Jenie Yoonoo Hwang

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.

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 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.

Assessment of the fatty liver index as an indicator of hepatic steatosis for predicting incident diabetes independently of insulin resistance in a Korean population

Fatty liver disease, especially non‐alcoholic fatty liver disease, is considered to be the hepatic manifestation of the metabolic syndrome, both closely associated with insulin resistance. Furthermore, fatty liver disease assessed by ultrasonography is known to be a predictor of the development of Type 2 diabetes mellitus. However, it remains unclear whether fatty liver disease plays a role in the pathogenesis of Type 2 diabetes independently of insulin resistance. In this study, we investigated whether fatty liver disease assessed by the fatty liver index can predict the development of Type 2 diabetes independently of systemic insulin resistance.

Association of metabolically healthy obesity with subclinical coronary atherosclerosis in a Korean population.

The degree of subclinical coronary atherosclerosis detected by coronary multidetector computed tomography (MDCT) in four groups defined by the state of metabolic health and obesity in an asymptomatic Korean population was compared.

Elevated Serum Ferritin Level Is Associated with the Incident Type 2 Diabetes in Healthy Korean Men: A 4 Year Longitudinal Study

Background Elevated ferritin concentration has been implicated in the etiology of type 2 diabetes. Accumulating evidence, mostly from studies conducted on western populations, has demonstrated a strong association between the elevated ferritin concentrations and incident type 2 diabetes. In Asian populations, however, the longitudinal studies investigating the association of elevated serum ferritin levels and type 2 diabetes are lacking. In present study, we aimed to determine whether elevated serum ferritin levels are related to the incident type 2 diabetes in healthy Korean men. Methodology/Principal Findings This 4 year longitudinal observational study was conducted at the Asan Medical Center, Seoul, Republic of Korea. The study population consisted of 2,029 men without type 2 diabetes who underwent routine health examination in 2007 (baseline) and 2011 (follow-up). Baseline serum ferritin concentrations were measured by chemiluminescent two-site sandwich immunoassay. In multiple-adjusted model, the relative risk (RR) for incident type 2 diabetes was significantly higher in highest compared with the lowest ferritin quartile category, even after adjusting for confounding variables including homeostasis model assessment of insulin resistance (RR = 2.17, 95% confidence interval 1.27–3.72, P for trend = 0.013). Conclusions/Significance These results demonstrated that elevated level of serum ferritin at baseline was associated with incident type 2 diabetes in an Asian population.

Long-term changes in serum IGF-1 levels after successful surgical treatment of growth hormone-secreting pituitary adenoma.

BACKGROUND Successful treatment of acromegaly is known to normalize serum insulin-like growth factor 1 (IGF-1) levels within days after surgery. However, our clinical observations indicate that many cases of acromegaly show delayed normalization of serum IGF-1 levels after complete tumor resection. OBJECTIVE To study long-term changes of the serum IGF-1 levels in acromegalic patients for whom surgical treatment was thought to be successful. METHODS A retrospective observational study was performed with 46 acromegalic patients with no residual tumor on sellar magnetic resonance imaging, and a nadir growth hormone of less than 0.4 μg/L on a postoperative oral glucose tolerance test. RESULTS In all patients, serum IGF-1 levels returned to the normal reference values for age and sex during the observational period (12-132 months). The mean duration from the time of surgery until IGF-1 normalization was 10 months (range, 3 days-57 months). Twenty-seven patients (59%) reached normal IGF-1 ranges within 3 months of surgery, whereas 19 patients (41%) experienced delayed (>3 months) IGF-1 normalization. Eleven patients (24%) recovered normal IGF-1 levels 12 to 57 months after surgery. The possibility of delayed IGF-1 cure was increased 8.8-fold with an immediate postoperative IGF-1 level increase of 100 μg/L. CONCLUSION Satisfactory remission of acromegaly by IGF-1 criteria was delayed in a large proportion of acromegalic patients, especially those with high postoperative IGF-1 levels. Hence, additional treatment can be delayed in clinically stable acromegalic patients who show no evidence of residual tumors on postoperative magnetic resonance imaging and a normal growth hormone suppressive response to a glucose load.

The Prevalence of Peripheral Arterial Disease in Korean Patients with Type 2 Diabetes Mellitus Attending a University Hospital

Background Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis and is associated with significant morbidity and mortality. Diabetes is known to increase the risk of PAD two- to four-fold. The prevalence of PAD in Korean diabetic patients has not been established. In this study, we investigated the prevalence of PAD in Korean patients with type 2 diabetes attending a large university hospital and analyzed the factors associated with PAD. Methods A total of 2,002 patients with type 2 diabetes who underwent ankle-brachial index (ABI) measurement in an outpatient clinic were enrolled. PAD was defined as an ABI ≤0.9. Clinical characteristics of 64 patients with PAD were compared with those of 192 age- and sex-matched control patients without PAD. Results Of the 2,002 type 2 diabetic patients, 64 (3.2%) were diagnosed as having PAD. PAD was associated with higher prevalences of retinopathy, nephropathy, neuropathy, cerebrovascular and coronary artery disease. Patients with PAD had higher systolic blood pressure and serum triglyceride level and reported higher pack-years of smoking. Multivariate analysis showed that the presence of micro- and macrovascular complications and high systolic blood pressure are factors independently associated with PAD. Conclusion The prevalence of PAD in diabetic patients was 3.2%, suggesting that the prevalence in Korean diabetic patients is lower than that of patients in Western countries.