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Background Few studies have examined the relationship of sarcopenia with the microcirculation. The current study investigated the relationship of sarcopenia with microcirculatory function, as assessed by skin perfusion pressure (SPP), in type 2 diabetes mellitus (T2DM) patients. Methods In total, 102 T2DM patients who underwent SPP measurements and bioelectrical impedance analysis (BIA) were enrolled in this cross-sectional study. SPP was assessed using the laser Doppler technique. Sarcopenia was defined as low height-adjusted appendicular muscle mass (men, l7 kg/m2; women, l5.7 kg/m2) using BIA. We divided the participants into two groups based on SPP (≤50 and g50 mm Hg), and an SPP below 50 mm Hg was considered to reflect impaired microcirculation. Results Fourteen patients (13.7%) were diagnosed with impaired microcirculatory function of the lower limb based on SPP. The prevalence of sarcopenia in all subjects was 11.8%, but the percentage of patients with an SPP ≤50 mm Hg who had sarcopenia was more than triple that of patients with an SPP g50 mm Hg (28.6% vs. 9.1%, P=0.036). A significant positive correlation was found between SPP and appendicular muscle mass adjusted for height (P=0.041 for right-sided SPP). Multiple logistic regression analysis showed that patients with sarcopenia had an odds ratio of 4.1 (95% confidence interval, 1.01 to 24.9) for having an SPP ≤50 mm Hg even after adjustment for confounding factors. Conclusion These results suggest that sarcopenia may be significantly associated with impaired microcirculation in patients with T2DM. Nonetheless, the small number of patients and wide CI require cautious interpretation of the results.

It is well known that patients with type 2 diabetes mellitus (T2DM) are at an increased risk of morbidity and mortality from atherosclerotic cardiovascular (CV) complications. Previously, the concept that diabetes mellitus (DM) is a "coronary artery disease (CAD) risk equivalent" was widely accepted, implying that all DM patients should receive intensive management. However, considerable evidence exist for wide heterogeneity in the risk of CV events among T2DM patients and the concept of a "CAD risk equivalent" has changed. Recent guidelines recommend further CV risk stratification in T2DM patients, with treatment tailored to the risk level. Although imaging modalities for atherosclerotic cardiovascular disease (ASCVD) have been used to improve risk prediction, there is currently no evidence that imaging-oriented therapy improves clinical outcomes. Therefore, controversy remains whether we should screen for CVD in asymptomatic T2DM. The coexistence of T2DM and heart failure (HF) is common. Based on recent CV outcome trials, sodium glucose cotransporter-2 inhibitors and glucagon like peptide-1 receptor agonists are recommended who have established ASCVD, indicators of high risk, or HF because of their demonstrated benefits for CVD. These circumstances have led to an increasing emphasis on ASCVD and HF in T2DM patients. In this review, we examine the literature published within the last 5 years on the risk assessment of CVD in asymptomatic T2DM patients. In particular, we review recent guidelines regarding screening for CVD and research focusing on the role of coronary artery calcium, coronary computed tomography angiography, and carotid intima-media thickness in asymptomatic T2DM patients.

Purpose In the present study, the authors investigated the effects of selenium on inflammation, hyaluronan production, and oxidative stress in primary cultured orbital fibroblasts of patients with Graves ophthalmopathy (GO). Methods Orbital adipose/connective tissue specimens were obtained during the course of orbital surgery for patients with GO (n = 7) and other noninflammatory problems (n = 5). After incubation with various concentrations of sodium selenite for 48 hours, supernatants from primary cultures were collected. Hyaluronan and cytokine levels were measured using commercially available enzyme-linked immunosorbent assay kits. To determine the effect of selenium on reactive oxygen species (ROS) production stimulated by H2O2 (100 μM) for 30 minutes, the cells were pretreated with various concentrations of sodium selenite for 60 minutes. Results Interleukin (IL)-6 and tumor necrosis factor-alpha levels were significantly higher in orbital fibroblasts of patients with GO than in orbital fibroblasts of control patients. Hyaluronan production was suppressed by selenium in cultured orbital fibroblasts of patients with GO. Inflammatory cytokines such as IL-1α, IL-8, and tumor necrosis factor-alpha were suppressed by selenium in cultured orbital fibroblasts of patients with GO. IL-1β and IL-6 were not suppressed by selenium in cultured orbital fibroblasts of patients with GO. Selenium pretreatment reduced intracellular ROS generation stimulated by H2O2 in cultured orbital fibroblasts of patients with GO. Conclusions In conclusion, hyaluronan production, inflammatory cytokines, and intracellular ROS generation were suppressed by selenium in cultured orbital fibroblasts of patients with GO. Several inflammatory cytokines may be suppressed by selenium in cultured orbital fibroblasts of patients with GO. This study provide the basis for use of selenium in the treatment of GO.

We aimed to evaluate the efficacy and safety profile of lobeglitazone compared with sitagliptin as an add-on to metformin in patients with type 2 diabetes as well as other components of metabolic syndrome. Patients inadequately controlled by metformin were randomly assigned to lobeglitazone (0.5 mg, n = 121) or sitagliptin (100 mg, n = 126) for 24 weeks. The mean changes in HbA1c of the lobeglitazone and sitagliptin groups were -0.79% and -0.86%, respectively; the between-group difference was 0.08% (95% confidence interval, -0.14% to 0.30%), showing non-inferiority. The proportion of patients having two or more factors of other metabolic syndrome components decreased to a greater extent in the lobeglitazone group than in the sitagliptin group (-11.9% vs. -4.8%; P < .0174). Favourable changes in the lipid metabolism were also observed with lobeglitazone, which had a similar safety profile to sitagliptin. Lobeglitazone was comparable with sitagliptin as an add-on to metformin in terms of efficacy and safety.

This population-based cross-sectional study aimed to investigate recent trends in the prevalence and treatment of gestational diabetes mellitus (GDM) in Korea. We also investigated trends in annual prevalence rate of pregnancy-induced hypertension (PIH) and cesarean section (C-section) in GDM patients.We used data from the Health Insurance Review and Assessment-National Patient Sample (HIRA-NPS) database, 2012-2016. Non-GDM (n = 53,698) and GDM (n = 7956) patient data were analyzed for each year.The annual increase in the prevalence of GDM was 11.1% over 2012-2016, with a significant continuously increasing trend (p 0.0001). Age-stratified analysis showed that the annual prevalence of GDM significantly increased in patients below 40 years of age, but was not statistically significant as an increasing trend in patients above 40 years of age. Annual PIH prevalence rate among GDM women showed decreasing trend but was not statistically significant. An annual increase in C-section rate above 5% in GDM patients was statistically significant in both unadjusted and adjusted for age and PIH models.The prevalence of GDM in Korean women and C-section rates in women with GDM showed a significantly increasing trend, 2012-2016. There is a need for further efforts to monitor this trend and to identify associated risk factors for GDM in Korean women.

