HbA1c and systolic blood pressure variation to predict all-cause mortality in patients with type 2 diabetes mellitus.

BACKGROUND: Glycated hemoglobin A1c (HbA1c) variation or blood pressure (BP) variation was known to be an independent predictor of all-cause mortality in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the combined effect of HbA1c and systolic blood pressure (SBP) variation on all-cause mortality and if there was a gender difference in patients with T2DM. METHODS: Patients with T2DM who had at least three HbA1c, SBP measurements within 12-24 months during 2001-2007 were included. Coefficient of variation (CV) was used to evaluate variation. The 75th percentile of HbA1c-CV and SBP-CV were set as a cutoff to define high and low variation. Hazard ratios (HRs) and 95% confidence intervals were estimated using Cox proportional hazard models. RESULTS: A total of 2744 patients were included, of whom 769 died during the 11.7 observation years. The associated risk of all-cause mortality was 1.22 [1.01- 1.48], P = 0.044, for low HbA1c-CV & high SBP-CV; 1.28 [1.04-1.57], P = 0.020, for high HbA1c-CV & low SBP-CV; and 1.68 [1.31-2.17], P < 0.001, for high HbA1c-CV & high SBP-CV. The associated risk remained unchanged in either males or females older than 50 years old, although there is only numerically higher for high HbA1c-CV & low SBP-CV in females older than 50 years old. CONCLUSIONS: Both HbA1c and SBP variation were significant predictors of all-cause mortality in patients with T2DM. The combined effect was higher than either alone and no gender difference in patients older than 50 years old.

Pyogenic Liver Abscess Risk in Patients With Newly Diagnosed Type 2 Diabetes Mellitus: A Nationwide, Population-Based Cohort Study.

Background: To date, no comprehensive epidemiological study exists on pyogenic liver abscess (PLA) risk in patients with newly diagnosed type 2 diabetes mellitus (T2DM) worldwide. Methods: We conducted a retrospective cohort study by using data from Taiwan National Health Insurance Research Database (NHIRD) to examine the association between newly diagnosed T2DM and PLA. The T2DM cohort included patients newly diagnosed as having T2DM (ICD-9-CM:250) from 2000 to 2009, with follow-up until December 31, 2011. The comparison cohort was then recruited through 1:4 random frequency matching with the T2DM cohort. Finally, the adjusted hazard ratios for PLA were compared between the T2DM and comparison cohorts, which included 44,728 patients with T2DM and 178,912 patients without DM respectively. Results: In T2DM cohort, 166 patients were diagnosed as having PLA (incidence rate = 5.87 per 10,000 person-years) and in comparison cohort, 238 patients were diagnosed as having PLA (incidence rate = 2.06 per 10,000 person-years). The T2DM cohort exhibited higher PLA risk than did the comparison cohort (hazard ratio = 2.83, 95% confidence interval = 2.32-3.46). Furthermore, the adjusted hazard ratio for PLA risk in T2DM cohort was the highest in those who were younger, man and with duration of DM <2 years. In the T2DM cohort, the most common PLA causative agent was Klebsiella pneumonia (KP). In addition, PLA risk was high in T2DM patients with gallstone and cholecystitis. Compared with comparison cohort, patients with T2DM prescribed acarbose has a lower PLA risk, however glyburide significantly increased PLA risk in T2DM cohort. Conclusion: In patients with newly diagnosed T2DM, PLA risk was high and acarbose might reduce PLA risk.

Experience of sorafenib treatment in differentiated thyroid cancer from Taiwan.

