Search

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.

Background: This study was performed to determine the factors associated with long-term oral hypoglycemic agent (OHA) re sponsiveness in Korean type 2 diabetic patients. Methods: Two groups of patients were selected among the type 2 diabetic patients who were followed for more than two years at a university hospital diabetes clinic. The OHA responsive group consisted of 197 patients whose HbA1c levels were maintained at ≤7% with OHA for more than two years. The OHA failure group consisted of 180 patients whose HbA1c levels were >8% in spite of optimal combined OHA therapy or patients who required insulin therapy within the two years of the study. Results: The OHA failure group had higher baseline values of fasting and postprandial glucose, HbA1c, and lower fasting, post prandial, and delta C-peptide compared to those of the OHA responsive group. The OHA failure group also had a higher pro portion of female patients, longer diabetic duration, and more family history of diabetes. There were no significant differences in body mass index (BMI) or insulin resistance index between the two groups. Multiple logistic regression analysis showed that the highest quartile of baseline fasting, postprandial glucose, and HbA1c and the lowest quartile of postprandial and delta C-peptide were associated with an increased odds ratio of OHA failure after adjustment for age, sex, body mass index, and family history of diabetes. Conclusion: Lower baseline values of postprandial and delta C-peptide and elevated fasting glucose and HbA1c are associated with long-term OHA responsiveness in Korean patients with type 2 diabetes mellitus.

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.

Primary intraoperative recurrent laryngeal nerve (RLN) reinnervation techniques demonstrated significant voice improvement at 24 months postoperatively and could be an effective alternative treatment for thyroidectomy-related permanent unilateral vocal fold paralysis (VFP).To assess the long-term efficacy of intraoperative RLN reinnervation techniques in the management of thyroidectomy-related unilateral VFP.A prospective study was conducted from January 2008 to June 2012 at Soonchunhyang University Bucheon Hospital. Nineteen patients who underwent RLN reinnervation with either direct reinnervation (neurorrhaphy) or ansa cervicalis to RLN (ansa-RLN) anastomosis and completed subjective and objective voice measurement over a 1-year follow-up period were included in this study.The causes of VFP were cancer involving the RLN (68.4%, 13/19) and iatrogenic nerve transection (31.5%, 6/19). Reinnervation techniques were direct neurorrhaphy (63.2%, 12/19) and ansa-RLN anastomosis (36.8%, 7/19). Subjective parameters such as the Voice Handicap Index (VHI), posterior glottic closure, and mucosal wave demonstrated significant improvement 6 months postoperatively, and the majority of parameters remained stable up to 24 months (p0.05). Objective parameters, such as maximum phonation time (MPT), jitter, shimmer, and the harmonics-to-noise ration (HNR), demonstrated significant improvement at 12 months and most remained stable at 24 months (p0.05).

We investigated the association between microalbuminuria and prediabetes in Korean population using data from the KNHANES 2011-2012. Prevalence of microalbuminuria was significantly increased in prediabetes group. However, the odds ratio became insignificant after adjustment for blood pressure, and the prevalence of microalbuminuria was not increased in prediabetic subjects without hypertension.

SummaryObjective Dyslipidaemia and central obesity are the major factors underlying the dramatic increase in metabolic syndrome (MS). We compared the effects of early combined therapy with pitavastatin and intensive lifestyle modification (LSM) on the amelioration of each component of MS with those of LSM only. Design/Participants/Measurements PROPIT (a PROspective comparative clinical study to evaluate the efficacy and safety of PITavastatin in patients with metabolic syndrome) was a prospective, randomized, multicenter open-label 48-week trial. We enrolled 187 patients with MS (central obesity and prediabetes) and randomized them into two treatment groups: 2 mg pitavastatin daily + intensive LSM or intensive LSM only. The primary outcome was the improvements in the components of MS and in the percentage of non-MS converters. Results After 1 year treatment, the improvement of MS score was significantly higher in the pitavastatin + LSM group (P = 0·039). However, non-MS converters (MS score ≤2) did not differ between the groups. The secondary outcomes, namely lipid profiles, the Apo B/A1 ratio, visceral fat/subcutaneous fat ratio and the Framingham risk score, were significantly improved in the pitavastatin group. There was no deterioration in glucose metabolism after treatment with pitavastatin for 1 year. Conclusions Early statin treatment can be an effective option in obese patients with MS, prediabetes and mild dyslipidaemia with further improvement of cardiovascular risk factors. We could not observe the increase rate of glucose intolerance in statin group. Future longitudinal studies are needed to test the benefits of early statin treatment compared with LSM.

