress. Not only dietary choices but also alcohol consumption, sleeping difficulty and insufficient physical activity were related to coping with work stress and demands. Finally, most participants who perceived work stress believed that their weight gain in adulthood was triggered by work stress. CONCLUSIONS: It is necessary to consider promoting behavioural modifications to support weight management and providing a means for stress management and the minimisation of stress-inducing working environments for workers to maintain or achieve a healthy weight and to prevent chronic disease incidence.

Glycemic Status, Insulin Resistance, and the Risk of Nephrolithiasis: A Cohort Study.

RATIONALE & OBJECTIVE: The effect of glycemic status on nephrolithiasis risk remains controversial. This study sought to examine the association of glycemic status and insulin resistance with incident nephrolithiasis. STUDY DESIGN: A retrospective cohort study. SETTING & PARTICIPANTS: 278,628 Korean adults without nephrolithiasis who underwent a comprehensive health examination between 2011 and 2017. EXPOSURES: Glucose level, glycated hemoglobin level, and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). OUTCOME: Nephrolithiasis ascertained using abdominal ultrasound. ANALYTICAL APPROACH: A parametric proportional hazard model was used to estimate adjusted HRs and 95% CIs. We explored prespecified potential sex differences in the association of glycemic status and incident nephrolithiasis. RESULTS: During a median follow-up of 4.2 years, 6,904 participants developed nephrolithiasis. Associations between levels of glycemic status and incident nephrolithiasis were examined separately in men and women (P for interaction = 0.003). Among men, multivariable-adjusted HRs for incident nephrolithiasis comparing glucose levels of 90-99, 100-125, and ≥ 126 mg/dL were 1.10 (95% CI, 1.01-1.19), 1.11 (95% CI, 1.02-1.21), and 1.27 (95% CI, 1.10-1.46), respectively, while HRs for incident nephrolithiasis comparing glycated hemoglobin levels of 5.7%-5.9%, 6.0%-6.4%, and 6.5%-<5.7% were 1.03 (95% CI, 0.96-1.10), 1.18 (95% CI, 1.07-1.31), and 1.20 (95% CI, 1.06-1.37), respectively. The HR for incident nephrolithiasis comparing the highest HOMA-IR quintile to the lowest quintile was 1.18 (95% CI, 1.06-1.31). Among women, no apparent association was found between glycemic status and nephrolithiasis risk. LIMITATIONS: Glucose tolerance testing and computed tomography assessment for nephrolithiasis were not available. CONCLUSIONS: Higher glycemic values, even within the normoglycemic range, and HOMA-IR were positively associated with increased risk for nephrolithiasis, associations that were only observed among men. Insulin resistance and hyperglycemia may contribute to the development of nephrolithiasis, particularly among men.

Nonheavy Drinking and Worsening of Noninvasive Fibrosis Markers in Nonalcoholic Fatty Liver Disease: A Cohort Study.

The effect of modest alcohol consumption on fibrosis progression in the general population with nonalcoholic fatty liver disease (NAFLD) remains unclear. We examined the association of nonheavy alcohol consumption with worsening of noninvasive fibrosis indices in a large-scale, low-risk population with NAFLD. A cohort study was performed in 58,927 Korean adults with NAFLD and low fibrosis scores who were followed for a median of 4.9 years. Non-, light, and moderate drinkers were defined as 0 g/day, 1-9.9 g/day, and 10-29.9 g/day (10-19.9 g/day for women), respectively. Progression from low to intermediate or high probability of advanced fibrosis was assessed using noninvasive indices including NAFLD fibrosis score (NFS) and Fibrosis-4 Index (FIB-4). A parametric proportional hazards model was used to estimate the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). During 347,925.4 person-years of follow-up, 5,630 subjects with low FIB-4 progressed to intermediate or high FIB-4. The multivariable-adjusted HRs (95% CI) for worsening of FIB-4 comparing light and moderate drinkers with nondrinkers were 1.06 (0.98-1.16) and 1.29 (1.18-1.40), respectively. Similarly, using NFS, corresponding HRs (95% CI) comparing light and moderate drinkers with nondrinkers were 1.09 (1.02-1.16) and 1.31 (1.23-1.40), respectively. Furthermore, the association of moderate drinkers with worsening of either FIB-4 or NFS remained significant after introducing alcohol use and confounders treated as time-varying covariates. Conclusion: In this large-scale cohort of young and middle-aged individuals with NAFLD, nonheavy alcohol consumption, especially moderate alcohol consumption, was significantly and independently associated with worsening of noninvasive markers of fibrosis, indicating that even moderate alcohol consumption might be harmful.

