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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.

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

BackgroundPatients with type 2 diabetes mellitus (DM) have a high prevalence of chronic kidney disease (CKD). Energy imbalance and inflammation may be involved in the pathogenesis of CKD. We examined the effects of brain-derived neurotrophic factor (BDNF) and vascular cell adhesion molecule-1 (VCAM-1) on CKD in patients with type 2 DM.MethodsPatients with type 2 DM were enrolled for this cross-sectional study. Fasting serum was prepared to measure the BDNF and VCAM-1 levels. An estimated glomerular filtration rate (eGFR)

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

BackgroundWe explore the effect of suboptimal glycemic control on the incidence of diabetic peripheral neuropathy (DPN) in both non-elderly and elderly patients with type 2 diabetes mellitus (T2DM).MethodsA 6-year follow-up study (2013-2019) enrolled T2DM patients aged >20 without DPN. Participants were classified into two groups: those below 65 years (non-elderly) and those 65 years or older (elderly). Biochemical measurements, including glycated hemoglobin (HbA1C), were recorded regularly. DPN was diagnosed using the Michigan Neuropathy Screening Instrument examination. The outcome was DPN occurrence in 2019.ResultsIn 552 enrollments (69% non-elderly), DPN occurred in 8.4% non-elderly and 24.0% elderly patients. A higher initial HbA1C level was significantly linked with a higher risk of future DPN in the non-elderly group (adjusted odds ratio [AOR] 1.46, 95% CI 1.13–1.89, p=0.004). In comparison, HbA1c at the end of the study period was not associated with DPN in the non-elderly group (AOR 1.17, 95% CI 0.72–1.90, p=0.526). In the elderly group, no statistical relationship was found between HbA1C levels and DPN, either in 2013 or in 2019.ConclusionSuboptimal glycemic control at baseline, rather than at the end of the study period, predicts an increased risk of future DPN in individuals with T2DM under age 65. This correlation is not seen in elderly patients. Therefore, we recommend implementing enhanced glycemic control early in middle-aged T2DM patients and propose individualized therapeutic strategies for diabetes in different age groups.

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 We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare “clumping-and-thresholding” (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs developed from multiple independent GWAS, perform best across all race/ethnic backgrounds. Stratified analysis in All of Us shows that PRSs are better predictive of BP in females compared to males, individuals without obesity, and middle-aged (40-60 years) compared to older and younger individuals.

IntroductionThe objective of this study was to investigate associations between baseline body constitutions (BCs) in traditional Chinese Medicine (TCM) and all-cause mortality in Chinese individuals with type 2 diabetes.MethodsA total of 887 individuals with type 2 diabetes who were enrolled in managed care in 2010 were included. These individuals were followed up until 2015, and their mortality status was determined through the use of Taiwan National Death Datasets. At baseline, BC status of participants, including Yin deficiency, Yang deficiency, and phlegm stasis, was assessed using a well-developed Body Constitutions Questionnaire. Hazard ratios (HR) were calculated using a multivariate Cox proportional hazards model.ResultsDuring 6807.2 person-years of follow-up of 887 participants, with an average follow-up period of 7.7 years, a total of 190 individuals died, resulting in an incidence density of 0.0279 person-years. Yin deficiency was associated with all-cause mortality (HR, 95% CI: 1.39, 1.02–1.90). This study indicates that individuals diagnosed with Yin deficiency in TCM, characterized by symptoms such as thirst, reduced urine volume, hard stool, and hot flushes, had a 39% higher risk of all-cause mortality.DiscussionThe findings may provide information for TCM practitioners on tailoring treatment plans for persons with type 2 diabetes. No conclusive statements can be made on the basis of the preliminary data presented here. Controlled prospective studies are warranted.

