Sodium-Glucose Cotransporter-2 Inhibitors and the Risk for Dialysis and Cardiovascular Disease in Patients With Stage 5 Chronic Kidney Disease.

BACKGROUND: No studies have reported the long-term outcomes of initiating sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients with estimated glomerular filtration rates less than 20 mL/min/1.73 m2 to predialysis. OBJECTIVE: To compare the risk for dialysis, cardiovascular events, and death between SGLT2i users and nonusers in patients with type 2 diabetes (T2D) and stage 5 chronic kidney disease (CKD). DESIGN: Target trial emulation study. SETTING: Taiwan's National Health Insurance Research Database (NHIRD). PARTICIPANTS: By applying sequential target trial emulation principle, 23 854 SGLT2i users and 23 892 SGLT2i nonusers were selected from the NHIRD for patients with T2D and stage 5 CKD from 1 May 2016 to 31 October 2021. MEASUREMENTS: Conditional Cox proportional hazards models were used to compare the risks for dialysis, hospitalization for heart failure, acute myocardial infarction (AMI), diabetic ketoacidosis (DKA), acute kidney injury (AKI), and all-cause mortality between SGLT2i users and nonusers. RESULTS: In the intention-to-treat model, compared with no SGLT2i use, SGLT2i use was associated with lower risks for dialysis (hazard ratio [HR], 0.34 [95% CI, 0.27 to 0.43]), hospitalization for heart failure (HR, 0.80 [CI, 0.73 to 0.86]), AMI (HR, 0.61 [CI, 0.52 to 0.73]), DKA (HR, 0.78 [CI, 0.71 to 0.85]), and AKI (HR, 0.80 [CI, 0.70 to 0.90]), but there was no difference in the risk for all-cause mortality (HR, 1.11 [CI, 0.99 to 1.24]). The Kaplan-Meier curves and subgroup analyses also showed that initiation of an SGLT2i in stage 5 CKD was associated with a lower risk for long-term dialysis than no SGLT2i use. LIMITATION: This result may not apply to patients without T2D. CONCLUSION: This emulated target trial showed that SGLT2i use was associated with a lower risk for dialysis, cardiovascular events, DKA, and AKI than no SGLT2i use in patients with T2D and stage 5 CKD. PRIMARY FUNDING SOURCE: National Health Research Institutes, Taiwan.

Dissecting the risk factors for hyperuricemia in vegetarians in Taiwan.

BACKGROUND: Vegetarian diets have been shown to lower the risks of hyperuricemia and gout. Little is known about the risk factors of hyperuricemia in vegetarians. METHODS: This community-based retrospective case-control study was conducted to establish prediction models for hyperuricemia. From September 5, 2005, to December 31, 2016, 7331 adult vegetarians were recruited at Taipei Tzu Chi Hospital. Hyperuricemia was defined as a serum uric acid concentration greater than 7 mg/dL. RESULTS: There were 593 (8.1%) vegetarians with hyperuricemia and 6738 (91.9%) without hyperuricemia. We stepwise built up three models for predicting hyperuricemia in vegetarians. The full model (model 3) has the highest area under the receiver operating characteristic curve (AUROC, 85.52%). Additionally, the AUROC of model 3 is 77.97% and 84.85% in vegetarians with or without prior gout history, respectively. Moreover, male gender, hyperlipidemia, body mass index, and serum albumin are independent risk factors for hyperuricemia in vegetarians. In contrast, estimated glomerular filtration rate and proteinuria are independently associated with lower risks of hyperuricemia in vegetarians. CONCLUSION: Our study revealed that risk factors for hyperuricemia, which includes clinical characteristics, account for more than 85% of discriminatory performance in Taiwanese vegetarians. This model may be helpful for monitoring and preventing hyperuricemia in the population.

Use of dipeptidyl peptidase-4 inhibitors was associated with a lower risk of Parkinson's disease in diabetic patients.

