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This study investigated whether a new sustained-release (SR) pregabalin formulation is noninferior to immediate-release (IR) pregabalin in alleviating peripheral neuropathic pain in Korean patients.This was a randomized, double-blind, active-controlled phase 3 study of patients with diabetic peripheral neuropathy or postherpetic neuralgia from 41 sites in South Korea in 2017-2018. Eligible patients were randomized (1:1) to receive once-daily SR pregabalin or twice-daily IR pregabalin (150 to 600 mg/d) in a double-dummy manner for 12 weeks according to a stratified permuted block randomization scheme. The primary endpoint was the Daily Pain Rating Scale score at the end of treatment, averaged from the last 7 available scores.A total of 319 of 371 (86.0%) randomized patients completed the 12-week treatment (SR pregabalin: n=154; IR pregabalin: n=165; per-protocol set: n=296). The least square mean difference between both groups for the primary endpoint was 0.06 (SE 0.19); (95% confidence interval -0.31 to 0.42), with the lower limit of the confidence interval above the pre-specified margin (-0.78; Pnoninferiority0.0001). Drug-related treatment-emergent adverse events (TEAEs) were comparable between both groups. The incidence of drug-related TEAEs leading to treatment discontinuation was low (SR pregabalin: 2.7%; IR pregabalin: 1.1%). No serious drug-related TEAEs or deaths occurred.The results demonstrate that the new once-daily SR pregabalin formulation is noninferior to twice-daily IR pregabalin in reducing peripheral neuropathic pain and is well tolerated in Korean patients with diabetic peripheral neuropathy or postherpetic neuralgia after 12 weeks of treatment.

DA-9801, a plant-based drug used for the treatment of diabetic neuropathy, is known to improve angiotensin II (Ang II)-induced vascular endothelial cell dysfunction. However, the underlying mechanism is not fully understood. We aimed to determine whether the protective effect of DA-9801 against Ang II-induced endothelial cell dysfunction was mediated via inhibition of endothelial cell inflammation and apoptosis. Ang II-induced oxidative stress was attenuated by pretreatment of human dermal microvascular endothelial cells (HDMECs) with DA-9801. This prevented the Ang II-induced upregulation of NAD(P)H oxidase (the NOX4 and p22phox subunits) and reactive oxygen species. Further, pretreatment of HDMECs with DA-9801 ameliorated Ang II-mediated nuclear factor kappa B activity via prevention of the upregulation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase. It also decreased the Ang II-stimulated increase in inducible nitric oxide synthase (NOS) and decreased endothelial NOS protein expression. DA-9801 decreased Ang II-induced upregulation of intercellular adhesion molecule 1, vascular adhesion molecule, and E-selectin in HDMECs. Moreover, TUNEL and annexin V-FITC fluorescence staining for apoptosis and the activities of caspases 9, 7, and 3 decreased in HDMECs pretreated with DA-9801, indicating that the drug enhanced anti-apoptotic pathways. Thus, DA-9801 modulated Ang II-induced endothelial cell dysfunction via inflammatory and apoptotic pathways.

Background/Aims Lymphocytic thyroiditis as cytology diagnosis from fine needle aspiration (FNA) is frequently detected in patients with thyroid nodules. However, the clinical outcome for upcoming hypothyroid events has been rarely clarified in euthyroid patients. Methods We retrospectively reviewed the data of patient who had lymphocytic thyroitidis on FNA cytology of thyroid nodule from January 2005 to December 2010 at a tertiary referral hospital. In total, 109 patients with follow-up thyroid function tests (TFT) were enrolled. Final outcomes included overt and subclinical hypothyroidism with thyroid stimulating hormone (TSH) levels ≥ 10 mIU/L. Potential parameters predicting clinical hypothyroidism were analyzed by multivariate analysis. Results Over the mean follow-up duration of 51.6 months, 14 out of 109 patients (12.8%) developed clinical hypothyroidism that required thyroid hormone replacement. The median onset time to hypothyroidism was 16 months (range, 3 to 88) and ≥ 60% of patients experienced clinical hypothyroidism within 1 year. By multivariate analysis, background thyroiditis (relative risk [RR], 9.78; p = 0.004), thyroid peroxidase antibody positivity (RR, 9.90; p = 0.003), nodule size (RR, 1.24; p < 0.001), and initial TSH (RR, 1.47; p = 0.009) were the independent risk factors for predicting hypothyroidism in euthyroid patients. Conclusions Hypothyroidism frequently occurs during the follow-up in euthyroid patients with thyroid nodules which show lymphocytic thyroiditis on FNA cytology. Close surveillance and regular TFT are needed in high-risk patients for upcoming clinical hypothyroidism.

