Association of dipeptidyl peptidase-4 inhibitor and recurrent pancreatitis risk among patients with type 2 diabetes: A retrospective cohort study.

Introduction: Following the introduction of incretin-based drugs to the market, instances of acute pancreatitis have been reported, leading the FDA to mandate a warning label. Incretin-based therapy has been linked to a rare yet significant adverse event known as acute pancreatitis. However, these concerns of use of incretin therapy remained an ongoing debate. Methods: This retrospective cohort study was extracted data from the National Health Insurance (NHI) program in Taiwan focused on those having prior hospitalization history of acute pancreatitis. We identified adult patients with type 2 diabetes, all patients who received new prescriptions one year after the diagnosis of hospitalization for acute pancreatitis for DPP-4 inhibitors (index date). Study participants were divided into two groups: those taking DPP-4 inhibitors (the DPP-4 inhibitors group, n = 331) and those not taking DPP-4 inhibitors (the non- DPP-4 inhibitors group, n = 918). The outcome of interest is the recurrence of hospitalization of acute pancreatitis. Results: The incidence density (per 1000 person-years) of acute pancreatitis was 23.16 for DPP-4 inhibitors group and 19.88 for non-DPP-4 inhibitor group. The relative risk is 0.86 (95% confidence interval (CI) 0.53-1.38). Results from the Cox proportional hazard model (HR) analysis, the DPP-4 inhibitor was associated with a neutral risk of acute pancreatitis HR 0.68; 95% CI: 0.42-1.09. Conclusions: In this extensive nationwide cohort study conducted in Taiwan, involving a substantial number of newly diagnosed cases, the utilization of DPP-4 inhibitors appears to show no significant correlation with an elevated risk of acute pancreatitis, even among diabetic patients deemed to be at a high risk. These results extend the safety reassurance of incretin-based therapy to individuals considered high-risk for such complications.

Hydrogen-Rich Water (HRW) Reduces Fatty Acid-Induced Lipid Accumulation and Oxidative Stress Damage through Activating AMP-Activated Protein Kinase in HepG2 Cells.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by excessive fat accumulation in the liver. Intracellular oxidative stress induced by lipid accumulation leads to various hepatocellular injuries including fibrosis. However, no effective method for mitigating MASLD without substantial side effects currently exists. Molecular hydrogen (H2) has garnered attention due to its efficiency in neutralizing harmful reactive oxygen species (ROS) and its ability to penetrate cell membranes. Some clinical evidence suggests that H2 may alleviate fatty liver disease, but the precise molecular mechanisms, particularly the regulation of lipid droplet (LD) metabolism, remain unclear. This study utilized an in vitro model of hepatocyte lipid accumulation induced by free fatty acids (FFAs) to replicate MASLD in HepG2 cells. The results demonstrated a significant increase in LD accumulation due to elevated FFA levels. However, the addition of hydrogen-rich water (HRW) effectively reduced LD accumulation. HRW decreased the diameter of LDs and reduced lipid peroxidation and FFA-induced oxidative stress by activating the AMPK/Nrf2/HO-1 pathway. Overall, our findings suggest that HRW has potential as an adjunctive supplement in managing fatty liver disease by reducing LD accumulation and enhancing antioxidant pathways, presenting a novel strategy for impeding MASLD progression.

The association of depression and sleep disorders in patients with type 1 diabetes in Taiwan.

