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Dutasteride, a dual inhibitor of both type I and II 5α-reductases, is used to treat male pattern hair loss (MPHL). However, patient response to dutasteride varies in each individual, the cause of which is yet to be identified. To identify genetic variants associated with response to dutasteride treatment for MPHL, a total of 42 men with moderate MPHL who had been treated with dutasteride for 6 months were genotyped and analysed by quantitative linear regression, case-control association tests, and Fisher’s exact test. The synonymous single nucleotide polymorphism (SNP) rs72623193 in DHRS9 was most significantly associated with response to dutasteride, followed by the non-synonymous SNP rs2241057 in CYP26B1. Additionally, variants in ESR1, SRD5A1, CYP19A1, and RXRG are suggested to be associated with response to dutasteride. Cumulative effect and interaction among these SNPs were presented in both additive and non-additive models.

Several factors increase the risk of fragility fracture, including low bone mineral density, falls, and poor physical performance. The associations among these factors have been investigated; however, most of the subjects of previous studies were either elderly men or elderly women, and the associations were controversial. The aim of this study was to evaluate the associations between physical performance and bone mineral density, and the history of falls and fractures, stratified by gender and age group. We analyzed 5368 subjects who were aged 50 years or older, including 1288 younger men (younger than 70 years), 1615 younger women (younger than 70 years), 1087 older men (70 years or older), and 1378 older women (70 years or older). We used the one-leg standing time (OLST) for assessing static balance and the timed up-and-go test (TUGT) for assessing dynamic balance. The subjects in the worst performance quartile for the OLST were more likely to have osteoporosis than those in the best performance quartile. Additionally, women who had experienced a fracture during the past 2 years were 1.68 times more likely to be in the worst performance quartile for the OLST than women without a previous fracture. Although the TUGT time was not associated with either the incidence of osteoporosis or the fracture history, the odds ratios for falling were 1.51 and 1.28 as the TUGT time increased by one standard deviation in younger men and younger women, respectively. The findings of the present study show that the OLST was associated with the incidence of osteoporosis and previous fracture and that the TUGT time was associated with the incidence of falling.

Background: This study aimed to compare the patterns of insulin secretion and resistance between Korean subjects in the 1990s and 2000s. Methods: Insulin secretion and resistance indices were calculated from subjects who underwent 75-g oral glucose tolerance tests in the year 1997 to 1999 and 2007 to 2011 at the Seoul St. Mary's Hospital, Korea. Results: A total of 578 subjects from the 1990s (mean age, 48.5 years) and 504 subjects from the 2000s (mean age, 50.2 years) were enrolled. Compared with the subjects from the 1990s, those from the 2000s exhibited increased insulin resistance (increased homeostatic model assessment for insulin resistance), and reduced insulin sensitivity (reduced Matsuda index and quantitative insulin sensitivity check index), regardless of their glucose tolerance status. However, insulinogenic index did not reveal significant differences between the 2 decades in subjects with or without diabetes. A distinct relationship was confirmed between Matsuda index and total area under the curve (insulin/glucose) in each glucose tolerance group. The mean product of the Matsuda index and the total area under the curve (insulin/glucose) as well as the oral disposition index, was lower in subjects with normal glucose tolerance from the 2000s than in those from the 1990s. Conclusion: After rapid economic growth and changes in lifestyle patterns, insulin resistance has worsened across the glucose tolerance status; however, the insulin secretory function remained unchanged, which resulted in an increase in the susceptibility to the development of type 2 diabetes mellitus among Korean subjects without diabetes. We could not rule out the potential selection bias and therefore, further studies in general Korean population are needed.

X-ray microbeam diffraction measurements were conducted for copper (Cu) through-silicon via (TSV) structures. This technique has the unique capability to measure stress and deformation in Cu and in silicon with submicron resolution, which enables direct observation of the local plasticity in Cu and the deformation induced by thermal stresses in TSV structures. Grain growth in Cu vias was found to play an important role in controlling the stress relaxation during thermal cycling and, thus, the residual stress and plasticity in the TSV structure. The implication of the local plasticity on TSV reliability is discussed based on the results from this study and finite element analysis.

In this study, we evaluated the association between bone mineral density (BMD) and 10 single-nucleotide polymorphisms (SNPs) within eight osteoporosis susceptibility genes that were previously identified in genome-wide association studies (GWASs). A total of 494 men and 493 postmenopausal women participating in the Chungju Metabolic Disease cohort study in Korea were included. The following 10 SNPs were genotyped: ZBTB40 rs6426749, MEF2C rs1366594, ESR1 rs2941740, TNFRSF11B rs3134070, TNFRSF11B rs2073617, SOX6 rs711785, LRP5 rs599083, TNFSF11 rs227438, TNFSF11 rs9594782, and FOXL1 rs10048146; and the association between these SNPs and bone metabolism-related markers was assessed. Two SNPs, TNFSF11 rs2277438 and FOXL1 rs1004816, were associated with lumbar spine BMD. TNFSF11 rs2277438 in men and SOX6 rs7117858 and FOXL1 rs10048146 in postmenopausal women were found to be associated with lumbar BMD. ZBTB40 rs6426749, MEF2C rs1366594, and LRP5 rs599083 showed significant associations with femur neck BMD. These three SNPs in men and MEF2C rs1366594 and ESR1 rs2941740 in postmenopausal women were associated with femur neck BMD. A significant association between MEF2C rs1366594 and serum calcium levels was observed in men. Serum phosphorus levels were related to SOX6 rs7117858. Serum PTH levels were significantly associated with TNFRSF11B rs3134070 in men, and SOX6 rs711858 in postmenopausal women. In conclusion, our study independently confirmed associations between several SNPs: ZBTB40, MEF2C, ESR1, SOX6, LRP5, TNFSF11, and FOXL1 and bone marrow density in the Korean population.

This study aimed to compare the effects of sitagliptin on glycemic change and 24-h blood glucose variability with those of the sulfonylurea glimepiride.A 4-week randomized double blind-labeled prospective design was used. We recruited 33 patients who had been treated with metformin for at least 2 months. Each participant prescribed with metformin was randomly assigned to either the sitagliptin (100 mg) or the glimepiride (2 mg) group. Continuous glucose monitoring (CGM) was used to monitor glycemic changes for 3 successive days in both groups at baseline and at the 4-week follow-up. Glycemic changes and glucose variability were obtained using CGM, and these data were averaged over all subjects.The comparison of glycated hemoglobin (HbA1c) between baseline and the 4-week follow-up showed that HbA1c was significantly reduced in the sitagliptin group (7.0 ± 0.5% to 6.6 ± 0.4%, P0.001) and the glimepiride group (7.3 ± 0.4% to 6.9 ± 0.4%, P0.001). The sitagliptin and glimepiride groups had similar HbA1c levels after 4 weeks, and there were no significant differences between the two groups. The mean amplitude of glycemic excursions (MAGE) decreased significantly in the sitagliptin group (4.9 ± 1.0 to 3.7 ± 0.9 mmol/L, P0.001), but no significant difference was observed in the glimepiride group (5.7 ± 1.5 to 5.0 ± 1.4 mmol/L, P=0.175). The SD and oxidative stress markers did not differ significantly between the two groups.When sitagliptin was combined with metformin, the patients showed much more efficient blood glucose controlling effects, not only the three indexes of fasting blood glucose, postprandial blood glucose, and glycated hemoglobin, but also MAGE.

