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Abstract We present an in‐depth analysis of dyslipidemia management strategies for patients with diabetes mellitus in Taiwan. It critically examines the disparity between established guideline recommendations and actual clinical practices, particularly in the context of evolving policies affecting statin prescriptions. The focus is on synthesizing the most recent findings concerning lipid management in patients with diabetes mellitus, with a special emphasis on establishing consensus regarding low‐density lipoprotein cholesterol treatment targets. The article culminates in providing comprehensive, evidence‐based recommendations tailored to the unique needs of those living with diabetes mellitus in Taiwan. It underscores the criticality of personalized care approaches, which incorporate multifaceted factors, and the integration of novel therapeutic options to enhance cardiovascular health outcomes.

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

Background: This study aimed to evaluate the performance of a modified U.S. (MUS) model for risk prediction of cardiovascular (CV) events in Asian patients and compare it to European and Japanese models. Methods: The MUS model, based on the US ACC/AHA 2018 lipid treatment guideline, was employed to stratify patients under primary or secondary prevention. Two multi-center prospective observational registry cohorts, T-SPARCLE and T-PPARCLE, were used to validate the scoring system, and the primary outcome was the time to first occurrence/recurrence of major adverse cardiac events (MACEs). The MUS model's performance was compared to other models from Europe and Japan. Results: A total of 10,733 patients with the mean age of 64.2 (SD: 11.9) and 36.5% female were followed up for a median of 5.4 years. The MUS model was validated, with an AUC score of 0.73 (95% CI 0.68–0.78). The European and Japanese models had AUC scores ranging from 0.6 to 0.7. The MUS model categorized patients into four distinct CV risk groups, with hazard ratios (HRs) as follows: very high- vs. high-risk group (HR = 1.91, 95% CI 1.53–2.39), high- vs. moderate-risk group (HR = 2.08, 95% CI 1.60–2.69), and moderate- vs. low-risk group (HR = 3.14, 95% CI 1.63–6.03). After adjusting for the MUS model, a history of atherosclerotic vascular disease (ASCVD) was not a significant predictor of adverse cardiovascular outcomes within each risk group. Conclusion: The MUS model is an effective tool for risk stratification in Asian patients with and without ASCVD, accurately predicting MACEs and performing comparably or better than other established risk models. Our findings suggest that patient management should focus on background risk factors instead of solely on primary or secondary prevention.

Compared with normative birthweight persons, individuals with a lower birthweight had a higher chance of developing type 2 diabetes at a younger age, a lower body mass index at diagnosis, a lesser family history of diabetes and greater probability of comorbidities.

Abstract Background Heterogeneity in type 2 diabetes presentation and progression suggests that precision medicine interventions could improve clinical outcomes. We undertook a systematic review to determine whether strategies to subclassify type 2 diabetes were associated with high quality evidence, reproducible results and improved outcomes for patients. Methods We searched PubMed and Embase for publications that used ‘simple subclassification’ approaches using simple categorisation of clinical characteristics, or ‘complex subclassification’ approaches which used machine learning or ‘omics approaches in people with established type 2 diabetes. We excluded other diabetes subtypes and those predicting incident type 2 diabetes. We assessed quality, reproducibility and clinical relevance of extracted full-text articles and qualitatively synthesised a summary of subclassification approaches. Results Here we show data from 51 studies that demonstrate many simple stratification approaches, but none have been replicated and many are not associated with meaningful clinical outcomes. Complex stratification was reviewed in 62 studies and produced reproducible subtypes of type 2 diabetes that are associated with outcomes. Both approaches require a higher grade of evidence but support the premise that type 2 diabetes can be subclassified into clinically meaningful subtypes. Conclusion Critical next steps toward clinical implementation are to test whether subtypes exist in more diverse ancestries and whether tailoring interventions to subtypes will improve outcomes.

