Ho Cheol Hong

Relationship between sarcopenia and nonalcoholic fatty liver disease: The Korean Sarcopenic Obesity Study

Previous studies have shown that nonalcoholic fatty liver disease (NAFLD) and sarcopenia may share pathophysiological mechanisms, such as insulin resistance, inflammation, vitamin D deficiency, and decreased physical activity. However, their direct relationship has not been investigated. The association between NAFLD and sarcopenia was examined in 452 apparently healthy adults enrolled in the Korean Sarcopenic Obesity Study (KSOS), an ongoing prospective observational cohort study. The liver attenuation index (LAI), which was measured using abdominal computed tomography (CT), was used as a parameter for the diagnosis of NAFLD. Sarcopenia was defined using a skeletal muscle mass index (SMI) [SMI (%) = total skeletal muscle mass (kg) / weight (kg) × 100] that was measured by dual energy X‐ray absorptiometry (DXA). After adjusting for age and sex, both SMI and LAI were negatively correlated with the homeostasis model assessment of insulin resistance (HOMA‐IR) (P < 0.001) and high sensitivity C‐reactive protein (hsCRP) (P < 0.001) as well as brachial‐ankle pulse wave velocity (baPWV), an indicator of arterial stiffness. Furthermore, SMI and LAI had positive relationships with high‐density lipoprotein (HDL)‐cholesterol, but both had a negative relationship with triglyceride, alanine aminotransferase (ALT), and total body fat. In a multiple logistic regression analysis, the odds ratio for NAFLD risk was 5.16 (95% confidence interval [CI] = 1.63‐16.33) in the lowest quartile of SMI compared to the highest after adjusting for potential confounding factors. Conclusion: Individuals with lower muscle mass exhibited increased risk of NAFLD. This result may provide a novel insight into the mechanism linking between sarcopenia and NAFLD. (Clinical trial no. NCT01594710.) (Hepatology 2014;59:1772–1778)

Effects of a three‐month combined exercise programme on fibroblast growth factor 21 and fetuin‐A levels and arterial stiffness in obese women

Objective  We examined the relationship between brachial‐ankle pulse wave velocity (baPWV) reflecting arterial stiffness and the levels of novel hepatokines fibroblast growth factor 21 (FGF21) and fetuin‐A. In addition, we evaluated the effect of a 3‐month combined aerobic and resistance exercise programme on FGF21 and fetuin‐A levels as well as arterial stiffness in obese women.

Association of circulating omentin-1 level with arterial stiffness and carotid plaque in type 2 diabetes

BackgroundAdipokines contribute directly to the atherosclerotic process, connecting metabolic disorders such as obesity and diabetes to cardiovascular disease. Omentin-1 is a recently discovered novel adipokine, so data about the relationship of this adipokine to vascular health in type 2 diabetes is limited.MethodsWe enrolled 60 people with type 2 diabetes, with or without carotid plaque, and 30 participants with normal glucose tolerance. We measured serum omentin-1, high-sensitivity C-reactive protein (hsCRP) levels, and the homeostasis model assessment of insulin resistance (HOMA-IR), as well as other cardiovascular risk factors. Vascular health was assessed by brachial ankle pulse wave velocity (baPWV) and carotid intima-media thickness (IMT).ResultsSerum omentin-1 levels were significantly decreased in type 2 diabetes patients compared to normal glucose controls and was further reduced in type 2 diabetes patients with carotid plaque compared to those without carotid plaque. Multiple stepwise regression analysis showed that age, systolic blood pressure, history of use of statins, angiotensin receptor blockers or angiotensin-converting enzyme inhibitors, and serum omentin-1 level were independent factors determining baPWV in people with type 2 diabetes (r2 = 0.637). Furthermore, in multivariate logistic regression analysis, circulating omentin-1 level was an independent decisive factor for the presence of carotid plaque in type 2 diabetes patients, even after adjusting for age, gender, body mass index, systolic blood pressure, fasting blood glucose, low density lipoprotein cholesterol, and history of smoking and medication (odds ratio, 0.621; 95% confidence interval, 0.420-0.919; P = 0.017).ConclusionsCirculating omentin-1 level was independently correlated with arterial stiffness and carotid plaque in type 2 diabetes, even after adjusting for other cardiovascular risk factors and detailed medication history.

