Metformin use and cirrhotic decompensation in patients with type 2 diabetes and liver cirrhosis.

AIMS: To compare the risks of all-cause mortality, hepatic outcomes, major adverse cardiovascular events between metformin users and nonusers for patients with diabetes and cirrhosis. METHODS: From the Taiwan's National Health Insurance Research Database, we selected propensity-score matched metformin users and nonusers from the cohorts of type 2 diabetes mellitus with compensated (n = 26 164) or decompensated liver cirrhosis (n = 15 056) between 1 January 2000 and 31 December 2009, and followed them until 31 December 2010. Cox proportional hazards models with robust sandwich standard error estimates were used to assess risk of investigated outcomes for metformin users. RESULTS: The incidence rates of mortality during follow-up were 3.8 and 3.3 per 100 patient-years (adjusted hazard ratio [aHR] 1.13, 95% confidence interval 1.01-1.25) for metformin users and nonusers, respectively. The incidence rates of cirrhotic decompensation during follow-up were 5.9 and 4.9 per 100 patient-years (aHR 1.15, 95% confidence interval 1.04-1.27) for metformin users and nonusers. The risk of death (P for trend <.01) and cirrhotic decompensation (P for trend <.0001) associated with metformin use was significant for those taking metformin for >40 defined daily doses in 90 days or >1000 mg/d. The outcomes of metformin use vs nonuse for type 2 diabetes mellitus with decompensated liver cirrhosis were not statistically different, except that metformin users had higher risk of mortality (aHR 1.15). CONCLUSION: Metformin use was associated with higher risks of mortality and cirrhotic decompensation in patients with compensated liver cirrhosis. Prospective studies are required to confirm our results.

Increased APOE glycosylation plays a key role in the atherogenicity of L5 low-density lipoprotein.

Low-density lipoprotein (LDL) is heterogeneous, composed of particles with variable atherogenicity. Electronegative L5 LDL exhibits atherogenic properties in vitro and in vivo, and its levels are elevated in patients with increased cardiovascular risk. Apolipoprotein E (APOE) content is increased in L5, but what role APOE plays in L5 function remains unclear. Here, we characterized the contributions of APOE posttranslational modification to L5's atherogenicity. Using two-dimensional electrophoresis and liquid chromatography-mass spectrometry, we studied APOE's posttranslational modification in L5 from human plasma. APOE structures with various glycan residues were predicted. Molecular docking and molecular dynamics simulation were performed to examine the functional changes of APOE resulting from glycosylation. We also examined the effects of L5 deglycosylation on endothelial cell apoptosis. The glycan sequence N-acetylgalactosamine, galactose, and sialic acid was consistently expressed on serine 94, threonine 194, and threonine 289 of APOE in L5 and was predicted to contribute to L5's negative surface charge and hydrophilicity. The electrostatic force between the negatively charged sialic acid-containing glycan residue of APOE and positively charged amino acids at the receptor-binding area suggested that glycosylation interferes with APOE's attraction to receptors, lipid-binding ability, and lipid transportation and metabolism functions. Importantly, L5 containing glycosylated APOE induced apoptosis in cultured endothelial cells through lectin-like oxidized LDL receptor-1 (LOX-1) signaling, and glycosylation removal from L5 attenuated L5-induced apoptosis. APOE glycosylation may contribute to the atherogenicity of L5 and be a useful biomarker for rapidly quantifying L5.

The role of postprandial very-low-density lipoprotein in the development of atrial remodeling in metabolic syndrome.