The association between depression and sleep disorders in patients with type 1 diabetes mellitus (T1DM) in Taiwan is underexplored. We used a nationwide population-based dataset to evaluate the association of T1DM with these conditions in Taiwan from 2001 to 2019. Patients with T1DM were identified as cases, and 2 control groups were used for comparison: patients with type 2 diabetes mellitus (T2DM) and nondiabetic patients. Age, sex, date of diagnosis, and multiple comorbidities were included and matched using propensity score matching between cases and controls. The primary outcome of this study was to identify new occurrences of the first diagnosis of depression or sleep disorders. After matching, this study included 27,029 T1DM cases, 54,058 T2DM controls, and 108,116 nondiabetic controls. Patients with T1DM exhibited a 1.55-fold higher risk of developing depression (hazard ratio [HR] 1.55, 95% confidence intervals [CI] 1.48-1.61) and a 1.41-fold higher risk of experiencing sleep disorders (HR 1.41, 95% CI 1.37-1.46) compared to nondiabetic controls. Similarly, patients with T2DM displayed elevated risks of both depression (HR 1.39, 95% CI 1.34-1.43) and sleep disorders (HR 1.40, 95% CI 1.37-1.44) relative to non-diabetic controls. When comparing the T1DM and T2DM groups, T1DM patients demonstrated a slightly higher risk of depression (HR 1.11, 95% CI 1.07-1.16) but no significant difference in the risk of sleep disorders compared to T2DM patients. These results were consistent regardless of different ages or sexes. This study demonstrates a significant association between diabetes mellitus and the risk of depression and sleep disorders in a large cohort of Taiwanese patients.

Risk of diabetes mellitus based on the interactive association between G6PD rs72554664 polymorphism and sex in Taiwan Biobank individuals.

The presence of glucose-6-phosphate dehydrogenase (G6PD) deficiency may increase the risk of type 2 diabetes mellitus (T2DM), with differing prevalence between males and females. Although G6PD deficiency is an X-linked genetic condition, its interaction with sex regarding T2DM risk among the Taiwanese population has not been fully explored. This study aimed to investigate the association between G6PD deficiency and T2DM risk in the Taiwanese population, focusing on the potential influence of sex. Data were obtained from the Taiwan Biobank (TWB) database, involving 85,334 participants aged 30 to 70 years. We used multiple logistic regression analysis to assess the interaction between G6PD rs72554664 and sex in relation to T2DM risk. The T2DM cohort comprised 55.35% females and 44.65% males (p < 0.001). The TC + TT genotype of rs72554664 was associated with an increased risk of T2DM, with an odds ratio (OR) of 1.95 (95% CI: 1.39-2.75), and males showed an OR of 1.31 (95% CI: 1.19-1.44). Notably, the G6PD rs72554664-T allelic variant in hemizygous males significantly elevated the T2DM risk (OR), 4.57; p < 0.001) compared to females with the CC genotype. Our findings suggest that the G6PD rs72554664 variant, in conjunction with sex, significantly affects T2DM risk, particularly increasing susceptibility in males. The association of the G6PD rs72554664-T allelic variant with a higher risk of T2DM highlights the importance of sex-specific mechanisms in the interplay between G6PD deficiency and T2DM.

Assessing herpes zoster vaccine efficacy in patients with diabetes: A community-based cohort study.

The effectiveness of herpes zoster (HZ) vaccines in patients with diabetes over the age of 50 remains an active area of research. Utilizing a real-world database from the US community, this study spanning from 2006 to 2023, aimed to evaluate the impact of HZ vaccination on newly diagnosed diabetes patients who received an HZ vaccination within 1 year of diagnosis. Exclusion criteria were established to omit patients with immune deficiencies. The cohort consisted of 53 885 patients, with an average age of 63.5 years, including 43% females and 58% whites. After implementing 1:1 propensity score matching for age, sex, race, comorbidities, diabetes medication, and hemoglobin A1c to ensure comparability, the study population was further stratified into four groups: N1 comparing any HZ vaccination to non-HZ vaccination (53 882 matched pairs), N2 for Shingrix versus non-HZ vaccination (16 665 matched pairs), N3 for Zostavax versus non-HZ vaccination (12 058 matched pairs), and N4 for Shingrix versus Zostavax (11 721 matched pairs). Cox proportional hazards regression analysis revealed a hazard ratio (HR) for HZ incidence post any HZ vaccination of 0.92 (95% confidence interval [CI]: 0.83-1.01). Additional analyses yielded HRs of 1.12 (95% CI: 0.93-1.34) for Shingrix versus non-HZ vaccine, 1.02 (95% CI: 0.86-1.20) for Zostavax versus non-HZ vaccine, and 1.06 (95% CI: 0.87-1.29) for Shingrix versus Zostavax. Subgroup analyses across age, sex, and follow-up duration also showed no significant differences. These findings underscore the lack of a significant benefit from HZ vaccination in newly diagnosed diabetes patients aged over 50, highlighting the necessity for further prospective research.