Effects of Exercise on sRAGE Levels and Cardiometabolic Risk Factors in Patients with Type 2 Diabetes: A Randomized Controlled Trial

CONTEXT Low levels of soluble receptor for advanced glycation end-products (sRAGE) have been linked to systemic inflammation and vascular complications in patients with type 2 diabetes mellitus (T2DM). OBJECTIVE We examined the effects of exercise on sRAGE and its association with diverse cardiometabolic risk factors and indicators of atherosclerosis in patients with T2DM. DESIGN, SETTING, AND PARTICIPANTS Seventy-five patients with T2DM were randomized into a control group and an aerobic exercise group (60 min at moderate intensity, five times/wk for 12 wk). MAIN OUTCOME MEASURES We evaluated sRAGE, energy expenditure, dietary energy intake, cardiorespiratory fitness, inflammatory markers, visceral fat area, pulse-wave velocity, and flow-mediated dilatation. RESULTS Baseline sRAGE concentrations were independently associated with age, glycated hemoglobin, glucose, triglyceride, and high-density lipoprotein cholesterol levels (R2=0.244). After 12 wk of exercise training, the exercise group showed significantly decreased body weight, waist circumference, blood pressure, glycated hemoglobin, apolipoprotein B, and free fatty acid levels. Concurrently, cardiorespiratory fitness assessed by oxygen uptake at anaerobic threshold was improved, and body fat percentage and visceral fat area were significantly decreased in the exercise group, although pulse-wave velocity and flow-mediated dilatation were not changed. Furthermore, sRAGE levels were increased and high-sensitivity C-reactive protein levels were decreased in the exercise group but not in the control group. Percent change of sRAGE level was negatively correlated with that of high-sensitivity C-reactive protein during the study period (r=-0.27; P=0.019). CONCLUSIONS Aerobic exercise increases sRAGE levels along with improvement of various cardiometabolic risk factors in patients with T2DM.

C1q/TNF-Related Protein-3 (CTRP-3) and Pigment Epithelium-Derived Factor (PEDF) Concentrations in Patients With Type 2 Diabetes and Metabolic Syndrome

Recent studies have suggested that a novel adipokine, C1q/tumor necrosis factor-related protein-3 (CTRP-3), a paralog of adiponectin, may play an important role in the regulation of glucose metabolism and innate immunity. Pigment epithelium-derived factor (PEDF), a multifunctional protein with antioxidant and anti-inflammatory properties, is associated with insulin resistance and metabolic syndrome. We examined circulating CTRP-3 and PEDF concentrations in 345 subjects with diverse glucose tolerance statuses. Furthermore, we evaluated the involvement of CTRP-3 and PEDF with cardiometabolic risk factors including insulin resistance, high-sensitivity C-reactive protein (hsCRP), estimated glomerular filtration rate (eGFR), and brachial-ankle pulse wave velocity (baPWV). CTRP-3 concentrations were significantly higher in patients with type 2 diabetes or prediabetes than the normal glucose tolerance group, whereas PEDF levels were not different. Subjects with metabolic syndrome showed significantly higher levels of both CTRP-3 and PEDF compared with subjects without metabolic syndrome. Both CTRP-3 and PEDF were significantly associated with cardiometabolic parameters, including waist-to-hip ratio, triglycerides, HDL-cholesterol, alanine aminotransferase, eGFR, hsCRP, and baPWV. In conclusion, circulating CTRP-3 concentrations were elevated in patients with glucose metabolism dysregulation. Both CTRP-3 and PEDF concentrations were increased in subjects with metabolic syndrome and associated with various cardiometabolic risk factors.