BACKGROUND Diabetic cardiac autonomic neuropathy (CAN) is one of the important complications of diabetes. It is characterized by reduced heart rate variability (HRV). METHODS In this randomized, double-blind, placebo-controlled, multicenter trial, 75 patients were randomly assigned to one of two groups. One group (n=41) received α-lipoic acid (ALA) at an oral dose of 600 mg/day for the first 12 weeks and then 1,200 mg/day for the next 12 weeks. The other group (n=34) received placebo treatment for 24 weeks. CAN was assessed by measuring HRVs in people with diabetes. RESULTS Most of the baseline measures for HRVs were similar between the ALA and placebo groups. Although there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial, we found a positive tendency in some of the HRV parameters of the ALA group. The standard deviations of normal-to-normal RR intervals in the standing position increased by 1.87 ms in the ALA group but decreased by -3.97 ms in the placebo group (P=0.06). The power spectrum of the low frequency (LF) band in the standing position increased by 15.77 ms² in the ALA group, whereas it declined by -15.04 ms² in the placebo group (P=0.08). The high frequency/LF ratio in the upright position increased by 0.35 in the ALA group, whereas it declined by -0.42 in the placebo group (P=0.06). There were no differences between the two groups regarding rates of adverse events. CONCLUSION Although a slight improvement tendency was seen in HRV in the ALA group, there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial. However, the high oral dose of ALA was well-tolerated.

Context The coexistence of differentiated thyroid cancer (DTC) and thyroid autoimmune disease could represent a better or worse prognosis. This study investigated the prognostic importance of preoperative anti-thyroglobulin antibody (TgAb) in DTC patients. Design and patients This retrospective hospital-cohort study enrolled 1,171 consecutive DTC patients with preoperative TgAb data, who underwent total thyroidectomy between January 2006 and December 2011. Clinical parameters studied included demographics, primary tumor characteristics, radioiodine therapy, thyroid function tests, preoperative thyroglobulin (Tg) and TgAb levels, and cancer persistence/recurrence. Results A total of 254 (21.7%) patients were preoperatively TgAb-positive. The percentage positive for thyroid peroxidase (TPO) antibody and lymphocytic thyroiditis was significantly higher in the TgAb-positive group. The TgAb-positive group had a significantly higher rate of lymphatic invasion and lymph node metastasis both overall and in patients without TPOAb and lymphocytic thyroiditis (non-HT group). The mean number of total and central lymph nodes dissected and rate of lateral lymph node dissection were significantly higher in the TgAb-positive group, both overall and in non-HT patients. In regression analysis, preoperative TgAb was an independent risk factor for lateral lymph node metastasis. Over 50.2±14.5 months follow-up, disease persistence/recurrence was not significantly different between patients with and without TgAb, both overall and in non-HT patients. Preoperative TgAb showed no significant correlation with final disease status. Conclusion Positive preoperative serum TgAb is associated with worse primary tumor characteristics but rarely showed poor prognosis, probably due to more aggressive treatment of these subjects. This article is protected by copyright. All rights reserved.

Background When patients with diabetes mellitus (DM) are first referred to a hospital from primary health care clinics, physicians have to decide whether to administer an oral hypoglycemic agent (OHA) immediately or postpone a medication change in favor of diabetes education regarding diet or exercise. The aim of this study was to determine the effect of diabetes education alone (without alterations in diabetes medication) on blood glucose levels. Methods The study was conducted between January 2009 and December 2013 and included patients with DM. The glycosylated hemoglobin (HbA1c) levels were evaluated at the first visit and after 3 months. During the first medical examination, a designated doctor also conducted a diabetes education session that mainly covered dietary management. Results Patients were divided into those who received no diabetic medications (n=66) and those who received an OHA (n=124). Education resulted in a marked decrease in HbA1c levels in the OHA group among patients who had DM for 10 years showed a slightly lower HbA1c target achievement rate of

Object: There are very few studies that evaluate the influence of obesity and weight variations on change in ankle-brachial index (ABI) in subjects with type 2 diabetes (T2D) but without peripheral artery disease (PAD). Methods: In this case-control study, T2D subjects who were without baseline PAD (0.9 ≤ ABI < 1.4), and received minimum 2-year interval ABI exams were included. Subjects with prior diagnosed or treated PAD were excluded. Baseline body mass index (BMI) of all subjects was categorized as normal weight (< 23 kg/m2), overweight (23∼25 kg/m2), and obesity (≥ 25 kg/m2). Weight changes during follow-up were categorized by the percentage of weight change; weight loss (< -3%), stable (-3∼3%), gain (> 3%). Subjects with ABI decline were defined as one or both legs worsened to the abnormal (ABI < 0.9) at follow-up exam. Results: A total of 575 subjects were analyzed (188 normal, 140 overweight, and 245 obesity). During the median 2.9 years of follow-up period, 122 (21.2%) subjects showed ABI decline. When split by category of BMI and weight change, the incidence rate of ABI decline showed stepwise increasing pattern according to the obesity and weight gain. Multivariable logistic regression analysis showed that baseline obesity (vs. normal) was significantly associated with the risk of developing ABI decline after adjusting for age, sex, smoking, diabetes duration, mean HbA1c, GFR, LDL cholesterol, blood pressure, hypertensive medication, insulin use, statin use, antiplatelet use, and weight change (OR = 2.06, 95% CI = 1.22 - 3.49). On the contrary, weight loss was significantly associated with reduction in risk of developing ABI decline (OR = 0.52, 95% CI = 0.31 - 0.86). Conclusion: Obesity is an independent risk factor for developing ABI decline in T2D subjects without PAD, whereas weight loss is an independent protective factor. Weight loss should be emphasized especially in obese subjects with T2D. Disclosure Y. Yang: None. J. Lim: None. E. Lee: None. K. Yoon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc. Speaker's Bureau; Self; Takeda Pharmaceutical Company Limited. B. Cha: None. S. Lee: None. Y. Cho: None.