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

Treating type 2 diabetes (T2D) patients with sodium–glucose cotransporter 2 (SGLT2) inhibitors may be associated with an increased risk of urinary tract infections (UTIs), such as diabetes-induced asymptomatic bacteriuria. Pyuria—a condition wherein leukocytes are detected in the urine—is a predictor of UTIs. The aim of this study was to examine the urinary microbiome of Taiwanese T2D patients, with or without pyuria, undergoing SGLT2 treatment. We recruited seven T2D patients, recorded their clinical and biochemical characteristics, and collected their urine samples for 16S metagenomic sequencing. The primary outcomes were the diversity of urinary microbiota and the relative abundance of different species. We found that the microbiome of the pyuria group was significantly less diverse than the non-pyuria group (0.24 ± 0.04 vs. 2.21 ± 0.28, p = 0.002), while the number of operational taxonomic units did not differ significantly (763.5 ± 78.67 and 747 ± 141.3, p = 0.92). Escherichia-Shigella spp. dominated the microbiome of the pyuria group (97.4%–99.4%), and these patients tended to have more comorbidities. In conclusion, pyuria is associated with urinary microbiota dysbiosis in T2D patients being treated with SGLT2 inhibitors.

This retrospective cohort study aimed to assess the mortality risk in patients with type 2 diabetes mellitus (DM) by screening for depressive symptoms and peripheral artery disease (PAD). We enrolled patients aged ≥60 years who had undergone assessments of both the ankle–brachial index (ABI) and the five-item Geriatric Depression Scale (GDS-5). PAD and depression were defined as ABI ≤ 0.90 and GDS-5 ≥ 1, respectively. The primary endpoint was total mortality. In 1673 enrolled patients, the prevalence of PAD was higher in those with depression than in those without depression (8.9% vs. 5.7%, p = 0.021). After a median follow-up of 56.6 months (interquartile range: 47.0–62.3 months), a total of 168 (10.0%) deaths occurred. The patients in the depression and PAD subgroup had the highest hazard ratio of mortality, followed by the PAD without depression subgroup and the depression without PAD subgroup (2.209, 95%CI: 1.158–4.217; 1.958, 95%CI: 1.060–3.618; and 1.576, 95%CI: 1.131–2.196; respectively) in comparison to the patients without depression and PAD after adjustment for associated factors. In conclusion, a combination of depression and PAD predicted the highest mortality risk. Screening for depression and PAD is recommended in patients aged ≥60 years with type 2 DM.

Key Points FORMOSAT-3/COSMIC and FORMOSAT-7/COSMIC-2 uniformly observe 3D electron density. FORMOSAT-3 and FORMOSAT-7 enable ionospheric weather forecasting. FORMOSAT-7/COSMIC-2 TGRS and IVM have a better understanding of the electrodynamics of ionospheric plasma.

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

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.

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 60 mL/min/1.73 m2.

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

ObjectivesDiabetic peripheral neuropathic pain (DPNP) is a prevalent chronic complication in patients with diabetes. Using a questionnaire is helpful for DPNP screening in outpatients. In this retrospective cohort, we aimed to examine whether DPNP diagnosed based on scoring questionnaires could predict long-term mortality in outpatients with type 2 diabetes.MethodsWe enrolled 2318 patients who had joined the diabetes pay-for-performance program and completed the annual assessments, including both the identification pain questionnaire (ID pain) and Douleur Neuropathique en 4 questionnaire (DN4), between January 2013 and October 2013. Information on registered deaths was collected up to August 2019.ResultsThere was high consistency in the scores between the ID pain and DN4 (r = 0.935, P < 0.001). During the median follow-up of 6.2 years (interquartile range: 5.9−6.4 years), 312 patients deceased. Patients with an ID pain score of ≥ 2 had a higher mortality risk than those with a score of < 2 (hazard ratio [HR] = 1.394, 95%CI: 1.090−1.782), and patients with a DN4 score of ≥ 4 had a higher mortality risk than those with a score of < 4 (HR = 1.668, 95% confidence interval [CI]: 1.211−2.297). Patients consistently diagnosed with DPNP by the ID pain and DN4 had a significantly higher mortality risk (HR = 1.713, 95% CI: 1.223−2.398, P = 0.002), but not those discrepantly diagnosed with DPNP (P = 0.107), as compared with those without DPNP.ConclusionsBoth the ID pain and DN4 for DPNP screening were predictive of long-term mortality in patients with type 2 diabetes. However, a discrepancy in the diagnosis of DPNP weakened the power of mortality prediction.

