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1. Glycemic variability’s impact on painful diabetic peripheral neuropathy in type 2 diabetes patients

Author

Kuo-Cheng Chang, Yen-Wei Pai, Ching-Heng Lin, I-Te Lee, and Ming-Hong Chang

Subjects
Peripheral neuropathic pain, Diabetic peripheral neuropathy, Glycemic variability, Coefficients of variation, Type 2 diabetes, Medicine, Science
Abstract

Abstract Hyperglycemia in type 2 diabetes leads to diabetic peripheral neuropathy (DPN) and neuropathic pain, yet the association between glycemic variability and painful DPN remains insufficiently evidenced. To address this, we conducted a prospective longitudinal cohort study involving adult type 2 diabetes patients at a medical center. DPN was identified using the Michigan Neuropathy Screening Instrument (MNSI), and neuropathic pain was assessed with the Taiwan version of the Douleur Neuropathique 4 (DN4-T) questionnaire. At baseline in 2013, all participants were free of DPN and were re-evaluated in 2019 for the development of painful DPN. We measured visit-to-visit glycemic fluctuations using the coefficient of variation (CV) of fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c). Patients were stratified into tertiles according to their FPG-CV and HbA1c-CV. Among the 622 participants, 267 developed DPN during the six-year follow-up. Following matching of age and sex, 210 patients without DPN and 210 with DPN (including 26 with neuropathic pain) were identified. Our findings revealed a significant association between high FPG-CV and painful DPN, with the highest tertile showing an adjusted odds ratio of 2.82 (95% confidence interval 1.04–7.64) compared to the lowest tertile. On the contrary, HbA1c-CV did not show a significant association with the risk of painful DPN. Our study indicates that higher FPG-CV is associated with an increased risk of painful DPN, supporting the role of glycemic variability in the development of painful DPN.

Published
2024
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2. Urinary non-albumin protein-creatinine ratio is an independent predictor of mortality in patients with type 2 diabetes: a retrospective cohort study

Author

Yu-Cheng Cheng, Chin-Li Lu, Chiann-Yi Hsu, Meei-Ling Sheu, and I-Te Lee

Subjects
Diabetes, Urinary albumin-to-creatinine ratio, Non-albumin proteinuria, Urinary non-albumin protein-creatinine ratio, Mortality, Medicine, Science
Abstract

Abstract Albuminuria is a well-known predictor of chronic kidney disease in patients with type 2 diabetes mellitus (DM). However, proteinuria is associated with chronic complications in patients without albuminuria. In this retrospective cohort study, we explored whether non-albumin proteinuria is associated with all-cause mortality and compared the effects of non-albumin proteinuria on all-cause mortality between patients with and without albuminuria. We retrospectively collected data from patients with type 2 DM for whom we had obtained measurements of both urinary albumin-to-creatinine ratio (UACR) and urinary protein-to-creatinine ratio (UPCR) from the same spot urine specimen. Urinary non-albumin protein-creatinine ratio (UNAPCR) was defined as UPCR–UACR. Of the 1809 enrolled subjects, 695 (38.4%) patients died over a median follow-up of 6.4 years. The cohort was separated into four subgroups according to UACR (30 mg/g) and UNAPCR (120 mg/g) to examine whether these indices are associated with all-cause mortality. Compared with the low UACR and low UNAPCR subgroup as the reference group, multivariable Cox regression analyses indicated no significant difference in mortality in the high UACR and low UNAPCR subgroup (hazard ratio [HR] 1.189, 95% confidence interval [CI] 0.889–1.589, P = 0.243), but mortality risks were significantly higher in the low UACR and high UNAPCR subgroup (HR 2.204, 95% CI 1.448–3.356, P

Published
2024
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3. Hepatitis C virus antibody seropositivity is associated with albuminuria but not peripheral artery disease in patients with type 2 diabetes

Author

Yu-Cheng Cheng, Teng-Yu Lee, Yu-Hsuan Li, Chin-Li Lu, Hsiu-Chen Liu, Meei Ling Sheu, and I-Te Lee

Subjects
Medicine, Science
Abstract

Abstract Hepatitis C virus (HCV) infection is prevalent in patients with type 2 diabetes mellitus (DM). We aimed to investigate whether HCV antibody (Ab) seropositivity is associated with diabetic micro- and macro-vascular diseases. In this hospital-based cross-sectional study, we retrospectively collected data from patients who participated in the diabetes pay-for-performance program and underwent HCV Ab screening in the annual comprehensive assessment between January 2021 and March 2022. We examined the relationships of HCV Ab seropositivity with the spot urinary albumin-to-creatinine ratio (UACR) and ankle-brachial index (ABI) in patients aged ≥ 50 years with type 2 DM. A total of 1758 patients were enrolled, and 85 (4.83%) of the enrolled patients had HCV Ab seropositivity. Multivariable regression analyses revealed that albuminuria showed a dose-dependent association with HCV Ab seropositivity (UACR [30–299 mg/g]: odds ratio [OR] = 1.463, 95% confidence interval [CI] 0.872‒2.456); UACR [≥ 300 mg/g]: OR = 2.300, 95% CI 1.160‒4.562; P for trend = 0.015) when compared with normal albuminuria (UACR

Published
2024
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4. Renal impairment is one of appropriate predictors of future diabetic peripheral neuropathy: a hospital-based 6-year follow-up study

Author

Chi-Sheng Wang, Yen-Wei Pai, Ching-Heng Lin, I-Te Lee, and Ming-Hong Chang

Subjects
Medicine, Science
Abstract

Abstract The relationship between renal impairment and diabetic peripheral neuropathy (DPN) remains inconclusive. We aim to investigate the risk factors for the occurrence of DPN in Taiwanese adults with type 2 diabetes mellitus (T2DM) and focus on renal impairment. A hospital-based study was conducted from 2013 to 2019 and 552 Taiwanese people who had T2DM without DPN at baseline were enrolled. DPN was diagnosed using the Michigan Neuropathy Screening Instrument. Potential risk factors were recorded, including patient’s sociodemographic factors, current medication usage and biochemical markers. As of 2019, 73 developed DPN and 479 had no DPN. The cumulative incidence during the 6-year period was 13.22%. Multivariable logistic regression analysis revealed that lower estimated glomerular filtration rate (eGFR) (odds ratio [OR] 0.98, p = 0.005), advanced age (OR 1.06, p = 0.001), increased body weight (OR 1.04, p = 0.018), duration of DM (OR 1.05, p = 0.036) and male gender (OR 3.69, p = 0.011) were significantly associated with future DPN. In addition, patients with T2DM under the age of 65 with higher serum creatinine concentration (OR 8.91, p = 0.005) and higher baseline HbA1C (OR 1.71, p

Published
2022
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5. The association between hyperlipidemia, lipid-lowering drugs and diabetic peripheral neuropathy in patients with type 2 diabetes mellitus.

Author

Kuo-Cheng Chang, Yen-Wei Pai, Ching-Heng Lin, I-Te Lee, and Ming-Hong Chang

Subjects
Medicine, Science
Abstract

AimsPrevious studies showed conflicting relationship between hyperlipidemia, lipid-lowering therapy and diabetic peripheral neuropathy (DPN). As most of these works emerges from the Western and Australian countries, our study aims to investigate whether hyperlipidemia or lipid-lowering therapy (LLT) is associated with DPN in Taiwanese patients with type 2 diabetes (T2D).MethodsA cross-sectional, hospital-based observation study in adults with T2D was conducted from January to October 2013. DPN was screened using the Michigan Neuropathy Screening Instrument. Data were obtained at the time of enrollment, including medication usage, anthropometric measurements and laboratory examinations.Results2,448 participants were enrolled, 524 (21.4%) of whom had DPN. Patients with DPN had significantly lower plasma total cholesterol (185.6 ± 38.6 vs 193.4 ± 42.3 mg/dL) and low-density lipoprotein cholesterol levels (114.6 ± 32.7 vs 119 ± 30.8 mg/dL). Multivariate analysis demonstrated that neither hyperlipidemia (adjusted OR (aOR), 0.81; 95% confidence interval (CI), 0.49-1.34) nor LLT (aOR, 1.10; 95% CI, 0.58-2.09) was associated with DPN. Subgroup analysis revealed that neither total cholesterol (aOR, 0.72; 95% CI, 0.2-2.62), low-density lipoprotein cholesterol levels (aOR, 0.75; 95% CI, 0.2-2.79), statin (aOR, 1.09; 95% CI, 0.59-2.03) nor fibrate (aOR, 1.73; 95% CI, 0.33-1.61) was associated with DPN.ConclusionOur results suggest that neither hyperlipidemia nor lipid-lowering medication was associated with DPN in adults with T2D. DPN is a multifactorial disease, and our findings indicate that lipid metabolism may play a minor role in its pathogenesis.

Published
2023
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6. Primary hypothyroidism with an episode of ventricular tachycardia in a patient with COVID-19

Author

Pin-Hsu Liao, MD, Yu-Cheng Cheng, MD, Po-Yu Liu, MD, and I-Te Lee, MD, PhD

Subjects
Medicine
Abstract

Abstract. Rationale:. Coronavirus disease 2019 (COVID-19) is a systemic disease with major clinical manifestations in the respiratory system. However, thyroid involvement has also been reported. We present a case of hypothyroidism with ventricular tachycardia following diagnosis with COVID-19. Patient concerns:. A 77-year-old man was admitted to the isolation ward due to COVID-19. After respiratory support and medical treatment, the patient was successfully weaned off the ventilator. However, an episode of short-run ventricular tachycardia was detected, and primary hypothyroidism was also diagnosed. Diagnosis:. Ventricular tachycardia was detected by electrocardiography. Interventions:. Intravenous amiodarone administration and oral levothyroxine replacement. Outcomes:. No arrhythmia detected following treatment. Lessons:. Awareness of the association between hypothyroidism and COVID-19 is important in preventing possible complications.

Published
2022
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7. Synergistic effect of renalase and chronic kidney disease on endothelin-1 in patients with coronary artery disease ‒ a cross-sectional study

Author

Yu-Hsuan Li, Wayne Huey-Herng Sheu, Wen-Jane Lee, Jun -Sing Wang, Chia-Po Fu, Kae-Woei Liang, and I-Te Lee

Subjects
Medicine, Science
Abstract

Abstract Endothelin-1 (ET-1) is associated with endothelial dysfunction and vasoconstriction. Increased circulating ET-1 levels are associated with long-term cardiovascular mortality. Renalase, released from kidney, metabolizes catecholamines and regulates blood pressure. An increase in circulating renalase levels has been reported in patients with chronic kidney disease (CKD) and is associated with coronary artery disease (CAD). We hypothesized the existence of a synergistic effect of serum renalase levels and CKD on ET-1 levels in patients with CAD. We evaluated 342 non-diabetic patients with established CAD. ET-1 and renalase levels were measured in all patients after an overnight fast. Patients with CKD had higher ET-1 (1.95 ± 0.77 vs. 1.62 ± 0.76 pg/ml, P the median of 36.2 ng/ml) exhibited the highest serum ET-1 (P value for the trend

Published
2018
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8. Reconfirmation of newly discovered risk factors of diabetic peripheral neuropathy in patients with type 2 diabetes: A case-control study.

Author

Yen-Wei Pai, Ching-Heng Lin, Shih-Yi Lin, I-Te Lee, and Ming-Hong Chang

Subjects
Medicine, Science
Abstract

AimsThe aim of the present study was to investigate the major determinants of diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D), considering the traditional and newly discovered risk factors, including hypoglycaemia and glycemic variability.MethodsThis retrospective case-control study was conducted in a tertiary care hospital in Taiwan. A total of 2,837 patients with T2D were recruited, medical history and biochemical data were obtained, and patients were screened for DPN using the Michigan Neuropathy Screening Instrument (MNSI). DPN was defined as an MNSI exam score > 2. A stepwise selection of variables was used based on the Akaike Information Criterion (AIC) and the Schwarz Criterion (SC). Multivariate analysis was performed using the identified variables obtained from the stepwise selection.ResultsAmong the recruited patients, 604 (21.3%) were found to have DPN. 275 patients with DPN were selected because of longer follow up period before enrollment and complete data of glycemic parameters, and paired with 351 patients with T2D without DPN and matched for age, gender, and diabetes duration. The results of the stepwise selection showed that the presence of moderately and severely increased albuminuria yielded the lowest values of AIC and SC, which indicate the best predictive performance. Multivariate analysis demonstrated that moderately and severely increased albuminuria and greater long-term glycemic variability significantly increased the risk of DPN, with a corresponding odds ratio of 1.85 and 1.61 (95%confidence intervals of 1.25-2.73and1.02-2.55, respectively), after adjusted for hypoglycaemia and types of diabetes treatment.ConclusionsAlbuminuria is a potent predictor of DPN, and greater long-term glycemic variabilityis clearly associated with DPN in adults with T2D. These findings indicate that, in addition to achieve average blood glucose control, screening for albuminuria and reducing blood glucose fluctuations might be useful for improving diabetic microvascular complications.

Published
2019
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9. Two-hour post-challenge hyperglycemia, but not fasting plasma glucose, associated with severity of coronary artery disease in patients with angina.

Author

Chia-Po Fu, Wayne H-H Sheu, Wen-Lieng Lee, Wen-Jane Lee, Jun-Sing Wang, Shih-Yi Lin, and I-Te Lee

Subjects
Medicine, Science
Abstract

INTRODUCTION:Postprandial hyperglycemia plays a pivotal role in cardiovascular disease. However, few studies have investigated associations between the severity of coronary artery disease (CAD) and postprandial glucose levels in angina patients without known diabetes before coronary angiography. METHODS:Subjects who were admitted for coronary angiography due to angina and were in stable condition after discharge were recruited. A standard 75-g oral glucose tolerance test (OGTT) was performed at outpatient visits approximately 2-4 weeks after hospital discharge, and fasting and post-challenge blood glucose were measured. Twenty-six volunteers in our hospital staff served as the healthy group. CAD severity was graded using the SYNTAX and Jeopardy scoring systems. RESULTS:The subjects in the angina group had a higher body mass index, higher fasting glucose, and higher 2-h postprandial glucose than those in the healthy group. The SYNTAX and Jeopardy scores were significantly associated with 2-h postprandial blood glucose (correlation coefficients = 0.164 and 0.187, respectively) but not with fasting glucose. Linear regression analyses revealed that SYNTAX and Jeopardy scores were independently associated with glucose levels at 120 min after OGTT (SYNTAX 95%CI = 0.003-0.103; Jeopardy score 0.002-0.027) but not with fasting glucose. CONCLUSION:CAD severity is associated with blood glucose levels after oral glucose challenge in patients without known diabetes before coronary angiography, suggesting that CAD patients should be routinely screened for post-challenge blood glucose.

Published
2018
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10. Hemoglobin glycation index as a useful predictor of therapeutic responses to dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes.

Author

Yu-Wei Chen, Jun-Sing Wang, Wayne H-H Sheu, Shih-Yi Lin, I-Te Lee, Yuh-Min Song, Chia-Po Fu, and Chia-Lin Lee

Subjects
Medicine, Science
Abstract

INTRODUCTION:A high hemoglobin glycation index (HGI) and glycated hemoglobin (HbA1c) level are associated with greater inflammatory status, and dipeptidyl peptidase-4 (DPP-4) inhibitors can suppress inflammation. We aimed to evaluate the relationship between HGI and the therapeutic effect of DPP-4 inhibitors. METHODS:This retrospective cohort study followed 468 patients with type 2 diabetes receiving DPP-4 inhibitor treatment for 1 year. Estimated HbA1c was calculated using a linear regression equation derived from another 2969 randomly extracted patients with type 2 diabetes based on fasting plasma glucose (FPG) level. The subjects were divided into two groups based on HGI (HGI = observed HbA1c - estimated HbA1c). Mixed model repeated measures were used to compare the treatment efficacy after 1 year in patients with a low (HGI

Published
2017
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11. Serum Renalase Levels Are Predicted by Brain-Derived Neurotrophic Factor and Associated with Cardiovascular Events and Mortality after Percutaneous Coronary Intervention

Author

I-Te Lee and Wayne Huey-Herng Sheu

Subjects
brain-derived neurotrophic factor, coronary artery disease, percutaneous coronary intervention, renalase, Medicine
Abstract

Circulating brain-derived neurotrophic factor (BDNF) predicts survival rate in patients with coronary artery disease (CAD). We examined the relationship between BDNF and renalase before and after percutaneous coronary intervention (PCI) and the role of renalase in patients with CAD. Serum BDNF and renalase levels were determined using blood samples collected before and after PCI. Incident myocardial infarction, stroke, and mortality were followed up longitudinally. A total of 152 patients completed the assessment. BDNF levels were not significantly changed after PCI compared to baseline levels (24.7 ± 11.0 vs. 23.5 ± 8.3 ng/mL, p = 0.175), although renalase levels were significantly reduced (47.5 ± 17.3 vs. 35.9 ± 11.3 ng/mL, p < 0.001). BDNF level before PCI was an independent predictor of reduction in renalase (95% confidence interval (CI): −1.371 to −0.319). During a median 4.1 years of follow-up, patients with serum renalase levels of ≥35 ng/mL had a higher risk of myocardial infarction, stroke, and death than those with renalase of

Published
2018
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12. A synergistic effect of variability in estimated glomerular filtration rate with chronic kidney disease on all-cause mortality prediction in patients with type 2 diabetes: a retrospective cohort study

Author

I-Te Lee, Yu-Hsuan Li, and Yu-Shan Chang

Subjects
Male, medicine.medical_specialty, Time Factors, Endocrinology, Diabetes and Metabolism, Renal function, Type 2 diabetes, Kidney, Annual, Risk Assessment, Estimated glomerular filtration, Interquartile range, Predictive Value of Tests, Risk Factors, Internal medicine, Cause of Death, Chronic kidney disease, Risk of mortality, medicine, Humans, Standard deviation, Diseases of the circulatory (Cardiovascular) system, Risk factor, Variability, Renal Insufficiency, Chronic, Mortality, Original Investigation, Aged, Retrospective Studies, Aged, 80 and over, Glycated Hemoglobin, business.industry, Hazard ratio, Retrospective cohort study, Middle Aged, medicine.disease, Prognosis, Lipids, Diabetes Mellitus, Type 2, RC666-701, Female, Cardiology and Cardiovascular Medicine, business, Biomarkers, Kidney disease, Glomerular Filtration Rate
Abstract

Background The combination of diabetes mellitus (DM) and chronic kidney disease (CKD) is associated with a high risk of mortality. Annual assessment of the estimated glomerular filtration rate (eGFR) is recommended for patients with DM. We investigated the effect of variability in annual eGFR values on all-cause mortality in patients with type 2 DM. Methods In this retrospective cohort study, we enrolled patients with eGFR data between 01 Aug 2017 and 31 July 2018. We defined the index eGFR as the first available eGFR value within the enrollment year and collected additional annual eGFR data from the previous three years. A total of 3592 patients with type 2 DM were enrolled, including 959 patients with CKD (index eGFR 2) and 2633 patients without CKD. We assessed eGFR variability by using the standard deviation (SD) of the three annual eGFR and index eGFR values. We divided patients into subgroups according to the median SD of their annual eGFR (7.62 mL/min/1.73 m2). The primary endpoint was all-cause mortality after the index eGFR was assessed. Results During a median follow-up of 19 months (interquartile range: 18‒20 months), 127 (3.5%) deaths occurred among all 3592 enrolled patients. The highest mortality risk was observed in the high SD with CKD group, with a hazard ratio (HR) of 2.382 [95% confidence interval (CI) 1.346‒4.215] in comparison to the low SD without CKD group after adjusting for the associated factors. In patients without CKD, a high SD was an independent risk factor for mortality (HR = 2.105, 95% CI 1.256‒3.528). According to the C-index, the mortality prediction ability was better for the index eGFR + SD model than for the index eGFR alone model (0.671 vs. 0.629, P Conclusion There was a synergistic effect of eGFR variability with single-measured eGFR for the prediction of mortality in patients with type 2 DM. The SD of the annual eGFR values was also an independent predictor of mortality in patients with an eGFR > 60 mL/min/1.73 m2.

