Assessing herpes zoster vaccine efficacy in patients with diabetes: A community-based cohort study.

The effectiveness of herpes zoster (HZ) vaccines in patients with diabetes over the age of 50 remains an active area of research. Utilizing a real-world database from the US community, this study spanning from 2006 to 2023, aimed to evaluate the impact of HZ vaccination on newly diagnosed diabetes patients who received an HZ vaccination within 1 year of diagnosis. Exclusion criteria were established to omit patients with immune deficiencies. The cohort consisted of 53 885 patients, with an average age of 63.5 years, including 43% females and 58% whites. After implementing 1:1 propensity score matching for age, sex, race, comorbidities, diabetes medication, and hemoglobin A1c to ensure comparability, the study population was further stratified into four groups: N1 comparing any HZ vaccination to non-HZ vaccination (53 882 matched pairs), N2 for Shingrix versus non-HZ vaccination (16 665 matched pairs), N3 for Zostavax versus non-HZ vaccination (12 058 matched pairs), and N4 for Shingrix versus Zostavax (11 721 matched pairs). Cox proportional hazards regression analysis revealed a hazard ratio (HR) for HZ incidence post any HZ vaccination of 0.92 (95% confidence interval [CI]: 0.83-1.01). Additional analyses yielded HRs of 1.12 (95% CI: 0.93-1.34) for Shingrix versus non-HZ vaccine, 1.02 (95% CI: 0.86-1.20) for Zostavax versus non-HZ vaccine, and 1.06 (95% CI: 0.87-1.29) for Shingrix versus Zostavax. Subgroup analyses across age, sex, and follow-up duration also showed no significant differences. These findings underscore the lack of a significant benefit from HZ vaccination in newly diagnosed diabetes patients aged over 50, highlighting the necessity for further prospective research.

Determinants of early chronic kidney disease in patients with recently diagnosed type 2 diabetes mellitus: a retrospective study from the Taiwan Diabetes Registry.

BACKGROUND: We tried to identify the risk factor associate with early chronic kidney disease (CKD) in recently diagnosed type 2 diabetes mellitus patients by utilizing real-world data from Taiwan Diabetes Registry. MATERIALS AND METHODS: Patients with type 2 diabetes mellitus recently diagnosed within 1 year. We divided the study participants into control group and early CKD group. Early CKD was defined as either CKD stage G1 with albuminuria, CKD stage G2 with albuminuria, or CKD stage G3a regardless of albuminuria (Urine-albumin to creatinine ratio (UACR) ≥ 3 mg/mmol). Control group was defined as CKD G1 or CKD G2 without albuminuria. Logistic regression analyses were used to compare differences in clinical characteristics between the subgroups. Linear regression models were employed to examine the factors predicting estimated glomerular filtration rate (eGFR) and UACR. RESULTS: Total 2217 patients with recently diagnosed type 2 diabetes mellitus were included. 1545 patients were assigned to control group and 618 patients were assigned to the early CKD group. Age (odds ratio (OR) 1.215, 95% confidence interval [CI] 1.122-1.316), systolic blood pressure (OR 1.203, 95% CI 1.117-1.296), glycated hemoglobin (OR 1.074, 95% CI 1.023-1.129) and triglyceride (OR 2.18, 95% CI 1.485-3.199) were found to be significant risk factors. Further, presence of bidirectional association between UACR and eGFR was found. CONCLUSIONS: We reported factors associated with early CKD in recently diagnosed type 2 diabetes mellitus patients. Variables that associated with eGFR and UACR were identified respectively, included a mutual influence between UACR and eGFR.

TASL, TADE, and DAROC consensus for the screening and management of hepatitis C in patients with diabetes.