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.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.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 ε4 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 ε4 carriership toward poor performances in the COWAT (β = -0.335, t = -2.285, p = 0.026).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 ε4carriers.

Objective We evaluated the prevalence of aspirin resistance and predictive factors for aspirin resistance in Korean type 2 diabetes patients. Approach and results A total of 1045 type 2 diabetes patients from 11 hospitals who were taking aspirin (100 mg/day for ≥2 weeks) and no other antiplatelet agents were studied to evaluate aspirin resistance. Aspirin resistance was measured in aspirin reaction units using VerifyNow ® . Aspirin resistance was defined as ≥550 aspirin reaction units. Aspirin resistance was detected in 102 of the 1045 subjects (prevalence 9.8%). Aspirin resistance was associated with total cholesterol ( P = 0.013), LDL-cholesterol ( P = 0.028), and non-HDL cholesterol ( P = 0.008) concentrations in univariate analysis. In multivariate logistic regression analysis, only non-HDL cholesterol was associated with aspirin resistance in obese (BMI >25 kg/m 2 ) type 2 diabetes patients (adjusted odds ratio 3.55, 95% CI: 1.25–10.05, P = 0.017). Conclusions The prevalence of aspirin resistance in Korean type 2 diabetes patients is 9.8%. Non-HDL cholesterol is an independent risk factor for aspirin resistance, especially in obese type 2 diabetes patients.

Introduction When a pulmonary nodular lesion is detected by F-18 fluorodeoxyglucose positron emission tomography-computed tomography in a patient with post-surgical papillary thyroid carcinoma with undetectable serum-stimulated thyroglobulin levels and negative 131I whole body scan, diagnosis and management of the nodule may be confusing. Case presentation We describe two post-surgical patients with papillary thyroid carcinoma who showed pulmonary nodular lesions detected by F-18 fluorodeoxyglucose positron emission tomography-computed tomography. In both cases serum-stimulated thyroglobulin levels were undetectable and nodular lesions were not detected by 131I whole body scan. In the first case, a 64-year-old Asian woman showed one focal increased fluorodeoxyglucose uptake lesion in the right lower lobe of one of her lungs. Based on the histologic study, the pulmonary nodular lesion was diagnosed as a solitary pulmonary metastasis from papillary thyroid carcinoma. In the second case, a 59-year-old Asian woman showed a new pulmonary nodule in the right lower lobe. The computed tomography scan of her chest revealed a 9mm nodule in the anterior basal segment and another tiny nodule in the posterior basal segment of the right lower lobe. Six months later, both nodules had increased in size and miliary disseminated nodules were also seen in both lungs. Based on their histology, the pulmonary nodular lesions were considered to be primary lung adenocarcinoma. Conclusions The present cases emphasize that physicians should be cautious and make efforts for an accurate diagnosis of pulmonary nodules detected on F-18 fluorodeoxyglucose positron emission tomography-computed tomography in patients with papillary thyroid carcinoma with no evidence of metastasis such as negative 131I whole body scan and undetectable stimulated serum thyroglobulin levels.

