Association between exercise habits and incident type 2 diabetes mellitus in patients with thyroid cancer: nationwide population-based study.

BACKGROUND: We investigated the association between exercise habits before or after thyroidectomy and incident type 2 diabetes mellitus (T2DM) in patients with thyroid cancer. METHODS: An observational cohort study of 69,526 thyroid cancer patients who underwent thyroidectomy for the treatment of thyroid cancer between 2010 and 2016 was performed using the Korean National Health Information Database. Regular exercise was defined as mid-term or vigorous exercise at least 1 day in a week based on a self-reported questionnaire. Patients were divided into four groups according to exercise habits before and after thyroidectomy: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. RESULTS: During a median follow-up of 4.5 years, 2,720 (3.91%) patients developed T2DM. The incidence of T2DM per 1,000 person years was lower in patients who performed regular exercise before or after thyroidectomy than in persistent non-exercisers (10.77 in persistent non-exerciser group, 8.28 in new exerciser group, 8.59 in exercise dropout group, and 7.61 in exercise maintainer group). Compared with the persistent non-exerciser group, the new exerciser group (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.78-0.97), the exercise dropout group (HR 0.81, 95% CI 0.72-0.91), and the exercise maintainer group (HR 0.84, 95% CI 0.76-0.93) had lower risks of incident T2DM. Exercising < 1,500 MET-minutes/week in the exercise maintainer group was associated with a lower risk of incident T2DM compared with persistent non-exercisers (< 500: HR 0.80, 95% CI 0.67-0.96, P = 0.002; 500 to < 1,000: HR 0.81, 95% CI 0.71-0.93, P < 0.001; 1,000 to < 1,500: HR 0.81, 95% CI 0.69-0.94, P < 0.001). CONCLUSIONS: Regular exercise before or after thyroidectomy was associated with a lower risk of incident T2DM in patients with thyroid cancer.

The association of diabetes duration and glycemic control with depression in elderly men with type 2 diabetes mellitus.

BACKGROUND: The prevalence of depression and type 2 diabetes mellitus (T2DM) are increasing in the elderly and are reportedly related to each other. We evaluated the relationship between T2DM-related factors and the degree of depression in elderly patients with T2DM based on gender. MATERIALS AND METHODS: A total of 155 patients with T2DM (56 males and 99 females aged ≥ 65 years) from seven hospitals were included in the study. To assess the status of depressive symptoms, the short form of the Geriatric Depression Scale-Korean version (SGDS-K) was used. We evaluated DM-related factors, such as T2DM duration, hemoglobin A1c (HbA1c) levels, and T2DM complications, as well as other possible factors that could affect depression, such as cognitive function, physical function, education level, and other personal factors. RESULTS: Mean age of the participants was 71.3 years with a mean HbA1c level of 7.6%. Males in the good glycemic control group (HbA1c <7%) showed lower SGDS-K scores compared to those in the poor glycemic control group, and the mean SGDS-K score was higher in the group with a longer duration of DM (M10 years); however, no difference was observed in females. Males and females with microvascular and macrovascular complications tended to have higher SGDS-K scores than participants with no microvascular or macrovascular complications. A multiple linear regression analysis revealed that DM duration and HbA1c level were independently associated with SGDS-K scores in males. CONCLUSION: Greater depression was associated with poorer glycemic control and a longer duration of DM in elderly males with T2DM.

The association between non-alcoholic fatty liver disease and carotid atherosclerosis in subjects with within-reference range alanine aminotransferase levels.

