The expert consensus on care and education for patients with diabetic kidney disease in Taiwan.

Increasing prevalence of type 2 DM (T2DM) and diabetic kidney disease (DKD) has posed a great impact in Taiwan. However, guidelines focusing on multidisciplinary patient care and patient education remain scarce. By literature review and expert discussion, we propose a consensus on care and education for patients with DKD, including general principles, specifics for different stages of chronic kidney disease (CKD), and special populations. (i.e. young ages, patients with atherosclerotic cardiovascular disease or heart failure, patients after acute kidney injury, and kidney transplant recipients). Generally, we suggest performing multidisciplinary patient care and education in alignment with the government-led Diabetes Shared Care Network to improve the patients' outcomes for all patients with DKD. Also, close monitoring of renal function with early intervention, control of comorbidities in early stages of CKD, and nutrition adjustment in advanced CKD should be emphasized.

Derivation and validation of a clinical prediction model for risks of venous thromboembolism in diabetic and general populations.

ABSTRACT: Most studies on the prediction of venous thromboembolism (VTE) focused on hospitalized, surgery, and cancer patients or women receiving hormonal contraceptives or menopausal hormone therapy. No study considered diabetic and general populations to establish a VTE prediction model, especially in Asia. We developed a predictive model for VTE among type 2 diabetic patients and the general population.This study considered 2 nationwide retrospective cohort studies consisting of 52,427 diabetic participants and 508,664 participants from the general population aged 30 to 85 years during 2001 to 2004 in Taiwan. All participants were followed up until VTE event, death, or December 2011. The outcome event was VTE, including deep venous thrombosis and pulmonary embolism. Candidate predictors consisted of socio-demographic factors, diabetes-related factors and biomarkers, comorbidities, and medicine use. Our study followed the procedures proposed by the Framingham Heart Study to develop prediction models by using a Cox regression model. The predictive accuracy and performance characteristics were assessed using the area under curve of receiver operating characteristics curve and calibration of a risk score were performed by Hosmer-Lemeshow goodness-of-fit test.The common factors for persons with type 2 diabetes and general population included age, hospitalization status 1 year before the baseline, hypertension, chronic kidney disease, chronic obstructive pulmonary disease, and anti-diabetes medications; the specific factors for persons with type 2 diabetes consisted of body mass index, glycosylated hemoglobin A1C, and creatinine; and the factors for general population included gender, peripheral vascular disease, cancer, hypertension medication, cardiovascular medication, and non-steroidal anti-inflammatory drug. The area under curve of 3-, 5-, and 8-year VTE prediction models were 0.74, 0.71, and 0.69 in the diabetic population and 0.77, 0.76, and 0.75 in the general population, respectively.The new clinical prediction models can help identify a high risk of VTE and provide medical intervention in diabetic and general populations.

The Effects of Bariatric Surgery on Renal, Neurological, and Ophthalmic Complications in Patients with Type 2 Diabetes: the Taiwan Diabesity Study.

BACKGROUND: Bariatric surgery has been shown to improve glycemic control in patients with type 2 diabetes. However, less is known whether it can also reduce diabetic renal, neurological, and ophthalmic complications. METHODS: This prospective multicenter cohort study compared renal, ophthalmic, and neurological complications between 49 patients with obesity/overweight receiving bariatric surgery and 338 patients receiving standard medical treatment after follow-up for 2 years. Patients received neurological examinations including toe tuning fork vibration test, ankle tendon reflex test, 10-g monofilament test, and ophthalmic examinations including visual acuity measurement and fundus examinations. Multiple regressions, propensity score weighting, and matching were employed to adjust for baseline differences. RESULTS: After 2 years of follow-up, patients with type 2 diabetes receiving bariatric surgery had greater reduction in BMI, HbA1c, and urine albumin-creatinine ratio, greater improvement in estimated glomerular filtration rate, and greater increase in tuning fork test score of right and left toes compared with the medical group. However, there is no improvement in 10 g-monofilament test, visual acuity, diabetic non-proliferative retinopathy, and proliferative retinopathy. Similar results were obtained using multiple regression adjustment, propensity-score weighting, or comparing age-, sex-, and BMI-matched subjects. CONCLUSIONS: After 2-year follow-up, patients with obesity/overweight and type 2 diabetes receiving bariatric surgery have increased glomerular filtration rate, reduced albuminuria, and improved tuning folk vibration sensation.