Aims/Introduction The associations between non-alcoholic fatty liver disease (NAFLD) and chronic vascular complications of type 2 diabetes remain uncertain. We assessed the relationships between NAFLD and chronic vascular complications in patients with type 2 diabetes. Materials and Methods Patients with type 2 diabetes (n = 929) attending a diabetes clinic of a university hospital were studied retrospectively. Patients who had any clinical evidence of cirrhosis or other causes of chronic liver disease were excluded. Prevalences of chronic microvascular and macrovascular complications were assessed. NAFLD was ascertained by ultrasonography. Results The prevalence of NAFLD in patients with type 2 diabetes was 63.3%. The prevalences of diabetic retinopathy and nephropathy were significantly lower in patients with NAFLD than those without NAFLD (33.0 vs 70.2%, P

Background Cardiac autonomic neuropathy (CAN) is a common complication of diabetes associated with poor prognosis. In addition, the autonomic imbalance is associated with cardiovascular disease (CVD) in diabetes. It is thought that adipocytokines contribute to the increased risk of vascular complications in patients with type 2 diabetes mellitus (T2DM). However, literature data on the association between CAN with adipocytokines such as leptin, tumor necrosis factor-alpha (TNF-alpha), adiponectin in subjects with T2DM is limited. Therefore, in the present study, we examined the relationship between fasting serum leptin, TNF- alpha and adiponectin and CAN in Korean T2DM patients. Methods A total of 142 T2DM patients (94 males, 48 females) were recruited. CAN was assessed by the five tests according to the Ewing's protocol and the time and frequency domain of the heart rate variability (HRV) was evaluated. Serum TNF-alpha and adiponectin levels were measured using enzyme-linked immunosorbent assay and serum leptin levels were measured using radioimmunoassay. Results Although, the mean levels of leptin, TNF-alpha and adiponectin were not significantly different between the groups with and without CAN, the levels of leptin and adiponectin had a tendency to increase as the score of CAN increased (p = 0.05, p = 0.036). Serum leptin levels demonstrated a negative correlation with low frequency (LF) in the upright position (p = 0.037). Regarding TNF-alpha, a significant negative correlation was observed with SDNN and RMSSD in the upright position (p = 0.023, p = 0.019). Adiponectin levels were not related to any HRV parameters. Multivariate logistic regression analysis demonstrated that the odds of CAN increased with a longer duration of diabetes (1.25, [1.07-1.47]) and higher homeostatic model of assessment-insulin resistance (HOMA-IR) (5.47, [1.8-16.5]). The relative risks for the presence of CAN were 14.1 and 51.6 for the adiponectin 2nd, 3rd tertiles when compared with first tertile (p-value for trend = 0.022). Conclusions In the present study, the higher serum adiponectin levels and HOMA-IR were associated with an increased risk for the presence of CAN. Also, the CAN score correlated with the serum adiponectin. Serum adipocytokines such as leptin and TNF-alpha were significantly correlated with parameters of HRV, representative markers of CAN. Future prospective studies with larger number of patients are required to establish a direct relationship between plasma adipocytokine concentrations and the development or severity of CAN.

Background/Aims The relationship between Runt-related transcription factor 3 (RUNX3) gene inactivation and various solid tumors has been reported; however, little information is available about RUNX3 in thyroid cancers. Methods We evaluated the DNA methylation of RUNX3 in 13 papillary thyroid cancer tissues and four thyroid cancer cell lines. Additionally, using reverse transcriptase-polymerase chain reaction, we analyzed RUNX3 gene expression in several thyroid cancer cell lines after treating with the demethylating agent 5-aza-2'-deoxycytidine (DAC). Results RUNX3 was hypermethylated in many thyroid cancer cell lines and in 10 of the 12 papillary thyroid cancer tissues. Treatment with DAC increased the expression of RUNX3 in some thyroid cancer cell lines. Conclusions We suggest that RUNX3 is associated with thyroid carcinogenesis, and RUNX3 methylation is a potentially useful diagnostic marker for papillary thyroid cancer.

This prospective study investigated the efficacy of injection laryn-goplasty in the management of postthyroidectomy vocal cord paralysis (VCP).From March 2005 to December 2008, 174 consecutive injection laryngoplasties were performed in patients with unilateral glottic insufficiency. This included 34 patients with post-thyroidectomy VCP: 15 with temporary VCP and 19 with permanent VCP. Percutaneous injection was performed under local anesthesia into the vocalis muscle, using disposable 25G-long needles through the cricothyroid membrane or directly through the thyroid cartilage. Patients completed the acoustic, aerodynamic, perceptual, stroboscopic, and voice handicap index evaluations before and at 3 and 6 months after the injection.All injection laryngoplasty could be performed under local anesthesia without morbidity. Acoustic and perceptual parameters (overall grade of hoarseness, roughness, breathiness, asthenia, and strain), maximum phonation time, jitter, and shimmer, voice handicap index, and grades of mucosal waves and glottic closure were significantly improved after the injection and they remained stable over 6 months in both the temporary VCP and permanent groups (p0.05).Based on these preliminary results, injection laryngoplasty improved the voice, and voice-related quality of life in patients with post-thyroidectomy VCP. It is a simple, safe, and useful method for rehabilitating post-thyroidectomy VCP patients.

