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Background: Recent evidence indicates that elevated COX-2 expression is associated with the carcinogenesis of numerous neoplasms. In this study, we investigated COX-2 expression in various thyroid specimens in order to elucidate its physiological role in pathologic conditions, and to evaluate the efficiency of COX-2 protein expression as a molecular marker of malignancy in the thyroid gland. Methods: COX-2 expression was studied immunohistochemically in 19 papillary carcinomas, 8 follicular carcinomas, 14 follicular adenomas, 2 Hurthle cell carcinomas, 4 Hurthle cell adenomas, 8 nodular hyperplasias, 3 Graves' diseases, 3 Hashimoto's thyroiditis, 2 medullary carcinomas, 1 anaplastic carcinoma, and 20 normal thyroid tissues. Results: COX-2 staining was not seen in any of the normal thyroid, Graves' disease, or nodular hyperplasia specimens. In contrast, COX-2 staining was observed in all of papillary carcinomas, Hashimoto's thyroiditis, Hurthle cell carcinomas, and Hurthle cell adenomas tissues. Moreover, 7 of 8 follicular carcinomas and 11 of 14 follicular adenomas showed COX-2 staining. Conclusion: These results indicate that COX-2 is not useful as a marker of malignancy. Since COX-2 expression was evident in follicular adenomas and in papillary and follicular carcinomas. Thus, the enzyme may be involved in the early process of thyroid tumorigenesis.

Objective Delaying embryo transfer (ET) enables us to select among the embryos available for transfer and is associated with positive effects on implantation and pregnancy outcomes. However, the optimal day for ET of human cleavage-stage embryos remains controversial. Methods A retrospective study of 3,124 in vitro fertilization/intracytoplasmic sperm injection cycles (2,440 patients) was conducted. We compared the effects of day 2 and 3 ET on rates of implantation and pregnancy outcomes between young maternal age (YMA

We appreciate your interests and comments on our study, "Predicting mortality of critically ill patients by blood glucose levels" which was published in Diabetes & Metabolism Journal 2013;37:385-90 [1]. As you mentioned, previous several studies demonstrated that the association of hyperglycemia and mortality was greater in individuals without known diabetes in comparison to those with known diabetes [2-4]. It was also reported that intensive glucose control improved the outcome of prolonged critically ill patients without known diabetes, but showed no survival benefits in those with known diabetes [5]. In their studies, glucose values were defined as mean glucose values throughout the entire intensive care unit (ICU) stay, which is in contrast with our study where we used the glucose values at the day of ICU admission. There appears to be some differences in the significance of hyperglycemia during ICU stay and at the day of ICU admission, partly in terms of its sustainability. Sustained uncontrolled hyperglycemia in nondiabetic subjects during ICU stay could implicate the effect of more critically ill conditions than that found in diabetic subjects and might be more harmful to the subjects who have not been previously exposed to hyperglycemia. However, our study was intended to evaluate whether single dysglycemia at the day of ICU admission, regardless of its sustainability, had a predictive value for hospital mortality. Lepper et al. [6] also used single random glucose concentration on admission in patients with pneumonia and showed that patients with pre-existing diabetes had a significantly increased overall mortality compared with those without diabetes (crude hazard ratio, 2.47; 95% confidence interval, 2.05 to 2.98; P

The aim of present study is to assess whether if basal insulin, glargine, could improve insulin secretory function of β-cells compared with glimepiride when metformin alone was failed. This was an open-label and multi-center study for 52 weeks in Korean patients with uncontrolled type 2 diabetes by metformin monotherapy. Subjects were randomized to glargine or glimepiride groups (n = 38 vs. 36, respectively). The primary endpoint was to compare changes in c-peptide via glucagon test after 48 weeks. Glycemic efficacy and safety endpoints (glycated hemoglobin (HbA1c), HOMA-B, fasting plasma glucose (FPG), lipid profiles, and hypoglycemic events) were also checked. The mean disease duration of all subjects was 88.2 months. Changes in C-peptide was no significant different between groups (P = 0.73), even though insulin secretion was not worsened in both groups at the endpoint. Glargine was not superior to glimepiride in other β-cell function indexes such as HOMA-B (P = 0.28). HbA1c and FPG reduced significantly in each groups but not different between two groups. Although, severe hypoglycemia did not occur, symptomatic hypoglycemia was more frequent in glimepiride group (P = 0.01). Insulin glargine was as effective as glimepiride in controlling hyperglycemia and maintaining β-cell function in Korean patients with type 2 diabetes during 48 weeks study period, after failure of metformin monotherapy. Hypoglycemic profile was favorable in the insulin glargine group and less weight gain was observed in the glimepiride group. Our results suggest that glargine and glimepiride can be considered after failure of metformin monotherapy.