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.

Optimizing lipid control in Taiwanese diabetic patients: A collaborative consensus by the Diabetes Association of the Republic of China (Taiwan) and the Taiwanese Association of Diabetes Educators.

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.

Association of COVID-19 Infection with Subsequent Thyroid Dysfunction: An International Population-Based Propensity Score Matched Analysis.

Background: The COVID-19 pandemic's impact on thyroid function is a growing concern. Previous studies have produced inconclusive results, and there is a lack of comprehensive research into the long-term risks of thyroid dysfunction following COVID-19 infection. Methods: In this retrospective cohort study, we used data from the TriNetX international database, which includes electronic health records from a broad, diverse patient population. We compared patients with COVID-19 (cases) to those without (controls), matching for age, sex, race, and comorbidities using propensity score matching. The primary outcome was the diagnosis of thyroid dysfunction (thyrotoxicosis or hypothyroidism) within a 12-month period, analyzed using hazard ratios (HRs) and Kaplan-Meier curves, and stratified by age and sex. Results: Initially, the study included 1,379,311 COVID-19 patients and 6,896,814 non-COVID-19 patients from the TriNetX database. After matching, the cohorts were comparable in demographics and baseline characteristics. This study consistently demonstrated a significant increase in the risk of thyroid dysfunction, including thyrotoxicosis and hypothyroidism, among COVID-19 patients compared to non-COVID-19 patients. In the short term (3 months postexposure), the COVID-19 group exhibited a HR of 2.07 (95% confidence interval [CI] 2.01-2.12) for thyroid dysfunction, which included both thyrotoxicosis (HR 2.10, CI 1.92-2.29) and hypothyroidism (HR 2.08, CI 2.01-2.13). This heightened risk persisted over the long term (up to 12 months), with HRs indicating an ∼2.01-fold increased risk for overall thyroid dysfunction, a 1.8-fold increased risk for thyrotoxicosis, and a 2.04-fold increased risk for hypothyroidism. Subgroup analysis, stratified by age and sex, revealed a notably higher risk of thyroid dysfunction in patients aged 65 and above (HR 2.18, CI 2.11-2.25), compared to those in the under-65 age group (HR 1.97, CI 1.91-2.03). Both male and female patients were associated with an elevated risk, with females showing a slightly higher association with thyroid dysfunction (HR 2.12, CI 2.06-2.16) compared to males (HR 1.76, CI 1.69-1.82). Conclusions: COVID-19 infection was associated with an increased risk of thyroid dysfunction, including thyrotoxicosis and hypothyroidism, regardless of age or sex, during a 12-month follow-up period. Further research is required to validate these findings.

The expert consensus on care and education for patients with diabetic kidney disease in Taiwan.

Increasing prevalence of type 2 DM (T2DM) and diabetic kidney disease (DKD) has posed a great impact in Taiwan. However, guidelines focusing on multidisciplinary patient care and patient education remain scarce. By literature review and expert discussion, we propose a consensus on care and education for patients with DKD, including general principles, specifics for different stages of chronic kidney disease (CKD), and special populations. (i.e. young ages, patients with atherosclerotic cardiovascular disease or heart failure, patients after acute kidney injury, and kidney transplant recipients). Generally, we suggest performing multidisciplinary patient care and education in alignment with the government-led Diabetes Shared Care Network to improve the patients' outcomes for all patients with DKD. Also, close monitoring of renal function with early intervention, control of comorbidities in early stages of CKD, and nutrition adjustment in advanced CKD should be emphasized.