Background Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are expected to improve the liver function of patients with non-alcoholic fatty liver disease (NAFLD) combined type 2 diabetes mellitus (T2DM) by its characteristic mechanism. This study was designed to investigate the effect of dapagliflozin, one of the SGLT2i, on the liver function of T2DM with NAFLD when combined with metformin. Methods Among patients who received dual oral hypoglycemic agents within the 3 months of diagnosing NAFLD, patients who had abnormal alanine aminotransferase (ALT) level (>40 IU/L) were included. Patients were divided into two groups: metformin+dapagliflozin group and metformin+dipeptidyl peptidase-4 inhibitors (DPP4i) group. Demographic data, biochemical data and the clinical and treatment histories of all patients were reviewed. Results A total of 102 patients were included (dapagliflozin group, n=50; DPP4i group, n=52). Dapagliflozin group showed more weight loss and more ALT decline than DPP4i group (-2.9 kg vs. -0.4 kg, P=0.005; -21.1 U/L vs. -9.5 U/L, P=0.008, respectively) and the proportion of patients with ALT normalization after treatment was also significantly higher in the dapagliflozin group (80.0% vs. 61.5%, P=0.041). The effect of dapagliflozin with metformin on ALT normalization remained significant after adjustment for confounding variables including body weight loss (odds ratio, 3.489; P=0.046). Conclusion ALT improvement was statistically significant in the dapagliflozin than the DPP4i when combined with metformin and the result was consistent after adjustment for confounding variables including body weight loss.

Background and aims To evaluate the efficacy and safety of evogliptin, a newly developed dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes (T2D) inadequately controlled by diet and exercise. Materials and methods In this randomized, double-blind, placebo-controlled, parallel-group, multicenter, phase III study, 160 patients with T2D were assigned to either an evogliptin 5 mg or placebo group for 24 weeks. The primary endpoint was the mean change in glycated hemoglobin (HbA1c) from baseline to week 24. Results The mean baseline HbA1c levels were similar between the evogliptin and the placebo groups (7.20 ± 0.56 vs. 7.20 ± 0.63%, respectively). At week 24, evogliptin significantly reduced HbA1c levels from baseline compared to placebo (−0.23 vs. 0.05%, respectively, P < .0001). Additionally, the proportion of patients achieving HbA1c < 6.5% was significantly higher in the evogliptin group than that in the placebo group (33.3 vs. 15.2%, respectively, P = .008). The overall incidence of adverse events, including hypoglycemia, was similar between the two groups. Conclusions In this 24-week study, once daily evogliptin monotherapy significantly improved glycemic control and was well tolerated in patients with T2D.

Aims The aim of this study was to investigate the association between the glycated albumin (GA) to glycated hemoglobin (HbA1c) (GA/HbA1c) ratio and grade of non-alcoholic fatty liver disease (NAFLD) on ultrasonography (US) in patients with type 2 diabetes mellitus (T2DM). Methods This retrospective, cross-sectional study was performed with data obtained from 186 T2DM patients. Participants were assessed for serum GA/HbA1c ratio and fatty liver using US. NAFLD was defined as ultrasonographically detected fatty liver and was graded as normal, mild, moderate, and severe fatty liver. Results A total of 98 subjects (53%) were diagnosed with NAFLD on US, of which 47 (48%) had moderate-to-severe grade of NAFLD. The mean GA level and GA/HbA1c ratio significantly decreased across increasing NAFLD stages (34% vs. 29% vs. 27% vs. 28%, p =0.023 for trend; 3.1vs. 2.9vs. 2.6vs. 2.7, p =0.001 for trend, respectively), whereas there was no significant difference in HbA1c level among groups ( p =0.714 for trend). There was a significant decrease in prevalence of NAFLD across GA/HbA1c ratio tertiles (67% vs. 58% vs. 41%, p for trend=0.007). Multivariate logistic regression analysis showed that individuals with the lowest GA/HbA1c ratio had an odds ratio (OR) of 2.75 (95% CI=1.06–7.13) for having any grade of NAFLD and an OR of 4.48 [1.20–16.74] for moderate-to-severe grade NAFLD compared with the highest GA/HbA1c ratio even after adjustment for confounding factors ( p =0.038, p =0.026, respectively). Conclusion The present study showed that GA/HbA1c ratio was significantly inversely associated with the presence and severity of NAFLD on US.

Aims This trial consisted of a 24-week multicenter, randomised, double-blind, double-dummy, active-controlled study and a 52-week open label extension study to assess the efficacy and safety of evogliptin, a novel dipeptidyl peptidase-4 inhibitor, compared to sitagliptin in patients with type 2 diabetes who have inadequate glycaemic control with metformin alone. Materials and Methods Adult type 2 diabetes mellitus patients (N = 222) with HbA1c 6.5–11% on stable metformin doses (≥1000 mg/day) were randomised 1:1 to add-on 5 mg evogliptin (N = 112) or 100 mg sitagliptin (N = 110) once daily for 24 weeks. The primary efficacy analysis consisted of a comparison of the change from baseline HbA1c at week 24. Non-inferiority was concluded if the upper limit of the two-sided 95% confidence interval for the HbA1c difference between the treatments was

Fine-needle aspiration biopsy (FNAB) cannot distinguish a follicular thyroid carcinoma (FTC) from a follicular adenoma in follicular lesions. We designed this study to determine whether the preoperative thyroglobulin (Tg) and change in serum Tg during thyroid-stimulating hormone (TSH) suppression can predict FTC in thyroid nodules with a cytological diagnosis of follicular lesion.Among 854 patients who underwent thyroid surgery, the 198 patients who presented with thyroid nodules with a cytological diagnosis of follicular lesion were analyzed. Predictive factors for malignancy were evaluated using multivariate logistic regression models. Subgroup analyses of patients with TSH suppression therapy by levothyroxine were also conducted.Thirty-two patients (16%) had FTC, and 166 patients had confirmed benign nodules. The median preoperative serum Tg levels were significantly higher in patients with FTC compared to those with benign pathology (449 vs. 34 ng/mL, p0.001). The serum Tg (odds ratios (OR) 10.311, p0.001) and tumor volume (OR 4.500, p = 0.035) were found to be independent predictors for FTC in all patients with a cytological diagnosis of follicular lesion. Forty-eight patients received TSH suppression therapy. When we performed subgroup analyses on the patients with TSH suppression therapy, decrease less than 15% in serum Tg during TSH suppression was found to be an independent predictor of FTC (OR 13.918, p = 0.018).Preoperative serum Tg and changes in serum Tg during TSH suppression independently predict FTC in thyroid nodules with a cytological diagnosis of follicular lesion.