BACKGROUND: Sorafenib has been shown to prolong the progression free survival (PFS) of advanced radioiodine (RAI) refractory differentiated thyroid cancer (DTC) and has been approved by the FDA as the result of the phase III DECISION trial. Sorafenib has been reimbursed for the treatment of RAI refractory DTC in Taiwan since Jan 2017. High percentage of adverse events (AE) was noted in DECISION trial. We conducted a study to show the real-world experience of sorafenib in Taiwan. METHODS: We retrospectively collected the clinical data, including dose, AE, and PFS of sorafenib, of the DTC patients who received sorafenib treatment in National Cheng Kung University Hospital and China Medical University Hospital by chart review from 2012 to 2018. RESULTS: Thirty-six advanced DTC patients with progression were included in this study. The starting dose of sorafenib in most patients was 200 mg twice daily and the mean daily maintenance dose was 433 mg. Five patients had partial response (13.9%) and 28 patients had stable disease (77.8%). The median PFS was 17.3 months (95% confidence interval: 11.9-33.6 months). Daily maintenance dose ≥ 600 mg was associated with better PFS (median PFS, not reached). The most common toxicity of sorafenib was hand foot skin reaction (69%), followed by diarrhea (42%), and skin rash (33%). Most of the toxicities were grade I/II. CONCLUSION: Higher maintenance dose of sorafenib is associated with longer PFS while starting from half dose is feasible to minimize the incidence of high grade toxicities in the real-world use of sorafenib.

Susceptible gene of stasis-stagnation constitution from genome-wide association study related to cardiovascular disturbance and possible regulated traditional Chinese medicine.

BACKGROUND: This study identified susceptible loci related to the Yu-Zhi (YZ) constitution, which indicates stasis-stagnation, found in a genome-wide association study (GWAS) in patients with type 2 diabetes and possible regulated traditional Chinese medicine (TCM) using docking and molecular dynamics (MD) simulation. METHODS: Non-aboriginal Taiwanese with type 2 diabetes were recruited. Components of the YZ constitution were assessed by a self-reported questionnaire. Genome-wide SNP genotypes were obtained using the Illumina HumanHap550 platform. The world's largest TCM database ( http://tcm.cmu.edu.tw/ ) was employed to investigate potential compounds for PON2 interactions. RESULTS: The study involved 1,021 unrelated individuals with type 2 diabetes. Genotyping data were obtained from 947 of the 1,021 participants. The GWAS identified 22 susceptible single nucleotide polymorphisms on 13 regions of 11 chromosomes for the YZ constitution. Genotypic distribution showed that PON2 on chromosome 7 was most significantly associated with the risk of the YZ constitution. Docking and MD simulation indicated 13-hydroxy-(9E_11E)-octadecadienoic acid was the most stable TCM ligand. CONCLUSIONS: Risk loci occurred in PON2, which has antioxidant properties that might protect against atherosclerosis and hyperglycemia, showing it is a susceptible gene for the YZ constitution and possible regulation by 13-hydroxy-(9E_11E)-octadecadienoic acid.

Management trajectories in the type 2 diabetes Integrated Delivery System project in Taiwan: accounting for behavioral therapy, nutrition education and therapeutics.

BACKGROUND AND AIM: Glycated hemoglobin (HbA1c) assessment is basic to diabetes management. Little is done to describe the whole spectrum of the trajectory, its related temporal patterns of metabolic indices, and comorbidities. METHODS AND RESULTS: This was a longitudinal study. In the Diabetes Management through Integrated Delivery System project in Taiwan, enrollees had diabetes, but no major comorbidities. They were randomized into intensive or conventional education (health, diet and exercise) groups. HbA1c was classified by a groupbased trajectory model on the basis of repeated six-monthly measurements. We analyzed data from 1091 subjects who had at least two measurements on HbA1c. HbA1c exhibited three distinct ranges of low (42-53 mmol/mol), intermediate (64-75 mmol/mol) and high (97 mmol/mol), all of which persisted for 4.5 years regardless of receiving intensive education or not. Temporal changes and a time-group interaction were found for triglycerides, total cholesterol, HDL-C and LDL-C. The high trajectory was associated with the major co-morbidities of retinopathy, nephropathy, neuropathy, stroke, hypoglycemia, and ketoacidosis. Patients in the intensive education group (62.4%), which were equally distributed in the three trajectories, had significantly lower HbA1cs (-0.14%= -1.5 mmol/mol, p=0.026). The intermediate trajectory patients with intensive education had HbA1cs higher than the low trajectory patients with conventional education (ß=0.189, p=0.033). Though not significant, a similar pattern was found for DM education in the high group (ß=0.223, p=0.154). CONCLUSIONS: Novel strategies beyond current education and pharmacotherapeutic regimens are needed to lower HbA1c at least 11 mmol/mol for the high HbA1c group to minimize comorbidities.