Background: Skeletal muscle is well established as a major target organ of insulin action, and is associated with the pathogenesis of type 2 diabetes. Therefore, we attempted to determine whether a variation in serum creatinine is related to the development of type 2 diabetes and other risk factors for diabetes. Methods: A total of 2,676 nondiabetic subjects with stable and normal renal function (estimated glomerular filtration rate >60 mL/min/1.73 m 2 ) were followed up for approximately 4.5 years. New onset diabetes was defined as fasting plasma glucose (FPG) ≥7.0 mmol/L, glycated hemoglobin (HbA1c) ≥6.5%, or subjects taking antidiabetic agents. Variation of serum creatinine (ΔCre) was defined as a difference between follow-up and baseline creatinine. In subgroup analysis, body composition was examined by bioelectric impedance analysis method. Results: A total of 106 subjects were diagnosed with new-onset diabetes during the follow-up period. Baseline serum creatinine was not different between the new-onset diabetes and no diabetes groups. Negative ΔCre (ΔCre

Background: Nonalcoholic fatty liver disease (NAFLD) is closely correlated with abnormal accumulation of visceral fat, but the role of skeletal muscle remains unclear. The aim of this study was to elucidate the role of skeletal muscle in development of NAFLD. Methods: Among 11,116 subjects (6,242 males), we examined the effects of skeletal muscle mass and visceral fat area (VFA, by bioelectric impedance analysis) on NAFLD using by the fatty liver index (FLI). Results: Of the total subjects (9,565 total, 5,293 males) included, 1,848 were classified as having NALFD (FLI ≥60). Body mass index, lipid profile, fasting plasma glucose, hemoglobin A1c, prevalence of type 2 diabetes (DM), hypertension (HTN), and met abolic syndrome were higher in males than females, but FLI showed no significant difference. The low FLI group showed the lowest VFA and highest skeletal muscle mass of all the groups. Skeletal muscle to visceral fat ratio (SVR) and skeletal muscle index had inverse correlations with FLI, when adjusted for age and gender. In multivariate regression analysis, SVR was negatively associated with FLI. Among SVR quartiles, the highest quartile showed very low risk of NAFLD when adjusted for age, gender, lipid profile, DM, HTN, and high sensitivity C-reactive protein from the lowest quartiles (odds ratio, 0.037; 95% confidence in terval, 0.029 to 0.049). Conclusion: Skeletal muscle mass was inversely associated with visceral fat area, and higher skeletal muscle mass may have a beneficial effect in preventing NAFLD. These results suggest that further studies are needed to ameliorate or slow the progression of sarcopenia.

Background The aim of this study is to observe the outcome of critically ill patients in relation to blood glucose level at admission and to determine the optimal range of blood glucose at admission predicting lower hospital mortality among critically ill patients. Methods We conducted a retrospective cohort study of a total 1,224 subjects (males, 798; females, 426) admitted to intensive care unit (ICU) from 1 January 2009 to 31 December 2010. Blood glucose levels at admission were categorized into four groups (group 1

Inhibition of CD36, a fatty acid transporter, has been reported to prevent glucotoxicity and ameliorate high glucose induced beta cell dysfunction. Ezetimibe is a selective cholesterol absorption inhibitor that blocks Niemann Pick C1-like 1 protein, but may exert its effect through suppression of CD36. We attempted to clarify the beneficial effect of ezetimibe on insulin secreting cells and to determine whether this effect is related to change of CD36 expression. mRNA expression of insulin and CD36, intracellular peroxide level and glucose stimulated insulin secretion (GSIS) under normal (5.6 mM) or high glucose (30 mM) condition in INS-1 cells and primary rat islet cells were compared. Changes of the aforementioned factors with treatment with ezetimibe (20 μM) under normal or high glucose condition were also assessed. mRNA expression of insulin was decreased with high glucose, which was reversed by ezetimibe in both INS-1 cells and primary rat islets. CD36 mRNA expression was increased with high glucose, but decreased by ezetimibe in INS-1 cells and primary rat islets. Three-day treatment with high glucose resulted in an increase in intracellular peroxide level; however, it was decreased by treatment with ezetimibe. Decrease in GSIS by three-day treatment with high glucose was reversed by ezetimibe. Palmitate uptake following exposure to high glucose conditions for three days was significantly elevated, which was reversed by ezetimibe in INS-1 cells. Ezetimibe may prevent glucotoxicity in pancreatic β-cells through a decrease in fatty acid influx via inhibition of CD36., Graphical Abstract