Objective: An increasing trend in the prevalence of gestational diabetes mellitus (GDM) has been reported in Taiwan. GDM has been linked to various adverse maternal outcomes over a long period, including cardiovascular disease (CVD) and chronic kidney disease (CKD). However, evidence implies that the effects of GDM on the mid-term surrogate risk factors for these diseases are limited. Furthermore, data from nationwide cohort studies are limited. The primary aim of this study was to investigate the risk of developing type 2 diabetes mellitus (T2DM), arterial hypertension (aHTN), and hyperlipidemia (HL) through a 5-year follow-up post-delivery of women with GDM in a nationwide cohort study in Taiwan. The second objective was to investigate the risk of developing insulin resistance syndrome (IRS)-related diseases, including CVD, acute myocardial infarction (AMI), peripheral artery occlusive disease (PAOD), non-alcoholic fatty liver diseases (NAFLD), and CKD. Methods: This was a retrospective, population-based nationwide cohort study. The data source comprises a merge of the Birth Certificate Application Database (BCA) and the National Health Insurance Research Database in Taiwan. Women aged between 15 and 45 years who gave birth in Taiwan between 2004 and 2011 were included. Women who were enrolled and had a GDM diagnosis were assigned to the exposure group. Women who were enrolled without a GDM diagnosis were assigned to the comparison group. The relative risk of developing T2DM, aHTN, HL, and IRS-related diseases, including CVD, AMI, PAOD, NAFLD, and CKD, were analyzed and presented as hazard ratio (HR) through Cox regression and log-rank regression analyses. Results: A total of 1,180,477 women were identified through the BCA database between 2004 and 2011. Of those, 71,611 GDM-diagnosed women and 286,444 women without GDM were included in the final analysis. After adjusting for age, pre-existing cancer, and parity, developing T2DM, aHTN, and HL were still significantly increased in the GDM group (HR and interquartile range (IQR): 2.83 (2.59, 3.08), 1.09 (1.01, 1.06), and 1.29 (1.20, 1.38), accordingly). CVD, NAFLD, and CKD had a very low incidence and showed insignificant results. Conclusion: Our findings provide nationwide cohort data showing that GDM increased the risk of developing T2DM, aHTN, and HL 5 years after delivery within the same group. The GDM complications and risk of CVD, AMI, PAOD, NAFLD, and CKD need further investigation.

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. 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.

Glycemic control in patients with type 2 diabetes may be disrupted due to restricted medical service access and lifestyle changes during COVID-19 lockdown period. This retrospective cohort study examined changes of HbA1c levels in adults with type 2 diabetes 12 weeks before and after May 19 in 2021, the date that COVID-19 lockdown began in Taiwan. The mean levels of HbA1c-after were significantly lower than HbA1c-before in 2019 (7.27 ± 1.27% vs 7.43 ± 1.38%, p < 0.001), 2020 (7.27 ± 1.28% vs 7.37 ± 1.34%, p < 0.001), and 2021 (7.03 ± 1.22% vs 7.17 ± 1.29%, p < 0.001). Considering the seasonal variation of HbA1c, ΔHbA1c values (HbA1c-after minus HbA1c-before) in 2020 (with sporadic COVID-19 cases and no lockdown) were not significantly different from 2021 (regression coefficient [95% CI] = 0.01% [−0.02%, 0.03%]), while seasonal HbA1c variation in 2019 (no COVID-19) was significantly more obvious than in 2021 (−0.05% [−0.07, −0.02%]). In conclusion, HbA1c level did not deteriorate after a lockdown measure during the COVID-19 pandemic in Taiwan. However, the absolute seasonal reduction in HbA1c was slightly less during the COVID-19 pandemic compared with the year without COVID-19.