BACKGROUND: Negatively charged very-low-density lipoprotein (VLDL-χ) in metabolic syndrome (MetS) patients exerts cytotoxic effects on endothelial cells and atrial myocytes. Atrial cardiomyopathy, manifested by atrial remodeling with a dilated diameter, contributes to atrial fibrillation pathogenesis and predicts atrial fibrillation development. The correlation of VLDL-χ with atrial remodeling is unknown. This study investigated the association between VLDL-χ and remodeling of left atrium. METHODS: Consecutively, 87 MetS and 80 non-MetS individuals between 23 and 74 years old (50.6% men) without overt cardiovascular diseases were included in the prospective cohort study. Blood samples were collected while fasting and postprandially (at 0.5, 1, 2, and 4 h after a unified meal). VLDL was isolated by ultracentrifugation; the percentile concentration of VLDL-χ (%) was determined by ultra-performance liquid chromatography. The correlations of left atrium diameter (LAD) with variables including VLDL-χ, LDL-C, HDL-C, triglycerides, glucose, and blood pressure, were analyzed by multiple linear regression models. A hierarchical linear model was conducted to test the independencies of each variable's correlation with LAD. RESULTS: The mean LAD was 3.4 ± 0.5 cm in non-MetS subjects and 3.9 ± 0.5 cm in MetS patients (P < 0.01). None of the fasting lipid profiles were associated with LAD. VLDL-χ, BMI, waist circumference, hip circumference, and blood pressure were positively correlated with LAD (all P < 0.05) after adjustment for age and sex. Significant interactions between VLDL-χ and blood pressure, waist circumference, and hip circumference were observed. When adjusted for obesity- and blood pressure-related variables, 2-h postprandial VLDL-χ (mean 1.30 ± 0.61%) showed a positive correlation with LAD in MetS patients. Each 1% VLDL-χ increase was estimated to increase LAD by 0.23 cm. CONCLUSIONS: Postprandial VLDL-χ is associated with atrial remodeling particularly in the MetS group. VLDL-χ is a novel biomarker and may be a therapeutic target for atrial cardiomyopathy in MetS patients. TRIAL REGISTRATION: ISRCTN 69295295 . Retrospectively registered 9 June 2020.

Determinants for quality of life trajectory patterns in patients with type 2 diabetes.

PURPOSE: The purpose of the study was to identify quality of life (QoL) trajectory patterns and the determinants in patients with Type 2 diabetes (T2DM). METHODS: A longitudinal design was employed. Totally, 466 patients with T2DM recruited from five diabetic clinics in Taiwan were participants of this study. Demographic and disease characteristics, biomedical factors (HbA1c levels and body mass index), psychosocial factors (self-care behaviors, social support, resilience, diabetes distress), and QoL were collected at baseline. QoL was further measured every 6 months for four waves after baseline. Latent class growth analysis was used to identify QoL trajectory patterns. The multinomial logistic regression was further applied to explore the important determinants of different QoL trajectory patterns. RESULTS: The "steadily poor" (n = 27, 5.8%), "consistently moderate" (n = 174, 37.3%), and "consistently good" (n = 265, 56.9%) trajectory patterns were identified. The HbA1c levels (OR 2.16) and diabetes distress (OR 1.18) were important for determining participants in the "steadily poor" QoL trajectory pattern. HbA1c levels (OR 1.25) and diabetes distress (OR 1.14) were important for determining participants in the "consistently moderate" QoL trajectory pattern. CONCLUSIONS: To prevent development of relatively worse QoL trajectory patterns in patients with T2DM in a timelier manner, healthcare providers could regularly assess the QoL and provide intervention, especially for those with high HbA1c levels and high diabetes distress. Meanwhile, early intervention for decreasing HbA1c levels and diabetes distress may improve the trajectory development of QoL in patients with T2DM.

GREATER LOW-DENSITY LIPOPROTEIN CHOLESTEROL VARIABILITY INCREASES THE RISK OF CARDIOVASCULAR EVENTS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS.

