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

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

Recent trends of low-density lipoprotein cholesterol control and lipid-lowering therapy in patients with atherosclerotic cardiovascular disease in Taiwan: 2015-2020.

OBJECTIVE: This study aimd to assess recent trends in the control of low-density lipoprotein cholesterol (LDL-C) and the utilization of lipid-lowering drugs (LLD) among patients with atherosclerotic cardiovascular disease (ASCVD) in Taiwan. METHODS: Patients with ASCVD and without a history of hemorrhagic stroke were identified from the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry. ASCVD patients were stratified into four categories: those who ever had acute coronary syndrome (ACS), those who underwent percutaneous coronary intervention or coronary artery bypass grafting (PCI/CABG) without ACS, those who ever had an ischemic stroke (IS) without ACS or PCI/CABG, and other ASCVD cases. We assessed their latest recorded LDL-C levels for the periods 2015-16, 2017-18, and 2019-20. LLD therapy patterns were presented as monotherapy, dual therapy, or combination therapy of three or more drugs, with statin use classified by intensity. RESULTS: We identified 3831 ASCVD patients in 2015-16, 3531 in 2017-18, and 1231 in 2019-20. LLD utilization rose from 58.4% in 2015-16 to 73.2% in 2019-20. The proportions of patients achieving LDL-C goals in 2015-16, 2017-18, and 2019-20 were 21.5%, 25.8%, and 33.3% in the ACS cohort (goal <70 mg/dL); 20.4%, 26.1%, and 39.0% in the PCI/CABG cohort (goal <70 mg/dL); 54.4%, 58.5%, and 58.9% in the IS cohort (goal <100 mg/dL); and 60.0%, 65.5%, and 67.0% in the other ASCVD cohort (goal <100 mg/dL), respectively. Over half of the patients were prescribed moderate-intensity statins. Statin use, age, history of diabetes mellitus, and hypertension were important factors for attaining LDL-C goal in ACS patients. CONCLUSION: Despite improvements in LDL-C management observed over recent years, significant gaps remain in guideline adherence, especially for patients with ACS or PCI/CABG in Taiwan, with over 60% not meeting LDL-C targets. Intensifying efforts to align clinical practice with guidelines are imperative.

Data from network meta-analyses can inform clinical practice guidelines and decision-making in diabetes management: perspectives of the taskforce of the guideline workshop.

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.

Therapeutic Potential of Tpl2 (Tumor Progression Locus 2) Inhibition on Diabetic Vasculopathy Through the Blockage of the Inflammasome Complex.

OBJECTIVE: Diabetic retinopathy, one of retinal vasculopathy, is characterized by retinal inflammation, vascular leakage, blood-retinal barrier breakdown, and neovascularization. However, the molecular mechanisms that contribute to diabetic retinopathy progression remain unclear. Approach and Results: Tpl2 (tumor progression locus 2) is a protein kinase implicated in inflammation and pathological vascular angiogenesis. Nε-carboxymethyllysine (CML) and inflammatory cytokines levels in human sera and in several diabetic murine models were detected by ELISA, whereas liquid chromatography-tandem mass spectrometry analysis was used for whole eye tissues. The CML and p-Tpl2 expressions on the human retinal pigment epithelium (RPE) cells were determined by immunofluorescence. Intravitreal injection of pharmacological inhibitor or NA (neutralizing antibody) was used in a diabetic rat model. Retinal leukostasis, optical coherence tomography, and H&E staining were used to observe pathological features. Sera of diabetic retinopathy patients had significantly increased CML levels that positively correlated with diabetic retinopathy severity and foveal thickness. CML and p-Tpl2 expressions also significantly increased in the RPE of both T1DM and T2DM diabetes animal models. Mechanistic studies on RPE revealed that CML-induced Tpl2 activation and NADPH oxidase, and inflammasome complex activation were all effectively attenuated by Tpl2 inhibition. Tpl2 inhibition by NA also effectively reduced inflammatory/angiogenic factors, retinal leukostasis in streptozotocin-induced diabetic rats, and RPE secretion of inflammatory cytokines. The attenuated release of angiogenic factors led to inhibited vascular abnormalities in the diabetic animal model. CONCLUSIONS: The inhibition of Tpl2 can block the inflammasome signaling pathway in RPE and has potential clinical and therapeutic implications in diabetes-associated retinal microvascular dysfunction.

