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Objective: It was hypothesized that the presence of nonalcoholic fatty liver disease (NAFLD) at baseline predicts future conversion from the metabolically healthy (MH) to the metabolically unhealthy (MU) phenotype according to body fat mass., Methods: A total of 22,551 Korean participants (13,601 men and 8,950 women) aged 18 to 78 years in the Kangbuk Samsung Health Study cohort were enrolled from 2007 to 2013., Results: During a median of 5.1 years of follow-up (interquartile range 2.1-9.8 years), 23.5% (n = 5,298) of MH individuals converted to the MU phenotype. NAFLD at baseline predicted conversion independent of age, sex, BMI, lifestyle factors, individual components of metabolic syndrome, and insulin resistance (HR, 1.29; 95% CI: 1.19-1.39; P < 0.0001). In participants with lower BMI and fat mass, NAFLD was strongly associated with conversion; however, as BMI and fat mass increased, the risk decreased, and there was no association in participants with higher BMI and fat mass (P < 0.0001 for trend)., Conclusions: NAFLD at baseline was independently associated with future conversion from the MH to the MU phenotype., (© 2019 The Obesity Society.)

Introduction: Non-alcoholic fatty liver disease (NAFLD) is considered as the hepatic manifestation of the metabolic syndrome (MetS), with insulin resistance as the common pathophysiology. In a current longitudinal cohort study, we evaluated the separate and combined effects of MetS and NAFLD on incident diabetes risk., Methods: Participants were categorized into four groups on the basis of the presence of NAFLD and MetS at baseline (i.e., with NAFLD, with MetS, with both, or without either). We compared the development of diabetes among these four groups., Results: During the mean follow up of 4years, 435 of the 7849 participants (5.5%) developed diabetes. The age, sex, and smoking-adjusted risk of incident diabetes was higher in the NAFLD only group (HR 1.51, 95% CI 1.14-1.99), MetS only group (HR 2.82, 95% CI 2.01-3.95), and both group (HR 5.45, 95% CI 4.32-6.82) compared with the group of neither. When compared with the NAFLD only group, the adjusted HR for incident diabetes was 1.87 (95% CI 1.29-2.72) in the MetS only group and 3.62 (95% CI 2.74-4.77) in both group. Among individuals with MetS, the presence of NAFLD showed a significant increase in risk of incident diabetes even after further adjustment for MetS components including fasting glucose, TG, BMI, systolic BP, and HDL-C (HR 1.53, 95% CI 1.09-2.16)., Conclusion: The presence of NAFLD further increased the risk of incident diabetes in individuals with metabolic syndrome. Our results suggest that the coexistence of NAFLD has an additive effect on the development of diabetes in individuals with MetS., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Dyslipidaemia and central obesity are the major factors underlying the dramatic increase in metabolic syndrome (MS). We compared the effects of early combined therapy with pitavastatin and intensive lifestyle modification (LSM) on the amelioration of each component of MS with those of LSM only., Design/participants/measurements: PROPIT (a PROspective comparative clinical study to evaluate the efficacy and safety of PITavastatin in patients with metabolic syndrome) was a prospective, randomized, multicenter open-label 48-week trial. We enrolled 187 patients with MS (central obesity and prediabetes) and randomized them into two treatment groups: 2 mg pitavastatin daily + intensive LSM or intensive LSM only. The primary outcome was the improvements in the components of MS and in the percentage of non-MS converters., Results: After 1 year treatment, the improvement of MS score was significantly higher in the pitavastatin + LSM group (P = 0·039). However, non-MS converters (MS score ≤2) did not differ between the groups. The secondary outcomes, namely lipid profiles, the Apo B/A1 ratio, visceral fat/subcutaneous fat ratio and the Framingham risk score, were significantly improved in the pitavastatin group. There was no deterioration in glucose metabolism after treatment with pitavastatin for 1 year., Conclusions: Early statin treatment can be an effective option in obese patients with MS, prediabetes and mild dyslipidaemia with further improvement of cardiovascular risk factors. We could not observe the increase rate of glucose intolerance in statin group. Future longitudinal studies are needed to test the benefits of early statin treatment compared with LSM., (© 2014 John Wiley & Sons Ltd.)

