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BACKGROUND Diabetic cardiac autonomic neuropathy (CAN) is one of the important complications of diabetes. It is characterized by reduced heart rate variability (HRV). METHODS In this randomized, double-blind, placebo-controlled, multicenter trial, 75 patients were randomly assigned to one of two groups. One group (n=41) received α-lipoic acid (ALA) at an oral dose of 600 mg/day for the first 12 weeks and then 1,200 mg/day for the next 12 weeks. The other group (n=34) received placebo treatment for 24 weeks. CAN was assessed by measuring HRVs in people with diabetes. RESULTS Most of the baseline measures for HRVs were similar between the ALA and placebo groups. Although there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial, we found a positive tendency in some of the HRV parameters of the ALA group. The standard deviations of normal-to-normal RR intervals in the standing position increased by 1.87 ms in the ALA group but decreased by -3.97 ms in the placebo group (P=0.06). The power spectrum of the low frequency (LF) band in the standing position increased by 15.77 ms² in the ALA group, whereas it declined by -15.04 ms² in the placebo group (P=0.08). The high frequency/LF ratio in the upright position increased by 0.35 in the ALA group, whereas it declined by -0.42 in the placebo group (P=0.06). There were no differences between the two groups regarding rates of adverse events. CONCLUSION Although a slight improvement tendency was seen in HRV in the ALA group, there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial. However, the high oral dose of ALA was well-tolerated.

Context The coexistence of differentiated thyroid cancer (DTC) and thyroid autoimmune disease could represent a better or worse prognosis. This study investigated the prognostic importance of preoperative anti-thyroglobulin antibody (TgAb) in DTC patients. Design and patients This retrospective hospital-cohort study enrolled 1,171 consecutive DTC patients with preoperative TgAb data, who underwent total thyroidectomy between January 2006 and December 2011. Clinical parameters studied included demographics, primary tumor characteristics, radioiodine therapy, thyroid function tests, preoperative thyroglobulin (Tg) and TgAb levels, and cancer persistence/recurrence. Results A total of 254 (21.7%) patients were preoperatively TgAb-positive. The percentage positive for thyroid peroxidase (TPO) antibody and lymphocytic thyroiditis was significantly higher in the TgAb-positive group. The TgAb-positive group had a significantly higher rate of lymphatic invasion and lymph node metastasis both overall and in patients without TPOAb and lymphocytic thyroiditis (non-HT group). The mean number of total and central lymph nodes dissected and rate of lateral lymph node dissection were significantly higher in the TgAb-positive group, both overall and in non-HT patients. In regression analysis, preoperative TgAb was an independent risk factor for lateral lymph node metastasis. Over 50.2±14.5 months follow-up, disease persistence/recurrence was not significantly different between patients with and without TgAb, both overall and in non-HT patients. Preoperative TgAb showed no significant correlation with final disease status. Conclusion Positive preoperative serum TgAb is associated with worse primary tumor characteristics but rarely showed poor prognosis, probably due to more aggressive treatment of these subjects. This article is protected by copyright. All rights reserved.

Background When patients with diabetes mellitus (DM) are first referred to a hospital from primary health care clinics, physicians have to decide whether to administer an oral hypoglycemic agent (OHA) immediately or postpone a medication change in favor of diabetes education regarding diet or exercise. The aim of this study was to determine the effect of diabetes education alone (without alterations in diabetes medication) on blood glucose levels. Methods The study was conducted between January 2009 and December 2013 and included patients with DM. The glycosylated hemoglobin (HbA1c) levels were evaluated at the first visit and after 3 months. During the first medical examination, a designated doctor also conducted a diabetes education session that mainly covered dietary management. Results Patients were divided into those who received no diabetic medications (n=66) and those who received an OHA (n=124). Education resulted in a marked decrease in HbA1c levels in the OHA group among patients who had DM for 10 years showed a slightly lower HbA1c target achievement rate of

