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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.

Background We aimed to examine the associations between the risk of decreased renal function, obesity, and weight changes in Korean type 2 diabetic patients with normal renal function. Methods Type 2 diabetic patients (n = 1060) who visited the diabetic clinic at Soonchunhyang University Bucheon Hospital between 2001 and 2007 with follow up surveys completed in 2016 to 2017 were recruited into the study. Decreased renal function was defined as an estimated glomerular filtration rate 2. Weight change was calculated between baseline and each follow-up survey. Multivariate analysis was used to evaluate the longitudinal association of baseline obesity and weight changes with the risk of decreased renal function. Results This study revealed that baseline obesity was associated with the risk of decreased renal function after adjusting for clinical variables in type 2 diabetic patients (odds ratio [OR] 1.40; 95% confidence intervals [CI] 1.08–2.04; p = 0.025). Follow-up (mean = 12 years) revealed that weight gain > 10% was associated with the risk of decreased renal function after adjusting for clinical variables in type 2 diabetic patients with normal renal function at baseline (OR 1.43; CI 1.11–2.00; p = 0.016). Weight loss was not associated with the risk of decreased renal function in type 2 diabetic patients with normal renal function at baseline. Conclusions Baseline obesity was associated with the increased risk of decreased renal function in Korean type 2 diabetic patients with normal renal function. Weight gain > 10% independently predicted the risk of decreased renal function. Large prospective studies are needed to clarify causal associations between obesity, weight change, and decreased renal function in patients with type 2 diabetes.

Background: Cardiovascular risk remains increased despite optimal low density lipoprotein cholesterol (LDL-C) level induced by intensive statin therapy. Therefore, recent guidelines recommend non-high density lipoprotein cholesterol (non-HDL-C) as a secondary target for preventing cardiovascular events. The aim of this study was to assess the efficacy and tolerability of omega-3 fatty acids (OM3-FAs) in combination with atorvastatin compared to atorvastatin alone in patients with mixed dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group, and phase III multicenter study included adults with fasting triglyceride (TG) levels ≥200 and

The only known, effective intervention for non-alcoholic fatty liver disease (NAFLD) is weight loss, and there is no approved pharmacotherapy. Recently, new hypoglycemic agents, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs), and their effects on NAFLD have received substantial interest. Herein, we review the currently available human studies regarding the effects of SGLT2 inhibitors and GLP-1RAs on NAFLD/non-alcoholic steatohepatitis in patients with type 2 diabetes mellitus, and we describe the possible mechanisms explaining the positive effects of these agents on NAFLD.

Objective:The aim of this study is to investigate the association between glucagon-to-insulin ratio and the presence of nonalcoholic fatty liver disease on ultrasonography in participants with type 2 diabetes mellitus.Research design and methods:This cross-sectional study was performed with data obtained from 172 participants with type 2 diabetes mellitus admitted to a University hospital of Korea. Participants were assessed for serum fasting and postprandial serum glucagon-to-insulin ratio and divided into tertiles. Nonalcoholic fatty liver disease was defined as ultrasonographically detected fatty liver.Results:Prevalence of nonalcoholic fatty liver disease was significantly decreased across tertile of fasting and postprandial glucagon-to-insulin ratio ( p = 0.009 for trend, p = 0.001 for trend, respectively). Lower glucagon-to-insulin ratio was significantly associated with the presence of nonalcoholic fatty liver disease even after adjustment for potential confounding variables [fasting glucagon-to-insulin ratio: odds ratio (95% confidence interval), 2.68 (1.08–6.86)], postprandial glucagon-to-insulin ratio: [2.72 (1.03–7.35)]. The participants in the lowest tertile of fasting glucagon-to-insulin ratio had higher body mass index, visceral fat thickness, subcutaneous fat thickness, homeostasis model assessment–insulin resistance and shorter duration of diabetes mellitus.Conclusion:This study suggests that lower glucagon relative insulin may be independently associated with nonalcoholic fatty liver disease in participants with type 2 diabetes.