The impact of neuropsychological functions on self-care/self-management of type 2 diabetes in middle-aged people: a scoping review and meta-analysis.

INTRODUCTION: This study aimed to investigate the impact of neuropsychological functions on self-care/self-management in middle-aged individuals with type 2 diabetes (T2DM). AREAS COVERED: A comprehensive literature search was conducted from January 2012 to April 2023 across multiple databases. Ten articles were included in the scoping review, and 3 articles were included in the meta-analysis. The findings consistently indicated an association between reduced neuropsychological functions and poor self-care/self-management in this population. Memory functions, executive functions, and other domains were found to be significantly related to self-care/self-management, including diet management, exercise, blood glucose monitoring, and foot care. EXPERT OPINION: This study highlights the importance of considering neuropsychological factors in understanding and improving diabetes management outcomes. The findings underscore the need for comprehensive neuropsychological assessments and the development of targeted interventions to address specific vulnerable domains. Future research should focus on elucidating underlying mechanisms, addressing methodological inconsistencies, and exploring the effectiveness of interventions targeting neuropsychological impairments. Incorporating technology and personalized approaches into diabetes management can enhance self-care/self-management and clinical outcomes in individuals with T2DM.

Abelmoschus esculentus (Okra) Prevents Insulin Resistance and Restores Neuron Autophagy by Regulating Dipeptidyl Peptidase-4 and Thus Improving Hippocampal Function.

Diabetes is highly linked to the occurrence of Alzheimer disease (AD), which is characterized by beta amyloid peptide (Aß) and hyperphosphorylation of tau (p-tau), and neuron damage particularly in hippocampus. Type 2 diabetes (T2D) is featured by insulin resistance, and phosphorylation of Ser307-IRS-1 is regarded as a resistance marker. Inhibitors of dipeptidyl peptidase-4 (DPP-4) are effective tools for treating T2D. Previously, we reported subfractions of Abelmoschus esculentus (AE, okra) (F1 rich in quercetin glycosides; F2 composed of polysaccharide) attenuated DPP-4 and its downstream signals of insulin resistance, thus preventing Aß-induced neuron damage. Since autophagy could be protective, we now explore if AE works to modulate neuron autophagy by regulating DPP-4 and insulin resistance and, thus, improves the hippocampal function and behavior. We demonstrated that AE subfractions attenuate Aß-induced insulin resistance and the expression of p-tau and normalize the autophagy and survival of hippocampal neurons. The action of AE may be attributed to the downregulation of DPP-4, which plays a critical role in mediating insulin resistance and hinders neuron autophagy. The in vivo findings reveal that the hippocampal insulin resistance appears to link with loss of memory, reduction of curiosity, and depression, whereas treatment with AE significantly improves the insulin sensitivity and hippocampal function. Noteworthy, even at only 5 µg/mL, F2 seems to exhibit a meaningful effect. In conclusion, we suggest that AE attenuates insulin resistance and recovers neuron autophagy which are regulated by DPP-4, thus preventing the damage to the hippocampus, improving recognition and emotion. AE may be an effective adjuvant or supplement to prevent insulin resistance-associated pathogenesis of AD if these results can be confirmed in human clinical trials.

Denosumab Attenuates Glucolipotoxicity-Induced ß-Cell Dysfunction and Apoptosis by Attenuating RANK/RANKL Signals.