Our aim was to investigate whether the evaluation of non-alcoholic fatty liver disease (NAFLD) by ultrasound provides additional benefit in assessing carotid atherosclerotic burden in subjects with alanine aminotransferase (ALT) concentrations within the reference range. This was a cross-sectional analysis of 769 healthy individuals (326 men and 443 women) with an ALT concentration ≤ 40 IU/L and alcohol consumption < 140 g/week. Mean carotid artery intima-media thickness (C-IMT) was measured using ultrasound. NAFLD was defined as a mild or greater degree of hepatic steatosis on ultrasound. Although all subjects had an ALT concentration within the reference range, the prevalence of NAFLD increased with increasing quartiles of ALT concentration (27.1%, 40.0%, 54.7%, 75.3% in men, P for trend < 0.001; 22.0%, 34.4%, 35.7%, 55.0% in women, P for trend < 0.001). In the 3rd and 4th quartiles of ALT concentration, women with NAFLD had a significantly higher C-IMT than those without NAFLD (0.671±0.019 mm vs. 0.742±0.025 mm, P=0.023 in Q3; 0.651±0.023 mm vs. 0.737±0.021 mm, P=0.005 in Q4). These differences remained significant even after adjusting for a broad spectrum of potential confounders. In contrast, although men with NAFLD tended to have a higher C-IMT than those without NAFLD in each quartile, these differences were not statistically significant. Women with an upper normal range ALT concentration showed increased C-IMT only when they had NAFLD. Therefore, in women with an elevated ALT level within the reference range, further evaluation for NAFLD, such as liver ultrasound, could potentially identify those patients at high risk for cardiovascular disease.

Different Molecular Phenotypes of Progression in BRAF- and RAS-Like Papillary Thyroid Carcinoma.

BACKGRUOUND: Papillary thyroid carcinoma (PTC) can be classified into two distinct molecular subtypes, BRAF-like (BL) and RASlike (RL). However, the molecular characteristics of each subtype according to clinicopathological factors have not yet been determined. We aimed to investigate the gene signatures and tumor microenvironment according to clinicopathological factors, and to identify the mechanism of progression in BL-PTCs and RL-PTCs. METHODS: We analyzed RNA sequencing data and corresponding clinicopathological information of 503 patients with PTC from The Cancer Genome Atlas database. We performed differentially expressed gene (DEG), Gene Ontology, and molecular pathway enrichment analyses according to clinicopathological factors in each molecular subtype. EcoTyper and CIBERSORTx were used to deconvolve the tumor cell types and their surrounding microenvironment. RESULTS: Even for the same clinicopathological factors, overlapping DEGs between the two molecular subtypes were uncommon, indicating that BL-PTCs and RL-PTCs have different progression mechanisms. Genes related to the extracellular matrix were commonly upregulated in BL-PTCs with aggressive clinicopathological factors, such as old age (≥55 years), presence of extrathyroidal extension, lymph node metastasis, advanced tumor-node-metastasis (TNM) stage, and high metastasis-age-completeness of resection- invasion-size (MACIS) scores (≥6). Furthermore, in the deconvolution analysis of tumor microenvironment, cancer-associated fibroblasts were significantly enriched. In contrast, in RL-PTCs, downregulation of immune response and immunoglobulin-related genes was significantly associated with aggressive characteristics, even after adjusting for thyroiditis status. CONCLUSION: The molecular phenotypes of cancer progression differed between BL-PTC and RL-PTC. In particular, extracellular matrix and cancer-associated fibroblasts, which constitute the tumor microenvironment, would play an important role in the progression of BL-PTC that accounts for the majority of advanced PTCs.

Crystal structure of LeuD from Methanococcus jannaschii.

3-Isopropylmalate/citramalate (IPM) isomerase catalyzes the second step in the leucine biosynthesis pathway. IPM isomerase from Methanococcus jannaschii is a complex protein consisting of a large (MjLeuC) and a small subunit (MjLeuD). It has broad substrate specificity, unlike other bacterial IPM isomerases. In order to understand the reasons for this broad substrate specificity, we determined the crystal structure of MjLeuD at a resolution of 2.0 Å. The asymmetric unit contained 6 molecules of LeuD, including three homodimers. The overall structure had a ß/ß/α sandwich-fold consisting of 8 α-helices and 7 ß-strands. The C-terminal helix, which is important in homodimer formation, showed conformational differences between two homodimer forms of MjLeuD. In addition, we identified a hydrophobic residue (Val28) near the substrate recognition region that may explain the broad substrate specificity of IPM isomerase. Therefore, we suggest that LeuD proteins can be divided into 2 subfamilies, LeuD subfamilies 1 and 2, which show differences in overall structure and in the substrate recognition region.