Diabetes mellitus is a risk factor for Parkinson's disease (PD). While animal studies have supported the benefits of incretin-based therapies, including dipeptidyl peptidase-4 (DPP4) inhibitors, in PD, clinical research has yielded controversial results. This cohort study aimed to assess the relationship between PD incidence and the utilization of DPP4 inhibitor in diabetic patients. Using Taiwan's National Health Insurance Research Database from 2009 to 2018, diabetic patients receiving metformin plus at least one second-line oral antidiabetic (OAD) were enrolled. The patients were categorized as DPP4 inhibitor users and non-users. Propensity score matching was employed to establish a 1:1 ratio between DPP4 inhibitor users and non-users. Among the 205,910 patients enrolled, 149 were diagnosed with PD during follow-up. The incidence rate was 0.29 per 1000 person-years for DPP4 inhibitor users and 0.55 per 1000 person-years for the non-users. DPP4 inhibitor users exhibited a significantly lower risk of PD (adjusted hazard ratio, 0.51; 95% CI 0.39-0.68). Among DPP4 inhibitor users, vildagliptin showed the strongest correlation with a reduction in the risk of PD. This study demonstrates that the use of DPP4 inhibitors along with metformin in diabetic patients is associated with a lower risk of PD compared to those using other OADs.

Parental Income Level and Risk of Developing Type 2 Diabetes in Youth.

Importance: In recent years, the global incidence of type 2 diabetes in young people has increased, especially among minoritized, Indigenous, or financially disadvantaged populations. However, few studies have examined whether poverty is associated with increased risk of youth-onset type 2 diabetes. Objective: To examine the association of family income level with the risk of youth-onset type 2 diabetes. Design, Setting, and Participants: This nationwide, population-based retrospective cohort study used data from the 2008 National Health Insurance Research Database of Taiwan, with follow-up through December 31, 2019. Participants included children and adolescents aged 0 to 19 years. Data analysis was performed from June 9, 2022, to January 16, 2023. Exposures: Family income, classified as very low, low, middle, and high. Main Outcomes and Measures: Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the risks of youth-onset type 2 diabetes and all-cause mortality for all income groups vs the high-income group. Results: The cohort included a total of 5 182 893 children and adolescents (mean [SD] age, 11.2 [5.2] years; 2 477 807 girls [48.3%]). The mean (SD) follow-up duration was 9.0 (0.3) years. The incidence rates of youth-onset type 2 diabetes were 0.52 cases per 1000 person-years for the very-low-income group, 0.40 cases per 1000 person-years for the low-income group, 0.35 cases per 1000 person-years for the middle-income group, and 0.28 cases per 1000 person-years for the high-income group. Children and adolescents from very-low-income (aHR, 1.55; 95% CI, 1.41-1.71), low-income (aHR, 1.34; 95% CI, 1.27-1.41), and middle-income (aHR, 1.27; 95% CI, 1.20-1.34) families had a significantly higher hazard of youth-onset type 2 diabetes than those from high-income families. Children and adolescents from very-low-income (aHR, 2.18; 95% CI, 1.97-2.41), low-income (aHR, 1.51; 95% CI, 1.42-1.60), and middle-income (aHR, 1.22; 95% CI, 1.14-1.31) families also had a significantly higher hazard of all-cause mortality than those from high-income families. Children and adolescents who were older, female, and obese and had dyslipidemia, gout, or psychiatric disorders had a significantly higher risk of youth-onset type 2 diabetes than children without those characteristics. Conclusions and Relevance: This population-based cohort study showed that children and adolescents from very-low-income to middle-income families had a higher hazard of youth-onset type 2 diabetes and mortality than those from high-income families. Further research to reveal the factors underlying this association may improve the accuracy of identifying individuals at greatest risk for developing type 2 diabetes in youth.

Risks of Topical Carbonic Anhydrase Inhibitors in Glaucoma Patients With Chronic Kidney Disease: A Nationwide Population-Based Study.

PURPOSE: To investigate the risks of metabolic acidosis and renal outcomes after topical carbonic anhydrase inhibitor (CAI) use in patients with both primary open-angle glaucoma (POAG) and advanced chronic kidney disease (CKD). DESIGN: Nationwide, population-based cohort study. METHODS: This study was conducted with population data from Taiwan's National Health Insurance (NHI) Research Database between January 2000 and June 2009. Patients with advanced CKD who were diagnosed with glaucoma (International Classification of Diseases, Ninth Revision [ICD-9] code 365) and had been receiving eye drops for glaucoma (including carbonic anhydrase inhibitors selected by NHI drug code) were enrolled. Using Kaplan-Meier methods, we compared the cumulative incidence of mortality, long-term dialysis, and cumulative incidence of metabolic acidosis over time between CAI users and CAI non-users. Primary outcomes comprised mortality, renal outcome (progression to hemodialysis), and metabolic acidosis. RESULTS: In this cohort, topical CAI users had a higher incidence of long-term dialysis than non-users (incidence = 1,216.85 vs 764.17 events per 100 patient-years; adjusted hazard ratio = 1.17, 95% CI = 1.01-1.37). Hospital admissions due to metabolic acidosis were higher in CAI users compared with non-users (incidence = 21.54 vs 11.87 events per 100 patient-years; adjusted hazard ratio = 1.89, 95% CI = 1.07-3.36). CONCLUSIONS: Topical CAIs may be associated with higher risks of long-term dialysis and metabolic acidosis in patients with POAG and pre-dialysis advanced CKD. Therefore, topical CAIs should be used with caution in advanced CKD patients.