Obesity is strongly associated with insulin sensitivity in type 2 diabetes (T2D), mainly because free fatty acids (FFAs) are released from excess fat tissue. Long-term exposure to high levels of FFAs and glucose leads to glucolipotoxicity, causing damage to pancreatic ß-cells, thus accelerating the progression of T2D. Therefore, the prevention of ß-cell dysfunction and apoptosis is essential to prevent the development of T2D. Unfortunately, there are currently no specific clinical strategies for protecting ß-cells, highlighting the need for effective therapies or preventive approaches to improve the survival of ß-cells in T2D. Interestingly, recent studies have shown that the monoclonal antibody denosumab (DMB), used in osteoporosis, displays a positive effect on blood glucose regulation in patients with T2D. DMB acts as an osteoprotegerin (OPG) by inhibiting the receptor activator of the NF-κB ligand (RANKL), preventing the maturation and function of osteoclasts. However, the exact mechanism by which the RANK/RANKL signal affects glucose homeostasis has not been fully explained. The present study used human 1.4 × 107 ß-cells to simulate the T2D metabolic condition of high glucose and free fatty acids (FFAs), and it investigated the ability of DMB to protect ß-cells from glucolipotoxicity. Our results show that DMB effectively attenuated the cell dysfunction and apoptosis caused by high glucose and FFAs in ß-cells. This may be caused by blocking the RANK/RANKL pathway that reduced mammalian sterile 20-like kinase 1 (MST1) activation and indirectly increased pancreatic and duodenal homeobox 1 (PDX-1) expression. Furthermore, the increase in inflammatory cytokines and ROS caused by the RANK/RANKL signal also played an important role in glucolipotoxicity-induced cytotoxicity, and DMB can also protect ß-cells by reducing the mechanisms mentioned above. These findings provide detailed molecular mechanisms for the future development of DMB as a potential protective agent of ß-cells.

Pioglitazone, SGLT2 inhibitors and their combination for primary prevention of cardiovascular disease and heart failure in type 2 diabetes: Real-world evidence from a nationwide cohort database.

OBJECTIVE: To evaluate the effect of SGLT2is, pioglitazone, and their combination on the risk of major adverse cardiovascular events (MACE) and heart failure in type 2 diabetes mellitus (T2DM) patients without a history of cardiovascular disease. RESEARCH DESIGN AND METHODS: Using Taiwan National Health Insurance Research Database, we identified four groups based on medication use, including 1) both SGLT2is and pioglitazone, 2) SGLT2i, 3) pioglitazone and 4) non-study drugs (reference group). The four groups were matched by propensity score. The primary outcome was 3-point MACE, which included myocardial infarction, stroke, cardiovascular death, and the secondary outcome was incidence of heart failure. RESULTS: After propensity-matching, each group included 15,601 patients. Compared with the reference group, the pioglitazone/SGLT2i combination group had a significantly lower risk for MACE (aHR 0.76, 95 % CI 0.66-0.88) and heart failure (aHR 0.67, 95 % CI 0.55-0.82). Pioglitazone was associated with a lower risk of MACE (aHR 0.82, 95 % CI 0.71-0.94) and there was no difference in risk of heart failure compared with the reference group. The incidence of heart failure was significantly decreased in the SGLT2i group (aHR 0.7, 95 % CI 0.58-0.86). CONCLUSION: Combination therapy with pioglitazone and SGLT2is is an effective treatment in the primary prevention of MACE and heart failure in patients with type 2 diabetes.

Unhealthy lifestyle associated with increased risk of macro- and micro-vascular comorbidities in patients with long-duration type 2 diabetes: results from the Taiwan Diabetes Registry.

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 <7 or >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.

TASL, TADE, and DAROC consensus for the screening and management of hepatitis C in patients with diabetes.

Diabetes mellitus (DM) and hepatitis C virus (HCV) infection are prevalent diseases globally and emerging evidence demonstrates the bidirectional association between the two diseases. Direct-acting antivirals (DAAs) for HCV have a high treatment success rate and can significantly reduce the risks of short and long-term complications of HCV infection. However, despite the evidence of the association between diabetes and HCV and the benefits of anti-HCV treatment, previously published guidelines did not focus on the universal HCV screening for patients with diabetes and their subsequent management once confirmed as having HCV viremia. Nonetheless, screening for HCV among patients with diabetes will contribute to the eradication of HCV infection. Thus, the three major Taiwan medical associations of diabetes and liver diseases endorsed a total of 14 experts in the fields of gastroenterology, hepatology, diabetology, and epidemiology to convene and formulate a consensus statement on HCV screening and management among patients with diabetes. Based on recent studies and guidelines as well as from real-world clinical experiences, the Taiwan experts reached a consensus that provides a straightforward approach to HCV screening, treatment, and monitoring of patients with diabetes.

