Gender differences of visceral fat area for predicting incident type 2 diabetes in Koreans.

AIMS: Visceral fat accumulation is known to be an independent risk factor for type 2 diabetes. We aimed to determine the optimal cutoff values of visceral fat area (VFA) for predicting incident type 2 diabetes in Koreans. METHODS: Our study population consisted of 13,004 individuals initially free of type 2 diabetes the ages between 20 and 69 years, who underwent routine health examinations between January 2012 and December 2012 and returned for follow-up examinations between January 2016 and December 2016. VFA values were derived from bioelectrical impedance analysis (BIA) at baseline. RESULTS: During a median follow-up of 4.02 years, a total of 481 (4.6% for men and 2.3% for women) incident cases of type 2 diabetes were identified. According to the receiver operating characteristic (ROC) curve, the optimal VFA cutoff values for predicting incident type 2 diabetes were 118.8 cm2 in men and 82.6 cm2 in women, respectively. In a multivariable-adjusted model including obesity and glycemic status, the odds ratios (ORs) of VFA over 120 cm2 in men and 80 cm2 in women were 1.72 and 3.56, respectively. CONCLUSIONS: Higher VFA at baseline was an independent risk factor for developing type 2 diabetes and the optimal VFA cutoff values were markedly different between men and women. Therefore, sex-specific reference values for visceral fat obesity such that men with a VFA ≥120 cm2 and women with a VFA ≥80 cm2 should be considered to predict incident type 2 diabetes.

Visceral adiposity index predicts the conversion of metabolically healthy obesity to an unhealthy phenotype.

OBJECTIVE: Some individuals with metabolically healthy obesity (MHO) convert to metabolically unhealthy obesity (MUO) phenotype, and visceral adiposity is one of proposed mechanisms underlying such conversion. Visceral adipose index (VAI) is a novel mathematical model which estimates visceral adiposity based on anthropometric and lipid profiles. We aimed to determine the association of VAI-estimated visceral adiposity with the MHO-to-MUO conversion and the predictive value of VAI in estimating such unfavorable outcomes. METHODS: A total of 2,204 Korean subjects with the MHO phenotype were enrolled and stratified by body mass index and metabolic health state according to Wildman criteria at baseline and last follow-up examinations. VAI was calculated at baseline. RESULTS: Over a median follow-up period of 41.1 months, 46.0% of subjects converted to MUO phenotype. Higher VAI quartiles were associated with a greater proportion of subjects who underwent MHO-to-MUO conversion, and also with increased odds ratios for such conversion even after multivariate analyses. The optimal VAI cut off value was around 1.00, and VAI had a greater power in the prediction of MHO-to MUO conversion than waist circumference in both genders. CONCLUSION: MHO phenotypes with high VAI values are associated with poor future metabolic outcomes. VAI-estimated visceral adiposity is well correlated with the prognosis of MHO subjects, and VAI has a good predictive value in determining the MHO-to-MUO conversion.

Fatty liver disease determines the progression of coronary artery calcification in a metabolically healthy obese population.

OBJECTIVES: Metabolically healthy obese (MHO) phenotype describes an obese state with a favorable metabolic profile. However, the prognosis of this subpopulation remains controversial. We aimed to examine whether MHO phenotype is associated with progression of atherosclerotic activity, reflected as the changes in coronary artery calcification (CAC) over time. If so, we sought to determine the role of fatty liver disease (FLD), the hallmark of hepatic steatosis, in this progression. METHODS: We enrolled 1,240 asymptomatic subjects who underwent repeated CAC score measurement during routine health examinations. CAC score progression was defined as either incident CAC in a population free of CAC at baseline, or an increase by ≥2.5 units between the baseline and final square root of CAC scores in participants with detectable CAC at baseline. Subjects were stratified by body mass index (cut-off, 25.0 kg/m2) and metabolic health state using Adult Treatment Panel-III criteria. FLD was assessed via ultrasonography. RESULTS: Over 2.9 years of follow-up, 25.2% of total subjects exhibited CAC score progression. The MHO phenotype was not significantly associated with CAC score progression (multivariate adjusted-odds ratio [OR], 1.45; 95% confidence interval [CI], 0.93-2.25), as compared to the metabolically healthy non-obese (MHNO) phenotype. However, subgroup analysis indicated that the MHO/FLD phenotype was significantly associated with CAC score progression (multivariate adjusted-OR, 2.37; 95% CI, 1.34-4.16), as compared to the MHNO/no FLD phenotype, whereas the MHO/no FLD phenotype was not (multivariate adjusted OR, 1.25; 95% CI, 0.71-2.24). CONCLUSIONS: Obese individuals with FLD have an increased risk of atherosclerosis progression, despite their healthy metabolic profile. Preventive interventions targeting cardiometabolic risk factors should be considered in such individuals, regardless of the weight status.