Vegan Diet Is Associated with a Lower Risk of Chronic Kidney Disease in Patients with Hyperuricemia.

Hyperuricemia is a well-known risk factor for chronic kidney disease (CKD). Little is known about whether a vegetarian diet is associated with a lower risk of CKD in patients with hyperuricemia. From 5 September 2005, to 31 December 2016, we retrospectively included clinically stable patients with hyperuricemia who received health check-ups at Taipei Tzu Chi Hospital. All participants completed a dietary habits questionnaire to determine whether they were omnivorous, lacto-ovo vegetarian, or vegan. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 or the presence of proteinuria. A total of 3618 patients with hyperuricemia were recruited for this cross-sectional study, consisting of 225 vegans, 509 lacto-ovo vegetarians, and 2884 omnivores. After adjusting for age and sex, vegans had a significantly lower odds ratio (OR) of CKD than omnivores (OR, 0.62; p = 0.006). The OR of CKD remained significantly lower in vegans after adjusting for additional confounders (OR, 0.69; p = 0.04). Additionally, age (per year OR, 1.06; p < 0.001), diabetes mellitus (OR, 2.12; p < 0.001), hypertension (OR, 1.73; p < 0.001), obesity (OR, 1.24; p = 0.02), smoking (OR, 2.05; p < 0.001), and very high uric acid levels (OR, 2.08; p < 0.001) were independent risk factors for CKD in patients with hyperuricemia. Moreover, structural equation modeling revealed that a vegan diet was associated with a lower OR of CKD (OR, 0.69; p < 0.05). A vegan diet is associated with a 31% lower risk of CKD in patients with hyperuricemia. A vegan diet may be beneficial in reducing the occurrence of CKD in patients with hyperuricemia.

Risk of Major Cardiovascular Disease after Exposure to Contrast Media: A Nationwide Population-Based Cohort Study on Dialysis Patients.

Contrast associated kidney injury is caused by side effects of iodinated contrast media (ICM), including inflammation. Chronic inflammation among dialysis patient contributes to atherosclerosis, which leads to simultaneous conditions of the kidney, brain, and vasculature. Data to investigate the pathologic effects of ICM on cardiovascular complications in dialysis patients are lacking. Dialysis patients who had been exposed to ICM from computed tomography (ICM-CT) were allocated as the ICM-CT cohort (N = 3751), whereas dialysis patients without ICM exposure were randomly allocated as the non-ICM cohort (N = 17,196). Furthermore, 540 pairs were selected for analyses through propensity score-matching in terms of age, sex, comorbidities, dialysis vintage, and index date. During a median follow-up of 10.3 years, ICM-CT cohort had significantly higher risks in the following, compared with non-ICM cohort: all-cause mortality (adjusted hazard ratio [aHR], 1.36; 95% confidence interval [CI], 1.26-1.47), cardiovascular events (aHR,1.67; 95% CI, 1.39-2.01), acute coronary syndrome (adjusted HR: 2.92; 95% CI, 1.72-4.94), sudden cardiac arrest (aHR, 1.69; 95% CI, 0.90-3.18), heart failure (aHR, 1.71; 95% CI,1.28-2.27), and stroke (aHR, 1.84; 95% CI,1.45-2.35). The proinflammatory ICM is significantly associated with an increased risk of major cardiovascular events in patients on dialysis.

The Risk of Severe Hypoglycemia and Mortality in Patients With Type 2 Diabetes and Discharged With Acute Liver Injury.