Association Between Thionamides and Acute Pancreatitis: A Case-Control Study.

Background: Thionamides have been extensively used to treat patients with hyperthyroidism worldwide. Recent pharmacovigilance studies have revealed a safety signal between carbimazole or methimazole and pancreatitis. The associated risk remains unclear. Methods: We identified patients with newly diagnosed acute pancreatitis from 2000 to 2013 as the case group from the Taiwan Longitudinal Health Insurance Database 2000, which contains data from 1996 to 2013. Each patient with acute pancreatitis was matched for age, sex, comorbidities, and cancer with four controls through propensity score matching. A total of 52 patients without matched controls were excluded. Sensitivity analyses including the 52 excluded patients were performed using a matching ratio of 1:2. Odds ratios (ORs) along with 95% confidence intervals (CIs) for the association were estimated using multivariate logistic regression. Results: We included 9204 and 36,816 patients in the case and control groups, respectively. The proportions of patients who had used thionamides, carbimazole, methimazole, and propylthiouracil were similar in these two groups. In addition, the adjusted OR (CI) for the association of acute pancreatitis with thionamides was 1.03 (0.86-1.24), with carbimazole it was 0.90 (0.63-1.30), with methimazole it was 1.05 (0.84-1.31), and with propylthiouracil it was 1.00 (0.74-1.34). The sensitivity analysis results were unchanged. Conclusions: We were unable to demonstrate an association between acute pancreatitis and usage of thionamides.

Graves' disease could increase polycystic ovary syndrome and comorbidities in Taiwan.

Background: To investigate the association between Graves' disease (GD) and polycystic ovary syndrome (PCOS) and its comorbidities.Methods: Logistic regression was performed to determine the association between the two conditions. Cumulative incidence curves were obtained using the Kaplan-Meier method and log-rank test. Hazard ratios were determined using the Cox proportional hazards regression model.Results: We included 5399 patients with GD as the study group and 10,798 patients without GD as the control group. The cumulative incidence curve of PCOS in patients with GD was significantly higher than that in patients without GD (p = .02). The adjusted hazard ratio for PCOS in patients with GD compared with patients without GD was 1.47 (95%CI = 1.09-1.98). The adjusted odds ratio of hyperlipidemia in patients with GD and PCOS was 2.18 (95%CI = 1.14-4.17) higher than that in patients with GD only.Conclusion: Our study demonstrated that women with GD could be at risk of developing PCOS; additionally, a higher incidence of comorbidities, including hyperlipidemia, was noted in women with GD and PCOS.

Increased Risk of Polycystic Ovary Syndrome and It's Comorbidities in Women with Autoimmune Thyroid Disease.

OBJECTIVE: To investigate the prevalence of polycystic ovary syndrome (PCOS) and its comorbidities in patients with autoimmune thyroid disease (AITD). POPULATION: In this cohort study, patients newly diagnosed as having Hashimoto thyroiditis (HT) or Grave disease (GD) were recruited into the AITD group. METHOD: The logistic regression model was used to investigate the association between exposure, endpoint, later diseases and treatment. MAIN OUTCOME MEASURES: We assessed the cumulative incidence using the Kaplan-Meier method and verified the difference by the log-rank test. RESULTS: The AITD group included 3599 GD patients and 1332 HT patients. PCOS risk in patients with AITD was higher than that in the control group (adjusted hazard ratio = 1.39; 95% confidence interval = 1.07-1.71). In patients with both AITD and PCOS, the odds ratios of diabetes, hyperlipidemia and coronary artery disease were 2.48, 2.05 and 2.63, respectively. CONCLUSIONS: The risks of PCOS and its comorbidities such as diabetes, dyslipidemia and cardiac artery disease are high in patients with AITD in Taiwan.

Study design and recruitment for a prospective controlled study of diabesity: Taiwan Diabesity Study.

