Chang Hee Jung

Background and Data Configuration Process of a Nationwide Population-Based Study Using the Korean National Health Insurance System

Background The National Health Insurance Service (NHIS) recently signed an agreement to provide limited open access to the databases within the Korean Diabetes Association for the benefit of Korean subjects with diabetes. Here, we present the history, structure, contents, and way to use data procurement in the Korean National Health Insurance (NHI) system for the benefit of Korean researchers. Methods The NHIS in Korea is a single-payer program and is mandatory for all residents in Korea. The three main healthcare programs of the NHI, Medical Aid, and long-term care insurance (LTCI) provide 100% coverage for the Korean population. The NHIS in Korea has adopted a fee-for-service system to pay health providers. Researchers can obtain health information from the four databases of the insured that contain data on health insurance claims, health check-ups and LTCI. Results Metabolic disease as chronic disease is increasing with aging society. NHIS data is based on mandatory, serial population data, so, this might show the time course of disease and predict some disease progress, and also be used in primary and secondary prevention of disease after data mining. Conclusion The NHIS database represents the entire Korean population and can be used as a population-based database. The integrated information technology of the NHIS database makes it a world-leading population-based epidemiology and disease research platform.

Molecular mechanisms of central leptin resistance in obesity

The rapidly increasing prevalence of obesity confers a huge health burden globally. The hypothalamus plays a central role in the regulation of energy homeostasis by integrating multiple metabolic signals from peripheral organs and modulating feeding behavior and energy metabolism. Leptin, a key appetite-regulating hormone derived from the white adipose tissue, primarily acts on hypothalamic neurons to activate catabolic pathway and inhibit anabolic pathway, which can result in anorexia and weight reduction. Despite striking obesity resulting from leptin deficiency, treatment with this hormone in human obesity has been unsuccessful due to leptin resistance. In this review, we describe recent researches extending our understanding of obesity-associated hypothalamic leptin resistance.

Vaspin protects vascular endothelial cells against free fatty acid-induced apoptosis through a phosphatidylinositol 3-kinase/Akt pathway.

Vaspin, an adipocytokine recently identified in a rat model of type 2 diabetes, has been suggested to have an insulin-sensitizing effect. However, the exact mechanism underlying this action has not been fully elucidated. Furthermore, the specific function of vaspin is largely unknown, especially in vascular cells. We examined whether vaspin affects the insulin-signaling pathway in cultured endothelial cells and is capable of preventing free fatty acid (FFA)-induced apoptosis in endothelial cells through its insulin sensitizing effect, specifically, through its stimulatory effect on PI3-kinase/Akt signaling pathways. Vaspin significantly increased Akt phosphorylation and prevented the impairment of Akt phosphorylation by linoleic acid (LA) in insulin-stimulated endothelial cells, which effects were abolished by pretreatment with the PI3-kinase inhibitor, Wortmannin. Moreover, pretreatment with vaspin prevented LA-induced apoptosis in insulin-stimulated endothelial cells; this anti-apoptotic effect of vaspin was also eliminated by pretreatment with Wortmannin. The present study indicates that vaspin protects vascular endothelial cells from FFA-induced apoptosis through upregulation of the PI3-kinase/Akt signaling pathway. Our study is the first to demonstrate that vascular cells can be targets of vaspin. Our results further suggest that vaspin could have beneficial effects on the atherosclerosis.

Higher serum bilirubin level as a protective factor for the development of diabetes in healthy Korean men: A 4 year retrospective longitudinal study

OBJECTIVE Bilirubin, a natural product of heme catabolism by heme oxygenase, one of key antioxidant enzymes, has been recognized as a substance with potent antioxidant and cytoprotective properties. Several studies have shown a significant negative relationship between serum bilirubin levels and the risk of metabolic disorders, including type 2 diabetes. However, longitudinal studies investigating the association of elevated serum bilirubin levels and type 2 diabetes are lacking. In the present study, we aimed to investigate the longitudinal effects of baseline serum bilirubin concentrations on the development of type 2 diabetes in healthy Korean men. MATERIALS AND METHODS This 4 year retrospective longitudinal observational study was conducted at the Asan Medical Center, Seoul, Republic of Korea. The study population consisted of 5960 men without type 2 diabetes who underwent routine health examinations in 2007 (baseline) and 2011 (follow-up). Baseline serum bilirubin concentrations were determined by the vanadate oxidation method. RESULTS During a 4 year period, 409 incident cases of diabetes (6.9 %) were identified. Incident type 2 diabetes decreased across the baseline bilirubin quartile categories (P for trend <0.001). In multivariable-adjusted model, the relative risk (RR) for the development of type 2 diabetes was significantly lower in the highest (i.e., 1.30-2.00 mg/dl) than in the lowest bilirubin quartile category (i.e., ≤ 0.90 mg/dl), even after adjustment for confounding variables (RR=0.69, 95% confidence interval 0.48-0.99, P for trend = 0.041). CONCLUSIONS The results indicate that serum total bilirubin level may provide additional information for predicting future development of type 2 diabetes in healthy subjects.