Objective: This study evaluates cardiac autonomic neuropathy and heart rate variability according to the vitamin D status in type 2 diabetes mellitus. Methods: A total of 163 patients were recruited. Cardiac autonomic neuropathy was assessed using five tests according to Ewing’s protocol. The time and frequency domains of the heart rate variability were also evaluated. Patients were separated into three groups: vitamin D sufficient [25(OH)D ⩾ 20 ng/mL], vitamin D insufficient [10 ⩽ 25(OH)D Results: Both standard deviation of normal-to-normal RR intervals and square root of the average of the sum of the squares of the differences between adjacent NN intervals in the supine position were significantly lower in vitamin D deficient group. Low frequency/high frequency ratio in the upright position was significantly higher in the vitamin D deficient group. 25(OH)D levels are positively correlated with standard deviation of normal-to-normal RR intervals in the supine position. In multivariate logistic analysis, patients with vitamin D levels of 10 Conclusion: Vitamin D deficiency was significantly correlated with heart rate variability parameters. However, there was only borderline significant association between vitamin D concentration and presence of cardiac autonomic neuropathy. Therefore, future studies are required to establish a relationship between vitamin D levels and cardiac autonomic neuropathy.

Background Thyroid hormones can influence energy metabolism and insulin sensitivity via their interaction with adipocytokines and gut hormones. The aims of this study were to evaluate differences in serum ghrelin and leptin concentrations according to thyroid hormone levels, and to investigate the correlation of insulin resistance. Methods A total of 154 patients (57 hyperthyroid patients, 61 euthyroid patients, and 36 hypothyroid patients; mean age, 47.9 years) were enrolled. Serum leptin, ghrelin, and insulin levels were measured and insulin resistance was calculated using the formula of the homeostasis model assessment of insulin resistance (HOMA-IR). Results There were no differences in mean concentrations of ghrelin or leptin among the three groups. There were no significant differences in insulin levels between the groups (P=0.06), although hyperthyroid patients had borderline statistically significantly higher levels of insulin than did euthyroid subjects by post hoc test (26.4 µIU/mL vs. 16.1 µIU/mL, P=0.057). Regarding HOMA-IR index, the mean levels were highest in the hyperthyroid group among those of the three groups (hyperthyroid vs. euthyroid vs. hypothyroid, 6.7 vs. 3.8 vs. 4.4, P=0.068). Plasma levels of ghrelin were significantly negatively correlated with age, insulin, glucose, body mass index (BMI), and HOMA-IR. Plasma levels of leptin showed significant positive correlation with BMI and triglyceride. There were no significant correlations among thyroid hormone, thyrotropin, ghrelin, leptin, or insulin. Conclusion The present study found that serum ghrelin, leptin, and insulin levels didn't differ according to thyroid function conditions. Further studies with larger numbers of patients are required to establish a direct relationship between plasma ghrelin, leptin, and thyroid hormone.

Background and Aims We undertook this study to compare the prevalence of coronary artery calcification (CAC) across glycated hemoglobin A1c (HbA1c) in nondiabetic males and to evaluate the impact of insulin resistance on CAC in relation to HbA1c levels. Methods A cross-sectional study was performed in 18,504 adult males without diabetes mellitus and cardiovascular disease (CVD). CAC scores were measured by multidetector computed tomography; CAC was defined as a CAC score >0. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). Subjects were grouped by HbA1c quartile (≤5.4%, 5.4–5.6%, 5.7%, 5.8–6.4%). Results Thirteen percent of subjects ( n = 2,406) had a CAC score >0. The prevalence of CAC increased with increasing HbA1c quartile (9.4%, 11.1%, 14.1%, 17.3%). Crude odds ratios (ORs) for CAC were 1.2, 1.58 and 2.01 for the HbA1c quartiles 2, 3, and 4 when compared with the first quartile. Mean HOMA-IR levels were different among HbA1C categories and CAC status. HOMA-IR levels were higher in subjects with CAC than in those without, except in the third HbA1c quartile. Stratification by HbA1c showed a significant association between CAC and insulin resistance only in the first (OR 1.67) and fourth (OR 1.33) HbA1c quartile. After adjustment for CV risk factors, insulin resistance remained an independent predictor of CAC only in the first HbA1c quartile. Conclusions Our study demonstrated that not only glucose status represented by HbA1c but also insulin resistance might be associated with CAC in non-diabetic Korean men. The magnitude of association of CAC with insulin resistance was greater in the lowest HbA1c quartile group.

Background: The aim of this study was to examine the clinical characteristics of adrenal incidentalomas discovered by computed tomography (CT) and to investigate metabolic features of subclinical Cushing’s syndrome (SCS) in patients with adrenal incidentalomas in a tertiary hospital in Korea. Methods: This retrospective study examined the clinical aspects of 268 patients with adrenal incidentalomas discovered by CT at Soonchunhyang University Bucheon Hospital. Clinical data and endocrine function of the patients as well as histological findings were obtained from medical records, while anatomic characteristics were analyzed by reviewing imaging studies. Hormonal tests for pheochromocytoma, Cushing’s syndrome, and aldosterone-secreting adenoma were performed. Results: Most (n=218, 81.3%) cases were nonfunctioning tumors. Of the 50 patients with functioning tumors (18.7%), 19 (7.1%) were diagnosed with SCS, nine (3.4%) with overt Cushing’s syndrome, 12 (4.5%) with primary aldosteronism, and 10 (3.7%) with pheochromocytoma. Malignant tumors (both primary and metastatic) were rare (n=2, 0.7%). Body mass index, fasting glucose, hemoglobin A1c, and total cholesterol were significantly higher in patients with SCS in comparison with those with nonfunctioning tumors. The prevalence of type 2 diabetes mellitus and hypertension were significantly higher in patients with SCS compared with those with nonfunctioning tumors. Conclusion: Functioning tumors, especially those with subclinical cortisol excess, are commonly found in patients with adrenal incidentalomas, although malignancy is rare. In addition, patients with SCS in adrenal incidentalomas have adverse metabolic and cardiovascular profiles.

Background: Many surgeons are reluctant to perform fat grafting in patients with diabetes because soft-tissue healing is impaired, but no previous study has reported data-driven outcomes of fat grafting in subjects with diabetes. Objective: The authors investigate whether diabetes affected survival and complication rates of autologous fat grafting (AFG) in Sprague-Dawley (SD) and Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Methods: In total, 16 male SD and 16 male OLETF rats were prepared for AFG. Fat tissue was harvested from the inguinal fat pad and cut into 1-g (800–1250 mg) sections. Each rat received fat in a subcutaneous pocket in the paraspinal area. The grafted fat tissue was measured by ultrasonography at 30, 60, and 90 days after implantation and evaluated by histological analyses. Results: Ultrasonographic analysis indicated that compared with the SD group, the AFG survival rate was lower in OLETF rats (40.52% vs 53.38%), and the failure rate was higher in OLETF rats (31.25% vs 6.25%). The histological analysis indicated that compared with the OLETF group, adipocytes were more dense (3.18 vs 2.33; P = .025), cyst formation occurred less frequently (3.00 vs 3.61; P = .030), and more capillaries were formed (2.31/field vs 1.61/field; P = .001) in the SD rat group. Conclusions: Diabetes causes marked deterioration in the survival and quality of AFG in the diabetic rat model.