Identified single-nucleotide polymorphisms and haplotypes at 16q22.1 increase diabetic nephropathy risk in Han Chinese population.

BACKGROUND: Diabetic nephropathy (DN) has become one of the most common causes of end-stage renal disease (ESRD) in many countries, such as 44.5% in Taiwan. Previous studies have shown that there is a genetic component to ESRD. Studies attempting to determine which genetic variants are related to DN in Han Chinese are limited. A case-control study was conducted to identify DN susceptibility variants in Han Chinese patients with type 2 diabetes. RESULTS: We included 574 unrelated type 2 diabetes patients (217 DN cases and 357 controls), who were genotyped using Illumina HumanHap550-Duo BeadChip. In single-SNP association tests, the SNPs rs11647932, rs11645214, and rs6499323 located at 16q22.1 under the additive-effect disease model were significantly associated with an approximately 2-fold increased risk of DN. In haplotype association tests, identified haplotypes located in the chromosome 16q22.1 region (containing ST3GAL2, COG4, SF3B3, and IL34 genes) raised DN risk. The strongest association was found with haplotype rs2288491-rs4985534-rs11645214 (C-C-G) (adjusted odds ratio [AOR] 1.93, 95% confidence interval [CI] 1.83-2.03, p = 6.25 × 10⁻7), followed by haplotype rs8052125-rs2288491-rs4985534-rs11645214 (G-C-C-G) (AOR 1.92, 95% CI 1.82-2.02, p = 6.56 × 10⁻7), and haplotype rs2303792-rs8052125-rs2288491-rs4985534-rs11645214 (A-G-C-C-G) (AOR 1.91, 95% CI 1.81-2.01, p = 1.15 × 10⁻6). CONCLUSIONS: Our results demonstrate that the novel SNPs and haplotypes located at the 16q22.1 region may involve in the biological pathways of DN in Han Chinese patients with type 2 diabetes. This study can provide new insights into the etiology of DN.

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.

Impact of obesity and hypertriglyceridemia on gout development with or without hyperuricemia: a prospective study.

OBJECTIVE: Hyperuricemia is the most important risk factor for the development of gout; however, not all patients with hyperuricemia develop gout, and patients experiencing a gout attack are not necessarily found to have hyperuricemia. We hypothesized that the interactions between serum uric acid (sUA) and other potential metabolic comorbidities increase the risk of gout development. METHODS: A prospective study was conducted to link baseline metabolic profiles from the MJ Health Screening Center to gout outcomes extracted from the Taiwan National Health Insurance database. A Cox proportional hazards model was used to assess the metabolic risks for incident gout stratified by hyperuricemia status (sUA level >7 mg/dl or not). RESULTS: During a mean followup period of 6.45 years (261,500 person-years), 1,189 patients with clinical gout (899 men, 202 women ages >50 years, and 88 women ages ≤50 years) were identified among the 40,513 examinees. The multivariate adjusted hazard ratios (HRs) of hyperuricemia for gouty arthritis were 5.80 (95% confidence interval [95% CI] 4.93-6.81) in men and 4.37 (95% CI 3.38-5.66) in women. Hypertriglyceridemia (triglyceride level >150 mg/dl) was found as an independent risk factor, with HRs of 1.38 (95% CI 1.18-1.60) in men with hyperuricemia and 1.40 (95% CI 1.02-1.92) in men without hyperuricemia. General obesity (body mass index >27 kg/m(2) ) was independently associated with gout in older women, with HRs of 1.72 (95% CI 1.15-2.56) in women with hyperuricemia and 2.19 (95% CI 1.47-3.26) in women without hyperuricemia. CONCLUSION: General obesity in women and hypertriglyceridemia in men may potentiate an sUA effect for gout development. Further investigation is needed.