Background This study was performed to investigate the association between the amount of alcohol consumption or binge drinking and obesity-related comorbidities in Korean men. Methods A total of 103,048 men aged 19 years or older were investigated in the 2016 Korean Community Health Survey. The participants were divided into five groups according to the standard number of alcoholic drinks consumed per week. Results Of the total participants, 20.7% were in the high alcohol consumption group, consuming more than 28 drinks per week. After adjustment for clinical factors, high alcohol consumption was significantly associated with higher odds ratios (ORs) of obesity (OR, 1.449; 95% confidence interval [CI], 1.412 to 1.591; P P P P = 0.0015) and high alcohol consumption was not associated with a higher risk of diabetes (OR, 0.945; 95% CI, 0.86 to 1.039; P = 0.0662). Among drinkers, except for social drinkers, binge drinking was significantly associated with higher risks of obesity, hypertension, diabetes, and dyslipidemia. Conclusions High alcohol consumption was associated with higher risks of obesity, hypertension, and dyslipidemia in Korean men. In contrast, high consumption was not associated with a higher risk of diabetes. In particular, binge drinkers were associated with higher risks of obesity, hypertension, diabetes, and dyslipidemia compared to non-binge drinkers.

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.

Aims Diabetic peripheral neuropathy (DPN) is one of the most common and early manifested complication in T2D. Previous reports have shown that painful sensation of diabetic peripheral neuropathy (DPN) results in sleep problems in type 2 diabetes (T2D)1, 2. However, it is not known that subtype of DPN, the painless DPN also is associated with poor sleep quality in T2D. The purpose of the current study was to investigate the association between painless DPN and poor sleep quality in T2D. Methods A total of 146 patients of T2D who did not previously diagnose with symptomatic DPN were recruited into the study. Among the patients, painless DPN was diagnosed by using the current perception threshold (CPT) test. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Results The percentage of painless DPN was significantly higher in the poor sleep quality group than the good sleep quality group (70.0% vs. 35.5%, P Conclusions The current study showed that painless DPN was associated with poor sleep quality. Future studies are required to clarify the pathophysiologic causal relationship between painless DPN and sleep quality. References 1. Gore M, Brandenburg NA, Dukes E, Hoffman DL, Tai K-S, Stacey B. Pain severity in diabetic peripheral neuropathy is associated with patient functioning, symptom levels of anxiety and depression, and sleep. Journal of pain and symptom management. 2005;30(4): 374-385. 2. Zelman DC, Brandenburg NA, Gore M. Sleep impairment in patients with painful diabetic peripheral neuropathy. Clin J Pain. 2006;22(8): 681-685.

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 This report presents the recent prevalence and comorbidities related to diabetes in Korea by analyzing the nationally representative data. Methods Using data from the Korea National Health and Nutrition Examination Survey for 2013 to 2014, the percentages and the total number of subjects over the age of 30 years with diabetes and prediabetes were estimated and applied to the National Population Census in 2014. Diagnosis of diabetes was based on fasting plasma glucose (≥126 mg/dL), current taking of antidiabetic medication, history of previous diabetes, or glycosylated hemoglobin (HbA1c) ≥6.5%. Impaired fasting glucose (IFG) was defined by fasting plasma glucose in the range of 100 to 125 mg/dL among those without diabetes. Results About 4.8 million (13.7%) Korean adults (≥30 years old) had diabetes, and about 8.3 million (24.8%) Korean adults had IFG. However, 29.3% of the subjects with diabetes are not aware of their condition. Of the subjects with diabetes, 48.6% and 54.7% were obese and hypertensive, respectively, and 31.6% had hypercholesterolemia. Although most subjects with diabetes (89.1%) were under medical treatment, and mostly being treated with oral hypoglycemic agents (80.2%), 10.8% have remained untreated. With respect to overall glycemic control, 43.5% reached the target of HbA1c

Background : Vitamin D deficiency is known to increase the incidence of metabolic syndrome. Nonalcoholic fatty liver disease is a common metabolic disease in patients with type 2 diabetes. This study evaluated nonalcoholic fatty liver disease and abdominal fat accumulation according to 25-hydroxyvitamin D status in patients with type 2 diabetes. Methods : The study comprised 302 patients with type 2 diabetes. Patients were divided into three groups based upon their 25-hydroxyvitamin D status: vitamin D deficient group (

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.

