Erectile dysfunction risk among patients with diabetes mellitus using sodium-glucose cotransporter 2 inhibitors.

To explore the incidence of new-onset erectile dysfunction (ED) in diabetes mellitus (DM) patients with sodium-glucose cotransporter 2 inhibitors (SGLT2I) use compared to a control group of non-SGLT2I use by propensity matching (PS) matching approach. Cox proportion hazards regression models were used to examine the effect of SGLT2I and risk factors on the risk of developing ED, presented as a hazard ratio (HR) with a 95% confidence interval (CI). 159773 DM patients using SGLT2I and 159773 PS-matching DM patients who had never used SGLT2I was included. SGLT2I users had a higher risk of ED than the non-SGLT2I users (adjusted HR = 1.55, 95% CI = 1.40-1.72). The likelihood of developing ED was higher in patients with SGLT2I use was found.

Effect of anti-diabetic agent on interstitial lung disease in patients with diabetes mellitus.

The objective was to assess the protective role of anti-diabetic agent (ADA) in predicting interstitial lung disease (ILD) among patients with diabetes mellitus (DM). We formed a cohort of DM patients between 2009 and 2016 using data from Taiwan. Univariable and multivariable Cox proportion hazards regression models were used to examine the effect of risk factor on the risk of developing ILD, presented as a hazard ratio (HR) with a 95% confidence interval (CI). Cox proportional hazard regression analysis for the risk of DM-associated ILD with joint effect of dipeptidyl peptidase-4 inhibitor (DPP4I), glucagon-like peptide-1 receptor agonist (GLP-1 RA), and sodium-glucose cotransporter 2 inhibitors (SGLT2I) showed that SGLT2I, GLP-1 RA, and DPP-4I had a decreased risk of ILD with adjusted HR of 0.14 (0.11, 0.18), 0.29 (0.24, 0.35), and 0.64 (0.62, 0.67), respectively. DPP4I, GLP-1 RA, and SGLT2I could be considered to be introduced to this DM population for ILD risk reduction in DM, especially with SGLT2I usage.

Psychiatric disorders in patients with type 2 diabetes mellitus on sodium-glucose cotransporter-2 inhibitors-a nationwide retrospective cohort study.

To compare the potential role of sodium-glucose cotransporter-2 inhibitors (SGLT2I) in the development of psychiatric disease among patients with type 2 diabetes mellitus (DM). Using a large population-based database, SGLT2I users and non-SGLT2I users were 1:1 matched according to the covariates of sex, age, comorbidities, adapted diabetes complications severity index (DCSI), medications, and index year using propensity score matching and a logistic regression model. We calculated the incidence of major psychiatric disorders and adjusted hazard ratios (HR) with 95% confidence interval (CI) for SGLT2I users and the non- SGLT2I users using a Cox proportional hazards model. SGLT2I were associated with a lower risk for psychiatric disorders than those not treated with SGLT2I (HR 0.80 and 95% CI 0.72-0.88). Among patients with DM, SGLT2I were associated with a lower risk of psychiatric disease.

Sodium-glucose cotransporter-2 inhibitor in risk of sepsis/septic shock among patients with type 2 diabetes mellitus-a retrospective analysis of nationwide medical claims data.

This research is an attempt to investigate the benefit of sodium-glucose cotransporter-2 inhibitor (SGLT2I) use in patients with diabetes mellitus (DM) for outcomes of sepsis/septic shock. We used Taiwan's national data set to identify patients and patients' characteristics to investigate sepsis/septic shock among diabetes patients who use SGLT2I compared to those who do not. We have compared the two groups for several relevant categories of potential risk factors for sepsis/septic shock and adjusted the Cox regression models accordingly. The adapted diabetes complications severity index (DCSI) was used for stratifying the advancing disease of DM. Compared to patients with DCSI = 0, patients with DCSI ≥ 2 had a significantly higher risk of sepsis/septic shock (adjusted HR = 1.52, 95% CI = 1.37-1.68). A significantly lower risk of sepsis/septic shock events was observed in the SGLT2I cohort than in the non-SGLT2I cohort with the DCSI groups [adjusted HR = 0.6 (DCSI group = 0), adjusted HR = 0.61 (DCSI group = 1), adjusted HR = 0.55 (DCSI group ≥ 2)]. Patients who received SGLT2I for a cumulative duration of ≥ 90 days had a significantly lower risk of sepsis/septic shock than patients with a duration of < 90 days (adjusted HR = 0.36, 95% CI = 0.34-0.39). We described a decreased risk of sepsis/septic shock among diabetic patients who took SGLT2I.