Object: There are very few studies that evaluate the influence of obesity and weight variations on change in ankle-brachial index (ABI) in subjects with type 2 diabetes (T2D) but without peripheral artery disease (PAD). Methods: In this case-control study, T2D subjects who were without baseline PAD (0.9 ≤ ABI < 1.4), and received minimum 2-year interval ABI exams were included. Subjects with prior diagnosed or treated PAD were excluded. Baseline body mass index (BMI) of all subjects was categorized as normal weight (< 23 kg/m2), overweight (23∼25 kg/m2), and obesity (≥ 25 kg/m2). Weight changes during follow-up were categorized by the percentage of weight change; weight loss (< -3%), stable (-3∼3%), gain (> 3%). Subjects with ABI decline were defined as one or both legs worsened to the abnormal (ABI < 0.9) at follow-up exam. Results: A total of 575 subjects were analyzed (188 normal, 140 overweight, and 245 obesity). During the median 2.9 years of follow-up period, 122 (21.2%) subjects showed ABI decline. When split by category of BMI and weight change, the incidence rate of ABI decline showed stepwise increasing pattern according to the obesity and weight gain. Multivariable logistic regression analysis showed that baseline obesity (vs. normal) was significantly associated with the risk of developing ABI decline after adjusting for age, sex, smoking, diabetes duration, mean HbA1c, GFR, LDL cholesterol, blood pressure, hypertensive medication, insulin use, statin use, antiplatelet use, and weight change (OR = 2.06, 95% CI = 1.22 - 3.49). On the contrary, weight loss was significantly associated with reduction in risk of developing ABI decline (OR = 0.52, 95% CI = 0.31 - 0.86). Conclusion: Obesity is an independent risk factor for developing ABI decline in T2D subjects without PAD, whereas weight loss is an independent protective factor. Weight loss should be emphasized especially in obese subjects with T2D. Disclosure Y. Yang: None. J. Lim: None. E. Lee: None. K. Yoon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc. Speaker's Bureau; Self; Takeda Pharmaceutical Company Limited. B. Cha: None. S. Lee: None. Y. Cho: None.

Background This study was a multicenter, parallel-group, double-blind, double-dummy, randomized, noninferiority trial to evaluate the efficacy and safety of γ-linolenic acid (GLA) relative to α-lipoic acid (ALA) over a 12-week treatment period in type 2 diabetes mellitus (T2DM) patients with painful diabetic peripheral neuropathy (DPN). Methods This study included 100 T2DM patients between 20 and 75 years of age who had painful DPN and received either GLA (320 mg/day) and placebo or ALA (600 mg/day) and placebo for 12 weeks. The primary outcome measures were mean changes in pain intensities as measured by the visual analogue scale (VAS) and the total symptom scores (TSS). Results Of the 100 subjects who initially participated in the study, 73 completed the 12-week treatment period. Per-protocol analyses revealed significant decreases in the mean VAS and TSS scores compared to baseline in both groups, but there were no significant differences between the groups. The treatment difference for the VAS (95% confidence interval [CI]) between the two groups was -0.65 (-1.526 to 0.213) and the upper bound of the 95% CI did not exceed the predefined noninferiority margin (δ₁=0.51). For the TSS, the treatment difference was -0.05 (-1.211 to 1.101) but the upper bound of the 95% CI crossed the noninferiority margin (δ₂=0.054). There were no serious adverse events associated with the treatments. Conclusion GLA treatment in patients with painful DPN was noninferior to ALA in terms of reducing pain intensity measured by the VAS over 12 weeks.

Objective To investigate the prevalence of subclinical hypothyroidism (SCH) in Korean adults and identify the risk factors for the occurrence of SCH by sex. Design and methods This study used data from the Sixth Korea National Health and Nutrition Examination Survey (KNHANES VI), a cross-sectional, nationally representative survey, which comprises a health interview survey, a health examination survey and a nutrition survey. To examine SCH, the reference range of thyroid-stimulating hormone (TSH) was defined using both the range provided by the test kit manufacturer (SCH-M) and a population-based range (SCH-P). We investigated the prevalence of SCH and its risk factors by sex using both reference ranges. Results The prevalence of SCH in Koreans according to SCH-M (0.35–5.5 µIU/mL) was 5.6%, and 3.3% with SCH-P (0.62–6.68 µIU/mL). For men, smoking significantly reduced the incidence of SCH, positive anti-thyroid peroxidase antibody (TPOAb) significantly increased the risk of SCH, and in an adjusted model, the risk of SCH in all quartiles increased as the urine iodine creatinine ratio (UICR) quartile increased. For women, positive TPOAb was confirmed as a risk factor for SCH, as was the highest UICR quartile. Furthermore, the odds ratio for SCH in urban vs rural residence was 1.78. Conclusions The prevalence rates of SCH were similar to those reported in the literature and previously known risk factors were confirmed using both TSH reference ranges. The notable findings from this study are that the increased risk of SCH with increased iodine intake was more marked in men than in women and that residential area may be a risk factor for SCH in women.

