Juhee Cho

Metabolically-healthy obesity and coronary artery calcification.

OBJECTIVES The purpose of this study was to compare the coronary artery calcium (CAC) scores of metabolically-healthy obese (MHO) and metabolically healthy normal-weight individuals in a large sample of apparently healthy men and women. BACKGROUND The risk of cardiovascular disease among obese individuals without obesity-related metabolic abnormalities, referred to as MHO, is controversial. METHODS We conducted a cross-sectional study of 14,828 metabolically-healthy adults with no known cardiovascular disease who underwent a health checkup examination that included estimation of CAC scores by cardiac tomography. Being metabolically healthy was defined as not having any metabolic syndrome component and having a homeostasis model assessment of insulin resistance <2.5. RESULTS MHO individuals had a higher prevalence of coronary calcification than normal weight subjects. In multivariable-adjusted models, the CAC score ratio comparing MHO with normal-weight participants was 2.26 (95% confidence interval: 1.48 to 3.43). In mediation analyses, further adjustment for metabolic risk factors markedly attenuated this association, which was no longer statistically significant (CAC score ratio 1.24; 95% confidence interval: 0.79 to 1.96). These associations did not differ by clinically-relevant subgroups. CONCLUSIONS MHO participants had a higher prevalence of subclinical coronary atherosclerosis than metabolically-healthy normal-weight participants, which supports the idea that MHO is not a harmless condition. This association, however, was mediated by metabolic risk factors at levels below those considered abnormal, which suggests that the label of metabolically healthy for obese subjects may be an artifact of the cutoff levels used in the definition of metabolic health.

Metabolically Healthy Obesity and Development of Chronic Kidney Disease: A Cohort Study.