Impaired colony-forming capacity of circulating endothelial progenitor cells in patients with emphysema.

Chronic obstructive pulmonary disease (COPD) is classified into emphysema and chronic bronchitis, which are thought to result from different pathophysiological pathways. Smoking-induced lung parenchymal destruction and inadequate repair are involved in the pathogenesis of emphysema. In addition, decreased expression of vascular endothelial growth factor and increased endothelial cell apoptosis in the lung may participate in emphysema pathogenesis. As stem cells, circulating endothelial progenitor cells (EPCs) may play a key role in the maintenance of vascular integrity by replacing and repairing the damaged endothelial cells in the tissues. To determine whether the lack of appropriate repair by circulating EPCs in cases of smoking-induced endothelial cell injury participates in emphysema pathogenesis, we determined the association between the colony-forming or migratory capacity of circulating EPCs and the presence of emphysema in 51 patients with COPD. The patients were divided into emphysema (n = 23) and non-emphysema groups (n = 28) based on high-resolution computed tomography. Twenty-two smokers with normal lung function and 14 normal non-smokers served as controls. Circulating EPCs isolated from patients with emphysema showed significantly lower colony-forming units (CFUs) than those from patients with non-emphysema group, smokers with normal lung function, and normal non-smokers. EPCs from patients with emphysema showed significantly lower migratory capacity than those from normal non-smoking controls (p < 0.05). On multivariate analysis, the EPC-CFU was independently associated with emphysema (OR 0.944, 95% CI = 0.903-0.987, p = 0.011). Thus, impaired functions of circulating EPCs may contribute to the development of emphysema.

Postprandial Free Fatty Acids at Mid-Pregnancy Increase the Risk of Large-for-Gestational-Age Newborns in Women with Gestational Diabetes Mellitus.

BACKGROUND: To investigate the association between free fatty acid (FFA) level at mid-pregnancy and large-for-gestational-age (LGA) newborns in women with gestational diabetes mellitus (GDM). METHODS: We enrolled 710 pregnant women diagnosed with GDM from February 2009 to October 2016. GDM was diagnosed by a 'two-step' approach with Carpenter and Coustan criteria. We measured plasma lipid profiles including fasting and 2-hour postprandial FFA (2h-FFA) levels at mid-pregnancy. LGA was defined if birthweights of newborns were above the 90th percentile for their gestational age. RESULTS: Mean age of pregnant women in this study was 33.1 years. Mean pre-pregnancy body mass index (BMI) was 22.4 kg/m2. The prevalence of LGA was 8.3% (n=59). Levels of 2h-FFA were higher in women who delivered LGA newborns than in those who delivered non-LGA newborns (416.7 µEq/L vs. 352.5 µEq/L, P=0.006). However, fasting FFA was not significantly different between the two groups. The prevalence of delivering LGA newborns was increased with increasing tertile of 2h-FFA (T1, 4.3%; T2, 9.8%; T3, 10.7%; P for trend <0.05). After adjustment for maternal age, pre-pregnancy BMI, and fasting plasma glucose, the highest tertile of 2h-FFA was 2.38 times (95% confidence interval, 1.11 to 5.13) more likely to have LGA newborns than the lowest tertile. However, there was no significant difference between groups according to fasting FFA tertiles. CONCLUSION: In women with GDM, a high 2h-FFA level (but not fasting FFA) at mid-pregnancy is associated with an increasing risk of delivering LGA newborns.

FGM-based remote intervention for adults with type 1 diabetes: The FRIEND randomized clinical trial.