Regulation of ROS/inflammasome Axis is Essential for Cardiac Regeneration in Aging Rats Receiving Transplantation of Mesenchymal Stem Cells.

BACKGROUND: Aging is a biological and gradual deterioration of function in living organisms. Aging is one of the risk factors for heart disease. OBJECTIVE: Although mesenchymal stem cell transplantation shows potential in heart disease treatment, the relationship between stem cell-based therapy and oxidative stress/inflammasome axis regulation remains unclear. This study hypothesized that intervention of stem cells showed a protective effect on heart aging induced by D-galactose through regulation of oxidative stress/inflammasome axis. METHODS: An aging animal model was designed to test the above hypothesis. Experimental animals were divided into three groups, including Sham, D-gal (aging rats induced by d-galactose), and D-gal+WJSC (aging rats receiving mesenchymal stem cells). RESULTS: Compared to the Sham, the experimental results indicate that structural alteration (HE stain and Masson's Trichrome stain), oxidative stress elevation (increase of TBARS level, expression of gp-91 and suppression of Sirt-1 as well as SOD2), increase of aging marker p53, suppression of cardiogenesis marker Troponin T, and inflammasome related protein markers expression (NLRP3, caspase-1 and IL-1 beta) were significantly observed in D-gal. In contrast, all pathological pathways were significantly improved in D-gal+WJSC when compared to D-gal. In addition, migration of stem cells to aging heart tissues was observed in the D-gal+WJSC group. CONCLUSION: These findings suggest that mesenchymal stem cell transplantation effectively ameliorates aging hearts through oxidative stress/inflammasome axis regulation. The results from this study provide clinical potential for stem cell-based therapy in the treatment of aging hearts.

Angiotensin Receptor-neprilysin Inhibitor Versus Renin-angiotensin System Inhibitor for Dementia Risk in Patients With Heart Failure.

ABSTRACT: The authors report the impact of angiotensin receptor-neprilysin inhibitor (ARNI) versus renin-angiotensin system inhibitor (RASI) on the management and outcomes in dementia among heart failure (HF) patients as obtained from the real-life nationwide registry. In this study, HF patients between January 1, 2017 and December 31, 2019 were divided into 2 groups, including subjects receiving RASI and ARNI. The incidence rate of dementia was calculated with the unit of 1000 person-years. Cox proportional hazard model was applied for the examination of the hazard ratio, and also presented with 95% confidence interval. Between 2017 and 2019, RASI and ARNI cohorts contain 18,154 subjects. After adjusting with age, sex, comorbidities, and medications, ARNI cohort had a lower risk of dementia (adjusted hazard ratio = 0.83; 95% confidence interval = 0.72, 0.95) than RASI cohort. The authors concluded that use of ARNI was associated with a lower risk of new-onset dementia in patients with HF.

Using progression in adapted diabetes complications severity index score to predict erectile dysfunction in men affected by type 2 diabetes mellitus.

OBJECTIVE: This study is on the use of the adapted Diabetes Complications Severity Index (aDCSI) for erectile dysfunction (ED) risk stratification in male patients with type 2 diabetes mellitus (DM). METHODS: This is a retrospective study with records obtained from Taiwan's National Health Insurance Research Database. Adjusted HRs (aHRs) were estimated by multivariate Cox proportional hazards models with 95% confidence intervals (CIs).. RESULTS: A population of 84 288 eligible male patients with type 2 DM were included. Compared with change in aDCSI score of 0.0-0.5 per year, the aHRs and the corresponding 95% CIs for other changes in aDCSI scores are summarised as follows: 1.10 (0.90 to 1.34) for change in aDCSI score of 0.5-1.0 per year; 4.44 (3.47 to 5.69) for change in aDCSI score of 1.0-2.0 per year; and 10.9 (7.47 to 15.9) for change in aDCSI score of >2.0 per year.. CONCLUSIONS: Progression in aDCSI score might be used for ED risk stratification in men affected by type 2 DM.

Angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and hemorrhoids: A nationwide, population-based study.

The authors investigated whether there is an association between angiotensin-converting-enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) users with hemorrhoids. A total of 21,670 ACEI users and 21,670 ARB users during 2000 - 2012 from a national health insurance database were included. Hemorrhoid incidences were monitored to the end of 2013. To examine the risk of hemorrhoids, the Cox proportional hazard model and the Kaplan-Meier method were used. The incidence rate of hemorrhoids in ARB users was 6.64 per 1000 person-years, which was higher than that of the ACEI users (5.48 per 1000 person-years). The adjusted hazard ratio of hemorrhoids in patients who received ACEI relative to those who received ARB was 0.83 (95% confidence intervals [CI] = 0.75, 0.92). Compared to ARB users, patients who used ACEI more than 740 days per year (adjusted hazard ratios = 0.44; 95% CI = 0.36, 0.54) and more than 7800 mg (adjusted hazard ratios = 0.54; 95% CI = 0.46, 0.65) had a lower risk of hemorrhoids. ACEI users who took a relatively long period or high cumulative dosage were found to less prone to develop hemorrhoids.

Weekend versus weekday hospitalization and clinical outcomes in atrial fibrillation patients with and without stroke.

PURPOSE: The relation between hospitalization timing and risk of clinical outcomes among patients with atrial fibrillation (AF) with and without stroke remained undetermined. METHODS: Rehospitalization due to AF, cardiovascular (CV) death and all-cause mortality were the outcomes of interest in this study. Multivariable Cox proportional hazard model was applied to estimate the adjusted hazard ratio (HR) and 95% confidence interval (CI). RESULTS: While considering patients with AF hospitalized during weekdays without stroke as the reference group, patients with AF hospitalized during weekends with stroke had the risk of AF rehospitalization, CV death and all-cause death by 1.48 (95% CI 1.44 to 1.51), 1.77 (95% CI 1.71 to 1.83) and 1.17 (95% CI 1.15 to 1.19) times, respectively. CONCLUSION: Patients with AF hospitalized during weekends with stroke had the worst clinical outcomes.

Statin versus ezetimibe-statin for incident atrial fibrillation among patients with type 2 diabetes mellitus with acute coronary syndrome and acute ischemic stroke.

The objective was to assess the role of the combination approach with ezetimibe 10 mg/simvastatin 20 mg versus atorvastatin 40 mg in predicting atrial fibrillation (AF) in type 2 diabetes mellitus patients with acute coronary syndrome and acute ischemic stroke. The authors formed a cohort of diabetic patients with extensive vascular diseases between 2000 and 2018 using data from the National Health Insurance Research Database in Taiwan. AF was the outcome of interest in this study. Cox proportional hazards regression analysis was performed to estimate the hazard ratios and 95% confidence intervals in the analysis. After controlling for sex, age, comorbidities and medications, the patients coexisting with type 2 diabetes mellitus, acute coronary syndrome and acute ischemic stroke with ezetimibe 10 mg/simvastatin 20 mg treatment were not significantly at risk of AF, compared to the patients with atorvastatin 40 mg treatment (adjusted hazard ratio, 0.85; 95% confidence interval, 0.52-1.38). A similar effect for AF risk between ezetimibe 10 mg/simvastatin 20 mg and atorvastatin 40 mg users was observed in the current investigation.

Comparisons of HATCH, HAVOC and CHA2DS2-VASc scores for all-cause mortality prediction in atrial fibrillation: a real-world evidence study.