Objective: Variability in lipid levels has been associated with poor cardiovascular outcomes in patients with coronary artery disease. The aim of this study was to investigate whether low-density lipoprotein cholesterol (LDLC) variability can be used to predict cardiovascular events in patients with type 2 diabetes mellitus (DM). Methods: A total of 5,354 patients with type 2 DM were enrolled in this study. Cardiovascular events including peripheral arterial disease, coronary artery disease, stroke, and cardiovascular death were defined as the study endpoints, and standard deviations of lipid levels were used to define intra-individual lipid variability. Results: Univariate Cox proportional hazards analysis showed that LDL-C standard deviation (hazard ratio [HR] = 1.016; 95% confidence interval [CI] = 1.006 to 1.022; P<.001) was associated with a higher risk of cardiovascular events. Multivariate Cox proportional hazards analysis showed that an increase in LDL-C standard deviation significantly increased the risk of cardiovascular events (HR = 1.063; 95% CI = 1.025 to 1.102; P = .01). Kaplan-Meier analysis of cardiovascular event-free survival showed that the patients in tertiles 2 and 3 of the standard deviation of LDL-C had worse cardiovascular event-free survival compared to those in tertile 1. Conclusion: Variability in LDL-C could predict cardiovascular events in the patients with type 2 DM in this study. Abbreviations: CAD = coronary artery disease; CI = confidence interval; CVD = cardiovascular disease; DM = diabetes mellitus; eGFR = estimated glomerular filtration rate; HbA1c = glycosylated hemoglobin; HDL-C = high-density lipoprotein cholesterol; HR = hazard ratio; KMUHRD = Kaohsiung Medical University Hospital Research Database; LDL-C = low-density lipoprotein cholesterol; SD = standard deviation; UACR = urine albumin to creatinine ratio.

Successful management of type IV hypersensitivity reactions to human insulin analogue with injecting mixtures of biphasic insulin aspart and dexamethasone.

Although hypersensitivity reaction to insulin was supposed to be less-frequent with current insulin analogue, case reports with different types of allergic reactions to insulin analogue were still reported. The most common form is type I hypersensitivity reaction with IgE-mediated. Besides, type III (IgG and IgM-mediated) and type IV (T-cell mediated delayed reaction) hypersensitivity reactions were also reported. Here we presented a long-standing type 2 diabetes with insulin requirements with hypersensitivity reactions to insulin actrapid, insulin aspart, insulin glargine, insulin detemir, and biphasic insulin aspart 30. Insulin desensitization was performed as initial management but failed as skin biopsy with immunohistochemical staining proved type IV hypersensitivity reaction. We continued with the next treatment approach using subcutaneous injection with the mixture of biphasic insulin aspart 30 and dexamethasone to alleviate allergy, and the result was successful with steroid-free biphasic insulin aspart 30 injection eight months later. Besides, the treatment effect had lasted after ten years even with switched type of insulin analogue from biphasic insulin aspart 30 to insulin glargine and insulin aspart. The case report demonstrated a good example of how clinicians deal with the rare but important questions of hypersensitivity reactions to insulin analogue.

Hospitalization in patients with type 2 diabetes mellitus in Taiwan: A nationwide population-based observational study.

BACKGROUND/PURPOSE: We investigated hospitalization rates of patients with type 2 diabetes mellitus (T2DM) and individuals without diabetes mellitus (non-DM) in a disease-specific manner from 2005 to 2014 in Taiwan. METHODS: This population-based study was conducted using data from the National Health Insurance Research Database. We analyzed the hospitalization rates of patients with and without T2DM. We collected up to five diagnostic codes given at discharge for each hospitalization, and the first one was considered the main diagnosis. Odds ratios were determined to assess the risk of hospitalization according to disease-specific classifications in patients with T2DM compared with those without T2DM. RESULTS: The hospitalization rates of non-DM patients was stable from 2005 to 2014. By contrast, the rate of hospitalization among patients with T2DM decreased from 395.4 (per 1000 person-years) in 2005 to 336.9 (per 1000 person-years) in 2014. An increase in hospitalization rates for malignancies and sepsis/infection (other than pneumonia) was observed from 2005 to 2014 in both patients with and without T2DM. Although patients with T2DM had a higher hospitalization risk for all the disease-specific classifications than non-DM patients, this difference in risk decreased from 2005 to 2014 for all diseases except pneumonia. CONCLUSION: Hospitalization rates for malignancies and sepsis/infection (other than pneumonia) continually increased from 2005 to 2014 in Taiwan. Although patients with T2DM had a greater risk of disease-specific hospitalization than those without, this difference in risk decreased from 2005 to 2014 for all diseases except for pneumonia.