The American College of Cardiology/American Heart Association (ACC/AHA) guidelines are based on studies with a limited number of Asian subjects; therefore, they are difficult to apply to Asian patients, including Korean patients.Data were extracted from the clinical data warehouse system of Seoul St. Mary's hospital (January 2010 - December 2012) to determine the percent change in low-density lipoprotein cholesterol (LDL-C) levels at an average 3 and 6 months from baseline. Statins with statistically similar lowering effects were placed in one group (group A, B, or C). The proportions of patients who achieved LDL-C 100 mg/dL were compared between baseline LDL-C levels: low ( 130 mg/dL), medium (130 - 160 mg/dL), and high ( 160 mg/dL).The majority of the 9 statins of various doses (2,349 patients) were effective at 3 months, with additional, smaller decreases at 6 months. The LDL-C lowering effect of group A (atorvastatin (20 mg), rosuvastatin (10 mg)) was ~ 45%; that of group B (atorvastatin (10 mg), pitavastatin (2 mg), pravastatin (40 mg), simvastatin (20 mg)) was 35 - 37%. groups A and B contained only moderate-intensity statins (ACC/AHA guidelines). With baseline LDL-C ≥ 130 mg/dL, greater proportions of patients achieved LDL-C 100 mg with atorvastatin (20 mg) and rosuvastatin (10 mg).Because of the demonstrated LDL-C lowering effects and target achievement rates, the ACC/AHA guidelines might not apply to Korean patients. Korean treatment guidelines should consider statins with relatively low potency. Additional studies regarding appropriate statin doses should be conducted with Asian populations.

Background/Aims: This study evaluated the relationship between thyroid nodules and metabolic syndrome (MS) and its components in apparently healthy Koreans. Methods: We reviewed the records of 3,298 subjects with no noticeable symptoms who underwent thyroid ultrasound imaging as part of a routine check-up between July 2009 and June 2010; of these, 1,308 were excluded based upon predefined criteria. Among the remaining 1,990 patients, we examined the associa tion between MS and its components and the incidence of thyroid nodules. Results: Of the 1,990 subjects included in this study, 38.4% (n = 764) had thyroid nodules and 12.7% (n = 253) had MS. Female sex, older age, higher body mass index, larger waist circumference, higher glycated hemoglobin level, lower thyroid stimulating hormone level, and presence of MS were all closely related with the presence of thyroid nodules (all p < 0.05). Furthermore, the relevant number of MS components showed a positive linear correlation with the occurrence of thyroid nodules (p < 0.001). Evidence of MS alone was not independently associated with thyroid nodules after adjusting for sex and age in a multivariate binary logistic regression analysis; however, glycated hemoglobin for females and waist circumference for males, as well as both age and thyroid stimulating hormone for all patients, were identified as independent predictors for the existence of thyroid nodules (all p < 0.05). Conclusions: This study suggests a positive relationship between the components of MS and thyroid nodules in an ostensibly healthy Korean population. Our data support the idea that the recent increase in thyroid nodules is partly due to increases in both MS and obesity.