BACKGROUND: Strong evidence has shown that metabolic surgery is more effective than medical treatment in the treatment of type 2 diabetic patients. However, no study demonstrated a survival benefit and reduction of diabetes-related end-organ damage. Here, we describe the study design of a large prospective cohort study, the Taiwan Diabesity Study (TDS) which would compare the long-term survival rate and end-organ damage between overweight/obese type 2 diabetic patients receiving metabolic surgery and medical treatment. METHODS: Eligibility criteria include type 2 diabetic patients with duration > 6 months, body mass index (BMI) over 25 kg/m2 and age between 20 and 67 years. Exclusion criteria are serum creatinine over 2.0 mg/dL, C-peptide below 1.0 ng/ml, recent history of cancer, and major diabetic complications. Eligible participants were recruited from six medical centers in Taiwan. The survival rate and diabetes-related end organ damage will be compared between the metabolic surgery group and medical group after follow-up for 10 years. RESULTS: In 3 years, 1016 participants were identified from 38,751 patients. The average BMI of patients was 30.6 (±2.6) kg/m2 and the average hemoglobin A1c was 8.2% (±1.5%) with 18% of them receiving insulin treatment. Among them, 126 patients received metabolic surgery and 890 patients received conventional medical treatment. The metabolic surgery group are younger, have a higher proportion of females, higher BMI and blood lipids as compared to the medical group. CONCLUSION: The TDS recruited 1016 overweight/obese type 2 diabetic patients including 126 patients receiving metabolic surgery and 890 patients receiving medical treatment.

Levels of high-mobility group box-1 in gingival crevicular fluid in nonsmokers and smokers with chronic periodontitis.

BACKGROUND/PURPOSE: High-mobility group box-1 (HMGB1), a proinflammatory cytokine, plays a role in inflammatory disorders. Smoking is a well-established risk factor for periodontal disease. The aim of this study was to compare the levels of HMGB1 in the gingival crevicular fluid from periodontally healthy nonsmokers, chronic periodontitis nonsmokers, and chronic periodontitis smokers. Furthermore, the relationship between levels of HMGB1 and periodontal parameters was examined. METHODS: Periodontal parameters of 17 nonsmokers with chronic periodontitis, nine smokers with chronic periodontitis, and nine periodontally healthy nonsmokers were examined. Gingival crevicular fluid samples were collected, and the levels of HMGB1 were analyzed using the enzyme-linked immunosorbent assay. RESULTS: The median level of HMGB1 was statistically significantly higher in chronic periodontitis nonsmokers (37.5 ng/mL) than in chronic periodontitis smokers (9.5 ng/mL) and periodontally healthy nonsmokers (3.7 ng/mL). There was no significant difference in the levels of HMGB1 between chronic periodontitis smokers and periodontally healthy nonsmokers. Levels of HMGB1 were positively correlated with plaque index, gingival index, probing depth, and clinical attachment level of nonsmokers. However, no significant correlations were found between levels of HMGB1 and all periodontal parameters examined in chronic periodontitis smokers. CONCLUSION: Chronic periodontitis nonsmokers had elevated levels of HMGB1 in gingival crevicular fluid. Moreover, the levels of HMGB1 were correlated with severity of periodontitis. Chronic periodontitis smokers exhibited lower levels of HMGB1 than chronic periodontitis nonsmokers. Further research is needed for understanding the role of HMGB1 in smoking and pathogenesis of periodontitis.

Andrographolide inhibits adipogenesis of 3T3-L1 cells by suppressing C/EBPß expression and activation.