Diabetes-related kidney, eye, and foot disease in Taiwan: An analysis of nationwide data from 2005 to 2014.

BACKGROUND/PURPOSE: Patients with diabetes have a higher risk of developing chronic complications and cause a huge burden to the public health care system as well as on patients and their families. We studied these diabetic complications about kidney, eye and peripheral vascular diseases to understand their prevalence and distributions in a national survey. METHODS: We analyzed diabetic complications using National-Health-Insurance claims filed from 2005 to 2014. We used this database to evaluate their developments of kidney, eye, and peripheral vascular diseases according to the International-Classification-of-Diseases, Ninth Revision using clinical modification diagnosis codes. RESULTS: The prevalence of diabetic kidney disease (DKD) significantly increased from 10.49% to 17.92% from 2005 to 2014. The prevalence rate of diabetic foot significantly decreased from 1.34% to 1.05% from 2005 to 2014, and the rate of severe infection also significantly decreased from 50.69% to 45.85%. The amputation rate significantly decreased from 24.91% to 17.47% among all patients with diabetic foot. CONCLUSION: In this study, the trends in DKD and dialysis prevalence were similar to those of the 2012 report. The rate of increase in dialysis prevalence is lower in this study than in the 2012 report. The prevalence of diabetic foot, severe infection, and amputation in this report exhibited significantly decreasing trends. This improvement may be attributable to care from multidisciplinary teams. We should dedicate more resources to our prevention program of DKD and retinopathy to further improve outcomes in the future.

ASSOCIATIONS BETWEEN TRIGLYCERIDE/HIGH-DENSITY LIPOPROTEIN CHOLESTEROL RATIO AND MICRO- AND MACROANGIOPATHIES IN TYPE 2 DIABETES MELLITUS.

OBJECTIVE: The triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio has been reported to be a marker of insulin resistance. The aim of this study was to investigate associations between the TG/HDL-C ratio and micro- and macroangiopathies in patients with type 2 diabetes mellitus (DM). METHODS: A total of 1,981 (851 male and 1,130 female) patients with type 2 DM were enrolled from our outpatient clinic. These patients were stratified into 4 groups according to TG/HDL-C ratio quartiles. RESULTS: There were significant trends for stepwise increases in albuminuria ≥30 mg/g ( P<.001), coronary artery disease (CAD, P = .040), cerebrovascular disease (CVA, P = .002) and ankle-brachial index (ABI) <0.9 ( P = .001) corresponding to TG/HDL-C ratio quartiles, but not diabetic retinopathy ( P = .105). Furthermore, quartile 4 of the TG/HDL-C ratio was significantly associated with albuminuria, CAD, CVA, and ABI <0.9 after multivariate analysis compared to quartile 1. CONCLUSION: A high TG/HDL-C ratio was significantly associated with albuminuria, CAD, CVA, and peripheral artery occlusive disease (PAOD) in patients with DM, which translated into an increased risk of cardiovascular disease. ABBREVIATIONS: ABI = ankle-brachial index; ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin II receptor blocker; BMI = body mass index; CAD = coronary artery disease; CI = confidence interval; CVA = cerebrovascular disease; DM = diabetes mellitus, DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin A1c; HDL-C = high-density lipoprotein cholesterol; OR = odds ratio; PAOD = peripheral artery occlusive disease; TGs = triglycerides.

Statin therapy prevents the onset of Parkinson disease in patients with diabetes.