Background/aims: The aim was to determine which of three sets of metabolic syndrome (MetS) criteria (International Diabetes Federation [IDF], National Cholesterol Education Program Adult Treatment Panel III [ATP III], and European Group for the Study of Insulin Resistance [EGIR]) best predicts the coronary artery calcification (CAC) score in a cross-sectional study. This has not been evaluated in previous studies., Methods: A total of 24,060 subjects were screened for CAC by multi-detector computed tomography. The presence of CAC was defined as a CAC score > 0. The odds ratio for the presence of CAC was analyzed for three different sets of MetS criteria and according to number of MetS components., Results: CAC was observed in 12.6% (3,037) of the subjects. Patients with MetS, as defined by the IDF, ATP III, and EGIR criteria, had a CAC rate of 23.0%, 25.1%, and 29.5%, respectively (p < 0.001). Comparisons of C statistics for multivariate regression models revealed no significant difference among the three sets of criteria. After adjustment for risk factors, the ATP III criteria produced a slightly higher odds ratio for CAC compared with the other criteria, but this difference was not significant. The risk factor-adjusted odds ratio for the presence of CAC increased from 1 to 1.679 as the number of MetS components defined by ATP III increased from 0 to ≥ 3 (p for trend < 0.001)., Conclusions: The presence of MetS was associated with the presence of CAC. There was no significant difference among the three sets of MetS criteria in terms of the ability to predict CAC. An increase in the number of MetS components was associated with an increased odds of CAC.

Purpose: Considerable amount of interest has been focused on the positive relationship between inflammation and the metabolic syndrome (MS). However, few studies have been performed to evaluate the relationship between baseline white blood cell (WBC) count and future risk for developing MS. Therefore, we investigated whether the baseline plasma levels of WBC count could be associated with future risk for MS in apparently healthy Korean., Materials and Methods: A total of 1135 subjects (781 men and 354 women with a mean age of 49 years), who underwent health examinations at Kangbuk Samsung Hospital in both 2002 and 2005 were enrolled. The presence of MS was defined using the modified criteria of the National Cholesterol Education Program Adult Treatment Panel III using BMI instead of waist circumference., Results: The baseline levels of WBC count were significantly higher among incident MS cases than among subjects without MS. The relative risks of incident MS were 1.4, 3.2 and 2.7 for WBC quartiles 2, 3, and 4, respectively, when compared with the first quartile (p-value for trend<0.001). These positive associations persisted after adjustment for baseline body mass index, blood pressure, fasting glucose, high density lipoprotein-cholesterol, triglyceride and homeostatic model assessment-insulin resistance; adjusted relative risk of incident MS for the 2nd, 3rd and 4th quartile groups vs. the lowest quartile were 1.2, 2.4 and 1.7, respectively (p-value for trend=0.011)., Conclusion: This retrospective cohort study suggests that an elevated WBC count could be associated with incident MS, suggesting that baseline inflammation mirrored by WBC level can impact future MS development.

Recent studies suggest an association of vitamin D with obesity, diabetes and cardiovascular diseases. We analyzed the association of serum vitamin D level assessed by 25-hydroxyvitamin D3 {25(OH)D3 } with nonalcoholic fatty liver disease (NAFLD) in apparently healthy men. We performed a cross-sectional study of 6,567 Korean men who participated in a health screening program, evaluating the association of serum 25(OH)D3 levels with the risk of NAFLD assessed by abdominal ultrasonogram. Of the participants, 43.6% had NAFLD and 21.1% had metabolic syndrome. Age, serum calcium, and aspartate aminotransferase levels showed weak but significant positive correlations with 25(OH)D3 level; total cholesterol, triglycerides, low-density lipoprotein cholesterol and fasting insulin level showed weak but significant negative correlations with 25(OH)D3 level. The mean 25(OH)D3 level was significantly lower in participants with NAFLD than in those without (38.7 ± 9.0 vs. 39.7 ± 9.7 nmol/L, p < 0.001). When participants were divided into tertiles based on mean 25(OH)D3 level, the proportion with NAFLD significantly increased as mean 25(OH)D3 level decreased (40.0, 45.0 and 45.9%, p for linear trend < 0.001). Multiple logistic regression analyses with NAFLD as the dependent variable showed that the tertiles with lower 25(OH)D3 levels had a significantly increased risk for NAFLD compared with the highest tertile, even after adjusting for body mass index and metabolic syndrome (OR 1.247 and 1.408 vs. the highest tertile, p < 0.001). Thus, participants with higher serum 25(OH)D3 showed a significantly reduced risk for NAFLD compared with the low 25(OH)D3 groups, independent of obesity and metabolic syndrome.