The Risk of Incident Type 2 Diabetes in a Korean Metabolically Healthy Obese Population: The Role of Systemic Inflammation

OBJECTIVE This study sought to investigate whether the metabolically healthy obese (MHO) phenotype is associated with an increased risk of incident type 2 diabetes in a Korean population and, if so, whether systemic inflammation affects this risk in MHO individuals. DESIGN AND METHODS The study population comprised 36 135 Koreans without type 2 diabetes. Participants were stratified by body mass index (cutoff value, 25.0 kg/m(2)) and metabolic health state (assessed using Adult Treatment Panel-III criteria). High-sensitive C-reactive protein (hsCRP) was used as a surrogate marker of systemic inflammation. Subjects were classified into low (ie, hsCRP < 0.5 mg/L) and high (ie, hsCRP ≥ 0.5 mg/L) systemic inflammation groups. RESULTS During a median followup of 36.5 months (range, 4.8-81.7 mo), 635 of the 36 135 individuals (1.8%) developed type 2 diabetes. The MHO group had a significantly higher risk of incident type 2 diabetes (multivariate-adjusted hazard ratio [HR], 1.57; 95% confidence interval [CI], 1.16-2.11) than the metabolically healthy nonobese (MHNO) group. However, the risk of the MHO group varied according to the degree of systemic inflammation. Compared with the MHNO/low systemic inflammation group, the risk of type 2 diabetes in the MHO/low systemic inflammation group was not significantly elevated (multivariate-adjusted HR, 1.61; 95% CI, 0.77-3.34). However, the MHO/high systemic inflammation group had an elevated risk of incident type 2 diabetes (multivariate-adjusted HR, 3.73; 95% CI 2.36-5.88). CONCLUSIONS MHO subjects show a substantially higher risk of incident type 2 diabetes than MHNO subjects. The level of systemic inflammation partially explains this increased risk.

A Novel Therapeutic Agent for Type 2 Diabetes Mellitus: SGLT2 Inhibitor

Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder, and a major public health problem that is rapidly increasing in prevalence. Although a wide range of pharmacotherapies for glycemic control is now available, management of T2DM remains complex and challenging. The kidneys contribute immensely to glucose homeostasis by reabsorbing glucose from the glomerular filtrate. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a new class of antidiabetic agents that inhibit glucose absorption from the kidney independent of insulin, offer a unique opportunity to improve the outcomes of patients with T2DM. In this review, we provide an overview of two globally-approved SGLT2 inhibitors, dapagliflozin and canagliflozin, and discuss their effects and safety. This information will help clinicians to decide whether these drugs will benefit their patients.

Serum bilirubin as a predictor of incident metabolic syndrome: A 4-year retrospective longitudinal study of 6205 initially healthy Korean men

AIM Serum bilirubin is an endogenous antioxidant with anti-inflammatory properties. Several cross-sectional studies have reported that bilirubin was negatively associated with oxidative stress-mediated diseases, including the metabolic syndrome (MetS). However, the clinical relevance of bilirubin as a risk factor for incident MetS remains controversial. For this reason, the longitudinal effects of baseline serum bilirubin concentrations on incident MetS were evaluated in Korean men. METHODS This 4-year retrospective longitudinal observational study involved 6205 Korean men without MetS. Subjects underwent routine health examinations in 2007 and returned for a follow-up examination in 2011. Baseline serum bilirubin concentrations were determined using the vanadate oxidation method. RESULTS During the 4-year period, 936 cases of incident MetS (15.1%) were identified. Its incidence decreased across baseline bilirubin quartile categories (P<0.001), with an odds ratio (OR) for developing MetS being significantly lower in the highest quartile group (≥ 1.40 mg/dL) compared with the lowest (≤ 0.90 mg/dL) after adjusting for all confounding variables [OR=0.70, 95% confidence interval (CI) 0.54-0.90; P for trend=0.019]. Among individual components of MetS, bilirubin was found to be negatively associated with only the risk of incident hypertriglyceridaemia. The OR (95% CI) for incident hypertriglyceridaemia in the highest vs lowest quartile was 0.75 (0.61-0.91; P for trend=0.002). CONCLUSION Serum total bilirubin level was negatively associated with incidence of MetS in healthy Korean men over a 4-year period.