OBJECTIVE: We studied the association between the statin dosage and the risk of Parkinson disease (PD) in diabetic patients in Taiwan. METHODS: One million patients were randomly sampled from a National Health Insurance (NHI) database and followed from 2001 to 2008. Diabetic patients were screened by diagnosis of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, and statin dosage was determined according to the NHI pharmacy database. PD was diagnosed on the basis of ICD-9-CM codes and anti-Parkinson medication use. Statin users was classified by statin dose-duration-day > 28 and matched with nonusers of statins using a coarsened exact matching method. There were 50,432 patients, and half of them were statin users. We examined the risk of PD between statin users and nonusers of statins and further tested the trends of the relative risk between the statin dosage and PD. RESULTS: The PD incidence rate was lower in statin users than in nonusers of statins. The crude hazard ratio of PD incidence in statin users was 0.65 (95% confidence interval [CI] = 0.57-0.74) in females and 0.60 (95% CI = 0.51-0.69) in males compared with nonusers of statins. After Cox regression analysis, all statins except lovastatin exerted protective effects on PD incidence and had a significant dose-dependent trend. INTERPRETATION: In Taiwanese diabetic patients, the risk of PD is lower in statin users than in nonusers of statins. Statin users, except lovastatin users, are dose-dependently associated with a decreased incidence of PD compared with nonusers of statins. This finding provides a new indication for statin beyond lipid control and cardiovascular events in diabetic patients. Ann Neurol 2016;80:532-540.

A diabetes pay-for-performance program and the competing causes of death among cancer survivors with type 2 diabetes in Taiwan.

OBJECTIVE: To examine associations between a diabetes pay-for-performance (P4P) program in Taiwan and all-cause of mortality and competing causes of death in cancer survivors with type 2 diabetes. DESIGN: A longitudinal observational intervention and comparison group study design. SETTING AND PARTICIPANTS: Cancer survivors with type 2 diabetes who enrolled in the P4P program compared with survivors who did not participate (non-P4P) under the Taiwan National Health Insurance program. INTERVENTION(S): A nationwide diabetes P4P program. MAIN OUTCOME MEASURES: The main outcome was a comparison of all-cause, diabetes-related and cancer mortality in P4P and non-P4P patients during a 5-year follow-up period. Total person-years and mortality rates per 1000 person-years for causes of death were calculated. Multivariate Cox proportional hazard models and competing risk regression were used in the analysis. RESULTS: Overall, our results indicate that P4P cancer survivors had lower risk of all-cause mortality and diabetes-related mortality than non-P4P survivors. Specifically, the hazard ratio (95% confidence interval) was 0.581 (0.447-0.756) for all-cause mortality; SHRs were 0.451 (0.266-0.765) for diabetes-related mortality and 0.791 (0.558-1.121) for cancer mortality. CONCLUSIONS: Our empirical findings provide evidence of potential benefits of diabetes P4P programs in reducing risks of deaths due to diabetes or cardiovascular diseases among cancer survivors, compared with survivors who did not enroll in the P4P program. In consideration of recommended care for long-term survival, the diabetes P4P program can serve as a care model for cancer survivors for reducing mortality due to diabetes or cardiovascular diseases.

A Diabetes Pay-for-Performance Program and Risks of Cancer Incidence and Death in Patients With Type 2 Diabetes in Taiwan.