Published
2021

13. Electronic dashboard‐based remote glycemic management program reduces length of stay and readmission rate among hospitalized adults

Author

I-Te Lee, Yi-Jing Sheen, Ching-Heng Lin, Huang Shih-Che, Wayne H-H Sheu, and Chien-Chung Huang

Subjects
Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Psychological intervention, Inpatient glycemic management, 030209 endocrinology & metabolism, Glycemic Control, Hypoglycemia, Patient Readmission, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Diabetes Mellitus, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Retrospective Studies, Glycemic, business.industry, Blood Glucose Self-Monitoring, Remote Consultation, Poor glycemic control, Retrospective cohort study, Articles, General Medicine, Middle Aged, Prognosis, medicine.disease, Readmission rate, RC648-665, Hospitalization, Glycemic management, Clinical Science and Care, Hyperglycemia, Emergency medicine, Length of stay, Female, Original Article, Electronics, business, Readmission, Follow-Up Studies
Abstract

Aims/Introduction Currently, the impact of hospital‐wide glycemic control interventions on length of hospital stay (LOS) and readmission rates are largely unknown. We investigated the impact of a 4‐year hospital‐wide remote glycemic management program on LOS and 30‐day readmission rates among hospitalized adults who received glucose monitoring. Materials and Methods In this retrospective study, hospitalized patients who received glucose monitoring were classified into groups 1 (high glucose variability), 2 (hypoglycemia), 3 (hyperglycemia) and 4 (relatively stable). The monthly percentage changes, and average monthly percentage changes of hyperglycemia, hypoglycemia and treat to target were determined using joinpoint regression analysis. Results A total of 106,528 hospitalized patients (mean age 60.9 ± 18.5 years, 57% men) were enrolled. We observed a significant reduction in the percentage of inpatients in poor glycemic control groups (groups 1, 2 and 3, all P

Published
2021

14. Multi-omics analysis identifies CpGs near G6PC2 mediating the effects of genetic variants on fasting glucose

Author

Thomas Quertermous, I-Shou Chang, I-Te Lee, Yen-Feng Chiu, Chao A. Hsiung, Yii-Der Ida Chen, Chii-Min Hwu, Wen Chang Wang, Yi-Jen Hung, Jerome I. Rotter, Ren-Hua Chung, and Lee-Ming Chuang

Subjects
0301 basic medicine, Genetics, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Genome-wide association study, Single-nucleotide polymorphism, Type 2 diabetes, Biology, Quantitative trait locus, medicine.disease, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Insulin resistance, DNA methylation, Internal Medicine, medicine, SNP, Genetic association
Abstract

An elevated fasting glucose level in non-diabetic individuals is a key predictor of type 2 diabetes. Genome-wide association studies (GWAS) have identified hundreds of SNPs for fasting glucose but most of their functional roles in influencing the trait are unclear. This study aimed to identify the mediation effects of DNA methylation between SNPs identified as significant from GWAS and fasting glucose using Mendelian randomisation (MR) analyses. We first performed GWAS analyses for three cohorts (Taiwan Biobank with 18,122 individuals, the Healthy Aging Longitudinal Study in Taiwan with 1989 individuals and the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance with 416 individuals) with individuals of Han Chinese ancestry in Taiwan, followed by a meta-analysis for combining the three GWAS analysis results to identify significant and independent SNPs for fasting glucose. We determined whether these SNPs were methylation quantitative trait loci (meQTLs) by testing their associations with DNA methylation levels at nearby CpG sites using a subsample of 1775 individuals from the Taiwan Biobank. The MR analysis was performed to identify DNA methylation with causal effects on fasting glucose using meQTLs as instrumental variables based on the 1775 individuals. We also used a two-sample MR strategy to perform replication analysis for CpG sites with significant MR effects based on literature data. Our meta-analysis identified 18 significant (p

Published
2021

15. Completion Rate and Safety of Programmatic Screening and Treatment for Latent Tuberculosis Infection in Elderly Patients With Poorly Controlled Diabetic Mellitus: A Prospective Multicenter Study

Author

Po-Liang Lu, Chau-Chyun Sheu, Inn-Wen Chong, Chun-Shih Chin, Kun-Der Lin, Hung-Ling Huang, Wei-Chang Huang, Shin-Shin Liu, Meng-Rui Lee, Jann-Yuan Wang, I-Te Lee, and Meng-Hsuan Cheng

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Tuberculosis, latent tuberculosis infection, 030106 microbiology, Population, Antitubercular Agents, QuantiFERON, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Latent Tuberculosis, Internal medicine, Correspondence, medicine, Diabetes Mellitus, Isoniazid, Humans, preventive therapy, 030212 general & internal medicine, Prospective Studies, education, Online Only Articles, Aged, education.field_of_study, Latent tuberculosis, business.industry, Middle Aged, medicine.disease, bacterial infections and mycoses, Rifapentine, Regimen, Major Articles and Commentaries, rifapentine, Infectious Diseases, AcademicSubjects/MED00290, chemistry, diabetic mellitus, treatment outcome, Drug Therapy, Combination, Glycated hemoglobin, business, medicine.drug, Kidney disease
Abstract

Background Poor control of diabetes mellitus (DM) increases active tuberculosis (TB) risk. Understanding risk factors for latent TB infection (LTBI) in this population and intervention completion rates is crucial for policy making. Methods Under a collaborative multidisciplinary team consisting of public health professionals, endocrinologists, and pulmonologists, patients aged >45 years with poorly controlled DM (pDM), defined as having a glycated hemoglobin level of ≥9% within the preceding year, were enrolled by endocrinologists from 2 hospitals; these patients underwent LTBI screening by using QuantiFERON (QFT). Once-weekly isoniazid and rifapentine for 12 weeks (3HP) or daily isoniazid for 9 months (9H) was administered by pulmonologists. QFT-positivity predictors were evaluated using logistic regression. Completion rates and safety were also investigated. Results Among 980 patients with pDM (age: 64.2 ± 9.7 years), 261 (26.6%) were QFT-positive. Age, DM duration, chronic kidney disease stage ≥3, and dipeptidyl peptidase-4 inhibitor use, not using metformin, were associated with QFT-positivity. Preventive therapy (3HP: 138; 9H: 62) was administered in 200 (76.6%) QFT-positive patients. The completion rates of 3HP and 9H were 84.1% and 79.0%, respectively (P = .494). Nine (6.5%) and zero patients in the 3HP and 9H groups, respectively, developed systemic drug reactions (P = .059); 78.3% and 45.2% had ≥1 adverse drug reactions (P, The latent tuberculosis infection prevalence exceeds 25% in elderly patients with poorly controlled diabetes mellitus (DM), particularly those with a long DM duration. The completion rate of preventive therapy, regardless of the regimen, approaches 80% in this population under a collaborative framework.

Published
2021

16. Subjects with coronary artery disease and reduced ejection fraction have longer (GT)n repeats in the heme-oxygenase 1 gene promoter

Author

Wen-Lieng Lee, Wayne Huey-Herng Sheu, I-Te Lee, Jen-Pey Wu, Jun-Sing Wang, Kae-Woei Liang, and Wen-Jane Lee

Subjects
medicine.medical_specialty, Ejection fraction, HMOX1, business.industry, Promoter, Odds ratio, 030204 cardiovascular system & hematology, medicine.disease, Heme oxygenase, Coronary artery disease, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, chemistry, Internal medicine, Medicine, 030212 general & internal medicine, Allele, Cardiology and Cardiovascular Medicine, business, Heme
Abstract

Heme oxygenase (HO)-1 is a rate-limiting enzyme for degrading heme into carbon monoxide. Longer (GT)n repeat of the HO-1 gene (HMOX1) promoter has a lower transcription rate. Subjects with longer GT repeats in the HMOX1 promoter are more likely to have coronary artery disease (CAD) and cardiovascular events. We retrospectively enrolled CAD subjects with an abnormal ejection fraction (EF) 30 repeats) (p

Published
2021

17. Hyperthyroidism and vascular cell adhesion molecule-1 are associated with a low ankle-brachial index

Author

I-Te Lee and Yu-Hsuan Li

Subjects
Adult, Male, medicine.medical_specialty, endocrine system, Antithyroid drugs, endocrine system diseases, Cross-sectional study, Cardiology, Vascular Cell Adhesion Molecule-1, lcsh:Medicine, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Gastroenterology, Article, 03 medical and health sciences, Peripheral Arterial Disease, 0302 clinical medicine, Endocrinology, Antithyroid Agents, Internal medicine, medicine, Humans, In patient, Ankle Brachial Index, Prospective Studies, Prospective cohort study, lcsh:Science, Multidisciplinary, Cell adhesion molecule, business.industry, lcsh:R, Case-control study, Middle Aged, Confidence interval, Graves Disease, Thyroxine, medicine.anatomical_structure, Cross-Sectional Studies, Case-Control Studies, cardiovascular system, Female, lcsh:Q, Ankle, business, Follow-Up Studies
Abstract

We aimed to assess the ankle-brachial index (ABI) in patients with Graves’ disease. In the cross-sectional assessments, 81 patients with drug-naïve Graves’ disease and 235 with euthyroidism were enrolled. ABI and vascular cell adhesion molecule-1 (VCAM-1) levels were assessed. In the prospective follow-up, 32 patients with Graves’ disease were assessed again after antithyroid drugs for at least 4 weeks, and 32 age- and sex-matched controls with euthyroidism were also followed up. Patients with Graves’ disease had a higher VCAM-1 level (1309 ± 292 vs. 1009 ± 168 ng/mL, P

Published
2020

18. Synergistic Association of Carcinoembryonic Antigen and Carbohydrate Antigen 19-9 on the Risk of Abnormal Glucose Regulation

Author

Chiann-Yi Hsu, I-Te Lee, Yu-Cheng Cheng, and Yu-Hsuan Li

Subjects
Pharmacology, medicine.medical_specialty, endocrine system diseases, biology, business.industry, 030209 endocrinology & metabolism, Type 2 diabetes, Odds ratio, 030204 cardiovascular system & hematology, medicine.disease, Gastroenterology, digestive system diseases, Confidence interval, 03 medical and health sciences, 0302 clinical medicine, Carcinoembryonic antigen, Antigen, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, biology.protein, CA19-9, Prediabetes, business
Abstract

Purpose Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are tumor-associated antigens. An increased serum level of CEA and CA19-9 separately has been reported in diabetes. In this study, we examined the composite effect of elevated serum levels of both CEA and CA19-9 on subjects with type 2 diabetes and prediabetes. Patients and Methods A total of 3568 adults who attended a health examination were enrolled into this cross-sectional study. Subjects were grouped into four groups according to the median serum CEA and CA19-9 levels. Results Subjects with high CEA and high CA19-9 levels had the highest proportions of diabetes (43.9%) and prediabetes (33.04%). There was a statistically significant trend in the proportion of diabetes across the four groups (P < 0.001). Multivariable logistic regression analysis revealed higher risks of type 2 diabetes in subjects with high CEA and low CA19-9 levels (odds ratio [OR] = 2.10, 95% confidence interval [CI]: 1.39-3.18, P < 0.001) and in those with high CA19-9 and low CEA levels (OR = 2.18, 95% CI: 1.42-3.34, P < 0.001) than in those with low CEA and low CA19-9 levels; among these four groups, the highest risk of type 2 diabetes was observed in subjects with high CEA and high CA19-9 levels (OR = 2.65, 95% CI: 1.81-3.88, P < 0.001). The risk of prediabetes was significantly higher only in subjects with high CEA and high CA19-9 levels compared to those with low CEA and low CA19-9 levels (OR = 1.32, 95% CI: 1.08-1.61, P = 0.006). Conclusion CEA and CA19-9 had a synergistic ability to increase the risk of type 2 diabetes and prediabetes.

Published
2020

19. Influence of Diabetic Retinopathy on the Relationship Between Body Mass Index and Mortality in Patients with Poorly Controlled Type 2 Diabetes

Author

Wayne Huey-Herng Sheu, I-Te Lee, and Yu-Hsuan Li

Subjects
Pharmacology, medicine.medical_specialty, business.industry, 030209 endocrinology & metabolism, Diabetic retinopathy, Type 2 diabetes, 030204 cardiovascular system & hematology, Overweight, medicine.disease, Obesity, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Internal medicine, Cohort, Internal Medicine, Medicine, medicine.symptom, business, Body mass index, Obesity paradox
Abstract

Purpose An "obesity paradox" has been observed in patients with type 2 diabetes. However, the optimal body mass index (BMI) for survival may be influenced by the stage of diabetes. We examined the relationship between BMI and mortality in patients with type 2 diabetes and the influence of diabetic retinopathy (DR). Patients and Methods This is a retrospective cohort composing patients with type 2 diabetes who were admitted due to poor glucose control. Presence of DR was confirmed by ophthalmologists. The primary outcome was all-cause mortality. The association between BMI and mortality was assessed using a Cox proportional hazards model with adjustment for age, sex, and traditional risk factors. Results A total of 2053 patients were enrolled. Over median follow-up of 6.7 years, there were 1060 deaths. Patients were classified into five categories based on admission BMI (kg/m2): 30. Mortality risk was significantly higher in the

Published
2020

20. Implementation of an Electronic Dashboard with A Remote Management System to Improve Glycemic Management Among Hospitalized Adults

Author

Shih-Yi Lin, Chien-Chung Huang, Ching-Heng Lin, Huang Shih-Che, Wayne Huey-Herng Sheu, I.-Te Lee, Y.-J. Sheen, and Ming-De Huang

Subjects
Adult, Blood Glucose, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Dashboard (business), Certified diabetes educator, 030209 endocrinology & metabolism, Hypoglycemia, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Diabetes mellitus, medicine, Humans, 030212 general & internal medicine, Blood Glucose Measurement, Glycemic, business.industry, Blood Glucose Self-Monitoring, Medical record, General Medicine, medicine.disease, Hyperglycemia, Emergency medicine, San Francisco, Observational study, business
Abstract

Objective: Better glycemic control for hospitalized diabetic patients significantly reduces health expenditures and improves disease outcomes. We developed a dynamic dashboard with a remote management system and evaluated its impact on inpatient glycemic control. Methods: This was an observational institution-wide study; study participants were enrolled from a 1,500-bed public medical center from 2016 to 2018. We evaluated the impact of a dynamic dashboard system, which analyzed and monitored all glucose data with virtual glycemic management recommendation by a team of endocrinologists, over 3 × 1-year periods: 2016 (pre-implementation), 2017 (development), and 2018 (implementation). Results: A total of 51,641 discharges with 878,159 blood glucose measurements were obtained during the 3-year period. After implementation of the dashboard system, the proportion of patients with poor glycemic control (hyperglycemia or hypoglycemia) was reduced by 31% (from 10.2 to 7.0 per day per 100 patients with glucose monitoring; P Conclusion: We successfully installed a dynamic, electronic medical records-based dashboard monitoring system to improve inpatient glycemic control. The system, supported by a team of endocrinologists via remote recommendations, could efficiently fill an important need for improved glycemic management among hospitalized adults. Abbreviations: CDE = certified diabetes educator; DM = diabetes mellitus; EMR = electronic medical record; POC = point-of-care; TCVGH = Taichung Veterans General Hospital; UCSF = University of California, San Francisco; U.S. = United States; vGMS = virtual glucose management service

Published
2020

21. The Relationship Between Abdominal Body Composition and Metabolic Syndrome After a Weight Reduction Program in Adult Men with Obesity

Author

Wen-Jane Lee, I-Te Lee, Shih-Yi Lin, Wayne Huey-Herng Sheu, and Chun-Cheng Liao

Subjects
Pharmacology, medicine.medical_specialty, Intra-Abdominal Fat, business.industry, 030209 endocrinology & metabolism, Odds ratio, 030204 cardiovascular system & hematology, medicine.disease, Gastroenterology, Obesity, Confidence interval, 03 medical and health sciences, 0302 clinical medicine, Weight loss, Internal medicine, Internal Medicine, medicine, Aerobic exercise, medicine.symptom, Metabolic syndrome, business, Body mass index
Abstract

Purpose To assess the relationship between changes in abdominal adipose tissue and metabolic syndrome (MetS) in men with obesity after a weight reduction program (WRP). Patients and Methods Adult men with obesity and MetS were recruited for this prospective single-arm intervention study. Participants consumed an energy-restricted diet of 1200 kcal/day and performed 50-mins aerobic exercise daily for 12 weeks. Changes in the components of MetS were recorded. Changes in subcutaneous abdominal fat area (SAFA) and intra-abdominal fat area (IAFA) at the umbilicus level were determined using magnetic resonance imaging. Results A total of 30 men (mean age, 42.3 ± 10.0 years; body mass index, 33.7 ± 4.1 kg/m2) were included in this study. A moderate (8.0%) weight reduction occurred. Reversion of MetS was observed in 15 (50%) participants after the WRP. There was significant reduction in SAFA (68.3 ± 20.2 vs. 51.5 ± 18.6 cm2; P < 0.001) and IAFA (96.3 ± 15.6 vs. 86.0 ± 16.5 cm2; P < 0.001); the magnitude of reduction was greater for SAFA than for IAFA (-16.8 ± 7.7 vs. -10.3 ± 8.3 cm2; P < 0.001). Multivariate logistic regression analysis showed a reduction in IAFA to be an independent factor to decrease the risk of persistent MetS after WRP by adjustment for age, baseline IAFA, and change in SAFA (odds ratio = 0.25, 95% confidence interval: 0.07-0.95, P = 0.041). Reduction in SAFA was not significantly associated with the reversion of MetS (P = 0.411). Conclusion Reduction in IAFA via a 12-week WRP may help reverse MetS in men with obesity and MetS.

Published
2020

22. Is renal impairment predictor of future diabetic peripheral neuropathy? A 6-year follow-up cohort study

Author

Ming-Hong Chang, Yen-Wei Pai, I-Te Lee, Ching-Heng Lin, and Chi-Sheng Wang

Subjects
medicine.medical_specialty, Peripheral neuropathy, business.industry, Internal medicine, Medicine, business, medicine.disease, Cohort study
Abstract

The relationship between renal impairment and diabetic peripheral neuropathy (DPN) remains inconclusive. We aim to investigate the risk factors for the occurrence of DPN in Taiwanese adults with type 2 diabetes mellitus (T2DM) and focus on renal impairment. A hospital-based cohort study was conducted from 2013 to 2019 and 552 Taiwanese people who had T2DM without DPN at baseline were enrolled. DPN was diagnosed using the Michigan Neuropathy Screening Instrument. Potential risk factors were recorded, including patient’s sociodemographic factors, current medication usage and biochemical markers. As of 2019, 73 developed DPN and 479 had no DPN. The cumulative incidence during the 6-year period was 13.22%. A multivariate logistic regression analysis revealed that lower estimated glomerular filtration rate (eGFR) (odds ratio [OR] 0.98, p=0.008), higher serum creatinine concentration in people under the age of 65 (OR 5.25, p=0.013), advanced age (OR 1.06, p=0.001), increased body weight (OR 1.04, p=0.018), duration of DM (OR 1.05, p=0.036) and male gender (OR 3.69, p=0.011) were significantly associated with future DPN. In conclusion, this is the first large scaled cohort study to investigate risk factors for DPN in Taiwanese. Lower eGFR, higher serum creatinine concentration, particularly in people under the age of 65, advanced age, increased body weight, duration of DM and male gender are predictors of future DPN. Our study not only confirms the association between renal impairment and future DPN but also provides a commonly available assessment to predict the future DPN.

Published
2021

23. Variability in Annual Fasting Glucose and the Risk of Peripheral Artery Disease in Patients with Diabetes Mellitus

Author

I-Te Lee, Liang-Yi Lee, and Yu-Shan Chang

Subjects
medicine.medical_specialty, Mean arterial pressure, Disease, percentage of the mean arterial pressure, Gastroenterology, Diabetes mellitus, Internal medicine, lower extremity arterial disease, Internal Medicine, Medicine, ankle-brachial index, Endothelial dysfunction, Risk factor, Targets and Therapy [Diabetes, Metabolic Syndrome and Obesity], Original Research, Pharmacology, business.industry, Odds ratio, medicine.disease, body regions, medicine.anatomical_structure, arterial stiffness, Arterial stiffness, Ankle, standard deviation, business
Abstract

Yu-Shan Chang,1,2 Liang-Yi Lee,3 I-Te Lee1,2,4 1Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung City, Taiwan; 2School of Medicine, Chung Shan Medical University, Taichung City, Taiwan; 3Mingdao High School, Taichung City, Taiwan; 4School of Medicine, National Yang Ming Chiao Tung University, Taipei, TaiwanCorrespondence: I-Te LeeDivision of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, 1650, Section 4, Taiwan Boulevard, Taichung City, 40705, TaiwanEmail itlee@vghtc.gov.twPurpose: High glucose concentrations and swings are associated with endothelial dysfunction. We examined the effects of variability in fasting plasma glucose on peripheral artery disease (PAD) in patients with diabetes mellitus (DM).Patients and Methods: In this screening study for the risk factors of PAD, we retrospectively collected data on the ankle-brachial index (ABI) and the percentage of mean arterial pressure (%MAP) at the ankle between August 01, 2016 and July 31, 2017. We defined low ABI ≤ 0.90, high %MAP ≥ 45%, or both as high-risk PAD and others as low-risk PAD. We compared the standard deviation (SD) of the first fasting plasma glucose data available each year after January 01, 2007.Results: In 2577 patients, a higher SD of annual fasting glucose was observed in those with an ABI ≤ 0.90 than in patients with an ABI > 0.90 (2.6 ± 2.1 vs 2.2 ± 2.3, P = 0.009), and in patients with %MAP ≥ 45% than in those with %MAP < 45% (2.4 ± 2.1 vs 2.2 ± 2.3, P = 0.034). A high-risk PAD was significantly associated with the SD (P = 0.032) but not with the mean (P = 0.338) of annual fasting glucose. The former was an independent risk factor for high-risk PAD (odds ratio = 1.424; 95% CI = 1.118‒1.814; P = 0.004).Conclusion: Variability but not mean of annual fasting plasma glucose was significantly associated with a high risk of PAD in patients with DM.Keywords: ankle-brachial index, arterial stiffness, lower extremity arterial disease, percentage of the mean arterial pressure, standard deviation

Published
2021

24. Predicting Long-Term Mortality in Patients with Angina across the Spectrum of Dysglycemia: A Machine Learning Approach

Author

Wayne Huey-Herng Sheu, Yung-Chun Chang, Wen-Chao Yeh, Yu-Hsuan Li, and I-Te Lee

Subjects
Medicine (General), Brier score, Clinical Biochemistry, 030204 cardiovascular system & hematology, oral glucose tolerance test, Machine learning, computer.software_genre, Cross-validation, Article, Coronary artery disease, Angina, 03 medical and health sciences, 0302 clinical medicine, R5-920, Heart rate, medicine, Clinical endpoint, Risk of mortality, angiography, 030212 general & internal medicine, medicine.diagnostic_test, business.industry, Harrell’s C-index, medicine.disease, machine learning, Angiography, Artificial intelligence, least absolute shrinkage and selection operator, business, computer
Abstract

We aimed to develop and validate a model for predicting mortality in patients with angina across the spectrum of dysglycemia. A total of 1479 patients admitted for coronary angiography due to angina were enrolled. All-cause mortality served as the primary endpoint. The models were validated with five-fold cross validation to predict long-term mortality. The features selected by least absolute shrinkage and selection operator (LASSO) were age, heart rate, plasma glucose levels at 30 min and 120 min during an oral glucose tolerance test (OGTT), the use of angiotensin II receptor blockers, the use of diuretics, and smoking history. This best performing model was built using a random survival forest with selected features. It had a good discriminative ability (Harrell’s C-index: 0.829) and acceptable calibration (Brier score: 0.08) for predicting long-term mortality. Among patients with obstructive coronary artery disease confirmed by angiography, our model outperformed the Global Registry of Acute Coronary Events discharge score for mortality prediction (Harrell’s C-index: 0.829 vs. 0.739, p &lt, 0.001). In conclusion, we developed a machine learning model to predict long-term mortality among patients with angina. With the integration of OGTT, the model could help to identify a high risk of mortality across the spectrum of dysglycemia.