Some papers have suggested that alkaline phosphatase (ALP) level is a predictor of the metabolic syndrome (MetS) in the general population. However, the association is still controversial, and the mechanisms underlying an association between ALP level and the MetS have not been elucidated. We analyzed the association between serum ALP level and the development of the MetS over a 4-year period. A total of 14,224 subjects who visited the Health Promotion Center for a medical examination in 2005 were followed up after 4 years. Serum ALP level correlated positively with body fat mass and visceral fat mass. The adjusted geometric mean ALP levels were higher in subjects with elevated C-reactive protein level or greater fat mass (P < 0.001). None of the subjects had the MetS at baseline, but 1,179 exhibited the MetS at the 4-year follow-up. After multiple adjustments, the odds ratio (OR) was substantially higher for development of the MetS (OR 1.56, 95% confidence intervals, 1.21-2.01) in subjects in the highest ALP quintile compared with those in the lowest quintile. After adjusting for various covariates, we found significant associations between the quintile of serum ALP level and abdominal obesity, low high-density lipoprotein cholesterol level, and high triglyceride level. Higher serum ALP level was a significant predictor of the MetS in middle-aged Koreans. Serum ALP level correlated positively with body fat mass and independently with a more atherogenic lipid profile in the general population in Korea.

Introduction: Several in vitro studies have suggested the effects of adipokines and insulin resistance on breast cancer cell proliferation and survival. However, little is known about the clinical significance of these findings., Methods: We examined associations between breast cancer recurrence and adiponectin, leptin, insulin resistance, and metabolic syndrome (MetS) in a cohort of 747 patients from 2001 to 2004., Results: Adjusted hazard ratios showed an inverse trend across the quartiles for serum adiponectin concentration in estrogen receptor (ER)/progesterone receptor (PR) -negative patients (P for trend = 0.027) but not in ER/PR-positive patients. Compared to the highest quartile for adiponectin level, the lowest quartile showed a hazard ratio of 2.82 (1.03 to 7.68). Homeostasis model assessment for insulin resistance (HOMA-IR) showed a positive trend for recurrence in the ER/PR-negative group (P for trend = 0.087) and a negative trend in the ER/PR-positive group (P for trend = 0.081). Leptin did not show any associations (P for trend >0.05). A linear trend was observed with the number of components of MetS in ER/PR-negative patients (P for trend = 0.044). This association disappeared when adjusted for adiponectin and HOMA-IR., Conclusions: Adiponectin and HOMA-IR have prognostic significance in breast cancer recurrence and interventions related to these factors may protect against recurrence in ER/PR-negative patients. These findings were not observed in the case of ER/PR-positive patients. Further evaluation of these insignificant associations is needed because it might be biased by adjuvant chemotherapy or other confounders.

The aim of the present study was to investigate the relationship of plasma resistin levels with determinants of the metabolic syndrome (MetS) and anthropometric parameters in healthy Korean subjects. Plasma resistin levels were determined in 276 subjects. In subjects with MetS, the plasma resistin levels were not significantly increased compared to those without MetS (8.3+/-4.3 ng/mL vs. 8.5+/-3.6 ng/mL, respectively, P=0.84). In addition, the plasma resistin levels were not correlated with the body mass index, the waist circumference, homeostasis model assessment-insulin resistance (HOMA-IR), fasting plasma glucose or insulin levels. However, the plasma resistin levels were positively correlated with the abdominal subcutaneous fat (r=0.18, P<0.01) in all subjects and correlated with TNF alpha(r=-0.16, P<0.05) and hsCRP (r=0.15, P<0.05) in subjects without MetS but not with MetS. With multiple linear regression analysis, these linear associations remained to be significant. The results of this study show that plasma resistin levels in humans were not associated with markers of insulin resistance, obesity or other determinants of the MetS.