Familial neurohypophyseal diabetes insipidus (FNDI; OMIM 192340) is a rare inherited disorder with an autosomal dominant inheritance pattern. It is characterized by persistent polydipsia and polyuria induced by deficient or absent secretion of arginine vasopressin (AVP). We report a Korean kindred in whom FNDI is associated with a novel deletion mutation in exon 2 of the AVP-NPII gene encoding the neurophysin II moiety. An 18-yr-old man with polyuria and polydipsia was shown to have central diabetes insipidus by using the water deprivation test. Four family members were suspected to have symptomatic vasopressin-deficient diabetes insipidus. Direct sequencing of the AVP-NPII gene showed a heterozygous GAG deletion mutation in exon 2, which results in in-frame deletion of glutamic acid (c.232_234delGAG; p.Glu78del). The mutation was predicted to yield an abnormal AVP precursor lacking Glu78 (E78) in its neurophysin II moiety. Because Glu78 is essential for neurophysin II molecules to form a salt bridge with AVP, the function of neurophysin as a carrier protein for AVP would be impaired. The proband's mother and sister have the same mutation. Presence of this mutation suggests that the portion of the neurophysin peptide encoded by this sequence is important for the appropriate expression of vasopressin.

Objectives This study prospectively evaluated postthyroidectomy syndrome (PTS) through objective and subjective voice changes following thyroidectomy of open vs. endoscopic thyroidectomy. Methods A prospective clinical trial (SCHBC IRB 09 26) was performed from Jan 2008 to Aug 2010 to compare the open thyroidectomy (OPEN group) and endoscopic thyroidectomy (ENDO group). Of the 110 patients, 75 completed the evaluation before and 1 and 6 months after surgery. Subjective parameters included perceptual analysis (GRBAS [grade, roughness, breathiness, asthenia, and strain] scale), stroboscopic or flexible fiberscopic analysis, voice handicap index, and 5-point visual analog scales for vocal fatigue, singing difficulty, difficulty with high-pitch phonation, and neck discomfort. Objective parameters included acoustic, aerodynamic analysis and the electroglottograph. Results For the ENDO group (n=36), the operation time was longer than in the OPEN group (n=39; P

Background: Thyroid incidentalomas detected by 2-deoxy-2- 18 F-fluoro-D-glucose positron emission tomography/computed to- mography ( 18 F-FDG PET/CT) have been reported in 1% to 4% of the population, with a risk of malignancy of 27.8% to 74%. We performed a retrospective review of FDG-avid thyroid incidentalomas in cancer screening subjects and patients with nonthyroid cancer. The risk of malignancy in thyroid incidentaloma and its association with the maximal standardized uptake value (SUVmax) in 18 F-FDG PET/CT were evaluated to define the predictor variables in assessing risk of malignancy. Methods: A total of 2,584 subjects underwent 18 F-FDG PET/CT for metastatic evaluation or cancer screening from January 2005 to January 2010. Among them, 36 subjects with FDG-avid thyroid incidentalomas underwent further diagnostic evaluation (thy- roid ultrasonography-guided fine needle aspiration cytology (FNAC) or surgical resection). We retrospectively reviewed the da- tabase of these subjects. Results: Of the 2,584 subjects who underwent 18 F-FDG PET/CT (319 for cancer screening and 2,265 for metastatic evaluation), 52 (2.0%) were identified as having FDG-avid thyroid incidentaloma and cytologic diagnosis was obtained by FNAC in 36 sub- jects. Of the subjects, 15 were proven to have malignant disease: 13 by FNAC and two by surgical resection. The positive predic- tive value of malignancy in FDG-avid thyroid incidentaloma was 41.7%. Median SUVmax was higher in malignancy than in be- nign lesions (4.7 (interquartile range (IQR), 3.4 to 6.0) vs. 2.8 (IQR, 2.6 to 4.0), P=0.001). Conclusion: Thyroid incidentalomas found on 18 F-FDG PET/CT have a high risk of malignancy, with a positive predictive value of 41.7%. FDG-avid thyroid incidentalomas with higher SUVmax tended to be malignant.