Inertia on hypoglycemia: highlight from a Taiwan subgroup analysis of Real-Life Effectiveness and Care Patterns of Diabetes Management (RECAP-DM) study.

Type 2 diabetes mellitus is a global health issue. Patients with poor glycemic control often suffer from cardiovascular, cerebrovascular, neuropathic, and nephropathic complications as well as other chronic conditions. Therapeutic guidelines recommend that diabetic patients should maintain their HbA(1c) level below a certain target in order to minimize the risk of developing complications. However, hypoglycemia is recognized as a major impediment to the adequate control of type 2 diabetes. Hypoglycemia can manifest symptoms of varying degrees of severity. Moreover, an association between hypoglycemia and cardiovascular morbidity and mortality has been reported. Here, we present a post hoc Taiwan subgroup analysis of these data collected in the RECAP-DM study to indicate probably more emphasis and concern on hypoglycemia in type 2 diabetic patients in Taiwan. In this analysis, we found no significant difference was observed in treatment-related satisfaction between Taiwanese patients with or without hypoglycemia. Another finding of our study further shows that varying order of hypoglycemic symptoms or severity has no effect on patients' assessment of health-related quality of life scores. We need to pay more attention to this issue because of its enduring impact on compliance and concerns about hypoglycemia in type 2 diabetic patients. Nevertheless, socio-demographic characteristics are also important factors influencing glycemic control and patients' health-related quality of life. Future interventions and therapeutic algorithms should emphasize the probable patients' unawareness or neglect on hypoglycemia in diabetic patients.

Association between copy number variation of complement component C4 and Graves' disease.

BACKGROUND: Gene copy number of complement component C4, which varies among individuals, may determine the intrinsic strength of the classical complement pathway. Presuming a major role of complement as an effecter in peptide-mediated inflammation and phagocytosis, we hypothesized that C4 genetic diversity may partially explain the development of Graves' disease (GD) and the variation in its outcomes. METHODS: A case-control study including 624 patients with GD and 160 healthy individuals were enrolled. CNV of C4 isotypes (C4A and C4B) genes were performed by quantitative real-time polymerase chain reaction analysis. Statistical comparison and identification of CNV of total C4, C4 isotypes (C4A and C4B) and C4 polymorphisms were estimated according to the occurrence of GD and its associated clinical features. RESULTS: Individuals with 4, 2, and 2 copies of C4, C4A and C4B genes, especially those with A2B2 polymorphism may associate with the development of GD (p = 0.001, OR = 10.994, 95% CI: 6.277-19.255; p = 0.008, OR = 1.732, 95% CI: 1.190-2.520; p = 2.420 × 10-5, OR = 2.621, 95% CI: 1.791-3.835; and p = 1.395 × 10-4, OR = 2.671, 95% CI: 1.761-4.052, respectively). Although the distribution of copy number for total C4, C4 isotypes as well as C4 polymorphisms did not associate with the occurrence of goiter, nodular hyperplasia, GO and myxedema, <2 copies of C4A may associate with high risk toward vitiligo in patients with GD (p = 0.001, OR = 5.579, 95% CI: 1.659-18.763). CONCLUSIONS: These results may be further estimated for its clinical application on GD and the vitiligo in patients with GD.

Association between insulin resistance and development of microalbuminuria in type 2 diabetes: a prospective cohort study.