Abstract In recent years, several novel agents have become available to treat individuals with type 2 diabetes (T2D), such as sodium-glucose cotransporter-2 inhibitors (SGLT-2i), tirzepatide, which is a dual glucose-dependent insulinotropic polypeptide receptor agonist (GIP RA)/glucagon-like peptide-1 receptor agonist (GLP-1 RA), and finerenone, a non-steroidal mineralocorticoid receptor antagonist (MRA) that confers significant renal and cardiovascular benefits in individuals with (CKD). New medications have the potential to improve the lives of individuals with diabetes. However, clinicians are challenged to understand the benefits and potential risks associated with these new and emerging treatment options. In this article, we discuss how use of network meta-analyses (NMA) can fill this need.

Abstract Background Epicardial adipose tissue (EAT) is a type of ectopic fat with endocrine and paracrine functions. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that responds to environmental stimuli. AhR expression is associated with obesity. In this cross-sectional study, we aimed to determine the relationship between circulating AhR concentrations and EAT. Methods A total of 30 men with obesity and 23 age-matched men as healthy controls were enrolled. Plasma AhR concentrations were determined at fasting. The EAT thickness was measured on the free wall of the right ventricle from the basal short-axis plane by magnetic resonance imaging. Results The participants with obesity had a higher plasma AhR level than the controls (81.0 ± 24.5 vs. 65.1 ± 16.4 pg/mL, P = 0.010). The plasma AhR level was positively correlated with EAT thickness (correlation coefficient = 0.380, P = 0.005). After adjusting for fasting glucose levels, plasma AhR levels were still significantly associated with EAT thickness (95% CI 0.458‒5.357, P = 0.021) but not with body mass index (P = 0.168). Conclusion Plasma AhR concentrations were positively correlated with EAT thickness on the free wall of the right ventricle in men. Further investigations are needed to evaluate the causal effects and underlying mechanisms between AhR and EAT.

Abstract Approximately 40 years ago, I was fortunate enough to step into the field of diabetes. When I had my fellowship training in the USA, I learned how to ask a good scientific question and conduct clinical research. With collaboration with my mentors, Prof. Gerald R Reaven and Prof. Ida Chen, we participated in many clinical trials. We established the Taiwan Diabetes Registry (TDR) to track long‐term changes in diabetes profiles. The ultimate purpose of medical research is to provide benefits to patients. Using electronic medical records and point‐of‐care glucometers, we reduced inpatients’ hyperglycemia and hypoglycemia greatly, which was also reflected by the reduction in hospital stays and readmission rates. With the advent of new technology and medications, we have to ponder where we are on the journey toward better diabetes care. We rigorously advocate diabetes care, hold many symposia and publish updated guidelines. We successfully hosted the congress of the 11th International Diabetes Federation Western Pacific Region & 8th Asian Association for the Study of Diabetes Scientific Meeting 2016 at Taipei, Taiwan. As the era of precision medicine is coming, Taiwan could be considered as one of the best places to run precision medicine. The Taiwan Precision Medicine Initiative has enrolled more than half a million residents, and is currently conducting genotyping and data analysis. In conclusion. I witnessed the early days of simple and few choices for diabetes management to the current various modalities in diabetes care. As these new technologies have become available, patients will always remain at the center of the care model with warmth and humility.

Abstract Objectives Type 2 diabetes mellitus (T2DM) imposes a great burden on healthcare systems, and these patients experience higher long-term risks for developing end-stage renal disease (ESRD). Managing diabetic nephropathy becomes more challenging when kidney function starts declining. Therefore, developing predictive models for the risk of developing ESRD in newly diagnosed T2DM patients may be helpful in clinical settings. Methods We established machine learning models constructed from a subset of clinical features collected from 53,477 newly diagnosed T2DM patients from January 2008 to December 2018 and then selected the best model. The cohort was divided, with 70% and 30% of patients randomly assigned to the training and testing sets, respectively. Results The discriminative ability of our machine learning models, including logistic regression, extra tree classifier, random forest, gradient boosting decision tree (GBDT), extreme gradient boosting (XGBoost), and light gradient boosting machine were evaluated across the cohort. XGBoost yielded the highest area under the receiver operating characteristic curve (AUC) of 0.953, followed by extra tree and GBDT, with AUC values of 0.952 and 0.938 on the testing dataset. The SHapley Additive explanation summary plot in the XGBoost model illustrated that the top five important features included baseline serum creatinine, mean serum creatine within 1 year before the diagnosis of T2DM, high-sensitivity C-reactive protein, spot urine protein-to-creatinine ratio and female gender. Conclusions Because our machine learning prediction models were based on routinely collected clinical features, they can be used as risk assessment tools for developing ESRD. By identifying high-risk patients, intervention strategies may be provided at an early stage.