Background Whereas visceral abdominal adipose tissue (VAT) is associated with cardiometabolic risk, there is debate regarding the role of subcutaneous abdominal adipose tissue (SAT). The aim of this study was to investigate the relationships of subcutaneous and visceral abdominal fat with carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Methods A total of 234 patients (men 131, women 103, mean age: 53 years) with T2DM were enrolled. Carotid intima-media thickness (CIMT), abdominal subcutaneous fat thickness (SFT) and visceral fat thickness (VFT) were assessed by high-resolution B-mode ultrasonography (US). Results Compared to women, men had significantly higher VFT and lower SFT (p = 0.002, p = 0.04, respectively). In partial correlation coefficient analyses between CIMT and abdominal fat thickness after adjustment for body mass index (BMI), SFT showed a negative correlation with CIMT in men (r = -0.27, p = 0.03). VFT was not correlated with CIMT in either men or women. In women, SFT was not correlated with CIMT (r = -0.01, p = 0.93). VFT/SFT ratio was not correlated with CIMT in either men or women. In multivariate regression analyses adjusted for BMI and other CVD risk factors, SFT but not VFT was independently inversely associated with CIMT in men but not in women (p

Vitamin D affects not only musculoskeletal health but also a range of nonskeletal diseases such as cancer, obesity, metabolic syndrome, type 2 diabetes and cardiovascular disease. Vitamin D deficiency and obesity have been recognized as pandemic diseases with much health consequences. The ‘cause-effect’ relationship of vitamin D to obesity has been the area of much recent activity. There is consistent association in the published literature between higher body mass index (BMI) and lower 25-hydroxyvitamin D (25(OH)D) concentrations, but the mechanisms are not fully understood. Although recent studies suggest that low serum vitamin D is the consequence of obesity, the results from randomized controlled trials are still scarce and inconclusive to establish the relationship between vitamin D and obesity. Moreover, the role of vitamin D in the pathophysiology of obesity is still debatable and there is little evidence for a direct effect of vitamin D supplementation on body weight. Therefore, randomized large-scale double-blind controlled trials are needed in the future to clearly establish the effects of vitamin D in obesity.

We would like to express our deep gratitude to the editor for giving us the opportunity to publish this article, and we are also deeply grateful to our reviewer, who read our manuscript and provided us with helpful comments and advice. Because few previous studies have been performed on the association between cardiac autonomic neuropathy (CAN) and carotid atherosclerosis, we investigated the relationship between these two conditions in patients with type 2 diabetes mellitus (T2DM). We assessed CAN using five standard cardiovascular reflex tests, according to Ewing's protocol. We diagnosed CAN when a patient showed at least two abnormalities or CAN score of ≥2. However, there is no widely accepted single approach to the diagnosis of CAN in diabetes. Moreover, the diagnostic criteria and staging of CAN are still being debated. Therefore, the wide ranges (2.5% to 50%) of CAN prevalence reported by different authors can be attributed to the heterogeneous methodology used as well as differences in the definition of CAN [1]. Among several methods that provide indexes of both parasympathetic and sympathetic autonomic function, the assessment of heart rate variability by simple bedside tests devised by Ewing et al. has been used widely in clinical settings. Cardiovascular reflex tests are the gold standard in clinical autonomic testing and these tests have good sensitivity, specificity, reproducibility and are easily performed [2]. Several authors suggest that the presence of one abnormal cardiovascular reflex test identifies possible or early CAN and at least two abnormal tests are required for a definite or confirmed diagnosis of CAN [1]. Numerous clinical studies that have examined the association between CAN and mortality or CAN and silent myocardial ischemia used the CAN definition of an abnormal result on at least two of the five tests [3,4]. Additionally, a study that examined the relationship between CAN and coronary artery calcification in Korean patients with T2DM used the same CAN definition as we used in the present study [5]. However, as mentioned in the letter from the reviewer, we also think that a CAN score ≥2 can be too high to detect early atherosclerotic condition. On the contrary, it should be considered that a low CAN score may lead to low specificity in the detection of subclinical atherosclerosis. In addition, the reviewer commented that the definition of 'two abnormal tests' contains many combinations of 'different two' types of abnormal CAN tests. Because each of the five CAN tests has a different meaning, each of those different combinations will also have unique clinical implications. Therefore, we agree with the reviewer's opinion. To our knowledge, however, no studies regarding the different clinical applications of the different combinations of CAN tests have been reported, even though each test or each different combination of the five tests has a different power in the sense of atherosclerotic progression, as mentioned above. In conclusion, although the diagnosis of CAN as 'two or more' abnormal tests or a CAN score ≥2 in our study has several limitations, this diagnostic criteria has been widely used in numerous clinical studies. Additionally, we agree that further studies are needed to standardize and unify the various diagnostic criteria of CAN, as the reviewer commented. Thank you again for your insightful and comprehensive review of our paper.