Andrographolide, a diterpenoid, is the most abundant terpenoid in Andrographis paniculata, a popular Chinese herbal medicine. Andrographolide displays diverse biological activities including hypoglycemia, hypolipidemia, anti-inflammation, and anti-tumorigenesis. Recent evidence indicates that andrographolide displays anti-obesity property by inhibiting lipogenic gene expression, however, the underlying mechanisms remain to be elucidated. In this study, the effects of andrographolide on transcription factor cascade and mitotic clonal expansion in 3T3-L1 preadipocyte differentiation into adipocyte were determined. Andrographolide dose-dependently (0-15µM) inhibited CCAAT/enhancer-binding protein α (C/EBPα) and C/EBPß mRNA and protein expression as well as peroxisome proliferator-activated receptor γ (PPARγ) protein level during the adipogenesis of 3T3-L1 cells. Concomitantly, fatty acid synthase and stearoyl-CoA desaturase expression and lipid accumulation were attenuated by andrographolide. Oil-red O staining further showed that the first 48h after the initiation of differentiation was critical for andrographolide inhibition of adipocyte formation. Andrographolide inhibited the phosphorylation of PKA and the activation of cAMP response element-binding protein (CREB) in response to a differentiation cocktail, which led to attenuated C/EBPß expression. In addition, ERK and GSK3ß-dependent C/EBPß phosphorylation was attenuated by andrographolide. Moreover, andrographolide suppressed cyclin A, cyclin E, and CDK2 expression and impaired the progression of mitotic clonal expansion (MCE) by arresting the cell cycle at the Go/G1 phase. Taken together, these results indicate that andrographolide has a potent anti-obesity action by inhibiting PKA-CREB-mediated C/EBPß expression as well as C/EBPß transcriptional activity, which halts MCE progression and attenuates C/EBPα and PPARγ expression.

Low-density lipoprotein electronegativity is a novel cardiometabolic risk factor.

BACKGROUND: Low-density lipoprotein (LDL) plays a central role in cardiovascular disease (CVD) development. In LDL chromatographically resolved according to charge, the most electronegative subfraction-L5-is the only subfraction that induces atherogenic responses in cultured vascular cells. Furthermore, increasing evidence has shown that plasma L5 levels are elevated in individuals with high cardiovascular risk. We hypothesized that LDL electronegativity is a novel index for predicting CVD. METHODS: In 30 asymptomatic individuals with metabolic syndrome (MetS) and 27 healthy control subjects, we examined correlations between plasma L5 levels and the number of MetS criteria fulfilled, CVD risk factors, and CVD risk according to the Framingham risk score. RESULTS: L5 levels were significantly higher in MetS subjects than in control subjects (21.9±18.7 mg/dL vs. 11.2±10.7 mg/dL, P:0.01). The Jonckheere trend test revealed that the percent L5 of total LDL (L5%) and L5 concentration increased with the number of MetS criteria (P<0.001). L5% correlated with classic CVD risk factors, including waist circumference, body mass index, waist-to-height ratio, smoking status, blood pressure, and levels of fasting plasma glucose, triglyceride, and high-density lipoprotein. Stepwise regression analysis revealed that fasting plasma glucose level and body mass index contributed to 28% of L5% variance. The L5 concentration was associated with CVD risk and contributed to 11% of 30-year general CVD risk variance when controlling the variance of waist circumference. CONCLUSION: Our findings show that LDL electronegativity was associated with multiple CVD risk factors and CVD risk, suggesting that the LDL electronegativity index may have the potential to be a novel index for predicting CVD. Large-scale clinical trials are warranted to test the reliability of this hypothesis and the clinical importance of the LDL electronegativity index.

Dual effect of a polymorphism in the macrophage migration inhibitory factor gene is associated with new-onset Graves disease in a Taiwanese Chinese population.

Graves disease (GD) is an autoimmune disease. Macrophage migration inhibitory factor (MIF) is a potent cytokine that plays an important role in the regulation of immune responses. Two polymorphisms in the promoter region of MIF, rs5844572 and rs755622, are known to affect MIF expression. The purpose of this study was to investigate the relationship between polymorphisms in the MIF gene promoter and the severity of GD. A total of 677 individuals, including 481 GD patients and 196 ethnically matched healthy controls, were genotyped to identify differences in the distribution of the MIF polymorphisms rs5844572 and rs755622. Although there were no significant differences in the allele or genotype distributions among patients with different grades of goiter in GD and healthy controls, the distribution of the C allele, especially C/C genotype, of the rs755622 single nucleotide polymorphism (SNP) in MIF, may be as a risk factor for goiter initiation whereas a protector against development of severe goiter in patients with untreated GD (p<0.05). A goiter-developmental model incorporating genetic (MIF SNP rs755622) and environmental risk factors (gender, radioiodine treatment, thyroid gland surgery and vitiligo) significantly increased the prediction accuracy. Further studies are required to address the role of MIF polymorphisms, as well as their association with other candidate genes, in GD.