Background: Recent studies suggest the role of liver enzymes, such as serum gamma-glutamyl transferase (GGT) and alanine aminotransferase (ALT) as the predictor for future development of metabolic syndrome (MetS), diabetes and cardiovascular disease in epidemiologic studies. We hypothesized that serum concentrations of GGT and ALT are associated with the development of MetS, according to newly recommended criteria from International Diabetes Federation (IDF) and American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) definition in Koreans., Methods: A total of 15,250 males (mean 38 y) and 6280 females (mean 41 y) who visited the Health Promotion Center at Kangbuk Samsung Hospital for medical check-up in 2002, were followed-up after 4 y. We analyzed the development of MetS in their follow-up data in 2006., Results: When the subjects were divided into quartiles by the baseline GGT levels, the odds ratio for the MetS defined by both criteria across the quartile groups increased as the quartile groups increased in both gender groups. This association remained significant even after adjustment for confounding factors, such as, age, alcohol intake, smoking status, physical activity, ALT, fasting insulin and HOMA-IR. Serum ALT concentration also showed significantly positive correlation with development of MetS defined by the two criteria even after adjustment for age and GGT in both gender groups. In addition, risk for the individual MetS components increased as the baseline GGT concentrations increased, except low high-density lipoprotein cholesterol (HDL-C) in female group. In receiver operating characteristic (ROC) curves, the area under the curves (AUC) of GGT and ALT to predict future MetS by both criteria was larger than the AUCs of blood pressure, fasting glucose and HDL-C., Conclusions: In this large prospective study in Koreans, high baseline GGT and ALT concentrations predicted future development of MetS defined by IDF and AHA/NHLBI criteria after 4 y of follow-up.

This study was performed to evaluate the relationship between serum phosphate levels and cardiovascular risk factors and metabolic syndrome components in a cross-sectional survey. Plasma phosphate was measured by immunoturbidimetry in 46,798 subjects over 20 years of age with an estimated GFR>or=60 mL/(min 1.73 m(2)) who participated in a health-check survey at the Kangbuk Samsung Hospital in South Korea. The median plasma phosphate level was 3.49+/-0.44 mg/dL and the mean estimated GFR was 77.46+/-8.51 mL/(min 1.73 m(2)). We found that serum phosphate levels had a positive correlation with total cholesterol, HDL-C, lipoprotein a, apolipoprotein A1, calcium, and albumin. In addition, serum phosphate levels had a negative correlation with age, body mass index, uric acid, fasting glucose, insulin, HOMA-IR, HS-CRP, triglyceride levels, systolic blood pressure, diastolic blood pressure, and waist circumference (P<0.001). In conclusion, we found that a high phosphate level is correlated with cardiovascular disease while a lower phosphate level is correlated with metabolic syndrome. Serum phosphate levels that were too high or too low correlated with cardiovascular risk factors and elements of metabolic syndrome, respectively, showing that it may be important to maintain an appropriate level of phosphate for the prevention of cardiovascular events and metabolic syndrome.

Background: The International Diabetes Federation consensus recently proposed a new definition for the diagnosis of metabolic syndrome, incorporating ethnically specific waist circumference (WC) cutoff points., Objective: We investigated the ethnically appropriate WC cutoff values for central obesity in Korean adults to predict increased risk of elevated triacylglycerol, reduced HDL cholesterol, elevated blood pressure, elevated fasting plasma glucose, or two or more of these factors., Design: We used data from 6561 adults, aged 20-80 years, who participated in the Korean Health and Nutritional Examination Survey of 1998, a cross-sectional health survey of a nationally representative sample of Koreans., Results: Based on the receiver operating characteristic curve analysis, the WC value for predicting metabolic risk factors in Koreans was about 85 cm for men and 80 cm for women. The odds ratio for the risk of two or more metabolic risk factors increased abruptly in men with WC >or= 90 cm and women with WC >or= 85 cm. The 80th percentile for WC in the Korean population was 90 cm for men and 86.5 cm for women. Thus, the appropriate WC cutoff point for central obesity in Koreans was determined to be 90 cm for men and 85 cm for women., Conclusions: Based on our criteria, the prevalence of central obesity was 19.8% in Korean men and 24.5% in Korean women. These findings suggest the applicability of ethnically specific cutoff points for WC in assessing central obesity.

Previous studies have shown that the CB1 receptor antagonist reverses steatohepatitis and its related features of metabolic syndrome, such as obesity and type 2 diabetes. However, the beneficial effects of CB1 receptor blockade on hepatic steatosis and inflammation have not been investigated independently of its effects on body weight and glycemic control. At 32 weeks of age, OLETF rats were administered with rimonabant (10 mg·kg−1·day−1) by oral gavage for 6 weeks. No significant changes in body weight, OGTT, and serum glucose were observed in spite of rimonabant-decreased food intake. Moreover, there was a significant difference between initial and final body weight, regardless of rimonabant administration, indicating that OLETF rats were severely diabetic rats. Rimonabant administration significantly decreased serum liver enzyme levels such as ALT and AST, hepatic fat accumulation, lipid peroxidation, and cell death as demonstrated by the number of TUNEL-positive cells in severely uncontrolled diabetic OLETF rats. Significant decreases in hepatic gene expression of proinflammatory cytokines (CD11b, F4/80, MCP1, and TNFα), negative inflammatory mediators (SOCS1 and SOCS3), and fibrosis-related proteins (TGFβ, collagen 1, and TIMP1) were found in rimonabant-treated OLETF rats. Six-week administration of rimonabant significantly upregulated mRNA levels of CPT1α and PPARα related to β-oxidation. Moreover, significant increases in Nrf2 gene expression and its downstream genes, NQO1, GSAT, HO-1, and TXNRD1 along with increased AMPK phosphorylation were noted in uncontrolled diabetic rats treated with rimonabant. The observed potent inhibitory effects of CB1 receptor blockade on hepatic fat infiltration and cellular death in severely uncontrolled diabetic rats indicate that CB1 receptor is a possible therapeutic target. Increased Nrf2 and AMPK phosphorylation may play a role in the mechanism of rimonabant action. [ABSTRACT FROM AUTHOR]