OBJECTIVE: This study focused on the predictive ability of the 3 scores for all-cause mortality in 6444 patients with atrial fibrillation (AF). METHODS: To assess the predictive accuracy of risk of death modelled by HATCH, HAVOC and CHA2DS2-VASc scores, the area under the curve of receiver operating characteristics (AUROC) was applied. RESULTS: Over follow-up time, the cumulative incidence of death was clearly associated with the three scores (log-rank test, p<0.001). The AUROC for the HATCH (0.6618) was significantly higher than HAVOC Score (0.5733) and CHA2DS2-VAScs Score (0.6423). CONCLUSIONS: HATCH score has better ability in predicting mortality in comparison to other two scores in patients with AF.

Association of Heart Failure Patients With and Without Sacubitril-Valsartan Use With Incident Cancer Risk.

ABSTRACT: This study was to evaluate the association between heart failure (HF) patients with and without sacubitril-valsartan use with incident cancer risk. This study consisted of 18,072 patients receiving sacubitril-valsartan and 18,072 control group participants. In the Fine and Gray model, which extends the standard Cox proportional hazards regression model, we estimated the relative risk of developing cancer between the sacubitril-valsartan cohort and the non-sacubitril-valsartan cohort by using subhazard ratios (SHRs) and 95% confidence intervals (CIs). The incidence rates of cancer were 12.02 per 1000 person-years for the sacubitril-valsartan cohort and 23.31 per 1000 person-years for the non-sacubitril-valsartan cohort. Patients receiving sacubitril-valsartan had a significantly lower risk of developing cancer with an adjusted SHR of 0.60 (0.51, 0.71). Sacubitril-valsartan users were less to be associated with the development of cancer.

Diabetic patients with and without sodium-glucose cotransporter-2 inhibitors use and cataract risk: real-world observational investigation.

PURPOSE: We tried to define the association of type 2 diabetes mellitus (T2DM) patients with and without sodium-glucose cotransporter-2 inhibitors (SGLT2I) use and incident cataract using nationwide data in Taiwan. METHODS: In a Cox proportional hazards regression model, we estimated the hazard ratios (HR) and 95% confidence intervals (95% CI). We considered risk factors for variables of sex, age, comorbidities and medications that we adjusted in multivariable Cox model. RESULTS: We identified 20,768 T2DM patients in this study; 10,384 patients in the SGLT2I cohort, and 10,384 controls in the non-SGLT2I cohort. Compared with the T2DM patients without SGLT2I, T2DM patients using SGLT2I had a 2.04-fold increased risk of cataract, after adjustment by sex, age, comorbidities and medications. CONCLUSION: Increased risk of cataract among diabetic patients who took SGLT2I was found in this study.

Sodium-Glucose Cotransporter-2 Inhibitor versus Beta-Blocker Use for Hepatocellular Carcinoma Risk among People with Hepatitis B or C Virus Infection and Diabetes Mellitus.

Objective: The current study detects the effect of sodium-glucose cotransporter-2 inhibitor (SGLT2I) versus beta-blocker (BB) in diabetes mellitus (DM) with chronic hepatitis B or C on hepatocellular carcinoma (HCC) outcomes. Methods: The multivariate logistic regression model, including all baseline characteristics and index year, was used to calculate the propensity scores, and we performed the greedy algorithm on propensity scores to create matched pairs of SGLT2I and BB users. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) of HCC were estimated by Cox proportional hazards regression models, and we adjusted for confounding factors by including the baseline characteristics in the regression models. Results: After matching in a ratio of 1:1, 7023 SGLT2I users and 7023 BB users were included in the following statistical analyses. The overall HRs showed a significantly lower risk of HCC in SGLT2I users in comparison to a reference group of BB users with an adjusted HR of 0.27 (0.21, 0.34). Conclusions: Compared to BB use, SGLT2I was associated with a significant risk reduction in HCC occurrence.

Patients with diabetes with and without sodium-glucose cotransporter-2 inhibitors use with incident cancer risk.