Metabolic syndrome is defined as a cluster of glucose intolerance, hypertension, dyslipidemia and central obesity with insulin resistance as the source of pathogenesis. Although several different combinations of criteria have been used to define metabolic syndrome, a recently published consensus recommends the use of ethnic‐specific criteria, including waist circumference as an indicator of central obesity, triglyceride and high‐density lipoprotein (HDL) cholesterol as indicators of dyslipidemia, and blood pressure greater than 130/85 mmHg. The definition of dysglycemia, and whether central obesity and insulin resistance are essential components remain controversial. Regardless of the definition, the prevalence of metabolic syndrome is increasing in Western and Asian countries, particularly in developing areas undergoing rapid socioenvironmental changes. Numerous clinical trials have shown that metabolic syndrome is an important risk factor for cardiovascular disease (CVD), type 2 diabetes mellitus and all‐cause mortality. Therefore, metabolic syndrome might be useful as a practical tool to predict these two major metabolic disorders. Comprehensive management of risk factors is very important to the improvement of personal and public health. However, recent studies have focused on the role metabolic syndrome plays as a risk factor for CVD; its importance in the prediction of incident diabetes is frequently overlooked. In the present review, we summarize the known evidence supporting metabolic syndrome as a predictor for type 2 diabetes mellitus and CVD. Additionally, we suggest how metabolic syndrome might be useful in clinical practice, especially for the prediction of diabetes.

Atypical antipsychotics have replaced conventional antipsychotics in the treatment of schizophrenia because they have less of a propensity to cause undesirable neurologic adverse events including extrapyramidal symptoms, tardive dyskinesia, and neuroleptic malignant syndrome (NMS). However, atypical antipsychotics have been known to result in various metabolic complications such as impaired glucose tolerance, diabetes and even diabetic ketoacidosis (DKA). In addition, a number of NMS cases have been reported in patients treated with atypical antipsychotics, although the absolute incidence of neurologic side effects is currently significantly low. Here, we report a patient who simultaneously developed DKA, acute renal failure and NMS with rhabdomyolysis after olanzapine treatment. Olanzapine-induced metabolic complications and NMS were dramatically improved with cessation of the olanzapine treatment and initiation of supportive management including fluid therapy, hemodialysis, and intensive glycemic control using insulin. At short-term follow-up, insulin secretion was markedly recovered as evidenced by a restoration of serum C-peptide level, and the patient no longer required any hypoglycemic medications. Despite the dramatic increase in the use of atypical antipsychotics treatment, individualized treatments along with careful monitoring may be prudent for high risk or vulnerable patients in order to avoid the development of metabolic side effects.

Background: The aims of this study are to investigate the glycemic efficacy and predictive parameters of vildagliptin therapy in Korean subjects with type 2 diabetes. Methods: In this retrospective study, we retrieved data for subjects who were on twice-daily 50 mg vildagliptin for at least 6 months, and classified the subjects into five treatment groups. In three of the groups, we added vildagliptin to their existing medication regi men; in the other two groups, we replaced one of their existing medications with vildagliptin. We then analyzed the changes in glucose parameters and clinical characteristics. Results: Ultimately, 327 subjects were analyzed in this study. Vildagliptin significantly improved hemoglobin A1c (HbA1c) levels over 6 months. The changes in HbA1c levels (ΔHbA1c) at month 6 were -2.24% ( P=0.000), -0.77% (P=0.000), -0.80% (P=0.001), -0.61% (P=0.000), and -0.34% (P=0.025) for groups 1, 2, 3, 4, and 5, respectively, with significance. We also found significant decrements in fasting plasma glucose levels in groups 1, 2, 3, and 4 (P

The aim of this study was to evaluate the effects of early intensive insulin therapy on body fat distribution, lean body mass and β-cell function in patients with newly diagnosed type 2 diabetes.Thirty-eight subjects with newly diagnosed type 2 diabetes participated in a 12-week course of intensive insulin therapy. Patients were administered a 75 g oral glucose tolerance test (OGTT), underwent measurement of visceral and subcutaneous adipose tissues (VAT and SAT) using computed tomography and appendicular skeletal muscle (ASM) mass was assessed using dual-energy X-ray absorptiometry.After intensive insulin therapy, fasting plasma glucose and HbA1c levels decreased. Homeostasis model assessment (HOMA)-B, the insulinogenic index, and the C-peptide-to-glucose area under the curve (AUC) ratio increased. The insulin sensitivity index and the glucose AUC decreased after 12 weeks. The body composition analysis revealed that the VAT and the ratio of VAT to SAT decreased, whereas body weight and total fat mass increased nonsignificantly. The ASM/weight and skeletal muscle mass index increased. The restoration of β-cell function, as identified by HOMA-B, the insulinogenic index, and the C-peptide-to-glucose AUC ratio, was correlated with the changes in VAT when controlled for age and gender. In multiple regression analyses, the decrease in VAT was shown to independently contribute to improved HbA1c over the study period, after adjusting for confounding factors.These results suggest that a shift in fat distribution from visceral to subcutaneous fat after early intensive insulin therapy is associated with improvements in glycemic control and β-cell function in patients with newly diagnosed type 2 diabetes.

Asians have a propensity to develop type 2 diabetes with a lower BMI than Western populations. This discrepancy may be due to differences in body fat and muscle mass for a given BMI. However, unlike adiposity, it is unclear whether muscle mass affects the risk of type 2 diabetes in Asian populations.We conducted a 2-yearly prospective assessment of 6895 participants who were free of diabetes at the baseline examination as part of the Korean Genome Epidemiology Study. The muscle mass index (MMI) was defined as the weight-adjusted appendicular skeletal muscle mass. Using Cox regression models, we evaluated the association between MMI and the risk of developing type 2 diabetes across sex-specific tertiles of MMI. Low muscle mass was defined as the sex-specific lowest tertile of MMI. Main covariates included age, sex, urban or rural residence, family history of diabetes, hypertension, smoking status, education level, monthly income, physical activity, alcohol consumption and diet. In addition, body fat mass, waist circumference and BMI were controlled as categorical variables. Obesity was defined as a BMI of ≥25 kg/mDuring a median follow-up of 9.06 years, 1336 participants developed type 2 diabetes. At baseline, the mean age was 52.1 years and the mean BMI was 24.4 kg/mLow muscle mass as defined by MMI was associated with an increased risk of type 2 diabetes, independent of general obesity, in middle-aged and older Korean adults.

Supplemental Digital Content is available in the text, Previous studies suggest that the future risk for type 2 diabetes is not similar among subjects in the same glucose tolerance category. In this study, we aimed to evaluate simple intuitive indices to identify subjects at high risk for future diabetes development by using 0, 30, 120 minute glucose levels obtained during 75 g OGTTs from participants of a prospective community-based cohort in Korea. Among subjects enrolled at the Chungju Metabolic disease Cohort, those who performed an OGTT between 2007 and 2010 and repeated the test between 2011 and 2014 were recruited after excluding subjects with diabetes at baseline. Subjects were categorized according to their 30 minute glucose (G30) and the difference between 120 and 0 minute glucose (G(120–0)) levels with cutoffs of 9.75 and 2.50 mmol/L, respectively. Among 1126 subjects, 117 (10.39%) developed type 2 diabetes after 4 years. In diabetes nonconverters, increased insulin resistance was accompanied by compensatory insulin secretion, but this was not observed in converters during 4 years of follow-up. Subjects with G(120–0) ≥ 2.50 mmol/L or G30 ≥ 9.75 mmol/L demonstrated lower degrees of insulin secretion, higher degrees of insulin resistance, and ∼6-fold higher risk of developing future diabetes compared to their lower counterparts after adjustment for possible confounding factors. Moreover, subjects with high G(120–0) and high G30 demonstrated 22-fold higher risk for diabetes development compared to subjects with low G(120–0) and low G30. By using the G(120–0) and G30 values obtained during the OGTT, which are less complicated measurements than previously reported methods, we were able to select individuals at risk for future diabetes development. Further studies in different ethnicities are required to validate our results.