Background: The use of flash glucose monitoring (FGM) in conjunction with proper education has been reported to improve glycemic control in people with diabetes on insulin therapy. However, there are still few randomized controlled trials on the educational effect, and an ideal educational model has not been established. This study aimed to estimate the efficacy of remote intervention for glycemic control in adults with type 1 diabetes using FGM. Methods: In this single-center, randomized controlled trial, we enrolled adults with type 1 diabetes (HbA1c ≥7.0%). The participants were randomly assigned (1:1) to either FGM use with remote intervention (intervention group) or FGM use only (control group). Changes in glycemic outcomes such as HbA1c levels and continuous glucose monitoring metrics were evaluated at 12 weeks. Results: Among 36 randomized participants (mean age, 44.3 years; mean baseline HbA1c, 8.9%), 34 completed the study. The remote intervention did not significantly reduce HbA1c levels. FGM use significantly improved HbA1c levels by -1.4% and -0.8% in both groups with and without remote intervention, respectively (P=0.003 and P=0.004, respectively). However, the intervention group showed significant increases in time with glucose in the range of 70-180 mg/dL (TIR; from 49.8% to 60.9%, P=0.001) and significant decreases in time with hyperglycemia (P=0.002) and mean glucose (P=0.017), but the control group did not. Moreover, the TIR (P=0.019), time with hyperglycemia >250 mg/dL (P=0.019), and coefficient of variation (P=0.018) were significantly improved in the intervention group compared to the control group. In particular, the CGM metrics improved gradually as the remote intervention was repeated. Furthermore, the intervention group reported higher treatment satisfaction (P=0.016). Conclusions: Ongoing, personalized education during FGM use may lead to amelioration of glycemic control in adults with type 1 diabetes, even remotely. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04936633, identifier NCT04936633.

Umbilical Cord-Mesenchymal Stem Cell-Conditioned Medium Improves Insulin Resistance in C2C12 Cell.

Background: Umbilical cord-mesenchymal stem cell-conditioned medium (UC-MSC-CM) has emerged as a promising cell-free therapy. The aim of this study was to explore the therapeutic effects of UC-MSC-CM on insulin resistance in C2C12 cell. Methods: Insulin resistance was induced by palmitate. Effects of UC-MSC-CM on insulin resistance were evaluated using glucose uptake, glucose transporter type 4 (GLUT4) translocation, the insulin-signaling pathway, and mitochondrial contents and functions in C2C12 cell. Results: Glucose uptake was improved by UC-MSC-CM. UC-MSC-CM treatment increased only in membranous GLUT4 expression, not in cytosolic GLUT4 expression. It restored the insulin-signaling pathway in insulin receptor substrate 1 and protein kinase B. Mitochondrial contents evaluated by mitochondrial transcription factor A, mitochondrial DNA copy number, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were increased by UC-MSC-CM. In addition, UC-MSC-CM significantly decreased mitochondrial reactive oxygen species and increased fatty acid oxidation and mitochondrial membrane potential. There was no improvement in adenosine triphosphate (ATP) contents, but ATP synthesis was improved by UC-MSC-CM. Cytokine and active factor analysis of UC-MSC-CM showed that it contained many regulators inhibiting insulin resistance. Conclusion: UC-MSC-CM improves insulin resistance with multiple mechanisms in C2C12 cell.

Vitamin D Deficiency at Mid-Pregnancy Is Associated with a Higher Risk of Postpartum Glucose Intolerance in Women with Gestational Diabetes Mellitus.

BACKGROUND: To evaluate the association between serum 25-hydroxyvitamin D (25(OH)D) at mid-pregnancy and postpartum glucose intolerance in women with gestational diabetes mellitus (GDM). METHODS: We enrolled 348 pregnant women diagnosed with GDM from August 2012 to October 2016. We measured serum 25(OH)D levels at mid-pregnancy and carried out a 75-g oral glucose tolerance test at 6 to 12 weeks after delivery. Vitamin D deficiency was defined as serum 25(OH)D <20 ng/mL. RESULTS: The prevalence of vitamin D deficiency was 76.7% (n=267). Women with vitamin D deficiency had a higher prevalence of postpartum glucose intolerance than did those without vitamin D deficiency (48.7% vs. 32.1%, P=0.011). Serum 25(OH)D level was negatively correlated with hemoglobin A1c at antepartum and postpartum period (antepartum: r=-0.186, P=0.001; postpartum: r=-0.129, P=0.047). Homeostasis model assessment of ß-cell function was positively correlated with serum 25(OH)D level only postpartum (r=0.138, P=0.035). The risk of postpartum glucose intolerance was 2.00 times (95% confidence interval, 1.13 to 3.55) higher in women with vitamin D deficiency than in those without vitamin D deficiency (P=0.018). CONCLUSION: In women with GDM, vitamin D deficiency at mid-pregnancy is associated with an elevated risk of postpartum glucose intolerance.