OBJECTIVE: To compare the risks of severe hypoglycemia and mortality between patients with type 2 diabetes (T2D) and discharged with and without acute liver injury. RESEARCH DESIGN AND METHODS: From 1 January 2000 to 31 December 2010, we identified patients with T2D and hospitalization for acute liver injury and hospitalization for other causes from the National Health Insurance Research Database of Taiwan. Multivariable-adjusted Cox proportional hazards models were used to compare the risks of severe hypoglycemia and mortality between the study and control groups. RESULTS: The incidence rates and adjusted hazard ratios (aHRs) for severe hypoglycemia within 90 days and 365 days after discharge were 12.28 and 5.59/1,000 person-years (aHR 1.92 [1.30-2.85]) and 7.35 and 2.9/1,000 person-years (aHR 1.98 [1.52-2.58]) for patients discharged with and without acute liver injury, respectively. The incidence rates and aHRs for mortality within 90 days and 365 days after discharge were 82.4 and 27.54/1,000 person-years (aHR 1.73 [1.46-2.05]) and 36.8 and 9.3/1,000 person-years (aHR 1.94 [1.69-2.24]) for patients discharged with and without acute liver injury, respectively. The subgroup analysis of hypoglycemia risk in patients discharged with acute liver injury revealed no significant interaction in risk factors of age, chronic kidney disease, and medications, except for sex difference, which has significant interaction. CONCLUSIONS: This cohort study demonstrated that patients with T2D and discharged with acute liver injury showed significantly higher risks of severe hypoglycemia and mortality within 90 days and 365 days after discharge than patients discharged with other causes.

Clinical course of adolescents with type 2 diabetes mellitus: A nationwide cohort study in Taiwan.

AIMS/INTRODUCTION: The global incidence of adolescents with type 2 diabetes mellitus is increasing. This cohort study was conducted aiming to describe the characteristics, drug-use condition, and long-term outcomes of adolescents with type 2 diabetes mellitus. MATERIALS AND METHODS: Two thousand seven hundred fifty-five newly diagnosed adolescents with type 2 diabetes mellitus (using ICD-9-CM: 250.x and having ≥3 clinic visits) were identified from the national health insurance dataset during 2000-2014. Treatments were classified into four groups: metformin, sulfonylurea (SU), metformin plus SU, and insulin with or without oral antidiabetic drugs. The multiple Cox regression model was used to compare the risks of mortality and hospitalization among these four groups. RESULTS: The mean follow-up period was 5.4 years. After 1 year of antidiabetic treatment, they gradually needed intensified therapy, and at 3 years, half of them showed treatment failure. The mortality rate was 2.08 per 1,000 person-years. Respiratory diseases (36.2%) and dysglycemia (16.4%) were the most common causes of hospitalization among these adolescents. Compared with persons taking metformin plus SU, metformin users were associated with a lower risk of all-cause hospitalization [0.82 (0.67-0.99)]; insulin users were associated with a higher risk of dysglycemia [4.38 (2.14-8.96)], cancer [3.76 (1.39-10.1)], and respiratory hospitalization [1.66 (1.14-2.41)]; and SU users were associated with a higher risk of hospitalization for respiratory diseases [1.91 (1.13-3.23)]. CONCLUSIONS: This nationwide cohort study demonstrated that adolescents with type 2 diabetes mellitus were prone to treatment failure. Furthermore, respiratory diseases and dysglycemia were the most common causes of hospitalization.

Early Comprehensive Kidney Care in Dialysis-Requiring Acute Kidney Injury Survivors: A Populational Study.

Background: For patients with Acute Kidney Injury (AKI), a strong and graded relationship exists between AKI severity and mortality. One of the most severe entities of AKI is Dialysis-Requiring Acute Kidney Injury (D-AKI), which is associated with high rates of mortality and end-stage renal disease (ESRD). For this high-risk population group, there is a lack of evidence regarding optimal post-AKI care. We propose that post-AKI care through the combined efforts of the nephrologist and the multidisciplinary care team may improve outcomes. Our aim here is to study for survivors of dialysis-requiring acute kidney injury, the effects of implementing early comprehensive kidney care. Methods: This is a retrospective longitudinal cohort study of Taiwanese through analyzing the National Health Insurance Research Database (NHIRD). We included patients with acute dialysis during hospitalization from January 1, 2015 to December 31, 2018. Propensity match was done at 1:1, including estimated glomerular filtration rate (eGFR) based on CKD-EPI which was performed due to large initial disparities between these two cohorts. Results: After the propensity match, each cohort had 4,988 patients. The mean eGFR based on CKD-EPI was 27.5 ml/min/1.73 m2, and the mean follow-up period was 1.4 years.The hazard ratio for chronic dialysis or ESRD was 0.55 (95% CI, 0.49-0.62; p < 0.001). The hazard ratio for all-cause mortality was 0.79 (95% CI, 0.57-0.88; p < 0.001). Both outcomes favored early comprehensive kidney care. Conclusions: For survivors of dialysis-requiring acute kidney injury, early comprehensive kidney care significantly lowered risks of chronic dialysis and all-cause mortality.