Background A 64-slice multidetector computed tomography (MDCT) is well known to be a useful noninvasive form of angiography for the general population, but not for certain patients with diabetes. The aim of this study was to investigate the diagnostic accuracy and usefulness of 64-slice MDCT coronary angiography for detecting coronary artery disease in Korean patients with type 2 diabetes mellitus (T2DM). Methods A total of 240 patients were included, 74 of whom had type 2 diabetes (M:F=40:33; 41.8±9.5 years). We compared significant coronary stenosis (>50% luminal narrowing) in MDCT with invasive coronary angiography (ICA) by segment, artery, and patient. We also evaluated the influence of obesity and coronary calcium score on MDCT accuracy. Results Of the 4,064 coronary segments studied, 4,062 segments (T2DM=1,109) were assessed quantitatively by both MDCT and ICA, and 706 segments (T2DM=226) were detected as a significant lesion by ICA in all patients. Sensitivity, specificity, as well as positive and negative predictive values for the presence of significant stenosis in T2DM were: by segment, 89.4%, 96.4%, 85.8%, and 97.4%, respectively; by artery (n=222), 95.1%, 92.9%, 94.4%, and 93.8%, respectively; by patients (n=74), 98.4%, 100.0%, 98.4%, and 90.0%, respectively. Regardless of presence of diabetes, there was no significant difference in diagnostic accuracy. Obesity (≥25 kg/m2) and coronary calcium score did not also affect the diagnostic accuracy of MDCT. Conclusion The 64-slice MDCT coronary angiography was found to have similar diagnostic accuracy with ICA, regardless of diabetes. These results suggest MDCT may be helpful to reduce unnecessary invasive studies for patients with diabetes.

The metabolic syndrome (MetS) is the clustering of cardiovascular risk factors and known as a powerful predictor of diabetes and cardiovascular disease. Glycated hemoglobin (HbA1c) is used as one of the diagnostic criteria for diabetes and category of increased risk for diabetes. We examined the usefulness of HbA1c as a diagnostic tool for MetS and to determine the cut-off value of HbA1c as a criterion for MetS, in non-diabetic Korean subjects. We analyzed 7,307 participants (male: 4,181, 57%) in a medical check-up program, and applied the newly recommended guidelines of the International Diabetes Federation for diagnosis of MetS. The mean HbA1c was 5.54% in all subjects and showed no significant difference between genders. Using receiver-operating characteristic curve, HbA1c value corresponding to the fasting plasma glucose value of 100 mg/dL was 5.65% (sensitivity 52.3%, specificity 76.7%). The prevalence of MetS was 8.5% according to the IDF guideline and 10.9% according to HbA1c value of 5.7%, showing 69.5% agreement rate. The detection rate of MetS increased to 25.7% using the HbA1c criterion of 5.7% instead of fasting hyperglycemia. This study suggests that HbA1c might be used as a diagnostic criterion for MetS and the appropriate cut-off value of HbA1c may be 5.65% in this Korean population.

Ectopic thyroid is a rare entity and can occur at any location in the midline position. A role for the ectopic thyroid in the pathogenesis of hypothyroidism and nongoitrous cretinism has been emphasized.To assess the clinical characteristics of an ectopic thyroid by analyzing 49 cases reported in Korea.This study was a retrospective review of 19 cases who were diagnosed by thyroid scan at our institutions together with 30 cases reported in the Korean medical literature, found using KoreaMed.Most cases of ectopic thyroid were diagnosed in patients aged between 1 and 29 years; it was more common in females (43 patients). A lingual thyroid was found in 23 patients, a sublingual thyroid in 17 patients, combined type in 7 patients, a prelaryngeal thyroid in 1 patient, and an intratracheal thyroid in 1 patient. Only four cases had the thyroid gland in the normal position. The chief complaints at presentation were palpable mass in 20 patients, growth retardation in 10 patients, and a lump sensation in the throat in 6 patients. Twenty-six of 42 patients (61.9%) had hypothyroidism, and 16 patients (38.1%) had euthyroidism. As for the treatment modalities, 18 of 26 patients with hypothyroidism and 4 of 16 patients with normal thyroid function received thyroid hormone medication; 3 of 26 patients with hypothyroidism and 8 of 16 patients with euthyroidism underwent resection of the ectopic thyroid.Our study suggests that radionuclide thyroid scanning and function testing may be useful not only for the diagnosis of an ectopic thyroid but also before deciding on the therapeutic modality; patients should be followed up to detect changes in thyroid function and malignant transformation.