2013 ACC/AHA Cholesterol Guideline Versus 2004 NCEP ATP III Guideline in the Prediction of Coronary Artery Calcification Progression in a Korean Population.

BACKGROUND: Since the release of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, significant controversy has surrounded the applicability of the new cholesterol guidelines and the Pooled Cohort Equations. In this present study, we investigated whether eligibility for statin therapy determined by the 2013 ACC/AHA guidelines on the management of blood cholesterol is better aligned with the progression of coronary artery calcification (CAC) detected by coronary computed tomography angiography (CCTA) than the previously recommended 2004 National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III guidelines. METHODS AND RESULTS: We enrolled 1246 asymptomatic participants who underwent repeated CAC score measurement during routine health examinations. The CAC score progression was defined as either incident CAC in a population free of CAC at baseline or increase ≥2.5 units between the baseline and final square root of CAC scores participants who had detectable CAC at baseline examination. Application of the ACC/AHA guidelines to the study population increased the proportion of statin-eligible subjects from 20.5% (according to ATP III) to 54.7%. Statin-eligible subjects, as defined by ACC/AHA guidelines, showed a higher odds ratio for CAC score progression than those considered statin eligible according to ATP III guidelines (2.73 [95% CI, 2.07-3.61] vs 2.00 [95% CI, 1.49-2.68]). CONCLUSIONS: Compared with the ATP III guidelines, the new ACC/AHA guidelines result in better discrimination of subjects with cardiovascular risk detected by CAC score progression in an Asian population.

The association of incident hypertension with metabolic health and obesity status: definition of metabolic health does not matter.

OBJECTIVE: Metabolically healthy obese (MHO) phenotype refers to obese individuals with a favourable metabolic profile. Its prognostic value remains controversial and may partly depend on differences in how the phenotype is defined. We aimed to investigate whether the MHO phenotype is associated with future development of incident hypertension in a Korean population according to various definitions of metabolic health. SUBJECTS AND METHODS: The study population comprised 31 033 Koreans without hypertension. Participants were stratified into metabolically healthy nonobese (MHNO), metabolically unhealthy nonobese (MUNO), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) by body mass index (cut-off value, 25·0 kg/m(2) ) and metabolic health state, using four different definitions: Adult Treatment Panel (ATP)-III, Wildman, Karelis and the homoeostasis model assessment (HOMA) criteria. RESULTS: Over the median follow-up period of 35·0 months (range, 4·5-81·4 months), 4589 of the 31 033 individuals (14·8%) developed incident hypertension. Compared with the MHNO group, the MHO group showed increased association with incident hypertension with multivariate-adjusted odds ratios of 1·56 (95% confidence interval [CI], 1·41-1·72), 1·58 (95% CI 1·42-1·75), 1·52 (95% CI 1·35-1·71) and 1·46 (95% CI 1·33-1·61), when defined by ATP-III, Wildman, Karelis and HOMA criteria, respectively. CONCLUSION: MUO individuals showed the highest association with the incident hypertension (adjusted odds ratios up to 2·00). MHO subjects showed an approximately 1·5-fold higher association with incident hypertension than their nonobese counterpart regardless of the definition of metabolic health used. Thus, considering both metabolic health and obesity is important for the assessment of potential cardiovascular outcomes.

Fatty liver index is a risk determinant of incident type 2 diabetes in a metabolically healthy population with obesity.