Published
2021

25. Multiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control

Author

Mark I. McCarthy, Weihua Meng, Brian L. Yaspan, M Imamura, Mark W. Christiansen, Niina Sandholm, Yii-Der Ida Chen, Sharon G. Adler, Lucia Sobrin, Craig L. Hanis, Valeriya Lyssenko, Shiro Maeda, Yang Hai, Paul Mitchell, Roberta McKean-Cowdin, Xiuqing Guo, John R. Sedor, David S. Siscovick, Sudha K. Iyengar, Heather Hancock, Jane Z. Kuo, Barbara E.K. Klein, David-Alexandre Tregouet, Elisabet Agardh, Kent D. Taylor, Andrew D. Morris, S. Mohsen Hosseini, Andrew D. Paterson, I-Te Lee, Wayne Huey-Herng Sheu, Emma Ahlqvist, Kathryn P. Burdon, Leif Groop, Ayellet V. Segrè, Samy Hadjadj, Samaneh Davoudi, Lynn K. Stanwyck, Emily Y. Chew, Xiaohui Li, Michael A. Grassi, Jie Jin Wang, Samuela Pollack, Albert V. Smith, Kyu Hyung Park, Michiaki Kubo, Mary Frances Cotch, Yucheng Jia, Ching J. Chen, Colin N. A. Palmer, Helen M. Colhoun, Alan D. Penman, R. Varma, Per-Henrik Groop, Tien Yin Wong, Barry I. Freedman, Eli Ipp, Alex S. F. Doney, Gavin Tan, Ronald Klein, Kaanan P. Shah, Jamie E Craig, Donald W. Bowden, Jerome I. Rotter, Robert P. Igo, Darryl Nousome, Ching-Yu Cheng, Michel Marre, Maggie C.Y. Ng, Latchezar Dimitrov, Jeeyun Ahn, Atsushi Takahashi, Richard A. Jensen, Aaron Leong, Jihye Kim, Iiro Toppila, Elizabeth J. Rossin, Alkes L. Price, Diabetes and Obesity Research Program, University of Helsinki, Department of Medicine, Nefrologian yksikkö, Research Programs Unit, Clinicum, HUS Abdominal Center, and Per Henrik Groop / Principal Investigator

Subjects
Blood Glucose, 0301 basic medicine, Oncology, medicine.medical_specialty, Genotype, Endocrinology, Diabetes and Metabolism, LOCI, 030209 endocrinology & metabolism, Genome-wide association study, VARIANTS, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Meta-Analysis as Topic, RESOURCE, Internal medicine, Diabetes mellitus, REVEALS, Genetic variation, Internal Medicine, medicine, Humans, Genetic Predisposition to Disease, CHINESE PATIENTS, Allele, METAANALYSIS, POLYMORPHISMS, Glycemic, Glycated Hemoglobin, Diabetic Retinopathy, business.industry, Diabetic retinopathy, medicine.disease, PREVALENCE, 3. Good health, SEVERITY, 030104 developmental biology, Diabetes Mellitus, Type 2, 3121 General medicine, internal medicine and other clinical medicine, Multiple comparisons problem, RISK-FACTORS, Medical genetics, Erratum, business, Genome-Wide Association Study, Protein Binding
Abstract

To identify genetic variants associated with diabetic retinopathy (DR), we performed a large multiethnic genome-wide association study. Discovery included eight European cohorts (n = 3,246) and seven African American cohorts (n = 2,611). We meta-analyzed across cohorts using inverse-variance weighting, with and without liability threshold modeling of glycemic control and duration of diabetes. Variants with a P value

Published
2018

26. Tempeh attenuates cognitive deficit, antioxidant imbalance, and amyloid β of senescence-accelerated mice by modulating Nrf2 expression via MAPK pathway

Author

Bi-Chun Liang, Wen-Chin Yeh, I-Te Lee, Yin-Ching Chan, and Ming-Fu Wang

Subjects
0301 basic medicine, MAPK/ERK pathway, Senescence, medicine.medical_specialty, Antioxidant, Cognitive, medicine.medical_treatment, Medicine (miscellaneous), medicine.disease_cause, Superoxide dismutase, Tempeh, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Amyloid precursor protein, TX341-641, Nutrition and Dietetics, biology, Nutrition. Foods and food supply, Senescence acceleration–prone mice, Amyloid β, Malondialdehyde, 030104 developmental biology, Endocrinology, chemistry, Catalase, biology.protein, 030217 neurology & neurosurgery, Oxidative stress, Food Science
Abstract

This study investigated the effects of tempeh on the cognitive and antioxidant status in senescence-accelerated mouse prone 8 (SAMP8) mice. Six-month-old SAMP8 mice were divided into one control and three tempeh groups; the tempeh groups were administered 300, 600, and 900 mg/kg body weight (BW) tempeh. The results revealed tempeh groups had stronger cognitive ability, lower malondialdehyde and carbonyl protein levels, and higher superoxide dismutase (SOD) and catalase (CAT) activities in the hippocampus, striatum, and cortex. Of them, the 900 mg/kg BW tempeh showed the most superior results on increasing SOD and CAT mRNA expressions and reducing amyloid β (Aβ) and β-site amyloid precursor protein cleaving enzyme 1 levels; it also increased nuclear factor erythroid 2-related factor 2 (Nrf2) levels by reducing p-p38 and p-JNK expression. In conclusion, tempeh may protect neurons against oxidative stress and Aβ-induced damage and reduce memory impairment by modulating Nrf2 via mitogen-activated protein kinase pathway.

Published
2018

27. The dawn phenomenon in type 2 diabetes: its association with glucose excursions and changes after oral glucose-lowering drugs

Author

Shih-Li Su, I-Te Lee, Wayne Huey-Herng Sheu, Shih-Yi Lin, Shi-Dou Lin, Shih-Te Tu, Wen-Jane Lee, and Jun-Sing Wang

Subjects
medicine.medical_specialty, endocrine system diseases, business.industry, Continuous glucose monitoring, dawn phenomenon, Medicine (miscellaneous), Dawn phenomenon, RM1-950, Type 2 diabetes, medicine.disease, Endocrinology, Internal medicine, Medicine, In patient, continuous glucose monitoring, Therapeutics. Pharmacology, type 2 diabetes, Oral glucose, glucose excursions, business, Original Research
Abstract

Background: We investigated the association between glucose excursions and the dawn phenomenon, and the effects of oral-glucose lowering drugs on the dawn phenomenon in patients with type 2 diabetes (T2D). Methods: We conducted a post hoc analysis using data from a previous randomized trial. Patients with T2D on metformin monotherapy were randomized to receive add-on acarbose or glibenclamide for 16 weeks. Ambulatory continuous glucose monitoring (CGM) was conducted before randomization and at the end of the study. Using the CGM data, we assessed glucose excursions as indicated by mean amplitude of glycemic excursions (MAGE). The magnitude of the dawn phenomenon was calculated as the difference between the nocturnal nadir (0:00 to 6:00 a.m.) and prebreakfast glucose level. Results: A total of 50 patients with T2D [mean age 53.5 ± 8.2 years, mean glycated hemoglobin (HbA1c) 8.4 ± 1.2%] were analyzed. There was an independent association between MAGE and the dawn phenomenon [β coefficient 0.199, 95% confidence interval (CI) 0.074–0.325, p = 0.003]. HbA1c improved significantly after treatment with acarbose or glibenclamide. However, only treatment with acarbose significantly improved glucose excursions. The dawn phenomenon decreased significantly only in patients treated with acarbose (from 35.9 ± 15.7–28.3 ± 16.5 mg/dl, p = 0.037), but not in those treated with glibenclamide (from 35.9 ± 20.6–34.6 ± 17.0 mg/dl, p = 0.776). Conclusion: Glucose excursions were independently associated with the dawn phenomenon in patients with T2D on metformin monotherapy. Both glucose excursions and the dawn phenomenon improved after treatment with acarbose, but not after treatment with glibenclamide.

Published
2021

28. The Clinical Influence after Implementation of Convolutional Neural Network-Based Software for Diabetic Retinopathy Detection in the Primary Care Setting

Author

Yu-Hsuan Li, Chieh Liang Wu, Wayne Huey-Herng Sheu, Chien-Chih Chou, Chun-Yuan Wang, Chun-Hsien Lin, Yuan-Shao Cheng, and I-Te Lee

Subjects
medicine.medical_specialty, area under the curve, education, Subspecialty, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Software, retinopathy, Medicine, Medical physics, 030212 general & internal medicine, image, Grading (education), lcsh:Science, Ecology, Evolution, Behavior and Systematics, Receiver operating characteristic, diabetes, business.industry, Deep learning, Paleontology, deep learning, Diabetic retinopathy, medicine.disease, Space and Planetary Science, 030221 ophthalmology & optometry, lcsh:Q, Artificial intelligence, business, Kappa, Retinopathy
Abstract

Deep learning-based software is developed to assist physicians in terms of diagnosis, however, its clinical application is still under investigation. We integrated deep-learning-based software for diabetic retinopathy (DR) grading into the clinical workflow of an endocrinology department where endocrinologists grade for retinal images and evaluated the influence of its implementation. A total of 1432 images from 716 patients and 1400 images from 700 patients were collected before and after implementation, respectively. Using the grading by ophthalmologists as the reference standard, the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) to detect referable DR (RDR) were 0.91 (0.87–0.96), 0.90 (0.87–0.92), and 0.90 (0.87–0.93) at the image level, and 0.91 (0.81–0.97), 0.84 (0.80–0.87), and 0.87 (0.83–0.91) at the patient level. The monthly RDR rate dropped from 55.1% to 43.0% after implementation. The monthly percentage of finishing grading within the allotted time increased from 66.8% to 77.6%. There was a wide range of agreement values between the software and endocrinologists after implementation (kappa values of 0.17–0.65). In conclusion, we observed the clinical influence of deep-learning-based software on graders without the retinal subspecialty. However, the validation using images from local datasets is recommended before clinical implementation.

Published
2021

29. Postchallenge glucose increment was associated with hemoglobin glycation index in subjects with no history of diabetes

Author

Shih-Yi Lin, Kae-Woei Liang, Jun-Sing Wang, Wen-Lieng Lee, Wayne Huey-Herng Sheu, Wen-Jane Lee, and I-Te Lee

Subjects
Blood Glucose, medicine.medical_specialty, endocrine system diseases, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, chemistry.chemical_compound, Hemoglobins, 0302 clinical medicine, Glycation, Internal medicine, Diabetes mellitus, Linear regression, medicine, Diabetes Mellitus, Outpatient clinic, Humans, Normal glucose tolerance, Glycated Hemoglobin, business.industry, nutritional and metabolic diseases, General Medicine, Glucose Tolerance Test, medicine.disease, Endocrinology, chemistry, Cohort, Hemoglobin, Glycated hemoglobin, business
Abstract

We investigated the association between postchallenge glucose increment and hemoglobin glycation index (HGI), the difference between observed and predicted glycated hemoglobin (HbA1c), in subjects with no history of diabetes. We enrolled 1381 subjects who attended our outpatient clinic for an oral glucose tolerance test (OGTT) to screen for diabetes. HGI was defined as observed HbA1c minus predicted HbA1c. The predicted HbA1c was calculated by entering fasting plasma glucose (FPG) level into an equation [HbA1c(%)=FPG(mg/dL)*0.029+2.9686] determined from an HbA1c versus FPG regression analysis using data from an independent cohort of 2734 subjects with no history of diabetes. The association between 2-hour glucose increment and HGI was analyzed using linear regression analyses with adjustment of relevant parameters. Overall, the proportions of subjects with normal glucose tolerance, pre-diabetes, and newly diagnosed diabetes were 42.3%, 41.3%, and 16.4%, respectively. Compared with subjects who had an HGI≤0, subjects with an HGI>0 had a lower FPG (95.0±13.3 vs 98.5±15.3 mg/dL, p

Published
2021

30. Generation of three induced pluripotent stem cell lines from type 2 diabetic patients with ocular complications

Author

Chia-Ning Shen, I-Te Lee, Wayne Huey-Herng Sheu, Edward Po-Fan Chu, Candy Hsin-Hua Cho, Ruei-Ying Chen, Tzu-Chien Kuo, Wen-Jane Lee, and I-Fen Cheng

Subjects
0301 basic medicine, Pathology, medicine.medical_specialty, endocrine system diseases, Induced Pluripotent Stem Cells, Type 2 diabetes, Lacrimal gland, Retinal Pigment Epithelium, Biology, Pathogenesis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Humans, Induced pluripotent stem cell, lcsh:QH301-705.5, Retinal pigment epithelium, Diabetic Retinopathy, Retinal, Cell Biology, General Medicine, Diabetic retinopathy, medicine.disease, eye diseases, 030104 developmental biology, medicine.anatomical_structure, chemistry, lcsh:Biology (General), Diabetes Mellitus, Type 2, sense organs, 030217 neurology & neurosurgery, Developmental Biology, Retinopathy
Abstract

Retinopathy is a well-known ocular complication that occurs in patients with type 2 diabetes (T2D). Recent evidence also indicates that diabetic patients have an increased prevalence of dry eye syndrome. However, the etiologies of both diabetic retinopathy (DR) and dry eye disease are complex, and their associations with T2D remains to be fully understood. Patient-derived human induced pluripotent stem cells (hiPSCs) enable the generation of disease-specific retinal tissues such as retinal pigment epithelium and lacrimal gland to model disease pathogenesis. Here, we describe the establishment of three hiPSC lines from T2D patients with PDR or dry eye disease.

Published
2020

31. Use of the ankle-brachial index combined with the percentage of mean arterial pressure at the ankle to improve prediction of all-cause mortality in type 2 diabetes mellitus: an observational study

Author

I-Te Lee, Wayne Huey-Herng Sheu, and Yu-Hsuan Li

Subjects
Male, medicine.medical_specialty, Mean arterial pressure, lcsh:Diseases of the circulatory (Cardiovascular) system, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, Risk Assessment, Peripheral Arterial Disease, Predictive Value of Tests, Risk Factors, Internal medicine, Diabetes mellitus, Risk of mortality, Medicine, Humans, Ankle Brachial Index, Arterial Pressure, cardiovascular diseases, Mortality, Original Investigation, Aged, Retrospective Studies, Aged, 80 and over, Peripheral artery disease, business.industry, Diabetes, Type 2 Diabetes Mellitus, Blood Pressure Determination, Middle Aged, medicine.disease, Lower extremity artery disease, Prognosis, Confidence interval, Percentage of the mean arterial pressure, body regions, Ankle-brachial index, Diabetes Mellitus, Type 2, lcsh:RC666-701, Cohort, Female, Cardiology and Cardiovascular Medicine, business, Complication
Abstract

BackgroundPeripheral artery disease (PAD) in the lower extremities is a common complication of type 2 diabetes and has been shown to be associated with mortality. The ankle-brachial index (ABI) is a simple noninvasive method to screen PAD, but this method has limited sensitivity. We hypothesized that using the percentage of mean arterial pressure (%MAP) in combination with the ABI would improve the prediction of mortality.MethodsWe retrospectively collected data from patients with type 2 diabetes who had undergone ABI and %MAP measurements at our hospital. We separated the cohort into four groups according to their ABI and %MAP values, and we examined whether these indices were associated with mortality.ResultsA total of 5569 patients (mean age, 65 ± 11 years) were enrolled. During the follow-up period (median, 22.9 months), 266 (4.8%) of the enrolled patients died. The combination of ABI and %MAP was significantly more effective than ABI alone for predicting mortality (C index of 0.62, 95% confidence interval [CI] of 0.57 to 0.65 vs. C index of 0.57, 95% CI of 0.53 to 0.62; P = 0.038). In multivariate analysis (with a reference group defined by ABI > 0.90 and %MAP ≤ 45%), the highest risk of mortality was seen in patients with ABI ≤ 0.90 and %MAP > 45% (hazard ratio = 2.045 [95% CI 1.420, 2.945], P ConclusionsThe use of %MAP alongside ABI appears to significantly improve the prediction of all-cause mortality in patients with type 2 diabetes.

Published
2020

32. Subjects with microvascular angina have longer GT repeats polymorphism in the haem oxygenase-1 gene promoter

Author

Wen-Jane Lee, Kae-Woei Liang, Wen-Lieng Lee, Jun-Sing Wang, Wayne Huey-Herng Sheu, Jen-Pey Wu, and I-Te Lee

Subjects
Male, HMOX1, Guanine, Genotype, Health, Toxicology and Mutagenesis, Clinical Biochemistry, Promoter polymorphism, 030204 cardiovascular system & hematology, Biology, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Polymorphism (computer science), Cardiac syndrome X, medicine, Humans, Promoter Regions, Genetic, Gene, Alleles, Microvascular Angina, Polymorphism, Genetic, digestive, oral, and skin physiology, Microvascular angina, Promoter, Middle Aged, medicine.disease, Molecular biology, Haem Oxygenase, 030220 oncology & carcinogenesis, Case-Control Studies, Female, Heme Oxygenase-1, Thymine, Microsatellite Repeats
Abstract

Objective: Few studies have investigated haem oxygenase-1 gene (HMOX1) promoter polymorphism in microvascular angina (MVA).Materials and methods: HMOX1 promoter (GT)n repeats were examined in healt...

Published
2020

33. Negative association between serum aryl hydrocarbon receptor concentrations and β-cell function in patients with no history of diabetes undergoing coronary angiography

Author

Shih-Yi Lin, I-Te Lee, Wen-Lieng Lee, Wayne Huey-Herng Sheu, Kae-Woei Liang, Jun-Sing Wang, Shing Jong Lin, and Wen-Jane Lee

Subjects
0301 basic medicine, medicine.medical_specialty, biology, business.industry, Endocrinology, Diabetes and Metabolism, Insulin, medicine.medical_treatment, medicine.disease, Aryl hydrocarbon receptor, Gastroenterology, Confidence interval, 03 medical and health sciences, 030104 developmental biology, Insulin resistance, Internal medicine, Diabetes mellitus, medicine, biology.protein, Blood sugar regulation, Prediabetes, business, Body mass index
Abstract

Background The aim of the present study was to investigate the association between serum aryl hydrocarbon receptor (AhR) levels and insulin resistance and β-cell function in patients undergoing coronary angiography with no history of diabetes. Methods Patients with no history of diabetes who had undergone coronary angiography underwent an oral glucose tolerance test (OGTT) 2-4 weeks after discharge from hospital; blood samples were collected for measurements of glucose, insulin, and AhR. Patients' glucose regulation status was determined on the basis of the OGTT. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). β-Cell function was assessed using the insulinogenic index (IGI). Results The study included 473 patients (mean (±SD) age 61 ±12 years, 81.8% male, mean body mass index 26.1 ±3.6 kg/m2 ). Overall, mean serum AhR concentrations were 25.1 ±12.2 pg/mL. Patients with normal glucose tolerance had a lower serum AhR concentrations than patients with prediabetes or newly diagnosed diabetes (23.4 ±10.8 vs 26.2 ±13.2 and 26.9 ±12.3 pg/mL, respectively; P = 0.029). Linear regression analysis revealed that serum AhR concentrations were not associated with HOMA-IR, but were negatively associated with IGI after adjustment for several confounders, including HOMA-IR (β = -0.162; 95% confidence interval - 0.302, -0.022; P = 0.023). Conclusions In patients with no history of diabetes, serum AhR concentrations were negatively associated with β-cell function, independent of several confounders, including insulin resistance.