The Relationship between Stasis-Stagnation Constitution and Peripheral Arterial Disease in Patients with Type 2 Diabetes.

Objectives. In traditional Chinese medicine, Yu-Zhi (YZ, indicating stasis and stagnation) constitution describes a body that tends to express abnormal circulatory conditions. This study identified the linkage between YZ constitution and peripheral arterial disease (PAD) in patients with type 2 diabetes. Methods. Patients over 20 years of age who had had type 2 diabetes for 5 years or longer were recruited. PAD was diagnosed if the ankle-brachial index score was ≤0.9 in either leg. Level of YZ constitution was accessed by an YZ Constitution Questionnaire. Results. A total of 712 patients (354 men and 358 women) with a mean age of 61.5 ± 10.6 years and diabetes duration of 13.1 ± 6.7 years were recruited. The prevalence of PAD among our patients was 7.2%. Multivariate logistic regression revealed significant correlations between PAD and, respectively, YZ score, age, diabetes duration, current smoking, and hs-CRP. Conclusion. In addition to traditional risk factors, YZ constitution was statistically associated with PAD in patients with type 2 diabetes. This result invites further research into the effectiveness of traditional Chinese medicine to treat YZ constitution.

Oral hypoglycaemic agents and the development of non-fatal cardiovascular events in patients with type 2 diabetes mellitus.

AIMS: This study aimed to assess the risk of non-fatal cardiovascular events among patients with type 2 diabetes mellitus (T2DM) who are taking metformin, glimepiride or glyburide. MATERIALS AND METHODS: Using the National Health Insurance Research database in Taiwan, this retrospective cohort study identified 1159 patients with newly diagnosed T2DM from 1998 to 2007, 30 years and older and without a history of cardiovascular disease at baseline. Patients with cancer, liver cirrhosis or chronic kidney disease were excluded. On the basis of prescription, patients were grouped into three medication subcohorts: metformin (N = 595), glimepiride (N = 234) or glyburide (N = 330) monotherapy for 100% of the follow-up period without any oral anti-diabetic agents added or changed, by the end of 2009. Incidence and hazard ratios of non-fatal cardiovascular events including coronary artery disease, peripheral artery disease, stroke and heart failure among these three subcohorts were compared. RESULTS: The overall incidence of non-fatal cardiovascular events was the highest for patients taking glyburide (169.1 per 1000 person-years), followed by for those taking glimepiride and metformin (95.2 and 49.1 per 1000 person-years, respectively). Compared with the adjusted hazard ratio for patients taking glyburide, the adjusted hazard ratio for those taking glimepiride was 0.52 (95% CI 0.40-0.69) and for those taking metformin was 0.31 (95% CI 0.24-0.40). CONCLUSIONS: T2DM patients taking metformin and glimepiride are at lower risk of non-fatal cardiovascular events than those taking glyburide.

Annual fasting plasma glucose variation increases risk of cancer incidence and mortality in patients with type 2 diabetes: the Taichung Diabetes Study.

The study aims to examine whether the annual variations in fasting plasma glucose (FPG) measurements, represented by the coefficient of variation (CV), predict cancer incidence and mortality in the subsequent years independent of traditional risk factors of type 2 diabetic patients. A computerized database of patients with type 2 diabetes of 30 years old and older (n=4805) enrolled in the Diabetes Care Management Program of a medical center before 2006 was analyzed using a time-dependent Cox's proportional hazards regression model. The mortality rates for the first, second, and third tertiles of the first annual FPG-CV were 8.64, 12.71, and 30.82 per 1000 person-years respectively. After adjusting for mean FPG, HbA1c, and other risk factors, the annual FPG-CV was independently associated with cancer incidence, cancer mortality, and cancer incidence or mortality, and the corresponding hazard ratios for the third vs first tertile of the annual FPG-CV were 3.03 (1.98, 4.65), 5.04 (2.32, 10.94), and 2.86 (1.91, 4.29) respectively. The annual variation in FPG was a strong predictor of cancer incidence and mortality in type 2 diabetic patients; therefore, glucose variation may be important in the clinical practice of care management and cancer prevention.