Adrenocorticotropic hormone (ACTH)-producing pheochromocytoma has been rarely reported, whereas only a few cases of Cushing syndrome accompanied by opportunistic infections have been reported. We experienced a patient with pheochromocytoma with ectopic Cushing syndrome complicated by invasive aspergillosis. A 35-year-old woman presented with typical Cushingoid features. Her basal plasma cortisol, ACTH, and 24-hour urine free cortisol levels were significantly high, and 24-hour urine metanephrine and catecholamine levels were slightly elevated. The endogeneous cortisol secretion was not suppressed by either low- or high-dose dexamethasone. Abdominal computed tomography (CT) revealed a heterogeneous enhancing mass measuring approximately 2.5 cm in size in the left adrenal gland. No definitive mass lesion was observed on sellar magnetic resonance imaging. On fluorine-18 fluorodeoxyglucose positron emission tomography/CT, a hypermetabolic nodule was observed in the left upper lung. Thus, we performed a percu- taneous needle biopsy, which revealed inflammation, not malignancy. Thereafter, we performed a laparo- scopic left adrenalectomy, and its pathologic finding was a pheochromocytoma with positive immunohisto- staining for ACTH. After surgery, the biochemistry was normalized, but the clinical course was fatal despite intensive care because of the invasive aspergillosis that included the lungs, retina, and central nervous system.

This study was performed to investigate the association between FSH receptor (FSHR) gene polymorphism at position 680 and the outcomes of controlled ovarian hyperstimulation (COH) for in vitro fertilization and embryo transfer (IVF-ET) in Korean women. Two hundred and sixty-three patients under 40 years of age who underwent IVF-ET procedures were included in this study. Patients with polycystic ovary syndrome, endometriosis, or a previous history of ovarian surgery were excluded. Following extraction of genomic DNA, the FSHR polymorphism at position 680 was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The FSHR genotype distribution was 41.8% for Asn/Asn, 45.6% for Asn/Ser, and 12.5% for Ser/Ser FSHR genotype groups. Although there was no difference among the three genotype groups in terms of the age and infertility diagnosis of study subjects, the basal levels of FSH (day 3) were significantly different [5.7 +/- 0.3 IU/l (mean+/-SEM), 6.0 +/- 0.3 IU/l, and 8.2 +/- 0.9 IU/l for Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively. The Ser/Ser group tended to require a higher dose of gonadotropins for COH, and tended to show lower serum estradiol levels at the time of hCG administration than the other two groups, though these differences did not reach statistical significance. The numbers of oocytes retrieved tended to be different for the three groups (9.6 +/- 0.6, 10.2 +/- 0.6, and 7.9 +/- 0.8 for Asn/Asn, Asn/Ser, and Ser/Ser groups, respectively). Clinical pregnancy rate was significantly higher in Asn/Asn, compared to the others (45.7 vs. 30.5%, P=0.013). The homozygous Ser/Ser genotype of FSHR polymorphism at position 680 may be associated with a reduced ovarian response to COH for IVF-ET, while Asn/Asn genotypes showed a higher pregnancy rate.

Focal adhesion kinase (FAK) is a tyrosine kinase that is found in cellular structures called focal adhesions. FAK appears to be a key element in signal transduction pathways involved in cell adhesion and locomotion. FAK is overexpressed in various tumors, including tumors derived from regions of the head and neck, colon, breast, prostate, and liver. In this study, we investigated immunohistochemically whether FAK expression was increased in thyroid cancers. FAK staining was not seen in any of the 20 normal thyroid tissues or the 6 nodular hyperplasia specimens. In contrast, FAK staining was observed in all of 17 papillary carcinomas, 9 follicular carcinomas, 8 medullary carcinomas, and 2 anaplastic carcinomas. Nine of 17 follicular adenomas showed FAK immunoreactivity. FAK was not expressed in normal tissue and nodular hyperplasia, but was expressed in some of the follicular adenoma, and all of the follicular, papillary, medullary and anaplastic thyroid carcinoma. This result indicates that the up-regulation of FAK may play a role in the development of thyroid carcinogenesis.

There has been an increase in the number of reports of atypical manifestations of Graves’ disease (GD), such as jaundice, anemia, thrombocytopenia and leukopenia. Pancytopenia also rarely occurs in GD. In this paper, a case of pancytopenia with GD that was successfully treated with an anti-thyroid drug is reported. In this case, a 69-year-old woman showed pancytopenia with a normal peripheral blood smear, bone marrow aspiration smear and bone marrow biopsy. Her thyroid function test and thyroid scintigraphy confirmed her hyperthyroid status. Her laboratory abnormality and clinical condition improved after she was treated with an anti-thyroid drug. This is a rare case of pancytopenia associated with GD.