Four kinds of subcutaneous continuous glucose monitoring (CGM) machines have been currently introduced in clinical practice. These machines exhibit real-time glucose on the monitor every 5 minutes and have alarms to indicate hypoglycaemia and hyperglycaemia. However, thus far, there is no clear consensus about the clinical indications for CGM in actual clinical practice. CGM should be an ideal and powerful tool for monitoring glucose variability. Glycaemic variability has become a major concern over the years with growing evidence on its detrimental impact with respect to the risk of diabetic complications. Although the HbA1c level is ubiquitously measures in clinical practice, this level does not adequately represent glycaemic variability. Currently available evidence indicates that CGM aids in lowering the HbA1c level without increasing the incidence of severe hypoglycaemic episodes in patients with type 1 diabetes. Thus far, CGM has not been indicated for preventing severe hypoglycaemia or for treating type 2 diabetes because sufficient supporting evidence has not been obtained. Promising results have been obtained for the use of CGM for pregnant women with diabetes and for patients with hospital hyperglycaemia. Predictions regarding the feasibility of the closed-loop system have proven to be optimistic. CGM-integrated communication systems using information technology such as smart phone help controlling blood glucose more easily and effectively.

Galectin-3 (G3) immunostaining of fine-needle aspiration (FNA) samples from thyroid nodules is very useful for the diagnosis of malignancy. The objective of the present study was to determine whether the absence of G3 immunostaining in preoperative FNA samples is associated with favorable clinicopathological parameters, including lymph node (LN) metastasis, in papillary thyroid carcinoma (PTC).The records of 868 patients with PTC who had prethyroidectomy ultrasonography-guided FNA with G3 immunostaining between January 2006 and December 2009 were retrospectively reviewed. G3 immunostaining was considered positive if the percentage of tumor cells showing definite cytoplasmic immunostaining exceeded 5%. Patients who had negative G3 immunostaining of FNA samples were assigned to the G3-negative (G3N) group; whereas those who had positive G3 immunostaining were assigned to the G3-positive (G3P) group.There were 92 patients who were assigned to the G3N group (10.6%) because of the negative staining for G3 in the preoperative FNA samples from their thyroid nodules. The proportion of PTC subtypes in the G3N and G3P groups was similar (p=0.376). There was less frequent thyroid capsular invasion (46.7% vs. 66.5%, p0.001), extrathyroidal extension (28.3% vs. 48.5%, p0.001), and LN metastasis (22.2% vs. 48.7%, p0.001) in the G3N group than the G3P group. In multivariate regression analysis, G3N expression predicted a lower risk of LN metastasis (odds ratio=0.37, 95% confidence interval 0.18-0.78) after adjustment for other clinicopathological parameters. Over a median follow-up of 33 months, no association was observed between G3N and disease-free survival.The absence of G3 expression in FNA samples from PTC is associated with pathological parameters considered less aggressive than is the case for PTCs with G3 expression, including being a negative predictor of negative LN involvement. Long-term follow-up studies, however, are needed to verify whether G3N patients have lower recurrence and mortality rates.

The aim of the present study was to evaluate the independent predictors of coronary artery stenosis in patients with type 2 diabetes mellitus (DM) and subclinical atherosclerosis. A total of 232 patients with type 2 DM and subclinical atherosclerosis underwent multislice computed tomography coronary angiography. Subclinical atherosclerosis was determined by the carotid intima-media thickness (IMT) or carotid plaque. Multislice computed tomography coronary angiography revealed significant coronary stenosis (>50% in diameter) in 71 subjects (31%). The subjects who had significant coronary stenosis were much older and had had a longer duration of DM. In particular, the log-transformed albumin/creatinine ratio (ACR) was greater in the subjects with significant coronary stenosis compared to the subjects without significant coronary stenosis. The age- and gender-adjusted odds ratio for significant coronary stenosis increased in proportion to albuminuria with a given estimated glomerular filtration rate. The ACR as a continuous variable (odds ratio 4.167, 95% confidence interval 1.497 to 11.599) or categorical variable (ACR >30 μg/mg, odds ratio 4.619, 95% confidence interval 1.562 to 13.659) was associated with an increased risk of significant coronary stenosis, independent of conventional cardiovascular risk factors. In receiver operating characteristic analysis, the ACR had an additive effect with carotid IMT for predicting significant coronary stenosis (area under the curve 0.625 with carotid IMT; area under the curve 0.710 with carotid IMT plus ACR, p = 0.0144). In conclusion, the presence of albuminuria is an independent predictor for significant coronary stenosis in patients with type 2 DM and subclinical atherosclerosis.

Background While many studies have shown the good efficacy and safety of exenatide in patients with diabetes, limited information is available about exenatide in clinical practice in Korean populations. Therefore, this retrospective cohort study was designed to analyze the effects of exenatide on blood glucose level and body weight in Korean patients with type 2 diabetes mellitus. Methods We reviewed the records of the patients with diabetes who visited Seoul St. Mary's Hospital and for whom exenatide was prescribed from June 2009 to October 2011. After excluding subjects based on their race/ethnicity, medical history, whether or not they changed more than 2 kinds of oral hypoglycemic agents with exenatide treatment, loss to follow-up, or whether they stopped exenatide therapy within 6 months, a total of 52 subjects were included in the final analysis. Results The mean glycated hemoglobin (HbA1c) level and weight remarkably decreased from 8.5±1.7% to 6.7±1.0% (P

Considerable evidence suggests that hypothyroidism could promote atherosclerotic vascular changes. We planned this study to investigate whether serum free thyroxine (FT4) or thyroid-stimulating hormone (TSH) levels are associated with coronary artery calcification measured in healthy euthyroid subjects.A cross-sectional analysis was performed among subjects who visited our hospital for a health checkup. Among 1849 subjects, 669 (mean age 55.3±8.8 years; 392 men) with FT4 and TSH in the normal ranges were included after excluding those with diabetes, a history of current smoking and cardiovascular disease (CVD), or the use of drugs for hypertension, antithyroid drugs, or thyroid hormone preparations. Coronary artery calcium scores (CACS) were measured by multi-detector computed tomography.Subjects with a CACS100 had lower FT4 levels than those with a lower CACS (p=0.017), whereas no difference was observed in the TSH levels among CACS categories. FT4 levels had an odds ratio of 0.06 for high CACS (95% confidence interval=0.01-0.74; p=0.028) after the adjustment for CVD risk factors. In multivariate regression analysis, CACS was negatively correlated with FT4 levels (β=-0.823, p=0.032), and the inverse association between FT4 and CACS remained significant only in men (p=0.011).FT4 levels were inversely associated with coronary artery calcification in euthyroid healthy subjects, especially in men independent of conventional CVD risk factors. Further studies are needed to validate whether subjects with decreased FT4 levels within the normal reference range are at a high CVD risk and have poor cardiovascular outcomes.

Due to increasing demand for higher performance, greater flexibility, smaller size, and lighter weight in electronic devices, extensive studies on flexible electronic packages have been carried out. However, there has been little research on flexible packages by wafer level package (WLP) technology using anisotropic conductive films (ACFs) and flex substrates, an innovative packaging technology that requires fewer process steps and lower process temperature, and also provides flexible packages. This study demonstrated and evaluated the reliability of flexible packages that consisted of a flexible Chip-on-Flex (COF) assembly and embedded Chip-in-Flex (CIF) packages by applying a WLP process. The WLP process was successfully performed for the cases of void-free ACF lamination on a 50 μm thin wafer, wafer dicing without ACF delamination, and a flip-chip assembly which showed stable bump contact resistances. The fabricated COF assembly was more flexible than the conventional COF whose chip thickness is about 700 μm. To evaluate the flexibility of the COF assembly, a static bending test was performed under different bending radiuses: 35 mm, 30 mm, 25 mm, and 20 mm. Adopting optimized bonding processes of COF assembly and Flex-on-Flex (FOF) assembly, CIF packages were then successfully fabricated. The reliability of the CIF packages was evaluated via a high temperature/humidity test (85 °C/85% RH) and high temperature storage test (HTST). From the reliability test results, the CIF packages showed excellent 85 °C/85% RH reliability. Furthermore, guideline of ACF material property was suggested by Finite Element Analysis (FEA) for better HTST reliability.