BackgroundCurrent predictive models for patients undergoing coronary angiography have complex parameters which limit their clinical application. Coronary catheterization reports that describe coronary lesions and the corresponding interventions provide information of the severity of the coronary artery disease and the completeness of the revascularization. This information is relevant for predicting patient prognosis. However, no predictive model has been constructed using the text content from coronary catheterization reports before.ObjectiveTo develop a deep learning model using text content from coronary catheterization reports to predict 5-year all-cause mortality and 5-year cardiovascular mortality for patients undergoing coronary angiography and to compare the performance of the model to the established clinical scores.MethodThis retrospective cohort study was conducted between January 1, 2006, and December 31, 2015. Patients admitted for coronary angiography were enrolled and followed up until August 2019. The main outcomes were 5-year all-cause mortality and 5-year cardiovascular mortality. In total, 11,576 coronary catheterization reports were collected. BioBERT (bidirectional encoder representations from transformers for biomedical text mining), which is a BERT-based model in the biomedical domain, was utilized to construct the model. The area under the receiver operating characteristic curve (AUC) was used to assess model performance. We also compared our results to the residual SYNTAX (SYNergy between PCI with TAXUS and Cardiac Surgery) score.ResultsThe dataset was divided into the training (60%), validation (20%), and test (20%) sets. The mean age of the patients in each dataset was 65.5 ± 12.1, 65.4 ± 11.2, and 65.6 ± 11.2 years, respectively. A total of 1,411 (12.2%) patients died, and 664 (5.8%) patients died of cardiovascular causes within 5 years after coronary angiography. The best of our models had an AUC of 0.822 (95% CI, 0.790–0.855) for 5-year all-cause mortality, and an AUC of 0.858 (95% CI, 0.816–0.900) for 5-year cardiovascular mortality. We randomly selected 300 patients who underwent percutaneous coronary intervention (PCI), and our model outperformed the residual SYNTAX score in predicting 5-year all-cause mortality (AUC, 0.867 [95% CI, 0.813–0.921] vs. 0.590 [95% CI, 0.503–0.684]) and 5-year cardiovascular mortality (AUC, 0.880 [95% CI, 0.873–0.925] vs. 0.649 [95% CI, 0.535–0.764]), respectively, after PCI among these patients.ConclusionsWe developed a predictive model using text content from coronary catheterization reports to predict the 5-year mortality in patients undergoing coronary angiography. Since interventional cardiologists routinely write reports after procedures, our model can be easily implemented into the clinical setting.

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: 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.

The canonical β-catenin-dependent wingless (Wnt) pathway is associated with endothelial function. We examined the effect of plasma dickkopf-1 (DKK-1), an inhibitor of the Wnt pathway, on the prediction of major adverse cardiac events (MACEs). We enrolled patients who had undergone selective coronary angiography for angina. DKK-1 levels were determined using plasma collected at the outpatient visit after fasting. MACEs served as the primary endpoint. All 470 enrolled patients were divided into four groups according to their median plasma DKK-1 levels and the presence of obstructive coronary artery disease (CAD). Forty-eight patients reached the primary endpoint during a median follow-up time of 4.8 years. Kaplan–Meier survival analysis indicated that the group with high DKK-1 and obstructive CAD had a significantly higher mortality rate than the other three groups (log-rank test p = 0.001). Compared with the low plasma DKK-1 without significant coronary obstruction group, the high DKK-1 with obstructive CAD group had a hazard ratio of 10.640 (95% confidence interval: 1.350–83.874) for MACEs, as determined by multivariable Cox proportional hazard regression analysis. In conclusion, we observed a synergistic effect between high plasma DKK-1 and obstructive CAD on the prediction of MACEs in patients with angina.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