OBJECTIVE: An association between insulin resistance and microalbuminuria in type 2 diabetes has often been found in cross-sectional studies. We aimed to reassess this relationship in a prospective Taiwanese cohort of type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: We enrolled 738 normoalbuminuric type 2 diabetic subjects, aged 56.6 ± 9.0 years, between 2003 and 2005 and followed them through the end of 2009. Average follow-up time was 5.2 ± 0.8 years. We used urine albumin-to-creatinine ratio to define microalbuminuria and the homeostasis model assessment of insulin resistance (HOMA-IR) to assess insulin resistance. The incidence rate ratio and Cox proportional hazards model were used to evaluate the association between HOMA-IR and development of microalbuminuria. RESULTS: We found incidences of microalbuminuria of 64.8, 83.5, 93.3, and 99.0 per 1,000 person-years for the lowest to highest quartiles of HOMA-IR. Compared with those in the lowest quartile of HOMA-IR, the incidence rate ratios for those in the 2nd, 3rd, and highest quartiles were 1.28 (95% CI 0.88-1.87), 1.44 (0.99-2.08), and 1.52 (1.06-2.20), respectively (trend test: P < 0.001). By comparison with those in the lowest quartile, the adjusted hazard ratios were 1.37 (0.93-2.02), 1.66 (1.12-2.47), and 1.76 (1.20-2.59) for those in the 2nd, 3rd, and highest HOMA-IR quartiles, respectively. CONCLUSIONS: According to the dose-response effects of HOMA-IR shown in this prospective study, we conclude that insulin resistance could significantly predict development of microalbuminuria in type 2 diabetic patients.

Anti-inflammatory activities of tormentic acid from suspension cells of Eriobotrya Japonicaex vivo and in vivo.

Anti-inflammatory effects of tormentic acid (TA) were investigated ex vivo and in vivo. TA decreased the paw edema at the 4th and 5thhour after λ-carrageenin (Carr) administration, and increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the liver tissue. TA also significantly attenuated the thiobarbituric acid reactive substances (TBARS) level in the edematous paw at the 5thhour after Carr injection. TA decreased the nitric oxide (NO) levels on the serum level and diminished the serum tumour necrosis factor (TNF-α) at the 5thhour after Carr injection. Western blotting revealed that the TA decreased Carr-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions. As per results, the anti-inflammatory mechanisms of TA might be correlated to the decrease in the level of TBARS, iNOS, and COX-2 in the edema paw via increasing the activities of CAT, SOD, and GPx in the liver.

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.

A genome-wide association study identifies susceptibility variants for type 2 diabetes in Han Chinese.

To investigate the underlying mechanisms of T2D pathogenesis, we looked for diabetes susceptibility genes that increase the risk of type 2 diabetes (T2D) in a Han Chinese population. A two-stage genome-wide association (GWA) study was conducted, in which 995 patients and 894 controls were genotyped using the Illumina HumanHap550-Duo BeadChip for the first genome scan stage. This was further replicated in 1,803 patients and 1,473 controls in stage 2. We found two loci not previously associated with diabetes susceptibility in and around the genes protein tyrosine phosphatase receptor type D (PTPRD) (P = 8.54x10(-10); odds ratio [OR] = 1.57; 95% confidence interval [CI] = 1.36-1.82), and serine racemase (SRR) (P = 3.06x10(-9); OR = 1.28; 95% CI = 1.18-1.39). We also confirmed that variants in KCNQ1 were associated with T2D risk, with the strongest signal at rs2237895 (P = 9.65x10(-10); OR = 1.29, 95% CI = 1.19-1.40). By identifying two novel genetic susceptibility loci in a Han Chinese population and confirming the involvement of KCNQ1, which was previously reported to be associated with T2D in Japanese and European descent populations, our results may lead to a better understanding of differences in the molecular pathogenesis of T2D among various populations.

Levels of retinol-binding protein 4 and uric acid in patients with type 2 diabetes mellitus.