Background: It is not clear whether microangiopathies are associated with subclinical atherosclerosis in type 2 diabetes mellitus (T2DM). We investigated the relation of cardiac autonomic neuropathy (CAN) and other microangiopathies with carotid atherosclerosis in T2DM. Methods: A total of 131 patients with T2DM were stratified by mean carotid intima-media thickness (CIMT) ≥ or

Aims/Introduction It is thought that adipocytokines contribute to the increased risk of vascular complications in type 2 diabetes. However, there is still limited information on the relationship between microangiopathies and adipocytokines, such as adiponectin, leptin and tumor necrosis factor-α (TNF-α) in patients with type 2 diabetes. Materials and Methods The present study examined the relationship between fasting serum adiponectin, leptin, and TNF-α levels and microangiopathies in Korean type 2 diabetes. A total of 153 patients were recruited and evaluated for diabetic nephropathy, retinopathy and neuropathy. Serum adiponectin, TNF-α and leptin levels were measured. Results Serum adiponectin levels were significantly lower in patients with nephropathy than in those without nephropathy (P = 0.017), and were significantly higher in patients with retinopathy or neuropathy than those without retinopathy or neuropathy (P = 0.01 and P = 0.002, respectively). The mean levels of leptin were significantly higher in patients with neuropathy than in those without neuropathy (P = 0.002). The mean levels of TNF-α were not significantly different according to any of the three microangiopathies. Multivariate logistic regression analysis showed that the odds ratio for the presence of neuropathy in the highest tertile of adiponectin was 4.3 (95% confidence interval 1.59–11.62), as compared with the patients in the lowest tertile of adiponectin level. Conclusions Levels of adipocytokines were significantly different according to the presence of each microangiopathy. In particular, higher serum adiponectin was independently associated with increased odds for the presence of neuropathy. Future prospective studies with larger numbers of patients are required to establish a direct relationship between plasma adipocytokine concentrations and the development or severity of diabetic microangiopathies.

Objective: We examined the relationship between serum fetuin-A, insulin resistance (IR), metabolic syndrome (MS) and vascular complications including cardiac autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 172 T2DM patients were recruited and evaluated for diabetic microangiopathies (nephropathy, retinopathy and peripheral neuropathy) including CAN. Serum fetuin-A levels were measured by enzyme-linked immunosorbent assay (ELISA), and the IR was assessed by the index of homeostasis model [homeostasis model assessment–insulin resistance (HOMA-IR)]. Atherosclerotic burden was assessed by ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV). Results: Serum fetuin-A levels showed significant positive correlations with HOMA-IR (r = 0.196, p = 0.022), and the mean levels of HOMA-IR were significantly increased progressively across fetuin-A tertiles ( p for trend = 0.044). Serum fetuin-A showed significant positive correlations with baPWV, systolic blood pressure (BP), total cholesterol, triglycerides, serum fasting c-peptide and negative correlations with ABI. Serum fetuin-A levels were also negatively correlated with serum adiponectin and positively correlated with serum tumour necrosis factor-α (TNF-α). The mean levels of serum fetuin-A were not significantly different according to the presence of each microangiopathies including CAN. Also, the mean levels of serum fetuin-A were not different between patients with MS and without MS. Conclusions: This present study showed that levels of serum fetuin-A are significantly associated with IR and arterial stiffness assessed by baPWV, while there are no associations with each microangiopathies in patients with T2DM.

Aims/Introduction Recently, patient‐tailored statin therapy was proven effective for achieving target low‐density lipoprotein (LDL) cholesterol levels. It is unclear, however, whether this therapeutic modality would be effective for atherogenic lipid profiles and inflammation in patients with type 2 diabetes. Materials and Methods The present study was an 8‐week, multicenter, single‐step titration trial of patient‐tailored atorvastatin therapy (10, 20 and 40 mg) according to baseline LDL cholesterol levels in 440 patients with type 2 diabetes. We measured the LDL particle size by polyacrylamide gel electrophoresis, and used high‐sensitivity C‐reactive protein (hsCRP) and adiponectin as surrogate markers of inflammation. Results In the intention‐to‐treat analysis, 91% of the patients achieved their LDL cholesterol targets (

Aims The aim of this study was to investigate the relationship between serum FGF21 level and all microvascular complication including cardiac autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM). Methods A total 227 T2DM patients were enrolled and serum FGF21 levels were assessed. Diabetic retinopathy, nephropathy, peripheral neuropathy (DPN), and CAN were evaluated. Results The prevalence of retinopathy and nephropathy among the FGF21 tertiles was significantly different ( p =0.001, p =0.006, respectively), whereas no difference was found in the prevalence of DPN and CAN. In multivariate analysis, the odds ratio (OR) for the presence of retinopathy was 0.08 for the FGF21 second tertile when compared with the first tertile ( p =0.029). OR of retinopathy in third tertile group was lower than first tertile and higher than second tertile, but statistically insignificant. Crude OR for nephropathy was 0.34 for the second FGF21 tertile, when compared with the first tertile ( p =0.015). However, FGF21 level was not significantly associated with nephropathy after multivariable adjustment. Conclusions In the present study, there was no association between diabetic nephropathy, DPN, and CAN and serum FGF21 levels. However, we found a U-shaped relationship between both lower and higher serum FGF21 levels and diabetic retinopathy. This result suggests that the very low serum FGF21 level itself may associate with diabetic retinopathy and also relatively elevated serum FGF21 level may be a compensatory increase to protect against microvascular injury.

Background: This study was performed to determine the factors associated with long-term oral hypoglycemic agent (OHA) re sponsiveness in Korean type 2 diabetic patients. Methods: Two groups of patients were selected among the type 2 diabetic patients who were followed for more than two years at a university hospital diabetes clinic. The OHA responsive group consisted of 197 patients whose HbA1c levels were maintained at ≤7% with OHA for more than two years. The OHA failure group consisted of 180 patients whose HbA1c levels were >8% in spite of optimal combined OHA therapy or patients who required insulin therapy within the two years of the study. Results: The OHA failure group had higher baseline values of fasting and postprandial glucose, HbA1c, and lower fasting, post prandial, and delta C-peptide compared to those of the OHA responsive group. The OHA failure group also had a higher pro portion of female patients, longer diabetic duration, and more family history of diabetes. There were no significant differences in body mass index (BMI) or insulin resistance index between the two groups. Multiple logistic regression analysis showed that the highest quartile of baseline fasting, postprandial glucose, and HbA1c and the lowest quartile of postprandial and delta C-peptide were associated with an increased odds ratio of OHA failure after adjustment for age, sex, body mass index, and family history of diabetes. Conclusion: Lower baseline values of postprandial and delta C-peptide and elevated fasting glucose and HbA1c are associated with long-term OHA responsiveness in Korean patients with type 2 diabetes mellitus.