OBJECTIVE: This study investigated the effect of fatty liver disease (FLD) on the risk of incident type 2 diabetes in a population with metabolically healthy obesity (MHO). METHODS: The study population comprised 34,258 Koreans without type 2 diabetes. Participants were stratified by BMI (cutoff value, 25.0 kg/m(2) ) and metabolic health state (using Wildman criteria). FLD was defined by the fatty liver index (FLI), a predictive algorithm to detect FLD. Subjects were classified into low and high FLI groups based on tertile. RESULTS: At baseline, there were significant differences in FLI between four study groups. During a median follow-up of 36.5 months, 1.7% individuals developed type 2 diabetes. The risk of incident type 2 diabetes varied for the MHO group according to the level of FLI. The risk of type 2 diabetes in the MHO with low FLI was not significantly elevated compared with the metabolically healthy individuals without obesity (MHNO) with low FLI (multivariate-adjusted HR, 1.19 [95% CI 0.66-2.14]). However, the MHO with high FLI had an elevated risk of incident type 2 diabetes (multivariate-adjusted HR, 1.99 [95% CI 1.36-2.92]). CONCLUSIONS: MHO subjects have a substantially higher risk of incident type 2 diabetes than MHNO subjects. The presence of FLD assessed by FLI partially explains this increased risk.

Association of prediabetes, defined by fasting glucose, HbA1c only, or combined criteria, with the risk of cardiovascular disease in Koreans.

BACKGROUND: The aim of the present study was to compare the association between cardiovascular diseases (CVD) and prediabetes defined by either fasting plasma glucose (FPG), HbA1c, or their combination in a Korean population. METHODS: In all, 76 434 South Koreans who voluntarily underwent a general health examination in the Health Screening & Promotion Center (Asan Medical Center) were analyzed after excluding patients with a previous history of CVD. Cardiovascular events and death due to CVD during a median follow-up period of 3.1 years (interquartile range 1.9-4.3 years) were identified from the Nationwide Health Insurance Claims Database and death certificates using ICD-10 codes. RESULTS: Age- and sex-adjusted hazard ratios (HRs) for overall CVD events were significantly greater for subjects with prediabetes defined by FPG only (HR 1.19; 95% confidence interval [CI] 1.08-1.31), HbA1c only (HR 1.28; 95% CI 1.16-1.42), and combined criteria (HR 1.20; 95% CI 1.09-1.32) compared with the normoglycemic group. After adjusting for multiple conventional risk factors (e.g. hypertension, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, smoking status, family history of CVD, and BMI), the HRs for overall CVD were significantly increased only for participants with prediabetes defined by HbA1c. Age- and sex-adjusted HRs for major ischemic heart disease events were significantly increased for subjects with prediabetes defined either by HbA1c or combined criteria. Similarly, age- and sex-adjusted HRs for percutaneous coronary intervention were significantly higher for subjects with prediabetes defined by HbA1c only. For diabetes, the multivariate-adjusted HRs for all outcomes were significantly increased by all three criteria. CONCLUSIONS: Adding an HbA1c criterion when defining prediabetes in Koreans can help identify individuals with an increased risk of CVD.

Association between serum gamma-glutamyltransferase and the progression of coronary artery calcification.

BACKGROUND: Elevated serum gamma-glutamyltransferase (GGT) has been demonstrated to be associated with coronary artery calcification (CAC). CAC progression is an important marker of atherosclerosis and correlates with future cardiovascular risk. However, there is a lack of research that directly examines the association between serum GGT and CAC progression. The aim of this study was to elucidate the association between serum GGT activity and CAC progression. METHODS: We enrolled 1246 asymptomatic participants who underwent repeated CAC score measurement during routine health examinations. To eliminate the dependence of the inter scan variability on the baseline CAC scores, square root-transformed CAC scores were used to analyze CAC progression. In addition, the annualized rate of change in CAC scores was computed. RESULTS: Serum GGT activities were significantly higher in "progressors" than "nonprogressors". The prevalence of progression increased with the GGT tertile (11.9%, 20.1% and 27.9% in the 1st, 2nd, and 3rd GGT tertiles, respectively; p < 0.001). In the multivariate logistic regression analysis, the odds ratio (95% confidence interval) for CAC score progression was 1.85 (1.14-3.00) in the highest GGT tertile group. By multivariate linear regression analysis, baseline serum GGT activity demonstrated a positive association with the annualized change in CAC score (ß = 0.002; p = 0.006) after adjusting for cardiovascular risk factors. CONCLUSION: Elevated serum GGT levels are independently associated with CAC progression. Serum GGT levels may be a potential biomarker of future coronary atherosclerosis and prognosis.