Published
2018

34. Synergistic effect of renalase and chronic kidney disease on endothelin-1 in patients with coronary artery disease ‒ a cross-sectional study

Author

I-Te Lee, Yu-Hsuan Li, Wayne Huey-Herng Sheu, Wen-Jane Lee, Jun-Sing Wang, Chia-Po Fu, and Kae-Woei Liang

Subjects
Male, medicine.medical_specialty, Science, Coronary Artery Disease, 030204 cardiovascular system & hematology, Kidney, Article, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Catecholamines, Internal medicine, medicine, Humans, 030212 general & internal medicine, Endothelial dysfunction, Renal Insufficiency, Chronic, Monoamine Oxidase, Renalase, Aged, Multidisciplinary, Endothelin-1, business.industry, Middle Aged, medicine.disease, Endothelin 1, Blood pressure, medicine.anatomical_structure, Cross-Sectional Studies, Cardiology, Medicine, Female, medicine.symptom, business, Vasoconstriction, Kidney disease
Abstract

Endothelin-1 (ET-1) is associated with endothelial dysfunction and vasoconstriction. Increased circulating ET-1 levels are associated with long-term cardiovascular mortality. Renalase, released from kidney, metabolizes catecholamines and regulates blood pressure. An increase in circulating renalase levels has been reported in patients with chronic kidney disease (CKD) and is associated with coronary artery disease (CAD). We hypothesized the existence of a synergistic effect of serum renalase levels and CKD on ET-1 levels in patients with CAD. We evaluated 342 non-diabetic patients with established CAD. ET-1 and renalase levels were measured in all patients after an overnight fast. Patients with CKD had higher ET-1 (1.95 ± 0.77 vs. 1.62 ± 0.76 pg/ml, P the median of 36.2 ng/ml) exhibited the highest serum ET-1 (P value for the trend

Published
2018

35. Prevalence and biochemical risk factors of diabetic peripheral neuropathy with or without neuropathic pain in Taiwanese adults with type 2 diabetes mellitus

Author

Ching-Heng Lin, I-Te Lee, Ming-Hong Chang, and Yen-Wei Pai

Subjects
Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Taiwan, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Diabetic Neuropathies, Risk Factors, Internal medicine, Diabetes mellitus, Prevalence, Internal Medicine, medicine, Humans, Aged, Lipoprotein cholesterol, Aged, 80 and over, Glycated Hemoglobin, Proteinuria, business.industry, Cholesterol, HDL, Type 2 Diabetes Mellitus, General Medicine, Middle Aged, medicine.disease, Cross-Sectional Studies, Peripheral neuropathy, Diabetes Mellitus, Type 2, Neuropathic pain, Albuminuria, Neuralgia, Female, Observational study, medicine.symptom, business, Biomarkers
Abstract

To investigate the prevalence and risk factors for diabetic peripheral neuropathy with or without neuropathic pain in Taiwanese.A cross-sectional, hospital-based observational study was conducted. We enrolled 2837 adults with type 2 diabetes mellitus. Diabetic peripheral neuropathy with or without pain were diagnosed using 2 validated screening tools, namely the Michigan Neuropathy Screening Instrument and Douleur Neuropathique 4 questionnaire.In our sample, 2233 participants had no neuropathy, 476 had diabetic peripheral neuropathy without pain, and 128 had diabetic peripheral neuropathy with neuropathic pain, representing an overall diabetic peripheral neuropathy prevalence of 21.3%, and the prevalence of neuropathic pain in diabetic peripheral neuropathy was 21.2%. Multivariate analysis revealed that older age (P0.001), treatment with insulin (P=0.004), microalbuminuria (P=0.001) or overt proteinuria (P0.001) were independently associated with diabetic peripheral neuropathy, whereas older age (P0.001), elevated glycated haemoglobin (P=0.011), lower high-density lipoprotein cholesterol (P=0.033), and overt proteinuria (P0.001) were independently associated with diabetic peripheral neuropathy with neuropathic pain.During clinical visits involving biochemical studies, the risk for diabetic peripheral neuropathy with neuropathic pain should be considered for people with older age, elevated glycated haemoglobin, low high-density lipoprotein cholesterol and overt proteinuria, with particular attention given to increased levels of albuminuria while concerning neuropathic pain.

Published
2018

36. Variability of fasting plasma glucose and the risk of painful diabetic peripheral neuropathy in patients with type 2 diabetes

Author

I-Te Lee, Ming-Hong Chang, Ching-Heng Lin, and Yen-Wei Pai

Subjects
Blood Glucose, Male, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Diabetic Neuropathies, Internal medicine, Internal Medicine, medicine, Humans, In patient, PDPN, Aged, Retrospective Studies, Aged, 80 and over, business.industry, nutritional and metabolic diseases, Retrospective cohort study, Fasting, General Medicine, Odds ratio, Middle Aged, medicine.disease, Confidence interval, Peripheral neuropathy, Diabetes Mellitus, Type 2, Quartile, Case-Control Studies, Female, business, 030217 neurology & neurosurgery
Abstract

Aim The relationship between glycaemic variability and painful diabetic peripheral neuropathy (PDPN) in patients with type 2 diabetes (T2D) is unclear. The aim of this study was to investigate whether variations in fasting plasma glucose (FPG), as represented by the coefficient of variation (CV), were associated with the risk of PDPN in patients with T2D. Methods This case-control, retrospective study was conducted at a tertiary care hospital in Taiwan. We enrolled adults with T2D from January 1 through October 31, 2013. PDPN was diagnosed using the Michigan Neuropathy Screening Instrument (MNSI) and Douleur Neuropathique 4 (DN4) questionnaire. Variability in FPG was defined as a CV of visit-to-visit FPG for every 3-month interval during follow-up period before enrolment. Results A total of 2,773 patients were enrolled. One hundred patients with PDPN were randomly selected and paired with 175 consecutive patients with non-painful diabetic peripheral neuropathy and 351 patients with T2D without diabetic peripheral neuropathy, matched for age, gender, and diabetic duration. After multivariate adjustment, the FPG-CV was significantly associated with a risk of PDPN with a corresponding odds ratio of 4.08 (95% confidence interval [CI] of 1.60-10.42) and 5.49 (95% CI of 2.14-14.06) for FPG-CV in the third and fourth versus first FPG-CV quartiles, respectively, after considering glycated haemoglobin (HbA1c). Conclusion Long-term variability as evaluated by FPG-CV was associated to the risk of PDPN in adults with T2D. However, further studies are needed to know whether the FPG-CV is not simply a marker of the ambient hyperglycaemia.

Published
2018

37. Trajectories of fasting plasma glucose variability and mortality in type 2 diabetes

Author

Yu-Fen Li, Jun-Sing Wang, Wen-Miin Liang, I-Te Lee, Shih-Yi Lin, Chia Lin Lee, and Wayne Huey-Herng Sheu

Subjects
Blood Glucose, Male, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Coefficient of variation, Taiwan, Renal function, 030209 endocrinology & metabolism, Kaplan-Meier Estimate, Type 2 diabetes, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, In patient, Aged, Retrospective Studies, Aged, 80 and over, Plasma glucose, business.industry, nutritional and metabolic diseases, Fasting, General Medicine, Middle Aged, medicine.disease, Diabetes Mellitus, Type 2, Poor control, Cardiology, Female, Trajectory analysis, business
Abstract

Aim To investigate the effect of changes in fasting plasma glucose (FPG) variability, as assessed by 2-year trajectories of FPG variability, on mortality risk in patients with type 2 diabetes (T2D). Methods From 2009 to 2012, outpatients with T2D, aged>18 years, were enrolled from a medical centre. FPG was measured every 3 months for 2 years in 3569 people. For each of the eight 3-month intervals, FPG variability and means were calculated, with variability defined as the coefficient of variation of FPG. Also, trajectories of FPG variability and means were determined separately, using group-based trajectory analysis with latent class growth models. These models were fitted using the SAS Proc Traj procedure. The primary outcome was all-cause mortality, which was followed-up to the end of 2014. Results Five distinct trajectories of FPG variability (low, increasing, fluctuating, decreasing and high) and means (well controlled, stable control, worsening control, improving control and poor control) were established. The five trajectories of mean FPG were all associated with the same mortality risk. In contrast, in comparison to the low FPG variability trajectory, the fluctuating, decreasing and high variability trajectories all had significantly higher risks of mortality, with respective hazards ratios of 2.63 (95% CI: 1.40–4.93; P = 0.003), 2.78 (95% CI: 1.33–5.80; P = 0.007) and 4.44 (95% CI: 1.78–11.06; P = 0.001) after multivariable adjustment. Conclusion Changes in FPG variability were independently associated with increased mortality risk in patients with T2D.

Published
2018

38. Genome-wide scan for circulating vascular adhesion protein-1 levels: MACROD2 as a potential transcriptional regulator of adipogenesis

Author

Po-Chu Lee, Yi-Jen Hung, Ming Wei Lin, Lee-Ming Chuang, Siow-Wey Hee, Tien-Jyun Chang, Themistocles L. Assimes, Wei-Jei Lee, Hung-Yuan Li, Kuan-Yi Hung, I-Te Lee, Yen-Feng Chiu, Yi-Cheng Chang, Joshua W. Knowles, and Jiun-Yi Nong

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Genetic Linkage, Hydrolases, Endocrinology, Diabetes and Metabolism, Quantitative Trait Loci, Taiwan, Adipose tissue, Quantitative trait locus, Polymorphism, Single Nucleotide, 03 medical and health sciences, Insulin resistance, Genetic linkage, MACRO domain containing 2 gene, Internal medicine, Internal Medicine, Humans, Medicine, Gene, Gene knockdown, Adipogenesis, business.industry, Articles, General Medicine, medicine.disease, respiratory tract diseases, DNA Repair Enzymes, Clinical Science and Care, 030104 developmental biology, Endocrinology, Gene Expression Regulation, Vascular adhesion protein‐1, Female, Original Article, Amine Oxidase (Copper-Containing), Insulin Resistance, Steatosis, business, Cell Adhesion Molecules, Biomarkers, Linkage analysis, Follow-Up Studies
Abstract

Aims/Introduction Vascular adhesion protein‐1 (VAP‐1) is a membrane‐bound amine oxidase highly expressed in mature adipocytes and released into the circulation. VAP‐1 has been strongly implicated in several pathological processes, including diabetes, inflammation, hypertension, hepatic steatosis and renal diseases, and is an important disease marker and therapeutic target. Here, we aimed to identify the genetic loci for circulating VAP‐1 levels. Materials and Methods We carried out a genomic‐wide linkage scan for the quantitative trait locus of circulating VAP‐1 levels in 1,100 Han Chinese individuals from 398 families in the Stanford Asian Pacific Program for Hypertension and Insulin Resistance study. Regional association fine mapping was carried out using additional single‐nucleotide polymorphisms. Results The estimated heritability of circulating VAP‐1 levels is high (h 2 = 69%). The most significant quantitative trait locus for circulating VAP‐1 was located at 38 cM on chromosome 20, with a maximum empirical logarithm of odds score of 4.11 (P = 6.86 × 10−6) in females. Regional single‐nucleotide polymorphism fine mapping within a 1‐unit support region showed the strongest association signals in the MACRO domain containing 2 (MACROD2) gene in females (P = 5.38 × 10−6). Knockdown of MACROD2 significantly suppressed VAP‐1 expression in human adipocytes, as well as the expression of key adipogenic genes. Furthermore, MACROD2 expression was found to be positively associated with VAP‐1 in human visceral adipose tissue. Conclusion MACROD2 is a potential genetic determinant of serum VAP‐1 levels, probably through transcriptional regulation of adipogenesis.

Published
2018

39. Management of gout and hyperuricemia: Multidisciplinary consensus in Taiwan

Author

Chang-Fu Kuo, Wen-Chan Tsai, Song-Chou Hsieh, Wen-Pin Tsai, Der-Yuan Chen, I-Te Lee, Toong-Hua Liang, Shih-Chang Lin, Hsiao-Yi Lin, Pai Feng Hsu, Tien-Tsai Cheng, Mei-Chuan Kuo, James Cheng-Chung Wei, Shyh-Ming Chen, Jiunn-Horng Chen, Gregory J. Tsay, Kuang-Hui Yu, Tsu-Yi Hsieh, Shih-Yang Chen, Hing-Chung Lam, and Chung-Han Yang

Subjects
musculoskeletal diseases, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Consensus, Gout, Taiwan, Down-Regulation, Comorbidity, Hyperuricemia, Disease, Gout Suppressants, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Rheumatology, Risk Factors, Internal medicine, Diabetes mellitus, Humans, Medicine, 030212 general & internal medicine, 030203 arthritis & rheumatology, business.industry, nutritional and metabolic diseases, Uricosuric Agents, medicine.disease, Uric Acid, Treatment Outcome, chemistry, Uric acid, Interdisciplinary Communication, Metabolic syndrome, business, Biomarkers, Kidney disease
Abstract

Gout is an inflammatory disease manifested by the deposition of monosodium urate (MSU) crystals in joints, cartilage, synovial bursa, tendons or soft tissues. Gout is not a new disease, which was first documented nearly 5,000 years ago. The prevalence of gout has increased globally in recent years, imposing great disease burden worldwide. Moreover, gout or hyperuricemia is clearly associated with a variety of comorbidities, including cardiovascular diseases, chronic kidney disease, urolithiasis, metabolic syndrome, diabetes mellitus, thyroid dysfunction, and psoriasis. To prevent acute arthritis attacks and complications, earlier use of pharmacotherapeutic treatment should be considered, and patients with hyperuricemia and previous episodes of acute gouty arthritis should receive long-term urate-lowering treatment. Urate-lowering drugs should be used during the inter-critical and chronic stages to prevent recurrent gout attacks, which may elicit gradual resolution of tophi. The goal of urate-lowering therapy should aim to maintain serum uric acid (sUA) level

Published
2018

40. IGF1 Gene Is Associated With Triglyceride Levels In Subjects With Family History Of Hypertension From The SAPPHIRe And TWB Projects

Author

I-Te Lee, Yen-Feng Chiu, Chien-Hsing Lee, Chao A. Hsiung, Thomas Quertermous, Kuan-Yi Hung, Wen Chang Wang, Yi-Cheng Chang, Ren-Hua Chung, Yii-Der Ida Chen, and Chii-Min Hwu

Subjects
Insulin-like growth factor 1, medicine.medical_specialty, Family history of hypertension, 030204 cardiovascular system & hematology, Triglyceride, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Genetic linkage, Internal medicine, Genetic model, medicine, Family history, Gene, Single-nucleotide polymorphism, business.industry, IGF1, General Medicine, medicine.disease, Large sample, Minor allele frequency, Endocrinology, chemistry, 030220 oncology & carcinogenesis, business, Research Paper
Abstract

Chromosome 12q23-q24 has been linked to triglyceride (TG) levels by previous linkage studies, and it contains the Insulin-like growth factor 1 (IGF1) gene. We investigated the association between IGF1 and TG levels using two independent samples collected in Taiwan. First, based on 954 siblings in 397 families from the Stanford Asian Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe), we found that rs978458 was associated with TG levels (β = -0.049, p = 0.0043) under a recessive genetic model. Specifically, subjects carrying the homozygous genotype of the minor allele had lower TG levels, compared with other subjects. Then, a series of stratification analyses in a large sample of 13,193 unrelated subjects from the Taiwan biobank (TWB) project showed that this association appeared in subjects with a family history (FH) of hypertension (β = -0.045, p = 0.0000034), but not in subjects without such an FH. A re-examination of the SAPPHIRe sample confirmed that this association appeared in subjects with an FH of hypertension (β = -0.068, p = 0.0025), but not in subjects without an FH. The successful replication in two independent samples indicated that IGF1 is associated with TG levels in subjects with an FH of hypertension in Taiwan.

Published
2018

41. Familial Hypercholesterolemia Genetic Variations and Long-Term Cardiovascular Outcomes in Patients with Hypercholesterolemia Who Underwent Coronary Angiography

Author

Wen-Jane Lee, Tzu-Hung Hsiao, I-Te Lee, Ching-Heng Lin, Hsueh-Ju Lin, Jun-Sing Wang, Wen-Lieng Lee, Hsin Tung, Wayne Huey-Herng Sheu, Kae-Woei Liang, Han-Ni Chuang, Yi-Ming Chen, and Jun-Peng Chen

Subjects
Adult, Male, medicine.medical_specialty, Apolipoprotein B, medicine.medical_treatment, DNA Mutational Analysis, Hypercholesterolemia, Taiwan, Familial hypercholesterolemia, Disease, QH426-470, Coronary Angiography, Revascularization, Article, Cohort Studies, Hyperlipoproteinemia Type II, Coronary artery disease, Risk Factors, Internal medicine, Prevalence, Genetics, medicine, Humans, gene, Genetics (clinical), Aged, familial hypercholesterolemia, biology, business.industry, Incidence (epidemiology), Genetic Variation, Odds ratio, Middle Aged, Prognosis, medicine.disease, mortality, Receptors, LDL, Cardiovascular Diseases, Apolipoprotein B-100, Cohort, biology.protein, Cardiology, Female, Proprotein Convertase 9, business, coronary artery disease, Follow-Up Studies
Abstract

Background: Familial hypercholesterolemia (FH) has been associated with early coronary artery disease (CAD) and increased risk of atherosclerotic cardiovascular disease. However, the prevalence of FH and its long-term outcomes in a CAD-high-risk cohort, defined as patients with hypercholesteremia who underwent coronary angiography, remains unknown. Besides, studies regarding the impact of genetic variations in FH on long-term cardiovascular (CV) outcomes are scarce. Methods and Results: In total, 285 patients hospitalized for coronary angiography with blood low-density lipoprotein cholesterol (LDL-C) levels ≥ 160 mg/dL were sequenced to detect FH genetic variations in LDL receptors apolipoprotein B and proprotein convertase subtilisin/kexin type 9. Risk factors associated with long-term CV outcomes were evaluated. The prevalence of FH was high (14.4%). CAD and early CAD were significantly more prevalent among FH variation carriers than non-carriers, despite comparable blood LDL-C levels. Moreover, the FH variation carriers also underwent more revascularization after a mean follow-up of 6.1 years. Multivariate logistic regression demonstrated that FH genetic variation was associated with increased incidence of cardiovascular disease and mortality (odds ratio = 3.17, p = 0.047). Two common FH variants, LDLR c.986G&gt, A and LDLR c.268G&gt, A, showed the most significant impacts on high blood LDL-C levels and early-onset CAD. Conclusions: Our results indicate that FH genetic variants may exhibit differential effects on early-onset CAD and revascularization risks in patients undergoing coronary angiography. FH genetic information might help identify high-risk patients with typical CAD symptoms for appropriate intervention.

Published
2021

42. Associations of fibroblast growth factor 21 with cardiovascular risk and β-cell function in patients who had no history of diabetes

Author

I-Te Lee, Shih-Yi Lin, Jun-Sing Wang, Wayne Huey-Herng Sheu, Wen-Lieng Lee, Shing Jong Lin, Wen-Jane Lee, and Kae-Woei Liang

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, β cell function, FGF21, medicine.medical_treatment, Clinical Biochemistry, 030209 endocrinology & metabolism, Biochemistry, Gastroenterology, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Risk Factors, Insulin-Secreting Cells, Diabetes mellitus, Internal medicine, medicine, Humans, In patient, business.industry, Insulin, Biochemistry (medical), General Medicine, Glucose Tolerance Test, Middle Aged, medicine.disease, Fibroblast Growth Factors, 030104 developmental biology, Endocrinology, Cardiovascular Diseases, Female, business, Cohort study
Abstract

We investigated the associations of fibroblast growth factor 21 (FGF-21) with cardiovascular risk and β-cell function in patients who had no history of diabetes.We enrolled 269 outpatients who had been referred for an oral glucose tolerance test (OGTT). Plasma glucose, insulin, and FGF-21 were measured before and at 2h after the OGTT. β-cell function was assessed using the insulinogenic index, corrected for insulin resistance. Patients' 10-year coronary heart disease (CHD) risk was assessed using the Chinese Multi-provincial Cohort Study functions.Overall, there was a 10% decrease in FGF-21 after OGTT (p0.001). The decrease of FGF-21 after OGTT in patients with normal glucose tolerance, prediabetes, and diabetes was 8%, 10%, and 21%, respectively (all p0.05). Patients with a history of admission for coronary angiography had a higher 10-year CHD risk and fasting FGF-21 (both p0.001). In multivariate regression analysis, fasting FGF-21 was positively associated with 10-year CHD risk, while FGF-21 relative change 2h after OGTT was positively associated with β-cell function.In patients who had no history of diabetes, fasting FGF-21 was positively associated with 10-year CHD risk, while FGF-21 relative change 2h after OGTT was positively associated with β-cell function.

Published
2017

43. Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease

Author

Alex Lopez, Jerome I. Rotter, Yii-Der Ida Chen, Lukas Habegger, Anders Berg Wulff, Richard L Dunbar, John Penn, Anita M. van den Hoek, An Zhao, Omri Gottesman, Cristopher V. Van Hout, Scott M. Damrauer, Tanya M. Teslovich, Aurelie Bouzelmat, Daniel J. Rader, Poulabi Banerjee, David J. Carey, Viktoria Gusarova, Shane McCarthy, Frederick E. Dewey, Kae-Woei Liang, David H. Ledbetter, Gary Herman, Rick Zhang, Alan R. Shuldiner, Svati H. Shah, Claudia Schurmann, Neil Stahl, Marylyn D. Ritchie, Sara Hamon, Colm O'Dushlaine, Ingrid B. Borecki, Daniel A. Gipe, Jesper Gromada, Hans M.G. Princen, Børge G. Nordestgaard, H. Lester Kirchner, Michael F. Murray, Shannon Bruse, Aris Baras, Jeffrey G. Reid, Wayne H-H Sheu, William E. Kraus, Xiuqing Guo, Aeron Small, Brad Shumel, William J. Sasiela, Anne Tybjærg-Hansen, Andrew J. Murphy, Joseph B. Leader, John D. Overton, Robert Pordy, Scott Mellis, Weiping Shao, George D. Yancopoulos, Hayes Dansky, and I-Te Lee

Subjects
0301 basic medicine, medicine.medical_specialty, Evinacumab, Population, 030204 cardiovascular system & hematology, Pharmacology, Coronary artery disease, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, ANGPTL3, Medicine, education, education.field_of_study, biology, business.industry, Cholesterol, General Medicine, medicine.disease, Human genetics, 030104 developmental biology, Endocrinology, chemistry, biology.protein, lipids (amino acids, peptides, and proteins), Antibody, business, Lipoprotein
Abstract

BackgroundLoss-of-function variants in the angiopoietin-like 3 gene (ANGPTL3) have been associated with decreased plasma levels of triglycerides, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. It is not known whether such variants or therapeutic antagonism of ANGPTL3 are associated with a reduced risk of atherosclerotic cardiovascular disease. MethodsWe sequenced the exons of ANGPTL3 in 58,335 participants in the DiscovEHR human genetics study. We performed tests of association for loss-of-function variants in ANGPTL3 with lipid levels and with coronary artery disease in 13,102 case patients and 40,430 controls from the DiscovEHR study, with follow-up studies involving 23,317 case patients and 107,166 controls from four population studies. We also tested the effects of a human monoclonal antibody, evinacumab, against Angptl3 in dyslipidemic mice and against ANGPTL3 in healthy human volunteers with elevated levels of triglycerides or LDL cholesterol. ResultsIn th...