Received: 3 August 2011, Accepted: 30 September 2011 Corresponding author: Ji Sung Yoon Department of Internal Medicine, Yeungnam University Medical Center, Yeungnam University College of Medicine, 170 Hyeonchung-ro, Nam-gu, Daegu 705-717, Korea Tel: +82-53-620-4049, Fax: +82-53-654-8386, E-mail: jsyoon9@ynu.ac.kr Ketoacidosis with Hypertriglyceridemia-Induced Pancreatitis in a Patient with Gestational Diabetes: A Case Report

Cystic parathyroid adenoma is one of rare causes of hyperparathyroidism, and tends to cause increased serum level of parathyroid hormone, alkaline phosphate and serum calcium level similar to when compared to those of solid adenoma. The possibility of a coincidental appearance of primary hyperparathyrodism and nonmedullary thyroid cancer is rare, and often neglected. A 40-year-old female presented with constipation and weight loss for 3 months. The serum calcium, phosphate and alkaline phosphate were 16.6 mg/dl, 2.2 mg/dl and 505 IU/L respectively and serum parathyroid hormone level was 1556.2 pg/mL. Neck US showed mixed nodules at both thyroid lobes, and PET-CT showed a right thyroid nodule without FDG uptake. The patient was diagnosed of primary hyperparathyroidism and underwent parathyroidectomy and a total thyroidectomy. Histopathologic results revealed parathyroid adenoma with cystic change (2 cm greater diameter) in the right lower parathyroid gland and coexistent papillary carcinoma of the right lobe of thyroid gland (infiltrating, 0.3 cm in greater diameter). She remained well and serum calcium, phosphate, parathyroid hormone level were normalized within 24 hours.

Background: The oral glucose tolerance test (OGTT) for detection of diabetes is difficult to perform in clinical settings. The aim of this study is to evaluate the performance of a more practical detection test, combined fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c), as a predictor of diabetes mellitus (DM) in a Korean sample. Methods: We examined 2,045 (M = 1,276, mean age = 47.8 ± 9.0 yrs) medical check-up program participants between January 2002 to December 2003. FPG, HbA1c and a number of other biochemical tests were performed at baseline and four after years after initial screening. Patients who originally presented with diabetes were excluded. The characteristics of newly-diagnosed DM patients and non-diabetic patients were compared. Results: The incidence of newly diagnosed diabetes was 1.6% (32/2,045) after four years of follow up. The subjects in the DM group were older, had higher levels of SBP, DBP, FPG, HbA1c, triglyceride, HDL cholesterol, GGT and LDH (P < 0.05). In multivariate logistic regression analysis, FPG (odds ratio (OR) 1.124) and HbA1c (OR 4.794) were significantly correlated with onset of diabetes (P < 0.05). The interaction parameter between FPG and HbA1c was more than 1.0, indicating that the two effects are synergistic. The predictive cut-off values of HbA1c and FPG were 5.35% (area under curve (AUC) = 0.944) and 102.5 mg/dL (AUC = 0.930), respectively. Conclusion: The combination of HbA1c above 5.35% and FPG above 102.5 mg/dL predicted the onset of diabetes in a Korean sample. These results suggest that the combination of FPG and HbA1c may be useful for predicting progression to type 2 diabetes in east Asians. (Korean Diabetes J 33:306-314, 2009)

Background: Microalbuminuria in type 2 diabetes is a predictor of development of clinical nephropathy and cardiovascular disease. But, it has been reported that reduced glomerular filtration rate (GFR) may occur in some normoalbuminuric diabetic patients. The aim of this study was to identify whether decreased GFR without microalbuminuria is to predict diabetic vascular complications. Methods: Between January 1998 and February 2001, 73 patients with type 2 diabetes who visited Yeungnam university medical center were divided into 5 groups according to initial GFR ranges: group 1 (GFR < 30 mL/min), group 2 (30 ≤ GFR < 60 mL/min), group 3 (60 ≤ GFR < 90 mL/min), group 4 (90 ≤ GFR < 125 mL/min), group 5 (125 mL/min ≤ GFR). They were examined for microvascular and macrovascular complications initially and after 4 years. Results: Decreased GFR had a negative correlation with age (r = -0.472, P = 0.001). Decreased GFR without microalbuminuria had a significant correlation with development of diabetic nephropathy (P = 0.016) after 4 years. There were no significant correlation with the prevalence of diabetic retinopathy, peripheral neuropathy, and macrovacular disease. But, our study showed that coronary artery disease had an increasing tendency with decreased GFR without statistical significance (P = 0.085). Conclusions: Our data suggest that reduced GFR, independent of albuminuria, may be an important predictor of diabetic nephropathy and coronary artery disease t o some extent. So we recommend that not only the microalbuminuria, but also the decrease in GFR should be evaluated at the follow-up of patients with type 2 diabetes. (KOREAN DIABETES J 32:252-258, 2008)