Alcoholic and non-alcoholic fatty liver disease and associations with coronary artery calcification: evidence from the Kangbuk Samsung Health Study.

OBJECTIVE: Recent evidence suggests that alcoholic fatty liver disease (AFLD) and non-alcoholic fatty liver disease (NAFLD) may differentially affect risk of cardiovascular mortality. To investigate whether early liver disease due to AFLD or NAFLD have similar or dissimilar effects on risk of early coronary artery atherosclerosis, we have investigated the associations between AFLD and NAFLD and coronary artery calcium (CAC). DESIGN: A cross-sectional study was performed in 105 328 Korean adults who attended a health check-up programme. CAC score was assessed using CT, daily alcohol intake was recorded as grams/day and liver fat by ultrasound. Logistic regression model was used to calculate ORs with 95% CIs for prevalent CAC. RESULTS: Both NAFLD and AFLD were positively associated with CAC score. After adjusting for potential confounders, multivariable-adjusted OR (95% CIs) for CAC >0 comparing NAFLD and AFLD to the reference (absence of both excessive alcohol use and fatty liver disease) were 1.10 (95% CI 1.05 to 1.16) and 1.20 (95% CI 1.11 to 1.30), respectively. In post hoc analysis, OR (95% CI) for detectable CAC comparing AFLD to NAFLD was 1.09 (95% CI 1.01 to 1.17). Associations of NAFLD and AFLD with CAC scores were similar in both non-obese and obese individuals without significant interaction by obesity (p for interaction=0.088). After adjusting for homeostasis model assessment of insulin resistance and high-sensitivity C reactive protein, the associations between fatty liver disease and CAC scores remained statistically significant. CONCLUSION: In this large sample of young and middle-aged individuals, early liver disease due to NAFLD and AFLD were both significantly associated with the presence of coronary artery calcification.

Smoking and the Risk of Non-Alcoholic Fatty Liver Disease: A Cohort Study.

OBJECTIVES: The role of smoking in the development of non-alcoholic fatty liver disease (NAFLD) remains controversial. We assessed the risk of incident NAFLD according to smoking status and urinary cotinine levels. METHODS: We performed a cohort study of 199,468 Korean adults without NAFLD at baseline who were followed annually or biennially for a median of 4.1 years. The presence of fatty liver was determined using ultrasound. NAFLD severity was assessed using NAFLD fibrosis score (NFS), a non-invasive fibrosis marker. RESULTS: During 1,070,991 person-years of follow-up, 45,409 participants developed NAFLD. Self-reported current smoking, pack-years, and urinary cotinine level were significantly associated with increased risk for NAFLD. For men, the multivariable-adjusted hazard ratios (aHR) (95% confidence intervals (CI)) for incident NAFLD comparing 10-19.9, and ≥20 pack-years to 0 pack-years were 1.25 (1.21- 1.29), and 1.36 (1.30-1.42), respectively; for women, aHR (95% CI) for NAFLD comparing 5-9.9, and ≥10 pack-years to 0 pack-years were 1.25 (1.04-1.50), and 1.46 (1.17-1.81), respectively. Smoking pack-years were also associated with increased risk for NAFLD plus intermediate or high fibrosis score. For men, the aHR (95% CI) for NAFLD plus intermediate or high NFS comparing ≥20 pack-years to 0 pack-years was 1.29 (1.18-1.42); for women, the aHR (95% CI) comparing ≥10 pack-years to 0 pack-years was 1.75 (1.12-2.73). CONCLUSIONS: In a large cohort of young and middle-aged men and women, current smoking, pack-years, and urinary cotinine levels were positively associated with the risk of incident NAFLD, suggesting that smoking contributes to the development of NAFLD.