The imbalance between three-repeat (3R) and four-repeat (4R) tau isoforms produced by the alternative splicing of tau exon 10 leads to neuronal instability and eventual neurodegeneration in tauopathy. However, the role of altered 3R/4R tau ratio in Alzheimer's disease (AD) remains controversial. It has been shown that the expression of 3R tau is modulated by peptide amyloid β (Aβ) and that 3R tau levels increase with the progression of AD. The incidence of AD increases in patients with type 2 diabetes mellitus (T2DM), and the comorbidity of these disorders is closely associated with both aging and disease duration. To investigate whether changes in 3R and 4R tau isoforms are involved in AD pathology pertaining to age-related T2DM, the expression of tau isoforms and their relationship with AD-like tau pathology were examined in a spontaneous T2DM model using aged Otsuka Long-Evans Tokushima Fatty (OLETF) rats with obesity. An AD-like pathology consisting of increased aggregates in the neuronal cytoplasm and a loss of synaptic proteins was observed in these rats. The aggregates were reactive with a 3R tau-specific, but not 4R tau-specific, antibody. In contrast to 4R tau, the level of 3R tau profoundly increased and the proteins were prone to taking toxic phosphorylated and truncated forms. Taken together, these findings suggest that increased 3R tau may contribute to AD-like tau pathology in a chronic T2DM model. Thus, the restoration of normal 3R tau expression should be considered as an important therapeutic strategy in the treatment of AD.

The association between subclinical hypothyroidism (SCH) and microvascular complications of type 2 diabetes is unclear. We examined whether SCH is associated with diabetic retinopathy or nephropathy in Korean patients with type 2 diabetes. Data from 489 patients who visited the diabetes clinic at a university hospital between 2001 and 2007 were analyzed retrospectively. Participants were evaluated for glycemic control, thyroid function, and diabetic retinopathy and nephropathy. Diabetic retinopathy was classified into five grades. Diabetic nephropathy was assessed by the presence of albuminuria. Patients in the SCH group had a higher proportion of women, older age, longer duration of diabetes, higher systolic and diastolic blood pressure, and higher insulin resistance index compared with the euthyroid group. No significant difference in family history of diabetes or body mass index was found between groups. The prevalence of severe diabetic retinopathy (severe nonproliferative diabetic retinopathy or proliferative diabetic retinopathy) was significantly higher in the SCH group than the euthyroid group (32.8% vs. 19.6%, P = 0.036), whereas no between-group difference was found in the prevalence of diabetic nephropathy. After adjustment for potential confounding factors (HbA1c, BMI, duration of diabetes, diabetic nephropathy, and hypertension) by multivariate logistic regression analysis, SCH remained significantly associated with severe diabetic retinopathy (odds ratio 2.086 (95% CI, 1.010-4.307), P = 0.047). These results suggest that SCH was independently associated with severe diabetic retinopathy in patients with type 2 diabetes. Further prospective studies are required to confirm the association between SCH and diabetic retinopathy.

Few studies were performed to evaluate the prevalence of latent autoimmune diabetes in adults (LADA) and the difference of chronic complications between LADA, T1DM, and T2DM in Korean. The aim of this study is to establish the prevalence of LADA in a diabetic clinic of Soonchunhyang University hospital and to compare the phenotypic characteristics according to DM classification based on positivity of glutamic acid decarboxylase antibodies (GADA). Also, another important point concerns the occurrence of diabetes chronic microvascular complications in LADA. 323 patients who were checked GADA among diabetic patients admitted at Soonchunhyang University hospital were recruited. Twenty-eight patients (8.7%) were identified as positive for GADA. 11.5% (n = 37) were diagnosed with T1DM and 5.3% (n = 17) were diagnosed with LADA. GADA titer showed significant negative correlation with age of onset, total cholesterol (TC), triglyceride (TG), fasting C-peptide, stimulated C-peptide, BMI, and positive correlation with HbA1C and HDL-C. Compared with those that tested negative for GADA, patients with GADA positive had lower values of onset age, BMI, TC, TG, LDL-C, fasting, and stimulated C-peptide levels and higher values of HbA1C. A significant gradual increase of values was observed for the onset age, BMI, SBP, DBP, fasting, and stimulated C-peptide across the T1DM, LADA, and T2DM subgroups. Concerning the chronic complications there was no difference in prevalence of retinopathy, neuropathy and nephropathy between three groups. Of LADA patients, 12 patients were receiving insulin treatment and mean time to insulin initiation was about 37 months. In conclusion, because our study suggests LADA subgroups in Korea appear to have a faster decline in C-peptide levels, it is worth detecting the patients with LADA early and effort to preserve beta cell function. Furthermore, our results showed that the prevalence of microvascular complication was comparable between the subgroups.

Because T2DM increases the risk of coronary atherosclerosis and CAD and new noninvasive techniques to assess CVD risk have gained considerable popularity, it is important to know how these tools relate to each other. The aim of this study was to evaluate the relationship between the extent of coronary artery calcification measured by MDCT, plasma OPG levels, baPWV and the established cardiovascular risk factors in Korean patients with T2DM. From November 2006 to December 2007, 110 asymptomatic Korean patients with T2DM without prior evidence of CAD were assessed (mean age 57.2 years). CAC imaging was performed using a 40-slice MDCT. Serum OPG levels were measured by an enzyme-linked immunosorbent assay (Oscotec, Korea) from the serum samples of each subject. We measured the baPWV as an index of arterial stiffness. In addition, we measured fasting glucose, HbA(1)C, hsCRP and lipid profiles. A total of 74 patients (67.3%) had minimal or insignificant CAC (10). The CACS, OPG and baPWV showed significant positive correlations with each other. The CACS was significantly associated with the baPWV, smoking and use of a statin. The baPWV was significantly associated with age, duration of DM, total cholesterol and CACS by multiple linear regression models of the dependent variables of CACS or baPWV. CAC and baPWV were significant predictors of each other (r = 0.359, P = 0.014 and r = 0.361, P = 0.004). The results of this study showed that CAC, baPWV and serum OPG levels were significantly correlated with each other in asymptomatic Korean patients with T2DM. Furthermore, our results suggest that arterial stiffness, as determined by baPWV, may predict the extent of coronary calcification by MDCT.