The adverse effects of prolonged exposure of pancreatic islets to supraphysiologic glucose concentrations(i.e. glucose toxicity) is mediated at least in part by glucose oxidation and the subsequent generation of reactive oxygen species(ROS) that can impair insulin gene expression and β cell function. Multiple biochemical pathways and mechanisms of action for glucose toxicity have been suggested. These include glucose autoxidation, protein kinase C activation, methylglyoxal formation and glycation, hexosamine metabolism, sorbitol formation, and oxidative phosphorylation. There are many potential mechanisms whereby excess glucose metabolites traveling along these pathways might cause β cell damage. However, all these pathways have in common the formation of reactive oxygen species that, in excess and over time, cause chronic oxidative stress, which in turn causes defective insulin gene expression and insulin secretion as well as increased apoptosis. The intracellular peroxide levels of the pancreatic islets(INS-1 cells, rat islets) by flow cytometry were increased in the high glucose media compared to 5.6 mM glucose media. The insulin, MafA, PDX-1 mRNA levels and glucose stimulated insulin secretion(GSIS) were decreased in high glucose media compared to 5.6 mM glucose media. The HO-1 seems to mediate the protective response of pancreatic islets against the oxidative stress that is due to high glucose conditions. Also, we observed decreased glutathione level, γ-GCS expression and increased oxidized LDL, malondialdehyde level at leukocytes and mesothelial cells from patients with Korean Type 2 Diabetes(esp, poorly controlled patients). In conclusion, this pathophysiologic sequence sets the scene for considering antioxidant therapy as an adjunct in the management of diabetes, especially type 2 Diabetes.(KOREAN DIABETES J 32:175-181, 2008)

Background: Lipid oxidation and formation of oxygen radicals have been identified to be the important factors of atherogenesis. Because bilirubin, a potent physiological antioxidant inhibits lipid oxidation, it is suggested that low serum concentrations of bilirubin is associated with atherosclerosis. The aim of this study was to evaluate the relationship between bilirubin levels and coronary atherosclerosis. Methods: The coronary calcium score (CCS) of 172 subjects (male 63, mean age 60.5 ± 1.0) with type 2 diabetes were evaluated in Yeungnam University Hospital between January 2005 and February 2007. The subjects were divided into two groups with CCS 10 as the cut off. Results: Higher CCS was significantly associated with lower bilirubin (P < 0.05), but after adjusted with age, no longer correlation were seen (P = 0.121). To determine the relationship between subclinical coronary atherosclerosis and bilirubin, the subjects with previous history of cardiovascular disease were excluded. In 138 subjects (male 54, mean age 58.4 ± 1.1), higher CCS was significantly associated with lower levels of bilirubin. After adjusted with age, duration of diabetes, and history of hypertension, CCS was also inversely related with bilirubin (P < 0.05). Conclusion: These results suggest that lower levels of bilirubin might be considered as a risk factor of coronary artery disease, especially in type 2 diabetics without cardiovascular disease. (KOREAN DIABETES J 32:338-345, 2008)

Background: Hyperglycemia is a well-recognized pathogenic factor of long term complications in diabetes mellitus and hyperglycemia also generates reactive oxygen species (ROS) in β cells when ROS accumulate in excess for prolonged periods of time, they cause chronic oxidative stress and adverse effects. Unfortunately, the islet contacts low capacity of endogenous antioxidant effects. But, γ-glutamylcysteine synthetase (γ-GCS), the rate-limiting enzyme for glutathione synthesis, is well represented in islets. Methods: This study is to evaluate the changes in the activity of γ-GCS, glutathione in β-cells exposed to high glucose, in pancreatic tissue of OLETF (Otsuka Long Evans Tokushima Fatty) and LETO (Long-Evans Tokushima Otsuka) rats, in leukocytes from patients with Korean type 2 DM (T2DM) and to disclose the effects of high blood glucose on this impairment in patients with T2DM. We divided our patients into 3 groups by HbA1c (controls: n = 20, well controls diabetes: n=24, poorly controlled diabetes: n = 36). Results: We observed that decreased glutathione level, γ-GCS expression, glucose-stimulated (GSIS) and increased intracellular peroxide level in the INS-1 cells exposed to 30 mM glucose condition. Also decreased glutathione level at erythrocytes, γ-GCS expression at leukocytes and increased oxidized LDL, MDA (malondialdehyde) level at plasma from patients with T2DM compared to controls (esp, poorly controlled patients). Conclusion: These results suggest that insufficient antioxidant defenses by the glutathione pathway may be one of the factors responsible for development of complications in T2DM. (J Kor Diabetes Assoc 31:302~309, 2007)