Some clinical manifestations of obesity include nonalcoholic fatty liver disease, type 2 diabetes, and cardiovascular disease. Calorie restriction may aid in weight loss in the short term. Exercise and physical activity are other means of weight loss. However, the efficacy of exercise and physical activity in weight reduction in obese populations is still unknown. In this review, we discuss the effects of exercise and physical activity in obese and overweight populations. We also discuss the effects of aerobic exercise and/or resistance training in weight loss and maintenance.

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.

Sarcopenia is more prevalent in diabetes than controls and is related with higher cardiovascular events such as critical limb ischemia and mortality in T2DM. Microvascular dysfunction in diabetes plays a crucial role in the development of diabetic complications. Skin perfusion pressure (SPP) using laser Doppler technique is valuable in the evaluation of microcirculation function and limb ischemia. Although previous study reported that sarcopenia is independently associated with diabetic foot disease and even it is regarded as a chronic complication of T2DM, no studies have examined the relationship of sarcopenia and microcirculation. The current analysis is an attempt to evaluate the undisclosed relationship of sarcopenia and skin perfusion pressure. We analyzed the data of 188 patients with T2DM performing laser Doppler technique for measuring SPP. Sarcopenia was defined low appendicular muscle mass adjusted for height (Men 50 mmHg. SPP below 50 mmHg was considered as impaired microcirculation. The mean age and SPP of total subjects were 51 years and 72 mmHg. A total of 26 patients (13.8%) were diagnosed with impaired function of microcirculation in limb on SPP. The prevalence of sarcopenia in total subjects was 8%. The prevalence of sarcopenia increased significantly in SPP ≤50 mmHg group than in SPP >50 mmHg (23% vs. 5.3%, p=0.028). Significant positive correlation was found between SPP and appendicular muscle mass adjusted for height (p=0.008). Multiple logistic regression analysis showed that patients with sarcopenia had an odds ratio of 6.1 (95% CI =1.2-31.7) for having of SPP ≤50 mmHg even after adjustment for confounding factors (p=0.032). Our results suggest that the sarcopenia is significantly associated with the presence of impaired function of microcirculation on SPP in T2DM. Disclosure C. Jung: None. D. Choi: None. C. Kim: None. J. Mok: None.

Background: Agranulocytosis is the most feared side effect of antithyroid-drug therapy. In the largest series, agranulocytosis occurred in 0.35 percent receiving methimazole. The causative antithyroid-drug should be stopped and treatment includes broad-spectrum antibiotics and granulocyte-colony stimulation factor may be needed in selected patients1. Here, we report a case of agranulocytosis relapse after the recovery of methimazole-induced agranulocytosis. Case: A 35-year-old woman was admitted to hospital by fever lasted 3 days. The patient was diagnosed hyperthyroidism 3 weeks ago, and she was taking methimazole 15mg daily. Lab finding of admission day was 370/mm3 of granulocyte count, normal C-reactive protein, 4.64ng/mL of T3, 7.66ng/dL of free T4, below 0.05uIU/dL of Thyroid-stimulating hormone. After isolated admission care including methimazole stop and follow-up of 3 days, granulocyte count was elevated to 1,190/mm3. The patient was discharged without restarting other antithyroid-drugs. 4 days later, the patient admitted again by fever and sore throat. The granulocyte count was 10/mm3 with normal range of C-reactive protein, above 6.51ng/mL of T3, above 7.77ng/dL of free T4, below 0.05uIU/dL of Thyroid-stimulating hormone. We used granulocyte-colony stimulation factor and intravenous cefepime. After 4 days, granulocyte count improved to 1,610/mm3 and fever was subsided. After recovery, total thyroidectomy was performed for hyperthyroidism. The patient is now taking levothyroxine in the outpatient clinic without further additional agranulocytosis episodes. Conclusion: We are reporting a relapse of agranulocytosis after recovery of methimazole-induced agranulocytosis. Even if the antithyroid-drug is not used again after the recovery of agranulocytosis, attention to relapse of agranulocytosis and education of the patient may be necessary. Reference: 1. David S. Cooper, M.D. (March 3, 2005). “Antithyroid drugs" New England Journal of Medicine 2005; 352:905-917