Published
2017

44. Magnesium-responsive genes are downregulated in diabetic patients after a three-month exercise program on a bicycle ergometer

Author

Fu-Chou Cheng, Sen-Wei Tsai, Martin Kolisek, Yueh-Feng Chiang, Jui-Hua Huang, Li-Sheng Chien, I-Te Lee, and Hsuan-Ying Chen

Subjects
Blood Glucose, Male, medicine.medical_specialty, Waist, Down-Regulation, TRPM Cation Channels, 030204 cardiovascular system & hematology, Protein Serine-Threonine Kinases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Diabetes mellitus, medicine, Humans, Magnesium, Prospective Studies, Prospective cohort study, Cation Transport Proteins, business.industry, Type 2 Diabetes Mellitus, Membrane Transport Proteins, General Medicine, Anthropometry, Middle Aged, medicine.disease, Exercise Therapy, Endocrinology, chemistry, Diabetes Mellitus, Type 2, 030220 oncology & carcinogenesis, Exercise Test, Female, Glycated hemoglobin, business, Body mass index, Homeostasis
Abstract

BACKGROUND Exercise is an effective therapy for the management of diabetes because it helps regulate glucose and magnesium homeostasis. Nevertheless, the mechanisms by which exercise exerts effects on magnesium transport remain unclear. This study investigated the expression of genes encoding magnesium transporters (GMTs) after a three-month exercise program in diabetic patients. METHODS This study was conducted with a within-subject pre-post design. A total of 15 adult patients with type 2 diabetes mellitus (T2DM) were recruited and underwent a three-month indoor bicycle exercise program. The expression of five GMTs (CNNM2, TRPM6, TRPM7, SLC41A1, and SLC41A3) was determined in blood samples. Relevant anthropometric values and biochemical parameters were also determined. RESULTS Although the body weight and body mass index decreased after three months exercise, there were no significant differences. Fasting blood glucose, glycated hemoglobin (HbA1c), waist circumference, and magnesium levels decreased after the exercise program (p < 0.05). The expression of SLC41A1 and SLC41A3 were downregulated after exercise, but only CNNM2, TRPM6, and TRPM7 showed significantly decreased expression levels compared with those before the exercise program (p < 0.05). CONCLUSION The three-month exercise program ameliorated blood glucose levels and downregulated the expression of magnesium-responsive genes in patients with T2DM.

Published
2019

45. Pay-for-performance for shared care of diabetes in Taiwan

Author

Shih-Yi Lin, Wayne Huey-Herng Sheu, Chih-Cheng Hsu, I-Te Lee, Shih-Li Su, and Yi-Ling Wu

Subjects
Male, medicine.medical_specialty, Databases, Factual, Taiwan, Pay for performance, 03 medical and health sciences, 0302 clinical medicine, Disease severity, Diabetes mellitus, Neoplasms, Medicine, Humans, In patient, Mortality, Reimbursement, Incentive, Aged, lcsh:R5-920, Shared care, business.industry, General Medicine, Middle Aged, medicine.disease, Incentive, National health insurance, Diabetes Mellitus, Type 2, Cardiovascular Diseases, 030220 oncology & carcinogenesis, Family medicine, 030211 gastroenterology & hepatology, Female, Diagnosis code, business, lcsh:Medicine (General)
Abstract

Background/Purpose: Comprehensive and continuous care is crucial for patients with diabetes. The diabetes pay-for-performance (P4P) program launched by the National Health Insurance (NHI) administration in Taiwan provides a financial incentive to facilitate this goal. In this study, we explored the characteristics of patients in the P4P program between 2005 and 2014. Methods: Data of patients with diabetes enrolled in the NHI program between 2005 and 2014 were extracted from the NHI research database. Patients were classed as having diabetes if they had three or more outpatient visits within 365 calendar days with an International Classification of Diseases, 9th Revision, Clinical Modification diagnostic code of 250 or hospitalization one or more times with such a diagnosis. The trends of participating in the P4P program were analyzed. Results: Participation rate of the P4P program increased from 12.1% to 19% between 2005 and 2014. Participants were younger and more likely to be female than those not participating in the program. Lower risks of cancer-related mortality, annual mortality and heart failure were seen in patients participating in the P4P program than in those not participating. Conclusion: Older, male patients with a high disease severity may be less likely to enroll in the P4P program. Although participation rate is increasing, a broad enrollment is expected. Keywords: Diabetes, National health insurance, Pay-for-performance

Published
2019

46. Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND randomised, placebo-controlled trial