Summary Objective To investigate the prevalence and identify the phenotype of individuals suspected to be metabolically obese but normal weight (MONW). Design and subjects Eight thousand nine hundred and eighty-seven nondiabetic subjects aged over 40 years were selected from the Chungju Metabolic disease Cohort study performed in 2003–2006 in Korea. Those within the highest quartile in the homeostasis model assessment of insulin resistance (HOMA-IR) with a normal body mass index (BMI) between 18·5 and 23 kg/m2 were classified as MONW. Measurements Data on anthropometry, lipid profiles and HOMA-IR values were analysed. Results The prevalence of MONW was 14·2% for men and 12·9% for women amongst normal-weight subjects. Multiple logistic regression analysis showed that total cholesterol (TC) levels over 5·17 mm (odds ratio, OR = 1·481; 95% confidence intervals, CI 1·086–2·021), triglyceride (TG) levels over 1·69 mm (OR = 1·507; 95% CI 1·093–2·077) and high-density lipoprotein-cholesterol levels lower than 1·03 mm (OR = 1·580; 95% CI 1·053–2·371) independently had higher odds of diagnosing MONW amongst men. For women, a BMI over 21·5 kg/m2 (OR = 1·405; 95% CI 1·034–1·909), TC levels over 5·17 mm (OR = 1·524; 95% CI 1·112–2·090) and TG levels over 1·69 mm (OR = 1·799; 95% CI 1·302–2·487) were independently associated with a diagnosis of MONW. Conclusions More than 10% of normal-weight subjects were classed as MONW in this cohort. Identification of these subjects based on lipid profiles could aid in the early detection of a high risk group of developing cardiometabolic diseases.

To determine the relationship between serum uric acid, metabolic syndrome (MetS), and albuminuria in type 2 diabetic patients.A total of 504 Korean patients with type 2 diabetes aged 57.3 years were retrospectively evaluated for clinical histories, anthropometric measurements, and biochemical studies. Urinary albumin excretion (UAE) was measured by a 24-h urine collection.Prevalence of MetS increased according to the quartiles of uric acid levels (≤3.7, 3.8 to 4.5, 4.6 to 5.5, and5.5 mg/dl; 52.1%, 52.1%, 57.5%, and 71.6%, respectively, P.001). Individual components of MetS (abdominal obesity, hypertriglyceridemia, low HDL-cholesterol, high blood pressure) were also significantly associated with the highest quintile of uric acid levels. Serum uric acid levels had significantly increased risk of albuminuria [odds ratio (OR) 1.425, 95% confidence interval (CI) 1.085-1.873] after adjusting for age, gender, and conventional risk factors. Uric acid level remains a significant predictor for abnormal albuminuria after adjusting for MetS presence as well as the use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) (OR 1.414, 95% CI 1.071-1.868).An elevated uric acid level was significantly associated with MetS and was an independent predictor of albuminuria after adjusting for conventional risk factors and MetS. Regular measurements of uric acid level could give information for predicting the presence of MetS and albuminuria in Korean type 2 diabetic patients.

Background: The present study was designed to develop criteria for screening patients with type 2 diabetes mellitus (T2DM) for asymptomatic coronary artery disease (CAD). Methods: A total of 213 patients with T2DM without typical angina or chest pain were studied between 2002 and 2007. We also evaluated 53 patients with T2DM who had reported chest discomfort using an exercise treadmill test (ETT). Results: Thirty-one of the 213 asymptomatic patients had positive ETT results. We performed coronary angiography on 23 of the 31 patients with a positive ETT and found that 11 of them had significant coronary stenosis. The main differences between the patients with significant stenosis and those with a negative ETT were age (63.1±9.4 vs. 53.7±10.1 years, P=0.008) and duration of diabetes (16.0±7.5 vs. 5.5±5.7 years, P

The association between autoimmune thyroiditis (AIT) and thyroid cancer is still not clear despite many previous reports. This study investigated whether serologic thyroid antibodies are predictive of thyroid cancer in patients with thyroid nodules.We retrospectively reviewed records of patients with thyroid nodules evaluated by ultrasonography-guided fine-needle aspiration cytology at our institution between January 2006 and December 2008. Thyroid autoimmunity was assessed by measuring thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb). The final outcome deciding a benign or malignant status involved a combination of cytology and histology.Of the 1638 patients, malignant nodules had a higher rate of positive TgAb (30.8% vs. 19.6%; p0.001) and elevated thyrotropin (TSH) levels (2.5 +/- 2.8 mIU/L vs. 2.1 +/- 2.0 mIU/L; p = 0.021) than benign nodules. The rate of positive TPOAb was not higher in malignant nodules, although both TPOAb and TgAb were well correlated with TSH levels and histological AIT. In the multivariate analysis, a positive TgAb was significantly associated with thyroid cancer (odds ratio [OR] = 1.61, 95% confidence interval [CI] 1.12-2.33) with upper tertile of normal range of TSH levels (OR = 1.72, 95% CI 1.12-2.63) and above normal range of TSH levels (OR = 1.98, 95% CI 1.06-3.70).We report for the first time that a positive serum TgAb test was an independent predictor for thyroid malignancy in thyroid nodules along with serum TSH levels regardless of the presence of AIT. Our results suggest that TgAb measurement could give additional information for predicting malignancy in cytologically indeterminate thyroid nodules in conjunction with clinical risk factors and TSH levels.

A 19-year-old girl presented at our emergency room with hypokalemic periodic paralysis. She had a thyrotoxic goiter and had experienced three paralytic attacks during the previous 2 years on occasions when she stopped taking antithyroid drugs. In addition to thyrotoxic periodic paralysis (TPP), she had metabolic acidosis, urinary potassium loss, polyuria and polydipsia. Her reduced ability to acidify urine during spontaneous metabolic acidosis was confirmed by detection of coexisting distal renal tubular acidosis (RTA). The polyuria and polydipsia were caused by nephrogenic diabetes insipidus, which was diagnosed using the water deprivation test and vasopressin administration. Her recurrent and frequent paralytic attacks may have been the combined effects of thyrotoxicosis and RTA. Although the paralytic attack did not recur after improving the thyroid function, mild acidosis and nephrogenic DI have been remained subsequently. Patients with TPP, especially females with atypical metabolic features, should be investigated for possible precipitating factors.

Previous studies suggested that estrogen might have an important role in thyroid nodule formation. Besides, it was recently reported that women with uterine fibroids, which estrogen has effects on, had an increased incidence of thyroid nodules. Our study was to identify the relationship between uterine fibroids and thyroid nodules and to find the factors that may have influences on the occurrence of thyroid nodules. We reviewed the records of 1144 participants who attended health check-ups from 2005 to 2008. Evaluated clinical variables included the size and number of thyroid nodules, presence of uterine fibroids, menopausal status, BMI, smoking, alcohol, medication status, serum levels of cholesterol, LH, FSH, and estradiol. A total of 925 participants were included and 163 (17.6%) subjects had thyroid nodules and uterine fibroids simultaneously. A significant association between both diseases existed (P=0.010), and closer relationship was observed in premenopausal women (n=445, P=0.001). In univariate analysis of systemic E2 level and the incidence of thyroid nodule in premenopausal women, systemic E2 levels had inverse correlation with the incidence of thyroid nodules (P=0.024, OR=0.631, CI: 0.424-0.940). In multivariate logistic regression analysis, older age and the presence of uterine fibroids were the independent factors for the presence of thyroid nodules. Our study suggested that uterine fibroids in women were definitely associated with thyroid nodules and estrogen might have a pivotal role in occurrence of both uterine fibroids and thyroid nodules.

Control of blood pressure is important in old age for prevention of hypertension-associated complications. This study aimed to investigate the factors associated with control of hypertension in elderly people (or=60 years old) diagnosed with hypertension.The subjects were those who had a self-reported diagnosis of hypertension (532 men and 1078 women) from a stratified random cluster sample of 4201 people aged 60 years or older. Controlled hypertension was defined as a systolic blood pressure (SBP)140 mmHg and diastolic blood pressure (DBP)90 mmHg, and SBP130 mmHg and DBP80 mmHg for subjects with diabetes.The prevalence of controlled hypertension (25.9%) was low. In older women, the prevalence of isolated uncontrolled SBP was increased. After adjusting for other covariates, uncontrolled hypertension was positively associated with body mass index (BMIor=23 kg/m(2)), and negatively associated with balanced diet and a past history of cardiovascular disease in men, whereas in women it was positively associated with waist circumference (or=80 cm).In elderly people diagnosed with hypertension general obesity (high BMI) appears to have an important influence on uncontrolled hypertension in men, whereas abdominal obesity (high waist circumference) appears to be an important factor in women.