Regression of the increased common carotid artery-intima media thickness in subclinical hypothyroidism after thyroid hormone replacement.

The association between subclinical hypothyroidism and cardiovascular disease and the beneficial effect of levothyroxine replacement in subclinical hypothyroidism are still under debate. The present study was designed to determine whether subclinical hypothyroidism is associated with an increase in the intima-media thickness of the common carotid artery (C-IMT) and whether thyroid hormone replacement can reverse this change in the C-IMT. Patients with newly-diagnosed subclinical (n=36) and overt (n=40) hypothyroidism and healthy euthyroid individuals (n=32) participated in this study. All the patients were examined for clinical characteristics, and the serum lipid levels and the C-IMT were measured. Patients with subclinical hypothyroidism had a C-IMT measurement after 18 months of levothyroxine replacement. There were meaningful differences in total cholesterol and LDL-cholesterol levels between patients with subclinical hypothyroidism and euthyroidism. The subjects with subclinical and overt hypothyroidism had a greater C-IMT compared with euthyroid controls (0.66+/- 0.10 and 0.70+/- 0.11 vs. 0.57+/- 0.08 mm, respectively; P < 0.05). After 12 months of euthyroidism, 28 of 36 patients with subclinical hypothyroidism completed the follow-up study. Thyroid hormone replacement significantly decreased the C-IMT (0.67+/- 0.11 to 0.60+/- 0.10 mm; P = 0.021) and improved the lipid profile. Based on multiple regression analysis, the decrement in LDL-cholesterol was independently associated with the regression of the C-IMT. Subclinical hypothyroidism was closely related to an increased C-IMT. Thyroid hormone replacement resulted in regression of the increased C-IMT, which was attributed to the improvement in the lipid profile.

Hyperleptinemia as a robust risk factor of coronary artery disease and metabolic syndrome in type 2 diabetic patients.

Leptin has been linked to adiposity, insulin resistance, and coronary artery disease (CAD). We examined whether the leptin concentrations are associated with the risk of CAD and metabolic syndrome (MS). The plasma leptin concentrations were measured in 556 diabetic patients (341 men and 215 women). The odds ratio (OR) of CAD and MS were increased on moving from the lowest quartile (Q1) of leptin concentration to the highest quartile (Q4) and remained significant after adjusting for age, sex, BMI, concentrations of total cholesterol, triglyceride, or high-sensitivity C-reactive protein (hsCRP), and treatment modalities for hyperglycemia. The frequency of CAD was highest in the insulin resistant group (Q4 of homeostasis model assessment-insulin resistance index [HOMA-IR]) at Q4 of leptin concentration (34.5%), compared with that of Q4 of leptin (26.4%) or HOMA-IR (21.9%). In multivariate analysis, plasma leptin concentration was identified as the most significantly independent predictor for CAD (OR 10.24, 95% CI 3.01 to 45.05). Other variables with associated with CAD were age, sex, hypertension, low-HDL cholesterolemia, and hsCRP. In conclusion, hyperleptinemia might be an independent risk factor for CAD and MS in diabetic subjects. And the simultaneous measurement of insulin resistance and leptin concentration might be helpful for screening subjects with a high-risk of CAD.

Higher Prevalence and Progression Rate of Chronic Kidney Disease in Elderly Patients with Type 2 Diabetes Mellitus.