Author

Hertzel C Gerstein, Helen M Colhoun, Gilles R Dagenais, Rafael Diaz, Mark Lakshmanan, Prem Pais, Jeffrey Probstfield, Fady T Botros, Matthew C Riddle, Lars Rydén, Denis Xavier, Charles Messan Atisso, Leanne Dyal, Stephanie Hall, Purnima Rao-Melacini, Gloria Wong, Alvaro Avezum, Jan Basile, Namsik Chung, Ignacio Conget, William C Cushman, Edward Franek, Nicolae Hancu, Markolf Hanefeld, Shaun Holt, Petr Jansky, Matyas Keltai, Fernando Lanas, Lawrence A Leiter, Patricio Lopez-Jaramillo, Ernesto German Cardona Munoz, Valdis Pirags, Nana Pogosova, Peter J Raubenheimer, Jonathan E Shaw, Wayne H-H Sheu, Theodora Temelkova-Kurktschiev, Mercedes Abella, Andrea Alebuena, Sandra Almagro, Eduardo Amoroso, Paula Anadon, Elizabeth Andreu, Guillermo Aristimuño, Maria Arzadun, Maria Barbieri, Raul Barcudi, Ines Bartolacci, Gabriel Bolobanich, Anselmo Bordonava, Miguel Bustamante Labarta, Betina Bustos, Alberto Caccavo, Alejandra Camino, Maria Cantero, Maria Carignano, Luis Cartasegna, Marcela Cipullo, Víctor Commendatore, Victoria Conosciuto, Osvaldo Costamagna, Claudia Crespo, Jose Cuello, Carlos Cuneo, Sandra Cusimano, Sofia Dean, Claudio Dituro, Andrea Dominguez, Miguel Farah, Alberto Fernandez, Florencia Fernandez, Adriana Ferrari, Patricia Flammia, Jose Fuentealba, Karina Beatriz Gallardo, Celso Garcia, Ruben Garcia Duran, Marcelo Garrido, Rodolfo Gavicola, Claudio Gerbaudo, Graciela Gilli, Ana Paula Giotto, Pedro Godoy Bolzán, Oscar Gomez Vilamajo, Fernando Guerlloy, Cristian Guridi, Narcisa Gutierrez Garrido, Eduardo Hasbani, Sonia Hermida, Miguel Hominal, Adrian Hrabar, Adrián Ingaramo, Alejandra Izzicupo, Mario Krynski, Mariana Lagrutta, Paulina Lanchiotti, Maria Langhe, Veronica Leonard, Javier Llanos, Ricardo Lopez Santi, Jorge Lowenstein, Cecilia Luquez, Ignacio Mackinnon, Melina Mana, Sara Manzur, Javier Marino, Carolina Martella, Roger Martinez, Re Matias, Javier Matkovich, Monica Meritano, Oscar Montaña, María Mulazzi, Juan Ochoa, Gustavo Paterlini, María Pelagagge, Maria Elena Peralta Lopez, Aldo Prado, Lorena Pruyas, Martín Racca, Carola Ricotti, Carolina Rodriguez, Mariano Romero Vidomlansky, Ricardo Ronderos, Ana Laura Sadowski, Jorgelina Sala, Alejandro Sánchez, Andrea Santoro, Lilia Schiavi, Mariano Sein, Virginia Sernia, Leonardo Serra, Maximiliano Sicer, Tomas Smith, Leonardo Soso, Georgina Sposetti, Andrea Steinacher, Jorge Stival, Jorge Tedesco, Hugo Tonin, Mauro Tortolo, Maria Ulla, Julio Vallejos, Marisa Vico, Luciana Virgillito, Virginia Visco, Daniel Vogel, Florencia Waisman, César Zaidman, Noemi Zucchiatti, Imran Badshah, Neale Cohen, Peter Colman, David Colquhoun, Timothy Davis, Spiros Fourlanos, Greg Fulcher, Jane Hamlyn, Cilla Haywood, Samantha Hocking, Maeve Huchinson, William Jeffries, Mervyn Kyl, Clement Lo, PeakMann Mah, Ashley Makepeace, Dolly Marope, Natalie Nanayakkar, Alison Nankervis, Neil Palmer, Barbara Palolus, Satish Pillai, Sarah Price, Joseph Proietto, Anne Reutens, Natassia Rodrigo, Abdul Sheikh, Greg Smith, Michelle So, Georgia Soldatos, Bronwyn Stuckey, Priya Sumithran, Helena Teede, Parind Vora, Lyn Williams, Eduardo Abib, Christiani Adão Poço, Érica Ferreira Alves, Janaina Andreatta Bernardi Barea, Livia Avezum Oliveira, Denise Ludovico da Costa de Castro, Ivan Correa da Cruz, Midiã Costa, Ivan Cruz, Sidney Cunha, Marco Antonio Vieira Da Silva, Renata de Carvalho Camara Bona, Bruna de Paula, Freddy Eliaschewitz, Guilherme Fazolli, Carlos Alberto Ferreira Filho, Jose Fortes, Cesar França, Denise Reis Franco, Paulo Roberto Genestreti, Flavio Giorgeto, Rodrigo Marques Gonçalves, Michele Elka Grossman, Ana Claudia Henrique Marcelino, Mauro Hernandes, Ana Horta, Cristiano Jaeger, Midia Kaneblai, Cecilia Kauffman Rutenberg, Jose Francisco Kerr Saraiva, Maria Angelica Lemos, Lilia Maia, Euler Roberto Manenti, Mariana Marques, Cynthia Melissa Valerio, Rodrigo Moreira, Flávia Mothé, Osana Maria Mouco, Philip Moura, José Carlos Moura Jorge, Carlos Nakashima, Marcelo Nakazone, Thiago Napoli, Cristiane Nunes, Joao Eduardo Nunes Salles, Karla Oliveira, Marcela Oliveira, Gracielly de Souza Pantano, Fabio Petri, Leonardo Piazza, Andreia Carla Pires, Patricia Pizzato, Sergio Prata, Dalton Precoma, Rafael Rech, Gilmar Reis, Heleno Reis, Elisabete Resende, Jose Ribas Fortes, Sylka Rodovalho, Fabio Rossi dos Santos, Joao Eduardo Salles, Célia Regina Sampaio, Thiago Santos, Vanessa Santos dos Santos, Tulio Silva e Quadros, Daniel Silveira, Katia Nunes Siqueira, M Teireira, Marcelo Uehara, C Valerio, Henrique Vianna, Maria Helena Vidotti, Guilherme de Lima Visconti, Maria Teresa Zanella, Viktoriya Andreeva, Radoslav Borisov, Nikolay Botushanov, Georgi Dimitrov, Kameliya Dimova, Tsvetan Dragoychev, Valentina Grigorova, Valentina Gushterova, Ivaylo Ivanov, Tatyana Kocelova, Dimo Kurktschiev, Milena Miletieva, Neli Nenkova-Gugusheva, Ralitsa Pancheva, Maria Pavlova, Dimitar Raev, Vesela Spasova, Anastas Stoikov, Dimitar Troev, Todor Yanev, Mariana Yoncheva-Mihaylova, Alexander Abitbol, Buki Ajala, Abdullh Alguwaihes, Jean-Luc Ardilouze, Nahla Aris-Jilwan, Amel Arnaout, Ronnie Aronson, Nadeem Aslam, Sandra Babin, Jean-Patrice Bailargeon, Allan Bailey, Harpreet Bajaj, Christian Beauchesne, Sorin Beca, Andre Belanger, Alan Bell, Diego Bellabarba, Lori Berard, Brian Berenbaum, Vincent Bergeron, Joseph Berlingieri, Frédéric Bernier, Phoebe Bishara, David Blank, Ian Blumer, Suzanne Brault, Donald Breton, André Carpentier, James Cha, Prakash Chandra, Jean-Louis Chiasson, James R Conway, Ghyslaine Couture, Nathalie Couture, Gilles Dagenais, Dyotirmoy Datta, Giuseppe D'Ignazio, Richard Dumas, Didier Fay, Andre Frechette, Louise Frenette, Daisy Fung, Nathalie Gagnon, Meri Galter, Jean Garon, Jean Sebastien Gauthier, Christian Geadah, Jeremy Gilbert, Ronald Girard, Ronald Goldenberg, Loren David Grossman, Nikhil Gupta, Jean-Pierre Halle, Marie-France Hivert, Ghislaine Houde, Robyn Houlden, Irene Hramiak, Ted Jablonski, Akshay Jain Jain, Hasnain Khandwala, Munish Khosla, C Lachance, Emilie Laflamme, Marie-France Langlois, Luc Larivee, Joanne Liutkus, Heather Lochnan, Saleem Malik, Charlotte McDonald, Pravinsagar Mehta, John Mihailidis, Alain Milot, Priya Narula, Patrice Nault, Arun Nayar, William Nisker, Gilles Ouellet, Jean Palardy, Minta Patel, Terri Paul, Sue Pedersen, Patrice Perron, Marie-Hélène Pesant, Paul Poirier, Marie-Claude Poulin, Zubin Punthakee, Waheed Rehman, Stuart Ross, P Sagar, Nouhad Saliba, Sam Sandler, Alicia Schiffrin, Robert Schlosser, Anila Seth-Sharma, Mark Sherman, David Sionit, Tharsan Sivakumar, Juan Soto, Eric St-Amour, Oren Steen, Jack Sussman, Adam Telner, Sheldon Tobe, David-Yaw Twum-Barima, Audrey Van Zanten, Nicole VanRossum, Jonathan Vecchiarelli, Rick Ward, John Wessengel, Stanley Weisnagel, Igor Wilderman, Vincent Woo, Natalia Yakubovich, Jean-Francois Yale, Zeina Yared, Monica Acevedo, Maria Loreto Aguirre, Andres Aizman, Maria Soledad Barroso, Leonardo Cobos, Alfredo Danin Vargas, Barbara Descalzi, Gonzalo Godoy, Elio Grumberg, Rodolfo Lahsen, Gladys Larenas, Eugenia Ortiz, Javier Paredes, Sergio Potthoff, Eva Retamal, Luis Rojas, Manuel Salgado, Claudio Santibanez, Carmen Solis, Benjamin Stokins, Jose Accini, Javier Acebedo, Lina Maria Agudelo Baena, Soraya Alarcon, Juliana Angel, Edgar Arcos, M Aroca Martinez, Leonor Atuesta, Jose Balaguera, Doris Ballestas, Sandra Isabel Barrera, Rosmy Barrios Reyes, Adolfo Bayona, Andres Bermudez, Diego Zarate Bernal, Marco Blanquicett, Victor Bravo, Wendy Bueno, Alvaro Burbano Delgado, Alberto Cadena, Andres Cadena, Sandra Caicedo, Carlos Celemin, Ricardo Consuegra, Cristhian Contreras Pimienta, Kelly Johenis Corredor, Carlos Cure, Lizeth Dayana De La Hoz Rueda, Erika Delgado, Sarahy Diaz, Marta Diego, Anabell Donado, William Encinales Sanabria, Juliana Escobar, Gillian Escorcia, Leonardo Forero, Laura Fuentes, Maria Garcia, Henry Garcia Lozada, Luis Garcia Ortiz, Angela Giraldo, Laura Gomez Gonzalez, Javier Granada, Corina Gutierrez, Natalia Henao, Edwin Hernandez, Olga Maria Herrera Uejbe, Juan Diego Higuera Cobos, Jaime Ibarra Gómez, Edwin Hernandez Jaimes, Monica Jaramillo, Nicolas Jaramillo, Carlos Jaramillo Gomez, Monica Jaramillo Sanchez, Ivonne Jarava Durán, Catalina Lopez Ceballos, Claudia Madrid, Elias María Amastha, Jennifer Mercado, Dora Ines Molina, Jessica Molina Soto, Carlos Montoya, Alexander Morales, Carolina Muñoz, Luis Alejandro Orozco, Oscar Osorio, Jorge Mario Palmera Sanchez, Adwar Peña, Jose Perez, Juan Perez Agudelo, Germán Pérez Amador, Carlos Pertuz, Irina Posada, Carlos Puerta, Adalberto Quintero, Diana Quiroz, Carmen Rendon, Alberto Reyes, Alvaro Reyes, Diana Ripoll, Carlos Rivera, Maria Rocha, Jose F Rodriguez, Kervis Asid Rodriguez Villanueva, Javier Emilio Rodriguez Zabala, Sindy Rojas, Maria Romero, Ricardo Rosero, Angelica Rocio Rosillo Cardenas, Lina Rueda, Gregorio Sanchez, Tatiana Sanchez, Arístides Sotomayor Herazo, Monica Suarez, Mariana Torres, Freddy Trujillo, Miguel Urina, Lazaro Van Strahlen, Carlos Velandia, Carolina Velasquez Guzman, Elizabeth Velazquez, Tatiana Vidal Prada, Juan Pablo Yepez Alvaran, Diego Zarate, Jana Andelova, Radka Benesova, Barbara Buzova, Vladimir Cech, Ida Chodova, Miroslav Choura, Antonin Dufka, Andrea Gamova, Jakub Gorgol, Tomas Hala, Hana Havlova, Dagmar Hlavkova, Petra Horanska, Juliana Ilcisin-Valova, Petra Jenickova, Ondrej Jerabek, Ilona Kantorova, Katerina Kolomaznikova, Iva Kopeckova, Miroslava Kopeckova, Karel Linhart, Tomas Linhart, Jan Malecha, Emilia Malicherova, Dana Neubauerova, Martina Oznerova, Radan Partys, Eva Pederzoliova, Maria Petrusova, Vera Prymkova, Eva Racicka, Ida Reissova, Eva Roderova, Libor Stanek, Alena Striova, Dana Svarcova, Petr Svoboda, Emilia Szeghy Malicharova, Jan Urge, Ladislav Vesely, Bedich Wasserburger, Hilde Wasserburgerova, Emil Zahumensky, Vaclav Zamrazil, Hasan Alawi, Ernestos Anastasiadis, Elisabeth Axthelm, Tasso Bieler, Christina Buhrig, Elizaveta Degtyareva, Frank Dellanna, Karl-Michael Derwahl, Stephan Diessel, Barbara Dogiami, Kirsten Dorn-Weitzel, Monika Ernst, Grit Faulmann, Baerbel Fetscher, Thomas Forst, Gabriele Freyer-Lahres, Klaus Funke, Xenia Ganz, Christiane Gleixner, Christoph Hanefeld, Sven Heinrichs, Stephanie Helleberg, Elena Henkel, Gerd Ruediger Hetzel, Caren Hoffmann, Frohmut Jacob, Stephan Jacob, Franziska John, Antonius Jonczyk, Wolfram Kamke, Christiane Klein, Martina Kleinhardt, Werner Kleophas, Christine Kosch, Kristin Kreutzmann, Achim Kühn, Young Hee Lee-Barkey, Alexander Lier, Sarah Maatouk, Joachim Minnich, Michael Mitry, Ilona Muessig, Diana Nicula, Martina Niemann, Joerg Nothroff, Petra Ott, Andreas Pfuetzner, Andreas Pfützner, Frank Pistrosch, Wildgard Pohl, Zdenka Prochazkova, Marlena Retkowska, Heiko Rosin, Daniela Sachsenheimer, Holger Samer, Mazin Sanuri, Axel Schaefer, Frank Schaper, Erik-Delf Schulze, Marita Schulze, Martina Schumann, Thomas Segiet, Veronika Sowa, Hans-Detlev Stahl, Franziska Steinfeldt, Madlen Teige, Bjoern Trieb, Diethelm Tschoepe, Peter Uebel, Bernd Warken, Ingo Weigmann, Klaus Weyland, Klara Wilhelm, Timea Balo, Miklos Balsay, Ilona Bende, Katalin Bezzegh, Zita Birkus, Barbara Buday, Melinda Csomai, Laszlo Deak, Eniko Dezso, Peter Faludi, M Faluvegi, Ilona Fazekas, Agota Feher, Csaba Fejer, Ervin Finta, Agnes Fulcz, Zsolt Gaal, Mihaly Gurzo, Krisztina Hati, Gabriella Herczeg, Ildiko Jozsef, Marta Juhasz, Katalin Keltai, Laszlo Koranyi, Eniko Kulcsar, Krisztina Kun, Andrea Laczko, Botond Literáti-Nagy, Izabella Mezo, Margit Mileder, I Moricz, Károly Nagy, Bela Nagybaczoni, Csaba Nemeth, Agnes Oze, Jozsef Pauer, Eva Peterfai, Bela Polocsanyi, Ferenc Poor, István Reiber, Csaba Salamon, Julia Sebestyen, Ildiko Torok, Marianna Tuu, Andrea Varga, Viktor Vass, Chul Min Ahn, Chulwoo Ahn, Park ByungWon, Hyuk-Jae Chang, Kiyuk Chang, Eui-Young Choi, Han Seok Choi, Jin-Wook Chung, Bum- Kee Hong, Young Joon Hong, Min Su Hyon, Myung Ho Jeong, Shinae Kang, Byeong-Keuk Kim, Ji-Hyun Kim, Ju Han Kim, Kee-Sik Kim, Moo Hyun Kim, Pum-Joon Kim, Soon-Kil Kim, Yong-Seok Kim, Young Kwon Kim, Yoon Seok Koh, Hyuck Moon Kwon, Byoung Kwon Lee, Byung-Wan Lee, Jin Bae Lee, Myoung-Mook Lee, Young-Mee Lim, Pil Ki Min, Jong Sung Park, Jongsuk Park, Keun Ho Park, Sungha Park, Wook Bum Pyun, Se Joong Rim, Dong-Ryeol Ryu, Hong-Seog Seo, Ki Bae Seung, Dong-Ho Shin, Doo Sun Sim, Young Won Yoon, Ilze Andersone, Kristine Babicka, Inga Balcere, Roberts Barons, Inguna Capkovska, Kristine Geldnere, Inese Grigane, Baiba Jegere, Ilze Lagzdina, Lija Mora, Sigita Pastare, Rota Ritenberga, Janina Romanova, Inta Saknite, Natalja Sidlovska, Jelena Sokolova, Sandra Steina, Iveta Strizko, Dace Teterovska, Brigita Vizina, Lina Barsiene, Gintare Belozariene, Laura Daugintyte-Petrusiene, Nijole Drungiliene, Nijole Garsviene, Ala Grigiene, Vytautas Grizas, Virginija Jociene, Dalia Kalvaitiene, Jugeta Kaupiene, Jurate Kavaliauskiene, Dalia Kozloviene, Ilona Lapteva, Birute Maneikiene, Jolanta Marcinkeviciene, Vaidilija Markauskiene, Salomeja Meiluniene, Almantas Norkus, Rita Norviliene, Vladimiras Petrenko, Ruta Radzeviciene, Gintare Sakalyte, Gediminas Urbonas, Skaiste Urbutiene, Donatas Vasiliauskas, Dzilda Velickiene, Carlos Aguilar, Marco Alcocer, Juan Antonio Avalos-Ramirez, Ramiro Banda-Elizondo, Rubria Bricio-Ramirez, Karla Cardenas Mejia, Francisco Cavazos, Jesus Chapa, Erika Cienfuegos, Astrid De la Peña, Gilberto de la Peña Topete, Manuel Odin De los Rios Ibarra, Daniel Elias, Claudia Flores-Moreno, Pedro Garcia Hernandez, Luis Gerardo Gonzalez, Rosa Linda Guerra Moya, Arturo Guerra-Lopez, Raymundo Hernandez Baylon, Carolina Herrera Colorado, Marisol Herrera-Marmolejo, Neri Islas-Palacios, Esteban Lopez, Fernando Lopez, Agustin Lopez Alvarado, Rosa Isela Luna Ceballos, Enrique Morales Villegas, Gualberto Moreno-Virgen, Rosa Linda Parra Perez, Sara Pascoe Gonzalez, Irving Peralta-Cantu, Roopa Previn, Rosa Ramirez, Rubria Ramirez, Maria Guadalupe Ramos Zavala, Monica Rodriguez, Rocio Salgado-Sedano, Ana Claudia Sanchez-Aguilar, Edith Santa Rosa Franco, Leobardo Sauque-Reyna, Rodrigo Suarez Otero, Ivonne Torres, Enrique Velarde-Harnandez, Juan Villagordoa, Efrain Villeda-Espinoza, Jorge Vital-Lopez, Cristian Jair Zavala- Bello, John Baker, Elaine Barrington-Ward, Thomas Brownless, Richard Carroll, Simon Carson, Michelle Choe, Andrew Corin, Brian Corley, Richard Cutfield, Neelam Dalaman, Paul Dixon, Paul Drury, Keith Dyson, Chris Florkowski, Monica Ford, William Frengley, Colin Helm, Colin Katzen, Jane Kerr, Manish Khanolkar, David Kim, Renata Koops, Jeremy Krebs, Robert Leikis, Kwan Low, Alison Luckey, Richard Luke, Susan Macaulay, Rodney Marks, Catherine McNamara, Dean Millar-Coote, Steven Miller, Naomi Mottershead, James Reid, Narcisa Robertson, Ian Rosen, David Rowe, Ole Schmiedel, Russell Scott, Jeffrey Sebastian, Davitt Sheahan, Victoria Stiebel, Ian Ternouth, Chris Tofield, Dirk Venter, Michael Williams, Miles Williams, Fiona Wu, Simon Young, Malgorzata Arciszewska, Anna Bochenek, Piotr Borkowski, Przemyslaw Borowy, Tomasz Chrzanowski, Edward Czerwinski, Marek Dwojak, Agnieszka Grodzicka, Izabela Janiec, Joanna Jaruga, Ewa Krystyna Jazwinska-Tarnawska, Krystyna Jedynasty, Danuta Juzwiak-Czapiewska, Jadwiga Karczewicz-Janowska, Jan Konieczny, Marek Konieczny, Marek Korol, Maciej Kozina, Ewa Krzyzagorska, Ewa Kucharczyk-Petryka, Roman Laz, Anna Majchrzak, Zdzislawa Mrozowska, Michal Mularczyk, Elzbieta Nowacka, Jadwiga Peczynska, Robert Petryka, Radoslaw Pietrzak, Dorota Pisarczyk-Wiza, Aleksandra Rozanska, Zofia Ruzga, Emilia Rzeszotarska, Malgorzata Sacha, Marzenna Sekulska, Anna Sidorowicz-Bialynicka, Teresa Stasinska, Agnieszka Strzelecka-Sosik, Teresa Swierszcz, Katarzyna Miroslawa Szymkowiak, Olga Turowska, Krystyna Wisniewska, Maciej Wiza, Iwona Wozniak, Katarzyna Zelazowska, Bernadetta Ziolkowska-Gawron, Danuta Zytkiewicz-Jaruga, Adrian Albota, Carmina Alexandru, Rodica Avram, Cornelia Bala, Diana Barbonta, Roxana Barbu, Daniela Braicu, Nicoleta Calutiu, Doina Catrinoiu, Anca Cerghizan, Alina Ciorba, Anca Craciun, Rodica Doros, Livia Duma, Ancuta Dumitrache, Ioana Ferariu, Anca Ferician Moza, Alexandrina Ghergan, Gheorghe Ghise, Mariana Graur, Mihaela Gribovschi, Bogdan Mihai, Laura Mihalache, Madalina Mihalcea, Nicoleta Mindrescu, Magdalena Morosanu, Andrea Morosoanu, Maria Mota, Anca Moza, Valerica Nafornita, Narcisa Natea, Simona Nicodim, Cristina Nita, Adriana Onaca, Mircea Onaca, Cristina Pop, Lavinia Pop, Amorin Popa, Alexandrina Popescu, Luchiana Pruna, Gabriela Roman, Mihaela Rosu, Alexandra Sima, Doina Sipciu, Carmen Narcisa Sitterli-Natea, Iosif Szilagyi, Minodora Tapurica, Adrian Tase, Adriana-Carmen Tutescu, Luminita Vanghelie, Ioana Verde, Adrian Vlad, Mihaela Zarnescu, Roman Akhmetov, Irina Allenova, Irina Avdeeva, Oksana Baturina, Irina Biserova, Nikolay Bokovin, Irina Bondar, Natalia Burova, Galina Chufeneva, Elena Chumachek, Marina Demidova, Alexander Demin, Vera Drobysheva, Irina Egorova, Lev Esenyan, Ekaterina Gelig, Sergey Gilyarevsky, Maria Golshmid, Arseniy Goncharov, Anastasia Gorbunova, Ivan Gordeev, Vera Gorelysheva, Tatiana Goryunova, Irina Grebenshchikova, Roman Ilchenko, Maria Ivannikova, Saule Karabalieva, Juliya Karpeeva, Elena Khaykina, Zhanna Kobalava, Irina Kononenko, Oxana Korolik, Anna Korshunova, Victor Kostenko, Irina Krasnopevtseva, Ludmila Krylova, Polina Kulkova, Irina Kuzmina, Alla Ledyaeva, Sergey Levashov, Natalia Lokhovinina, Vadim Lvov, Narine Martirosyan, Sergey Nedogoda, Rostislav Nilk, Yulia Osmolovskaya, Alexey Panov, Olga Paramonova, Ekaterina Pavlova, Elena Pekareva, Nina Petunina, Svetlana Ponamareva, Galina Reshedko, Alla Salasyuk, Malvina Sepkhanyan, Alexandr Serebrov, Olesya Shabelnikova, Andrey Skvortsov, Olga Smirnova, Oxana Spiridonova, Svetlana Strogova, Evgeny Taratukhin, Sergey Tereschenko, Lubov Trukhina, Olga Tsarkova, Vera Tsoma, Farid Tumarov, Natalya Tyan, Tatiana Tyurina, Svetlana Villevalde, Elena Yankovaya, Ludmila Zarutskaya, Elena Zenkova, Aysha Badat, Frederik Bester, Suzanne Blignaut, Dirk Blom, Susan Booysen, Warren Boyd, Brigitte Brice, Susan Brown, Lesley Burgess, Reina Cawood, Kathleen Coetzee, Hillet Conradie, Tanja Cronje, Douwe de Jong, Graham Ellis, Shaunagh Emanuel, Ingrid Engelbrecht, Sharne Foulkes, Done Fourie, Gilbert Gibson, Thirumani Govender, Sumayah Hansa, Allana Colleen Hemus, Firzana Hendricks, Marshall Heradien, Chantelle Holmgren, Zaheer Hoosain, Emile Horak, Johannes Howard, Ignatius Immink, E. Janari, Daksha Jivan, Karl Klusmann, Weik Labuschagne, Yen-yu Lai, Gulam Latiff, J. Lombaard, Hanlie Lottering, Ronel Meeding, Shirley Middlemost, Haroon Mitha, Ismail Mitha, Sandile Mkhwanazi, Rajendran Moodley, Almeri Murray, Dany Musungaie, Yasmin Osman, Kirsten Peacey, Larisha Pillay-Ramaya, Catharina Pretorius, Hans Prozesky, Mahomed Sarvan, E Scholtz, Attila Sebesteny, Bianca Skinner, Michael Skriker, M Smit, Anna-Marie Stapelberg, Nicolaas Swanepoel, Dorothea Urbach, Dina van Aswegen, Francois van Zyl, Louis Van Zyl, Esme Venter, Shahid Wadvalla, Jeffrey Wing, Karen Wolmarans, Cristina Abreu, Pilar Aguilà, Eva Aguilera, Nuria Alonso, Carmen Alvarez, Priscila Cajas, Jose Carlos Castro, Roger Codinachs, Jose Contreras, Maria Jose Coves, Carmen Fajardo, Juan Carlos Ferrer, Neus Font, Mar Garcia, Maria Apolonia Gil, Fernando Gomez, Lluis Alberto Gomez, Jose Gonzalbez, Jose Luis Griera, Luís Masmiquel, Didac Mauricio, Silvia Narejos Perez, Juana Ana Nicolau, Olga Noheda Contreras, Josefina Olivan, Josefina Olivares, Emilio Ortega, Silvia Pellitero, Salvador Pertusa, Ferran Rius, Irene Rodriguez, Carlos Sánchez-Juan, Dolores Santos, Berta Soldevila, David Subias, Manel Terns, Carlos Trescoli, Judith Vilaplana, Alicia Villanueva, Jaan Albo, Kjell Antus, Mattias Axelsson, Lisa Bergström, Emil Binsell-Gerdin, Kurt Boman, Fabian Botond, Annika Dotevall, Anna Graipe, C Jarnet, Jessica Kaminska, Anders Kempe, Michael Korhonen, Carina Linderfalk, Bo Liu, Karl Ljungstroem, Karl Ljungström, Lennart Malmqvist, Linda Mellbin, Thomas Mooe, Peter Nicol, Anders Norrby, Ake Ohlsson, Annika Rosengren, Jan Saaf, Staffan Salmonsson, Olof Strandberg, Karl-Axel Svensson, Bengt-Olov Tengmark, Georgios Tsatsaris, Anders Ulvenstam, Peter Vasko, Chwen-Tzuei Chang, Hsin-Mei Chang, Jung-Fu Chen, To-Pang Chen, Ming-Min Chung, Chia-Po Fu, Te-Lin Hsia, Shih-Che Hua, Ming-Chun Kuo, Chia-ln Lee, I-Te Lee, Kae-Woei Liang, Shih Yi Lin, Chieh-Hsiang Lu, Wen-Ya Ma, Dee Pei, Feng-Chih Shen, Ching-Chieh Su, Shuo-Wei Su, Tsai-Sung Tai, Wan-Ni Tsai, Yi-Ting Tsai, Shih-Chen Tung, Jun-Sing Wang, Hui-I Yu, Ahmed Al-Qaissi, Vijayaraman Arutchelvam, Stephen Atkin, Simon Au, Myint Myint Aye, Stephen Bain, Cristina Bejnariu, Patrick Bell, Deepak Bhatnagar, Rudy Bilous, Neil Black, Ursula Brennan, Barbara Brett, Jana Bujanova, Elaine Chow, Andrew Collier, Amanda Combe, Christopher Courtney, Hamish Courtney, James Crothers, Patrick Eavis, Jackie Elliott, Salvatore Febbraro, Jim Finlayson, Rajiv Gandhi, Sharon Gillings, Jonathan Hamling, Roy Harper, Tim Harris, Kahal Hassan, Simon Heller, Alison Jane, Zeeshan Javed, Tim Johnson, Stephen Jones, Adele Kennedy, David Kerr, Brian Kilgallon, Judith Konya, John Lindsay, Lina Lomova-Williams, Helen Looker, David MacFarlane, Sandra Macrury, Iqbal Malik, Rory McCrimmon, Douglas McKeith, John McKnight, Biswa Mishra, Racha Mukhtar, Ciara Mulligan, Maurice O'Kane, Tolu Olateju, Ian Orpen, Tristan Richardson, Desmond Rooney, Shorsha Bae Ross, Thozhukat Sathyapalan, Naveen Siddaramaiah, Lee Euan Sit, Jeffrey Stephens, Frances Turtle, Ammar Wakil, Emma Walkinshaw, Asem Ali, Robert Anderson, Richard Arakaki, Omar Aref, Mehrdad Kevin Ariani, David Arkin, Salomon Banarer, George Barchini, Arti Bhan, Kelley Branch, Donald Brautigam, Stephen Brietzke, Maridez Brinas, Yudit Brito, Casey Carter, Kimberely Casagni, Sabina Casula, Simon Chakko, Seth Charatz, Dale Childress, Lisa Chow, Malgorzata Chustecka, Subha Clarke, Lisa Cohen, Barry Collins, Gildred Colon Vega, Angel Comulada-Rivera, Gregorio Cortes-Maisonet, Matthew Davis, Jose de Souza, Cyrus Desouza, Mary Dinnan, Bobbi Duffy-Hidalgo, Barbara Dunn, Julia Dunn, Marshall Elman, James Felicetta, Stuart Finkelstein, David Fitz-Patrick, Hermes Florez, Alan Forker, Wayne Fowler, Sonja Fredrickson, Zachary Freedman, Brooke Gainey Narron, Kristin Gainey-Ferree, Michael Gardner, Christian Gastelum, Stephen Giddings, Eve Gillespie, Michael Paul Gimness, Gary Goldstein, Maria Gomes, Nelson Gomez, Timothy Gorman, Ketan Goswami, Arthur Graves, Scott Hacking, Charles Hall, Lenita Hanson, Sherman Harman, David Heber, Robert Henry, Janette Hiner, Irl Hirsch, Priscilla Hollander, Thomas Hooker, Barry Horowitz, Laura Hoste, Loli Huang, Minh Huynh, Dan Hyman, Soha Idriss, Ali Iranmanesh, Dennis Karounos, Moti Kashyap, Lois Katz, William Kaye, Yevgeniy Khaiton, Romesh Khardori, Timothy Kitchen, Andrew Klein, Wendi Knffem, Mikhail Kosiborod, Nicola Kreglinger, Davida Kruger, Anubhav Kumar, Ivan Laboy, Patricia Larrabee, Laura Larrick, Donna Lawson, Mike Ledet, James Lenhard, James Levy, George Li, Zhaoping Li, David Lieb, April Limcolioc, Jane Lions-Patterson, Daniel Lorber, Daniel Lorch, Michael Lorrello, Peter Lu, Kathryn Jean Lucas, Siu-Ling Ma, Michael MacAdams, Michelle Magee, Alexander Magno, Aparna Reddy Mahakala, Jennifer Marks, Anthony McCall, William McClanahan, Carole McClary, Lydia Melendez, John Melish, Deanna Michaud, Christopher Miller, Neil Miller, Pablo Mora, Marriyam Moten, Sunder Mudaliar, Gregory Myrick, Puneet Narayan, Mike Nassif, Karena Neri, Tabitha Newton, Patricia Niblack, Philip Nicol, Ebenezer Nyenwe, A. Ola Odugbesan, Yolanda Okorocha, Ramón Ortiz Carrasquillo, Kwame Osei, Coromoto Palermo, Hiren Patel, Krishna Patel, Cindy Pau, Michael Perley, Sanford Plevin, Elena Plummer, Richard Powell, Mohammed Qintar, Rex Rawls, John Reyes-Castano, Lillian Reynolds, Robert Richards, Julio Rosenstock, Caroline Rowe, Jahandar Saleh, Sony Sam, Alfredo Sanchez, Donald Sander, Bruce Sanderson, Virginia Savin, Elizabeth Seaquist, Jayendra Shah, Serena Shi, Vijay Shivaswamy, Tammi Shlotzhauer, David Shore, Bobbie Skukowski, Kyaw Soe, Vesna Solheim, Joseph Soufer, Helmut Steinberg, Jaime Steinsapir, Phillip Tarkington, Debra Thayer, Stephen Thomson, James Thrasher, Joseph Tibaldi, Jeff Tjaden, Oberto Tores, Dace Trence, Subbulaxmi Trikudanathan, Jagdeesh Ullal, Gabriel Uwaifo, Anthony Vo, Kenny Vu, Damandeep Walia, Karen Weiland, Fred Whitehouse, Thomas Wiegmann, Kathleen Wyne, Alan Wynne, Kevin Yuen, Joel Zaretzky, James Zebrack, Franklin Zieve, William Zigrang, and Everest

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Recombinant Fusion Proteins, Placebo-controlled study, Glucagon-Like Peptides, 030204 cardiovascular system & hematology, Placebo, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, law, Internal medicine, Medicine, Albuminuria, Humans, Hypoglycemic Agents, Diabetic Nephropathies, 030212 general & internal medicine, Renal replacement therapy, Aged, Intention-to-treat analysis, business.industry, Hazard ratio, General Medicine, Middle Aged, medicine.disease, Immunoglobulin Fc Fragments, Diabetes Mellitus, Type 2, Creatinine, Dulaglutide, Female, business, medicine.drug, Kidney disease, Glomerular Filtration Rate
Abstract

Digital, Background: Two glucagon-like peptide-1 (GLP-1) receptor agonists reduced renal outcomes in people with type 2 diabetes at risk for cardiovascular disease. We assessed the long-term effect of the GLP-1 receptor agonist dulaglutide on renal outcomes in an exploratory analysis of the REWIND trial of the effect of dulaglutide on cardiovascular disease. Methods: REWIND was a multicentre, randomised, double-blind, placebo-controlled trial at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo and followed up at least every 6 months for outcomes. Urinary albumin-to-creatinine ratios (UACRs) and estimated glomerular filtration rates (eGFRs) were estimated from urine and serum values measured in local laboratories every 12 months. The primary outcome (first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes), secondary outcomes (including a composite microvascular outcome), and safety outcomes of this trial have been reported elsewhere. In this exploratory analysis, we investigate the renal component of the composite microvascular outcome, defined as the first occurrence of new macroalbuminuria (UACR >33·9 mg/mmol), a sustained decline in eGFR of 30% or more from baseline, or chronic renal replacement therapy. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01394952. Findings: Between Aug 18, 2011, and Aug 14, 2013, 9901 participants were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). At baseline, 791 (7·9%) had macroalbuminuria and mean eGFR was 76·9 mL/min per 1·73 m2 (SD 22·7). During a median follow-up of 5·4 years (IQR 5·1-5·9) comprising 51 820 person-years, the renal outcome developed in 848 (17·1%) participants at an incidence rate of 3·5 per 100 person-years in the dulaglutide group and in 970 (19·6%) participants at an incidence rate of 4·1 per 100 person-years in the placebo group (hazard ratio [HR] 0·85, 95% CI 0·77-0·93; p=0·0004). The clearest effect was for new macroalbuminuria (HR 0·77, 95% CI 0·68-0·87; p, Ciencias Médicas y de la Salud