Vegetarian Diet Was Associated With a Lower Risk of Chronic Kidney Disease in Diabetic Patients.

Introduction: Diabetes mellitus (DM) is a pathological hyperglycemic state related to the dysregulation of insulin. Chronic kidney disease (CKD) is a common chronic complication in diabetic patients. A vegetarian diet could be one of the preventive strategies for the occurrence of CKD in patients with diabetes mellitus. However, it is still unknown whether a vegetarian diet lowers the occurrence of CKD in DM patients. Research Design and Methods: This retrospective study was conducted at Taipei Tzu Chi Hospital from 5 September 2005 to 31 December 2016. Subjects with an HbA1c level > 6.5% or previous history of diabetes mellitus elder than 40 years were grouped based on self-reported dietary habits (vegetarians, lacto-ovo vegetarians and omnivores) in the structured questionnaire. Structural equation modeling (SEM) was applied to estimate the direct and indirect effects of variables on the occurrence of chronic kidney disease. Results: Among these 2,797 subjects, the participants were grouped into dietary habits as vegans (n = 207), lacto-ovo vegetarians (n = 941) and omnivores (n = 1,649). The incidence of overall CKD was higher in the omnivore group [36.6% vs 30.4% (vegans) and 28.5% (lacto-ovo vegetarian), p < 0.001]. In the SEM model, after adjusting for age and sex, the lacto-ovo vegetarian [OR: 0.68, 95% confidence interval (CI): 0.57-0.82] and vegan groups (OR 0.68, 95% CI: 0.49-0.94) were both associated with a lower risk of CKD occurrence than the omnivore group. The vegan diet and lacto-ovo diet lowered the risk related to a high BMI (OR: 0.45, p < 0.001, OR: 0.58, p < 0.001) and hyperuricemia (OR: 0.53, p < 0.001; OR: 0.55, p < 0.001) for the occurrence of CKD. Conclusion: Vegetarian dietary habits were associated with a lower occurrence of CKD in DM patients.

Association of anemia and iron parameters with mortality among prevalent peritoneal dialysis patients in Taiwan: the AIM-PD study.

In 1996, the National Health Insurance Administration of Taiwan applied a restrictive reimbursement criteria for erythropoiesis-stimulating agents (ESAs) use in patients with chronic kidney disease. The maximal ESAs dosage allowed by insurance is capped at 20,000 U of epoetin per month. Nephrologists avoided the use of high ESA dosages to achieve a hemoglobin level of 10-11 g/dL using iron supplementation. We assessed the association of anemia and iron parameters with mortality among peritoneal dialysis (AIM-PD) patients. A retrospective cohort study was conducted based on the Taiwan Renal Registry Data System. From January 1, 2000 to December 31, 2008, we enrolled 4356 well-nourished PD patients who were older than 20 years and had been receiving PD for more than 12 months. All patients were divided into subgroups according to different hemoglobin, ferritin and transferrin saturation (TSAT) values. Patients were followed until death or December 31, 2008. In a median 2.9-year study period, 694 (15.9%) patients died. By multivariate adjustment, a hemoglobin level lower than 10 g/dL was significantly associated with a higher risk for all-cause and cardiovascular deaths. Moreover, a serum ferritin level higher than 800 ng/mL was associated with a higher risk for all-cause deaths, and a TSAT value between 20 and 50% was associated with the lowest all-cause mortality. In conclusions, we recommend avoiding a low hemoglobin level and a serum ferritin level of more than 800 ng/mL and maintaining a TSAT value between 20 and 50%, as these conditions were associated with lower risks of all-cause mortality in the AIM-PD study.