Abstract Background Unhealthy lifestyle has been associated with obesity and type 2 diabetes. Whereas its association with vascular complications in patients with long-duration of type 2 diabetes is still uncertain. Methods A total of 1188 patients with long-duration of type 2 diabetes from the Taiwan Diabetes Registry (TDR) data were analyzed. We stratified the severity of unhealthy lifestyle via scoring three factors (sleep duration 9 h, sit duration ≥ 8h, and meal numbers ≥ with night snack) and analyzed their associations with the development of vascular complications using logistic regression analysis. Besides, we also included 3285 patients with newly diagnosed type 2 diabetes as the comparison. Results Increased numbers of factors that stand for unhealthy lifestyle were significantly associated with the development of cardiovascular disease, peripheral arterial occlusion disease (PAOD) and nephropathy in patients with long-duration of type 2 diabetes. After adjusting multiple covariables, having ≥ 2 factors of unhealthy lifestyle remained significant associations with cardiovascular disease and PAOD, with an odds ratio (OR) of 2.09 (95% confidence interval [CI] 1.18–3.69) and 2.68 (95% CI 1.21–5.90), respectively. Among individual factor for unhealthy lifestyle behaviors, we revealed that eating ≥ 4 meals per day with night snack increased the risk of cardiovascular disease and nephropathy after multivariable adjustment (OR of 2.60, 95% CI 1.28–5.30; OR of 2.54, 95% CI 1.52–4.26, respectively). Whereas sit duration for ≥ 8 h per day increased the risk of PAOD (OR of 4.32, 95% CI 2.38–7.84). Conclusion Unhealthy lifestyle is associated with increased prevalence of macro- and micro-vascular comorbidities in Taiwanese patients with long-duration type 2 diabetes.

Abstract Background We examined the relationship between brain-derived neurotrophic factor (BDNF) and chronic kidney disease (CKD). Methods First, a cross-sectional study was conducted in 480 participants without known diabetes. An oral glucose tolerance test (OGTT) was administered after overnight fasting, and blood samples were collected at 0, 30, and 120 min. Second, a total of 3003 participants were enrolled for the case–control genetic analysis. After assigning them to a case or a control group based on age and CKD status, we investigated the association between BDNF gene variants and susceptibility to CKD. Results A higher fasting serum BDNF quartile was significantly associated with a lower prevalence of CKD (P value for trend

Medical personnel need to learn occupational safety knowledge in clinical workplaces, not only to ensure their own safety, but also to further ensure patients safety. Based on Human-centered artificial intelligence (HAI) technology, this study will provide HAI-based occupational safety training system for two training topics, Needle Stick/Sharps Injury (NSSI) prevention and appropriate Clinical Waste Management (CWM). From April 2018 to December 2021, this clinical occupational safety HAI training is used by 342 medical personnel (doctors and non-doctors). This study aims to investigate the learning performance and effectiveness including decreasing anxiety and increasing mastering level of users. This study shows that, for the first-time and feel-friendly users of this HAI training system, not only can they achieve significant learning improvement, but they can also effectively decrease their anxiety and increase their mastery level of clinical work safety knowledge and skill. In terms of learning performance and effectiveness, this study found that doctors are significantly benefited by the HAI training system in contrast to non-doctors.

We summarize updates of hyperglycemia in pregnancy as well as debate of diagnosis of criteria of gestational diabetes. We also point out several unsovled issues of gestataional diabetes that remain further investigations.