Diabetes mellitus (DM) and hepatitis C virus (HCV) infection are prevalent diseases globally and emerging evidence demonstrates the bidirectional association between the two diseases. Direct-acting antivirals (DAAs) for HCV have a high treatment success rate and can significantly reduce the risks of short and long-term complications of HCV infection. However, despite the evidence of the association between diabetes and HCV and the benefits of anti-HCV treatment, previously published guidelines did not focus on the universal HCV screening for patients with diabetes and their subsequent management once confirmed as having HCV viremia. Nonetheless, screening for HCV among patients with diabetes will contribute to the eradication of HCV infection. Thus, the three major Taiwan medical associations of diabetes and liver diseases endorsed a total of 14 experts in the fields of gastroenterology, hepatology, diabetology, and epidemiology to convene and formulate a consensus statement on HCV screening and management among patients with diabetes. Based on recent studies and guidelines as well as from real-world clinical experiences, the Taiwan experts reached a consensus that provides a straightforward approach to HCV screening, treatment, and monitoring of patients with diabetes.

Denosumab Attenuates Glucolipotoxicity-Induced ß-Cell Dysfunction and Apoptosis by Attenuating RANK/RANKL Signals.

Obesity is strongly associated with insulin sensitivity in type 2 diabetes (T2D), mainly because free fatty acids (FFAs) are released from excess fat tissue. Long-term exposure to high levels of FFAs and glucose leads to glucolipotoxicity, causing damage to pancreatic ß-cells, thus accelerating the progression of T2D. Therefore, the prevention of ß-cell dysfunction and apoptosis is essential to prevent the development of T2D. Unfortunately, there are currently no specific clinical strategies for protecting ß-cells, highlighting the need for effective therapies or preventive approaches to improve the survival of ß-cells in T2D. Interestingly, recent studies have shown that the monoclonal antibody denosumab (DMB), used in osteoporosis, displays a positive effect on blood glucose regulation in patients with T2D. DMB acts as an osteoprotegerin (OPG) by inhibiting the receptor activator of the NF-κB ligand (RANKL), preventing the maturation and function of osteoclasts. However, the exact mechanism by which the RANK/RANKL signal affects glucose homeostasis has not been fully explained. The present study used human 1.4 × 107 ß-cells to simulate the T2D metabolic condition of high glucose and free fatty acids (FFAs), and it investigated the ability of DMB to protect ß-cells from glucolipotoxicity. Our results show that DMB effectively attenuated the cell dysfunction and apoptosis caused by high glucose and FFAs in ß-cells. This may be caused by blocking the RANK/RANKL pathway that reduced mammalian sterile 20-like kinase 1 (MST1) activation and indirectly increased pancreatic and duodenal homeobox 1 (PDX-1) expression. Furthermore, the increase in inflammatory cytokines and ROS caused by the RANK/RANKL signal also played an important role in glucolipotoxicity-induced cytotoxicity, and DMB can also protect ß-cells by reducing the mechanisms mentioned above. These findings provide detailed molecular mechanisms for the future development of DMB as a potential protective agent of ß-cells.

An Effective Strategy to Activate Physicians to Promote High Cardiovascular Risk Patients to Quit Smoking.

Background: Adult patients cared for by cardiologists, neurologists, and diabetologists are highly vulnerable to cardiovascular diseases (CVDs), which are worsened by smoking. In the past, physicians of these three specialties at major hospitals in Taiwan always referred patients to family medicine and chest medicine departments for smoking cessation programs. However, the participation rate in these programs was unsatisfactory. Objectives: To encourage cardiologists, neurologists, and diabetologists to provide smoking cessation treatment services (SCTSs) to their patients through an annual contest. Methods: Sequential expert meetings, group training, a contest to reward service quantity and abstinence rate, and an annual awards ceremony were held over the past 3 years. Results: More than 350 cardiologists, neurologists, and diabetologists were certified to provide SCTSs, and in the second half of 2020, 3716 high CVD risk patients entered smoking cessation treatment programs, with an abstinence rate exceeding 30% at 3 months. Conclusions: The strategy used in this study was effective in overcoming physician inertia to provide SCTSs and encourage high CVD risk smokers to quit smoking.

Early combination versus initial metformin monotherapy in the management of newly diagnosed type 2 diabetes: An East Asian perspective.