Association Between Sonographically Diagnosed Nephrolithiasis and Subclinical Coronary Artery Calcification in Adults.

BACKGROUND: Although recent studies suggest an association between nephrolithiasis and clinical cardiovascular events, this association has been underexplored. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: 62,091 asymptomatic adults without known coronary heart disease who underwent a screening health examination that included cardiac tomography. PREDICTOR: Nephrolithiasis. OUTCOME: Coronary artery calcification (CAC). MEASUREMENTS: Nephrolithiasis assessed using ultrasonography of the abdomen. CAC scoring assessed using cardiac computed tomography. RESULTS: The prevalence of CAC scores > 0 was 13.1% overall. Participants with nephrolithiasis had a higher prevalence of coronary calcification than those without (19.1% vs 12.8%). In Tobit models adjusted for age and sex, the CAC score ratio comparing participants with nephrolithiasis with those without nephrolithiasis was 1.56 (95% CI, 1.19-2.05). After further adjustment for screening center, year of screening examination, physical activity, alcohol intake, smoking status, education level, body mass index, family history of cardiovascular disease, total energy intake, glucose concentration, systolic blood pressure, triglyceride concentration, high-density lipoprotein cholesterol concentration, uric acid concentration, and estimated glomerular filtration rate, the CAC score ratio was attenuated, but remained significant (CAC score ratio, 1.31; 95% CI, 1.00-1.71). LIMITATIONS: Computed tomographic diagnosis of nephrolithiasis was unavailable. CONCLUSIONS: Nephrolithiasis was associated with the presence of CAC in adults without known coronary heart disease, supporting the hypothesis that these 2 health conditions share a common pathophysiology.

Sleep Duration, Sleep Quality, and Markers of Subclinical Arterial Disease in Healthy Men and Women.

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.

Dietary sodium and potassium intake in relation to non-alcoholic fatty liver disease.

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.

Human Placental Extract as a Subcutaneous Injection Is Effective in Chronic Fatigue Syndrome: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study.

Chronic fatigue (CF) is a common reason for consulting a physician due to affecting quality of life, but only a few effective treatments are available. The aim of this study was to examine the effectiveness of subcutaneous injection of the human placental extract (HPE) on medically indescribable cases of CF and safety in a randomized, double-blind, placebo-controlled clinical trial. A total of 78 subjects with CF were randomly assigned to either a HPE group or a placebo group. Subjects in the HPE group were treated with HPE three times a week subcutaneously for 6 weeks, whereas those in the placebo group with normal saline. Then, the fatigue severity scale (FSS), visual analog scale (VAS) and multidimensional fatigue inventory (MFI) were measured in both CF group and chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF) subgroup. The FSS, VAS and MFI score at baseline were not different between the HPE and placebo group in total subjects with CF. In CFS group, the FSS (p=0.0242), VAS (p=0.0009) and MFI (p=0.0159) scores measured at the end of the study period decreased more in the HPE group than in the placebo group when compared with those at the baseline. There were no significant differences between the HPE group and placebo group in the mean change from baseline in FSS, VAS, and MFI in subjects with ICF during the study period. The subcutaneous injection of HPE was effective in the improvement of CFS.

Composition of dietary macronutrient intake is not associated with prevalence of coronary artery calcification in healthy Korean adults.

BACKGROUND AND AIMS: There is little information supporting the relationships between macronutrients and pre-clinical atherosclerosis. The aim of this study was to identify whether dietary macronutrient content is related with CAC. METHODS: 10,793 healthy Korean adults in a cohort were enrolled. Subjects were divided into CAC (CAC score >0) or non-CAC group (CAC score = 0). Intake of energy, carbohydrate (CHO), protein and fat were obtained using food frequency questionnaire (FFQ). Macronutrient composition was expressed as the ratio of energy from each macronutrient to total energy. Subjects were classified into three groups according to tertiles of intake for each macronutrient. To investigate the association between macronutrient intake and CAC, multiple regression analysis was conducted according to tertile groups of each macronutrient. RESULTS: The prevalence of CAC significantly differed among tertile groups of CHO and fat intake in men (p < 0.001, p < 0.01) and women (p < 0.05, p < 0.01). However, multiple logistic regression analysis revealed that the odds ratios (ORs) for CAC were not significantly different among tertile groups of each macronutrient intake after adjustment in men (CHO: OR = 0.965 [95% CI = 0.826-1.129]; protein: OR = 1.029 [95% CI = 0.881-1.201]; fat: OR = 1.015 [95% CI = 0.868-1.188]) and women (CHO: OR = 1.158 [95% CI = 0.550-2.438]; protein: OR = 1.261 [95% CI = 0.629-2.528]; fat: OR = 0.625 [95% CI = 0.286-1.365]). CONCLUSIONS: The prevalence of CAC may not be associated with composition of dietary macronutrient intake in in healthy Korean adults.