Background Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes.Methods We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18-85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR) 25-75 mL/min per 1.73 m(2) of body surface area, and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g who had received maximum labelled or tolerated renin-angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0.75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders) were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0.75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for >= 30 days) or end-stage kidney disease (eGFR = 90 days, chronic dialysis for >= 90 days, kidney transplantation, or death from kidney failure) in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials. gov, number NCT01858532.Findings Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325) or placebo group (n=1323). Median follow-up was 2.2 years (IQR 1.4-2.9). 79 (6.0%) of 1325 patients in the atrasentan group and 105 (7.9%) of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR] 0.65 [95% CI 0.49-0.88]; p=0.0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3.5%) of 1325 patients in the atrasentan group and 34 (2.6%) of 1323 patients in the placebo group (HR 1.33 [95% CI 0.85-2.07]; p=0.208). 58 (4.4%) patients in the atrasentan group and 52 (3.9%) in the placebo group died (HR 1.09 [95% CI 0.75-1.59]; p=0.65).Interpretation Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

Purpose: Metabolic disorders are known to cause poor sleep quality. However, there is not much research about the association of diabetic complications and poor sleep quality. Our aim was to find out which diabetic complications are associated with poor sleep quality in type 2 diabetes (T2D). Methods: In this cross-section study, sleep quality of 151 T2D patients were assessed by using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. PSQI score was interpreted as good sleep quality for ≤ 5 and poor sleep quality for > 5. Microvascular complications were assessed with the presence of diabetic retinopathy, diabetic polyneuropathy (DPN) and microalbuminuria. Macrovascular complications were assessed with ankle-brachial index, pulse wave velocity, and carotid intima-media thickness. Results: Fasting c-peptide, insulin, triglyceride (TG) and waist-hip ratio (WHR) were higher in the poor sleep quality group. Among the complications, the proportion of DPN was higher in the poor sleep quality group (31.7% vs. 15.2%, p=0.020). Other diabetic complications did not show a significant difference between both groups (Table). After adjustment for sex, age, usage of insulin, TG, WHR and DPN, fasting c-peptide was the only significant marker for poor sleep quality in T2D (OR = 2.207, p = 0.048). Conclusion: DPN was higher in the poor sleep quality group. Other diabetic complications showed no significant difference in both groups. Disclosure D. Choi: None. B. Kim: None. C. Jung: None. C. Kim: None. S. Kang: None. J. Mok: None.

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.

Primary empty sella syndrome is a phenomenon caused by cerebrospinal fluid filling resulting from the herniation of the subarachnoid space within the sella. The pituitary function of primary empty sella syndrome is usually normal. But sometimes this syndrome causes some degree of pituitary dysfunction associated with hypersecretion or deficiency of pituitary hormone. Central diabetes insipidus with primary empty sella syndrome is rarely reported. Furthermore, most of those cases are accompanied by other pituitary dysfunction. We report here on a 35-year-old female who suffered from polyuria, polydipsia since childhood. She was diagnosed with central diabetes insipidus with primary empty sella syndrome. She had no anterior pituitary dysfunction except mild hyperprolactinemia.

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 and Aim To quantify the differential contribution of sleep duration on fasting plasma glucose level by traditional regular daytime work and shift work in subjects without diabetes. Methods Self-reported sleep duration and work type and timing were determined in a cross-sectional sample of 9123 participants aged 20–65 years from the Korea National Health and Nutrition Examination Survey (KNHANES) 2010–2015. Those who responded that they worked between 6 am and 6 pm were classified as “traditional regular daytime workers; ”those who worked in the afternoon, at night, or in several types of shift work were classified as “shift workers.” FBG was compared between short ( 8 h) sleep duration groups according to work time. Results In the traditional daytime workers group, mean FBG level showed a U-shaped trend according to sleep duration (p = 0.027), whereas in shift workers group, FBG level was significantly decreased across sleep duration (p = 0.001). In the regular daytime workers group, short sleep duration was associated with higher FBG (B, 95% [CI]: 1.33 [0.26–2.4]), whereas after adjustment for potential confounding variables, long sleep duration significantly increased the risk of higher FBG (2.01 [0.35–3.68]). On the other hand, the reverse was true in the shift workers. Long sleep duration was significantly associated with lower FBG by both unadjusted analysis and after multivariable adjustment (−3.79 [−5.97 to −1.62], −2.19 [−4.35 to −0.03], respectively). Conclusion Our results suggest that the impact of sleep duration on FBG level differs according to work shift.