Abstract Background The year 2013 marks a watershed in the history of medical education in Taiwan. Following Taiwan’s Taskforce of Medical School Curriculum Reform recommendations, the medical school curriculum was reduced from 7 to 6 years. This study aimed to analyze the impact of medical school curriculum reform on medical students’ performance in objective structured clinical examinations (OSCEs). Methods We retrospectively analyzed the OSCE records at Taipei Veterans General Hospital (Taipei VGH), one of Taiwan’s largest tertiary medical centers, between November 2016 and July 2020. The eligibility criteria were medical students receiving a full one-year clinical sub-internship training at Taipei VGH and in their last year of medical school. All medical students received a mock OSCE-1 at the beginning of their sub-internship, a mock OSCE-2 after six months of training, and a national OSCE at the end of their sub-internship. The parameters for performance in OSCEs included “percentage of scores above the qualification standard” and “percentage of qualified stations.” Results Between November 2016 and July 2020, 361 undergraduates underwent clinical sub-internship training at Taipei VGH. Among them, 218 were taught under the 7-year curriculum, and 143 were instructed under the 6-year curriculum. Based on baseline-adjusted ANCOVA results, medical students under the 7-year curriculum had a higher percentage of scores above the qualification standard than those under the 6-year curriculum at the mock OSCE-1 (7-year curriculum vs. 6-year curriculum: 33.8% [95% CI 32.0–35.7] vs. 28.2% [95% CI 25.9–30.4], p

ObjectivesChronic kidney disease (CKD) is a risk factor for coronary artery disease (CAD). We examined the effects of circulating brain-derived neurotrophic factor (BDNF) on long-term mortality in patients with CAD and CKD.Materials and MethodsWe enrolled patients with established CAD in the present study. Serum BDNF and estimated glomerular filtration rate (eGFR) were assessed after overnight fasting. All-cause mortality served as the primary endpoint.ResultsAll 348 enrolled patients were divided into four groups according to their median BDNF level and CKD status, defined according to eGFR

Abstract In patients with atherosclerotic cardiovascular disease (ASCVD) under statin treatment, the influence of on-treatment level of high-density lipoprotein cholesterol (HDL-C) on cardiovascular (CV) events is controversial. Statin-treated patients were selected from the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry, a multicenter, observational study of adult patients with ASCVD in Taiwan. Low HDL-C was defined as

Abstract Background Peripheral 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. Methods We 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. Results A 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

Background: The recommended target low-density lipoprotein cholesterol (LDL-C) level for coronary artery disease (CAD) patients has been lowered from 100 to 70 mg/dL in several clinical guidelines for secondary prevention. We aimed to assess whether initiating statin treatment in CAD patients with baseline LDL-C 70–100 mg/dL in Taiwan could be cost-effective. Methods: A Markov model was developed to simulate a hypothetical cohort of CAD patients with a baseline LDL-C level of 90 mg/dL. The incidence and recurrence of MI and stroke related to specific LDL-C levels as well as the statin effect, mortality rate, and health state utilities were obtained from the literature. The direct medical costs and rate of fatal events were derived from the national claims database. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALYs) was calculated, and sensitivity analyses were performed. Results: Moderate-intensity statin use, a treatment regimen expected to achieve LDL

The prevalence of obesity in Asia is of epidemic proportions, with an estimated 1 billion overweight/obese individuals in the region. The majority of patients with type 2 diabetes mellitus (T2DM) are overweight/obese, which increases the risk of cardiorenal outcomes in these patients; hence, sustained reductions in body weight and visceral adiposity are important management goals. However, most of the glucose-lowering therapies such as insulin, sulfonylureas, glinides, and thiazolidinediones induce weight gain, which makes the management of overweight/obese T2DM patients challenging. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are the only oral glucose-lowering agents that have been shown to reduce body weight and visceral adiposity. In addition, SGLT-2 inhibitors therapy reduces ectopic fat deposition and improves adipose tissue function and weight-related quality of life. In this article, we aim to consolidate the existing literature on the effects of SGLT-2 inhibitors in Asian patients with T2DM and to produce clinical recommendations on their use in overweight or obese patients with T2DM. Recommendations from international and regional guidelines, as well as published data from clinical trials in Asian populations and cardiovascular outcomes trials are reviewed. Based on the available data, SGLT-2 inhibitors represent an evidence-based therapeutic option for the management of overweight/obese patients with T2DM.