Objectives. Patients with diabetic peripheral neuropathy (DPN) is the most common complication. However, patients are usually suffering from not only diverse sensory deficit but also neuropathy-related discomforts. The aim of this study is to identify distinct groups of patients with DPN with respect to its clinical impacts on symptom patterns and comorbidities. Methods. A hierarchical cluster analysis and factor analysis were performed to identify relevant subgroups of patients with DPN (n=1338) and symptom patterns. Results. Patients with DPN were divided into three clusters: asymptomatic (cluster 1, n=448, 33.5%), moderate symptoms with disturbed sleep (cluster 2, n=562, 42.0%), and severe symptoms with decreased quality of life (cluster 3, n=328, 24.5%). Patients in cluster 3, compared with clusters 1 and 2, were characterized by higher levels of HbA1c and more severe pain and physical impairments. Patients in cluster 2 had moderate pain levels but disturbed sleep patterns comparable to those in cluster 3. The frequency of symptoms on each item of MNSI by “painful” symptom pattern showed a similar distribution pattern with increasing intensities along the three clusters. Conclusions. Cluster and factor analysis endorsed the use of comprehensive and symptomatic subgrouping to individualize the evaluation of patients with DPN.

Distant metastases from papillary thyroid carcinoma (PTC) are rare and are associated with a poor prognosis. Here, we describe a patient with metastatic PTC who was treated with a tyrosine kinase inhibitor (TKI, sorafenib) for several months that was acutely exacerbated by discontinuation. A 43-year-old male was diagnosed with PTC in February 2004 and underwent total thyroidectomy followed by two courses of high-dose radioactive iodine (RAI) therapy. Despite two additional courses of high-dose RAI therapy, lung and muscle metastases were developed. Treatment with sorafenib was begun in September 2010. After 11 months treatment of sorafenib, newly developed metastatic lesions were found in mediastinal lymph nodes, liver, and bones. Considered as treatment failure, the administration of sorafenib was discontinued. Two weeks after sorafenib treatment was stopped, the disease progressed abruptly and caused death of the patient by respiratory failure. In our patient, PTC progressed rapidly after the cessation of sorafenib treatment. Patients with several other types of cancer have also experienced such rapid disease progression, termed "flare-ups." Physicians should be aware that flare-ups may occur in advanced PTC patients following the cessation of TKI therapy.

Aims/Introduction Early initiation of basal insulin therapy is recommended for normalizing fasting blood glucose in type 2 diabetes mellitus. However, basal insulin treatment might not adequately control postprandial glucose levels. The present study evaluated whether the combination of the α-glucosidase inhibitor, acarbose, and basal insulin improved blood glucose control under daily-life treatment conditions in a large sample of Korean patients. Materials and Methods The present study was a multicenter, prospective, observational study under daily-life treatment conditions. A total of 539 patients with type 2 diabetes who were treated with basal insulin and additional acarbose were enrolled and followed up for 20 weeks. Changes in hemoglobin A1c, fasting and postprandial blood glucose were evaluated at baseline and at the end of the observation period. The physician and patient satisfaction of the combination treatment and safety were assessed. Results Hemoglobin A1c decreased by 0.55 ± 1.05% from baseline (P

Background The Korea National Health and Nutrition Examination Survey (KNHANES) III (2005) reported that 22.9% of individuals with diabetes have a glycated hemoglobin (HbA1c) 5 years. HbA1c in the group taking only oral hypoglycemic agents (OHAs) was significantly lower than that in the group administered only insulin or OHA and insulin in combination. In logistic regression analysis, a longer duration of diabetes, insulin use and the absence of chronic renal failure were associated with HbA1c levels >6.5%. Conclusion The level of adequate glycemic control was similar to but slightly improved compared with previous levels. The glycemic control of long-standing diabetes patients is more difficult even though they receive insulin treatment.

Diabetic peripheral neuropathy (DPN) is the most common complication associated with diabetes. DPN can present as a loss of sensation, may lead to neuropathic ulcers, and is a leading cause of amputation. Reported estimates of the prevalence of DPN vary due to differences in study populations and diagnostic criteria. Furthermore, the epidemiology and clinical characteristics of DPN in Korean patients with type 2 diabetes mellitus (T2DM) are not as well understood as those of other complications of diabetes such as retinal and renal disease. Recently, the Diabetic Neuropathy Study Group of the Korean Diabetes Association (KDA) conducted a study investigating the impact of DPN on disease burden and quality of life in patients with T2DM and has published some data that are representative of the nation. This review investigated the prevalence and associated clinical implications of DPN in Korean patients with diabetes based on the KDA study.