BACKGROUND: To evaluate the prevalence of chronic kidney disease (CKD) and progression rate to CKD in elderly patients with type 2 diabetes mellitus (T2DM). METHODS: We investigated the medical records of 190 elderly patients (65 years or older) with T2DM from 2005 to 2011 in 6-month increments. Mean follow-up duration was 64.5 months. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² and/or the presence of albuminuria. RESULTS: The mean age was 70.4 years and mean diabetes duration was 10.6 years. Among all the participants, 113 patients (59.5%) had CKD. The eGFR was significantly decreased between baseline (65.7±15.0 mL/min/1.73 m²) and the end of follow-up (52.7±17.5 mL/min/1.73 m², P<0.001). At the end of follow-up, the prevalence of eGFR <60 mL/min/1.73 m² had increased by 61.6% (at baseline, 44.2%). Furthermore, in patients with eGFR ≥60 mL/min/1.73 m², the progression rate to more than CKD stage 3 was 39.6% at the end of follow-up; 30.2% of elderly diabetic patients had progressed to albuminuria from normoalbuminuria. Kaplan-Meier analysis showed that the time interval to worsening nephropathy was significantly shorter in elderly patients with diabetes duration ≥10 years than in those with diabetes duration <5 years (P=0.018). CONCLUSION: CKD was commonly observed in older patients with T2DM, and the progression rate to CKD is also high. Consequently, it is important to identify and manage CKD as early as possible in elderly patients with T2DM, especially in those with diabetes duration ≥10 years.

Higher Prevalence and Progression Rate of Chronic Kidney Disease in Elderly Patients with Type 2 Diabetes Mellitus.

BACKGROUND: To evaluate the prevalence of chronic kidney disease (CKD) and progression rate to CKD in elderly patients with type 2 diabetes mellitus (T2DM). METHODS: We investigated the medical records of 190 elderly patients (65 years or older) with T2DM from 2005 to 2011 in 6-month increments. Mean follow-up duration was 64.5 months. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² and/or the presence of albuminuria. RESULTS: The mean age was 70.4 years and mean diabetes duration was 10.6 years. Among all the participants, 113 patients (59.5%) had CKD. The eGFR was significantly decreased between baseline (65.7±15.0 mL/min/1.73 m²) and the end of follow-up (52.7±17.5 mL/min/1.73 m², P<0.001). At the end of follow-up, the prevalence of eGFR <60 mL/min/1.73 m² had increased by 61.6% (at baseline, 44.2%). Furthermore, in patients with eGFR ≥60 mL/min/1.73 m², the progression rate to more than CKD stage 3 was 39.6% at the end of follow-up; 30.2% of elderly diabetic patients had progressed to albuminuria from normoalbuminuria. Kaplan-Meier analysis showed that the time interval to worsening nephropathy was significantly shorter in elderly patients with diabetes duration ≥10 years than in those with diabetes duration <5 years (P=0.018). CONCLUSION: CKD was commonly observed in older patients with T2DM, and the progression rate to CKD is also high. Consequently, it is important to identify and manage CKD as early as possible in elderly patients with T2DM, especially in those with diabetes duration ≥10 years.

The increase in abdominal subcutaneous fat depot is an independent factor to determine the glycemic control after rosiglitazone treatment.

OBJECTIVE: The goal was to investigate the interrelationships between the hypoglycemic effects of rosiglitazone and the changes in the regional adiposity of type 2 diabetic patients. DESIGN AND METHODS: We added rosiglitazone (4 mg/day) to 173 diabetic patients (111 males and 62 females) already taking a stable dose of conventional antidiabetic medications except for thiazolidinediones. The abdominal fat distribution was assessed by ultrasonography at baseline and 12 weeks later. Using ultrasonographic images, the s.c. and visceral fat thickness (SFT and VFT respectively) were measured. RESULTS: Rosiglitazone treatment for 3 months improved the glycemic control. However, the response to rosiglitazone was no more than 36.4%; the deterioration of the glycemic control was found in 16.8% of subjects. In addition, rosiglitazone treatment significantly increased the body fat mass, especially the s.c. fat. However that did not alter the visceral fat content. The percentage changes in fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) concentrations after treatment were inversely correlated with the increase in SFT (r=-0.327 and -0.353, P<0.001 respectively) and/or body weight (r=-0.316 and -0.327, P<0.001 respectively). Multiple regression analysis revealed that the improvement in the FPG after rosiglitazone treatment was correlated with the baseline FPG (P<0.001) and the change in the SFT (P=0.019), and the reduction in the HbA1c was related with the baseline FPG (P=0.003) and HbA1c (P<0.001) and the changes in the SFT (P=0.010) or VFT (P=0.013). CONCLUSIONS: The increase in the s.c. fat depot after rosiglitazone treatment may be an independent factor that determines the hypoglycemic efficacy.