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.

Background/Purpose: The objectives of this study were to evaluate the associations between clinical parameters and quality of life (QOL) of patients with acromegaly in Taiwan and to identify the impacts of hormone control, regimens, or co-morbidities on acromegalic patients' daily life. Methods: From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. Clinical data were recorded. The QOL of enrolled patients were assessed by using Acromegaly Quality of Life Questionnaire (AcroQoL). Results: This study enrolled 272 acromegalic subjects (117 males, 155 females). Remission, defined by normalization of IGF-1, had significant positive association with QOL scores in psychological/appearance (PSY/APP) dimension (β = 6.760, p = 0.023). Somatostatin analogues therapy had negative associations with total score and score in psychological (PSY) dimension (β = −4.720, p = 0.046 and β = −5.388, p = 0.035, respectively). Diabetes mellitus had negative associations with score in PSY dimension and psychological/personal relations (PSY/PER) dimensions (β = −5.839, p = 0.034 and β = −7.516, p = 0.013, respectively). Cerebral vascular accident (CVA) had significant negative associations with total score and scores in physical (PHY), PSY, and PSY/PER dimensions (β = −26.632, p = 0.013; β = −28.353, p = 0.024; β = −25.648, p = 0.026; and β = −34.586, p = 0.006, respectively). All these associations remained significant even after adjusted with sex and age. Conclusion: Our analysis suggested that not only hormone control but also therapeutic regimens and presence of co-morbidities might affect QOL of patients with acromegaly in some dimensions. Keywords: Taiwan acromegaly registry, Quality of life, Clinical parameters

Background/purpose: The objectives of this study were to describe epidemiological data, treatment outcomes, and quality of life (QOL) of patients with acromegaly in Taiwan. Methods: From 2013 to 2015, subjects with acromegaly were recruited through five medical centers. After enrollment, each patient was kept on observation for 1 year. Results: The analyzed cohort included 272 acromegalic subjects (117 males, 155 females) with a mean age of 51.4 ± 12.9 years. Their mean age at diagnosis was 41.8 ± 12.1 years. About 83.8% patients presented symptoms of facial changes. Galactorrhea was noted at the earliest age of 32.7 ± 9.1 years. The duration between the onset of symptoms/signs and diagnosis was 6.9 ± 8.1 years. Around 70.3% patients harbored a macroadenoma. At enrollment, percentages of patients ever received surgical intervention, radiotherapy, somatostatin analogs, and dopamine agonists were 94.8%, 27.9%, 64%, and 30%, respectively. At the final following-up visit, the random growth hormone (GH), nadir GH after oral glucose tolerance test, and the insulin-like growth factor 1 levels were 2.7 ± 4.9 μg/L, 2.4 ± 6.1 μg/L, and 291.5 ± 162.4 ng/mL, respectively. The remission rate assessed by random GH level (≦2 μg/L) was 63.8%. The mean AcroQoL scores for the total 22 items were 64.0 ± 19.7. About 42.8% patients never sensed or felt discomfort about their changes in appearance. Conclusion: This study described the profiles of acromegaly in Taiwan. It is important to enhance early diagnosis and timely commencement of treatment to prevent serious complications of acromegaly. Keywords: Acromegaly, Patient registry, Taiwan, Health outcome, Quality of life