Similar cardiovascular outcomes in patients with diabetes and established or high risk for coronary vascular disease treated with dulaglutide with and without baseline metformin.

OBJECTIVE: Recent European Guidelines for Diabetes, Prediabetes and Cardiovascular Diseases introduced a shift in managing patients with type 2 diabetes at high risk for or established cardiovascular (CV) disease by recommending GLP-1 receptor agonists and SGLT-2 inhibitors as initial glucose-lowering therapy. This is questioned since outcome trials of these drug classes had metformin as background therapy. In this post hoc analysis, the effect of dulaglutide on CV events was investigated according to the baseline metformin therapy by means of a subgroup analysis of the Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial. RESEARCH DESIGN AND METHODS: Patients in REWIND (n = 9901; women: 46.3%; mean age: 66.2 years) had type 2 diabetes and either a previous CV event (31%) or high CV risk (69%). They were randomized (1:1) to sc. dulaglutide (1.5 mg/weekly) or placebo in addition to standard of care. The primary outcome was the first of a composite of nonfatal myocardial infarction, nonfatal stroke, and death from cardiovascular or unknown causes. Key secondary outcomes included a microvascular composite endpoint, all-cause death, and heart failure. The effect of dulaglutide in patients with and without baseline metformin was evaluated by a Cox regression hazard model with baseline metformin, dulaglutide assignment, and their interaction as independent variables. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by a Cox regression model with adjustments for factors differing at baseline between people with vs. without metformin, identified using the backward selection. RESULTS: Compared to patients with metformin at baseline (n = 8037; 81%), those without metformin (n = 1864; 19%) were older and slightly less obese and had higher proportions of women, prior CV events, heart failure, and renal disease. The primary outcome occurred in 976 (12%) participants with baseline metformin and in 281 (15%) without. There was no significant difference in the effect of dulaglutide on the primary outcome in patients with vs. without metformin at baseline [HR 0.92 (CI 0.81-1.05) vs. 0.78 (CI 0.61-0.99); interaction P = 0.18]. Findings for key secondary outcomes were similar in patients with and without baseline metformin. CONCLUSION: This analysis suggests that the cardioprotective effect of dulaglutide is unaffected by the baseline use of metformin therapy.

Comparison of OSCE performance between 6- and 7-year medical school curricula in Taiwan.

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 < 0.001), and mock OSCE-2 (7-year curriculum vs. 6-year curriculum: 89.4% [95% CI 87.4-91.4] vs. 84.0% [95% CI 81.5-86.4], p = 0.001). Moreover, medical students in the 7-year curriculum had a higher percentage of qualified stations in mock OSCE-1 (7-year curriculum vs. 6-year curriculum: 89.4% [95% CI 87.4-91.4] vs. 84.0% [95% CI 81.5-86.4], p = 0.001) and mock OSCE-2 (7-year curriculum vs. 6-year curriculum: 91.9% [95% CI 90.1-93.8] vs. 86.1% [95% CI 83.8-88.3], p = 0.001). After clinical sub-internship training, there were no differences in the percentage of scores above the qualification standard (7-year curriculum vs. 6-year curriculum: 33.5% [95% CI 32.2-34.9] vs. 34.6 [95% CI 32.9-36.3], p = 0.328) and percentage of qualified stations (7-year curriculum vs. 6-year curriculum: 89.4% [95% CI 88.1-90.7] vs. 90.2% [95% CI 88.6-91.8], p = 0.492). CONCLUSIONS: At the beginning of the sub-internship, medical students under the 7-year curriculum had better OSCE performance than those under the 6-year curriculum. After the clinical sub-internship training in Taipei VGH, there was no difference in the national OSCE score between the 6- and 7-year curricula. Our study suggests that clinical sub-internship is crucial for the development of clinical skills and performance in the national OSCE.

Community-based multiple screening for metabolic syndrome by innovative theory: A longitudinal study.