Antidiabetes drugs correlate with decreased risk of lung cancer: a population-based observation in Taiwan.

BACKGROUND: The risk of some forms of cancer has been found to be higher in patients with diabetes mellitus (DM) than in the general population. The aim of this study was to examine, with sufficient statistical power, the association between DM and lung cancer and the impact of antidiabetes drugs on lung cancer risk in Taiwan. MATERIALS AND METHODS: From a randomly selected data set of 1 million National Health Insurance (NHI) claims in Taiwan from 2000-2005, 19,624 cases (patients ≥ 20 years of age) of newly diagnosed DM were identified. From the same data set, 78,496 enrollees with no record of DM were selected as controls and were matched in sex and age to the first group. The incidence of newly diagnosed lung cancer was compared between patients with DM and controls for a period of 9 years (2000-2008). RESULTS: The multivariate Cox model analysis showed a slightly increased hazard ratio (HR) of 1.05 of lung cancer in patients with DM, but the association was not statistically significant. However the use of antidiabetes drugs, such as metformin, thiazolidinediones, or alpha-glucosidase inhibitors, correlates with a decreased lung cancer risk of 39%-45%. A significant association was found between lung cancer risk and male sex (HR, 2.23), pulmonary tuberculosis (HR, 1.60), chronic obstructive pulmonary disease (HR, 1.21), and age (HR, 1.07). CONCLUSION: Patients with DM are not at increased risk for the development of lung cancer, but the use of antidiabetes drugs would considerably decrease the risk. In this cohort, male sex, age, pulmonary tuberculosis, and chronic obstructive pulmonary disease were all associated with an increased risk of lung cancer, consistent with findings in the literature and indicative of the validity of our study.

Coffee consumption is inversely associated with type 2 diabetes in Chinese.

BACKGROUND: Coffee consumption has been shown to be inversely associated to type 2 diabetes mellitus (T2DM), but evidence in Chinese populations is limited. We investigated the relationship between coffee consumption and T2DM in a population-based cohort of middle-aged Chinese. MATERIALS AND METHODS: We studied 2332 subjects who participated in the Taichung Community Health Study in Taiwan in 2004. The relationships between coffee consumption, T2DM and fasting glucose were assessed. RESULTS: The prevalence of T2DM was 14·0% and 10·4% in men and women. After adjustment for age, body mass index, blood pressure, smoking, alcohol drinking, betel nut chewing, physical activity, income, education level, fat%, protein%, carbohydrate% and magnesium, coffee intake was inversely associated with T2DM. Habitual coffee drinkers had 38-46% lower risk of T2DM than nondrinkers. Compared to nondrinkers, the adjusted odds ratios (ORs) for T2DM according to subjects with habitual coffee consumption (<1, 1-6, ≥7 times per week) were 0·77 (0·52-1·13), 0·46 (0·28-0·76) and 0·37 (0·16-0·83), respectively. The decreasing ORs indicate a dose-response effect of coffee consumption on the likelihood of having T2DM (P<0·001). A similar relationship was also evident in newly diagnosed T2DM (P<0·05). The adjusted mean fasting glucose levels gradually decreased as the frequency of coffee consumption increased (P<0·05). CONCLUSIONS: Coffee intake is inversely associated with T2DM in Chinese. Coffee may be a protective agent for T2DM in Chinese.

Chylous ascites as a manifestation of thyrotoxic cardiomyopathy in a patient with untreated Graves' disease.