Increased Selenoprotein P Levels in Subjects with Visceral Obesity and Nonalcoholic Fatty Liver Disease

Background Selenoprotein P (SeP) has recently been reported as a novel hepatokine that regulates insulin resistance and systemic energy metabolism in rodents and humans. We explored the associations among SeP, visceral obesity, and nonalcoholic fatty liver disease (NAFLD). Methods We examined serum SeP concentrations in subjects with increased visceral fat area (VFA) or liver fat accumulation measured with computed tomography. Our study subjects included 120 nondiabetic individuals selected from participants of the Korean Sarcopenic Obesity Study. In addition, we evaluated the relationship between SeP and cardiometabolic risk factors, including homeostasis model of insulin resistance (HOMA-IR), high sensitivity C-reactive protein (hsCRP), adiponectin values, and brachial-ankle pulse wave velocity (baPWV). Results Subjects with NAFLD showed increased levels of HOMA-IR, hsCRP, VFA, and several components of metabolic syndrome and decreased levels of adiponectin and high density lipoprotein cholesterol than those of controls. Serum SeP levels were positively correlated with VFA, hsCRP, and baPWV and negatively correlated with the liver attenuation index. Not only subjects with visceral obesity but also those with NAFLD exhibited significantly increased SeP levels (P<0.001). In multiple logistic regression analysis, the subjects in the highest SeP tertile showed a higher risk for NAFLD than those in the lowest SeP tertile, even after adjusting for potential confounding factors (odds ratio, 7.48; 95% confidence interval, 1.72 to 32.60; P=0.007). Conclusion Circulating SeP levels were increased in subjects with NAFLD as well as in those with visceral obesity and may be a novel biomarker for NAFLD.

Implication of Progranulin and C1q/TNF-Related Protein-3 (CTRP3) on Inflammation and Atherosclerosis in Subjects with or without Metabolic Syndrome

Objective Progranulin and C1q/TNF-related protein-3 (CTRP3) were recently discovered as novel adipokines which may link obesity with altered regulation of glucose metabolism, chronic inflammation and insulin resistance. Research Design and Methods We examined circulating progranulin and CTRP3 concentrations in 127 subjects with (n = 44) or without metabolic syndrome (n = 83). Furthermore, we evaluated the relationship of progranulin and CTRP3 levels with inflammatory markers and cardiometabolic risk factors, including high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), estimated glomerular filtration rate (eGFR), and adiponectin serum concentrations, as well as carotid intima-media thickness (CIMT). Results Circulating progranulin levels are significantly related with inflammatory markers, hsCRP (r = 0.30, P = 0.001) and IL-6 (r = 0.30, P = 0.001), whereas CTRP3 concentrations exhibit a significant association with cardiometabolic risk factors, including waist circumference (r = −0.21), diastolic blood pressure (r = −0.21), fasting glucose (r = −0.20), triglyceride (r = −0.34), total cholesterol (r = −0.25), eGFR (r = 0.39) and adiponectin (r = 0.26) levels. Serum progranulin concentrations were higher in patients with metabolic syndrome than those of the control group (199.55 [179.33, 215.53] vs. 185.10 [160.30, 204.90], P = 0.051) and the number of metabolic syndrome components had a significant positive correlation with progranulin levels (r = 0.227, P = 0.010). In multiple regression analysis, IL-6 and triglyceride levels were significant predictors of serum progranulin levels (R 2 = 0.251). Furthermore, serum progranulin level was an independent predictor for increased CIMT in subjects without metabolic syndrome after adjusting for other cardiovascular risk factors (R 2 = 0.365). Conclusions Serum progranulin levels are significantly associated with systemic inflammatory markers and were an independent predictor for atherosclerosis in subjects without metabolic syndrome. Trial Registration ClinicalTrials.gov NCT01668888

Impact of Visceral Fat on Skeletal Muscle Mass and Vice Versa in a Prospective Cohort Study: The Korean Sarcopenic Obesity Study (KSOS)