INTRODUCTION: We sought to evaluate the effects of diabetes disease management through a diabetes pay-for-performance (P4P) program in Taiwan on risks of incident cancer and mortality among patients with type 2 diabetes. METHODS: We conducted a longitudinal observational cohort study using 3 population-based databases in Taiwan. Using propensity score matching, we compared patients with type 2 diabetes who enrolled in a P4P program with a similar group of patients who did not enroll in the in P4P program (non-P4P). Primary end points of interest were risks of incident cancer and all-cause, cancer-specific, and diabetes-related mortality. Total person-years and incidence and mortality rates per 1,000 person-years were calculated. Multivariable Cox proportional hazard models and competing risk regression were used in the analysis. RESULTS: Overall, our findings indicated that the diabetes P4P program was not significantly associated with lower risks of cancer incidence, but it was associated with lower risks of all-cause mortality (adjusted subdistribution hazard ratio [aSHR], 0.59; 95% confidence interval [CI], 0.55-0.63), cancer-specific mortality (aSHR, 0.85; 95% CI, 0.73-1.00), and diabetes-related mortality (aSHR, 0.54: 95% CI, 0.49-0.60). Metformin, thiazolidinediones, and α glucosidase inhibitors were associated with lower risks of cancer incidence and cancer-specific mortality. CONCLUSION: Our findings provide evidence of the potential benefit of diabetes P4P programs in reducing risks of all-cause mortality and competing causes of death attributable to cancer-specific and diabetes-related mortality among type 2 diabetes patients.

The effectiveness of multimedia education for patients with type 2 diabetes mellitus.

AIMS: The aim of this study was to explore the effectiveness of two types of health education on improving knowledge concerning diabetes and insulin injection, insulin injection skills and self-efficacy, satisfaction with health education and glycated haemoglobin (HbA1c) and creatinine levels among patients with type 2 diabetes who began insulin therapy using a pen injector. BACKGROUND: Insulin therapy is recommended to facilitate the regulation of plasma glucose; however, patient's acceptance of insulin therapy is generally low. Healthcare providers should help them improve their knowledge of diabetes and insulin injection, as well as their insulin injection skills. DESIGN: A randomized repeated measures experimental study design. METHODS: The experimental (n = 21) and control (n = 21) groups received multimedia and regular health education programmes, respectively from October 2013-August 2014. Four structured questionnaires were used and videotapes were applied to demonstrate injection skills. RESULTS: Generalized estimating equations showed that the experimental group's scores were significantly higher than those of the control group for diabetes and insulin injection knowledge, insulin injection skills, self-efficacy in insulin injection and satisfaction with health education. On the other hand, an analysis of covariance revealed glycated hemoglobin (HbA1c) and creatinine levels did not differ significantly between the two groups. CONCLUSIONS: Implementation of a multimedia diabetes education programme could improve patients' diabetes and insulin injection knowledge, insulin injection skills, self-efficacy in insulin injection and satisfaction with health education. Healthcare providers should improve quality of patient care by providing multimedia diabetes health education.

Associations of changes in psychosocial factors and their interactions with diabetes distress in patients with type 2 diabetes: a longitudinal study.

AIM: To assess the associations of changes in self-management behaviours, diabetes self-efficacy, resilience, social support, patient empowerment and their interactions with changes in diabetes distress in patients with type 2 diabetes mellitus. BACKGROUND: Many patients with type 2 diabetes mellitus experience diabetes distress. Few longitudinal studies have investigated the associations of changes in various psychosocial factors with changes in diabetes distress in patients with type 2 diabetes mellitus. DESIGN: This study adopted a longitudinal design. Data were collected at baseline and 12 months later. METHODS: Overall, 304 patients with type 2 diabetes were recruited from four hospitals in southern Taiwan by convenience sampling. A self-report questionnaire and medical record were used to collect demographic data, clinical indicators, self-management behaviours, diabetes self-efficacy, resilience, social support, patient empowerment, and diabetes distress. Data were collected from February 2014-March 2015. RESULTS/FINDINGS: An increase in resilience or diabetes self-efficacy significantly associated with a decrease in diabetes distress, whereas an increase in patient empowerment significantly associated with an increase in diabetes distress. The interactions between increase in patient empowerment and increase in self-management behaviours significantly associated with decrease in diabetes distress. CONCLUSION: Nurses could endeavour to improve the diabetes self-efficacy and resilience to reducing diabetes distress. Arbitrarily empowering patients may increase diabetes distress. Increasing self-care management behaviours and patient empowerment might need to be simultaneously addressed to reduce the diabetes distress in patients with type 2 diabetes.