Vaspin inhibits cytokine-induced nuclear factor-kappa B activation and adhesion molecule expression via AMP-activated protein kinase activation in vascular endothelial cells

BackgroundVaspin is an adipocytokine that was recently identified in the visceral adipose tissue of diabetic rats and has anti-diabetic and anti-atherogenic effects. We hypothesized that vaspin prevents inflammatory cytokine-induced nuclear factor-kappa B (NF-κB) activation by activating AMP-activated protein kinase (AMPK) in vascular endothelial cells.MethodsWe examined the effects of vaspin on NF-κB activation and the expression of the NF-κB-mediated genes intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and monocyte chemoattractant protein-1 (MCP-1). Human aortic endothelial cells (HAECS) were used. Tumor necrosis factor alpha (TNFα) was used as a representative proinflammatory cytokine.ResultsTreatment with vaspin significantly increased the phosphorylation of AMPK and acetyl-CoA carboxylase, the down-stream target of AMPK. Furthermore, treatment with vaspin significantly decreased TNFα-induced activation of NF-κB, as well as the expression of the adhesion molecules ICAM-1, VCAM-1, E-selectin, and MCP-1. These effects were abolished following transfection of AMPKα1-specific small interfering RNA. In an adhesion assay using THP-1 cells, vaspin reduced TNFα-induced adhesion of monocytes to HAECS in an AMPK-dependent manner.ConclusionsVaspin might attenuate the cytokine-induced expression of adhesion molecule genes by inhibiting NF-κB following AMPK activation.

Vaspin Increases Nitric Oxide Bioavailability through the Reduction of Asymmetric Dimethylarginine in Vascular Endothelial Cells

Vaspin is an adipocytokine recently identified in the visceral adipose tissue of diabetic rats and having anti-diabetic effects. We have recently shown that vaspin has anti-atherogenic effect through Akt-mediated inhibition of endothelial cell apoptosis. Decreased activity of endothelial nitric oxide synthase (eNOS) plays an important role in the pathogenesis of atherosclerosis. Asymmetric dimethylarginine (ADMA) is a well-known endogenous competitive inhibitor of eNOS and risk factor of cardiovascular diseases. The aim of this study was to examine whether vaspin might protect against atherosclerosis through its beneficial effects on the ADMA-eNOS system. Treatment of vaspin significantly increased NO secretion from endothelial cells and isolated aorta from Sprague-Dawley (SD) rats. Furthermore, treatment of vaspin prevented fatty acid-induced decrease in endothelium-dependent vasorelaxation in isolated aorta of SD rat. For the mechanism of vaspin-induced NO biosynthesis, vaspin activated the STAT3 signaling pathway and stimulated eNOS phosphorylation (Ser 1177), a marker of eNOS activation, through STAT3-dependent mechanism. Furthermore, vaspin treatment increased the expression of dimethylarginine dimethylaminohydrolase (DDAH) II, the responsible enzyme for the degradation of ADMA, leading to a reduction in ADMA levels. Vaspin-induced increase in DDAH II gene expression was through STAT3-mediated stimulation of DDAH II promoter activity. These results suggest that vaspin increases eNOS activity by reducing ADMA level through STAT3-mediated regulation of DDAH II expression. Our findings provide a novel molecular mechanism of antiatherogenic actions of vaspin.

The risk of chronic kidney disease in a metabolically healthy obese population

Obesity has become an important risk factor for chronic kidney disease (CKD). The metabolically healthy obese (MHO) phenotype refers to obese individuals with a favorable metabolic profile. However, its prognostic value remains controversial and may depend on the health outcome being investigated. To assess this, we examined the risk of MHO phenotype with incident CKD in a Korean population of 41,194 people without CKD. Individuals were stratified by body mass index (cutoff value, 25.0 kg/m(2)) and metabolic health state (assessed using Adult Treatment Panel-III criteria). Incident CKD was defined as a glomerular filtration rate of <60 ml/min per 1.73 m(2) calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Over the median follow-up period of 38.7 months, 356 of the individuals developed incident CKD. Compared with the metabolically healthy nonobese (MHNO) group, the MHO group showed increased risk of incident CKD with a multivariate-adjusted hazard ratio of 1.38 (95% CI, 1.01-1.87). Nonobese but metabolically unhealthy individuals were at an increased risk of incident CKD (multivariate-adjusted hazard ratio, 1.37 (95% CI, 1.02-1.93)) than the MHNO group. Metabolically unhealthy obese individuals were at the highest risk of incident CKD. Thus, a healthy metabolic profile does not protect obese adults from incident CKD. Hence, it is important to consider metabolic health along with obesity when evaluating CKD risk.