Type 2 diabetes (T2D) in the East Asian population is characterized by phenotypes such as low body mass index, an index of ß-cell dysfunction, and higher percentage of body fat, an index of insulin resistance. These phenotypes/pathologies may predispose people to early onset of diabetes with increased risk of stroke and renal disease. Less than 50% of patients with T2D in East Asia achieve glycaemic targets recommended by national or regional guidelines, which may be attributable to knowledge and/or implementation gaps. Herein, we review the latest evidence with special reference to East Asian patients with T2D and present arguments for the need to use early combination therapy to intensify glycaemic control. This strategy is supported by the 5-year worldwide VERIFY study, which reported better glycaemic durability in newly diagnosed patients with T2D with a mean HbA1c of 6.9% treated with early combination therapy of vildagliptin plus metformin versus those treated with initial metformin monotherapy followed by addition of vildagliptin only with worsening glycaemic control. This paradigm shift of early intensified treatment is now recommended by the American Diabetes Association and the European Association for the Study of Diabetes. In order to translate these evidence to practice, increased awareness and strengthening of the healthcare system are needed to diagnose and manage patients with T2D early for combination therapy.

Distinct associations of self-monitoring of blood glucose with glycemic control and hypoglycemia between groups of recently diagnosed and long-term follow-up type 2 diabetes: The Taiwan Diabetes Registry.

BACKGROUND: We investigated the uses and frequency of self-monitoring of blood glucose (SMBG) with glycemic control and hypoglycemia in two groups of type 2 diabetes (T2D) (recently diagnosed and long-term follow-up) using real-world data in Taiwan (the Taiwan Diabetes Registry). METHODS: Patients with T2D recently diagnosed within 6 months (n = 3297, mean age 54.4 ± 13.9 years) and T2D patients with long-term follow-up (n = 1201, mean age 65.5 ± 12.1 years, mean diabetes duration 14.3 ± 7.8 years) from the Taiwan Diabetes Registry were analysed. All patients were interviewed by certified diabetes educators. Information about SMBG and hypoglycemia was recorded. Demography, personal history, and laboratory data were obtained from electronic medical records. Logistic regression analyses were used to examine the associations of SMBG with glycated haemoglobin (HbA1c) <7% and hypoglycemia. RESULTS: Mean HbA1c values were 8.4 ± 2.5 and 7.6 ± 1.4%, respectively, in the recently diagnosed and long-term follow-up T2D groups. The self-reported rates of hypoglycemic events within 3 months were 10.5% and 19.0%, respectively. SMBG was associated with higher odds of HbA1c <7% (OR 1.21, 95% CI 1.01-1.44) in patients with recently diagnosed T2D, but with lower odds of HbA1c <7% in T2D patients with long-term follow-up (OR 0.60, 95% CI 0.44-0.82). In both study populations, SMBG was independently associated with hypoglycemia (OR 3.90 [95% CI 2.99-5.08] and OR 3.93 [95% CI 2.73-5.66], respectively). The aforementioned findings were consistent across the strata of SMBG frequency. CONCLUSION: We reported different associations between SMBG and glycemic control in patients recently diagnosed with T2D and in T2D patients with long-term follow-up. SMBG was associated with higher detection of hypoglycemic episodes in both study populations.

The Risk of Thyroid Cancer in Patients with Thyroid Nodule 3 Cm Or Larger.

OBJECTIVE: There are conflicting data on the risk of thyroid cancer in thyroid nodules 3 cm or larger, and few such studies on this issue have been conducted in Asia. This study aimed to examine the risk of thyroid cancer in patients with thyroid nodules 3 cm or larger. METHODS: This was a 7-year retrospective study conducted in a tertiary referral hospital in Taiwan. All patients with a thyroid nodule measuring ≥3 cm who underwent thyroid operation with or without fine-needle aspiration biopsy (FNAB) were included. The prevalence rate of thyroid cancer, as well as the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and false-negative rate of FNAB for thyroid nodule ≥3 cm were also examined. RESULTS: A total of 132 patients were included in this study. Thyroid cancer was detected in 19 of 132 (14.4%) thyroid nodules measuring ≥3 cm. The performance of FNAB for detecting cancer in nodules 3 cm or larger without considering other ultrasonography parameters was relatively poor with a sensitivity of 50%, but the specificity (100%), PPV (100 %), and NPV (93.4 %) were excellent. CONCLUSION: The risk of thyroid cancer for thyroid nodules ≥3 cm in this study was low. The PPV and NPV of FNAB were high for the detection of cancer in large nodules. The decision to perform thyroidectomy should not be solely based on nodule size and should include other factors, such as ultrasound characteristics and surgical risk.