PURPOSE: The study compared the incidence of cancer between patients with diabetes with and without sodium-glucose cotransporter-2 (SGLT2) inhibitors use. METHODS: This study identified a non-SGLT2 inhibitor cohort of 325,989 patients and a SGLT2 inhibitor cohort of 325,990 patients. The primary interest of this study was the occurrence of cancer. Hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox proportional hazard models. RESULTS: Patients receiving SGLT2 inhibitors (adjusted HR = 0.79, 95 % CI = 0.76-0.83) had a significantly lower risk of developing cancer than patients without receiving SGLT2 inhibitors. CONCLUSION: The results demonstrated that patients with diabetes receiving SGLT2 inhibitors had a significantly lower risk of cancer.

Clinical outcomes in heart failure patients with and without atrial fibrillation receiving sodium-glucose cotransporter-2 inhibitor.

We report a retrospective analysis of a nationwide health database to study the association between sodium-glucose cotransporter-2 inhibitor (SGLT2I) use and the incidence of adverse clinical outcomes among heart failure (HF) patients with and without atrial fibrillation (AF) stratified by CHA2DS2-VASc score. The outcome of this study was on the development of adverse events, including acute myocardial infarction (AMI), hemorrhagic stroke, ischemic stroke, cardiovascular (CV) death, and all-cause mortality. By dividing the number of adverse events by the total person-years, the incidence rate was calculated. The hazard ratio (HR) was estimated by the Cox proportional hazard model. A total of 95% confidence interval (CI) was also presented to show the risk of adverse events for HF patients with and without AF taking SGLT2I. SGLT2I users had a lower risk of AMI (adjusted HR = 0.83; 95% CI = 0.74, 0.94), CV death (adjusted HR = 0.47; 95% CI = 0.42, 0.51), and all-cause death (adjusted HR = 0.39; 95% CI = 0.37, 0.41). Considering HF patients without AF and SGLT2I as the reference group, HF patients without AF but with SGLT2I had a reduced risk of adverse outcomes of 0.48 (95% CI = 0.45, 0.50), and HF patients with AF and SGLT2I had the decreased hazard ratio of 0.55 (95% CI = 0.50, 0.61). The adjusted HR of adverse outcomes for HF patients with CHA2DS2-VASc score less than 2 and SGLT2I without and with AF relative to HF patients without AF nor SGLT2I were 0.53 (95% CI = 0.41, 0.67) and 0.24 (95% CI = 0.12, 0.47), respectively. Compared to HF patients with no history of AF and SGLT2I, if patients additionally with SGLT2I and CHA2DS2-VASc score ≥ 2, the risk of the adverse outcomes was reduced with adjusted HR of 0.48 (95% CI = 0.45, 0.50); if patients additionally with AF and CHA2DS2-VASc score ≥ 2, the risk of the adverse outcomes was decreased with adjusted HR of 0.88 (95% CI = 0.80, 0.97); if patients additionally with AF, SGLT2I, and CHA2DS2-VASc score ≥ 2, the risk of the adverse outcomes was diminished with adjusted HR of 0.52 (95% CI = 0.47, 0.58). We concluded that SGLT2I has a protective effect in HF patients, and the risk reduction is greater with a score of < 2 and without AF.

Role of sodium-glucose cotransporter-2 inhibitors in risk of chronic kidney disease among patients with type 2 diabetes mellitus.

AIM: This retrospective analysis aims to explore the risk of chronic kidney disease (CKD) among type 2 diabetes mellitus (DM) patients with different scores of adapted diabetes complications severity index (DCSI) who received sodium-glucose cotransporter-2 inhibitors (SGLT2Is). METHODS: This study includes 113,449 DM patients from the Taiwan National Health Insurance Research Database (NHIRD). We analyzed the data collected from 107,440 patients showing a DCSI score change of < 1 per year, 3720 patients with a score change of 1 to 2 per year and 2289 patients with a score change of > 2 per year. Cox proportional hazard models were used to evaluate the CKD risk throughout the overall follow-up period, and were adjusted for sex, age, comorbidities and medications of a-glucosidase inhibitors, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, biguanides, dipeptidyl peptidase-4 inhibitors, glucagon like peptide-1 receptor agonists, insulin, meglitinides, sulphonylurea and thiazolidinedione. RESULTS: The incidence of CKD increased from 18.30 per 1000 person-years in patients with a score change of < 1 per year to 137.55 per 1000 person-years for those with a score change of > 2 per year. Patients with a higher score change (> 2 per year) and receiving SGLT2Is had a lower risk of developing CKD than patients who did not receive SGLT2Is. CONCLUSION: The use of SGLT2Is was significantly associated with the reduction in CKD incidence in diabetic patients with a higher DCSI.