A1C and coronary artery calcification in nondiabetic men and women.

OBJECTIVE: This study aimed to examine the association between glycohemoglobin (A1C) and coronary artery calcification (CAC) in nondiabetic men and women without overt cardiovascular disease or diabetes mellitus after accounting for fasting glucose and traditional cardiovascular disease risk factors. APPROACH AND RESULTS: A cross-sectional study was performed in 25,564 Korean adults (41.4 ± 7.0 years) with no diabetes mellitus (fasting glucose, ≥ 7.0 mmol/L or a history of diabetes mellitus) and no clinically evident cardiovascular disease, who underwent a health checkup, including a cardiac computed tomography estimation of CAC scores and measurements of cardiovascular risk factors. The presence of CAC was defined as a CAC score >0; CAC was observed in 12.0% of men and 4.9% of women. Age-adjusted odds ratios (95% confidence interval) for CAC comparing A1C of 5.5% to 5.6%, 5.7% to 5.9%, and 6.0% to 6.4% with A1C <5.5% were 1.12 (0.99-1.28), 1.44 (1.27-1.63), and 1.63 (1.39-1.90) in men and 1.76 (0.96-3.25), 1.86 (1.05-3.29), and 3.09 (1.68-5.70) in women, respectively. After adjusting for potential confounders, the odds ratios (95% confidence interval) comparing A1C of 5.5% to 5.6%, 5.7% to 5.9%, and 6.0% to 6.4% with A1C of <5.5% were 1.04 (0.91-1.19), 1.21 (1.07-1.38), and 1.25 (1.05-1.48) in men and 1.75 (0.94-3.29), 1.59 (0.88-2.87), and 2.48 (1.29-4.74) in women, respectively. These associations persisted in subjects without any metabolic abnormalities, including fasting glucose ≥ 100 mg/dL. CONCLUSIONS: A higher A1C level was found to have a modest and independent association with the subclinical coronary atherosclerosis, even in metabolically healthy individuals.

Glycemic status, insulin resistance, and mortality from lung cancer among individuals with and without diabetes.

BACKGROUND: The effects of glycemic status and insulin resistance on lung cancer remain unclear. We investigated the associations between both glycemic status and insulin resistance, and lung cancer mortality, in a young and middle-aged population with and without diabetes. METHODS: This cohort study involved individuals who participated in routine health examinations. Lung cancer mortality was identified using national death records. Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% CIs for lung cancer mortality risk. RESULTS: Among 666,888 individuals (mean age 39.9 ± 10.9 years) followed for 8.3 years (interquartile range, 4.6-12.7), 602 lung cancer deaths occurred. Among individuals without diabetes, the multivariable-adjusted HRs (95% CI) for lung cancer mortality comparing hemoglobin A1c categories (5.7-5.9, 6.0-6.4, and ≥ 6.5% or 39-41, 42-46, and ≥ 48 mmol/mol, respectively) with the reference (< 5.7% or < 39 mmol/mol) were 1.39 (1.13-1.71), 1.72 (1.33-2.20), and 2.22 (1.56-3.17), respectively. Lung cancer mortality was associated with fasting blood glucose categories in a dose-response manner (P for trend = 0.001) and with previously diagnosed diabetes. Insulin resistance (HOMA-IR ≥ 2.5) in individuals without diabetes was also associated with lung cancer mortality (multivariable-adjusted HR, 1.41; 95% CI, 1.13-1.75). These associations remained after adjusting for changing status in glucose, hemoglobin A1c, insulin resistance, smoking status, and other confounders during follow-up as time-varying covariates. CONCLUSIONS: Glycemic status within both diabetes and prediabetes ranges and insulin resistance were independently associated with an increased risk of lung cancer mortality.