Context The risk for chronic kidney disease (CKD) among obese patients without metabolic abnormalities is unknown. Contribution In this cohort study of South Korean men and women, metabolically healthy overweight and obese participants had increased incidence of CKD compared with normal-weight participants. Caution Body mass index was a marker of obesity and was assessed only once at baseline. Implication Physicians should monitor metabolically healthy obese and overweight patients for CKD and counsel them about maintaining a healthy weight and lifestyle. Chronic kidney disease (CKD) is a major clinical and public health problem (1). It is a precursor for end-stage renal disease and a strong risk factor for cardiovascular morbidity and mortality (2). Its prevalence is increasing worldwide along with the growing prevalence of obesity and metabolic disease (3). Indeed, obesitymediated by hypertension, insulin resistance, hyperglycemia, dyslipidemia, and other metabolic abnormalitiesis a major risk factor for CKD (4). Although the role of obesity-induced metabolic abnormalities in CKD development is well-established, metabolically healthy obese (MHO) persons, seem to have a favorable profile with no metabolic abnormalities (5, 6). The association between MHO and CKD, however, is largely unknown. The only study available found no association (7), but the comparison between MHO and normal-weight participants could be biased because the reference group included overweight participants, and metabolically healthy participants were defined as those with fewer than 2 metabolic components. Therefore, we examined the association between categories of body mass index (BMI) and CKD in a large sample of metabolically healthy men and women who had health screening examinations. Methods Study Population The Kangbuk Samsung Health Study is a cohort study of South Korean men and women aged 18 years or older who had a comprehensive annual or biennial health examination at the clinics of the Kangbuk Samsung Hospital Health Screening Centers in Seoul and Suwon, South Korea (8). More than 80% of participants were employees of various companies and local governmental organizations and their spouses. In South Korea, the Industrial Safety and Health Act requires all employees to receive annual or biennial health screening examinations, offered free of charge. The remaining participants registered for the screening examinations on their own. Our analysis included all persons who had comprehensive health examinations from 1 January 2002 to 31 December 2009 and had at least 1 other screening examination before 31 December 2013 (that is, they all had a baseline visit and 1 follow-up visit [n=175859]) (Figure 1). We excluded persons who had metabolic abnormalities (5, 9, 10) or evidence of kidney disease at baseline (n=108263). We excluded those with fasting glucose levels of 100 mg/dL or greater or who used glucose-lowering agents; blood pressure (BP) of 130/85 mm Hg or greater or who used BP-lowering agents; triglyceride levels of 150 mg/dL or greater or who used lipid-lowering agents; high-density lipoprotein (HDL) cholesterol levels less than 40 mg/dL in men or less than 50 mg/dL in women; insulin resistance, defined as homeostasis model assessment of insulin resistance (HOMA-IR) scores of 2.5 or greater (11); estimated glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2; proteinuria; history of CKD; or history of cancer. Among eligible participants (n=67596), we further excluded those with missing values in any of the study variables (n=5347 [7.9%]). The final sample size was 62249 participants (Figure 1), all of whom were metabolically healthy and did not have markers of kidney disease at baseline. This study was approved by the Institutional Review Board of the Kangbuk Samsung Hospital, which exempted the requirement for informed consent because we only accessed deidentified data routinely collected as part of health screening examinations. Figure 1. Study flow diagram. CKD = chronic kidney disease; HDL = high-density lipoprotein. * Participants in the screening program could have >1 criterion that made them ineligible for the study. Eligible participants could have missing data in >1 study variable. Measurements Data on medical history, medication use, family history, physical activity, alcohol intake, smoking habits, and education level were collected by a standardized, self-administered questionnaire. Anthropometry data, BP, and blood samples were obtained by trained staff during the examinations (8, 12). Smoking status was categorized as never, former, or current. Alcohol consumption was categorized as none, moderate (20 g per day), or high (>20 g per day). The weekly frequency of moderate- or vigorous-intensity physical activity was also assessed. Sitting BP, height, and weight were measured by trained nurses. Height was measured to the nearest 1 cm with a stadiometer while the participant stood barefoot. Weight was measured to the nearest 0.1 kg on a bioimpedance analyzer (InBody 3.0 and Inbody 720, Biospace), which was validated for reproducibility and accuracy of body composition measurements (13) and calibrated every morning before testing started. Body mass index was calculated as weight in kilograms divided by height in meters squared and was classified according to Asian-specific criteria (14) (underweight, BMI <18.5 kg/m2; normal weight, BMI of 18.5 to 22.9 kg/m2; overweight, BMI of 23 to 24.9 kg/m2; and obese, BMI 25 kg/m2). Blood specimens were sampled from the antecubital vein after at least a 10-hour fast. The methods for measuring serum levels of glucose, uric acid, total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, HDL cholesterol, aspartate aminotransferase, alanine aminotransferase, -glutamyltransferase, insulin, and high-sensitivity C-reactive protein (hsCRP) have been reported elsewhere (8, 12). The Department of Laboratory Medicine of the Kangbuk Samsung Hospital has been accredited by the Korean Society for Laboratory Medicine and the Korean Association of Quality Assurance for Clinical Laboratories and participates in the College of American Pathologists Proficiency Testing survey. Insulin resistance was assessed with the HOMA-IR equation (fasting insulin [uU/mL]fasting glucose [mmol/L] 22.5). An ultrasonographic diagnosis of fatty liver was defined as a diffuse increase of fine echoes in the liver parenchyma compared with the kidney or spleen parenchyma (15, 16). During the study period, serum creatinine levels were measured with the kinetic alkaline picrate method (Jaffe method) in an automated chemistry analyzer (from 2002 to 2009, we used the Advia 1650a Autoanalyzer [Bayer Diagnostics]; from 2010 to 2013, we used the Modular D2400 [Roche]). The within-batch and total coefficients of variation were 1.8% to 3.9% for low-level and 1.4% to 1.8% for high-level quality control specimens throughout the study. Because the laboratory method that was used to measure serum creatinine levels from 2002 to 2009 was not traceable to isotope-dilution mass spectrometry, we estimated GFR by using the 4-variable Modification of Diet in Renal Disease Study equation (17). The conclusions did not change if we used the Chronic Kidney Disease Epidemiology Collaboration equation (18) for GFR estimation (data not shown). Urine protein was measured semiquantitatively by urine dipstick (URiSCAN Urine test strips, YD Diagnostics) tested on fresh, midstream urine samples and was reported in the following 6 grades: absent, trace, 1+, 2+, 3+, and 4+ (corresponding to protein levels of undetectable, 10 mg/dL, 30 mg/dL, 100 mg/dL, 300 mg/dL, and 1000 mg/dL, respectively). Proteinuria was defined as a grade of 1+ or greater. Statistical Analysis Person-years of follow-up were calculated from the date of the baseline health examination until the date of CKD diagnosis or the last screening examination, whichever came first. The cumulative incidence of CKD for baseline BMI categories (<18.5, 18.5 to 22.9, 23.0 to 24.9, or 25.0 kg/m2) were standardized to the empirical distribution of baseline confounders in the overall study sample with inverse probability weighting (19, 20). We first fitted a multinomial logistic regression to estimate each participants probability of being in his or her own BMI category given the observed confounders. Stabilized weights were then calculated as the inverse of the estimated conditional probabilities of exposure, further rescaled by the overall proportion of participants in each BMI category to reduce variability of weights across groups and to avoid influential observations involving extremely obese persons (19). For risk analyses, we fitted a spline-based, parametric survival model (21) according to the stabilized weights and stratified by BMI category to obtain smooth estimates of the CKD cumulative incidence curves that would have been seen in the entire population if every participant had been in each category (20). This survival model parameterized stratum-specific log cumulative hazards as distinct natural cubic splines of log time with 3 internal knots at the 25th, 50th, and 75th percentiles; allowed for interval-censored events (incident CKD occurred at an unknown time point between the visit at which CKD was diagnosed and the previous visit); and used robust SEs for spline parameters that accounted for the correlation induced by weighting (21). For comparison, we also applied weighted KaplanMeier methods to estimate nonparametric cumulative incidence curves for each BMI category. We used the previously mentioned weighted, spline-based survival model to calculate adjusted differences in cumulative incidences of CKD at 2, 5, and 10 years of follow-up of normal-weight participants compared with those in the other BMI categories. We calculated 95% CIs by applying delta methods to the robust variance estimates of spline parameters. In addition to risk differences, we