Association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and susceptibility to Graves' ophthalmopathy.

The pathogenesis of Graves' ophthalmopathy (GO) remains to be entirely elucidated. The present study aimed to determine the association between phenotypic expression of the MTHFR gene and susceptibility to GO in patients with Graves' disease (GD). A prospective case­controlled study was conducted with 122 patients with GD and GO (n=72) or without GO (n=50) and 100 healthy controls in South Korea. Patient history, including smoking, nutritional status, thyroid function and antithyroid antibodies were investigated and clinical activity score, VISA classification (which includes vision, inflammation, strabismus and appearance/exposure) and orbit computed tomography were evaluated. Fasting plasma total homocysteine (tHcy) concentration was measured, and genotype analysis of the MTHFR gene was conducted. The TT homozygous genotype was associated with a two­fold increased risk of GO [adjusted odds ratio (AOR), 2.19; 95% confidence interval (CI), 0.78­6.14]. However, this result was not significant. The TT genotype significantly increased the risk of GO compared with that in healthy controls (AOR, 2.92; 95% CI, 1.11­7.65). The MTHFR 677CT/1298AA genotype decreased the risk of GO in patients with GD (AOR, 0.26; 95% CI, 0.08­0.91). tHcy levels in patients with GD without GO were significantly higher than in patients with GO, however, they were within the normal limit. The current study identified an association between MTHFR polymorphisms and GO. These results will aid understanding of the pathogenesis of GO and facilitate development of genetic therapeutic strategies.

Reappraisal of waist circumference cutoff value according to general obesity.

BACKGROUND: Current criterion of waist circumference (WC) for abdominal obesity is not enough to demonstrate characteristics of obese and non-obese populations defined by BMI. The aim of this study was to redefine the cutoff values of WC according to general obesity (BMI ≥ 25 kg/m(2)). METHODS: The receiver operating characteristic curve analysis was performed to determine cutoff values of WC for predicting atherosclerosis according to BMI in 1,063 non-diabetic subjects. To validate this new criterion, diabetic patients (n = 3,690) were divided into three groups based on the current (WC of 90/80 cm for men/women) and new cutoff values of WC: 1) group with WC below the lowest value of two criteria; 2) intermediate group defined as having a WC between them; and 3) group with WC more than the highest value of them. RESULTS: The new cutoff values of WC for predicting atherosclerosis in non-diabetic subjects were 84/76 cm for non-obese men/women, and 93/87 cm for obese men/women, respectively. Of non-obese diabetic patients, the intermediate group (WC 84 ~ 90/76 ~ 80 cm for men/women) was more insulin resistant and showed elevated odds ratio (OR) for having 2 or more metabolic risk factors compared to group with WC below 84/76 cm for men/women [OR 2.48 (95 % CI 1.89-3.25) in men, 2.01 (95% CI 1.45-2.78) in women]. In contrast, among obese diabetic patients, insulin resistance and the likelihood of having 2 or more metabolic risk factors were not different from the intermediate group (WC 90 ~ 93/80 ~ 87 cm for men/women) and group with WC below 90/80 cm for men/women. CONCLUSIONS: The current universal cutoff values of WC may under- or over-estimate the metabolic risks of intermediate groups. Therefore, the WC criteria for abdominal obesity should be applied differently depending on the BMI.

Effects of pentoxifylline on proteinuria and glucose control in patients with type 2 diabetes: a prospective randomized double-blind multicenter study.