Severe hypoglycemia in patients with liver cirrhosis and type 2 diabetes.

Introduction: Advanced liver disease with massive liver damage may affect the metabolism of hypoglycemic agents and increase the risk of hypoglycemia. We conduct this research to compare the risk of severe hypoglycemia between patients with type 2 diabetes, with and without compensated liver cirrhosis. Methods: From Taiwan's National Health Insurance Research Database, we identified persons with type 2 diabetes with cirrhosis (n = 18,209) and without cirrhosis (n = 538,510) from January 1, 2000, to December 31, 2010. Cox proportional hazards models were adopted to assess risks of all-cause mortality and severe hypoglycemia. Results: The mean follow-up period of this study was 3.7 years. The incidence rates of death during follow-up were 26.54 and 2.75 per 1,000 patient-years [aHR 7.63 (6.70-8.70)] for patients with cirrhosis and without cirrhosis, respectively. The incidence rates of severe hypoglycemia during follow-up were 0.53 and 0.14 per 1,000 patient-years [aHR 2.74 (1.52-4.92)] for patients with and without cirrhosis, respectively. The subgroup analysis of hypoglycemia risks in patients with and without cirrhosis disclosed no significant interaction for variables such as age, sex, chronic kidney disease, sulfonylurea use, number of oral antidiabetic drugs, insulin, b-blocker, and fibrate. Conclusion: This cohort study demonstrated that patients with type 2 diabetes and compensated cirrhosis showed a higher risk of mortality and severe hypoglycemia than those without liver cirrhosis.

Spectrum of cancer patients receiving renal biopsy.

BACKGROUND: The frontier of onco-nephrology, particularly renal complications of cancer and treatment, remains unexplored. We revisit the fundamental tool of diagnosing kidney disease, renal biopsy, in cancer patients with renal manifestation. METHODS: Patients who received renal biopsy from July 2015 to July 2019 were analyzed. Primary outcomes included end-stage renal disease (ESRD), mortality, and catastrophic outcome defined as either ESRD or mortality. A Cox proportional hazards model and Kaplan-Meier technique were used to assess the association with outcome measurements and survival analyses. Immunosuppression after renal biopsy and response to the treatment were evaluated. RESULTS: Among the 77 patients, the median age was 66 years (interquartile range [IQR] 59-73 years) and 46 (59.7%) were male. At the time of renal biopsy, 57 patients (74%) had various degrees of renal insufficiency. Tubulointerstitial damage score, quantified by renal pathology, were associated with higher hazards of ESRD (hazard ratio [HR], 1.77; 95% confidence interval [95% CI], 1.20 to 2.61; P = 0.004) and catastrophic outcome (HR, 1.30; 95% CI, 0.99 to 1.70; P = 0.058). The response rate to immunosuppression was lower in those diagnosed with tubulointerstitial nephritis (1 of 4 patients, 25%) than those with glomerulopathy (10 of 20 patients, 50%). CONCLUSION: Renal biopsy may improve diagnostic accuracy and assist in treatment guidance of cancer patients with renal manifestation. Renal biopsy should be encouraged with clinical indication. Collaboration between oncologists and nephrologists is of paramount importance to provide more comprehensive care for caner patients.

Outcomes of second-line oral antidiabetic drugs in persons with young-onset type 2 diabetes.

AIM: People with young-onset diabetes (YOD) exhibit a higher risk of morbidity and mortality than those with late-onset diabetes. Few studies have explored the preferred management of diabetes in such patients. We compared the risks of hospitalization and mortality among people with YOD to whom second-line oral antidiabetic drugs (OADs) were administered. METHODS: 7257 people taking second-line OADs after initial metformin therapy were enrolled during 2009-2014. Using add-on sulfonylureas (SUs) as a reference, the multivariable Cox regression model was used to compare the hospitalization and mortality risks among 5 categories of second-line OADs: alpha-glucosidase inhibitors, meglitinide, dipeptidyl peptidase-4 (DPP-4) inhibitors, SUs, and thiazolidinediones. RESULTS: After baseline characteristics, comorbidities, duration of diabetes, and drug use were controlled, the adjusted hazard ratios and 95% confidence interval for all-cause, cardiovascular, and non-infection hospitalization and all-cause mortality for metformin plus DPP-4 inhibitors were 0.62 (0.52-0.73), 0.49 (0.29-0.85), 0.64 (0.54-0.76), and 0.50 (0.27-0.92), respectively, when compared with the data for metformin plus SUs. CONCLUSIONS: Among people with YOD, taking add-on DPP-4 inhibitors was associated with lower risks of all-cause hospitalization and mortality than taking add-on SUs. DPP-4 inhibitors thus seem to be a suitable second-line OAD for such patients.