The purpose of this research is to elucidate whether metabolic syndrome affects the rate of adoption of a new multiple cancer screening programme, based on the Diffusion of Innovation theory. The time to attend the screening programme, conducted in Keelung, Taiwan, within 10 years was assessed by innovativeness (innovators, early adaptors, early majority, late majority and laggard) using data from 79,303 residents, with the information on metabolic syndrome accrued from routine adult health check-ups. The median time of adopting the programme and the relative rates of early adoption by metabolic syndrome and its severity score were estimated. The results show that the estimated times to adopt the programme ranged from 3 months for innovators to 10 years for the laggard. The rate of early adoption was 34% higher for participants without metabolic syndrome than for those with the disease, and the gradient relationship of disease severity was noted. The adjusted median time to adopt innovativeness was 0.82 years earlier for participants who were disease-free than those with the disease. Meanwhile, the adjusted median time was wider by up to 2.25 years for those with severe disease. The study suggests that innovation should prioritise the potential risk of the metabolic syndrome population.

Use of sodium-glucose co-transporter-2 inhibitors in Asian patients with type 2 diabetes and kidney disease: An Asian perspective and expert recommendations.

Early onset of type 2 diabetes and a high prevalence of co-morbidities predispose the Asian population to a high risk for, and rapid progression of, diabetic kidney disease (DKD). Apart from renin-angiotensin system inhibitors, sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been shown to delay renal disease progression in patients with DKD. In this review article, we consolidate the existing literature on SGLT-2 inhibitor use in Asian patients with DKD to establish contemporary guidance for clinicians. We extensively reviewed recommendations from international and regional guidelines, data from studies on Asian patients with DKD, global trials (DAPA-CKD, CREDENCE and DELIGHT) and cardiovascular outcomes trials. In patients with DKD, SGLT-2 inhibitor therapy significantly reduced albuminuria and the risk of hard renal outcomes (defined as the onset of end-stage kidney disease, substantial decline in renal function from baseline and renal death), cardiovascular outcomes and hospitalization for heart failure. In all the cardiovascular and renal outcomes trials, there was an initial decline in the estimated glomerular filtration rate (eGFR), which was followed by a slowing in the decline of renal function compared with that seen with placebo. Despite an attenuation in glucose-lowering efficacy in patients with low eGFR, there were sustained reductions in body weight and blood pressure, and an increase in haematocrit. Based on the available evidence, we conclude that SGLT-2 inhibitors represent an evidence-based therapeutic option for delaying the progression of renal disease in Asian patients with DKD and preserving renal function in patients at high risk of kidney disease.

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

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

Dyslipidemia, Not Inflammatory Markers or Adipokines, Contributes Significantly to a Higher SYNTAX Score in Stable Coronary Artery Disease (from the Taichung CAD Study).

BACKGROUND: The SYNTAX score is an index of coronary severity used to determine the revascularization strategy of a patient. Our previous study confirmed that the SYNTAX score is helpful in predicting major adverse cardiac events in patients with stable coronary artery disease (CAD). However, few studies have comprehensively investigated the predictors for SYNTAX scores in patients with stable CAD, including conventional risk factors, lipid parameters, inflammatory markers and adipokines. METHODS: The coronary severities of 181 revascularization-naïve CAD patients who had received coronary angiograms were coded using SYNTAX scores. Conventional risk factors, inflammatory markers, and adipokines were investigated in order to determine the independent predictors for SYNTAX severity in the patients with stable CAD. RESULTS: The SYNTAX severity score was divided according to the generally accepted criterion (low: ≤ 22, intermediate-high: ≥ 23). In univariate comparisons, the intermediate-high SYNTAX group had a significantly higher low-density lipoprotein cholesterol (LDL-C) level compared to the low SYNTAX score group (p = 0.046). In binary logistic regression, LDL-C, total cholesterol, ratio of total cholesterol/high-density lipoprotein cholesterol (HDL-C) and pre- admission statin use were significant predictors for a higher SYNTAX severity score in the patients with stable CAD. In contrast, circulating adipokines, high-sensitivity C-reactive protein and HDL-C alone were not. CONCLUSIONS: In revascularization-naïve CAD patients, dyslipidemia, including elevated LDL-C, total cholesterol, total cholesterol/HDL-C ratio and pre-index admission statin use, were associated with an intermediate-high SYNTAX severity score.

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

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 < 0.001). CONCLUSIONS: The use of  %MAP alongside ABI appears to significantly improve the prediction of all-cause mortality in patients with type 2 diabetes.