Serum Triglyceride Levels and Cardiovascular Disease Events in Koreans.

OBJECTIVES: Hypercholesterolemia, especially elevated levels of LDL-cholesterol, is a well-known risk factor for cardiovascular disease (CVD). However, the role of triglycerides in CVD risk remains controversial. METHODS: We enrolled 86,476 individuals who had undergone a general health checkup at Asan Medical Center between January 2007 and June 2011. After exclusion criteria were applied to the total cohort, 76,434 participants were included. CVD events and death were gathered from the nationwide health insurance claims database and death certificates using ICD-10 codes. RESULTS: Age- and sex-adjusted odds ratios (ORs) of the higher triglyceride group were significantly increased: 1.52 (95% CI: 1.27-1.82) for major CVD events, 1.53 (95% CI: 1.24-1.88) for major ischemic heart disease events, and 1.49 (95% CI: 1.37-1.63) for overall CVD events. After adjustment for multiple risk factors including HDL-cholesterol, ORs for overall CVD events were significantly increased in the higher triglyceride group. When the analysis was stratified according to BMI, hypertension, and glycemic status at baseline, age- and sex-adjusted ORs for the outcomes were significantly increased in the higher triglyceride group with nonobese, normotensive, or nondiabetic subjects. CONCLUSIONS: Hypertriglyceridemia is independently associated with an increased risk for CVD, especially in nonobese, normotensive, or nondiabetic individuals.

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.

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

OBJECTIVE: 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. METHODS: The data of 4009 asymptomatic subjects who participated in a routine health screening examination were collected. Significant coronary artery stenosis defined as >50% stenosis, plaque, and coronary artery calcium scores (CACS) were assessed by MDCT. Participants were stratified by BMI (cut-off value, 25 kg/m(2) ) and metabolically healthy state, which was defined by Wildman criteria. RESULTS: Metabolically healthy obese (MHO) subjects had a significantly higher prevalence of significant subclinical coronary atherosclerotic burden compared with metabolically healthy nonobese (MHNO) subjects. The adjusted odds ratios of the MHO group for various coronary MDCT findings (MHNO group as the reference), such as coronary artery stenosis, any plaque, calcified plaque, mixed plaque, CACS > 0, and CACS > 100, were 1.87 (95% CI 1.15-3.03), 1.31 (1.01-1.71), 1.40 (1.05-1.86), 1.57 (1.01-2.48), 1.38 (1.04-1.82), and 1.69 (1.03-2.78), respectively. CONCLUSIONS: Our data illustrate that MHO subjects have substantial subclinical coronary atherosclerotic burden. Thus, it is important to consider the metabolic health state and obesity in evaluating cardiovascular risk.

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.

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.

Association of apolipoprotein b/apolipoprotein A1 ratio and coronary artery stenosis and plaques detected by multi-detector computed tomography in healthy population.

Despite the noninvasiveness and accuracy of multidetector computed tomography (MDCT), its use as a routine screening tool for occult coronary atherosclerosis is unclear. We investigated whether the ratio of apolipoprotein B (apoB) to apolipoprotein A1 (apoA1), an indicator of the balance between atherogenic and atheroprotective cholesterol transport could predict occult coronary atherosclerosis detected by MDCT. We collected the data of 1,401 subjects (877 men and 524 women) who participated in a routine health screening examination of Asan Medical Center. Significant coronary artery stenosis defined as > 50% stenosis was detected in 114 subjects (8.1%). An increase in apoB/A1 quartiles was associated with increased percentages of subjects with significant coronary stenosis and noncalcified plaques (NCAP). After adjustment for confounding variables, each 0.1 increase in serum apoB/A1 was significantly associated with increased odds ratios (ORs) for coronary stenosis and NCAP of 1.23 and 1.18, respectively. The optimal apoB/A1 ratio cut off value for MDCT detection of significant coronary stenosis was 0.58, which had a sensitivity of 70.2% and a specificity of 48.2% (area under the curve, 0.61; 95% CI, 0.58-0.63, P < 0.001). Our results indicate that apoB/A1 ratio is a good indicator of occult coronary atherosclerosis detected by coronary MDCT.