Background This study was a multicenter, parallel-group, double-blind, double-dummy, randomized, noninferiority trial to evaluate the efficacy and safety of γ-linolenic acid (GLA) relative to α-lipoic acid (ALA) over a 12-week treatment period in type 2 diabetes mellitus (T2DM) patients with painful diabetic peripheral neuropathy (DPN). Methods This study included 100 T2DM patients between 20 and 75 years of age who had painful DPN and received either GLA (320 mg/day) and placebo or ALA (600 mg/day) and placebo for 12 weeks. The primary outcome measures were mean changes in pain intensities as measured by the visual analogue scale (VAS) and the total symptom scores (TSS). Results Of the 100 subjects who initially participated in the study, 73 completed the 12-week treatment period. Per-protocol analyses revealed significant decreases in the mean VAS and TSS scores compared to baseline in both groups, but there were no significant differences between the groups. The treatment difference for the VAS (95% confidence interval [CI]) between the two groups was -0.65 (-1.526 to 0.213) and the upper bound of the 95% CI did not exceed the predefined noninferiority margin (δ₁=0.51). For the TSS, the treatment difference was -0.05 (-1.211 to 1.101) but the upper bound of the 95% CI crossed the noninferiority margin (δ₂=0.054). There were no serious adverse events associated with the treatments. Conclusion GLA treatment in patients with painful DPN was noninferior to ALA in terms of reducing pain intensity measured by the VAS over 12 weeks.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent liver disease encompassing a broad spectrum of pathologic changes in the liver. Metabolic derangements are suggested to be main causes of NAFLD. As thyroid hormone is a main regulator of energy metabolism, there may be a link between NAFLD and thyroid function. In previous studies, the association between NAFLD and thyroid function was not conclusive. The aim of this study was to clarify the relationship between NAFLD and thyroid function, focusing on subclinical hypothyroidism, using nationwide survey data representing the Korean population. NAFLD was defined as a hepatic steatosis index of 36 or higher. Based on the analysis of nationwide representative data, subclinical hypothyroidism was related to a high risk of NAFLD in males, but not in females. Our study showed that thyroid function might play a substantial role in the development of NAFLD, especially in males. Further study to elucidate the underlying mechanism of gender specific association of mild thyroid dysfunction and NAFLD would be required.

Objective To investigate the prevalence of subclinical hypothyroidism (SCH) in Korean adults and identify the risk factors for the occurrence of SCH by sex. Design and methods This study used data from the Sixth Korea National Health and Nutrition Examination Survey (KNHANES VI), a cross-sectional, nationally representative survey, which comprises a health interview survey, a health examination survey and a nutrition survey. To examine SCH, the reference range of thyroid-stimulating hormone (TSH) was defined using both the range provided by the test kit manufacturer (SCH-M) and a population-based range (SCH-P). We investigated the prevalence of SCH and its risk factors by sex using both reference ranges. Results The prevalence of SCH in Koreans according to SCH-M (0.35–5.5 µIU/mL) was 5.6%, and 3.3% with SCH-P (0.62–6.68 µIU/mL). For men, smoking significantly reduced the incidence of SCH, positive anti-thyroid peroxidase antibody (TPOAb) significantly increased the risk of SCH, and in an adjusted model, the risk of SCH in all quartiles increased as the urine iodine creatinine ratio (UICR) quartile increased. For women, positive TPOAb was confirmed as a risk factor for SCH, as was the highest UICR quartile. Furthermore, the odds ratio for SCH in urban vs rural residence was 1.78. Conclusions The prevalence rates of SCH were similar to those reported in the literature and previously known risk factors were confirmed using both TSH reference ranges. The notable findings from this study are that the increased risk of SCH with increased iodine intake was more marked in men than in women and that residential area may be a risk factor for SCH in women.

The association of parathyroid hormone (PTH) and vitamin D with Metabolic syndrome (MetS) was evaluated using representative data from the Korean population. Data from 7004 subjects aged 50 or older with preserved renal function (excluding chronic kidney disease stage 3b to 5) who were included in the Korean National Health and Nutrition Examination Survey between 2008 and 2010 were analysed. Higher PTH levels (pg/ml) were observed in subjects with MetS than in those without MetS among both genders (60.1 (58.6–61.6) vs. 62.4 (60.7–64.2) in males p = 0.018, 60.7 (59.4–62.1) vs. 63.9 (62.4–65.6) in females, p 0.001). For females, PTH levels were significantly higher in subjects with MetS than in those without MetS after adjustment for possible covariates. Lower 25(OH)D levels were significantly associated with MetS only in male subjects (p = 0.004). As the number of MetS components increased, a significant rise in PTH levels (p for trend 0.005 in males and 0.024 in females) and a decrease in 25(OH)D levels (p for trend