Angiopoietin-2 is associated with metabolic syndrome in chronic kidney disease.

BACKGROUNDS: Metabolic syndrome is a subclinical status in promoting atherosclerotic cardiovascular disease and type 2 diabetes mellitus. The significance of metabolic syndrome and pathophysiology in chronic kidney disease is not investigated. METHODS: We enrolled adult patients with CKD stages 3 to 5 from December 2006 to December 2007. Metabolic syndrome was defined by the US National Cholesterol Education Programme Adult Treatment Panel III guidelines. Plasma levels of angiogenic growth factors were measured. Univariate and multivariate logistic regression analyses were used. RESULTS: Total 451 patients were analyzed with median estimated glomerular filtration rate of 27.0 ml/min per 1.73m2 (interquartile range 14.3-41.3). Patients with metabolic syndrome were older (P = 0.002), had higher percentage using diuretics (P = 0.002) but lower percentage using pentoxifylline (P = 0.017). Patients with metabolic syndrome had higher levels of high-sensitivity C-reactive protein (P < 0.0001), uric acid (P = 0.009) and angiopoietin-2 (P = 0.001). Multivariate logistic regression analyses revealed significant association between plasma levels of angiopoietin-2 and metabolic syndrome (P = 0.042). CONCLUSION: The prevalence of metabolic syndrome in advanced CKD was higher than general population. CKD patients with metabolic syndrome had higher levels of high-sensitivity C-reactive protein, uric acid and angiopoietin-2. Plasma levels of angiopoietin-2 were significantly associated with metabolic syndrome in patients with CKD. Metabolic syndrome in CKD may be not only a prognostic factor but also an interventional target, possibly through ameliorating inflammation. Prospective and interventional studies are necessary to establish the pathophysiology.

Comparative effectiveness of bisoprolol and carvedilol among patients receiving maintenance hemodialysis.

BACKGROUND: Despite widespread use, there is no trial evidence to inform ß-blocker's (BB) relative safety and efficacy among patients undergoing hemodialysis (HD). We herein compare health outcomes associated with carvedilol or bisoprolol use, the most commonly prescribed BBs in these patients. METHODS: We created a cohort study of 9305 HD patients who initiated bisoprolol and 11 171 HD patients who initiated carvedilol treatment between 2004 and 2011. We compared the risk of all-cause mortality and major adverse cardiovascular events (MACEs) between carvedilol and bisoprolol users during a 2-year follow-up. RESULTS: Bisoprolol initiators were younger, had shorter dialysis vintage, were women, had common comorbidities of hypertension and hyperlipidemia and were receiving statins and antiplatelets, but they had less heart failure and digoxin prescriptions than carvedilol initiators. During our observations, 1555 deaths and 5167 MACEs were recorded. In the multivariable-adjusted Cox model, bisoprolol initiation was associated with a lower all-cause mortality {hazard ratio [HR] 0.66 [95% confidence interval (CI) 0.60-0.73]} compared with carvedilol initiation. After accounting for the competing risk of death, bisoprolol use (versus carvedilol) was associated with a lower risk of MACEs [HR 0.85 (95% CI 0.80-0.91)] and attributed to a lower risk of heart failure [HR 0.83 (95% CI 0.77-0.91)] and ischemic stroke [HR 0.84 (95% CI 0.72-0.97)], but not to differences in the risk of acute myocardial infarction [HR 1.03 (95% CI 0.93-1.15)]. Results were confirmed in propensity score matching analyses, stratified analyses and analyses that considered prescribed dosages or censored patients discontinuing or switching BBs. CONCLUSIONS: Relative to carvedilol, bisoprolol initiation by HD patients was associated with a lower 2-year risk of death and MACEs, mainly attributed to lower heart failure and ischemic stroke risk.

Persons with type 2 diabetes and high insulin persistence were associated with a lower risk of mortality: A nationwide retrospective cohort study.