Serum uric acid levels predict incident nonalcoholic fatty liver disease in healthy Korean men

The objective of the study was to assess the prospective association between serum uric acid levels and incident nonalcoholic fatty liver disease in a cohort of healthy Korean men. A cohort study was performed on 5741 Korean men, 30 to 59 years of age, with no evidence of fatty liver disease on liver ultrasound and with no major risk factors for liver disease at baseline. Study participants were followed in annual or biennial health examinations between 2002 and 2008. The presence of fatty liver was determined at each examination by ultrasound. Cox proportional hazards models were used to evaluate the association of baseline and time-dependent levels of serum uric acid with incident fatty liver, adjusted for potential confounders. During 23,995 person-years of follow-up, 1717 participants developed fatty liver on ultrasound examination. After adjustment for age, body mass index, smoking, and alcohol intake, the hazard ratios (95% confidence intervals) for incident fatty liver comparing quartiles 2 to 4 of serum uric acid to quartile 1 were 1.17 (1.01-1.37), 1.28 (1.11-1.48), and 1.51 (1.31-1.73), respectively (P for trend = .001). The adjusted hazard ratio comparing participants with hyperuricemia (serum uric acid ≥7.0 mg/dL) to those with normouricemia (<7.0 mg/dL) was 1.29 (1.14-1.46). A graded and statistically significant association persisted after adjusting for other cardiometabolic factors and also in time-dependent models. Serum uric acid was an independent risk factor of incident fatty liver detected by ultrasonography. Additional research should clarify the mechanisms underlying this association and the role of hyperuricemia in the development of fatty liver.

Cohort Study of Non-alcoholic Fatty Liver Disease, NAFLD fibrosis score, and the Risk of Incident Diabetes in a Korean population