Published
2019

47. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial

Author

Hertzel C Gerstein, Helen M Colhoun, Gilles R Dagenais, Rafael Diaz, Mark Lakshmanan, Prem Pais, Jeffrey Probstfield, Jeffrey S Riesmeyer, Matthew C Riddle, Lars Rydén, Denis Xavier, Charles Messan Atisso, Leanne Dyal, Stephanie Hall, Purnima Rao-Melacini, Gloria Wong, Alvaro Avezum, Jan Basile, Namsik Chung, Ignacio Conget, William C Cushman, Edward Franek, Nicolae Hancu, Markolf Hanefeld, Shaun Holt, Petr Jansky, Matyas Keltai, Fernando Lanas, Lawrence A Leiter, Patricio Lopez-Jaramillo, Ernesto German Cardona Munoz, Valdis Pirags, Nana Pogosova, Peter J Raubenheimer, Jonathan E Shaw, Wayne H-H Sheu, Theodora Temelkova-Kurktschiev, Mercedes Abella, Andrea Alebuena, Sandra Almagro, Eduardo Amoroso, Paula Anadon, Elizabeth Andreu, Guillermo Aristimuño, Maria Arzadun, Maria Barbieri, Raul Barcudi, Ines Bartolacci, Gabriel Bolobanich, Anselmo Bordonava, Miguel Bustamante Labarta, Betina Bustos, Alberto Caccavo, Alejandra Camino, Maria Cantero, Maria Carignano, Luis Cartasegna, Marcela Cipullo, Víctor Commendatore, Victoria Conosciuto, Osvaldo Costamagna, Claudia Crespo, Jose Cuello, Carlos Cuneo, Sandra Cusimano, Sofia Dean, Claudio Dituro, Andrea Dominguez, Miguel Farah, Alberto Fernandez, Florencia Fernandez, Adriana Ferrari, Patricia Flammia, Jose Fuentealba, Karina Beatriz Gallardo, Celso Garcia, Ruben Garcia Duran, Marcelo Garrido, Rodolfo Gavicola, Claudio Gerbaudo, Graciela Gilli, Ana Paula Giotto, Pedro Godoy Bolzán, Oscar Gomez Vilamajo, Fernando Guerlloy, Cristian Guridi, Narcisa Gutierrez Garrido, Eduardo Hasbani, Sonia Hermida, Miguel Hominal, Adrian Hrabar, Adrián Ingaramo, Alejandra Izzicupo, Mario Krynski, Mariana Lagrutta, Paulina Lanchiotti, Maria Langhe, Veronica Leonard, Javier Llanos, Ricardo Lopez Santi, Jorge Lowenstein, Cecilia Luquez, Ignacio Mackinnon, Melina Mana, Sara Manzur, Javier Marino, Carolina Martella, Roger Martinez, Re Matias, Javier Matkovich, Monica Meritano, Oscar Montaña, María Mulazzi, Juan Ochoa, Gustavo Paterlini, María Pelagagge, Maria Elena Peralta Lopez, Aldo Prado, Lorena Pruyas, Martín Racca, Carola Ricotti, Carolina Rodriguez, Mariano Romero Vidomlansky, Ricardo Ronderos, Ana Laura Sadowski, Jorgelina Sala, Alejandro Sánchez, Andrea Santoro, Lilia Schiavi, Mariano Sein, Virginia Sernia, Leonardo Serra, Maximiliano Sicer, Tomas Smith, Leonardo Soso, Georgina Sposetti, Andrea Steinacher, Jorge Stival, Jorge Tedesco, Hugo Tonin, Mauro Tortolo, Maria Ulla, Julio Vallejos, Marisa Vico, Luciana Virgillito, Virginia Visco, Daniel Vogel, Florencia Waisman, César Zaidman, Noemi Zucchiatti, Imran Badshah, Neale Cohen, Peter Colman, David Colquhoun, Timothy Davis, Spiros Fourlanos, Greg Fulcher, Jane Hamlyn, Cilla Haywood, Samantha Hocking, Maeve Huchinson, William Jeffries, Mervyn Kyl, Clement Lo, PeakMann Mah, Ashley Makepeace, Dolly Marope, Natalie Nanayakkar, Alison Nankervis, Neil Palmer, Barbara Palolus, Satish Pillai, Sarah Price, Joseph Proietto, Anne Reutens, Natassia Rodrigo, Abdul Sheikh, Greg Smith, Michelle So, Georgia Soldatos, Bronwyn Stuckey, Priya Sumithran, Helena Teede, Parind Vora, Lyn Williams, Eduardo Abib, Christiani Adão Poço, Érica Ferreira Alves, Janaina Andreatta Bernardi Barea, Livia Avezum Oliveira, Denise Ludovico da Costa de Castro, Ivan Correa da Cruz, Midiã Costa, Ivan Cruz, Sidney Cunha, Marco Antonio Vieira Da Silva, Renata de Carvalho Camara Bona, Bruna de Paula, Freddy Eliaschewitz, Guilherme Fazolli, Carlos Alberto Ferreira Filho, Jose Fortes, Cesar França, Denise Reis Franco, Paulo Roberto Genestreti, Flavio Giorgeto, Rodrigo Marques Gonçalves, Michele Elka Grossman, Ana Claudia Henrique Marcelino, Mauro Hernandes, Ana Horta, Cristiano Jaeger, Midia Kaneblai, Cecilia Kauffman Rutenberg, Jose Francisco Kerr Saraiva, Maria Angelica Lemos, Lilia Maia, Euler Roberto Manenti, Mariana Marques, Cynthia Melissa Valerio, Rodrigo Moreira, Flávia Mothé, Osana Maria Mouco, Philip Moura, José Carlos Moura Jorge, Carlos Nakashima, Marcelo Nakazone, Thiago Napoli, Cristiane Nunes, Joao Eduardo Nunes Salles, Karla Oliveira, Marcela Oliveira, Gracielly de Souza Pantano, Fabio Petri, Leonardo Piazza, Andreia Carla Pires, Patricia Pizzato, Sergio Prata, Dalton Precoma, Rafael Rech, Gilmar Reis, Heleno Reis, Elisabete Resende, Jose Ribas Fortes, Sylka Rodovalho, Fabio Rossi dos Santos, Joao Eduardo Salles, Célia Regina Sampaio, Thiago Santos, Vanessa Santos dos Santos, Tulio Silva e Quadros, Daniel Silveira, Katia Nunes Siqueira, M Teireira, Marcelo Uehara, C Valerio, Henrique Vianna, Maria Helena Vidotti, Guilherme de Lima Visconti, Maria Teresa Zanella, Viktoriya Andreeva, Radoslav Borisov, Nikolay Botushanov, Georgi Dimitrov, Kameliya Dimova, Tsvetan Dragoychev, Valentina Grigorova, Valentina Gushterova, Ivaylo Ivanov, Tatyana Kocelova, Dimo Kurktschiev, Milena Miletieva, Neli Nenkova-Gugusheva, Ralitsa Pancheva, Maria Pavlova, Dimitar Raev, Vesela Spasova, Anastas Stoikov, Dimitar Troev, Todor Yanev, Mariana Yoncheva-Mihaylova, Alexander Abitbol, Buki Ajala, Abdullh Alguwaihes, Jean-Luc Ardilouze, Nahla Aris-Jilwan, Amel Arnaout, Ronnie Aronson, Nadeem Aslam, Sandra Babin, Jean-Patrice Bailargeon, Allan Bailey, Harpreet Bajaj, Christian Beauchesne, Sorin Beca, Andre Belanger, Alan Bell, Diego Bellabarba, Lori Berard, Brian Berenbaum, Vincent Bergeron, Joseph Berlingieri, Frédéric Bernier, Phoebe Bishara, David Blank, Ian Blumer, Suzanne Brault, Donald Breton, André Carpentier, James Cha, Prakash Chandra, Jean-Louis Chiasson, James R Conway, Ghyslaine Couture, Nathalie Couture, Gilles Dagenais, Dyotirmoy Datta, Giuseppe D'Ignazio, Richard Dumas, Didier Fay, Andre Frechette, Louise Frenette, Daisy Fung, Nathalie Gagnon, Meri Galter, Jean Garon, Jean Sebastien Gauthier, Christian Geadah, Jeremy Gilbert, Ronald Girard, Ronald Goldenberg, Loren David Grossman, Nikhil Gupta, Jean-Pierre Halle, Marie-France Hivert, Ghislaine Houde, Robyn Houlden, Irene Hramiak, Ted Jablonski, Akshay Jain Jain, Hasnain Khandwala, Munish Khosla, C Lachance, Emilie Laflamme, Marie-France Langlois, Luc Larivee, Joanne Liutkus, Heather Lochnan, Saleem Malik, Charlotte McDonald, Pravinsagar Mehta, John Mihailidis, Alain Milot, Priya Narula, Patrice Nault, Arun Nayar, William Nisker, Gilles Ouellet, Jean Palardy, Minta Patel, Terri Paul, Sue Pedersen, Patrice Perron, Marie-Hélène Pesant, Paul Poirier, Marie-Claude Poulin, Zubin Punthakee, Waheed Rehman, Stuart Ross, P Sagar, Nouhad Saliba, Sam Sandler, Alicia Schiffrin, Robert Schlosser, Anila Seth-Sharma, Mark Sherman, David Sionit, Tharsan Sivakumar, Juan Soto, Eric St-Amour, Oren Steen, Jack Sussman, Adam Telner, Sheldon Tobe, David-Yaw Twum-Barima, Audrey Van Zanten, Nicole VanRossum, Jonathan Vecchiarelli, Rick Ward, John Wessengel, Stanley Weisnagel, Igor Wilderman, Vincent Woo, Natalia Yakubovich, Jean-Francois Yale, Zeina Yared, Monica Acevedo, Maria Loreto Aguirre, Andres Aizman, Maria Soledad Barroso, Leonardo Cobos, Alfredo Danin Vargas, Barbara Descalzi, Gonzalo Godoy, Elio Grumberg, Rodolfo Lahsen, Gladys Larenas, Eugenia Ortiz, Javier Paredes, Sergio Potthoff, Eva Retamal, Luis Rojas, Manuel Salgado, Claudio Santibanez, Carmen Solis, Benjamin Stokins, Jose Accini, Javier Acebedo, Lina Maria Agudelo Baena, Soraya Alarcon, Juliana Angel, Edgar Arcos, M Aroca Martinez, Leonor Atuesta, Jose Balaguera, Doris Ballestas, Sandra Isabel Barrera, Rosmy Barrios Reyes, Adolfo Bayona, Andres Bermudez, Diego Zarate Bernal, Marco Blanquicett, Victor Bravo, Wendy Bueno, Alvaro Burbano Delgado, Alberto Cadena, Andres Cadena, Sandra Caicedo, Carlos Celemin, Ricardo Consuegra, Cristhian Contreras Pimienta, Kelly Johenis Corredor, Carlos Cure, Lizeth Dayana De La Hoz Rueda, Erika Delgado, Sarahy Diaz, Marta Diego, Anabell Donado, William Encinales Sanabria, Juliana Escobar, Gillian Escorcia, Leonardo Forero, Laura Fuentes, Maria Garcia, Henry Garcia Lozada, Luis Garcia Ortiz, Angela Giraldo, Laura Gomez Gonzalez, Javier Granada, Corina Gutierrez, Natalia Henao, Edwin Hernandez, Olga Maria Herrera Uejbe, Juan Diego Higuera Cobos, Jaime Ibarra Gómez, Edwin Hernandez Jaimes, Monica Jaramillo, Nicolas Jaramillo, Carlos Jaramillo Gomez, Monica Jaramillo Sanchez, Ivonne Jarava Durán, Catalina Lopez Ceballos, Claudia Madrid, Elias María Amastha, Jennifer Mercado, Dora Ines Molina, Jessica Molina Soto, Carlos Montoya, Alexander Morales, Carolina Muñoz, Luis Alejandro Orozco, Oscar Osorio, Jorge Mario Palmera Sanchez, Adwar Peña, Jose Perez, Juan Perez Agudelo, Germán Pérez Amador, Carlos Pertuz, Irina Posada, Carlos Puerta, Adalberto Quintero, Diana Quiroz, Carmen Rendon, Alberto Reyes, Alvaro Reyes, Diana Ripoll, Carlos Rivera, Maria Rocha, Jose F Rodriguez, Kervis Asid Rodriguez Villanueva, Javier Emilio Rodriguez Zabala, Sindy Rojas, Maria Romero, Ricardo Rosero, Angelica Rocio Rosillo Cardenas, Lina Rueda, Gregorio Sanchez, Tatiana Sanchez, Arístides Sotomayor Herazo, Monica Suarez, Mariana Torres, Freddy Trujillo, Miguel Urina, Lazaro Van Strahlen, Carlos Velandia, Carolina Velasquez Guzman, Elizabeth Velazquez, Tatiana Vidal Prada, Juan Pablo Yepez Alvaran, Diego Zarate, Jana Andelova, Radka Benesova, Barbara Buzova, Vladimir Cech, Ida Chodova, Miroslav Choura, Antonin Dufka, Andrea Gamova, Jakub Gorgol, Tomas Hala, Hana Havlova, Dagmar Hlavkova, Petra Horanska, Juliana Ilcisin-Valova, Petra Jenickova, Ondrej Jerabek, Ilona Kantorova, Katerina Kolomaznikova, Iva Kopeckova, Miroslava Kopeckova, Karel Linhart, Tomas Linhart, Jan Malecha, Emilia Malicherova, Dana Neubauerova, Martina Oznerova, Radan Partys, Eva Pederzoliova, Maria Petrusova, Vera Prymkova, Eva Racicka, Ida Reissova, Eva Roderova, Libor Stanek, Alena Striova, Dana Svarcova, Petr Svoboda, Emilia Szeghy Malicharova, Jan Urge, Ladislav Vesely, Bedich Wasserburger, Hilde Wasserburgerova, Emil Zahumensky, Vaclav Zamrazil, Hasan Alawi, Ernestos Anastasiadis, Elisabeth Axthelm, Tasso Bieler, Christina Buhrig, Elizaveta Degtyareva, Frank Dellanna, Karl-Michael Derwahl, Stephan Diessel, Barbara Dogiami, Kirsten Dorn-Weitzel, Monika Ernst, Grit Faulmann, Baerbel Fetscher, Thomas Forst, Gabriele Freyer-Lahres, Klaus Funke, Xenia Ganz, Christiane Gleixner, Christoph Hanefeld, Sven Heinrichs, Stephanie Helleberg, Elena Henkel, Gerd Ruediger Hetzel, Caren Hoffmann, Frohmut Jacob, Stephan Jacob, Franziska John, Antonius Jonczyk, Wolfram Kamke, Christiane Klein, Martina Kleinhardt, Werner Kleophas, Christine Kosch, Kristin Kreutzmann, Achim Kühn, Young Hee Lee-Barkey, Alexander Lier, Sarah Maatouk, Joachim Minnich, Michael Mitry, Ilona Muessig, Diana Nicula, Martina Niemann, Joerg Nothroff, Petra Ott, Andreas Pfuetzner, Andreas Pfützner, Frank Pistrosch, Wildgard Pohl, Zdenka Prochazkova, Marlena Retkowska, Heiko Rosin, Daniela Sachsenheimer, Holger Samer, Mazin Sanuri, Axel Schaefer, Frank Schaper, Erik-Delf Schulze, Marita Schulze, Martina Schumann, Thomas Segiet, Veronika Sowa, Hans-Detlev Stahl, Franziska Steinfeldt, Madlen Teige, Bjoern Trieb, Diethelm Tschoepe, Peter Uebel, Bernd Warken, Ingo Weigmann, Klaus Weyland, Klara Wilhelm, Timea Balo, Miklos Balsay, Ilona Bende, Katalin Bezzegh, Zita Birkus, Barbara Buday, Melinda Csomai, Laszlo Deak, Eniko Dezso, Peter Faludi, M Faluvegi, Ilona Fazekas, Agota Feher, Csaba Fejer, Ervin Finta, Agnes Fulcz, Zsolt Gaal, Mihaly Gurzo, Krisztina Hati, Gabriella Herczeg, Ildiko Jozsef, Marta Juhasz, Katalin Keltai, Laszlo Koranyi, Eniko Kulcsar, Krisztina Kun, Andrea Laczko, Botond Literáti-Nagy, Izabella Mezo, Margit Mileder, I Moricz, Károly Nagy, Bela Nagybaczoni, Csaba Nemeth, Agnes Oze, Jozsef Pauer, Eva Peterfai, Bela Polocsanyi, Ferenc Poor, István Reiber, Csaba Salamon, Julia Sebestyen, Ildiko Torok, Marianna Tuu, Andrea Varga, Viktor Vass, Chul Min Ahn, Chulwoo Ahn, Park ByungWon, Hyuk-Jae Chang, Kiyuk Chang, Eui-Young Choi, Han Seok Choi, Jin-Wook Chung, Bum- Kee Hong, Young Joon Hong, Min Su Hyon, Myung Ho Jeong, Shinae Kang, Byeong-Keuk Kim, Ji-Hyun Kim, Ju Han Kim, Kee-Sik Kim, Moo Hyun Kim, Pum-Joon Kim, Soon-Kil Kim, Yong-Seok Kim, Young Kwon Kim, Yoon Seok Koh, Hyuck Moon Kwon, Byoung Kwon Lee, Byung-Wan Lee, Jin Bae Lee, Myoung-Mook Lee, Young-Mee Lim, Pil Ki Min, Jong Sung Park, Jongsuk Park, Keun Ho Park, Sungha Park, Wook Bum Pyun, Se Joong Rim, Dong-Ryeol Ryu, Hong-Seog Seo, Ki Bae Seung, Dong-Ho Shin, Doo Sun Sim, Young Won Yoon, Ilze Andersone, Kristine Babicka, Inga Balcere, Roberts Barons, Inguna Capkovska, Kristine Geldnere, Inese Grigane, Baiba Jegere, Ilze Lagzdina, Lija Mora, Sigita Pastare, Rota Ritenberga, Janina Romanova, Inta Saknite, Natalja Sidlovska, Jelena Sokolova, Sandra Steina, Iveta Strizko, Dace Teterovska, Brigita Vizina, Lina Barsiene, Gintare Belozariene, Laura Daugintyte-Petrusiene, Nijole Drungiliene, Nijole Garsviene, Ala Grigiene, Vytautas Grizas, Virginija Jociene, Dalia Kalvaitiene, Jugeta Kaupiene, Jurate Kavaliauskiene, Dalia Kozloviene, Ilona Lapteva, Birute Maneikiene, Jolanta Marcinkeviciene, Vaidilija Markauskiene, Salomeja Meiluniene, Almantas Norkus, Rita Norviliene, Vladimiras Petrenko, Ruta Radzeviciene, Gintare Sakalyte, Gediminas Urbonas, Skaiste Urbutiene, Donatas Vasiliauskas, Dzilda Velickiene, Carlos Aguilar, Marco Alcocer, Juan Antonio Avalos-Ramirez, Ramiro Banda-Elizondo, Rubria Bricio-Ramirez, Karla Cardenas Mejia, Francisco Cavazos, Jesus Chapa, Erika Cienfuegos, Astrid De la Peña, Gilberto de la Peña Topete, Manuel Odin De los Rios Ibarra, Daniel Elias, Claudia Flores-Moreno, Pedro Garcia Hernandez, Luis Gerardo Gonzalez, Rosa Linda Guerra Moya, Arturo Guerra-Lopez, Raymundo Hernandez Baylon, Carolina Herrera Colorado, Marisol Herrera-Marmolejo, Neri Islas-Palacios, Esteban Lopez, Fernando Lopez, Agustin Lopez Alvarado, Rosa Isela Luna Ceballos, Enrique Morales Villegas, Gualberto Moreno-Virgen, Rosa Linda Parra Perez, Sara Pascoe Gonzalez, Irving Peralta-Cantu, Roopa Previn, Rosa Ramirez, Rubria Ramirez, Maria Guadalupe Ramos Zavala, Monica Rodriguez, Rocio Salgado-Sedano, Ana Claudia Sanchez-Aguilar, Edith Santa Rosa Franco, Leobardo Sauque-Reyna, Rodrigo Suarez Otero, Ivonne Torres, Enrique Velarde-Harnandez, Juan Villagordoa, Efrain Villeda-Espinoza, Jorge Vital-Lopez, Cristian Jair Zavala- Bello, John Baker, Elaine Barrington-Ward, Thomas Brownless, Richard Carroll, Simon Carson, Michelle Choe, Andrew Corin, Brian Corley, Richard Cutfield, Neelam Dalaman, Paul Dixon, Paul Drury, Keith Dyson, Chris Florkowski, Monica Ford, William Frengley, Colin Helm, Colin Katzen, Jane Kerr, Manish Khanolkar, David Kim, Renata Koops, Jeremy Krebs, Robert Leikis, Kwan Low, Alison Luckey, Richard Luke, Susan Macaulay, Rodney Marks, Catherine McNamara, Dean Millar-Coote, Steven Miller, Naomi Mottershead, James Reid, Narcisa Robertson, Ian Rosen, David Rowe, Ole Schmiedel, Russell Scott, Jeffrey Sebastian, Davitt Sheahan, Victoria Stiebel, Ian Ternouth, Chris Tofield, Dirk Venter, Michael Williams, Miles Williams, Fiona Wu, Simon Young, Malgorzata Arciszewska, Anna Bochenek, Piotr Borkowski, Przemyslaw Borowy, Tomasz Chrzanowski, Edward Czerwinski, Marek Dwojak, Agnieszka Grodzicka, Izabela Janiec, Joanna Jaruga, Ewa Krystyna Jazwinska-Tarnawska, Krystyna Jedynasty, Danuta Juzwiak-Czapiewska, Jadwiga Karczewicz-Janowska, Jan Konieczny, Marek Konieczny, Marek Korol, Maciej Kozina, Ewa Krzyzagorska, Ewa Kucharczyk-Petryka, Roman Laz, Anna Majchrzak, Zdzislawa Mrozowska, Michal Mularczyk, Elzbieta Nowacka, Jadwiga Peczynska, Robert Petryka, Radoslaw Pietrzak, Dorota Pisarczyk-Wiza, Aleksandra Rozanska, Zofia Ruzga, Emilia Rzeszotarska, Malgorzata Sacha, Marzenna Sekulska, Anna Sidorowicz-Bialynicka, Teresa Stasinska, Agnieszka Strzelecka-Sosik, Teresa Swierszcz, Katarzyna Miroslawa Szymkowiak, Olga Turowska, Krystyna Wisniewska, Maciej Wiza, Iwona Wozniak, Katarzyna Zelazowska, Bernadetta Ziolkowska-Gawron, Danuta Zytkiewicz-Jaruga, Adrian Albota, Carmina Alexandru, Rodica Avram, Cornelia Bala, Diana Barbonta, Roxana Barbu, Daniela Braicu, Nicoleta Calutiu, Doina Catrinoiu, Anca Cerghizan, Alina Ciorba, Anca Craciun, Rodica Doros, Livia Duma, Ancuta Dumitrache, Ioana Ferariu, Anca Ferician Moza, Alexandrina Ghergan, Gheorghe Ghise, Mariana Graur, Mihaela Gribovschi, Bogdan Mihai, Laura Mihalache, Madalina Mihalcea, Nicoleta Mindrescu, Magdalena Morosanu, Andrea Morosoanu, Maria Mota, Anca Moza, Valerica Nafornita, Narcisa Natea, Simona Nicodim, Cristina Nita, Adriana Onaca, Mircea Onaca, Cristina Pop, Lavinia Pop, Amorin Popa, Alexandrina Popescu, Luchiana Pruna, Gabriela Roman, Mihaela Rosu, Alexandra Sima, Doina Sipciu, Carmen Narcisa Sitterli-Natea, Iosif Szilagyi, Minodora Tapurica, Adrian Tase, Adriana-Carmen Tutescu, Luminita Vanghelie, Ioana Verde, Adrian Vlad, Mihaela Zarnescu, Roman Akhmetov, Irina Allenova, Irina Avdeeva, Oksana Baturina, Irina Biserova, Nikolay Bokovin, Irina Bondar, Natalia Burova, Galina Chufeneva, Elena Chumachek, Marina Demidova, Alexander Demin, Vera Drobysheva, Irina Egorova, Lev Esenyan, Ekaterina Gelig, Sergey Gilyarevsky, Maria Golshmid, Arseniy Goncharov, Anastasia Gorbunova, Ivan Gordeev, Vera Gorelysheva, Tatiana Goryunova, Irina Grebenshchikova, Roman Ilchenko, Maria Ivannikova, Saule Karabalieva, Juliya Karpeeva, Elena Khaykina, Zhanna Kobalava, Irina Kononenko, Oxana Korolik, Anna Korshunova, Victor Kostenko, Irina Krasnopevtseva, Ludmila Krylova, Polina Kulkova, Irina Kuzmina, Alla Ledyaeva, Sergey Levashov, Natalia Lokhovinina, Vadim Lvov, Narine Martirosyan, Sergey Nedogoda, Rostislav Nilk, Yulia Osmolovskaya, Alexey Panov, Olga Paramonova, Ekaterina Pavlova, Elena Pekareva, Nina Petunina, Svetlana Ponamareva, Galina Reshedko, Alla Salasyuk, Malvina Sepkhanyan, Alexandr Serebrov, Olesya Shabelnikova, Andrey Skvortsov, Olga Smirnova, Oxana Spiridonova, Svetlana Strogova, Evgeny Taratukhin, Sergey Tereschenko, Lubov Trukhina, Olga Tsarkova, Vera Tsoma, Farid Tumarov, Natalya Tyan, Tatiana Tyurina, Svetlana Villevalde, Elena Yankovaya, Ludmila Zarutskaya, Elena Zenkova, Aysha Badat, Frederik Bester, Suzanne Blignaut, Dirk Blom, Susan Booysen, Warren Boyd, Brigitte Brice, Susan Brown, Lesley Burgess, Reina Cawood, Kathleen Coetzee, Hillet Conradie, Tanja Cronje, Douwe de Jong, Graham Ellis, Shaunagh Emanuel, Ingrid Engelbrecht, Sharne Foulkes, Done Fourie, Gilbert Gibson, Thirumani Govender, Sumayah Hansa, Allana Colleen Hemus, Firzana Hendricks, Marshall Heradien, Chantelle Holmgren, Zaheer Hoosain, Emile Horak, Johannes Howard, Ignatius Immink, E. Janari, Daksha Jivan, Karl Klusmann, Weik Labuschagne, Yen-yu Lai, Gulam Latiff, J. Lombaard, Hanlie Lottering, Ronel Meeding, Shirley Middlemost, Haroon Mitha, Ismail Mitha, Sandile Mkhwanazi, Rajendran Moodley, Almeri Murray, Dany Musungaie, Yasmin Osman, Kirsten Peacey, Larisha Pillay-Ramaya, Catharina Pretorius, Hans Prozesky, Mahomed Sarvan, E Scholtz, Attila Sebesteny, Bianca Skinner, Michael Skriker, M Smit, Anna-Marie Stapelberg, Nicolaas Swanepoel, Dorothea Urbach, Dina van Aswegen, Francois van Zyl, Louis Van Zyl, Esme Venter, Shahid Wadvalla, Jeffrey Wing, Karen Wolmarans, Cristina Abreu, Pilar Aguilà, Eva Aguilera, Nuria Alonso, Carmen Alvarez, Priscila Cajas, Jose Carlos Castro, Roger Codinachs, Jose Contreras, Maria Jose Coves, Carmen Fajardo, Juan Carlos Ferrer, Neus Font, Mar Garcia, Maria Apolonia Gil, Fernando Gomez, Lluis Alberto Gomez, Jose Gonzalbez, Jose Luis Griera, Luís Masmiquel, Didac Mauricio, Silvia Narejos Perez, Juana Ana Nicolau, Olga Noheda Contreras, Josefina Olivan, Josefina Olivares, Emilio Ortega, Silvia Pellitero, Salvador Pertusa, Ferran Rius, Irene Rodriguez, Carlos Sánchez-Juan, Dolores Santos, Berta Soldevila, David Subias, Manel Terns, Carlos Trescoli, Judith Vilaplana, Alicia Villanueva, Jaan Albo, Kjell Antus, Mattias Axelsson, Lisa Bergström, Emil Binsell-Gerdin, Kurt Boman, Fabian Botond, Annika Dotevall, Anna Graipe, C Jarnet, Jessica Kaminska, Anders Kempe, Michael Korhonen, Carina Linderfalk, Bo Liu, Karl Ljungstroem, Karl Ljungström, Lennart Malmqvist, Linda Mellbin, Thomas Mooe, Peter Nicol, Anders Norrby, Ake Ohlsson, Annika Rosengren, Jan Saaf, Staffan Salmonsson, Olof Strandberg, Karl-Axel Svensson, Bengt-Olov Tengmark, Georgios Tsatsaris, Anders Ulvenstam, Peter Vasko, Chwen-Tzuei Chang, Hsin-Mei Chang, Jung-Fu Chen, To-Pang Chen, Ming-Min Chung, Chia-Po Fu, Te-Lin Hsia, Shih-Che Hua, Ming-Chun Kuo, Chia-ln Lee, I-Te Lee, Kae-Woei Liang, Shih Yi Lin, Chieh-Hsiang Lu, Wen-Ya Ma, Dee Pei, Feng-Chih Shen, Ching-Chieh Su, Shuo-Wei Su, Tsai-Sung Tai, Wan-Ni Tsai, Yi-Ting Tsai, Shih-Chen Tung, Jun-Sing Wang, Hui-I Yu, Ahmed Al-Qaissi, Vijayaraman Arutchelvam, Stephen Atkin, Simon Au, Myint Myint Aye, Stephen Bain, Cristina Bejnariu, Patrick Bell, Deepak Bhatnagar, Rudy Bilous, Neil Black, Ursula Brennan, Barbara Brett, Jana Bujanova, Elaine Chow, Andrew Collier, Amanda Combe, Christopher Courtney, Hamish Courtney, James Crothers, Patrick Eavis, Jackie Elliott, Salvatore Febbraro, Jim Finlayson, Rajiv Gandhi, Sharon Gillings, Jonathan Hamling, Roy Harper, Tim Harris, Kahal Hassan, Simon Heller, Alison Jane, Zeeshan Javed, Tim Johnson, Stephen Jones, Adele Kennedy, David Kerr, Brian Kilgallon, Judith Konya, John Lindsay, Lina Lomova-Williams, Helen Looker, David MacFarlane, Sandra Macrury, Iqbal Malik, Rory McCrimmon, Douglas McKeith, John McKnight, Biswa Mishra, Racha Mukhtar, Ciara Mulligan, Maurice O'Kane, Tolu Olateju, Ian Orpen, Tristan Richardson, Desmond Rooney, Shorsha Bae Ross, Thozhukat Sathyapalan, Naveen Siddaramaiah, Lee Euan Sit, Jeffrey Stephens, Frances Turtle, Ammar Wakil, Emma Walkinshaw, Asem Ali, Robert Anderson, Richard Arakaki, Omar Aref, Mehrdad Kevin Ariani, David Arkin, Salomon Banarer, George Barchini, Arti Bhan, Kelley Branch, Donald Brautigam, Stephen Brietzke, Maridez Brinas, Yudit Brito, Casey Carter, Kimberely Casagni, Sabina Casula, Simon Chakko, Seth Charatz, Dale Childress, Lisa Chow, Malgorzata Chustecka, Subha Clarke, Lisa Cohen, Barry Collins, Gildred Colon Vega, Angel Comulada-Rivera, Gregorio Cortes-Maisonet, Matthew Davis, Jose de Souza, Cyrus Desouza, Mary Dinnan, Bobbi Duffy-Hidalgo, Barbara Dunn, Julia Dunn, Marshall Elman, James Felicetta, Stuart Finkelstein, David Fitz-Patrick, Hermes Florez, Alan Forker, Wayne Fowler, Sonja Fredrickson, Zachary Freedman, Brooke Gainey Narron, Kristin Gainey-Ferree, Michael Gardner, Christian Gastelum, Stephen Giddings, Eve Gillespie, Michael Paul Gimness, Gary Goldstein, Maria Gomes, Nelson Gomez, Timothy Gorman, Ketan Goswami, Arthur Graves, Scott Hacking, Charles Hall, Lenita Hanson, Sherman Harman, David Heber, Robert Henry, Janette Hiner, Irl Hirsch, Priscilla Hollander, Thomas Hooker, Barry Horowitz, Laura Hoste, Loli Huang, Minh Huynh, Dan Hyman, Soha Idriss, Ali Iranmanesh, Dennis Karounos, Moti Kashyap, Lois Katz, William Kaye, Yevgeniy Khaiton, Romesh Khardori, Timothy Kitchen, Andrew Klein, Wendi Knffem, Mikhail Kosiborod, Nicola Kreglinger, Davida Kruger, Anubhav Kumar, Ivan Laboy, Patricia Larrabee, Laura Larrick, Donna Lawson, Mike Ledet, James Lenhard, James Levy, George Li, Zhaoping Li, David Lieb, April Limcolioc, Jane Lions-Patterson, Daniel Lorber, Daniel Lorch, Michael Lorrello, Peter Lu, Kathryn Jean Lucas, Siu-Ling Ma, Michael MacAdams, Michelle Magee, Alexander Magno, Aparna Reddy Mahakala, Jennifer Marks, Anthony McCall, William McClanahan, Carole McClary, Lydia Melendez, John Melish, Deanna Michaud, Christopher Miller, Neil Miller, Pablo Mora, Marriyam Moten, Sunder Mudaliar, Gregory Myrick, Puneet Narayan, Mike Nassif, Karena Neri, Tabitha Newton, Patricia Niblack, Philip Nicol, Ebenezer Nyenwe, A. Ola Odugbesan, Yolanda Okorocha, Ramón Ortiz Carrasquillo, Kwame Osei, Coromoto Palermo, Hiren Patel, Krishna Patel, Cindy Pau, Michael Perley, Sanford Plevin, Elena Plummer, Richard Powell, Mohammed Qintar, Rex Rawls, John Reyes-Castano, Lillian Reynolds, Robert Richards, Julio Rosenstock, Caroline Rowe, Jahandar Saleh, Sony Sam, Alfredo Sanchez, Donald Sander, Bruce Sanderson, Virginia Savin, Elizabeth Seaquist, Jayendra Shah, Serena Shi, Vijay Shivaswamy, Tammi Shlotzhauer, David Shore, Bobbie Skukowski, Kyaw Soe, Vesna Solheim, Joseph Soufer, Helmut Steinberg, Jaime Steinsapir, Phillip Tarkington, Debra Thayer, Stephen Thomson, James Thrasher, Joseph Tibaldi, Jeff Tjaden, Oberto Tores, Dace Trence, Subbulaxmi Trikudanathan, Jagdeesh Ullal, Gabriel Uwaifo, Anthony Vo, Kenny Vu, Damandeep Walia, Karen Weiland, Fred Whitehouse, Thomas Wiegmann, Kathleen Wyne, Alan Wynne, Kevin Yuen, Joel Zaretzky, James Zebrack, Franklin Zieve, William Zigrang, and Everest