Background In general, obesity is a major contributor to metabolic syndrome (MetS) and is associated with insulin resistance (IR). Metabolically obese but normal weight (MONW) individuals present metabolic abnormalities and features of MetS despite having a normal range of body mass index (BMI). In recent years, different subtypes of obesity have been introduced, including metabolically healthy obese (MHO) and metabolically obese obese (MOO). Also, it has been reported that vitamin D and parathyroid hormone (PTH) are possibly linked with MetS. Methods and findings In this study, we aimed to evaluate the association between serum 25(OH)D, serum PTH, and the risk of metabolic obesity in four subtypes using nationally representative survey data for a Korean population conducted between 2008 and 2010. Of the 29,235 Korean participants, 18,997 subjects aged under 50 years were excluded. Participants with diabetes (n = 1,520), renal insufficiency (glomerular filtration rate [GFR] < 45 ml/min/1.73 m2, chronic kidney disease [CKD] stage 3b, 4, and 5 according to KDOQI classification [1]) (n = 49), history of treatment for osteoporosis (n = 455), insufficient data (n = 1,613), and fasting time less than 8 hours prior to blood collection (n = 771) were excluded for analysis. Ultimately, 5,830 adults (2,582 men and 3,248 women) were eligible for the present study. And, subtypes of obesity were divided into four types: Metabolically healthy normal weight (MHNW), Metabolically healthy obese (MHO), Metabolically obese but normal weight (MONW), and Metabolically obese obese (MOO). Female subjects with metabolic obesity were more likely to have higher levels of PTH and Male subjects with metabolic health were more likely to have higher serum 25(OH)D levels Conclusion We concluded that a positive association between serum PTH concentration and metabolic obesity among female subjects and an inverse relationship between serum 25(OH)D levels and the risk of metabolic obesity were found among male subjects. Further prospective studies are necessary to explore the biological mechanisms underlying these sex-specific findings.

Objectives. Patients with diabetic peripheral neuropathy (DPN) is the most common complication. However, patients are usually suffering from not only diverse sensory deficit but also neuropathy-related discomforts. The aim of this study is to identify distinct groups of patients with DPN with respect to its clinical impacts on symptom patterns and comorbidities. Methods. A hierarchical cluster analysis and factor analysis were performed to identify relevant subgroups of patients with DPN (n=1338) and symptom patterns. Results. Patients with DPN were divided into three clusters: asymptomatic (cluster 1, n=448, 33.5%), moderate symptoms with disturbed sleep (cluster 2, n=562, 42.0%), and severe symptoms with decreased quality of life (cluster 3, n=328, 24.5%). Patients in cluster 3, compared with clusters 1 and 2, were characterized by higher levels of HbA1c and more severe pain and physical impairments. Patients in cluster 2 had moderate pain levels but disturbed sleep patterns comparable to those in cluster 3. The frequency of symptoms on each item of MNSI by “painful” symptom pattern showed a similar distribution pattern with increasing intensities along the three clusters. Conclusions. Cluster and factor analysis endorsed the use of comprehensive and symptomatic subgrouping to individualize the evaluation of patients with DPN.

Distant metastases from papillary thyroid carcinoma (PTC) are rare and are associated with a poor prognosis. Here, we describe a patient with metastatic PTC who was treated with a tyrosine kinase inhibitor (TKI, sorafenib) for several months that was acutely exacerbated by discontinuation. A 43-year-old male was diagnosed with PTC in February 2004 and underwent total thyroidectomy followed by two courses of high-dose radioactive iodine (RAI) therapy. Despite two additional courses of high-dose RAI therapy, lung and muscle metastases were developed. Treatment with sorafenib was begun in September 2010. After 11 months treatment of sorafenib, newly developed metastatic lesions were found in mediastinal lymph nodes, liver, and bones. Considered as treatment failure, the administration of sorafenib was discontinued. Two weeks after sorafenib treatment was stopped, the disease progressed abruptly and caused death of the patient by respiratory failure. In our patient, PTC progressed rapidly after the cessation of sorafenib treatment. Patients with several other types of cancer have also experienced such rapid disease progression, termed "flare-ups." Physicians should be aware that flare-ups may occur in advanced PTC patients following the cessation of TKI therapy.

Aims/Introduction Early initiation of basal insulin therapy is recommended for normalizing fasting blood glucose in type 2 diabetes mellitus. However, basal insulin treatment might not adequately control postprandial glucose levels. The present study evaluated whether the combination of the α-glucosidase inhibitor, acarbose, and basal insulin improved blood glucose control under daily-life treatment conditions in a large sample of Korean patients. Materials and Methods The present study was a multicenter, prospective, observational study under daily-life treatment conditions. A total of 539 patients with type 2 diabetes who were treated with basal insulin and additional acarbose were enrolled and followed up for 20 weeks. Changes in hemoglobin A1c, fasting and postprandial blood glucose were evaluated at baseline and at the end of the observation period. The physician and patient satisfaction of the combination treatment and safety were assessed. Results Hemoglobin A1c decreased by 0.55 ± 1.05% from baseline (P

Background The Korea National Health and Nutrition Examination Survey (KNHANES) III (2005) reported that 22.9% of individuals with diabetes have a glycated hemoglobin (HbA1c) 5 years. HbA1c in the group taking only oral hypoglycemic agents (OHAs) was significantly lower than that in the group administered only insulin or OHA and insulin in combination. In logistic regression analysis, a longer duration of diabetes, insulin use and the absence of chronic renal failure were associated with HbA1c levels >6.5%. Conclusion The level of adequate glycemic control was similar to but slightly improved compared with previous levels. The glycemic control of long-standing diabetes patients is more difficult even though they receive insulin treatment.