Metastasis to the primary thyroid carcinoma is extremely rare. We report here a case of colonic adenocarcinoma metastasis to medullary thyroid carcinoma in a 53-yr old man with a history of colon cancer. He showed a nodular lesion, suggesting malignancy in the thyroid gland, in a follow-up examination after colon cancer surgery. Fine needle aspiration biopsy (FNAB) of the thyroid gland showed tumor cell clusters, which was suspected to be medullary thyroid carcinoma (MTC). The patient underwent a total thyroidectomy. Using several specific immunohistochemical stains, the patient was diagnosed with colonic adenocarcinoma metastasis to MTC. To the best of our knowledge, the present patient is the first case of colonic adenocarcinoma metastasizing to MTC. Although tumor-tumor metastasis to primary thyroid carcinoma is very rare, we still should consider metastasis to the thyroid gland, when a patient with a history of other malignancy presents with a new thyroid finding. Graphical Abstract

Objective Insulin resistance (IR) is a distinct and early feature of type 2 diabetes mellitus and metabolic syndrome. IR is thought to play a vital role in cognitive impairment. We conducted this study to understand the early characteristics of cognitive dysfunctions attributable to IR. Methods This study included 85 consecutive non-diabetic elderly participants with mild cognitive impairment (MCI). IR was estimated with the homeostasis model assessment of insulin resistance (HOMA-IR). Cognitive performances were analyzed as a function of scores on the HOMA-IR. Results The group analysis those with and without IR did not show any differences in the cognitive performance although higher HOMA-IR was closely associated with lower performances in immediate recall on the Seoul Verbal Learning Test (SVLT-I) (r = −0.244, p = 0.026) and Controlled Oral Word Association Test (COWAT) (r = −0.270, p = 0.013). In subgroup analysis by APOE status, SVLT-delayed (p = 0.027) and COWAT (p = 0.016) scores were found to be significantly lower in the IR than the non-IR among those with APOE e4 allele. In multiple regression analysis, impairment on the COWAT remained significantly correlated with scores on HOMA-IR (β = −0.271, t = −2.340, p = 0.022). However, IR status was identified to interact with APOE e4 carriership toward poor performances in the COWAT (β = −0.335, t = −2.285, p = 0.026). Conclusion This study found a domain-specific impact of HOMA-IR scores on cognitive performances in non-diabetic patients with MCI. This association was profound only in APOE e4carriers. Copyright © 2014 John Wiley & Sons, Ltd.

To examine the impact of hemoglobin A1c (HbA1c) criterion on the diagnosis of prediabetes in Koreans, we analyzed nationally representative cross-sectional data of 5,845 Korean adults aged ≥20 years from the Fifth Korea National Health and Nutrition Examination Survey 2011. Standardized prevalence rates of prediabetes in Korean adults by fasting plasma glucose (FPG; 5.6–6.9 mmol/L), HbA1c (5.7–6.4% [39–46 mmol/mol]), and combined criteria were 16.9, 28.4 and 33.8%, respectively. Among the subjects with prediabetes, 16% met FPG criteria only, 55% met HbA1c criteria only and 29% met both criteria. Prediabetic subjects who met HbA1c criteria only were significantly older, more likely to be women, and had lower hemoglobin and serum iron concentrations, whereas those who met FPG criteria only had higher body mass index, waist circumference, systolic and diastolic blood pressure. In conclusion, introduction of HbA1c criterion markedly increased the prevalence of prediabetes in Koreans, and the two criteria identified people with different characteristics.

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.