The preventive effect of uncarboxylated osteocalcin against free fatty acid-induced endothelial apoptosis through the activation of phosphatidylinositol 3-kinase/Akt signaling pathway.

OBJECTIVE: Increasing evidence suggests that osteocalcin (OC), one of the osteoblast-specific proteins, has been associated with atherosclerosis, but results are conflicting. The aim of this study was to elucidate the independent effect of uncarboxylated osteocalcin (ucOC), an active form of osteocalcin which has been suggested to have an insulin sensitizing effect, on vascular endothelial cells. MATERIALS AND METHODS: We used human aortic endothelial cells and treated them with ucOC. Linoleic acid (LA) was used as a representative free fatty acid. Apoptosis was evaluated using various methods including a terminal deoxyribonucleotide transferase-mediated deoxyuridine triphosphate nick-end labeling analysis kit and Western blotting for cleaved caspase 3, cleaved poly (ADP-ribose) polymerase and Bcl-xL. The phosphorylations of Akt and endothelial nitric oxide synthase (eNOS) as well as the level of NO were measured to confirm the effect of ucOC on insulin signaling pathway. RESULTS: Pretreatment of ucOC (30 ng/ml) prevented LA-induced apoptosis in insulin-stimulated endothelial cells; effects were abolished by pretreatment with the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, wortmannin. Treatment of ucOC (ranged from 0.3 to 30 ng/ml) significantly increased the phosphorylation of Akt and eNOS and nitric oxide secretion from endothelial cells in a PI3-kinase dependent manner. CONCLUSIONS: Our study is the first to demonstrate the independent effect of ucOC on vascular endothelial cells. Our results further suggest that ucOC could have beneficial effects on atherosclerosis.

Association between serum ceruloplasmin levels and arterial stiffness in Korean men with type 2 diabetes mellitus.

BACKGROUND: Increased oxidative stress contributes to the development of arterial stiffness. Arterial stiffness, as measured by brachial-ankle pulse wave velocity (baPWV), has been known to be correlated with oxidative stress. Serum ceruloplasmin (CP), a copper-carrying protein, may indicate the overall level of oxidative stress in the body. The present study investigated whether serum CP levels are associated with baPWV in Korean men with type 2 diabetes mellitus (DM). SUBJECTS AND METHODS: Serum CP levels and conventional risk factors were measured in 760 Korean men with type 2 DM. Arterial stiffness was assessed by baPWV obtained with an automatic device (model VP-1000; Colin, Komaki, Japan). RESULTS: Correlation analysis indicated a significant positive association between serum CP and baPWV (r = 0.109, P = 0.003). Age-adjusted baPWV increased gradually according to serum CP quartiles (Q1, 1,500.3 ± 18.4 cm/s; Q2, 1,511.6 ± 17.8 cm/s; Q3, 1,551.8 ± 17.9 cm/s; Q4, 1,622.1 ± 17.8 cm/s; P for trend < 0.001). Multivariate linear regression analysis showed that serum CP was independently associated with baPWV in various models. CONCLUSIONS: A positive relationship was identified between CP and baPWV in adult male subjects with type 2 DM, which was independent of conventional cardiovascular risk factors. Further studies are needed to confirm whether CP contributes to the pathogenesis of increased arterial stiffness in subjects with type 2 DM.

The duration of sulfonylurea treatment is associated with ß-cell dysfunction in patients with type 2 diabetes mellitus.

