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Background: To evaluate the safety and effectiveness of empagliflozin in routine clinical settings, we collected and assessed the clinical profiles of Korean patients with type 2 diabetes mellitus.Methods: This was a post-marketing surveillance study of empagliflozin 10 and 25 mg. Information on adverse events and adverse drug reactions (ADRs) was collected as safety data sets. Available effectiveness outcomes, including glycosylated hemoglobin (HbA1c) level, fasting plasma glucose, body weight, and blood pressure, were assessed.Results: The incidence rate of ADRs was 5.14% in the safety dataset (n=3,231). Pollakiuria, pruritis genital, and weight loss were the most common ADRs. ADRs of special interest accounted for only 1.18%, and there were no serious events that led to mortality or hospitalization. In the effectiveness data set (n=2,567), empagliflozin significantly reduced the mean HbA1c level and body weight during the study period by –0.68%±1.39% and –1.91±3.37 kg (both P

Obesity and obesity-associated morbidity continues to be a major public health issue worldwide. Dementia is also a major health concern in aging societies and its prevalence has increased rapidly. Many epidemiologic studies have shown an association between obesity and cognitive impairment, but this relationship is not as well established as other comorbidities. Conflicting results related to the age and sex of participants, and the methodology used to define obesity and dementia may account for the uncertainty in whether obesity is a modifiable risk factor for dementia. More recently, sarcopenia and sarcopenic obesity have been reported to be associated with cognitive impairment. In addition, new mediators such as the muscle-myokine-brain axis and gut-microbiota-brain axis have been suggested and are attracting interest. In this review, we summarize recent evidence on the link between obesity and cognitive impairment, especially dementia. In particular, we focus on various metrics of obesity, from body mass index to sarcopenia and sarcopenic obesity.

Diabetes mellitus and cognitive dysfunction are highly prevalent in the aging population. In the aging society, clinicians will be increasingly tasked with managing elderly patients who have both cognitive dysfunction and diabetes. A growing number of epidemiological and clinical studies confirmed that diabetes is associated with an increase in the risk of cognitive dysfunction and dementia. Cognitive dysfunction is of particular importance because it is associated with poor self-management ability, poor diabetes management with more frequent severe hypoglycemic episodes, and increased risk of cardiovascular morbidity and mortality. Current diabetes guidelines recommend screening for cognitive dysfunction in older and high-risk patients and providing individualized guidance for patients with cognitive dysfunction. Nonetheless, there is limited awareness among clinicians regarding this subject compared to other diabetic micro- and macrovascular complications. Recently, there has been increasing understanding in this field through multimodal neuroimaging and biomarkers for early detection of cognitive dysfunction in diabetes. In addition, new agents such as glucagon-like peptide 1 receptor agonists showed promising protective effects against cognitive dysfunction and dementia in patients with type 2 diabetes. In this review, we summarize the relationship between diabetes and cognitive dysfunction, especially dementia, and some contributing factors and pathogenesis of dementia in diabetes. We also review how anti-diabetic medications may influence cognitive dysfunction and clinical management guidance.

Two European cohort studies have suggested that Graves’ disease is associated with the development of Parkinson’s disease, although the results were limited and controversial. We evaluated whether patients with Graves’ disease had an increased risk of developing Parkinson’s disease according to treatment modality. We included 65 380 Graves’ disease patients and 326 900 healthy controls matched according to age and sex, using the Korean National Health Insurance database. The primary outcome was the incidences of Parkinson’s disease amongst Graves’ disease patients and controls. Subgroup analyses of Graves’ disease patients were performed according to anti-thyroid drug treatment, radioactive iodine therapy and surgery. The cumulative dose and duration values of anti-thyroid drug were calculated for each patient and categorized into highest, middle and lowest tertiles. Amongst 65 380 Graves’ disease patients, 301 Parkinson’s disease cases were diagnosed during 453 654 person-years of follow-up. Relative to the controls, and regardless of age, sex or comorbidities, the Graves’ disease patients had a 33% higher risk of developing Parkinson’s disease (hazard ratio: 1.33, 95% confidence interval: 1.17–1.51). Most Graves’ disease patients (96%) had received medical therapy, and increased risks of Parkinson’s disease were observed in the various subgroups for cumulative dose and treatment duration. This study revealed that Graves’ disease was an independent risk factor for developing Parkinson’s disease, and that the risk remained elevated regardless of demographic factors or treatment duration/dosage of the anti-thyroid drug. Clinicians should be aware that Graves’ disease patients have an increased risk of developing Parkinson’s disease, even though Graves’ disease patients are often relatively young.

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.

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.

Background This study aimed to investigate the recent prevalence, management, and comorbidities of diabetes among Korean adults aged ≥30 years by analyzing nationally representative data. Methods This study used data from the Korea National Health and Nutrition Examination Survey from 2016 to 2018, and the percentage and total number of people ≥30 years of age with diabetes and impaired fasting glucose (IFG) were estimated. Results In 2018, 13.8% of Korean adults aged ≥30 years had diabetes, and adults aged ≥65 years showed a prevalence rate of 28%. The prevalence of IFG was 26.9% in adults aged ≥30 years. From 2016 to 2018, 35% of the subjects with diabetes were not aware of their condition. Regarding comorbidities, 53.2% and 61.3% were obese and hypertensive, respectively, and 72% had hypercholesterolemia as defined by low-density lipoprotein cholesterol (LDL-C) ≥100 mg/dL in people with diabetes. Of the subjects with diabetes, 43.7% had both hypertension and hypercholesterolemia. With regard to glycemic control, only 28.3% reached the target level of

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 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.

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 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 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.

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.

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.

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

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

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

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

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

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

Total thyroidectomy can be accomplished in one of two ways. The first is an open conventional approach, and the other is an endoscopic unilateral axillobreast approach (UABA). However, the two have not been thoroughly compared. In the study described herein, we compare the technical feasibility, safety, and surgical completeness of open versus endoscopic total thyroidectomy procedures. A total of 152 patients who underwent open (n = 102) or endoscopic (n = 50) total thyroidectomy via UABA for papillary microcarcinoma from January to December 2011 were enrolled in this study. Data were collected prospectively after obtaining informed consent. We analyzed the clinical characteristics, pathologic results, postoperative thyroglobulin (Tg) levels, and results of radioactive iodine treatment between the two groups. We conclude that endoscopic thyroidectomy resulted in a younger age, lower body mass index, longer operation time and drain maintenance, and larger drain amount. There were no significant differences with respect to gender, hospital stay, tumor size, time for central compartment neck dissection, number of harvested ipsilateral lymph nodes, or bleeding amount between groups. The proportion of extrathyroidal extension, multifocality, and bilaterality did not differ, and the surgical complication rate was similar. In addition, the postoperative stimulated and non-stimulated Tg levels did not differ significantly, nor did the thyroid bed/brain iodine uptake ratio. Based on our results, endoscopic total thyroidectomy via UABA is technically feasible and has comparable surgical completeness to open total thyroidectomy for papillary microcarcinoma within 1 cm.