Dipeptidyl-Peptidase 4 Inhibitors did not Improve Renal Endpoints in Advanced Diabetic Kidney Disease.

OBJECTIVE: The efficacy of dipeptidyl-peptidase 4 inhibitors (DPP4is) in advanced diabetic kidney disease (DKD) is unknown. We investigated whether DPP4is confer renal protective benefits in DKD patients. METHODS: We conducted a retrospective cohort study between 2012 and 2018 in Taiwan. We only included type 2 diabetes patients with estimated glomerular filtration rate (eGFR) between 30 and 90 mL/min/1.73 m2 and urine albumin to creatinine ratio between 300 and 5,000 mg/g. Patients with DPP4i prescriptions were selected as cases, while non-DPP4i users served as controls. We followed these patients until the presence of composite primary renal endpoints, which was defined by the earliest occur-rence of clinical renal outcomes. RESULTS: A total of 522 patients were included in the analysis, comprising 273 patients with a DPP4i prescription who were selected as cases and 249 patients without DPP4i prescription who were assigned as controls. Median follow-up duration for DPP4i users and nonusers was 2.2 years and 3.4 years, respectively. At baseline, the mean glycated hemoglobin levels for DPP4i users and nonusers were 8.1% and 8.3%, respectively. Among patients with DPP4i prescriptions, there was no reduction in composite primary renal outcome, with a crude hazard ratio (HR) of 1.50 (95% confidence interval [CI], 0.95 to 2.36). Similar results were observed for the risk of persistent eGFR <15 mL/min/1.73 m2, with a HR of 1.68 (95% CI, 0.90 to 3.13), doubling of serum creatinine level, with a HR of 1.05 (95% CI, 0.15 to 7.45), and end-stage renal disease, with a HR of 0.87 (95% CI, 0.14 to 5.19). CONCLUSION: DPP4i prescription did not reduce the risk of composite renal endpoints in DKD patients. ABBREVIATIONS: BMI = body mass index; CI = confidence interval; CVOT = cardiovascular outcomes trial; DPP4i = dipeptidyl-peptidase 4 inhibitor; DKD = diabetic kidney disease; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease; HbA1c = glycated hemoglobin; HR = hazard ratio; SGLT2i = sodium-glucose cotransporter 2 inhibitor; T2D = type 2 diabetes; UACR = urine albumin to creatinine ratio.

PM2.5 exposure and DLEC1 promoter methylation in Taiwan Biobank participants.

BACKGROUND: Particulate matter (PM) < 2.5 µm (PM2.5) or fine PM is a serious public health concern. It affects DNA methylation and heightens carcinogenesis. Deleted in lung and esophageal cancer 1 (DLEC1) is a tumor suppressor gene. However, aberrant methylation of the gene is associated with several cancers. We evaluated the association between PM2.5 and DLEC1 promoter methylation in Taiwanese adults based on regular outdoor exercise. METHODS: We obtained DNA methylation and exercise data of 496 participants (aged between 30 and 70 years) from the Taiwan Biobank (TWB) database. We also extracted PM2.5 data from the Air Quality Monitoring Database (AQMD) and estimated participants' exposure using residential addresses. RESULTS: DLEC1 methylation and PM2.5 were positively associated: beta coefficient (ß) = 0.114 × 10-3; p value = 0.046. The test for interaction between exercise and PM2.5 on DLEC1 methylation was significant (p value = 0.036). After stratification by exercise habits, PM2.5 and DLEC1 methylation remained significantly associated only among those who exercised regularly (ß = 0.237 × 10-3; p value = 0.007). PM2.5 quartile-stratified analyses revealed an inverse association between regular exercise and DLEC1 methylation at PM2.5 < 27.37 µg/m3 (ß = - 5.280 × 10-3; p value = 0.009). After combining exercise habits and PM2.5 quartiles, one stratum (i.e., regular exercise and PM2.5 < 27.37 µg/m3) was inversely associated with DLEC1 methylation (ß = -5.160 × 10-3, p value = 0.007). CONCLUSIONS: We found significant positive associations between PM2.5 and DLEC1 promoter methylation. Regular exercise at PM2.5 < 27.37 µg/m3 seemingly regulated DLEC1 promoter methylation.