Abstract Diabetes remains a global epidemic and a tremendous health challenge, especially in the Asian population. Dramatic increases in the prevalence of diabetes across different countries or areas in Asia have been reported in recent epidemiological studies. Although clinical guidelines have strengthened appropriate antihyperglycemic medications and lifestyle modifications for optimal diabetes management, inadequate glycemic control still occurs in many patients with an increased risk of developing microvascular and macrovascular complications. Insulin administration is the main therapy for diabetes in response to the inability to secrete insulin, and is recommended in current guidelines to treat patients with type 2 diabetes after failure of oral antidiabetic drugs. Clinical studies have shown that long‐acting insulin analogs improve basal glycemic control with reduced risk of hypoglycemia. In the present review, we discuss previous challenges with basal insulin therapy in Asia, the pharmacological development of insulin analogs to overcome the unmet medical needs and recent clinical studies of the new ultra‐long‐acting insulin analog, insulin glargine U300. Furthermore, relevant findings of current real‐world evidence are also included for the comparison of the efficacy and safety of different insulin formulations. Based on the accumulating evidence showing a low incidence of hypoglycemia and technical benefits of dose titration, treatment with glargine U300 can be a promising strategy for Asian diabetes patients to achieve glycemic targets with favorable safety.

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.

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

Abstract C-reactive protein (CRP) encoded by CRP gene is a reflection of systemic inflammation. Many studies associated CRP level with diabetes and glucose levels, but the association of CRP gene with these traits is unclear. We conducted a cross-sectional study consisting of 945 siblings from 330 families collected by the Stanford Asian Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe) to investigate associations between CRP polymorphisms, circulating CRP, diabetes, and glucose levels. Five single-nucleotide polymorphisms were analyzed: rs3093059, rs2794521, rs1417938, rs1800947, and rs1205. The generalized estimating equation approach was used to deal with correlated data within families. CRP level was positively correlated with diabetes prevalence and levels of fasting and 2-hour glucose (each P

Background/purpose: Diabetes mellitus (DM) prevalence has been rapidly increasing in Taiwan and globally. Team care for DM has been provided through diabetes shared-care networks in Taiwan more than 20 years. Methods: The study analyzed the National Health Insurance (NHI) claims data from 2005 to 2014 to better understand diabetes care accountability and utilization in Taiwan. Results: The completion rate of annual check-ups for various metabolic measurements increased significantly, which indicates improvement in diabetes management quality. The average annual visits and drug cost for each patient increased enormously from 2005 to 2014. The annual number of outpatient department/inpatient department (OPD/IPD) patients with diabetes undergoing dialysis increased. The number of OPD visits in patients with diabetes was 1.9 times higher than that in all patients in general. IPD cost appeared to increase, whereas both drug cost and the average length of hospitalization per patient decreased. Endocrine and metabolic diseases were still the leading cause of OPD expenses. The leading cause of IPD expenses was respiratory diseases. An increasing trend was noted in the medical cost for patients with microvascular instead of macrovascular complications. OPD care for patients with diabetes was rather evenly distributed since 2009. Regarding IPD care, medical centers and regional hospitals each hospitalized 37% of the diabetic outpatients in 2014. Conclusion: Accountability of diabetes care in Taiwan improved significantly till 2014. The ongoing fight against DM and tracing, examining and learning from the overall outcomes in future decades is still required. Keywords: Accountability, Complication, Cost, Diabetes mellitus, Utilization

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

Background/Purpose: Diabetes mellitus (DM) and DM-related complications place a high socioeconomic burden on individuals and society. Updating nationwide information periodically is thus pivotal to preventing DM and improving its management in Taiwan. Methods: We used the National Health Insurance Research Database; disease diagnosis codes were assigned according to the International Classification of Diseases, 9th Revision, Clinical Modification. DM was defined as ≥3 outpatient visits or 1 hospitalization within a year. We excluded individuals with gestational DM, those with missing data, and those aged >100 years. Type 1 DM (T1DM) was defined based on information from the catastrophic illness registry. Results: From 2005 to 2014, total population with DM increased by 66% and age-standardized prevalence in patients aged 20–79 years increased by 41%. The DM prevalence was generally higher in men; however, the prevalence was higher in women aged ≥65 years. The prevalence of DM was approximately 50% in those aged >80 years. DM incidence increased by 19%; the increase was most obvious in patients aged 20–39 years (p

The 2019 Diabetes Atlas delineated both accomplishments and challenges in diabetes care in Taiwan between 2005 and 2014. The series reported that Taiwan had significantly improved aspects of care quality for patients with diabetes. For example, the mortality rate decreased, the difference between the life expectancies of patients with diabetes and those of the general population decreased, and the rates of hospitalization because of heart diseases, cerebrovascular diseases, chronic kidney diseases, and unsatisfactory glycemic control decreased. However, despite these achievements, the 2019 Diabetes Atlas also reported some substantial challenges that have not been overcome. For example, the incidence of diabetes among women aged

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 < 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.