Associations of fear of hypoglycemia with second-line use of insulin secretagogues or insulin and subsequent glycemic control in patients with type 2 diabetes: An analysis using data from the DISCOVER study.

BACKGROUND: Associations of fear of hypoglycemia with prescription of second-line insulin secretagogues (IS) or insulin and subsequent glycemic control in patients with type 2 diabetes were analysed using data from the DISCOVER study-a large, prospective, observational study. METHODS: Patients with type 2 diabetes initiating a second-line treatment after a first-line oral therapy were enrolled. Fear of hypoglycemia was assessed using baseline Hypoglycemia Fear Survey (HFS) worry score. Glycemic control was assessed using glycated haemoglobin (HbA1c) levels at 6-month and 1-year follow-up, and HbA1c change from baseline was analysed. To examine the association of baseline HFS worry scores with second-line use of IS or insulin, a hierarchical logistic model with country as random effect was used. RESULTS: A total of 6217 patients were analysed. The mean HFS worry score was 6.9 ± 11.4, while patients in the upper quartile had an HFS worry score ≥9. We divided patients into three groups according to their baseline HFS worry score (0, 1-8, ≥9). HFS worry score was associated with the use of first-line IS, but not the second-line treatment. Compared to treatments with no IS and insulin, a better HbA1c response to second-line IS or insulin was noted in patients with a baseline HFS worry score of 0 or 1-8, but not in patients with a baseline HFS worry score ≥9. CONCLUSION: HFS worry score was associated with the use of first-line IS and glycemic response to second-line IS or insulin in patients with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02322762. Registered 23 December 2014.

Use of Facebook by Academic Medical Centers in Taiwan During the COVID-19 Pandemic: Observational Study.

BACKGROUND: The battle against COVID-19 remains ongoing, and social media has played an important role during the crisis for both communication and health promotion, particularly for health care organizations. Taiwan's success during the COVID-19 outbreak is well known and the use of social media is one of the key contributing factors to that success. OBJECTIVE: This nationwide observational study in Taiwan aimed to explore the use of Facebook by academic medical centers during the COVID-19 pandemic. METHODS: We conducted a nationwide observational study of all Facebook fan page posts culled from the official accounts of all medical centers in Taiwan from December 2019 to April 2020. All Facebook posts were categorized into either COVID-19-related posts or non-COVID-19-related posts. COVID-19-related posts were split into 4 categories: policy of Taiwan's Center for Disease Control (TCDC), gratitude notes, news and regulations from hospitals, and education. Data from each post was also recorded as follows: date of post, headline, number of "likes," number of messages left, number of shares, video or non-video post, and date of search. RESULTS: The Facebook fan pages of 13 academic medical centers, with a total of 1816 posts, were analyzed. From January 2020, the percentage of COVID-19 posts increased rapidly, from 21% (January 2020) to 56.3% (April 2020). The trends of cumulative COVID-19 posts and reported confirmed cases were significantly related (Pearson correlation coefficient=0.93, P<.001). Pages from private hospitals had more COVID-19 posts (362 versus 289), as well as more video posts (72 posts, 19.9% versus 36 posts, 12.5%, P=.011), when compared to public hospitals. However, Facebook pages from public hospitals had significantly more "likes," comments, and shares per post (314, 5, 14, respectively, P<.001). Additionally, medical centers from different regions displayed different strategies for using video posts on Facebook. CONCLUSIONS: Social media has been a useful tool for communication during the COVID-19 pandemic. This nationwide observational study has helped demonstrate the value of Facebook for academic medical centers in Taiwan, along with its engagement efficacy. We believe that the experience of Taiwan and the knowledge it can share will be helpful to health care organizations worldwide during our global battle against COVID-19.

Brain-Derived Neurotrophic Factor during Oral Glucose Tolerance Test Predicts Cardiovascular Outcomes.

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.

TPL2 (Therapeutic Targeting Tumor Progression Locus-2)/ATF4 (Activating Transcription Factor-4)/SDF1α (Chemokine Stromal Cell-Derived Factor-α) Axis Suppresses Diabetic Retinopathy.