Association between body fat and bone mineral density in Korean adults: a cohort study.

Although obesity was once considered protective against osteoporosis, various factors influence the relationship between fat and bone mineral density (BMD). To establish the importance of healthy body composition in decelerating declines in BMD, we conducted a study to compare the association between body fat composition and BMD in Korean adults. Using data collected from the Kangbuk Samsung Health Study from 2012 to 2019, this cohort study compared the incidence of decreased BMD among the following four groups: normal BMI and normal adiposity (NBMI-NA), normal BMI and high adiposity (NBMI-HA), overweight, and obesity. Decreased BMD was defined as a Z-score ≤ - 2.0 in premenopausal women and men < 50 years of age or a T-score < - 1.0 in postmenopausal women and men ≥ 50 years of age. Individuals who were diagnosed with osteoporosis or compression fracture after their second visit were categorized as having decreased BMD. The incidence rate of decreased BMD in the NBMI-NA group was 3.37, and that in the NBMI-HA group was 4.81, which was the highest among all groups. After adjusting for confounding factors, NBMI-HA led to a significantly greater risk of decreased BMD compared to NBMI-NA (HR 1.47; 95% CI 1.09-1.99). Even with a normal BMI, a high BFP was associated with an increased risk of decreased BMD. Therefore, healthy body composition management, not simply BMI, is important in preventing decreased BMD.

Long or Irregular Menstrual Cycles and Risk of Prevalent and Incident Nonalcoholic Fatty Liver Disease.

CONTEXT: The association of menstrual cycle length and irregularity with the risk of non-alcoholic fatty liver disease (NAFLD) is unknown. OBJECTIVE: We examined this association in large cross-sectional and cohort studies. METHODS: The cross-sectional study included 72 092 women younger than 40 years who underwent routine health examinations; the longitudinal analysis included the subset of 51 118 women without NAFLD at baseline. Long or irregular cycles were defined as menstrual cycles of 40 days or longer or too irregular to estimate. Abdominal ultrasonography was performed to identify NAFLD. Multivariable Cox proportional hazard regression analyses were performed to estimate hazard ratios (HRs) and 95% CIs for incident NAFLD according to menstrual cycle regularity and length, with 26- to 30-day cycles as the reference. RESULTS: At baseline, 27.7% had long or irregular menstrual cycles and 7.1% had prevalent NAFLD. Long or irregular menstrual cycles were positively associated with prevalent NAFLD. During a median follow-up of 4.4 years, incident NAFLD occurred in 8.9% of women. After adjustment for age, body mass index, insulin resistance, and other confounders, the multivariable-adjusted HR for NAFLD comparing long or irregular menstrual cycles to the reference group was 1.22 (95% CI, 1.14-1.31); this association strengthened in the time-dependent analysis with an HR of 1.49 (95% CI, 1.38-1.60). CONCLUSION: Long or irregular menstrual cycles were associated with increased risk of both prevalent and incident NAFLD in young, premenopausal women. Women with long or irregular menstrual cycles may benefit from lifestyle modification advice to reduce the risk of NAFLD and associated cardiometabolic diseases.

Fasting ketonuria is inversely associated with coronary artery calcification in non-diabetic individuals.