Diabetic peripheral neuropathy (DPN) is the most common complication associated with diabetes. DPN can present as a loss of sensation, may lead to neuropathic ulcers, and is a leading cause of amputation. Reported estimates of the prevalence of DPN vary due to differences in study populations and diagnostic criteria. Furthermore, the epidemiology and clinical characteristics of DPN in Korean patients with type 2 diabetes mellitus (T2DM) are not as well understood as those of other complications of diabetes such as retinal and renal disease. Recently, the Diabetic Neuropathy Study Group of the Korean Diabetes Association (KDA) conducted a study investigating the impact of DPN on disease burden and quality of life in patients with T2DM and has published some data that are representative of the nation. This review investigated the prevalence and associated clinical implications of DPN in Korean patients with diabetes based on the KDA study.

FDG (2-[(18)F]Fluoro-2-D-deoxyglucose-positron emission tomography (PET)/computed tomography (CT), which can detect a change in glucose metabolism in cancer cells, has been introduced as a diagnostic and prognostic tool in papillary thyroid carcinoma (PTC). However, differences in the clinicopathological and biological characteristics between primary PTCs with FDG uptake and those without FDG uptake are not well established.A total of 188 patients with PTC who had preoperative PET/CT scans were enrolled to compare the differences of clinicopathological parameters between FDG-avid (F-PTC; n = 150) and non-FDG-avid tumors (FN-PTC; n = 38). Immunohistochemical staining for glucose transporter (GLUT)-1 and hypoxia-inducible factor-1 alpha (HIF-1α) was performed.FN-PTCs were smaller; had a lower incidence of lymphatic invasion, vascular invasion, multifocality, and central lymph node metastasis; and had a lower maximum standardized uptake value than F-PTCs. After exclusion of high-risk patients for recurrence, FN-PTCs remained smaller (p0.001) and had less lymphatic invasion (p = 0.061). Among tumors larger than the spatial resolution of the PET/CT scan, macrocalcification was more frequent in FN-PTC than in F-PTC (p = 0.043). While FN-PTC and F-PTC showed no difference in GLUT-1 expression (50% vs. 75%, p = 0.363), FN-PTC showed lower HIF-1α immunoreactivity than F-PTC (25.0% vs. 75.0%, p = 0.032).Tumor size and macrocalcification are clinicopathological differences between FN-PTC and F-PTC. Biologically, HIF-1α may be responsible for increased FDG uptake in PTC.

Background Due to the inconvenience of performing oral glucose tolerance tests and day to day variability in glucose level, glycated hemoglobin (HbA1c) has been recommended by the American Diabetes Association as a method to diagnose diabetes. In addition, the Korean Diabetes Association has also recommended the use of HbA1c as a diagnostic test for diabetes. In this study, we evaluated the prevalence of diabetes according to fasting plasma glucose (FPG) level only or the combination of FPG and HbA1c tests. Methods Data from the 2011 Korea National Health and Nutrition Examination Survey (KNHANES) were analyzed. Among 5,811 subjects aged 30 years or older, 5,020 were selected after excluding the data of fasting time

Aims/Introduction: Sleep disturbances caused by painful diabetic neuropathy (PDN) might have substantial impacts on the multifaceted aspects of PDN, including quality of life. There are no convincing data on the validation or reliability of sleep problem measurements in patients with PDN in Korea. This large population-based cross-sectional study examined psychometric properties of the Medical Outcomes Study (MOS) Sleep Scale in patients with PDN in Korea. Materials and Methods: Measurements of patient-reported outcomes (Brief Pain Inventory-short form, MOS Sleep Scale and EuroQoL Health [EQ-5D]) were documented. PDN was diagnosed if the average daily pain intensity was ‡ 4b ased on the visual analog scale or if patients were taking medication for their current pain. Results: There were 577 patients with PDN (41.6% with diabetic peripheral neuropathy). The internal consistency of reliability for the MOS Sleep Scale was 0.80 as measured by Cronbach’s alpha. The extent to which multiple items in a dimension were intercorrelated and formed a dimension measuring the same underlying concept (Pearson’s correlation coefficient) ranged from 0.24 to 0.71 (all P < 0.001). Each item of the MOS Sleep Scale was significantly correlated with the average pain score and the pain interference score (Pearson’s correlation coefficients ranged from 0.20 to 0.28 and from 0.29 to 0.40, respectively; all P < 0.001). The correlations between the EQ-5D index and the MOS Sleep Scale ranged from -0.27 to -0.31 (all P < 0.001). Conclusions: The MOS Sleep Scale showed good reliability in the evaluation of PDN in Korean type 2 diabetic patients. (J Diabetes Invest, doi: 10.1111/jdi.12066, 2013)