Cardiogenic shock after stress-induced cardiomyopathy is very rare and serious, and a reversible, clinical consequence of untreated adrenal insufficiency that is attributable to Sheehan’s syndrome. A 53-year-old female presented with confusion, congestive heart failure, and hypotension. Endocrine testing, prior medical history, and brain MRI confirmed the presence of hypopituitarism and secondary adrenal insufficiency owing to undiagnosed Sheehan’s syndrome. After glucocorticoid replacement therapy, her cardiac function recovered completely. Stress-induced cardiomyopathy should be considered as a possible cause of unexplained heart failure in patients with Sheehan’s syndrome and adrenal insufficiency. (Korean J Med 2014;87:347-351)

Background/Aims This study was performed to compare the mucosal findings after esophagogastroduodenoscopy in two groups before and after the use of alendronate only and following administration of the enteric-coated alendronate (5 mg) and calcitriol (0.5 µg) combined drug (Maxmarvil, Yuyu Co.). Methods The study population consisted of 33 postmenopausal healthy female volunteers, aged 50 to 70 years (mean age, 58 ± 5) without gastrointestinal symptoms and with normal baseline endoscopic findings. Esophagogastroduodenoscopy was performed at baseline and was repeated 2 weeks later after daily intake of Maxmarvil (n = 17 subjects) or alendronate only (n = 16 subjects). Mucosal injury scores were reported by an endoscopist after 2 weeks of treatment with each medication schedule. Results Esophageal mucosal injuries developed in two of 16 subjects in the alendronate only group and 0 of 17 in the Maxmarvil group. Gastric mucosal injuries developed in eight subjects in the alendronate group and four subjects in the Maxmarvil group; this difference was statistically significant. Conclusions The mucosal damage scores for the alendronate group (total score 24) were significantly higher than those for the Maxmarvil group (total score 9) in the esophagus and stomach. Therefore, this study suggested that enteric-coated Maxmarvil is less harmful to gastrointestinal mucosa than alendronate, and may improve the tolerability of osteoporosis medication in clinical practice.

Purpose Considerable amount of interest has been focused on the positive relationship between inflammation and the metabolic syndrome (MS). However, few studies have been performed to evaluate the relationship between baseline white blood cell (WBC) count and future risk for developing MS. Therefore, we investigated whether the baseline plasma levels of WBC count could be associated with future risk for MS in apparently healthy Korean. Materials and Methods A total of 1135 subjects (781 men and 354 women with a mean age of 49 years), who underwent health examinations at Kangbuk Samsung Hospital in both 2002 and 2005 were enrolled. The presence of MS was defined using the modified criteria of the National Cholesterol Education Program Adult Treatment Panel III using BMI instead of waist circumference. Results The baseline levels of WBC count were significantly higher among incident MS cases than among subjects without MS. The relative risks of incident MS were 1.4, 3.2 and 2.7 for WBC quartiles 2, 3, and 4, respectively, when compared with the first quartile (p-value for trend