BACKGROUND: Pentoxifylline is a methylxanthine derivative with significant anti-inflammatory, anti-fibrotic, and anti-proliferative properties. Studies have shown that pentoxifylline may have renoprotective effects in patients with diabetic nephropathy. However, most of these studies were limited by small sample sizes. Therefore, we investigated whether pentoxifylline could reduce proteinuria in patients with diabetic nephropathy and residual proteinuria who received an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB). We also studied the effects of pentoxifylline on glycemic control, insulin resistance, and inflammatory parameters. METHODS: This was a prospective, randomized double-blind, placebo-controlled, multi-center study. A total of 174 patients with type 2 diabetes and albuminuria (>30 mg/g of creatinine) who were taking the recommended dosage of ACEI or ARB for > 6 months and receiving conventional therapy for diabetes were randomly assigned to receive pentoxifylline (1200 mg, daily; n = 87) or a placebo (n = 87) for 6 months. The endpoints were the effects of pentoxifylline on proteinuria, renal function, glucose control, and inflammatory parameters. RESULTS: The percentage changes in proteinuria from baseline in the pentoxifylline and placebo groups were a decrease of 23 % and 4 %, respectively (p = 0.012). In addition, significant reductions in fasting plasma glucose, glycated hemoglobin, and insulin resistance according to the homeostasis model assessment were observed in the pentoxifylline group compared to those in the placebo group. However there was no significant difference in serum tumor necrosis factor (TNF)-α between the groups. CONCLUSIONS: Pentoxifylline therapy reduced proteinuria and improved glucose control and insulin resistance without significant change of serum TNF-α in patients with type 2 diabetic nephropathy. Therefore, pentoxifylline is a potential therapeutic alternative for treating diabetes and diabetic nephropathy. TRIAL REGISTRATION: NCT01382303.

Combined use of basal insulin analog and acarbose reduces postprandial glucose in patients with uncontrolled type 2 diabetes.

AIMS/INTRODUCTION: Early initiation of basal insulin therapy is recommended for normalizing fasting blood glucose in type 2 diabetes mellitus. However, basal insulin treatment might not adequately control postprandial glucose levels. The present study evaluated whether the combination of the α-glucosidase inhibitor, acarbose, and basal insulin improved blood glucose control under daily-life treatment conditions in a large sample of Korean patients. MATERIALS AND METHODS: The present study was a multicenter, prospective, observational study under daily-life treatment conditions. A total of 539 patients with type 2 diabetes who were treated with basal insulin and additional acarbose were enrolled and followed up for 20 weeks. Changes in hemoglobin A1c, fasting and postprandial blood glucose were evaluated at baseline and at the end of the observation period. The physician and patient satisfaction of the combination treatment and safety were assessed. RESULTS: Hemoglobin A1c decreased by 0.55 ± 1.05% from baseline (P < 0.0001). Fasting and postprandial blood glucose levels were reduced by 0.89 ± 3.79 and 2.59 ± 4.77 mmol/L (both P < 0.0001). The most frequently reported adverse drug reactions were flatulence (0.37%) and abnormal gastrointestinal sounds (0.37%), and all were mild in intensity and transient. In the satisfaction evaluation, 79.0% of physicians and 77.3% of patients were 'very satisfied' or 'satisfied' with the combined basal insulin and acarbose therapy. CONCLUSIONS: Combination therapy of basal insulin and acarbose in patients with type 2 diabetes improved glucose control, and had no drug-specific safety concerns, suggesting that the treatment might benefit individuals who cannot control blood glucose with basal insulin alone.

Use of ultrasound Doppler to determine tooth vitality in a discolored tooth after traumatic injury: its prospects and limitations.

When a tooth shows discoloration and does not respond to the cold test or electric pulp test (EPT) after a traumatic injury, its diagnosis can be even more difficult due to the lack of proper diagnostic methods to evaluate its vitality. In these case reports, we hope to demonstrate that ultrasound Doppler might be successfully used to evaluate the vitality of the tooth after trauma, and help reduce unnecessary endodontic treatments. In all three of the present cases, the teeth were discolored after traumatic injuries and showed negative responses to the cold test and EPT. However, they showed distinctive vital reactions in the ultrasound Doppler test during the whole observation period. In the first case, the tooth color returned to normal, and the tooth showed a positive response to the cold test and EPT at 10 wk after the injury. In the second case, the tooth color had returned to its normal shade at 10 wk after the traumatic injury but remained insensitive to the cold test and EPT. In the third case, the discoloration was successfully treated with vital tooth bleaching.