Background/Aims: Gastrointestinal (GI) symptoms are common among patients with non-insulin dependent diabetes mellitus (NIDDM). Our aim was to investigate the frequency of chronic GI symptoms in Korean patients with NIDDM. Methods: A cross-sectional survey, using a reliable and valid questionnaire, was performed in diabetes clinics from seven hospitals of the Catholic University of Korea. Results: A total of 608 patients (249 males and 359 females, mean age 53.7±10.9 years) were investigated. The frequencies of weekly heartburn and acid regurgitation (esophageal symptoms) were 7.1% (95% confidence interval [CI], 5.0 to 9.2) and 4.4% (95% CI, 2.8 to 6.1), respectively. The frequency of dyspepsia was 13.2% (95% CI, 10.5 to 15.8). The frequencies of constipation and diarrhea were 15.0% (95% CI, 12.2 to 18.0) and 5.3% (95% CI, 3.5 to 7.1), respectively. Nausea and the use of manual maneuvers to facilitate defecation were more prevalent in women than in men. Constipation and fecal incontinence were more common in diabetes patients with long duration (>10 years). Fecal incontinence and using laxatives were more frequent in the complicated diabetes group. Using laxatives was more frequent in the uncontrolled diabetes group. Conclusions: Two-thirds of diabetic patients experienced GI symptoms. The prevalence of GI symptoms was more common in patients who had diabetic complications and a long duration of diabetes. (Korean J Intern Med 2009;24:309-317)

We aimed to establish the prevalence and characteristics of latent autoimmune diabetes in adults (LADA) and compare it with type 2 diabetes in 1370 Korean patients. The prevalence of LADA was 5.1%. Low C-peptide level and absence of metabolic syndrome were variables independently associated with the diagnosis of LADA.

The efficacy and safety of sitagliptin as monotherapy were evaluated in Chinese, Indian, and Korean patients with type 2 diabetes inadequately controlled by diet and exercise. In a randomized, placebo-controlled, double-blind, 18-week trial, 530 patients with HbA(1c) >or=7.5% and

OBJECTIVE—We investigated whether cardiovascular autonomic dysfunction was associated with glycemic control status over time in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—From 1999 to 2000, cardiovascular autonomic nerve function testing (AFT) was performed on patients with type 2 diabetes (n = 1,021) and was followed-up in 2006 and February 2008. Tests for cardiovascular autonomic functions measured heart rate variability parameters (expiration-to-inspiration [E/I] ratio, responses to the Valsalva maneuver, and standing). AFT scores were determined from the results of the each test as follows: 0 for normal and 1 for abnormal. We began with those who had a score of 0 and assessed the changes in total score along with biannual A1C levels. RESULTS—At follow-up, the development of cardiovascular autonomic dysfunction was 34.5% (E/I ratio 21.9%, Valsalva maneuver 77.8%, and posture 58.9%; n = 783). The development of cardiovascular autonomic dysfunction was higher in older patients (P < 0.001); in those with longer duration of diabetes (P < 0.001); of hypertension (P = 0.005), and of diabetic retinopathy (P < 0.001); and in those who had higher levels of microalbuminuria (P = 0.002). Logistic regression analysis revealed that the development of cardiovascular autonomic dysfunction was strongly associated with the mean A1C level during the follow-up period (mean A1C >9.0% vs. ≤7.0%, odds ratio 2.984, 95% CI 1.177–7.561; P = 0.021). CONCLUSIONS—The development of cardiovascular autonomic dysfunction was independently associated with microvascular complications and glycemic control status during this 7.5-year follow-up in patients with type 2 diabetes.

Changes in bone and mineral metabolism that occur after gastrectomy have long been recognized. Gastrectomy has been identified as a risk factor for decreased bone mass and the increased fracture incidence. Previous investigations concerning postgastrectomy bone disease have been observational studies. No prospective studies have been reported that quantify the amount of bone loss after gastrectomy within the same patients. This study investigated 46 patients undergoing gastrectomy for gastric adenocarcinoma and analyzed 36 patients (58.1+/-10.8 years, 24 men and 12 women) who had dual energy X-ray absorptiometry (DXA) performed before and 1 year after gastrectomy. Systemic adjuvant chemotherapy was administered to 14 patients. Blood was sampled from all patients to determine serum calcium, phosphorous, and bone turnover marker levels before gastrectomy and at 1, 3, 6 and 12 months after surgery and for serum parathyroid hormone (PTH) and 25-hydroxyvitamin D levels before and 12 months after surgery. The mean bone loss in the lumbar spine, total hip, femoral neck, and trochanter, which was calculated as the percentage change from the baseline to the level measured at 12 months, was 5.7% (P

Papillary thyroid microcarcinoma (PTMC) detection has been increasing explosively with the recent improvement and application of new diagnostic tools. However, the associations between clinical, histopathological, and molecular findings are often not fully evaluated in reaching a decision for the treatment of PTMC.To retrospectively evaluate the patients diagnosed with PTMC in terms of the clinical and histopathological features and the immunohistochemical findings of specific molecular markers, and thereby provide an association with the disease prognosis for the Korean patients.We have reviewed the clinical records of patients who underwent surgery for thyroid cancer (during January 2000 to August 2006 interval) at St. Mary's Hospital, Seoul, Korea. The clinical and histopathological characteristics of 217 PTMCs were evaluated cross-sectionally after surgery, and immunohistochemical staining of p53, epidermal growth factor receptor (EGFR), Ki-67, and cyclooxygenase-2 (COX-2) for 87 isolated specimens was performed.The proportions of extrathyroid extension, lymphatic invasion, and lymph node metastasis cited were 31.9%, 19.2%, and 17.8%, respectively. However, distant metastasis was not noted. Fifty-three (27.1%) patients had multiplicity, and 39 patients (20.0%) had bilateral disease. A primary tumor larger than 5 mm was significantly associated with extrathyroid extension, lymphatic invasion, and lymph node metastasis. The absence of EGFR expression shown by immunohistochemical analysis was closely correlated with extrathyroid extension and lymph node metastasis, while the absence of COX-2 expression was associated with multiplicity and bilaterality.Many patients with PTMC had clinical and histopathological poor prognostic factors. The expression of molecular markers, such as EGFR and COX-2, may have a role in the prognosis of PTMC. When considering all of the prognostic factors, a more tailored management approach appears to be necessary for patients with PTMC.

Recently, wafer-level packaging (WLP) has become one of the promising packaging technologies due to its advantages, such as fewer processing steps, lower cost, and enhanced device performance compared to conventional single-chip packaging. Many developments on new WLP design, material, and process have been accomplished according to performance and reliability requirement of the devices to be packaged [1], [2]. For a lower cost, higher performance, and environmentally green packaging process, anisotropic conductive film (ACF) flip chip assembly has been widely used, such as in ultrafine-pitch flat panel display (FPD) and general semiconductor packaging applications, too. However, there has been no previous attempt on the wafer-level flip chip assembly using ACFs. In this paper, wafer-level flip chip packages using preapplied ACFs were investigated. After ACF prelamination on an electroplated Au bumped wafer, and subsequent singulation, singulated chips were flip-chip assembled on an organic substrate using a thermocompression bonding method. Au-plated bumps were well assembled on Ni/Au pads of organic substrates. The electrical, mechanical properties and the reliabilities of wafer-level flip chip assemblies (WL-FC As) were evaluated and compared with conventional ACF flip chip assemblies using the thermocompression method. Contact resistance measurement was performed after thermal cycling, high temperature/humidity, and pressure cooker test. ACF joints between electroplated Au bumps and substrate metal pads showed stable contact resistance of 5 mOmega per a bump, strong bump adhesion, and similar reliability behaviors compared with conventional ACF flip chip joints using a thermocompression bonding. As a summary, new wafer-level packages using preapplied ACFs were successfully demonstrated for flip chip assembly. The new wafer-level packages using preapplied ACFs can be widely used for many nonsolder flip chip assembly applications such as chip-on-board (COB), chip-on-flex (COF), and chip-on-glass (COG).