OBJECTIVES:No study has evaluated an association between non-alcoholic fatty liver disease (NAFLD) severity and the incidence of diabetes. We examined whether NAFLD and its severity—using the NAFLD fibrosis score (NFS)—predict the development of diabetes.METHODS:A cross-sectional study was performed in 43,166 apparently healthy Koreans aged 30–59 years, who underwent a health checkup in 2005 and 2006. Of these, 38,291 subjects without diabetes were followed annually or biennially until December 2011 for the cohort study. NAFLD was defined as hepatic steatosis on ultrasonography in the absence of excessive alcohol use or other identifiable causes. The NFS was used to categorize the severity of fibrosis. Diabetes was defined as fasting serum glucose ≥126 mg/dl, glycated hemoglobin (HbA1c) ≥6.5%, or medication use for diabetes.RESULTS:During 175,996 person-years of follow-up, 2,025 participants developed diabetes. An increase across NAFLD categories was positively associated with an increased risk of diabetes in both the cross-sectional and cohort studies in a dose–response manner (P-trend <0.001). In multivariate-adjusted models, the hazard ratios (95% confidence intervals) for diabetes comparing NAFLD with low NFS and NAFLD with intermediate or high NFS vs. no NAFLD were 2.00 (1.79–2.24) and 4.74 (3.67–6.13), respectively. This association remained significant even in subjects with fasting glucose <100 mg/dl and subjects with HbA1c <5.8%.CONCLUSIONS:In this cohort study of a healthy Korean population, NAFLD and its severity using NFS were independently and strongly associated with increased incidence of diabetes in men and women—even with a euglycemic range of glucose and HbA1c.

Relationship of sitting time and physical activity with non-alcoholic fatty liver disease

BACKGROUND & AIMS The goal of this study was to examine the association of sitting time and physical activity level with non-alcoholic fatty liver disease (NAFLD) in Korean men and women and to explore whether any observed associations were mediated by adiposity. METHODS A cross-sectional study was performed on 139,056 Koreans, who underwent a health examination between March 2011 and December 2013. Physical activity level and sitting time were assessed using the validated Korean version of the international Physical Activity Questionnaire Short Form. The presence of fatty liver was determined using ultrasonographic findings. Poisson regression models with robust variance were used to evaluate the association of sitting time and physical activity level with NAFLD. RESULTS Of the 139,056 subjects, 39,257 had NAFLD. In a multivariable-adjusted model, both prolonged sitting time and decreased physical activity level were independently associated with increasing prevalence of NAFLD. The prevalence ratios (95% CIs) for NAFLD comparing 5-9 and ⩾10 h/day sitting time to <5h/day were 1.04 (1.02-1.07) and 1.09 (1.06-1.11), respectively (p for trend <0.001). These associations were still observed in subjects with BMI <23 kg/m(2). The prevalence ratios (95% CIs) for NAFLD comparing minimally active and health-enhancing physically active groups to the inactive group were 0.94 (0.92-0.95) and 0.80 (0.78-0.82), respectively (p for trend <0.001). CONCLUSIONS Prolonged sitting time and decreased physical activity level were positively associated with the prevalence of NAFLD in a large sample of middle-aged Koreans, supporting the importance of reducing time spent sitting in addition to promoting physical activity.

Changes of quality of life in gastric cancer patients after curative resection: a longitudinal cohort study in Korea.

Objective:Little is known about how quality of life (QOL) changes over time after gastrectomy. We prospectively examined changes of QOL in Korean patients with gastric cancer after curative resection. Background:As early detection and improved treatment have led to higher survival rates and an increasing number of long-term survivors, the importance of QOL has increased. Methods:Patients newly diagnosed with gastric cancer, who were expected to undergo curative resection, were studied. QOL was assessed, using the European Organization for Research and Treatment of Cancer QLQ-C30 and its gastric module QLQ-STO22, before and after 3 and 12 months of gastrectomy. Results:In total, 465 patients were included in the study, and 377 and 88 patients underwent subtotal gastrectomy and total gastrectomy, respectively. For most of the functional or symptom scales, the mean score deteriorated at 3 months and generally improved during follow-up period. Patients with total gastrectomy had more functional and symptomatic problems related to QOL than those with subtotal gastrectomy during the follow-up. For both groups, there were temporal, unrecovered, improved, and unchanged problems in QOL. Fatigue; digestive symptoms such as diarrhea, dysphagia, and eating restrictions; body image disturbance; and cognitive functioning were the representative unrecovered problems, which persisted at 12 months after surgery. Conclusions:Our findings show that there are various functional and symptomatic problems, which health care providers need to manage during the postsurgical period. We need to continuously address fatigue, diarrhea, dysphagia, eating restrictions, body image disturbance, and cognitive functioning. In addition, it would be necessary to inform patients about possible QOL outcomes while they are receiving information about surgery and signing informed consent for surgery.