Electronegative low density lipoprotein induces renal apoptosis and fibrosis: STRA6 signaling involved.

Dyslipidemia has been proven to capably develop and aggravate chronic kidney disease. We also report that electronegative LDL (L5) is the most atherogenic LDL. On the other hand, retinoic acid (RA) and RA receptor (RAR) agonist are reported to be beneficial in some kidney diseases. "Stimulated by retinoic acid 6" (STRA6), one retinol-binding protein 4 receptor, was recently identified to regulate retinoid homeostasis. Here, we observed that L5 suppressed STRA6 cascades [STRA6, cellular retinol-binding protein 1 (CRBP1), RARs, retinoid X receptor α, and retinol, RA], but L5 simultaneously induced apoptosis and fibrosis (TGFß1, Smad2, collagen 1, hydroxyproline, and trichrome) in kidneys of L5-injected mice and L5-treated renal tubular cells. These L5-induced changes of STRA6 cascades, renal apoptosis, and fibrosis were reversed in kidneys of LOX1(-/-) mice. LOX1 RNA silencing and inhibitor of c-Jun N-terminal kinase and p38MAPK rescued the suppression of STRA6 cascades and apoptosis and fibrosis in L5-treated renal tubular cells. Furthermore, crbp1 gene transfection reversed downregulation of STRA6 cascades, apoptosis, and fibrosis in L5-treated renal tubular cells. For mimicking STRA6 deficiency, efficient silencing of STRA6 RNA was performed and was found to repress STRA6 cascades and caused apoptosis and fibrosis in L1-treated renal tubular cells. In summary, this study reveals that electronegative L5 can cause kidney apoptosis and fibrosis via the suppression of STRA6 cascades, and implicates that STRA6 signaling may be involved in dyslipidemia-mediated kidney disease.

Effectiveness of Pay-for-Performance Incentive Designs on Diabetes Care.

BACKGROUND: Taiwan's National Health Insurance program implemented a pay-for-performance (P4P) program based on process measures in 2001. In late 2006, the P4P was revised to also include achievement of outcome measures. OBJECTIVES: This study examined whether a change in P4P incentive design structure affected diabetes outcomes. RESEARCH DESIGN AND METHOD: We used a longitudinal cohort study design using 2 population-based databases. Newly enrolled P4P patients with diabetes in 2002-2003 (phase 1) and 2007-2008 (phase 2) made up the study cohorts. Propensity score matching was used to match comparable cohorts in each phase. In total, 46,286 matched cohorts in phase 1 and 2 were analyzed. Process measures were defined as the provision of tests of glycosylated hemoglobin A1c (HbA1c), low-density lipoprotein cholesterol, and blood pressure, and outcome measures as changes in those values between baseline and last follow-up within 3 years. Patient-level generalized linear regression models were used and patient characteristics, physician characteristics, and health care facility characteristics were adjusted for. RESULTS: Our results indicated that the process measures of HbA1c and low-density lipoprotein cholesterol tests did not differ significantly between the 2 phases. In addition, better improvements were noted in outcome measures for the phase 2 patients (ie, HbA1c level and lipid profiles), whereas nonincentivized intermediate measures (eg, blood pressure) showed no negative unintended consequences. CONCLUSIONS: Quality of care tended to be better when both process and targeted outcome measures were combined as quality metrics in the P4P program in Taiwan.

The association between participation in a pay-for-performance program and macrovascular complications in patients with type 2 diabetes in Taiwan: A nationwide population-based cohort study.