Aspirin and Risk of Specific Breast Cancer Subtype in Women with Diabetes.

Purpose: Low-dose aspirin was associated with a reduced risk of breast cancer in women with diabetes. However, whether the protective effect of aspirin varies as a function of the hormone receptor status of breast cancer remained an unanswered question. This study aims to explore the association between aspirin use and the risk of specific breast cancer subtypes in women with diabetes. Methods: Population-based retrospective cohort study of women with diabetes, using the Taiwan National Health Insurance reimbursement database (year 1998 to 2011). Patients diagnosed to have diabetes with new low-dose aspirin use (75-165 mg per day) for at least 28 days of prescription were identified as the study population, while patients without low-dose aspirin use were selected as controls. The main outcome measure was breast cancer by aspirin use and hormone receptor status. Results: We studied a total of 148,739 patients with diabetes. Their mean (standard deviation) age was 63.3 (12.8) years. During follow-up, a total of 849 breast cancers occurred, including 329 hormone receptor-positive and 529 hormone receptor-negative tumors. A total of 27,378 patients were taking aspirin. The reduction in risk with aspirin use was seen among those with hormone receptor-positive breast cancer (Hazard ratio [HR]: 0.73; 95% confidence interval [CI]: 0.59-0.91) but not for women with hormone receptor-negative breast cancer (HR: 0.88; 95% CI: 0.74-1.05). A cumulative dose of aspirin use of more than 8,600 mg was found to reduce the risk of hormone receptor-positive breast cancer by 31% (HR: 0.69; 95% CI: 0.50-0.97). A cumulative dose of aspirin use of more than 88,900 mg was found to reduce both the risk of hormone receptor-positive and negative breast cancer. Conclusion: These data add to the growing evidence that supports the use of low-dose aspirin as a potential chemopreventive agent for specific subtypes of breast cancer. Further studies are necessary to confirm these findings.

Trends in hospitalizations and emergency department visits among women with hyperglycemia in pregnancy between 2008 and 2017 in Taiwan.

Introduction: We investigated health service utilization, including hospitalizations and emergency department visits, for women with hyperglycemia in pregnancy between 2008 and 2017 in Taiwan. Methods: Data from the Health and Welfare Data Science Center were used to conduct this nationwide population-based study. We identified pregnant women and the date of childbirth according to Birth Certificate Applications from 2007 to 2018. The study population was divided into four groups: known DM, newly diagnosed DM, GDM, and no DM/GDM. To assess quality of healthcare during the gestation period, trends in 30-day readmission rate, number of emergency department visits/hospitalizations per 100 childbirths, and length of hospital stay from 2008 to 2017 were examined. Results: A total of 1830511 childbirths and 990569 hospitalizations were identified for analyses. Between 2008 and 2017, women with hyperglycemia in pregnancy (known DM, newly diagnosed DM, and GDM) had a higher rate of hospitalization, a longer length of hospital stay, and higher rates of various maternal and fetal outcomes, compared with women with no DM/GDM. Nevertheless, the differences between women with GDM and those with no DM/GDM in the aforementioned outcome measures were modest. Women with GDM had a modest decrease in the 30-day readmission rate (p for trend 0.046) with no significant difference in the number of emergency department visits during the study period. Discussion: Our findings provide evidence of the quality of healthcare for women with GDM between 2008 and 2017 in Taiwan.

Liraglutide Attenuates Glucolipotoxicity-Induced RSC96 Schwann Cells' Inflammation and Dysfunction.