BACKGROUND: Thyrotoxicosis is an uncommon cause of heart failure, and patients with heart failure rarely present with chylous ascites. In this report, we describe a patient with uncontrolled Graves' disease with thyrotoxicosis, heart failure, and chylous ascites. SUMMARY: A 39-year-old woman with no previous cardiac disease presented with dyspnea, orthopnea, palpitations, exophthalmos, goiter, distended abdomen, and pedal edema. The thyroid function tests demonstrated hyperthyroid Graves' disease (serum-free triiodothyronine level, 7.12 pg/mL [reference range, 2.0-4.0]; free thyroxine level, 4.33 ng/dL [reference range, 0.54-1.40]; thyroid-stimulating hormone level, <0.015 microU/mL [reference range, 0.34-5.60]; and thyrotropin receptor antibodies, 84.5% [reference value, <15%]). The chest radiograph showed moderate cardiomegaly and bilateral pleural effusions, electrocardiogram revealed atrial fibrillation, and the abdominal sonography found ascites. Chylous ascites was diagnosed by paracentesis and analysis of the ascitic fluid (triglyceride level, 347 mg/dL). Laboratory and imaging studies demonstrated no apparent hepatic dysfunction, abnormal tumor, lymphadenopathy, or lymphatic drainage deficit. With aggressive treatment of the heart failure and hyperthyroid state, her dyspnea, pleural effusion, chylous ascites, and edema resolved completely within a few days. CONCLUSIONS: Chylous ascites may develop as a result of heart failure secondary to thyrotoxic cardiomyopathy and resolve promptly if treated appropriately.

In addition to insulin resistance and obesity, brachial-ankle pulse wave velocity is strongly associated with metabolic syndrome in Chinese--a population-based study (Taichung Community Health Study, TCHS).

AIM: To investigate the association between arterial stiffness (present with brachial-ankle pulse wave velocity (baPWV)) and metabolic syndrome (MetS) in a population-based study of middle-aged Chinese. METHODS: MetS was defined using the AHA/NHLBI criteria. A total of 1,018 subjects aged 40 years and over were recruited in 2004. Homeostasis model assessment was applied to estimate the degree of insulin resistance (HOMA-IR). The baPWV was divided into four groups by quartiles. RESULTS: The prevalence of MetS and its individual components increased by the increase in baPWV quartiles. After adjusting for age, BMI, HOMA-IR, smoking, alcohol drinking, betel nut chewing, and physical activity status, multiple logistic regression revealed that baPWV groups were significantly associated with MetS. Compared with the lowest baPWV quartile, the adjusted odds ratio of having MetS in baPWV quartile II, III, IV was 2.10 (1.034.28), 4.48 (2.169.26), 10.4 (4.5324.0) in men, and 4.20 (1.4712.0), 14.6 (5.2240.6), 16.3 (5.4848.2) in women, respectively. The prevalence of MetS increased with the increase of age, HOMA-IR, and BMI groups. The optimal cut-off values of baPWV for MetS were 1,539 cm/sec in men and 1,482 cm/sec in women, respectively. CONCLUSIONS: In addition to insulin resistance and obesity, baPWV was strongly related to MetS in middle-aged Taiwan Chinese. The cut-off value of baPWV for cardiovascular disease differed between genders.

Regulation of insulin-response element binding protein-1 in obesity and diabetes: potential role in impaired insulin-induced gene transcription.

One of the major mechanisms by which insulin modulates glucose homeostasis is through regulation of gene expression. Therefore, reduced expression of transcription factors that are required for insulin-regulated gene expression may contribute to insulin resistance. We recently identified insulin response element-binding protein-1 (IRE-BP1) as a transcription factor that binds and transactivates multiple insulin-responsive genes, but the regulation of IRE-BP1 in vivo is largely unknown. In this study, we show that IRE-BP1 interacts with the insulin response sequence of the IGF-I, IGFBP-1, and IGFBP-3 genes using chromatin immunoprecipitation assay. Furthermore, activation by IRE-BP1 is sequence specific and mimics that of the insulin effect on gene transcription. Tissue expression of IRE-BP1 is 50- to 200-fold higher in classical insulin target compared with nontarget tissues in lean animals, with a significantly reduced level of expression in the skeletal muscle and adipose tissue in obese and diabetic animals. In the liver, IRE-BP1 is localized to the nucleus in lean rats but is sequestered to the cytoplasm in obese and diabetic animals. Cytoplasmic sequestration appears to be related to inhibition of insulin-mediated phosphatidylinositol-3 kinase signaling. Therefore, in diabetes and obesity, the mechanisms involved in reducing the transactivation of the insulin response sequence by IRE-BP1 include decreased gene transcription and nuclear exclusion to prevent DNA binding. Our study supports the notion that IRE-BP1 may be relevant to the action of insulin in vivo and may play a role in the development of insulin resistance and diabetes.