Liraglutide protects against glucolipotoxicity-induced RIN-m5F ß-cell apoptosis through restoration of PDX1 expression.

Prolonged exposure to high levels of glucose and fatty acid (FFA) can induce tissue damage commonly referred to as glucolipotoxicity and is particularly harmful to pancreatic ß-cells. Glucolipotoxicity-mediated ß-cell failure is a critical causal factor in the late stages of diabetes, which suggests that mechanisms that prevent or reverse ß-cell death may play a critical role in the treatment of the disease. Transcription factor PDX1 was recently reported to play a key role in maintaining ß-cell function and survival, and glucolipotoxicity can activate mammalian sterile 20-like kinase 1 (Mst1), which, in turn, stimulates PDX1 degradation and causes dysfunction and apoptosis of ß-cells. Interestingly, previous research has demonstrated that increased glucagon-like peptide-1 (GLP-1) signalling effectively protects ß cells from glucolipotoxicity-induced apoptosis. Unfortunately, few studies have examined the related mechanism in detail, especially the role in Mst1 and PDX1 regulation. In the present study, we investigate the toxic effect of high glucose and FFA levels on rat pancreatic RINm5F ß-cells and demonstrate that the GLP-1 analogue liraglutide restores the expression of PDX1 by inactivating Mst1, thus ameliorating ß-cell impairments. In addition, liraglutide also upregulates mitophagy, which may help restore mitochondrial function and protect ß-cells from oxidative stress damage. Our study suggests that liraglutide may serve as a potential agent for developing new therapies to reduce glucolipotoxicity.

Early cardiovascular risk and all-cause mortality following an incident of severe hypoglycaemia: A population-based cohort study.

AIMS: Severe hypoglycaemia is associated with a high risk of cardiovascular events in patient with diabetes. The aim of this study was to clarify the temporal relationship between hypoglycaemia and cardiovascular events. MATERIALS AND METHODS: This observational cohort study was conducted using Taiwan's Longitudinal Cohort of Diabetes Patients Database, which included 360 000 patients with newly diagnosed diabetes during the period 1999 to 2001. Patients with the first severe hypoglycaemia after 2002 served as the study cohort. Each patient in the study cohort was matched with two control patients without severe hypoglycaemia, based on a propensity score. A joinpoint regression model was used to determine trends in all-cause mortality and incidence of cardiovascular disease (CVD) events in both cohorts. RESULTS: A total of 10 157 patients with severe hypoglycaemia and 20 314 matched controls were recruited. Patients with severe hypoglycaemia had a significantly higher risk of CVD (HR, 7.28; 95% CI, 5.19-10.20) and all-cause mortality (HR, 19.92; 95% CI, 13.42-29.56) during the first month compared with those without. In patients with severe hypoglycaemia, the incidence of CVDs dropped by 17.29% monthly during the first 4 months and slowly decreased (-0.67%) during subsequent months. All-cause mortality decreased by 16.55% and 3.24% monthly during months 0-6 and months 6-17, respectively. CONCLUSIONS: Severe hypoglycaemia is associated with a greater risk of cardiovascular events and death, especially during the first month following a hypoglycaemic episode. Patients prone to severe hypoglycaemia should be made aware of the elevated risk of subsequent cardiovascular events.

Trends in prevalence and incidence of diabetes mellitus from 2005 to 2014 in Taiwan.