Retinol-binding protein 4 (RBP4) is a novel adipocytokine. It was observed that retinoid intoxication was related to acute attacks of gout. Furthermore, animal study has shown that colchicine inhibits RBP secretion. The aim of this study was to explore the association between RBP4 level and metabolic parameters especially uric acid in patients with type 2 diabetes mellitus. Serum RBP4 level was measured by a commercial competitive enzyme-linked immunosorbent assay kit, and its correlation with clinical and metabolic parameters was analyzed. Data on 885 subjects were used in the analysis. Pearson correlations revealed that serum RBP4 level correlated positively with age, waist circumference, waist-to-hip ratio, systolic blood pressure, total cholesterol, triglyceride, uric acid, creatinine, and urine albumin-to-creatinine ratio. Serum RBP4 level correlated negatively with estimated glomerular filtration rate but did not correlate with body mass index, homeostasis model assessment, A(1C), or high-sensitivity C-reactive protein. Multiple linear regression analysis with serum RBP4 level as the dependent variable revealed that total cholesterol, triglyceride, uric acid, and albumin-to-creatinine ratio correlated independently and positively with serum RBP4 level and that estimated glomerular filtration rate correlated independently and negatively with serum RBP4 level. In conclusion, RBP4 level was independently associated with uric acid level.

p53 codon 72 proline/arginine polymorphism and autoimmune thyroid diseases.

p53 protein participates in the processes of apoptosis, which is involved in a number of immunological reactions. In order to test whether the p53 gene could be used as a genetic marker for the prediction of the development of autoimmune thyroid diseases (AITD), we screened, by using polymerase chain reaction (PCR) analysis, for the C (CCC)/G (CGC) polymorphism at the p53 codon 72 (Pro 72/Arg 72) to determine the genotypes of 107 Hashimoto's thyroiditis (HT) and 90 Graves' disease (GD) patients, and 105 normal controls. The data demonstrated that, for the genotype analysis, HT patients featured an enhanced numerical ratio for the Arg/Arg homozygous genotype (33.7%) and a diminished ratio for the Arg/Pro heterozygous genotype (41.1%) at the p53 codon 72 than was the case for normal controls (Arg/Arg: 17.1% and Arg/Pro: 61.9%; P=0.005). The odds ratio for the risk of the Arg/Arg genotype's appearance, compared with that of the Arg/Pro and Pro/Pro genotypes combined, for the HT patient group was 2.450 (95% confidence interval: 1.274-4.716). With respect to allelic analysis, we did not observe significant difference in the frequency of appearance of the Arg allelic variant and the Pro allelic variant for the p53 codon 72 when comparing the HT patient group with the control group (P=0.208). On the other hand, GD patients presented no significant difference in distribution for both genotype and allelic frequencies (P=0.344 and 0.245, respectively) when compared with normal controls. In conclusion, HT patients feature a greater ratio of arginine homozygosity at p53 codon 72 than in the case for normal subjects. The p53 codon 72 proline/arginine polymorphism may be a genetic marker to predict the increased susceptibility of development of HT.

Effect of glyburide-metformin combination tablet in patients with type 2 diabetes.