Objectives Sarcopenia and visceral obesity have been suggested to aggravate each other, resulting in a vicious cycle. However, evidence based on prospective study is very limited. Our purpose was to investigate whether visceral fat promotes a decrease in skeletal muscle mass and vice versa. Methods We observed changes in anthropometric and body composition data during a follow-up period of 27.6±2.8 months in 379 Korean men and women (mean age 51.9±14.6 years) from the Korean Sarcopenic Obesity Study (KSOS). Appendicular lean soft tissue (ALST) mass was calculated using dual-energy X-ray absorptiometry, and visceral fat area (VFA) was measured using computed tomography at baseline and follow-up examination. Results ALST mass significantly decreased, whereas trunk and total fat mass increased in both men and women despite no significant change in weight and body mass index. In particular, women with visceral obesity at baseline had a greater decrease in ALST mass than those without visceral obesity (P = 0.001). In multiple linear regression analysis, baseline VFA was an independent negative predictor of the changes in ALST after adjusting for confounding factors including age, gender, life style and body composition parameters, insulin resistance, high sensitivity C-reactive protein and vitamin D levels (P = 0.001), whereas the association between baseline ALST mass and changes in VFA was not statistically significant (P = 0.555). Conclusions This longitudinal study showed that visceral obesity was associated with future loss of skeletal muscle mass in Korean adults. These results may provide novel insight into sarcopenic obesity in an aging society.

Association of metabolically abnormal but normal weight (MANW) and metabolically healthy but obese (MHO) individuals with arterial stiffness and carotid atherosclerosis

OBJECTIVE Despite recent interest in differential impact of body size phenotypes on cardiovascular outcomes and mortality, studies evaluating the association between body size phenotypes and indicators of atherosclerosis are limited. This study investigated the relationship of metabolically abnormal but normal weight (MANW) and metabolically healthy but obese (MHO) individuals with arterial stiffness and carotid atherosclerosis in Korean adults without cardiovascular disease. METHODS A total of 1012 participants (575 men and 437 women, mean age 50.8 years), who underwent a health examination between April 2012 and May 2013 were prospectively enrolled based on inclusion and exclusion criteria. Study subjects were classified according to body mass index (BMI) and the presence/absence of metabolic syndrome. RESULTS The prevalence of metabolically healthy normal weight (MHNW), MANW, MHO, and metabolically abnormal obese (MAO) were 54.84%, 6.42%, 22.83%, and 15.91%, respectively. Individuals with MANW had significantly higher brachial-ankle pulse wave velocity and maximal carotid intima-media thickness values than those with MHO, after adjusting for age and gender (P = 0.026 and P = 0.018, respectively). The odds ratio (OR) of arterial stiffness and carotid atherosclerosis in the MANW group were significantly higher than in the MHNW group in unadjusted models. Furthermore, multivariable models showed that increased OR of carotid atherosclerosis in the MANW group persisted even after adjusting for confounding factors (OR = 2.98, 95% CI = [1.54, 5.73], P = 0.011). CONCLUSIONS Compared to MHNW or MHO subjects, Korean men and women with the MANW phenotype exhibited increased arterial stiffness and carotid atherosclerosis. CLINICAL TRIALS NO NCT01594710.

Implication of circulating irisin levels with brown adipose tissue and sarcopenia in humans.

CONTEXT Irisin is an exercise-induced novel myokine that drives brown-fat-like conversion of white adipose tissue and has been suggested to be a promising target for the treatment of obesity-related metabolic disorders. OBJECTIVE To assess the association of circulating irisin concentrations with brown adipose tissue (BAT) and/or sarcopenia in humans. SETTING AND DESIGN We examined irisin levels in 40 BAT-positive and 40 BAT-negative women detected by (18)F-fluorodeoxyglucose positron emission tomography ((18)FDG-PET). In a separate study, we also examined 401 subjects with or without sarcopenia defined by skeletal muscle mass index (SMMI) and appendicular skeletal muscle (ASM)/height(2) using dual-energy x-ray absorptiometry. RESULTS Among 6877 consecutive (18)FDG-PET scans in 4736 subjects, 146 subjects (3.1%) had positive BAT scans. The BAT-detectable group and the matched BAT-undetectable group did not differ in circulating irisin levels measured using two different ELISA kits (P = .747 and P = .160, respectively). Serum irisin levels were not different between individuals with sarcopenia and those without sarcopenia using either kit (P = .305 and P = .569, respectively). Also, serum irisin levels were not different between groups defined by ASM/height(2) using either kit (P = .352 and P = .134, respectively). Although visceral fat area and skeletal muscle mass showed significant difference according to tertiles of SMMI levels, irisin concentrations did not differ. CONCLUSIONS Circulating irisin levels were not different in individuals with detectable BAT or those with sarcopenia compared with control subjects and were not correlated with SMMI.