Background: Secondary failure of oral hypoglycemic agents is defined as tha t blood glucose is no longer controlled with sulfonylurea after a proven period of good glycemic control. There are many causes of secondary failure, including that drug problem, acute illnesses, inappropriate drug dosages, oxidative stress & glucose toxicity of β-cell, etc. And many studies have suggested role of immunologic process such as islet cell antibody (ICA) and/or glutamic acid decarboxylase antibody (GADA) for the causes of secondary failure. So we evaluated the prevalence of ICA & GADA in type 2 diabetes with secondary failure of oral hypoglycemic agents and the pathogenesis of the secondary failure. Methods: We studied 267 patients with type 2 diabetes. We regarded 84 pa tients who could not control HbA1c less than 8% after good glycemic control for at least 1 y ear as secondary failure group (group 1) and regarded the other 183 patients as group 2. We measured GADA in both group, and measured the prevalence of GADA and ICA in secondary failure group who were especially divided into obese group and nonobese group according to BMI and were divided into insulin deficiency group and noninsulin deficiency group according to fasting C-peptide level. Results: The prevalence of GADA in all subjects was 4.1%, which was 9.5 % in group 1 and 1.6% in group 2 (P < 0.05). Among 35 patients of the group 1 who could be checked ICA, the prevalence of GADA & ICA were 33% & 25% in insulin deficiency group and 4.3% & 0% in non-insulin deficiency group, respectively (P < 0.05). The prevalence of GADA & ICA were none in obese group and 33.3% & 20% in nonobese group, respectively (P < 0.05). The prevalence of GADA & ICA were 36.4% & 27.3% in nonobese and insulin deficiency, 4.2% & 0% in obese and non-insulin deficiency. Conclusion: We suggest that autoimmune mechanism is associated with increased risk for secondary failure of oral hypoglycemic agents in type 2 diabetes, so the measurement of GADA and ICA could help to predict the potential risk and insulin treatment. (J Kor Diabetes Assoc 31:402~409, 2007)

Background: Diabetic retinopathy is a leading cause of adult blindness. Some patients show early development and progression of diabetic retinopathy despite of apparently good glycemic control. This is suggesting the involvement of other contributing factors. Recent studies have shown that retinopathy and GAD autoantibody (GADA) show an inverse relationship immunologically. This study is designed to investigate the clinical manifes tation of diabetes who are positive for GADA and the relationship between GADA and diabetic retinopathy. Methods: Type 1 diabetic patients & LADA patients who had visited Yeungnam university Medical Center from 1988 to 2005 were involved. We reviewed the pathologic and laboratory records of these patients and investigated the development of diabetic microvascular complications. Results: Compared with patients who had GADA negative diabetes, patients with GADA positive diabetes had lower prevalence of diabetic retinopathy (GADA negative subject: 25.8% vs. GADA positive subject: 9.6%, P < 0.05). Conclusion: We confirmed that diabetic retinopathy and GADA showed an inverse relationship. It seems quite probable that GADA may contribute to the prevention of retinopathy. Further research should be needed concerning the effect of GADA on diabetic retinopathy. (J Kor Diabetes Assoc 31:429~434, 2007)

Table 1. Summary of heme oxygenase (HO) isoforms HO-1 HO-2 HO-3 HO-2 amino acid homology ~40% 100% ~90% Physiological roles Heme catabolism Anti-oxidant defense Modulation of vascular tone & liver perfusion Neural signaling Anti-inflammatory actions Down-modulation of Adhesion molecule expression Regulation of hemo-proteins activity Heme catabolism Heme binding Maintenance of vascular tone Neural signaling Heme binding Regulation of heme dependent genes

Aging processes are time-dependent, deteriorative functional changes. These functional changes lead to a progressive loss of the organism’s ability to withstand both internal and environmental stresses, causing the failure of cellular homeostasis. Among the modern hypotheses, the ‘Oxidative Stress Hypothesis’ offers the best mechanistic elucidation of aging phenomena. Based on the ‘Free Radical Theory of Aging’, this hypothesis has gained popularity among researchers in the field of gerontology as well as other biomedical fields. Its primary premise proposes that aging and its related disease processes are the net result of free radical-induced damage, asserting further that an organism’s inability to produce counterbalancing antioxidative defences, i.e. defences that offset disturbances in the redox state, underlies its cause.