The possibility of postsurgical hypothyroidism after hemithyroidectomy is no longer a new subject. Although many previous studies have mentioned posthemithyroidectomy hypothyroidism, the incidence and contributing factors for hypothyroidism remain uncertain. We intended to evaluate the incidence and the time of development of hypothyroidism after hemithyroidectomy and to analyze the relationship of posthemithyroidectomy hypothyroidism with preoperative biochemical parameters and postoperative histopathological findings. From February 2001 through December 2004, 287 consecutive cases of hemithyroidectomized patients were retrospectively analyzed; 136 of these patients were included in this study after the exclusion criteria were applied. The relationship between posthemithyroidectomy hypothyroidism and several parameters such as sex, age, preoperative free T4, TSH, microsomal antibody (Ab), thyroglobulin antibody (Ab) levels and lymphocytic infiltration of the resected gland was statistically analyzed. Postoperative hypothyroidism developed in 58 patients (42.6%). In hypothyroid group, 11 patients (19%) showed overt hypothyroidism and 47 patients (81%) showed subclinical hypothyroidism. Preoperative TSH value was significantly higher in the hypothyroid group (2.15+/-1.30 microU/ml) compared to the euthyroid group (1.29+/-0.9 microU/ml). Positive ratio of preoperative microsomal Ab and thyroglobulin Ab were significantly higher in hypothyroid group (38.9 and 41.9%) compared to euthyroid group (3.6 and 19.3%) (P0.05). In addition, patients with a higher grade of lymphocytic infiltration were found to have a higher probability of developing hypothyroidism. About 85% of postoperative hypothyroidism was detected between 1 and 6 months postoperatively. We might predict the possibility of developing the posthemithyroidectomy hypothyroidism especially in case of preoperatively positive microsomal antibody, thyroglobulin antibody and high-grade lymphocytic infiltration of the resected gland. In addition, our findings support the recommendation for regular serum TSH follow-up at least for 12 months after hemithyroidectomy.

We aimed to investigate the association between serum 25-hydroxyvitamin D (25[OH]D) and microvascular complications in type 2 diabetes mellitus (T2DM) patients. It was hypothesized that lower 25(OH)D would be associated with increased microvascular complications in T2DM. A total of 257 T2DM patients (111 men, 146 women) who underwent diabetic microvascular complication (peripheral neuropathy, nephropathy, retinopathy) studies were recruited. Patients were categorized into 3 groups according to vitamin D status: vitamin D sufficient (n = 41, 25[OH]D ≥ 20 ng/mL), vitamin D insufficient (n = 132, 10 ≤ 25[OH]D < 20 ng/mL), and vitamin D deficient (n = 84, 25[OH]D < 10 ng/mL). In men, the prevalence of diabetic peripheral neuropathy (DPN) was significantly higher in patients with vitamin D deficiency than in those with insufficiency or sufficiency (38%, 11.7%, and 10%, respectively; P = .005). In addition, the prevalence of diabetic nephropathy (DN) was significantly higher in women with vitamin D deficiency than in the other 2 groups (40%, 20.6%, and 0%; P = .007). Compared with men in the vitamin D-sufficient group (reference), men in the vitamin D-deficient group had an increased risk of DPN after adjusting for confounding factors (odds ratio, 7.79; 95% confidence interval, 1.52-40.05). For women, when the vitamin D-sufficient group was used as a reference, those in the vitamin D-deficient group had an increased risk of DN after adjusting for confounding factors (odds ratio, 4.27; 95% confidence interval, 1.58-11.56). This present study found that a serum 25(OH)D level less than 10 ng/mL is independently associated with increased DPN in male patients and increased DN in female patients with T2DM.

We investigated the association between microalbuminuria and prediabetes in Korean population using data from the KNHANES 2011-2012. Prevalence of microalbuminuria was significantly increased in prediabetes group. However, the odds ratio became insignificant after adjustment for blood pressure, and the prevalence of microalbuminuria was not increased in prediabetic subjects without hypertension.

SummaryObjective 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.

Objective We evaluated the prevalence of aspirin resistance and predictive factors for aspirin resistance in Korean type 2 diabetes patients. Approach and results A total of 1045 type 2 diabetes patients from 11 hospitals who were taking aspirin (100 mg/day for ≥2 weeks) and no other antiplatelet agents were studied to evaluate aspirin resistance. Aspirin resistance was measured in aspirin reaction units using VerifyNow ® . Aspirin resistance was defined as ≥550 aspirin reaction units. Aspirin resistance was detected in 102 of the 1045 subjects (prevalence 9.8%). Aspirin resistance was associated with total cholesterol ( P = 0.013), LDL-cholesterol ( P = 0.028), and non-HDL cholesterol ( P = 0.008) concentrations in univariate analysis. In multivariate logistic regression analysis, only non-HDL cholesterol was associated with aspirin resistance in obese (BMI >25 kg/m 2 ) type 2 diabetes patients (adjusted odds ratio 3.55, 95% CI: 1.25–10.05, P = 0.017). Conclusions The prevalence of aspirin resistance in Korean type 2 diabetes patients is 9.8%. Non-HDL cholesterol is an independent risk factor for aspirin resistance, especially in obese type 2 diabetes patients.

Aims/Introduction The associations between non-alcoholic fatty liver disease (NAFLD) and chronic vascular complications of type 2 diabetes remain uncertain. We assessed the relationships between NAFLD and chronic vascular complications in patients with type 2 diabetes. Materials and Methods Patients with type 2 diabetes (n = 929) attending a diabetes clinic of a university hospital were studied retrospectively. Patients who had any clinical evidence of cirrhosis or other causes of chronic liver disease were excluded. Prevalences of chronic microvascular and macrovascular complications were assessed. NAFLD was ascertained by ultrasonography. Results The prevalence of NAFLD in patients with type 2 diabetes was 63.3%. The prevalences of diabetic retinopathy and nephropathy were significantly lower in patients with NAFLD than those without NAFLD (33.0 vs 70.2%, P