FDG (2-[(18)F]Fluoro-2-D-deoxyglucose-positron emission tomography (PET)/computed tomography (CT), which can detect a change in glucose metabolism in cancer cells, has been introduced as a diagnostic and prognostic tool in papillary thyroid carcinoma (PTC). However, differences in the clinicopathological and biological characteristics between primary PTCs with FDG uptake and those without FDG uptake are not well established.A total of 188 patients with PTC who had preoperative PET/CT scans were enrolled to compare the differences of clinicopathological parameters between FDG-avid (F-PTC; n = 150) and non-FDG-avid tumors (FN-PTC; n = 38). Immunohistochemical staining for glucose transporter (GLUT)-1 and hypoxia-inducible factor-1 alpha (HIF-1α) was performed.FN-PTCs were smaller; had a lower incidence of lymphatic invasion, vascular invasion, multifocality, and central lymph node metastasis; and had a lower maximum standardized uptake value than F-PTCs. After exclusion of high-risk patients for recurrence, FN-PTCs remained smaller (p0.001) and had less lymphatic invasion (p = 0.061). Among tumors larger than the spatial resolution of the PET/CT scan, macrocalcification was more frequent in FN-PTC than in F-PTC (p = 0.043). While FN-PTC and F-PTC showed no difference in GLUT-1 expression (50% vs. 75%, p = 0.363), FN-PTC showed lower HIF-1α immunoreactivity than F-PTC (25.0% vs. 75.0%, p = 0.032).Tumor size and macrocalcification are clinicopathological differences between FN-PTC and F-PTC. Biologically, HIF-1α may be responsible for increased FDG uptake in PTC.

Background Due to the inconvenience of performing oral glucose tolerance tests and day to day variability in glucose level, glycated hemoglobin (HbA1c) has been recommended by the American Diabetes Association as a method to diagnose diabetes. In addition, the Korean Diabetes Association has also recommended the use of HbA1c as a diagnostic test for diabetes. In this study, we evaluated the prevalence of diabetes according to fasting plasma glucose (FPG) level only or the combination of FPG and HbA1c tests. Methods Data from the 2011 Korea National Health and Nutrition Examination Survey (KNHANES) were analyzed. Among 5,811 subjects aged 30 years or older, 5,020 were selected after excluding the data of fasting time

Aims/Introduction: Sleep disturbances caused by painful diabetic neuropathy (PDN) might have substantial impacts on the multifaceted aspects of PDN, including quality of life. There are no convincing data on the validation or reliability of sleep problem measurements in patients with PDN in Korea. This large population-based cross-sectional study examined psychometric properties of the Medical Outcomes Study (MOS) Sleep Scale in patients with PDN in Korea. Materials and Methods: Measurements of patient-reported outcomes (Brief Pain Inventory-short form, MOS Sleep Scale and EuroQoL Health [EQ-5D]) were documented. PDN was diagnosed if the average daily pain intensity was ‡ 4b ased on the visual analog scale or if patients were taking medication for their current pain. Results: There were 577 patients with PDN (41.6% with diabetic peripheral neuropathy). The internal consistency of reliability for the MOS Sleep Scale was 0.80 as measured by Cronbach’s alpha. The extent to which multiple items in a dimension were intercorrelated and formed a dimension measuring the same underlying concept (Pearson’s correlation coefficient) ranged from 0.24 to 0.71 (all P < 0.001). Each item of the MOS Sleep Scale was significantly correlated with the average pain score and the pain interference score (Pearson’s correlation coefficients ranged from 0.20 to 0.28 and from 0.29 to 0.40, respectively; all P < 0.001). The correlations between the EQ-5D index and the MOS Sleep Scale ranged from -0.27 to -0.31 (all P < 0.001). Conclusions: The MOS Sleep Scale showed good reliability in the evaluation of PDN in Korean type 2 diabetic patients. (J Diabetes Invest, doi: 10.1111/jdi.12066, 2013)

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

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.

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.

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

Diabet. Med. 29, e290-e296 (2012) Abstract Aims Diabetic peripheral neuropathy is a common complication of diabetes. This cross-sectional study investigated the prevalence and clinical characteristics of this neuropathy in patients with Type 2 diabetic mellitus treated at hospitals in Korea. Methods Questionnaires and medical records were used to collect data on 4000 patients with Type 2 diabetes from the diabetes clinics of 40 hospitals throughout Korea. Diabetic peripheral neuropathy was diagnosed based on a review of medical records or using the Michigan Neuropathy Screening Instrument score and monofilament test. Results The prevalence of neuropathy was 33.5% (n = 1338). Multivariate analysis revealed that age, female sex, diabetes duration, lower glycated haemoglobin, treatment with oral hypoglycaemic agents or insulin, presence of retinopathy, history of cerebrovascular or peripheral arterial disease, presence of hypertension or dyslipidaemia, and history of foot ulcer were independently associated with diabetic peripheral neuropathy. Of the patients with neuropathy, 69.8% were treated for the condition and only 12.6% were aware of their neuropathy. Conclusion There was a high prevalence of peripheral neuropathy in patients with Type 2 diabetes in Korea and those patients were far more likely to have complications or co-morbidities. The proper management of diabetic peripheral neuropathy deserves attention from clinicians to ensure better management of diabetes in Korea.