Acromegaly is caused by excessive secretion of growth hormone (GH), and a resultant persistent elevation of insulin-like growth factor-1 (IGF-1) levels. Diabetes mellitus is accompanied in some acromegalic patients with insulin resistance. We encountered a type-2 diabetic patient who had a poorly controlled glycemic state and was diagnosed as acromegaly with normal IGF-1 levels. The patient showed definite acromegalic features. However, in the first screening test, GH levels were high and IGF-1 levels were inappropriately normal so the results were not close to the diagnosis of acromegaly. After moderate glycemic control, an oral glucose suppression test was performed, showing no suppressed GH response. TRH test revealed paradoxical increases in growth hormone levels and a brain MRI discovered a pituitary adenoma. After several-months insulin treatment, IGF-1 levels were increased to the abnormal state and GH levels were decreased without treatment for acromegaly. Here we report the rare case of acromegaly that presents inappropriately normal IGF-1 levels at the time of diagnosis in uncontrolled type 2 diabetic patient and shows increased IGF-1 levels after glycemic control with insulin therapy. When evaluating acromegaly in type 2 diabetes under poorly controlled glycemia, cautious IGF-1 analysis is needed after sufficient glycemic control.

We report a patient with combined polycystic ovary syndrome (PCOS) and autoimmune polyglandular syndrome (APS) type 2. A 26-year-old female presented with polyuria, polydipsia and acute weight loss. She was diagnosed with: (1) type 1 diabetes, with hyperglycemia, impaired insulin secretion, and positive autoantibodies for GAD-65 and IA-2; (2) autoimmune thyroiditis, with hypothyroidism, positive anti-microsomal and antithyroglobulin antibodies; and (3) PCOS, with hyperandrogenic signs that had developed 5 years earlier, amenorrhea for the previous 6 months, and characteristic multiple microcystic appearance of both ovaries on ultrasonography. She is being treated with multiple subcutaneous insulin injections, thyroxine replacement, and cyclic medroxyprogesterone for the aforementioned diseases, respectively. Although several investigations have reported a relationship between PCOS and the individual components of APS, this is the first report of both syndromes occurring simultaneously. Potential mechanisms for their interrelation and the possibility that PCOS is an autoimmune disease are discussed.

The spirometric measurement of pulmonary function by measuring the forced expiratory volume in one second (FEV1) is a heritable trait that reflects the physiological condition of the lung and airways. Genome-wide linkage and association studies have identified a number of genes and genetic loci associated with pulmonary function. However, limited numbers of studies have been reported for Asian populations. In this study, we aimed to investigate genetic evidence of pulmonary function in a population in northeast Asia. We conducted a family-based association test with 706 GENDISCAN study participants from 72 Mongolian families to determine candidate genetic determinants of pulmonary function. For the replication, we chose seven candidate single nucleotide polymorphisms (SNPs) from the 5 loci, and tested 1062 SNPs for association with FEV1 from 2,729 subjects of the Korea Healthy Twin study. We identified TMEM132C as a potential candidate gene at 12q24.3, which is a previously reported locus of asthma and spirometric indices. We also found two adjacent candidate genes (UNC93A and TTLL2) in the 6q27 region, which has been previously identified as a pulmonary function locus in the Framingham cohort study. Our findings suggest that novel candidate genes (TMEM132C, UNC93A and TTLL2) in two different regions are associated with pulmonary function in a population in northeast Asia.

This study prospectively investigated the changes of the serum levels of the sex steroids, IL-7, soluble receptor activator of nuclear factor kappaB ligand (sRANKL) and osteoprotegerin (OPG) in bone marrow transplantation (BMT) recipients. This study also examined whether the changes of these cytokine levels and sex steroids actually influence bone turnover and post-BMT bone loss by correlation analysis. Data were analyzed from 39 patients (33.6+/-6.4 years, 19 men and 20 women) who had DXA performed before BMT and at 1 year after BMT. The bone turnover markers, sex steroids and the cytokine levels were measured before BMT and serially after BMT. The mean bone loss in the lumbar spine and the total proximal femur was 5.9% (P < 0.01) and 11.3% (P < 0.01), respectively. During the immediate post-BMT period, bone formation decreased, whereas the bone resorption increased. For the female recipients, the estradiol levels declined at 1 week after BMT, and they did not recover to the basal levels. For the male recipients, the testosterone levels decreased at 1 week and then it increased to its baseline level. The IL-7 levels reached their maximum at 1 week and then declined to baseline level by 3 months. The serum sRANKL, OPG levels and the sRANKL/OPG ratio showed their peak at post-BMT 3 weeks. The mean daily dose of steroid was associated with suppressed bone formation, enhanced bone resorption and increased sRANKL levels. The IL-7 levels were also noted to be either positively correlated with the levels of ICTP or they were negatively correlated with the levels of osteocalcin at 1 and 3 weeks after BMT. Bone loss at the lumbar spine and the proximal femur was influenced by the decreased sex steroids and increased IL-7 levels. During the observation period, the IL-7 levels showed positive correlations with the sRANKL levels and the sRANKL/OPG ratio. For the female patients, the serum IL-7 levels were negatively associated with the estradiol levels at 1 and 3 weeks after BMT. All these findings suggest that IL-7 plays an important role for post-BMT bone loss, and this possibly happens via the RANKL pathway. These data also suggest that the up-regulation of IL-7 during the early post-BMT period may result from a deficiency of estrogen.

OBJECTIVE—To investigate the long-term effectiveness of the Internet-based glucose monitoring system (IBGMS) on glucose control in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS—We conducted a prospective, randomized, controlled trial in 80 patients with type 2 diabetes for 30 months. The intervention group was treated with the IBGMS, while the control group made conventional office visits only. HbA1c (A1C) was performed at 3-month intervals. For measuring of the stability of glucose control, the SD value of A1C levels for each subject was used as the A1C fluctuation index (HFI). RESULTS—The mean A1C and HFI were significantly lower in the intervention group (n = 40) than in the control group (n = 40). (A1C [mean ± SD] 6.9 ± 0.9 vs. 7.5 ± 1.0%, P = 0.009; HFI 0.47 ± 0.23 vs. 0.78 ± 0.51, P = 0.001; intervention versus control groups, respectively). Patients in the intervention group with a basal A1C ≥7% (n = 27) had markedly lower A1C levels than corresponding patients in the control group during the first 3 months and maintained more stable levels throughout the study (P = 0.022). Control patients with a basal A1C CONCLUSIONS—Long-term use of the IBGMS has proven to be superior to conventional diabetes care systems based on office visits for controlling blood glucose and achieving glucose stability.

Cushing's disease is a disorder of hypercortisolism caused by a pituitary micro- or macro-adenoma. Most patients with Cushing's disease have a bilateral adrenal enlargement, which depends on the duration of the disease, as a result of the long standing ACTH stimulation of both adrenal glands. However, in macronodular adrenocortical hyperplasia (MNH) that is caused by Cushing's disease, if the MNH gains autonomy, a bilateral adrenalectomy, as well as the removal of pituitary adenoma, is often essential. We encountered a patient diagnosed with Cushing's disease with bilateral adrenal tuberculosis simulating MNH. She had taken anti-tuberculosis medications one year prior to admission due to spinal tuberculosis. Sellar MRI revealed a pituitary macroadenoma, but adrenal CT showed enlargement in both adrenal glands that appeared to be MNH. A hormonal study and bilateral inferior petrosal sinus sampling revealed Cushing's disease. Therefore, she underwent trans-sphenoidal surgery of the pituitary mass. The pituitary surgery was successful and the serum cortisol returned to normal range. However, the adrenal mass rapidly enlarged after removing the pituitary tumor without showing evidence of a recurrence or adrenal autonomy of hypercortisolism. Accordingly, a laparoscopic left adrenalectomy was performed to examine the nature of the mass. The resected left adrenal gland was pathologically determined to have a lesion of tuberculosis with some part of the intact cortex. So we assumed that the cause of rapid adrenal enlargement might be due to adrenal tuberculosis. In summary, to the best of our knowledge, this is the first case of Cushing's disease coexisting with both adrenal tuberculosis simulating a bilateral MNH.