Background Cardiac autonomic neuropathy (CAN) is a common complication of diabetes associated with poor prognosis. In addition, the autonomic imbalance is associated with cardiovascular disease (CVD) in diabetes. It is thought that adipocytokines contribute to the increased risk of vascular complications in patients with type 2 diabetes mellitus (T2DM). However, literature data on the association between CAN with adipocytokines such as leptin, tumor necrosis factor-alpha (TNF-alpha), adiponectin in subjects with T2DM is limited. Therefore, in the present study, we examined the relationship between fasting serum leptin, TNF- alpha and adiponectin and CAN in Korean T2DM patients. Methods A total of 142 T2DM patients (94 males, 48 females) were recruited. CAN was assessed by the five tests according to the Ewing's protocol and the time and frequency domain of the heart rate variability (HRV) was evaluated. Serum TNF-alpha and adiponectin levels were measured using enzyme-linked immunosorbent assay and serum leptin levels were measured using radioimmunoassay. Results Although, the mean levels of leptin, TNF-alpha and adiponectin were not significantly different between the groups with and without CAN, the levels of leptin and adiponectin had a tendency to increase as the score of CAN increased (p = 0.05, p = 0.036). Serum leptin levels demonstrated a negative correlation with low frequency (LF) in the upright position (p = 0.037). Regarding TNF-alpha, a significant negative correlation was observed with SDNN and RMSSD in the upright position (p = 0.023, p = 0.019). Adiponectin levels were not related to any HRV parameters. Multivariate logistic regression analysis demonstrated that the odds of CAN increased with a longer duration of diabetes (1.25, [1.07-1.47]) and higher homeostatic model of assessment-insulin resistance (HOMA-IR) (5.47, [1.8-16.5]). The relative risks for the presence of CAN were 14.1 and 51.6 for the adiponectin 2nd, 3rd tertiles when compared with first tertile (p-value for trend = 0.022). Conclusions In the present study, the higher serum adiponectin levels and HOMA-IR were associated with an increased risk for the presence of CAN. Also, the CAN score correlated with the serum adiponectin. Serum adipocytokines such as leptin and TNF-alpha were significantly correlated with parameters of HRV, representative markers of CAN. Future prospective studies with larger number of patients are required to establish a direct relationship between plasma adipocytokine concentrations and the development or severity of CAN.

This prospective study investigated the efficacy of injection laryn-goplasty in the management of postthyroidectomy vocal cord paralysis (VCP).From March 2005 to December 2008, 174 consecutive injection laryngoplasties were performed in patients with unilateral glottic insufficiency. This included 34 patients with post-thyroidectomy VCP: 15 with temporary VCP and 19 with permanent VCP. Percutaneous injection was performed under local anesthesia into the vocalis muscle, using disposable 25G-long needles through the cricothyroid membrane or directly through the thyroid cartilage. Patients completed the acoustic, aerodynamic, perceptual, stroboscopic, and voice handicap index evaluations before and at 3 and 6 months after the injection.All injection laryngoplasty could be performed under local anesthesia without morbidity. Acoustic and perceptual parameters (overall grade of hoarseness, roughness, breathiness, asthenia, and strain), maximum phonation time, jitter, and shimmer, voice handicap index, and grades of mucosal waves and glottic closure were significantly improved after the injection and they remained stable over 6 months in both the temporary VCP and permanent groups (p0.05).Based on these preliminary results, injection laryngoplasty improved the voice, and voice-related quality of life in patients with post-thyroidectomy VCP. It is a simple, safe, and useful method for rehabilitating post-thyroidectomy VCP patients.

Background: Thyroid incidentalomas detected by 2-deoxy-2- 18 F-fluoro-D-glucose positron emission tomography/computed to- mography ( 18 F-FDG PET/CT) have been reported in 1% to 4% of the population, with a risk of malignancy of 27.8% to 74%. We performed a retrospective review of FDG-avid thyroid incidentalomas in cancer screening subjects and patients with nonthyroid cancer. The risk of malignancy in thyroid incidentaloma and its association with the maximal standardized uptake value (SUVmax) in 18 F-FDG PET/CT were evaluated to define the predictor variables in assessing risk of malignancy. Methods: A total of 2,584 subjects underwent 18 F-FDG PET/CT for metastatic evaluation or cancer screening from January 2005 to January 2010. Among them, 36 subjects with FDG-avid thyroid incidentalomas underwent further diagnostic evaluation (thy- roid ultrasonography-guided fine needle aspiration cytology (FNAC) or surgical resection). We retrospectively reviewed the da- tabase of these subjects. Results: Of the 2,584 subjects who underwent 18 F-FDG PET/CT (319 for cancer screening and 2,265 for metastatic evaluation), 52 (2.0%) were identified as having FDG-avid thyroid incidentaloma and cytologic diagnosis was obtained by FNAC in 36 sub- jects. Of the subjects, 15 were proven to have malignant disease: 13 by FNAC and two by surgical resection. The positive predic- tive value of malignancy in FDG-avid thyroid incidentaloma was 41.7%. Median SUVmax was higher in malignancy than in be- nign lesions (4.7 (interquartile range (IQR), 3.4 to 6.0) vs. 2.8 (IQR, 2.6 to 4.0), P=0.001). Conclusion: Thyroid incidentalomas found on 18 F-FDG PET/CT have a high risk of malignancy, with a positive predictive value of 41.7%. FDG-avid thyroid incidentalomas with higher SUVmax tended to be malignant.

Background Whereas visceral abdominal adipose tissue (VAT) is associated with cardiometabolic risk, there is debate regarding the role of subcutaneous abdominal adipose tissue (SAT). The aim of this study was to investigate the relationships of subcutaneous and visceral abdominal fat with carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Methods A total of 234 patients (men 131, women 103, mean age: 53 years) with T2DM were enrolled. Carotid intima-media thickness (CIMT), abdominal subcutaneous fat thickness (SFT) and visceral fat thickness (VFT) were assessed by high-resolution B-mode ultrasonography (US). Results Compared to women, men had significantly higher VFT and lower SFT (p = 0.002, p = 0.04, respectively). In partial correlation coefficient analyses between CIMT and abdominal fat thickness after adjustment for body mass index (BMI), SFT showed a negative correlation with CIMT in men (r = -0.27, p = 0.03). VFT was not correlated with CIMT in either men or women. In women, SFT was not correlated with CIMT (r = -0.01, p = 0.93). VFT/SFT ratio was not correlated with CIMT in either men or women. In multivariate regression analyses adjusted for BMI and other CVD risk factors, SFT but not VFT was independently inversely associated with CIMT in men but not in women (p

Vitamin D affects not only musculoskeletal health but also a range of nonskeletal diseases such as cancer, obesity, metabolic syndrome, type 2 diabetes and cardiovascular disease. Vitamin D deficiency and obesity have been recognized as pandemic diseases with much health consequences. The ‘cause-effect’ relationship of vitamin D to obesity has been the area of much recent activity. There is consistent association in the published literature between higher body mass index (BMI) and lower 25-hydroxyvitamin D (25(OH)D) concentrations, but the mechanisms are not fully understood. Although recent studies suggest that low serum vitamin D is the consequence of obesity, the results from randomized controlled trials are still scarce and inconclusive to establish the relationship between vitamin D and obesity. Moreover, the role of vitamin D in the pathophysiology of obesity is still debatable and there is little evidence for a direct effect of vitamin D supplementation on body weight. Therefore, randomized large-scale double-blind controlled trials are needed in the future to clearly establish the effects of vitamin D in obesity.