Summary Objective Patients with type 2 diabetes mellitus are at greater risk of bone fractures than nondiabetics. However, the risk factors for fractures in patients with diabetes have not been fully evaluated. This study was designed to evaluate the relative frequency of fractures at different sites and the diabetes-associated factors that affect nontraumatic bone fracture in patients with type 2 diabetes. Patients and design This retrospective case–control study recruited 144 patients with type 2 diabetes, who presented with nontraumatic fractures between March 2004 and March 2009 and 150 age-, gender-, body mass index (BMI)- and duration of diabetes-matched control subjects. Nontraumatic fractures were confirmed using patients’ medical records and radiological findings. All subjects were examined for their diabetes status and associated factors for fracture, including bone mineral density (BMD). Results Of 150 reported bone fractures, the hip was the most frequent fracture site (32·7%), followed by the upper extremity (19·3%). Nontraumatic fractures were associated with diabetic retinopathy, diabetic peripheral neuropathy, stroke history, previous fracture and insulin treatment (P

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

Bone morphogenetic protein 4 (BMP-4) is involved in the earliest stages of adipocyte differentiation and is recognized as an adipogenic factor for white adipose tissue. The association of serum BMP-4 levels with anthropometric and metabolic parameters has not been previously studied. We aimed to explore the relationship of serum BMP-4 levels with obesity and metabolic syndrome. Serum BMP-4 levels were measured in 104 non-diabetic individuals from the Chungju Metabolic Disease Cohort Study. Anthropometric measurements and components of metabolic syndrome were assessed in all patients. Serum BMP-4 levels were significantly increased in individuals with obesity or metabolic syndrome. After adjusting for age and gender, serum BMP-4 levels were positively correlated with body mass index, waist circumference (WC), waist-to-hip ratio, fasting plasma insulin, homeostasis model assessment index, and triglycerides and were negatively correlated with high-density lipoprotein (HDL) cholesterol. Among these parameters, WC and HDL cholesterol were found to be independent contributing factors for serum BMP-4 levels. Serum BMP-4 levels were also significantly higher in subjects with positive diagnostic criteria for each component of metabolic syndrome. The area under the receiver operating characteristic curve for BMP-4 was 0.661 (P = 0.022, 95% CI = 0.528 to 0.794) and the cut-off value was 2.84 pg/mL. This is the first demonstration that serum BMP-4 levels are associated with adiposity, insulin resistance, and the presence of metabolic syndrome. Whether BMP-4 may be involved in the pathogenesis of obesity and metabolic syndrome deserves further investigation.

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.

Background: This study aimed to investigate the association between the presence and severity of cardiovascular autonomic neu ropathy (CAN) and development of long-term glucose fluctuation in subjects with type 2 diabetes mellitus. Methods: In this retrospective cohort study, subjects with type 2 diabetes mellitus who received cardiovascular autonomic reflex tests (CARTs) at baseline and at least 4-year of follow-up with ≥6 measures of glycosylated hemoglobin (HbA1c) were included. The severity of CAN was categorized as normal, early, or severe CAN according to the CARTs score. HbA1c variability was mea sured as the standard deviation (SD), coefficient of variation, and adjusted SD of serial HbA1c measurements. Results: A total of 681 subjects were analyzed (294 normal, 318 early, and 69 severe CAN). The HbA1c variability index values showed a positive relationship with the severity of CAN. Multivariable logistic regression analysis showed that CAN was signifi cantly associated with the risk of developing higher HbA1c variability (SD) after adjusting for age, sex, body mass index, diabetes duration, mean HbA1c, heart rate, glomerular filtration rate, diabetic retinopathy, coronary artery disease, insulin use, and anti hypertensive medication (early CAN: odds ratio [OR], 1.65; 95% confidence interval [CI], 1.12 to 2.43) (severe CAN: OR, 2.86; 95% CI, 1.47 to 5.56). This association was more prominent in subjects who had a longer duration of diabetes (>10 years) and lower mean HbA1c (

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.

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.