OBJECTIVE—The effect of lipoprotein(a) [Lp(a)] on the progression of diabetic nephropathy has not been evaluated yet. The aim of this study was to determine whether Lp(a) is an independent risk factor for deteriorating renal function in type 2 diabetic patients with nephropathy. RESEARCH DESIGN AND METHODS—We conducted this prospective study in type 2 diabetic patients with overt proteinuria. Patients were divided into two groups according to their baseline serum Lp(a) level. Group 1 had Lp(a) levels ≤30 mg/dl (n = 40) and group 2 had Lp(a) levels >30 mg/dl (n = 41). Patients were followed for 2 years. Progression of diabetic nephropathy was defined as a greater than twofold increase of follow-up serum creatinine concentration from the baseline value. RESULTS—At baseline and during the follow-up, there was no difference in HbA1c and lipid profile between groups 1 and 2. However, serum creatinine was significantly higher in group 2 than in group 1 after 1 year (148.3 ± 78.0 vs. 108.1 ± 34.9 μmol/l, P = 0.004) and after 2 years (216.9 ± 144.5 vs. 131.3 ± 47.3 μmol/l, P = 0.001), although baseline serum creatinine did not differ significantly between groups. In all, 13 of 14 patients with progression of diabetic nephropathy (progressors) were from group 2. Baseline Lp(a) levels were higher in the progressors than in the nonprogressors (62.9 ± 26.7 vs. 33.5 ± 27.5 mg/dl, P < 0.001). Multiple logistic regression showed that baseline Lp(a) level was a significant and independent predictor of the progression of diabetic nephropathy. CONCLUSIONS—Our study demonstrated that Lp(a) is an independent risk factor for the progression of diabetic nephropathy in type 2 diabetic patients with overt proteinuria.

The prevalence of type 2 diabetes is increasing exponentially in Asia and globally1. Of even greater concern is the fact that the incidence of type 2 diabetes has increased rapidly over a very short period of time in Asian countries2. There are many causes for this; chief among them are the decline of β‐cell function in Asians, and increased obesity resulting from rapid lifestyle changes with increased abdominal obesity and a reduction in muscle mass being issues of particular concern1. These changes have triggered rapid growth in type 2 diabetes prevalence, even among younger people1. At the same time, achievement of glucose target rates for the successful management of diabetes mellitus is far from satisfactory both globally and in Asian countries. Therefore, this requires urgent improvement. There is also a serious economic aspect to this problem; the use of antidiabetic medications and expensive oral agents aggravates the economic burden for most countries experiencing an explosive increase in the number of diabetes patients. The use of insulin also increases medical expenses. Given that the most effective and basic method of diabetes management is a well‐balanced lifestyle, there is an urgent need for the development of new treatment models aimed at lifestyle monitoring for diabetes management. Rapid developments in information technology (IT) have led to the adoption of several interactive communication systems to treat diabetes patients (Figure 1). With these interactive IT‐based systems, patients can upload glucose data that they have measured with a glucometer using high‐speed internet lines or cell phones. Medical teams can then review the uploaded data and send feedback to patients. With this feedback, patients can control their diabetes more efficiently by managing their lifestyle and/or treatment medication. This system has been introduced not only in Korea, but also in the USA and UK, and is a rising star in the effective management of diabetes mellitus. Figure 1 Patients can upload their data, such as glucose levels, bodyweight, blood pressure and so on measured at home or outdoors with some devices through a high‐speed internet line or telecommunication network. Physicians can review the uploaded data ... According to a 2006 study by Cho et al., an internet‐based glucose management system helped patients with type 2 diabetes to lower their blood glucose level and maintain this level within the target range for approximately 3 years3. In another study, a cell phone‐based diabetes management system that allowed patients to check their glucose level with their cell phones and transmit that data directly also showed promising results4. This encouraging clinical evidence prompted the development and launch of a large‐scale national project named SMART Care in Korea 2 years ago. SMART Care is a new management system for type 2 diabetes, which uses a new communications device; results from the clinical trials currently underway seem to suggest the wait is worthwhile. However, despite many positive clinical results and evidence of positive long‐term effects, much work is required before such diabetes management systems can be widely adopted. Legal and systematic issues in individual countries can also present hurdles. First, there are concerns about patient privacy. For example, there are limitations in terms of sending patient information outside the hospital. In addition, administering medical treatment over the internet can give rise to legal issues. The most important factor, however, is cost effectiveness. Questions remain as to who would be responsible for building the IT infrastructure, such as high‐speed internet networks, that is necessary for such systems to operate effectively. There is also the issue of payment of maintenance costs incurred by medical staff to run such interactive systems. A longer‐term view would suggest that the use of these new IT‐based glucose management systems could reduce medical welfare spending by lowering the rate of diabetes‐related complications and leading to better management of diabetes patients. However, because these systems require high initial set‐up and maintenance costs, their simple large‐scale deployment appears unlikely. Nonetheless, with the development of home healthcare devices and IT‐based communication technology, the development of new diabetes management system using IT is accelerating. Glucometers have been widely used for many years at home, and recent progress in biotechnology and nanotechnology is expediting the development of new home medical devices that can measure various human biosignals. Devices that can assess total cholesterol or triglyceride levels are already available, while a device that will allow measurement of liver enzymes, such as aspartate aminotransferase and alanine transaminase, will be available soon. These devices could play a crucial role in monitoring hyperlipemia, alcoholic hepatitis or viral hepatitis. Furthermore, clinical trials of a system that can wirelessly transfer continuously‐monitored patients' pulse, electrocardiography and/or activity rate to the medical team are currently undergoing clinical trials. Closer monitoring of lifestyle for patients with type 2 diabetes could be possible using the aforementioned devices, and lifestyle could be standardized and categorized for real application in diabetes management. The aforementioned systems could be even more beneficial in countries that have a rapidly increasing rate of patients with type 2 diabetes, but that do not have well‐developed medical infrastructure. Although such systems can require good IT infrastructure, such as high‐speed Internet networks, the expansion of cellular phone networks in many countries without widely available high‐speed internet networks could still signify benefits from IT‐based diabetes management systems. In addition, the growing popularity of smart phones could be very useful in the application of IT‐based diabetes management systems. Recently, for example, there has been strong interest in the clinical decision supporting system (CDSS) software program that allows feedback to be provided automatically to patients after analysis of clinical data; this is a more effective and economical way to provide care to patients. Although still in the development stage, CDSS is expected to handle even more complex data in the future, as well as having a better logic system that yields optimal answers for patients. We expect this software to open up new horizons in diabetes treatment. Its use should also reduce the burden on medical staff and maximize cost effectiveness for healthcare systems. Another study by Cho et al. noted that this new software can automatically feed suggestions to patients or provide certain data to physicians after analyzing glucose data that patients have provided over the internet. Thus, there are positive clinical effects, and the medical workload is reduced as well5. Advances in smart phone technology have made it possible for patients to send data, including glucose levels, personal information, questionnaires, events and image‐based information, to medical staff. These medical staff can now also transmit feedback and various forms of data, including graphs, images and movie clips. This allows for more intimate communication and information exchange between patients and medical staff. It also makes it possible to gather more diverse patient data, and analysis of this data should pave the way for more in‐depth patient care software. For example, when patients transmit bodyweight data and information on the amount of exercise carried out alongside simple glucose level data, medical professionals are able to carefully examine the causes of changes in glucose levels. This means they can make on‐the‐spot diagnoses, thus helping patients manage their glucose levels. Furthermore, when visible diabetic complications, such as diabetic foot ulcers, are noticed by patients, they can send images to physicians at an early stage; this will, in turn, help doctors to treat the complications more effectively. For those patients who live in remote areas and have limited immediate access to hospitals, this form of glucose management will even be more effective. As aforementioned, many Asian countries are experiencing exponential growth in the number of patients with type 2 diabetes, and this is believed to be the result of increasing obesity. Abdominal obesity and accelerating muscle mass reduction as a result of a lack of exercise are a particular problem. To make matters worse, unlike in Western countries, Asian countries are seeing increasing numbers of patients in their early 30s with type 2 diabetes1. Given this, the use of the IT‐based glucose and lifestyle management system will not only help control glucose levels, but will also bring about fundamental changes in bodyweight management. It will also promote more exercise among patients with type 2 diabetes. Furthermore, with the younger generation being more familiar with IT‐based systems, results could be more effective. More effective glycemic control for diabetes mellitus patients is now vital. However, advances in in‐home health devices and communication technology are about to usher in a new era in diabetes management. New IT‐based diabetes management systems might curb the exponential growth of diabetes and diabetes‐related complications in many Asian countries.