This paper provides an overview of the contributions of the space-based global navigation satellite system (GNSS) radio occultation (RO) measurements from the FORMOSAT-7/COSMIC2 (F7/C2) mission in advancing our understanding of ionospheric plasma physics in the purview of space weather. The global positioning system (GPS) occultation experiment (GOX) onboard FORMOSAT-3/COSMIC (F3/C), with more than four and half million ionospheric RO soundings during April 2006–May 2020, offered a unique three-dimensional (3D) perspective to examine the global electron density distribution and unravel the underlying physical processes. The current F7/C2 carries TGRS (Tri-GNSS radio occultation system) has tracked more than 4000 RO profiles within ±35° latitudes per day since 25 June 2019. Taking advantage of the larger number of low-latitude soundings, the F7/C2 TGRS observations were used here to examine the 3D electron density structures and electrodynamics of the equatorial ionization anomaly, plasma depletion bays, and four-peaked patterns, as well as the S4 index of GNSS signal scintillations in the equatorial and low-latitude ionosphere, which have been previously investigated by using F3/C measurements. The results demonstrated that the denser low-latitude soundings enable the construction of monthly global electron density maps as well the altitude-latitude profiles with higher spatial and temporal resolution windows, and revealed longitudinal and seasonal characteristics in greater detail. The enhanced F7/C2 RO observations were further applied by the Central Weather Bureau/Space Weather Operation Office (CWB/SWOO) in Taiwan and the National Oceanic and Atmospheric Administration/Space Weather Prediction Center (NOAA/SWPC) in the United States to specify the ionospheric conditions for issuing alerts and warnings for positioning, navigation, and communication customers. A brief description of the two models is also provided.

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.

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.

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

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

Nonalcoholic fatty liver disease (NAFLD) shows extensive liver cell destruction with lipid accumulation, which is frequently accompanied by metabolic comorbidities and increases mortality. This study aimed to investigate the effects of coffeeberry (CB) on regulating the redox status, the CaMKII/CREB/BDNF pathway, autophagy, and apoptosis signaling by a NAFLD rodent model senescence-accelerated mice prone 8 (SAMP8). Three-month-old male SAMP8 mice were divided into a control group and three CB groups (50, 100, and 200 mg/kg BW), and fed for 12 weeks. The results show that CB reduced hepatic malondialdehyde and carbonyl protein levels. CB significantly enhanced Ca2+/calmodulin-dependent protein kinase II (CaMKII) and brain-derived neurotrophic factor (BDNF) and reduced the phospho-cAMP response element-binding protein (p-CREB)/CREB ratio. In addition, CB increased the silent information regulator T1 level, promoted Beclin 1 and microtubule-associated protein light chain 3 II expressions, and reduced phosphorylated mammalian target of rapamycin and its downstream p-p70s6k levels. CB also inhibited the expressions of apoptosis-related factors poly (ADP-ribose) polymerase-1 and the apoptosis-inducing factor. In conclusion, CB might protect the liver by reducing oxidative stress, activating the CaMKII/CREB/BDNF pathway, and improving autophagic and apoptotic expressions in a dose-dependent manner.

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>A and LDLR c.268G>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.

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.

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.

We investigated if brain-derived neurotrophic factor (BDNF) accumulation after glucose intake could predict cardiovascular outcomes. We enrolled patients admitted for angiography due to angina. After their conditions stabilized, serum BDNF levels were detected at 0, 30, and 120 min during oral glucose tolerance test (OGTT). Area under the curve (AUC) of BDNF was calculated. The first occurrence of nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality served as the primary composite endpoint. Of 480 enrolled patients, 428 completed the follow-up, and 36 primary endpoint events occurred during a median follow-up of 4.4 years. The area under the receiver operating characteristic curve significantly increased from 0.61 (95% confidence interval (CI): 0.52–0.73) for the Framingham risk score (FRS) alone model to 0.72 (95%CI: 0.63–0.81) for the AUC of BDNF plus FRS model (p = 0.016) for predicting the primary endpoint, but not to 0.65 (95%CI: 0.55–0.75) for the fasting BDNF plus FRS model (p = 0.160). Grouped by median AUC of BDNF of 38.0 (ng/mL) × h, the low BDNF group had a significantly higher risk of the endpoint than the high BDNF group (hazard ratio = 3.410, 95%CI: 1.520–7.653, p = 0.003). In conclusion, AUC of BDNF during OGTT could be superior to fasting BDNF for predicting a low cardiovascular risk.

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.

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

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

Genome-wide association studies (GWAS) have identified ~100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P