Obesity and insulin resistance are hallmarks of the metabolic syndrome, which is associated with low-grade chronic inflammation. Clusterin/apolipoprotein J is an abundant plasma chaperone protein that has recently been suggested as a potential biomarker that reflects the inflammatory process in Alzheimer's disease. In the present study, we investigated anthropometric and clinical factors affecting the plasma levels of clusterin in healthy Korean subjects. We measured fasting plasma clusterin levels in healthy Korean adults (111 men and 93 women) using ELISA kit. We analyzed the relationship between plasma clusterin concentrations and anthropometric and clinical parameters. Fasting plasma clusterin concentrations were higher in overweight and obese subjects than in lean subjects. Correlation analysis revealed that the plasma clusterin levels were positively associated with indices of obesity such as body mass index (BMI), waist circumference and waist-hip ratio and markers of systemic inflammation such as high sensitivity C-reactive protein (hsCRP), uric acid, ferritin and retinol binding protein-4. Multiple linear regression analysis showed that sex, BMI and hsCRP were independent determinants of plasma clusterin levels. Furthermore, plasma clusterin levels showed an upward trend with increasing numbers of metabolic syndrome components. These findings suggest that fasting plasma clusterin levels correlate with the parameters of adiposity and systemic inflammation in healthy adults. Therefore, the circulating clusterin level may be a surrogate marker for obesity-associated systemic inflammation. [ABSTRACT FROM AUTHOR]

The prevalence of metabolic syndrome, obesity and insulin resistance has become an epidemic in the world. A strong association exists between metabolic syndrome and non-alcoholic fatty liver disease ( NAFLD), though the etiology of NAFLD is still unclear. This close association leads to numerous clinical studies to investigate the effects of insulin sensitizers, thiazolidinediones ( TZDs), on hepatic fat accumulation. Thiazolidinediones affect glucose and lipid metabolism in insulin-sensitive tissues, which in turn reduces the lipid content in the liver by modulating several mediators. In the present review, we discuss key modulators - adiponectin and sirtulin-adenosine monophosphate activated protein kinase signaling - as the mechanisms responsible for NAFLD related to metabolic syndrome. [ABSTRACT FROM AUTHOR]

Abstract: Adipocyte-specific fatty acid-binding protein (A-FABP) is a cytoplasmic protein that is expressed in adipocytes and is closely associated with insulin resistance, metabolic syndrome, and Type 2 diabetes. We investigated the relationship between A-FABP as a surrogate marker of metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) in apparently healthy subjects. We assessed clinical and biochemical metabolic parameters and measured serum levels of A-FABP, high-sensitivity C-reactive protein and tumor necrosis factor-α (TNF-α) in 494 subjects who were divided into two groups according to the presence of NAFLD by abdominal ultrasonography. All parameters associated with metabolic syndrome were significantly higher in patients with NAFLD (P<.001). A-FABP showed positive correlation with TNF-α, homeostasis model assessment index of insulin resistance (HOMA-IR), and metabolic syndrome (P<.001) when adjusted for age and sex. The odds ratio for the risk of NAFLD in the highest tertile of A-FABP compared with the lowest tertile was 7.36 (CI 3.80–14.27, P<.001) after adjustment for age and sex; 4.52 (CI 2.22–9.20, P<.001) after adjustment for age, sex, HOMA-IR and metabolic syndrome and 2.86 (CI 1.11–7.35, P<.05) after further adjustment for all metabolic parameters including TNF-α. The serum level of A-FABP was independently associated with NAFLD and showed significant correlation with TNF-α, HOMA-IR, and metabolic syndrome. [Copyright &y& Elsevier]