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.

OBJECTIVES: To assess whether chronic glycemic control and stress-induced hyperglycemia, determined by the gap between admission glucose levels and A1C-derived average glucose (ADAG) levels adversely affects outcomes in diabetic patients with pyogenic liver abscess (PLA). METHODS: Clinical, laboratory, and multi-detector computed tomography (MDCT) findings of 329 PLA patients (2004-2010) were retrospectively reviewed. HbA1C levels were used to determine long-term glycemic control status, which were then converted to estimated average glucose values. For the gap between admission glucose levels and ADAG levels, we used receiver operating characteristic (ROC) curve to determine the optimal cut-off values predicting adverse outcomes. Univariate and multivariate logistic regressions were used to identify predictors of adverse outcomes. RESULTS: Diabetic PLA patients with poorer glycemic control had significantly higher Klebsiella pneumoniae (KP) infection rates, lower albumin levels, and longer hospital stays than those with suboptimal and good glycemic control. The ROC curve showed that a glycemic gap of 72 mg/dL was the optimal cut-off value for predicting adverse outcomes and showed a 22.3% relative increase in adverse outcomes compared with a glycemic gap

Sepsis caused by Gram-negative bacterial infection is characterized by extensive inflammatory cytokine production, which leads to multiple organ failure and a high lethality rate. Therefore, compounds that are able to alleviate profound inflammatory responses may have therapeutic potential in relation to sepsis. Quercetin, one of the flavonoids found widely in the human diet, has been reported to have many health benefits, but the mechanisms underlying its biological effects remain obscure. In the present study, our aim was to investigate the molecular mechanisms by which quercetin inhibits lipopolysaccharide (LPS)-induced pro-inflammatory cytokine production and to evaluate the capacity of quercetin to attenuate the mortality rate in a mice model of lethal sepsis. Our results show that quercetin significantly attenuates LPS-induced production of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in RAW264.7 macrophages. The LPS-stimulated phosphorylations of the inhibitors of κB kinase (IKKs), Akt, and c-Jun N-terminal kinase (JNK) are also inhibited by quercetin. Quercetin causes a significant reduction in the phosphorylation and degradation of inhibitor of κBα (IκBα) and in the nuclear level of nuclear factor-κB (NF-κB), the latter being associated with decreased NF-κB binding activity. Most importantly, acute administration of quercetin reduces the lethality rate and circulating levels of TNF-α and IL-1β in C57BL/6J mice with endotoxemia induced by LPS, whereas chronic dietary supplementation with quercetin shows no inhibitory effect on serum TNF-α and IL-1β levels. These findings provide clues that quercetin may be a promising agent for the prevention of systemic inflammatory diseases such as sepsis.

Although the clinical symptoms of patients with benign parathyroid adenoma are usually nonspecific and benign, a malignant presentation of the benign disease may sometimes occur. Here, we report a case of a 58-year-old woman who presented with aggravated sacrum pain, general malaise, and polydipsia. Initial laboratory findings revealed hypercalcemia, normocytic anemia, and impaired renal function. Acute hyper-calcemic crisis manifested and primary hyperparathyroidism was diagnosed together with myelofibrosis on account of the result of bone marrow biopsy. Excision of a parathyroid adenoma was performed, and the anemia and bone marker regressed later. These findings suggested that benign parathyroid adenoma may mimic the clinical presentation of parathyroid carcinoma, releasing excess parathyroid hormone and resulting in hyperparathyroid crisis. In addition, primary hyperparathyroidism can be associated with anemia and myelofibrosis. [J Formos Med Assoc 2007;106(2 Suppl):S13-S16]