BACKGROUND AND AIMS: Increased levels of ketone bodies, an alternative fuel when glucose availability is low, may exert beneficial effects on cardiovascular disease (CVD) risk factors. Whether increased ketone bodies are associated with coronary artery calcium (CAC), a recognized and strong cardiovascular risk factor, remains unknown. We investigated the association of fasting ketonuria with CAC and its progression. METHODS: Cross-sectional and longitudinal studies were conducted in adults without diabetes or CVD. Subjects underwent routine health examinations including cardiac computed tomography estimations of CAC scores. Logistic regression models were performed to compute the odds ratios (ORs), 95% confidence intervals (CIs), for prevalent CAC scores >0 according to fasting ketonuria categories (0, 1, and ≥2). Linear mixed models with random intercepts and random slopes were used to estimate CAC progression. RESULTS: Of 144,346 subjects, 12.3% had CAC scores >0 at baseline. Overall, higher fasting ketonuria was associated with decreased prevalence of coronary calcification than no ketonuria. Multivariable-adjusted ORs (95% CIs) for prevalent CAC by comparing ketonuria categories 1 and ≥2 with no ketonuria, were 0.94 (0.84-1.06) and 0.82 (0.71-0.95), respectively. The associations did not differ according to clinically relevant subgroups. Ketonuria was associated with lower CAC progression over time; the multivariable adjusted ratio of progression rates comparing ketonuria ≥2 versus no ketonuria was 0.976 (0.965-0.995). CONCLUSIONS: We found an inverse association between fasting ketonuria and subclinical coronary atherosclerosis, in both prevalence and progression. The potentially protective role of increased ketone body formation in CVD requires further investigation.

The association between cotinine-measured smoking intensity and sleep quality.

INTRODUCTION: Cigarette smoking is suggested to be associated with sleep problems. This study evaluated the quantitative association between urinary cotinine-verified smoking intensity and sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI). METHODS: This was a cross-sectional study of 189970 participants from the Kangbuk Samsung Health Study recruited between 2016 and 2018. Logistic regression analysis adjusted for covariates was performed to estimate the association between urinary cotinine levels assessed by quartiles and poor sleep quality, defined as global PSQI score >5. RESULTS: The odds ratios (OR) and 95% confidence intervals (CI) for poor sleep quality comparing the highest urinary cotinine quartile to non-smokers were: 1.23 (95% CI: 1.16-1.30) for overall, 1.19 (95% CI: 1.12-1.26) for males, and 1.55 (95% CI: 1.29-1.87) for females. Among self-reported never smokers, cotinineverified smokers had higher odds for decreased sleep quality compared to cotinineverified never smokers with OR of 1.26 (95% CI: 1.08-1.46). CONCLUSIONS: Elevated urinary cotinine levels were associated with poor sleep quality in relatively young and middle-aged South Korean adults. Higher odds for poor sleep quality among cotinine-verified smokers who self-reported as never smokers also demonstrate the value of quantitative measurement of urinary cotinine. Prospective studies are warranted to clarify the cause-effect relationship between smoking and sleep quality.

Depression and increased risk of non-alcoholic fatty liver disease in individuals with obesity.

Abstract. AIMS: The longitudinal relationship between depression and the risk of non-alcoholic fatty liver disease is uncertain. We examined: (a) the association between depressive symptoms and incident hepatic steatosis (HS), both with and without liver fibrosis; and (b) the influence of obesity on this association. METHODS: A cohort of 142 005 Korean adults with neither HS nor excessive alcohol consumption at baseline were followed for up to 8.9 years. The validated Center for Epidemiologic Studies-Depression score (CES-D) was assessed at baseline, and subjects were categorised as non-depressed (a CES-D < 8, reference) or depression (CES-D ⩾ 16). HS was diagnosed by ultrasonography. Liver fibrosis was assessed by the fibrosis-4 index (FIB-4). Parametric proportional hazards models were used to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 4.0 years, 27 810 people with incident HS and 134 with incident HS plus high FIB-4 were identified. Compared with the non-depressed category, the aHR (95% CIs) for incident HS was 1.24 (1.15-1.34) for CES-D ⩾ 16 among obese individuals, and 1.00 (0.95-1.05) for CES-D ⩾ 16 among non-obese individuals (p for interaction with obesity <0.001). The aHR (95% CIs) for developing HS plus high FIB-4 was 3.41 (1.33-8.74) for CES-D ⩾ 16 among obese individuals, and 1.22 (0.60-2.47) for CES-D ⩾ 16 among non-obese individuals (p for interaction = 0.201). CONCLUSIONS: Depression was associated with an increased risk of incident HS and HS plus high probability of advanced fibrosis, especially among obese individuals.