Diabetic neuropathy (DN) is a type of sensory nerve damage that can occur in patients with diabetes. Although the understanding of pathophysiology is incomplete, DN is often associated with structural and functional alterations of the affected neurons. Among all possible causes of nerve damage, Schwann cells (SCs) are thought to play a key role in repairing peripheral nerve injury, suggesting that functional deficits occurring in SCs may potentially exhibit their pathogenic roles in DN. Therefore, elucidating the mechanisms that underlie this pathology can be used to develop novel therapeutic targets. In this regard, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have recently attracted great attention in ameliorating SCs' dysfunction. However, the detailed mechanisms remain uncertain. In the present study, we investigated how GLP-1 RA Liraglutide protects against RSC96 SCs dysfunction through a diabetic condition mimicked by high glucose and high free fatty acid (FFA). Our results showed that high glucose and high FFAs reduced the viability of RSC96 SCs by up to 51%, whereas Liraglutide reduced oxidative stress by upregulating antioxidant enzymes, and thus protected cells from apoptosis. Liraglutide also inhibited NFκB-mediated inflammation, inducing SCs to switch from pro-inflammatory cytokine production to anti-inflammatory cytokine production. Moreover, Liraglutide upregulated the production of neurotrophic factors and myelination-related proteins, and these protective effects appear to be synergistically linked to insulin signaling. Taken together, our findings demonstrate that Liraglutide ameliorates diabetes-related SC dysfunction through the above-mentioned mechanisms, and suggest that modulating GLP-1 signaling in SCs may be a promising strategy against DN.

A Randomized Controlled Trial of R-Form Verapamil Added to Ongoing Metformin Therapy in Patients with Type 2 Diabetes.

CONTEXT: There is a medical need for effective insulin-independent antidiabetic drugs that can promote pancreatic ß-cell function and have a low risk of hypoglycemia in type 2 diabetes mellitus (T2DM) patients. R-form verapamil (R-Vera), which is able to enhance the survival of ß-cells and has higher cardiovascular safety margin compared with racemic verapamil, was developed as a novel approach for T2DM treatment. OBJECTIVE: This randomized, double-blind, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of 3 dosages of R-Vera added to ongoing metformin therapy in T2DM patients who had inadequate glycemic control on metformin alone. METHODS: Participants were randomly assigned in an equal ratio to receive R-Vera 450, 300, or 150 mg per day, or matching placebo, in combination with metformin. The primary endpoint was change in hemoglobin A1c (HbA1c) after 12 weeks of treatment. RESULTS: A total of 184 eligible participants were randomized to receive either R-Vera or placebo plus metformin. At week 12, significant reductions in HbA1c were observed for R-Vera 300 mg/day (-0.36, P = 0.0373) and 450 mg/day (-0.45, P = 0.0098) compared with placebo. The reduction in HbA1c correlated with decreasing fasting plasma glucose levels and improved HOMA2-ß score. Treatment with R-Vera was well tolerated with no hypoglycemic episodes occurring during the trial. CONCLUSION: Addition of R-Vera twice daily to ongoing metformin therapy significantly improved glycemic control in T2DM patients. The favorable efficacy and safety profile of R-Vera 300 mg/day can be considered as the appropriate dose for clinical practice.

An Effective Strategy to Activate Physicians to Promote High Cardiovascular Risk Patients to Quit Smoking.

Background: Adult patients cared for by cardiologists, neurologists, and diabetologists are highly vulnerable to cardiovascular diseases (CVDs), which are worsened by smoking. In the past, physicians of these three specialties at major hospitals in Taiwan always referred patients to family medicine and chest medicine departments for smoking cessation programs. However, the participation rate in these programs was unsatisfactory. Objectives: To encourage cardiologists, neurologists, and diabetologists to provide smoking cessation treatment services (SCTSs) to their patients through an annual contest. Methods: Sequential expert meetings, group training, a contest to reward service quantity and abstinence rate, and an annual awards ceremony were held over the past 3 years. Results: More than 350 cardiologists, neurologists, and diabetologists were certified to provide SCTSs, and in the second half of 2020, 3716 high CVD risk patients entered smoking cessation treatment programs, with an abstinence rate exceeding 30% at 3 months. Conclusions: The strategy used in this study was effective in overcoming physician inertia to provide SCTSs and encourage high CVD risk smokers to quit smoking.