BACKGROUND/PURPOSE: Diabetes mellitus (DM) and DM-related complications place a high socioeconomic burden on individuals and society. Updating nationwide information periodically is thus pivotal to preventing DM and improving its management in Taiwan. METHODS: We used the National Health Insurance Research Database; disease diagnosis codes were assigned according to the International Classification of Diseases, 9th Revision, Clinical Modification. DM was defined as ≥3 outpatient visits or 1 hospitalization within a year. We excluded individuals with gestational DM, those with missing data, and those aged >100 years. Type 1 DM (T1DM) was defined based on information from the catastrophic illness registry. RESULTS: From 2005 to 2014, total population with DM increased by 66% and age-standardized prevalence in patients aged 20-79 years increased by 41%. The DM prevalence was generally higher in men; however, the prevalence was higher in women aged ≥65 years. The prevalence of DM was approximately 50% in those aged >80 years. DM incidence increased by 19%; the increase was most obvious in patients aged 20-39 years (p < 0.001). The standardized incidence of T1DM slightly decreased by 11% (p = 0.118) and standardized prevalence of T1DM increased from 0.04% to 0.05%. Number of T1DM accounted for 0.51-0.59% of the entire diabetic population during the observation period. CONCLUSION: DM prevalence is continually increasing, but the incidence only marginally increased from 2005 to 2014. Moreover, DM is a major problem in elderly people. The higher incidence of DM in men is consistent with the pandemic of overweight and obesity in men in Taiwan.

Efficacy and safety of dulaglutide monotherapy compared with glimepiride in East-Asian patients with type 2 diabetes in a multicentre, double-blind, randomized, parallel-arm, active comparator, phase III trial.

AIMS: To compare the efficacy and safety of once-weekly glucagon-like peptide-1 receptor agonist dulaglutide 1.5 and 0.75 mg with glimepiride in East-Asian patients with type 2 diabetes (T2D). MATERIALS AND METHODS: In this phase III, multinational, multicentre, double-blind, randomized, parallel-arm, 26-week study, patients with inadequate glycaemic control were randomized 1:1:1 to once-weekly dulaglutide 1.5 or 0.75 mg or daily glimepiride (1-3 mg/d). The primary endpoint was assessment of the non-inferiority of dulaglutide (1.5 mg), as measured by change in glycated haemoglobin (HbA1c), compared with glimepiride using a 0.4% non-inferiority margin. RESULTS: A total of 737 patients were randomized (dulaglutide 1.5 mg, n = 244; dulaglutide 0.75 mg, n = 248; glimepiride, n = 245). At week 26, both doses of dulaglutide were non-inferior and also superior to glimepiride for HbA1c reduction from baseline with a least squares mean difference of -6.34 mmol/mol (95% confidence interval [CI] -8.31, -4.26) or -0.58% (95% CI -0.76, -0.39) for dulaglutide 1.5 mg and -3.50 mmol/mol (95% CI -5.47, -1.42) or -0.32% (95% CI -0.50, -0.13) for dulaglutide 0.75 mg (P < .001). A greater proportion of patients in the dulaglutide 1.5 mg group achieved the HbA1c target of <53 mmol/mol (<7.0%) compared with the glimepiride group (74.1% vs 57.4%; P < .001). The mean body weight decreased (P < .005) and total hypoglycaemia rates were lower (P < .001) in the dulaglutide groups compared with the glimepiride group. The most common drug-related adverse events in both dulaglutide groups (≥5% of patients) included diarrhoea, nausea, increased lipase, decreased appetite, abdominal distension and vomiting. CONCLUSIONS: Dulaglutide (both doses) demonstrated superior glycaemic control vs glimepiride, with a favourable tolerability and safety profile in East-Asian patients with T2D.