BACKGROUND: This study investigated the incidence of ß-cell dysfunction and the clinical and biochemical factors affecting that in patients with type 2 diabetes having more than 3 years of follow-up. SUBJECTS AND METHODS: ß-Cell dysfunction was assessed by measuring changes in the fasting serum C-peptide concentrations. Patients were classified into two groups: cases showing a decreased (Group D) or an unchanged or increased (Group I) C-peptide concentration from the baseline. RESULTS: Of the 504 patients included in this study, 259 (51%) showed decreased C-peptide concentrations, of whom 20% showed a decrease of ≥50%. Most patients, however, had a final C-peptide concentration of ≥1 ng/mL, with only 18 (4%) individuals having a level <0.6 ng/mL. Patients in Group D had a longer duration of diabetes, higher initial hemoglobin A1c concentration, and longer treatment durations with sulfonylurea and insulin compared with Group I. After adjusting for diabetes duration and C-peptide follow-up period, the duration of sulfonylurea treatment was found to be the only factor independently associated with decreases in the C-peptide concentration. CONCLUSIONS: Although ß-cell function deteriorates over time in patients with type 2 diabetes, these cases mainly have fasting serum C-peptide concentrations of ≥1 ng/mL. A longer treatment duration with sulfonylurea is associated with a more rapid decline in the C-peptide concentration.

Various oscillation patterns of serum fibroblast growth factor 21 concentrations in healthy volunteers.

BACKGROUND: Fibroblast growth factor 21 (FGF21) was originally identified as a paroxysm proliferator activated receptor-α target gene product and is a hormone involved in metabolic regulation. The purpose of this study was to investigate the diurnal variation of serum FGF21 concentration in obese and non-obese healthy volunteers. METHODS: Blood samples were collected from five non-obese (body mass index [BMI] ≤23 kg/m(2)) and five obese (BMI ≥25 kg/m(2)) healthy young men every 30 to 60 minutes over 24 hours. Serum FGF21 concentrations were determined by radioimmunoassay. Anthropometric parameters, glucose, free fatty acid, insulin, leptin, and cortisol concentrations were also measured. RESULTS: The serum FGF21 concentrations displayed various individual oscillation patterns. The oscillation frequency ranged between 6 and 12 times per day. The average duration of oscillation was 2.52 hours (range, 1.9 to 3.0 hours). The peaks and troughs of FGF21 oscillation showed no circadian rhythm. However, the oscillation frequency had a diurnal variation and was lower during the light-off period than during the light-on period (2.4 vs. 7.3 times, P<0.001). There was no difference in the total frequency or duration of oscillations between non-obese and obese subjects, but obese individuals had increased numbers of larger oscillations (amplitude ≥0.19 ng/mL). CONCLUSION: Various oscillation patterns in serum FGF21 concentration were observed, and reduced oscillation frequencies were seen during sleep. The oscillation patterns of serum FGF21 concentration suggest that FGF21 may be secreted into systemic circulation in a pulsatile manner. Obesity appeared to affect the amplitude of oscillations of serum FGF21.

The value of apolipoprotein B/A1 ratio in the diagnosis of metabolic syndrome in a Korean population.

OBJECTIVE: The ratio of apolipoprotein B (apoB) to apolipoprotein A1 (apoA1) has been reported to be associated with the metabolic syndrome (MetS). However, the optimal cut-off value of apoB/A1 ratio for detecting subjects with MetS has remained undetermined. In the present study, we aimed to investigate whether apoB/A1 ratio can be an indicator of MetS and to determine the optimal cut-off value of apoB/A1 ratio in detecting subjects with MetS in a Korean population. DESIGN: This cross-sectional study was conducted at the Asan Medical Center, Seoul, Republic of Korea. SUBJECTS AND MEASUREMENTS: We collected the data of 10,940 subjects who participated in a routine health screening examination regarding conventional risk factors and serum levels of apoB and apoA1. RESULTS: The odds for MetS were significantly higher in the highest compared with the lowest apoB/A1 ratio quartiles, after adjustment for confounding variables, in both men [odds ratio (OR) = 4·07, 95% CI = 3·42-4·84] and women (OR = 8·41, 95% CI = 5·85-12·08). The optimal apoB/A1 ratio cut-off value for the detection of MetS was 0·65, which had a sensitivity of 63·5% and a specificity of 61·3% (area under the curve = 0·67, 95% CI = 0·66-0·68, P < 0·001) in men and 0·62, which had a sensitivity of 67·9% and a specificity of 61·9% (area under the curve = 0·70, 95% CI = 0·69-0·71, P < 0·001) in women. CONCLUSIONS: These results suggest that apoB/A1 ratio is independently associated with MetS and that an apoB/A1 ratio >0·65 in men and 0·62 in women is a marker of MetS independent from conventional risk factors.