RATIONALE: Diabetic retinopathy is characterized by vasopermeability, vascular leakage, inflammation, blood-retinal barrier breakdown, capillary degeneration, and neovascularization. However, the mechanisms underlying the association between diabetes mellitus and progression retinopathy remain unclear. OBJECTIVE: TPL2 (tumor progression locus 2), a serine-threonine protein kinase, exerts a pathological effect on vascular angiogenesis. This study investigated the role of Nε-(carboxymethyl)lysine, a major advanced glycation end products, and the involved TPL2-related molecular signals in diabetic retinopathy using models of in vitro and in vivo and human samples. METHODS AND RESULTS: Serum Nε-(carboxymethyl)lysine levels and TPL2 kinase activity were significantly increased in clinical patients and experimental animals with diabetic retinopathy. Intravitreal administration of pharmacological blocker or neutralizing antibody inhibited TPL2 and effectively suppressed the pathological characteristics of retinopathy in streptozotocin-induced diabetic animal models. Intravitreal VEGF (vascular endothelial growth factor) neutralization also suppressed the diabetic retinopathy in diabetic animal models. Mechanistic studies in primary human umbilical vein endothelial cells and primary retinal microvascular endothelial cells from streptozotocin-diabetic rats, db/db mice, and samples from patients with diabetic retinopathy revealed a positive parallel correlation between Nε-(carboxymethyl)lysine and the TPL2/chemokine SDF1α (stromal cell-derived factor-α) axis that is dependent on endoplasmic reticulum stress-related molecules, especially ATF4 (activating transcription factor-4). CONCLUSIONS: This study demonstrates that inhibiting the Nε-(carboxymethyl)lysine-induced TPL2/ATF4/SDF1α axis can effectively prevent diabetes mellitus-mediated retinal microvascular dysfunction. This signaling axis may include the therapeutic potential for other diseases involving pathological neovascularization or macular edema.

2019 Diabetes Atlas: Achievements and challenges in diabetes care in Taiwan.

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 <19 years and 20-39 years increased by 27% and 33%, respectively. Furthermore, a high prevalence of macrovascular complications, a continuous increase in the dialysis prevalence rates among men with diabetes of all ages, and a low participation rate (<20%) of patients with diabetes in the pay-for-performance program were observed. The publication of the 2019 Diabetes Atlas is a milestone that demonstrates a strong will in medical societies to improve the quality of diabetes care. We expect this initiative can be reorganized every 5 years to report the results of continuous monitoring and surveillance and update the epidemiological features of diabetes in Taiwan.

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

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

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

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.

Accountability and utilization of diabetes care from 2005 to 2014 in Taiwan.

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.

Testing for HbA1c, in addition to the oral glucose tolerance test, in screening for abnormal glucose regulation helps to reveal patients with early ß-cell function impairment.

BACKGROUND: The oral glucose tolerance test (OGTT) is recommended to screen for diabetes in patients with coronary artery disease. We hypothesized that testing for glycated hemoglobin (HbA1c), in addition to the OGTT, in screening for abnormal glucose regulation may help to reveal patients with ß-cell function impairment. METHODS: Patients with no history of diabetes who were admitted for coronary angiography were recruited to undergo an OGTT and HbA1c test 2-4 weeks after hospital discharge. ß-cell function and insulin resistance were assessed using the homeostasis model assessment (HOMA-ß and HOMA-IR, respectively). For patients with normal glucose tolerance (NGT) based on the OGTT, we compared HOMA-ß between two subgroups of patients using an HbA1c cutoff of 39 mmol/mol or 42 mmol/mol. For patients with prediabetes based on an OGTT, we compared the HOMA-ß between two subgroups of patients using an HbA1c cutoff of 48 mmol/mol. RESULTS: A total of 1044 patients were analyzed. In patients with NGT by OGTT (n=432), those with an HbA1c ≥42 mmol/mol had a lower HOMA-ß compared to those with an HbA1c <42 mmol/mol (107±82 vs. 132±96, p=0.018). In patients with prediabetes by OGTT (n=423), those with an HbA1c ≥48 mmol/mol had a lower HOMA-ß compared to those with an HbA1c <48 mmol/mol (91±52 vs. 120±88, p=0.003). No significant between-group difference in HOMA-IR was noted. CONCLUSIONS: The use of HbA1c in addition to the OGTT in screening for abnormal glucose regulation helped to reveal patients with early ß-cell function impairment.