We evaluated whether ramipril, one of long-acting ACEIs, has a direct effect on pancreas islets in animal model of type 2 diabetes. OLETF rats were treated with ramipril for 24 weeks. We assessed the body weight, glucose tolerance, and the amount of islet fibrosis. RT-PCR and Western blot analysis of transforming growth factor-beta with its downstream signals were performed from the pancreas. Ramipril treatment remarkably reduced weight gain and the area under the curve of glucose. Islet fibrosis and the expression of TGF-beta with its downstream signal molecules were significantly reduced in the pancreas of ramipril-treated group than in control and paired-feeding group. These beneficial effects of ramipril might be related to the downregulation of TGF-beta and its downstream signals in OLETF rats. To our knowledge, this is the first report suggesting the potential effect of ramipril on the prevention of islet destruction by fibrosis in the animal model of type 2 diabetes mellitus.

Background The Modality of Insulin Treatment Evaluation (MOTIV) study was performed to provide real-world data concerning insulin initiation in Korean type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control with oral hypoglycemic agents (OHAs). Methods This multicenter, non-interventional, prospective, observational study enrolled T2DM patients with inadequate glycemic control (glycosylated hemoglobin [HbA1c] ≥7.0%) who had been on OHAs for ≥3 months and were already decided to introduce basal insulin by their physician prior to the start of the study. All treatment decisions were at the physician's discretion to reflect real-world practice. Results A total of 9,196 patients were enrolled, and 8,636 patients were included in the analysis (mean duration of diabetes, 8.9 years; mean HbA1c, 9.2%). Basal insulin plus one OHA was the most frequently (51.0%) used regimen. After 6 months of basal insulin treatment, HbA1c decreased to 7.4% and 44.5% of patients reached HbA1c

Background It has been reported that many peripheral vasodilating drugs might improve insulin resistance. Cilostazol, a antithrombotic agent, increases peripheral blood flow in non-insulin dependent diabetic patients. The effect of cilostazol treatment on insulin resistance in streptozotocin (STZ)-induced non-insulin dependent diabetic Wistar rats was examined. Methods About a half of two-day old neonate siblings were injected intraperitoneally with STZ and maintained for six months, at which time they were compared with age-matched control rats for intraperitoneal glucose tolerance test (IPGTT) and for glucose infusion rate (GINF) in a euglycemic hyperinsulinemic glucose-clamp study. After that, these studies were also performed after feeding rat chow containing cilostazol (100 mg/kg/day) to rats with STZ-induced non-insulin dependent diabetes mellitus for four-weeks and compared with those of age-matched control rats. Results In the intraperitoneal glucose tolerance test studies, plasma glucose levels of STZ-induced non-insulin dependent diabetic rats were significantly higher and plasma insulin levels significantly lower than those of age-matched control rats in the age of six months. Glucose infusion rate was lower in STZ-induced non-insulin dependent diabetic rats than those of age-matched control rats. However, after a four-week cilostazol treatment, glucose infusion rate of STZ-induced non-insulin dependent diabetic rats was not significantly different from that of control rats. Conclusion These findings suggested that cilostazol may improve insulin resistance in STZ-induced non-insulin dependent diabetic rats.

Background : To compare the 1997 American Diabetes Association (ADA) criteria with the 1985 World Health Organization (WHO) criteria in categorization of the diabetes diagnostic status of Koreans and to define clinical characteristics of subjects diagnosed differently by the two criteria. Methods : In 810 Korean subjects, we analyzed blood glucose and insulin response during 75 g oral glucose tolerance test (OGTT). According to current WHO criteria, the cutoff values of FPG which distinguish normal and IGT from diabetes were determined. Then the subjects were categorized according to both WHO and ADA criteria. The clinical characteristics of the subjects with different diagnostic categories by the two criteria were defined. Results : The FPG cut point distinguishing diabetes from IGT was 117 mg/dl, and from normal was 110 mg/dl. The overall agreement between the ADA criteria and the WHO criteria was moderate, as reflected in the κof 0.45. 141 of subjects categorized diabetes by WHO criteria were not diagnosed with ADA criteria. These discordant subjects were older in age and showed blunted early insulin response than concordant normal subjects. Conclusion : These results suggest that mild diabetes by the WHO criteria, especially in the elderly, would not be diagnosed as diabetes by the ADA FPG criteria only. Thus, in a group at high risk for developing diabetes or in a relatively older age group, we should continue using the OGTT.

To investigate whether duration of diabetes has an impact on the effectiveness of insulinization in diabetes management. This open-label, noninterventional, observational registry was conducted at >500 centers in Korea. Patients with diabetes, on oral antidiabetic drugs, with HbA1c ≥7 % (53 mmol/mol) in the preceding 3 months, being considered for initiation of basal insulin by their physicians, were included. Data were collected at baseline and at 3 and 6 months. Of 6,616 patients evaluated, 62.5 % had diabetes for

Recently, three-dimensional stacked chip package using through-silicon vias (TSVs) is a major paradigm which leads the transition of semiconductor technology from 2-D to 3-D IC in the electronic industry. However, lots of reliability concerns lie in the developing stage and we should clear away doubtful suspicion prior to mass production of 3-D stacked chip package. In this paper, an overview of reliability issues of 3-D TSV integration is introduced dividing into three categories: zero-level reliability of FEOL (front-end of the-line) such as transistors and capacitors, 1st level of BEOL (back-end of the-line) metallization and TSV interconnections, and 2nd level of micro-bumps of stacked chip interfaces. This paper describes the essential scope of the reliability challenges in 3-D IC packaging technology by dealing with reliability issues from transistor-level of the memory device to package micro-bump level of chip-to-chip interconnections.

The characteristics of thermal stresses in a five-stacked memory dies containing through-silicon vias (TSVs) were measured with synchrotron x-ray microdiffraction. The measurements were performed in and around the Cu vias for both the top and bottom dies. With scanning white beam x-ray microdiffraction, high resolution mappings of stress distribution were obtained. The results provided a direct observation of the local plasticity in Cu TSV and the stress and deformation in the surrounding Si. Thermo-mechanical modeling using finite element analysis (FEA) was carried out for the stacked structure. Results from the modeling analysis were correlated to the synchrotron observation to examine the effect of the die stacking on the stress behavior of the TSV at different die levels. Overall, the stress distribution obtained by FEA showed good agreement with the synchrotron measurement. The presence of plasticity was predicted by FEA and confirmed by the synchrotron observation. The implication of the residual stress on reliability of the memory structure was discussed. The results from this work demonstrate the capability of synchrotron based x-ray technique in studying the stress characteristics of multi-stack TSV structures.