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.

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.

Aims Patient education is a very important part of diabetes care. However, until now, little data has been presented about the long-term effectiveness of structured intensive diabetes education programmes (SIDEP) for people with Type 2 diabetes mellitus. Methods People with Type 2 diabetes (n = 547) hospitalized from December 1999 to December 2000 were randomly assigned to two groups. Two hundred and nineteen patients undertook an inpatient SIDEP and the remaining patients received conventional glycaemic control without intensive education. After discharge, all patients were monitored regularly. Laboratory data were obtained, and adherence to self-care behaviour was determined on a five-point scale by questionnaires completed annually. Results Of the patients who completed the SIDEP, 160 (73.1%) were followed up for more than 4 years. The mean HbA1c (7.9 ± 1.2 vs. 8.7 ± 1.6%; P

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 three major forms of treatment for Graves thyrotoxicosis are antithyroid drugs, radioactive iodine therapy and thyroidectomy. Surgery is the definitive treatment for Graves thyrotoxicosis that is generally recommended when other treatments have failed or are contraindicated. Generally, thyrotoxic patients should be euthyroid before surgery to minimize potential complications which usually requires preoperative management with thionamides or inorganic iodine. But several cases of refractory Graves' disease have shown resistance to conventional treatment. Here we report a 40-year-old female patient with Graves' disease who complained of thyrotoxic symptoms for 7 months. Her thyroid function test and thyroid autoantibody profiles were consistent with Graves' disease. One kind of thionamides and β-blocker were started to control her disease. However, she was resistant to nearly all conventional medical therapies, including β-blockers, inorganic iodine, and two thionamides. She experienced hepatotoxicity from the thionamides. What was worse is her past history of serious allergic reaction to corticosteroids, which are often used to help control symptoms. A 2-week regimen of high-dose cholestyramine improved her uncontrolled thyrotoxicosis and subsequent thyroidectomy was successfully performed. In conclusion, cholestyramine could be administered as an effective and safe adjunctive agent for preoperative preparation in patients with severe hyperthyroid Graves's disease that is resistant to conventional therapies.

ObjectiveFine needle aspiration cytology (FNAC) and measurement of thyroglobulin (Tg) in needle washout (FNA-Tg) are recommended for the diagnosis of metastatic or recurrent lymph nodes (LNs) in differentiated thyroid cancer (DTC). However, the effect of serum Tg antibody (TgAb) on FNA-Tg levels still remains unclear in the preoperative setting. We analyze the interference of serum TgAb on FNA-Tg levels as proof of concept in the diagnostic advantage of serum TgAb combined with FNA-Tg.Subjects and methodsA total of 370 suspicious cervical LNs from 273 patients with DTC were included. The primary tumor was confirmed as DTC on preoperative pathology in all patients. We performed FNA-Tg measurement and FNAC on suspicious LNs and evaluated the diagnostic performance of FNAC and FNA-Tg according to TgAb status. Final diagnoses were confirmed by histological examination of excised specimens or by follow-up ultrasonography for at least 6 months.ResultsData from 273 subjects with suspicious 370 LNs were evaluated. Fifty-five LNs (14.9%) were from TgAb+ positive serum TgAb (TgAb+) patients. Serum Tg and FNA-Tg levels were significantly lower in patients with TgAb+ than in those with TgAb-negative (TgAb−). Final pathology confirmed 109 LNs (29.5%) asmalignant. Diagnostic performance of FNA-Tg at the same cutoff level was lower in the TgAb+ than TgAb− group. FNA-Tg cutoff levels determined by ROC curve were lower in the TgAb+ group.ConclusionThe results suggested that the cutoff value of FNA-Tg should be lowered in suspicious LN before thyroidectomy in thyroid cancer patients with TgAb.

Background. The measurement of stimulated thyroglobulin (sTg) after total thyroidectomy and remnant radioactive iodine (RAI) ablation is the gold standard for monitoring disease status in patients with papillary thyroid carcinomas (PTCs). The aim of this study was to determine whether sTg measurement during follow-up can be avoided in intermediate- and high-risk PTC patients.Methods. A total of 346 patients with PTCs with an intermediate or high risk of recurrence were analysed. All of the patients underwent total thyroidectomy as well as remnant RAI ablation and sTg measurements. Preoperative and postoperative parameters were included in the analysis.Results. Among the preoperative parameters, age below 45 years and preoperative Tg above 19.4 ng/mL were significant risk factors for predicting detectable sTg during follow-up. Among the postoperative parameters, thyroid capsular invasion, lymph node metastasis, and ablative Tg above 2.9 ng/mL were independently correlated with a detectable sTg range. The combination of ablative Tg less than 2.9 ng/mL with pre- and postoperative independent risk factors for detectable sTg increased the negative predictive value for detectable sTg up to 98.5%.Conclusions. Based on pre- and postoperative parameters, a substantial proportion of patients with PTCs in the intermediate- and high-risk classes could avoid aggressive follow-up measures.