Objective: To further understand the characteristics of insulin resistance contributing to Alzheimer disease(AD), we studied the relationship between insulin resistance and impaired cognitive domain including the patients with mild cognitive impairment(MCI) and AD. Background Large scale epidemiological studies demonstrated that diabetes increases the risk of AD. In postmortem AD brain, altered insulin receptor activities and downstream molecule of insulin are frequently noted. Accordingly, various laboratory researches have revealed that diabetes and AD has common pathogenic mechanism. Design/Methods: The consecutive one hundred participants were enrolled. All of them were satisfied with our inclusion criteria. They didn9t have diabetes on history taking, and fasting glucose and insulin level. After taking comprehensive interview, neuropsychological test and neuroimaging study with MRI, we grouped them into AD(29persons), MCI(41persons) and subjective memory impairments(SMI, 21persons) groups. Insulin resistance was estimated with the homeostasis model assessment of insulin resistance(HOMA-IR). The patients were divided into 9insulin resistance(HOMA-IR>2.43)9or9non-insulin resistance(HOMA-IR≤2.43)9. We compared the various cognitive dysfunction domains depending on insulin resistance and HOMA index in AD, MCI, and SMI groups. Results: The incidence of insulin resistance tended to be more frequent in AD compared to SMI group. Among the various cognitive domains, verbal memory adjusted by education and age was more severely impaired in insulin resistance group. While the other cognitive dysfunction such as attention, language, visuospatial and executive function was not different depending on insulin resistance. The analysis to identify the contribution of APOE4 toward relationship between verbal memory impairment and insulin resistance demonstrated that verbal memory impairment was most severe in patients having both insulin resistance and APOE4genotype. Conclusions: This study suggests that insulin resistance is associated with cognitive impairment of verbal memory in non-diabetic patients. The further study is being taken including larger number of patients to identify its clinical value predicting any clinical characteristics including disease progress in MCI and AD. Supported by: A grant of the Korean Health Technology R & D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea(A092004). Disclosure: Dr. Kim has nothing to disclose. Dr. Kim has nothing to disclose. Dr. Kim has nothing to disclose. Dr. Park has nothing to disclose. Dr. Lee has nothing to disclose. Dr. Sung has nothing to disclose. Dr. Park has nothing to disclose.

Purpose: We evaluated whether the clinicopathological factors of papillary thyroid microcarcinoma (PTMC), especially tumoe size, are associated with subcinical central lymph node metastasis. Materials and Methods: A total of 160 patients diagnosed with PTMC who underwent total thyroidectomy with bilateral central lymph node dissection were enrolled in this study. All patients were clinically lymph node negative PTMC. Patients were divided into 2 groups according to the size of tumor (≤5 mm vs. >5 mm). Clinicopathologic risk factors for subclinical central lymph node metastasis were analyzed. Results: Subclinical central lymph node metastasis was detected in 61 (38.1%). Patients with tumors ≤5 mm had a lower frequency of extrathyroidal extension, multifocality and subclinical central lymph node metastasis. On multivariate analysis, only male and tumor size >5 mm were independent predictors of subclinical central lymph node metastasis; age, multifocality, bilaterality, extrathyroidal extension, lymphvascular invasion and lymphocytic thyroiditis were not. Conclusion: In this study, male and tumor size >5 mm were two independent predictive factors for subclinical central lymph node metastasis in PTMC. These are easier factors to assess before surgery than other factors when planning the central lymph node dissection. However, further long-term follow-up studies are needed to confirm the prognostic significance of subclinical central lymph node metastasis in PTMC.