The aim of this study was to evaluate the effects of early intensive insulin therapy on body fat distribution, lean body mass and β-cell function in patients with newly diagnosed type 2 diabetes.Thirty-eight subjects with newly diagnosed type 2 diabetes participated in a 12-week course of intensive insulin therapy. Patients were administered a 75 g oral glucose tolerance test (OGTT), underwent measurement of visceral and subcutaneous adipose tissues (VAT and SAT) using computed tomography and appendicular skeletal muscle (ASM) mass was assessed using dual-energy X-ray absorptiometry.After intensive insulin therapy, fasting plasma glucose and HbA1c levels decreased. Homeostasis model assessment (HOMA)-B, the insulinogenic index, and the C-peptide-to-glucose area under the curve (AUC) ratio increased. The insulin sensitivity index and the glucose AUC decreased after 12 weeks. The body composition analysis revealed that the VAT and the ratio of VAT to SAT decreased, whereas body weight and total fat mass increased nonsignificantly. The ASM/weight and skeletal muscle mass index increased. The restoration of β-cell function, as identified by HOMA-B, the insulinogenic index, and the C-peptide-to-glucose AUC ratio, was correlated with the changes in VAT when controlled for age and gender. In multiple regression analyses, the decrease in VAT was shown to independently contribute to improved HbA1c over the study period, after adjusting for confounding factors.These results suggest that a shift in fat distribution from visceral to subcutaneous fat after early intensive insulin therapy is associated with improvements in glycemic control and β-cell function in patients with newly diagnosed type 2 diabetes.

Galectin-3 (G3) immunostaining of fine-needle aspiration (FNA) samples from thyroid nodules is very useful for the diagnosis of malignancy. The objective of the present study was to determine whether the absence of G3 immunostaining in preoperative FNA samples is associated with favorable clinicopathological parameters, including lymph node (LN) metastasis, in papillary thyroid carcinoma (PTC).The records of 868 patients with PTC who had prethyroidectomy ultrasonography-guided FNA with G3 immunostaining between January 2006 and December 2009 were retrospectively reviewed. G3 immunostaining was considered positive if the percentage of tumor cells showing definite cytoplasmic immunostaining exceeded 5%. Patients who had negative G3 immunostaining of FNA samples were assigned to the G3-negative (G3N) group; whereas those who had positive G3 immunostaining were assigned to the G3-positive (G3P) group.There were 92 patients who were assigned to the G3N group (10.6%) because of the negative staining for G3 in the preoperative FNA samples from their thyroid nodules. The proportion of PTC subtypes in the G3N and G3P groups was similar (p=0.376). There was less frequent thyroid capsular invasion (46.7% vs. 66.5%, p0.001), extrathyroidal extension (28.3% vs. 48.5%, p0.001), and LN metastasis (22.2% vs. 48.7%, p0.001) in the G3N group than the G3P group. In multivariate regression analysis, G3N expression predicted a lower risk of LN metastasis (odds ratio=0.37, 95% confidence interval 0.18-0.78) after adjustment for other clinicopathological parameters. Over a median follow-up of 33 months, no association was observed between G3N and disease-free survival.The absence of G3 expression in FNA samples from PTC is associated with pathological parameters considered less aggressive than is the case for PTCs with G3 expression, including being a negative predictor of negative LN involvement. Long-term follow-up studies, however, are needed to verify whether G3N patients have lower recurrence and mortality rates.

Asians have a propensity to develop type 2 diabetes with a lower BMI than Western populations. This discrepancy may be due to differences in body fat and muscle mass for a given BMI. However, unlike adiposity, it is unclear whether muscle mass affects the risk of type 2 diabetes in Asian populations.We conducted a 2-yearly prospective assessment of 6895 participants who were free of diabetes at the baseline examination as part of the Korean Genome Epidemiology Study. The muscle mass index (MMI) was defined as the weight-adjusted appendicular skeletal muscle mass. Using Cox regression models, we evaluated the association between MMI and the risk of developing type 2 diabetes across sex-specific tertiles of MMI. Low muscle mass was defined as the sex-specific lowest tertile of MMI. Main covariates included age, sex, urban or rural residence, family history of diabetes, hypertension, smoking status, education level, monthly income, physical activity, alcohol consumption and diet. In addition, body fat mass, waist circumference and BMI were controlled as categorical variables. Obesity was defined as a BMI of ≥25 kg/mDuring a median follow-up of 9.06 years, 1336 participants developed type 2 diabetes. At baseline, the mean age was 52.1 years and the mean BMI was 24.4 kg/mLow muscle mass as defined by MMI was associated with an increased risk of type 2 diabetes, independent of general obesity, in middle-aged and older Korean adults.