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 loss of bone mass often occurs after bone marrow transplantation (BMT), particularly during the early posttransplant period. There are few reports on the role of growth factors and osteoprotegerin (OPG) in the post-BMT bone loss. This study prospectively investigated 110 patients undergoing BMT and analyzed 36 patients who had dual-energy x-ray absorptiometry performed before BMT and 1 yr after BMT. The biochemical markers of bone formation and resorption were measured at the short-term intervals during the year-long follow-up. The serum IGF-I, IGF binding protein (IGFBP)-3, fibroblast growth factor-2, macrophage-colony stimulating factor (M-CSF), and OPG levels were measured before and 1 wk, 3 wk, and 3 months after BMT. The mean bone loss in the lumbar spine and the total proximal femur, which was calculated as the percent change from the baseline to the level at 1 yr, was 5.2% (P < 0.05) and 11.6% (P < 0.01), respectively. During the immediate post-BMT period, bone formation decreased, whereas bone resorption increased, which was indicated by the biochemical markers of bone turnover. The serum IGF-I levels also decreased progressively until 3 wk and then increased to the basal values at 3 months. The serum IGFBP-3 levels decreased progressively until 3 months. The serum fibroblast growth factor-2 levels decreased to the nadir at 1 wk and gradually recovered to the basal values at 3 months. The serum M-CSF levels increased immediately after BMT, which declined to its baseline level by 3 months. The serum OPG levels increased progressively, reached a peak at 3 weeks, and declined thereafter. There were significant correlations between the IGF-I and osteocalcin levels before BMT and at 3 wk after BMT (r = 0.45, P < 0.01; r = 0.54, P < 0.01). During the observation period, the serum IGFBP-3 and M-CSF levels showed positive correlations with the osteocalcin and serum collagen I carboxyl-terminal telopeptide levels, respectively. Although statistically not significant, the OPG levels tended to be positively associated with the serum collagen I carboxyl-terminal telopeptide levels. Significant correlations were observed between the percent changes from the baseline to 1 yr in the bone mineral density at the proximal femur and the serum IGF-I levels at 3 wk and 3 months after BMT (r = 0.52, P < 0.01; r = 0.41, P < 0.05).

Background This study aimed to evaluate the effect of sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, on insulin secretion and glucagon suppression in Korean subjects with type 2 diabetes mellitus. Methods Twenty-four subjects underwent a 75-g oral glucose tolerance test (OGTT) before and after 6 months of sitagliptin treatment. Sitagliptin, insulin, and sulfonylurea were withdrawn for 3 days before OGTT to eliminate any acute effects on β-cell insulin or α-cell glucagon secretion. Venous samples were drawn five times during each OGTT to measure plasma glucose, insulin, and glucagon. Indices on insulin secretion and resistance were calculated. Results Early phase insulin secretion, measured by the insulinogenic index significantly increased after 6 months of sitagliptin treatment, especially in the higher baseline body mass index group and higher baseline glycosylated hemoglobin (HbA1c) group. There were no significant differences in the insulin resistance indices before and after sitagliptin treatment. Although no significant differences were observed in the absolute levels of glucagon and the glucagon-to-insulin ratio, there was a significant reduction in the percentile change of glucagon-to-insulin ratio at 30- and 120-minute during the OGTT. Conclusion Although the HbA1c level did not decrease significantly after 6 months of sitagliptin treatment, an increase in insulin secretion and reduction in early phase postprandial plasma glucagon-to-insulin ratio excursion was confirmed in Korean subjects with type 2 diabetes.