Acupuncture decreases risk of stroke among patients with atrial fibrillation: A nationwide investigation.

The authors aim to investigate retrospectively the association between acupuncture and risk of stroke in patients with atrial fibrillation (AF). Using the Taiwan National Health Insurance Research Database, AF patients without any acupuncture treatment record were classified as non-acupuncture cohort and 1:1 matching with acupuncture cohort by age, gender, and all comorbidities. To calculate the risk of stroke in case and control groups, cox proportional hazard models were used and presented by hazard ratios, adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Two equally distributed groups of AF individuals with and without acupuncture were included. After adjusting for risk factors, AF subjects with acupuncture conferred a lower risk of stroke (aHR = 0.46, 95% confidence intervals [CI] = 0.38-0.54), ischemic stroke (aHR = 0.47, 95% CI = 0.39-0.56) and hemorrhagic stroke (aHR = 0.35, 95% CI = 0.19-0.67), compared to the controls. AF patients receiving acupuncture was associated with a decreased risk of stroke.

Mesenchymal Stem Cell Transplantation Increases Antioxidant Protein Expression and Ameliorates GP91/ROS/Inflammasome Signals in Diabetic Cardiomyopathy.

BACKGROUND: Cardiomyopathy is one of the complications associated with diabetes. Due to its high prevalence, diabetic cardiomyopathy has become an urgent issue for diabetic patients. Various pathological signals are related to diabetic cardiomyopathy progress, including inflammasome. Mesenchymal stem cell transplantation is full of potential for the treatment of diabetic cardiomyopathy because of stem cell cardiac regenerative capability. This study investigates whether mesenchymal stem cell transplantation shows therapeutic effects on diabetic cardiomyopathy through inflammasome signaling regulation. METHODS: Wistar male rats were divided into three groups including Sham, T1DM (rats with type 1 diabetes) and T1DM + WJSC (T1DM rats receiving 1 × 106 stem cells per rat). RESULTS: Compared to the Sham, experimental results indicated that several pathological conditions can be observed in heart tissues with T1DM, including structural change, fibrosis, oxidative stress elevation and inflammasome related protein expression. All of these pathological conditions were significantly improved in T1DM rats receiving mesenchymal stem cell transplantation (T1DM + WJSC). Furthermore, the experimental findings suggest that mesenchymal stem cell transplantation exerted antioxidant protein expression in diabetic heart tissues, resulting in a decrease in oxidative stress and inflammasome signaling blockage. CONCLUSION: These findings imply that mesenchymal stem cell transplantation shows therapeutic effects on diabetic cardiomyopathy through inflammasome regulation induced by oxidative stress.

The risk of suicide in patients with critical illness: A population-based study in Taiwan.

The authors investigated retrospectively the association between critical illness and risk of suicide attempts. The data are from Taiwan's National Health Insurance Research Database. Propensity score matching, multivariable models, Kaplan-Meier analysis, and competing risk analysis were used to explore this association. The authors found that patients having an critical illness were associated with increased risk of suicide attempts after adjusting for risk factors (adjusted hazard ratio = 2.98; 95% confidence interval = 1.46-6.08). Among different subtypes of critical illness, patients with sepsis/septic shock exhibited the highest risk of suicide attempts (adjusted hazard ratio = 3.43, 95% confidence interval = 1.52-7.74). An association between critical illness and suicide attempts was shown. Sepsis/septic shock was found to confer the highest risk in these specific population.