Division of Endocrinology & Metabolism, Department of Internal Medicine, The Catholic University of Korea, Seoul, Department of Internal Medicine, Inje University College of Medicine, Goyang, Division of Endocrinology & Metabolism, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Division of Endocrinology, Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Department of Diabetes Education, Samsung Medical Center, Seoul, Department of Clinical Nutrition, Kyung Hee University Medical Center, Seoul, Department of Socialwork, Hallym University Kangnam Sacred Heart Hospital, Seoul, Department of Internal Medicine, Korea University College of Medicine, Ansan, Division of Endocrinology and Metabolism, Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Division of Endicrinology & Metabolism, Sejong General Hospital, Seoul, Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Seoul, 13 Division of Endocrinology & Metabolism, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine, Bucheon, Korea

Background We investigated the relationships of adiponectin/leptin (A/L) ratio with cardiovascular risk factors, insulin resistance index, and metabolic syndrome (MS) in apparently healthy Korean male adults. Methods Sixty-eight male subjects were enrolled among the participants of an annual health check-up program (mean age, 55.1 years). Percent body fat (%) was measured using a bioelectric impedance analyzer. Serum leptin level was measured via radioimmunoassay, and adiponectin level was measured using an enzyme-linked immunosorbent assay. Homeostasis model assessment (HOMA)-insulin resistance (IR) index was calculated, and the presence of metabolic syndrome was assessed. Results Adiponectin, leptin, and A/L ratio showed significant correlations with percent body fat, lipid profile, and HOMA-IR. Mean leptin and HOMA-IR levels were significantly higher, while A/L ratio was significantly lower in subjects with MS. With increasing number of MS components, the mean values of leptin and HOMA-IR increased and the A/L ratio decreased. In multiple regression analysis, HOMA-IR was significantly correlated with triglyceride, fasting glucose, and A/L ratio, while A/L ratio was significantly correlated with body mass index and HOMA-IR. HOMA-IR and A/L ratio were significant predictors for each other after adjustment for other factors. Conclusion A/L ratio correlated well with lipid profile, HOMA-IR, and the presence and number of MS components in Korean male subjects.

Pheochromocytoma not only decreases insulin secretion but also increases insulin resistance. One third of patients with pheochromocytoma have diabetes mellitus and their clinical prognosis showed improvement after surgery. Until now, those patients whose prognosis for diabetes mellitus improved after the operation of pheochromocytoma had typical characteristics such as hypertension, palpitation, headache and elevated hormones such as Vanillylmandelic acid, metanephrine, epinephrine and norepinephrine. We present the case of a 75-year-old woman with asymptomatic adrenal incidentaloma identified as pheochromocytoma which exhibited normal biochemical test results, and after removal of the abdominal mass, her severe hyperglycemia improved.

Antithyroid hormone autoantibodies can be present in the sera of patients with thyroid and non-thyroid disorders. Antithyroid hormone autoantibodies in a patient's serum interfere with radioimmunoassay of thyroid hormones. Clinically, this interference can result in discordance between the serum thyroid hormone levels and the clinical features of the patient, which can lead to misdiagnosis or inappropriate treatment. We experienced a woman who had primary hypothyroidism with unexpectedly high concentrations of serum total triiodothyronine (T3) and free T3, and she had been treated for Graves' disease in the past. Through the use of a polyethylene glycol precipitation method, we detected the anti-triiodothyronine autoantibodies in her serum. We report on this case along with a review of the related literature. (J Kor Endocrinol Soc 21:428~432, 2006)

Metastasis to the thyroid from distant cancer is rarely diagnosed clinically and renal cell carcinoma is the most common group of neoplasm to metastasize to the thyroid. Papillary thyroid carcinoma is known as the most frequent primary thyroid cancer. But coexistence with metastatic renal cell carcinoma to thyroid and papillary thyroid carcinoma is very rare. We are reporting this highly unusual case of metastatic renal cell carcinoma to thyroid, which harbored papillary thyroid cancer. To our knowledge, this is the first case reported in Korea. A 57-year-old woman presented with hoarseness and palpable anterior neck mass. She had a history of renal cell carcinoma of right kidney, which had been resected 10 years previously and had undergone lower anterior resection due to sigmoid colon cancer 2 months before. Fine needle aspiration cytology suggested follicular neoplasm, and total thyroidectomy was performed. The pathology from the thyroid nodules showed papillary thyroid cancer combined metastatic renal cell carcinoma.