Aim As serum beta-2-microglobulin (B2M) levels are usually elevated in patients with renal failure, they have been suggested as a surrogate marker of cardiovascular mortality for patients with chronic kidney disease. Glycation of B2M is cytotoxic and may contribute to the risk of diabetic complications in patients with diabetes. Our objective was to evaluate the relationship between B2M and diabetic complications in patients with type 2 diabetes (T2D) and normal kidney function. Methods A total of 366 patients with T2D and preserved renal function with no clinical evidence of cardiovascular disease were enrolled consecutively into this study. High B2M was defined as a median serum B2M level ≥ 1.8mg/L. Subclinical atherosclerosis was defined as a carotid artery intima–media thickness (C-IMT) ≥ 0.9mm or the presence of carotid plaque. The definition of diabetic nephropathy was based on the presence of albuminuria (≥ 30mg/g creatinine). Results Patients with high B2M were older, and had diabetes of longer duration, higher serum creatinine, microalbuminuria, and increased vascular stiffness and C-IMT compared with patients with low B2M. B2M levels were positively correlated with C-IMT and vascular stiffness, and these associations remained constant after adjusting for age. In addition, after adjusting for age, gender, body mass index, serum creatinine, hypertension, smoking and alcohol consumption, the adjusted odds ratio (OR) for atherosclerosis was 2.01 [95% confidence interval (CI): 1.02–3.94] per 1mg/L increase in B2M. The prevalences of diabetic retinopathy and nephropathy were significantly higher with a high B2M than with a low B2M. The multiple adjusted OR for diabetic nephropathy was 2.29 (95% CI: 1.11–4.72) per 1mg/L increase of B2M. Conclusion Higher serum B2M was an independent risk factor for subclinical atherosclerosis and diabetic nephropathy in patients with T2D without renal impairment.

Recently the Korea Diabetes Association participated in the ‘Cambodia-Korea Twinning Project’ to help Cambodia establish its own modernized diabetes center and to raise awareness of the seriousness of diabetes. Here we report the status of diabetes in an urban area of Cambodia as obtained through this project.

Organ transplantation is now the treatment of choice for many patients with life-threatening chronic diseases. A new set of side effects unique to these groups of patients has become recognized, and bone disease is one of these complications. However, little is known about the effects of myeloablative treatment followed by bone marrow transplantation (BMT) on bone mineral metabolism. We have prospectively investigated 31 patients undergoing BMT for hematologic diseases. Serum concentrations of calcium, phosphorus, creatinine, gonadotropins, sex hormones, and the biochemical markers of bone turnover were measured. The samples were collected before BMT and 1, 2, 3, 4, and 12 weeks, 6 months, and 1 year after BMT. Bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry before BMT and 1 year after BMT. The serum carboxy-terminal cross-linked telopeptide of type I collagen increased progressively until 4 weeks after BMT. Thereafter, it began to decrease and reached basal values after 1 year. Serum osteocalcin decreased progressively until 3 weeks after BMT. After that, it increased and reached basal values after 3 months. No distinct differences were observed in the serum biochemical turnover markers between males and females, or between patients who received total body irradiation and those who did not. One year after BMT, lumbar spine BMD had decreased by 2.2%, and total proximal femoral BMD had decreased by 6.2%. Eighty-six percent of the women (12/14) went into a menopausal state immediately after BMT. This was caused by high gonadotropin levels and low estradiol levels. In contrast, gonadotropin levels and testosterone levels did not change significantly in the male patients after BMT. In conclusion, the rapid impairment of bone formation and the increase in bone resorption, as shown by the biochemical markers in this study, might play a role in post-BMT bone loss.

Summary Aims To examine whether long-term glycaemic control affects lipoprotein(a) (Lp(a)) levels in patients with Type 2 diabetes mellitus. Methods Eighty-nine Type 2 diabetic patients (38 men, 51 women) were recruited from the diabetes clinic. Based on HbA1c concentrations at baseline, patients were divided into two groups: those with HbA1c

Aims To determine the prevalence and risk factors for painful diabetic peripheral neuropathy (PDPN) and evaluate sleep impairment and quality of life in patients with PDPN. Methods Data from the Korean Diabetes Association Neuropathy Study Group were used to evaluate 3999 patients with type 2 diabetes. PDPN was diagnosed using visual analogue scales (VAS) and medical history. The patients were asked to answer the Brief Pain Inventory-Short Form (BPI-SF), Medical Outcomes Study Sleep (MOS-Sleep) Scale, EuroQol (EQ-5D), and VAS. Results Among the patients with diabetic peripheral neuropathy ( n =1338), 577 (43.1%) were diagnosed with PDPN (14.4% of all patients with type 2 diabetes). PDPN was independently associated with age, female gender, fasting plasma glucose, hypertension, and previous cerebrovascular events. All pain severity and interference measures were higher in patients with PDPN than in non-PDPN patients, and patients with PDPN reported more impaired sleep and lower EQ-5D and VAS scores. Conclusions The prevalence of PDPN in Koreans was comparable to that in Western populations. PDPN may impair sleep and quality of life compared with non-PDPN, and physicians should carefully consider pain symptoms in patients with diabetic peripheral neuropathy.