EGFR Mutation Testing in Patients with Advanced Non-Small Cell Lung Cancer: A Comprehensive Evaluation of Real-World Practice in an East Asian Tertiary Hospital

Introduction Guidelines for management of non-small cell lung cancer (NSCLC) strongly recommend EGFR mutation testing. These recommendations are particularly relevant in Asians that have higher EGFR mutation prevalence. This study aims to explore current testing practices, logistics of testing, types of EGFR mutation, and prevalence of EGFR mutations in patients with advanced NSCLC in a large comprehensive cancer center in Korea. Methods Our retrospective cohort included 1,503 NSCLC patients aged ≥18 years, with stage IIIB/IV disease, who attended the Samsung Medical Center in Seoul, Korea, from January 2007 through July 2010. Trained oncology nurses reviewed and abstracted data from electronic medical records. Results This cohort had a mean age (SD) of 59.6 (11.1) years, 62.7% were males, and 52.9% never-smokers. The most common NSCLC histological types were adenocarcinoma (70.5%) and squamous cell carcinoma (18.0%). Overall, 39.5% of patients were tested for EGFR mutations. The proportion of patients undergoing EGFR testing during January 2007 through July 2008, August 2008 through September 2009, and October 2009 through July 2010 were 23.3%, 38.3%, and 63.5%, respectively (P<0.001). The median time elapsed between cancer diagnoses and receiving EGFR testing results was 21 days. EGFR testing was most frequently ordered by oncologists (57.7%), pulmonologists (31.9%), and thoracic surgeons (6.6%). EGFR testing was more commonly requested for women, younger patients, stage IV disease, non-smokers, and adenocarcinoma histology. Of 586 cases successfully tested for EGFR mutations, 209 (35.7%) were positive, including 118 cases with exon 19 deletions and 62 with L858R mutations. EGFR mutation positive patients were more likely to be female, never-smokers, never-drinkers and to have adenocarcinoma. Conclusions In a large cancer center in Korea, the proportion of EGFR testing increased from 2007 through 2010. The high frequency of EGFR mutation positive cases warrants the need for generalized testing in Asian NSCLC patients.

Association between cancer stigma and depression among cancer survivors: a nationwide survey in Korea

Cancer patients are more likely to experience depression than the general population. This study aims to evaluate the possible association between cancer stigma and depression among cancer patients.

Metabolically Healthy Obesity and the Development of Nonalcoholic Fatty Liver Disease.

OBJECTIVES:The risk of nonalcoholic fatty liver disease (NAFLD) among obese individuals without obesity-related metabolic abnormalities, a condition referred to as metabolically healthy obese (MHO), is largely unexplored. Therefore, we examined the association between body mass index (BMI) categories and the development of NAFLD in a large cohort of metabolically healthy men and women.METHODS:A cohort study was conducted in 77,425 men and women free of NAFLD and metabolic abnormalities at baseline, who were followed-up annually or biennially for an average of 4.5 years. Being metabolically healthy was defined as not having any metabolic syndrome component and having a homeostasis model assessment of insulin resistance <2.5. The presence of fatty liver was determined using ultrasound.RESULTS:During 348,193.5 person-years of follow-up, 10,340 participants developed NAFLD (incidence rate, 29.7 per 1,000 person-years). The multivariable adjusted hazard ratios (95% confidence intervals) for incident NAFLD comparing overweight and obese with normal-weight participants were 2.15 (2.06–2.26) and 3.55 (3.37–3.74), respectively. In detailed dose–response analyses, increasing baseline BMI showed a strong and approximately linear relationship with the incidence of NAFLD, with no threshold at no risk. This association was present in both men and women, although it was stronger in women (P for interaction <0.001), and it was evident in all clinically relevant subgroups evaluated, including participants with low inflammation status.CONCLUSIONS:In a large cohort of strictly defined metabolically healthy men and women, overweight and obesity were strongly and progressively associated with an increased incidence of NAFLD, suggesting that the obese phenotype per se, regardless of metabolic abnormalities, can increase the risk of NAFLD.

Impact of chemotherapy-induced alopecia distress on body image, psychosocial well-being, and depression in breast cancer patients.

This study aims to evaluate the impact of chemotherapy‐induced alopecia (CIA) distress on body image, psychosocial well‐being, and depression among breast cancer patients.