We would like to express our deep gratitude to the editor for giving us the opportunity to publish this article, and we are also deeply grateful to our reviewer, who read our manuscript and provided us with helpful comments and advice. Because few previous studies have been performed on the association between cardiac autonomic neuropathy (CAN) and carotid atherosclerosis, we investigated the relationship between these two conditions in patients with type 2 diabetes mellitus (T2DM). We assessed CAN using five standard cardiovascular reflex tests, according to Ewing's protocol. We diagnosed CAN when a patient showed at least two abnormalities or CAN score of ≥2. However, there is no widely accepted single approach to the diagnosis of CAN in diabetes. Moreover, the diagnostic criteria and staging of CAN are still being debated. Therefore, the wide ranges (2.5% to 50%) of CAN prevalence reported by different authors can be attributed to the heterogeneous methodology used as well as differences in the definition of CAN [1]. Among several methods that provide indexes of both parasympathetic and sympathetic autonomic function, the assessment of heart rate variability by simple bedside tests devised by Ewing et al. has been used widely in clinical settings. Cardiovascular reflex tests are the gold standard in clinical autonomic testing and these tests have good sensitivity, specificity, reproducibility and are easily performed [2]. Several authors suggest that the presence of one abnormal cardiovascular reflex test identifies possible or early CAN and at least two abnormal tests are required for a definite or confirmed diagnosis of CAN [1]. Numerous clinical studies that have examined the association between CAN and mortality or CAN and silent myocardial ischemia used the CAN definition of an abnormal result on at least two of the five tests [3,4]. Additionally, a study that examined the relationship between CAN and coronary artery calcification in Korean patients with T2DM used the same CAN definition as we used in the present study [5]. However, as mentioned in the letter from the reviewer, we also think that a CAN score ≥2 can be too high to detect early atherosclerotic condition. On the contrary, it should be considered that a low CAN score may lead to low specificity in the detection of subclinical atherosclerosis. In addition, the reviewer commented that the definition of 'two abnormal tests' contains many combinations of 'different two' types of abnormal CAN tests. Because each of the five CAN tests has a different meaning, each of those different combinations will also have unique clinical implications. Therefore, we agree with the reviewer's opinion. To our knowledge, however, no studies regarding the different clinical applications of the different combinations of CAN tests have been reported, even though each test or each different combination of the five tests has a different power in the sense of atherosclerotic progression, as mentioned above. In conclusion, although the diagnosis of CAN as 'two or more' abnormal tests or a CAN score ≥2 in our study has several limitations, this diagnostic criteria has been widely used in numerous clinical studies. Additionally, we agree that further studies are needed to standardize and unify the various diagnostic criteria of CAN, as the reviewer commented. Thank you again for your insightful and comprehensive review of our paper.

Background/Aims This study was performed to compare the mucosal findings after esophagogastroduodenoscopy in two groups before and after the use of alendronate only and following administration of the enteric-coated alendronate (5 mg) and calcitriol (0.5 µg) combined drug (Maxmarvil, Yuyu Co.). Methods The study population consisted of 33 postmenopausal healthy female volunteers, aged 50 to 70 years (mean age, 58 ± 5) without gastrointestinal symptoms and with normal baseline endoscopic findings. Esophagogastroduodenoscopy was performed at baseline and was repeated 2 weeks later after daily intake of Maxmarvil (n = 17 subjects) or alendronate only (n = 16 subjects). Mucosal injury scores were reported by an endoscopist after 2 weeks of treatment with each medication schedule. Results Esophageal mucosal injuries developed in two of 16 subjects in the alendronate only group and 0 of 17 in the Maxmarvil group. Gastric mucosal injuries developed in eight subjects in the alendronate group and four subjects in the Maxmarvil group; this difference was statistically significant. Conclusions The mucosal damage scores for the alendronate group (total score 24) were significantly higher than those for the Maxmarvil group (total score 9) in the esophagus and stomach. Therefore, this study suggested that enteric-coated Maxmarvil is less harmful to gastrointestinal mucosa than alendronate, and may improve the tolerability of osteoporosis medication in clinical practice.

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

Background We investigated the relationships of adiponectin/leptin (A/L) ratio with cardiovascular risk factors, insulin resistance index, and metabolic syndrome (MS) in apparently healthy Korean male adults. Methods Sixty-eight male subjects were enrolled among the participants of an annual health check-up program (mean age, 55.1 years). Percent body fat (%) was measured using a bioelectric impedance analyzer. Serum leptin level was measured via radioimmunoassay, and adiponectin level was measured using an enzyme-linked immunosorbent assay. Homeostasis model assessment (HOMA)-insulin resistance (IR) index was calculated, and the presence of metabolic syndrome was assessed. Results Adiponectin, leptin, and A/L ratio showed significant correlations with percent body fat, lipid profile, and HOMA-IR. Mean leptin and HOMA-IR levels were significantly higher, while A/L ratio was significantly lower in subjects with MS. With increasing number of MS components, the mean values of leptin and HOMA-IR increased and the A/L ratio decreased. In multiple regression analysis, HOMA-IR was significantly correlated with triglyceride, fasting glucose, and A/L ratio, while A/L ratio was significantly correlated with body mass index and HOMA-IR. HOMA-IR and A/L ratio were significant predictors for each other after adjustment for other factors. Conclusion A/L ratio correlated well with lipid profile, HOMA-IR, and the presence and number of MS components in Korean male subjects.

Pheochromocytoma not only decreases insulin secretion but also increases insulin resistance. One third of patients with pheochromocytoma have diabetes mellitus and their clinical prognosis showed improvement after surgery. Until now, those patients whose prognosis for diabetes mellitus improved after the operation of pheochromocytoma had typical characteristics such as hypertension, palpitation, headache and elevated hormones such as Vanillylmandelic acid, metanephrine, epinephrine and norepinephrine. We present the case of a 75-year-old woman with asymptomatic adrenal incidentaloma identified as pheochromocytoma which exhibited normal biochemical test results, and after removal of the abdominal mass, her severe hyperglycemia improved.

Antithyroid hormone autoantibodies can be present in the sera of patients with thyroid and non-thyroid disorders. Antithyroid hormone autoantibodies in a patient's serum interfere with radioimmunoassay of thyroid hormones. Clinically, this interference can result in discordance between the serum thyroid hormone levels and the clinical features of the patient, which can lead to misdiagnosis or inappropriate treatment. We experienced a woman who had primary hypothyroidism with unexpectedly high concentrations of serum total triiodothyronine (T3) and free T3, and she had been treated for Graves' disease in the past. Through the use of a polyethylene glycol precipitation method, we detected the anti-triiodothyronine autoantibodies in her serum. We report on this case along with a review of the related literature. (J Kor Endocrinol Soc 21:428~432, 2006)