Distribution of Cytotoxic T Lymphocyte-Associated Antigen-4 Promoter Polymorphisms in Taiwanese Patients with Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is associated with chronic inflammation, suggesting the metabolic abnormalities are originated from or exacerbated by cytokine overproduction. Cytokines and counter-regulatory molecules are crucial in keeping the balance of immune responses and, therefore, are potential candidates involved in T2DM etiology, development and complications. Our previous reports identify several significant associations between the genotypes of cytokine genes and T2DM and/or the clinical lipid parameters, which strongly suggest the participation of immune-regulatory molecules in lipid metabolism. The aim of this study is to determine the distribution of gene encoding cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), a T-cell negative regulator, in T2DM patients and health subjects. Genomic DNA was extracted from 287 Taiwanese T2DM patients and 278 ethnic- and age- matched healthy subjects, and two CTLA-4 polymorphisms (-318 C/T and +49 A/G) were analyzed by polymerase chain reaction-restriction fragment length polymorphism. Intriguingly, CTLA-4 -318 genotype was associated with circulatory triglycerides in T2DM subjects (P=0.019) although no significant association between CTLA-4 -318 (P=0.119) and +49 (P=0.2) genotypes with T2DM was identified. In addition, CTLA-4 +49 genotype was significantly associated with the ratio between total cholesterol and high-density lipoprotein (P=0.004) in control subjects. Our results suggest that CTLA-4 may be involved in lipid metabolism and affect T2DM disease progression and/or the development of diabetic complications although this gene does not represent a major risk factor for T2DM.

THE TRENDS OF HYPERTHYROIDISM TREATMENT IN TAIWAN: A NATIONWIDE POPULATION-BASED STUDY.

OBJECTIVE: Few studies on hyperthyroidism treatment have been reported in the past 3 decades. We used a nationwide population-based database to evaluate the current practices and management of hyperthyroidism in Taiwan. METHODS: This retrospective study included a random selection of 1 million people in Taiwan between 2004 and 2010. We identified patients with hyperthyroidism who received antithyroid drugs (ATD), radioactive iodine (RAI), or surgery. We calculated the proportions and treatment trends of those 3 treatment options annually. A Poisson regression model was used to determine whether trends changed. RESULTS: The prevalence of overt hyperthyroidism in Taiwan steadily increased from 2,666 (0.27%) in 2004 to 3,464 (0.37%) in 2010. The incidence of hyperthyroidism (per 1,000 persons) also increased from 0.97 in 2004 to 1.06 in 2010. The major proportion of hyperthyroidism in this study was Graves disease (95%), followed by toxic nodular goiter (2%), and other causes (3%). ATD is the most commonly used (96-97%) treatment for hyperthyroidism, followed by surgery (2-3%) and RAI (<1%). There was a significant decreasing trend for surgery, from 2.9% in 2004 to 2% in 2010, especially in female patients (3.3% in 2004 to 2.3% in 2010, P<.01) and patients younger than 40 (3.8% in 2004 to 2.9% in 2010, P<.01). Meanwhile, the proportions of ATD and RAI remained unchanged. The most common ATD prescription was methimazole (45-50%), followed by propylthiouracil (30-32%) and carbimazole (19-21%). CONCLUSION: Between 2004 and 2010, ATD was the treatment of choice in Taiwan, followed by surgery and RAI. ABBREVIATIONS: ATA = American Thyroid Association; ATD = antithyroid drug; LHID2005 = Longitudinal Health Insurance database 2005 dataset; NHI = National Health Insurance; RAI = radioactive iodine.

A Three-MicroRNA Signature as a Potential Biomarker for the Early Detection of Oral Cancer.

Oral squamous cell carcinoma (OSCC) is often diagnosed at a late stage and may be malignantly transformed from oral leukoplakia (OL). This study aimed to identify potential plasma microRNAs (miRNAs) for the early detection of oral cancer. Plasma from normal, OL, and OSCC patients were evaluated. Small RNA sequencing was used to screen the differently expressed miRNAs among the groups. Next, these miRNAs were validated with individual samples by quantitative real-time polymerase chain reaction (qRT-PCR) assays in the training phase (n = 72) and validation phase (n = 178). The possible physiological roles of the identified miRNAs were further investigated using bioinformatics analysis. Three miRNAs (miR-222-3p, miR-150-5p, and miR-423-5p) were identified as differentially expressed among groups; miR-222-3p and miR-423-5p negatively correlated with T stage, lymph node metastasis status, and clinical stage. A high diagnostic accuracy (Area under curve = 0.88) was demonstrated for discriminating OL from OSCC. Bioinformatics analysis reveals that miR-423-5p and miR-222-3p are significantly over-expressed in oral cancer tissues and involved in various cancer pathways. The three-plasma miRNA panel may be useful to monitor malignant progression from OL to OSCC and as potential biomarkers for early detection of oral cancer.