AIMS/INTRODUCTION: Studies assessing the long-term outcomes of insulin persistence are scant. We compared the risk of all-cause mortality among patients with different degrees of insulin persistence. MATERIALS AND METHODS: In total, 293,210 patients with type 2 diabetes mellitus undergoing insulin therapy were enrolled during 2002-2014. Insulin persistence was defined as continual insulin treatment without a 90-day gap of discontinuation in the 2-year observation period. Mortality rates were compared between 111,220 patients with ≥90% insulin persistence and 111,220 matched patients with <90% insulin persistence during the observational period. RESULTS: During the mean 5.37-year follow-up period, the mortality rates were 58.26 and 73.21 per 1,000 person-years for patients with ≥90% and <90% of insulin persistence. The adjusted hazard ratio for mortality was 0.80 (95% confidence interval 0.79-0.81, P < 0.001). Patients with high insulin persistence had significantly lower risks than did those with low insulin persistence of death due to hypertension, diabetes, cardiovascular disease, liver disease, kidney disease, respiratory disease, sepsis and cancer. CONCLUSIONS: This study showed that patients with ≥90% insulin persistence were associated with lower risks of all-cause mortality than did patients with <90% insulin persistence.

Effect of Renin-Angiotensin-Aldosterone System Blockade on Long-Term Outcomes in Postacute Kidney Injury Patients With Hypertension.

OBJECTIVES: Renal replacement therapy-requiring acute kidney injury frequently occurs in ICUs, which require evidence-based medical attention. However, in the postacute kidney injury patient population, the evidence regarding effective therapies to improve patient outcomes is lacking. Therefore, we aimed to examine whether the renin-angiotensin-aldosterone system blockade is effective in improving renal outcomes in postacute kidney injury patients who experienced temporary renal replacement therapy and have hypertension. DESIGN: A retrospective cohort study. SETTING: A nationwide database in Taiwan. PATIENTS: From January 1, 2000, to December 31, 2013, we identified 8,558 acute kidney injury patients with hypertension in the national registry database. All these patients experienced an acute kidney injury episode, which required temporary renal replacement therapy for at least once. INTERVENTIONS: Users (n = 3,885) and nonusers (n = 4,673) of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. MEASUREMENTS AND MAIN RESULTS: We used Cox proportional hazards regression models to analyze hazard ratios for the commencement of end-stage renal disease and all-cause mortality for angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users (n = 3,885) and nonusers (n = 4,673).In a median follow-up of 4.3 years, 5,880 patients (68.7%) required long-term dialysis, and 4,841 patients (56.6%) died. Compared with postacute kidney injury patients who did not use angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users are marginally less likely to progress to end-stage renal disease (adjusted hazard ratio 0.95; 95% CI 0.90-1.01; p = 0.06) and significantly less likely to suffer from all-cause mortality (adjusted hazard ratio 0.93; 95% CI 0.87-0.98; p = 0.011). CONCLUSIONS: In patients who experienced renal replacement therapy-requiring acute kidney injury and have hypertension, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use is associated with better survival outcomes compared with nonuser.

The factors associated with insulin nonpersistence in persons with type 2 diabetes.

AIMS: Implementation of insulin therapy among those with diabetes is often suboptimal as a result of non-adherence or non-persistence. Studies regarding factors leading to insulin nonpersistence are limited. Therefore, we conducted this retrospective cohort study to determine the factors affecting insulin nonpersistence. METHODS: A total of 274,852 persons with type 2 diabetes mellitus under insulin therapy during the period 2000-2014 were enrolled. Persons who stopped insulin therapy for >90 days were defined as having insulin nonpersistence. We searched for factors associated with insulin nonpersistence during the long-term follow-up period. RESULTS: According to the multiple Cox regression model with a mean follow-up of 13.9 years, the factors associated with higher risk of insulin nonpersistence were age <40 years, men, residing in a rural area, Charlson comorbidity index score = 4, use of two or more oral antidiabetic drugs, and hypoglycemia during follow-up. The Kaplan-Meier graph showed that patients aged <40 years had significantly less insulin persistence. CONCLUSIONS: This nationwide cohort study indicated that persons with young-onset type 2 diabetes, less medical resources, and more comorbidities are at risk of insulin nonpersistence. Healthcare providers should regularly assess insulin persistence and help patients who are having difficulty with insulin-taking.