Subjects
Male, medicine.medical_specialty, Recombinant Fusion Proteins, Population, Placebo-controlled study, Glucagon-Like Peptides, Myocardial Infarction, Type 2 diabetes, 030204 cardiovascular system & hematology, Placebo, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Double-Blind Method, law, Internal medicine, medicine, Humans, Hypoglycemic Agents, 030212 general & internal medicine, education, Aged, education.field_of_study, business.industry, Semaglutide, Hazard ratio, General Medicine, Middle Aged, medicine.disease, Immunoglobulin Fc Fragments, Stroke, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Dulaglutide, Female, business, medicine.drug
Abstract

Digital, Background Three different glucagon-like peptide-1 (GLP-1) receptor agonists reduce cardiovascular outcomes in people with type 2 diabetes at high cardiovascular risk with high glycated haemoglobin A1c (HbA1c) concentrations. We assessed the effect of the GLP-1 receptor agonist dulaglutide on major adverse cardiovascular events when added to the existing antihyperglycaemic regimens of individuals with type 2 diabetes with and without previous cardiovascular disease and a wide range of glycaemic control. Methods This multicentre, randomised, double-blind, placebo-controlled trial was done at 371 sites in 24 countries. Men and women aged at least 50 years with type 2 diabetes who had either a previous cardiovascular event or cardiovascular risk factors were randomly assigned (1:1) to either weekly subcutaneous injection of dulaglutide (1·5 mg) or placebo. Randomisation was done by a computer-generated random code with stratification by site. All investigators and participants were masked to treatment assignment. Participants were followed up at least every 6 months for incident cardiovascular and other serious clinical outcomes. The primary outcome was the first occurrence of the composite endpoint of non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes), which was assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01394952. Findings Between Aug 18, 2011, and Aug 14, 2013, 9901 participants (mean age 66·2 years [SD 6·5], median HbA1c 7·2% [IQR 6·6–8·1], 4589 [46·3%] women) were enrolled and randomly assigned to receive dulaglutide (n=4949) or placebo (n=4952). During a median follow-up of 5·4 years (IQR 5·1–5·9), the primary composite outcome occurred in 594 (12·0%) participants at an incidence rate of 2·4 per 100 person-years in the dulaglutide group and in 663 (13·4%) participants at an incidence rate of 2·7 per 100 person-years in the placebo group (hazard ratio [HR] 0·88, 95% CI 0·79–0·99; p=0·026). All-cause mortality did not differ between groups (536 [10·8%] in the dulaglutide group vs 592 [12·0%] in the placebo group; HR 0·90, 95% CI 0·80–1·01; p=0·067). 2347 (47·4%) participants assigned to dulaglutide reported a gastrointestinal adverse event during follow-up compared with 1687 (34·1%) participants assigned to placebo (p, Ciencias Médicas y de la Salud

Published
2019

48. Serum Renalase Levels Are Predicted by Brain-Derived Neurotrophic Factor and Associated with Cardiovascular Events and Mortality after Percutaneous Coronary Intervention

Author

Wayne Huey-Herng Sheu and I-Te Lee

Subjects
medicine.medical_specialty, medicine.medical_treatment, lcsh:Medicine, 030204 cardiovascular system & hematology, Article, Coronary artery disease, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Myocardial infarction, cardiovascular diseases, Survival rate, Stroke, Renalase, business.industry, Hazard ratio, lcsh:R, brain-derived neurotrophic factor, percutaneous coronary intervention, Percutaneous coronary intervention, General Medicine, medicine.disease, Conventional PCI, Cardiology, business, renalase, 030217 neurology & neurosurgery, coronary artery disease
Abstract

Circulating brain-derived neurotrophic factor (BDNF) predicts survival rate in patients with coronary artery disease (CAD). We examined the relationship between BDNF and renalase before and after percutaneous coronary intervention (PCI) and the role of renalase in patients with CAD. Serum BDNF and renalase levels were determined using blood samples collected before and after PCI. Incident myocardial infarction, stroke, and mortality were followed up longitudinally. A total of 152 patients completed the assessment. BDNF levels were not significantly changed after PCI compared to baseline levels (24.7 &plusmn, 11.0 vs. 23.5 &plusmn, 8.3 ng/mL, p = 0.175), although renalase levels were significantly reduced (47.5 &plusmn, 17.3 vs. 35.9 &plusmn, 11.3 ng/mL, p &lt, 0.001). BDNF level before PCI was an independent predictor of reduction in renalase (95% confidence interval (CI): &minus, 1.371 to &minus, 0.319). During a median 4.1 years of follow-up, patients with serum renalase levels of &ge, 35 ng/mL had a higher risk of myocardial infarction, stroke, and death than those with renalase of &lt, 35 ng/mL (hazard ratio = 5.636, 95% CI: 1.444&ndash, 21.998). In conclusion, our results show that serum BDNF levels before PCI were inversely correlated with the percentage change in renalase levels after PCI. Nevertheless, post-PCI renalase level was a strong predictor for myocardial infarction, stroke, and death.

Published
2018

49. Glycaemic control for painful diabetic peripheral neuropathy is more than fasting plasma glucose and glycated haemoglobin

Author

I-Te Lee, Ming-Hong Chang, Shih-Yi Lin, Ching-Heng Lin, C.-L. Tang, and Yen-Wei Pai

Subjects
Adult, Blood Glucose, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Glycemic Control, Type 2 diabetes, 030204 cardiovascular system & hematology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Diabetic Neuropathies, Internal medicine, Internal Medicine, medicine, Humans, In patient, Screening instrument, Glycated haemoglobin, Glycated Hemoglobin, Plasma glucose, business.industry, nutritional and metabolic diseases, Fasting, General Medicine, medicine.disease, Cross-Sectional Studies, Peripheral neuropathy, Postprandial, Increased risk, business
Abstract

Background The relationship between postprandial hyperglycaemia and diabetic peripheral neuropathy (DPN), whether painful or painless, has yet to be determined. Thus, the aim of this study was to investigate the relationship in patients with type 2 diabetes (T2D). Methods This cross-sectional study was conducted in adults with T2D between January and October 2013. Blood samples were collected after overnight fasting every 3 months prior to enrolment. For this study, increased postprandial glycaemic exposure was defined as high glycated haemoglobin (HbA1c) and near-normal mean fasting plasma glucose (FPG) levels. Both painless and painful DPN were evaluated using two validated tools, the Michigan Neuropathy Screening Instrument (MNSI) and Douleur Neuropathique 4 (DN4) questionnaire. Results This study included 1040 participants with mean FPG levels Conclusion This study is the first to reveal that increased postprandial glycaemic exposure, as assessed by high HbA1c and near-normal FPG levels, is associated with an increased risk of painful DPN in adults with T2D.

Published
2021

50. Glycemic excursions are positively associated with HbA1c reduction from baseline after treatment with acarbose in patients with type 2 diabetes on metformin monotherapy

Author

Shi-Dou Lin, Shih-Te Tu, Shih-Li Su, Wayne Huey-Herng Sheu, Shih-Yi Lin, I-Te Lee, Yao-Hsien Tseng, Jun-Sing Wang, and Wen-Jane Lee

Subjects
medicine.medical_specialty, Randomization, endocrine system diseases, business.industry, Endocrinology, Diabetes and Metabolism, nutritional and metabolic diseases, 030209 endocrinology & metabolism, Type 2 diabetes, medicine.disease, Gastroenterology, Metformin, Glibenclamide, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Diabetes mellitus, Ambulatory, medicine, 030212 general & internal medicine, business, Glycemic, medicine.drug, Acarbose
Abstract

Background The aim of the present study was to examine the association between glycemic excursions before treatment and HbA1c reduction after treatment intensification with acarbose or glibenclamide in patients with type 2 diabetes (T2D). Methods Patients receiving single or dual oral antidiabetic drug treatment with an HbA1c of 7.0–11.0 % (53–97 mmol/mol) were switched to metformin monotherapy (500 mg, t.i.d.) for 8 weeks, followed by randomization to either acarbose (100 mg, t.i.d.) or glibenclamide (5 mg, t.i.d.) as add-on treatment for 16 weeks. Glycemic excursions were assessed as mean amplitude of glycemic excursions (MAGE) with 72-h ambulatory continuous glucose monitoring. Treatment efficacy was evaluated as relative HbA1c reduction (%), calculated as (baseline HbA1c – post-treatment HbA1c)/baseline HbA1c × 100. Results Fifty patients (mean [±SD] age 53.5 ± 8.2 years, 48 % men, mean baseline HbA1c 8.4 ± 1.2 %) were analyzed. Baseline MAGE was positively correlated with relative HbA1c reduction from baseline in patients treated with acarbose (r = 0.421, P = 0.029) but not glibenclamide (r = 0.052, P = 0.813). Linear regression analysis revealed that the association between baseline MAGE and relative HbA1c reduction from baseline (β = 0.125, P = 0.029) in patients treated with acarbose remained significant after adjustment for several confounders (P

Published
2016

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