Considerable evidence shows that increased serum calcium levels are associated with metabolic disorders, cardiovascular disease, and increased mortality. This study investigated whether serum calcium, within a normal range, is significantly associated with serum fibrinogen and homocysteine, markers of increased cardiovascular disease risk in nondiabetic Korean subjects. A cross-sectional analysis was performed on 1096 subjects (mean age, 55.1 ± 11.1 years; 36.1% women) undergoing a general health checkup. Serum biochemistry was analyzed including serum albumin-corrected calcium (Cac), insulin resistance (IR, using homeostasis model assessment [HOMA]), fibrinogen, and homocysteine. Compared with patients within the lowest Cac quartile, those with higher Cac levels had increased fibrinogen and homocysteine levels as well as an increased proportion of smoking, dyslipidemia, and HOMA-IR. Correlation analyses revealed linear relationships for Cac with fibrinogen and homocysteine in both genders. After adjustment for confounding factors, serum Cac was significantly associated with high fibrinogen (odds ratio [OR] for the highest vs the lowest quartile = 1.76, 95% confidence interval [CI] = 1.09–2.83, P = 0.02) and homocysteine (OR = 1.83, 95% CI = 1.07–3.11, P = 0.027). Multivariate regression models showed that Cac was linearly associated with fibrinogen (standardized β = 0.14, P

BMI, metabolic health status, and their interactions should be considered for estimating mortality risk; however, the data are controversial and unknown in Asians. We aimed to investigate this issue in Korean population. Total 323175 adults were followed-up for 96 (60–120) (median [5–95%]) months in a nationwide population-based cohort study. Participants were classified as “obese” (O) or “non-obese” (NO) using a BMI cut-off of 25 kg/m2. People who developed ≥1 metabolic disease component (hypertension, diabetes, dyslipidaemia) in the index year were considered “metabolically unhealthy” (MU), while those with none were considered “metabolically healthy” (MH). The MUNO group had a significantly higher risk of all-cause (hazard ratio, 1.28 [95% CI, 1.21–1.35]) and cardiovascular (1.88 [1.63–2.16]) mortality, whereas the MHO group had a lower mortality risk (all-cause: 0.81 [0.74–0.88]), cardiovascular: 0.73 [0.57–0.95]), compared to the MHNO group. A similar pattern was noted for cancer and other-cause mortality. Metabolically unhealthy status was associated with higher risk of all-cause and cardiovascular mortality regardless of BMI levels, and there was a dose-response relationship between the number of incident metabolic diseases and mortality risk. In conclusion, poor metabolic health status contributed more to mortality than high BMI did, in Korean adults.

The aim of the present study was to evaluate the independent predictors of coronary artery stenosis in patients with type 2 diabetes mellitus (DM) and subclinical atherosclerosis. A total of 232 patients with type 2 DM and subclinical atherosclerosis underwent multislice computed tomography coronary angiography. Subclinical atherosclerosis was determined by the carotid intima-media thickness (IMT) or carotid plaque. Multislice computed tomography coronary angiography revealed significant coronary stenosis (>50% in diameter) in 71 subjects (31%). The subjects who had significant coronary stenosis were much older and had had a longer duration of DM. In particular, the log-transformed albumin/creatinine ratio (ACR) was greater in the subjects with significant coronary stenosis compared to the subjects without significant coronary stenosis. The age- and gender-adjusted odds ratio for significant coronary stenosis increased in proportion to albuminuria with a given estimated glomerular filtration rate. The ACR as a continuous variable (odds ratio 4.167, 95% confidence interval 1.497 to 11.599) or categorical variable (ACR >30 μg/mg, odds ratio 4.619, 95% confidence interval 1.562 to 13.659) was associated with an increased risk of significant coronary stenosis, independent of conventional cardiovascular risk factors. In receiver operating characteristic analysis, the ACR had an additive effect with carotid IMT for predicting significant coronary stenosis (area under the curve 0.625 with carotid IMT; area under the curve 0.710 with carotid IMT plus ACR, p = 0.0144). In conclusion, the presence of albuminuria is an independent predictor for significant coronary stenosis in patients with type 2 DM and subclinical atherosclerosis.

Background While many studies have shown the good efficacy and safety of exenatide in patients with diabetes, limited information is available about exenatide in clinical practice in Korean populations. Therefore, this retrospective cohort study was designed to analyze the effects of exenatide on blood glucose level and body weight in Korean patients with type 2 diabetes mellitus. Methods We reviewed the records of the patients with diabetes who visited Seoul St. Mary's Hospital and for whom exenatide was prescribed from June 2009 to October 2011. After excluding subjects based on their race/ethnicity, medical history, whether or not they changed more than 2 kinds of oral hypoglycemic agents with exenatide treatment, loss to follow-up, or whether they stopped exenatide therapy within 6 months, a total of 52 subjects were included in the final analysis. Results The mean glycated hemoglobin (HbA1c) level and weight remarkably decreased from 8.5±1.7% to 6.7±1.0% (P