Efficacy and safety of fixed-dose combination therapy, alogliptin plus metformin, in Asian patients with type 2 diabetes: A phase 3 trial.

This study evaluated the efficacy and safety of 26 weeks of twice-daily (BID) alogliptin + metformin fixed-dose combination (FDC) therapy in Asian patients with type 2 diabetes. Patients aged 18 to 75 years with hemoglobin A1c (HbA1c) of 7.5% to 10.0% after ≥2 months of diet and exercise and a 4-week placebo run-in were enrolled. Eligible patients were randomized (1:1:1:1) to placebo, alogliptin 12.5 mg BID, metformin 500 mg BID or alogliptin 12.5 mg plus metformin 500 mg FDC BID. The primary endpoint was change in HbA1c from baseline to end of treatment (Week 26). In total, 647 patients were randomized. The least-squares mean change in HbA1c from baseline to Week 26 was -0.19% with placebo, -0.86% with alogliptin, -1.04% with metformin and -1.53% with alogliptin + metformin FDC. Alogliptin + metformin FDC was significantly more effective ( P < .0001) in lowering HbA1c than either alogliptin or metformin alone. The safety profile of alogliptin + metformin FDC was similar to that of the individual components alogliptin and metformin. The study demonstrated that treatment with alogliptin + metformin FDC BID resulted in better glycaemic control than either monotherapy and was well tolerated in Asian patients with type 2 diabetes.

Mevastatin promotes neuronal survival against Aß-induced neurotoxicity through AMPK activation.

Statins or HMG-CoA reductase inhibitors have been shown to be effective at lowering cholesterol levels, and the application of these molecules has gradually emerged as an attractive therapeutic strategy for neurodegenerative diseases. Epidemiological studies suggest that statin use is associated with a decreased incidence of Alzheimer's disease (AD). Thus, statins may play a beneficial role in reducing amyloid ß (Aß) toxicity, the most relevant pathological feature and pathogenesis of AD. However, the precise mechanisms involved in statin-inhibited Aß toxicity remain unclear. In the present study, we report that mevastatin significantly protects against Aß-induced neurotoxicity in SK-N-MC neuronal cells by restoring impaired insulin signaling. This protection appears to be associated with the activation of AMP-activated protein kinase (AMPK), which has long been known to increase insulin sensitivity. Our results also indicate that high levels of cholesterol likely underlie Aß-induced neurotoxicity and that activation of AMPK by mevastatin alleviates insulin resistance. Signaling through the insulin receptor substrate-1/Akt pathway appears to lead to cell survival. These findings demonstrate that mevastatin plays a potential therapeutic role in targeting Aß-mediated neurotoxicity. The molecule presents a novel therapeutic strategy for further studies in AD prevention and therapeutics.

Impact of polyphenolic components from mulberry on apoptosis of vascular smooth muscle cells.

BACKGROUND: Previous studies have shown that mulberry polyphenolic compounds have an anti-atherosclerotic effect in rabbits. Apoptosis of vascular smooth muscle cells (VSMCs) is the key determinant of the number of VSMCs in remodeling. To examine the effect of mulberry polyphenol extracts (MPEs) on the apoptosis of VSMCs and thus the prevention of atherosclerosis, this study investigated the ability of MPEs to induce apoptosis in vitro and the underlying mechanism. RESULTS: It was found that MPEs initially activated JNK/p38 and p53, which in turn activated both Fas-ligand and mitochondrial pathways, thereby causing mitochondrial translocation of Bax and a reduction in Bcl-2. This then triggered the cleavage of procaspases, finally resulting in apoptosis of VSMCs. CONCLUSION: This study shows that MPEs may suppress atherosclerosis through stimulating apoptosis of VSMCs via activating JNK/p38 and p53 signaling.