Background: Chronic exposure of pancreatic islets to supraphysiologic concentrations of glucose causes beta cell dysfunction that is a process known as glucose toxicity. It has been reported that hyperglycemia increases the production of reactive oxygen species (ROS) in human islets and that ROS accumulation causes beta cell dysfunction associated with low capacity of intrinsic antioxidant enzymes. Also it has been postulated that this increase in ROS is prevented by an inhibitor of electron transport chain complex. The purpose of this study were to determine whether prolonged exposure of pancreatic islets to supraphysiologic glucose concentrations disrupts the intracellular balance between ROS thereby causing defective insulin secretion and to evaluate the site of hyperglycemiainduced ROS production. Methods: INS-1 cells & rat islets were incubated in increasing concentrations of glucose and either an inhibitor of complex I & II (TTFA), an uncoupler of oxidative phosphorylation (CCCP), aCCA, etc and also incubated in increasing concentration of glyceraldehyde and N-acetylcystein. Then intracellular peroxide levels by flow cytometric analysis and glucose induced insulin secretion were detected. Results: We observed that incubation with 30 mM glucose increased intracellular peroxide levels but decreased glucose-stimulated insulin secretion (GSIS) (P

Background: Cardiovascular disease including coronary heart disease (CHD) is the most common cause of morbidity and mortality in patients with diabetes. But traditional risk factor assessment is limited to predict CHD in asymptomatic high-risk individuals. In this study, relationship between coronary calcium score (CCS) and CHD was evaluated to determine value of coronary artery calcification detected by multi-slice spiral computed tomography to predict CHD in high risk asymptomatic patients with type 2 diabetes. Methods: 127 patients were enrolled who admitted in Yeungnam University Hospital between December 2004 and May 2005. Standard cardiovascular risk factors and the CCS measured by multi-slice spiral computed tomography were assessed. Results: Enrolled subjects were consisted of 56 subjects with diabetes and 71 subjects without diabetes. The mean CCS was significantly greater in patients with diabetes than without diabetics (P

Rhabdomyolysis is the consequence of extensive muscle injury with the release of muscle cell constituents into plasma. It can arise from trauma and also from a variety of nontraumatic causes. Trauma, drugs, toxins and infection are the major causes of rhabdomyolysis, but it is rarely associated with metabolic disorders such as severe electrolyte disturbance, diabetic ketoacidosis, hyperosmolar nonketotic coma, hypothyroidism and thyrotoxicosis. There have been several reported cases of metabolic rhabdomyolysis, but panhypopituitarism as a cause has never been identified. We experienced a case of acute rhabdomyolysis associated with panhypopituitarism. Thus, So we report this case with the review of related literature. Metabolic disorder is a rare cause of rhabdomyolysis, but it should always be considered in a patient having and unexplained increased of the creatine kinase concentration (J Kor Soc Endocrinol 20:174～178, 2005).

Kallmann's syndrome is defined as the combination of hypogonadotropic hypogonadism and anosmia/hyposmia. The syndrome is a result of defect in the embryonic migratory pathway of gonadotropin-releasing hormone, which synthesizes neurons and olfactory axons. The hypogonadotropic hypogonadism results due to absence of or incomplete pubertal development and may be associated with anosmia, hyposmia, midline defect (color blindness, cleft-lip, cleft-palate, unilateral renal agenesis, sensorineural deafness), cryptorchidism and skeletal anomaly. Till date in Korea, few cases of Kallmann's syndrome have been reported but there are no available reports on cases of Kallmann's syndrome with unilateral renal aplasia and diabetes mellitus. We handled a case of Kallmann's syndrome associated with unilateral renal agenesis and diabetes mellitus. In the current work, we present a peculiar case as afore mentioned with the review of related literature (J Kor Soc Endocrinol 20:96～102, 2005).

Central diabetes insipidus (DI) is a syndrome characterized by thirst, polydipsia and polyuria. Langerhans cell histiocytosis is one of the etiologies of DI. Recently we experienced a central DI associated with Langerhans cell histiocytosis. The 44 years old female patient complained right hip pain, polydipsia and polyuria. We carried out water deprivation test. After vasopressin injection, urine osmotic pressure was increased from 109 mOsmol/kg to 327 mOsmol/kg (300%). Brain MRI showed a thickened pituitary stalk and air bubble like lesions sized with 5cm, 7cm was shown on fifth L-spine and right hip bone at hip bone CT. CT guided biopsy revealed abnormal histiocytes proliferation and abundant lymphocytes. The final diagnosis was central DI associated with systemic Langerhans cell histiocytosis invading hip bone, L-spine and pituitary stalk. Desmopressin and etoposide chemotherapy were performed to the patient.

Pure primary hepatic rhabdomyosarcoma in adult is very uncommon. There have been only five previous case of primary rhabdomyosarcoma of the adult liver. A case of hepatic rhabdomyosarcoma was diagnosed in a 52 year-old female. She was admitted to the hospital due to the epigastric pain and weight loss. A CT scan of the abdomen showed a large hypodense mass with focal calcification occupies most of the both lobes of the liver. The liver biopsy showed massive liver tumor composed entirely of oval shaped cells showing light microscopic and immunohistochemical evidence of rhabdomyoblastic differentiation. We report a case of hepatic rhabdomyosarcoma with review of literature.