BACKGROUND: To evaluate the efficacy and safety of glyburide/metformin combined tablet compared to glyburide or metformin alone in patients with type 2 diabetes. METHODS: In this 16-week, multicenter, randomized, double-blind, 4-arm and parallel clinical trial study, 100 patients with type 2 diabetes mellitus were recruited and 76 patients were available for statistical analysis at the end of the study. After 1 week of placebo washout period, eligible patients were randomly assigned into 1 of 4 treatment groups: glyburide 5 mg b.i.d.; metformin 500 mg b.i.d.; glyburide/metformin 2.5 mg/500 mg b.i.d.; or glyburide/metformin 5.0 mg/500 mg b.i.d. The doses were titrated every 2 weeks to a maximum of 4 tablets per day if the patients fasting plasma glucose (FPG) still exceeded 140 mg/dL. Efficacy was evaluated by the changes from baseline in glycosylated hemoglobin (HbA1c) and FPG at week 16. Adverse events were recorded and summarized by treatment group. RESULTS: At week 16, patients who received glyburide/metformin 2.5 mg/500 mg or 5.0 mg/500 mg tablets had greater reductions in FPG (all p<0.001) compared with glyburide or metformin monotherapy. Patients who took glyburide/ metformin 2.5 mg/500 mg tablet and glyburide/metformin 5.0 mg/500 mg tablet had significant decreases in HbA1c (both p<0.0125). Furthermore, treatment with glyburide/metformin 2.5 mg/500 mg resulted in significantly greater reduction in HbA1c compared to glyburide or metformin (-1.77%, p<0.001 and -1.34%, p=0.002), and treatment with glyburide/metformin 5.0 mg/500 mg resulted in significant lowering of HbA1c compared to glyburide or metformin alone (-1.73%, p<0.001 and -1.30%, p=0.005). Both the glyburide/metformin 2.5 mg/500 mg and glyburide/metformin 5.0 mg/500 mg combination therapy groups experienced fewer gastrointestinal adverse events than the metformin monotherapy group. CONCLUSION: Both glyburide/metformin 2.5 mg/500 mg and glyburide/metformin 5.0 mg/500 mg combination therapy were efficacious and well tolerated in the treatment of Chinese patients with type 2 diabetes mellitus.

Lack of association between interleukin-4 gene polymorphisms and autoimmune thyroid diseases amongst Taiwanese Chinese.

Graves' disease (GD) and Hashimoto's thyroiditis (HT) are both common autoimmune diseases of the thyroid gland (AITD). The IL-4 is involved in both humoral and cellular immunity. The aim of this study was to test whether the IL-4 gene could be used as a genetic marker to predict the development of AITD amongst the Chinese population of Taiwan. For this study, a normal control group of 105 healthy subjects and two experimental groups featuring individuals afflicted with either GD (104 patients) or HT (109 patients) were examined. Polymerase chain reaction (PCR) was used to analyze the variable number of tandem repeats (VNTRs) polymorphism for the IL-4 gene intron 3 and PCR-based restriction analysis using endonuclease BsmFI was undertaken for the same gene at the promoter -590 position. We found no significant difference in the frequencies of presence of genotype and allelic variants for the IL-4 gene at both the intron 3 and the promoter regions between the normal control group and each of the two patient groups. These findings suggest that the IL-4 gene polymorphisms that arise at either intron 3 or promoter -590 positions are not suitable genetic markers for AITD among Taiwanese Chinese.

Association between vitamin-D receptor gene FokI polymorphism and Graves' disease among Taiwanese Chinese.

1,25(OH)(2)D(3), exerting its biological effects through the vitamin-D receptor (VDR), plays a role in the modulation of the human immune system. The aim of this study was to test for the presence of an association between VDR gene polymorphism and the susceptibility to Graves' disease (GD) for Taiwanese Chinese. Using a polymerase chain reaction (PCR)-based restriction analysis, we screened the VDR exon 2 start codon T/C (VDR-FokI) polymorphism to determine the genotypes for 88 GD patients and 90 normal controls. From the genotype analysis, GD patients featured a greater proportion of the CC genotype (44.3%) and a smaller proportion of the TT genotype (12.5%) than was the case for normal controls (CC: 23.3% and TT: 28.9%; chi-squared test, P=0.003). The odds ratios (ORs) for the risk of the CC genotype's appearance compared with the corresponding values for the TT and TC genotypes, for the GD patient group, were, 4.39 (95% confidence interval [CI]: 1.82-10.61) and 2.10 (95% CI: 1.06-4.18), respectively. With respect to the allelic analysis, we observed significantly increased C-allele (65.9%) and decreased T-allele (34.1%) frequencies among GD patients compared to normal controls (C: 47.2% and T: 52.8%; chi-squared test, P=0.002). The OR for the risk of appearance of the C allele in the GD-patient group was 1.93 (95% CI: 1.27-2.95). In conclusion, the VDR-FokI T/C polymorphism might be able to be used as a genetic marker to predict the likelihood of GD development.