OBJECTIVE: Diabetes and diabetes-related complications are major causes of morbidity and mortality worldwide and contribute substantially to health care costs. Proper care can prevent or delay vascular complications in people with type 2 diabetes. We sought to examine whether a diabetes pay-for-performance (P4P) program under Taiwan's National Health Insurance program decreased risk of macrovascular complications in type 2 diabetes patients, and associated risk factors. RESEARCH DESIGN AND METHOD: We conducted a longitudinal observational case and control cohort study using two nationwide population-based databases in Taiwan, 2007-2012. Type 2 diabetes patients with a primary diabetes diagnosis in year 2007 and 2008 were included. We excluded patients with any diabetes complications within 2years before the index date. A propensity score matching approach was used to determine comparable P4P and non-P4P groups. We followed each P4P and non-P4P patient until December 31, 2012. Complication incidence rates per 1000 person-years for each complication were calculated. RESULTS: Overall, our results indicated that P4P patients had lower risk of macrovascular complications than non-P4P patients. Specifically, hazard ratios (95% confidence intervals) were 0.84 (0.80-0.88) for stroke, 0.83 (0.75-0.92) for myocardial infarction, 0.72 (0.60-0.85) for atrial fibrillation, 0.93 (0.87-0.98) for heart failure, 0.61 (0.50-0.73) for gangrene, and 0.83 (0.74-0.93) for ulcer of lower limbs. CONCLUSIONS: Compared with patients not enrolled in the P4P program, P4P patients had lower risk of developing serious vascular complications. Our empirical findings provide evidence for the potential long-term benefit of P4P programs in reducing risks of macrovascular complications.

Rapid point-of-care identification of oral medications in gastric lavage content by ambient mass spectrometry in the emergency room.

RATIONALE: Acute poisoning should be handled with high efficiency in order to minimize morbidity and mortality in the emergency room. Unfortunately, history-taking and physical examination are not always reliable. Mis-swallowing of oral medications is common in the pediatric group. This study aimed at developing a rapid point-of-care ambient mass spectrometric method for the early identification of ingested oral medications in gastric lavage content. METHODS: Four different types of oral medications that are most commonly mis-swallowed by children were diluted to different concentrations. Each of these chemical solutions was mixed with human gastric lavage content. A direct metallic sampling probe was dipped into the solution. It was then inserted promptly into the thermal desorption electrospray ionization source to carry out ionization and subsequent mass spectrometric analysis of the medications. The corresponding compounds were identified through matching of the obtained mass spectrometric data with those provided by well-established databases. RESULTS: Since no pretreatment of the specimen was required, the sampling step, and the subsequent thermal desorption electrospray ionization and mass spectrometric detection of the medications were completed within 30 s. Mass spectra were obtained for four different kinds of oral medication. The limit-of-detection of the four tested oral medications in gastric lavage content is at sub-ppm level, which is sensitive enough for emergency medicine applications since the quantities of medications ingested by pediatric patients are usually much higher. CONCLUSIONS: Thermal desorption electrospray ionization mass spectrometry, with informational support provided by an online mass spectral database, allows for early point-of-care identification of mis-swallowed oral medications in the evacuated gastric lavage contents obtained from gastric lavage of patients in the emergency room, and it is promising in providing important toxicological information to ensure the appropriateness of the subsequent medical management. Copyright © 2016 John Wiley & Sons, Ltd.

Association of Serum Uric Acid Concentration with Diabetic Retinopathy and Albuminuria in Taiwanese Patients with Type 2 Diabetes Mellitus.

Patients with type 2 diabetes mellitus (DM) may experience chronic microvascular complications such as diabetic retinopathy (DR) and diabetic nephropathy (DN) during their lifetime. In clinical studies, serum uric acid concentration has been found to be associated with DR and DN. The goal of this study was to evaluate the relationship between the increases in serum uric acid level and the severity of DR and albuminuria in Taiwanese patients with type 2 DM. We recorded serum uric acid concentration, the severity of DR, and the severity of albuminuria by calculating urinary albumin-to-creatinine ratio (UACR) in 385 patients with type 2 DM. In multivariate logistic regression analysis, a high uric acid concentration was a risk factor for albuminuria (odds ratio (OR), 1.227; 95% confidence interval (CI) = 1.015-1.482; p = 0.034) and DR (OR, 1.264; 95% CI = 1.084-1.473; p = 0.003). We also demonstrated that there was a higher concentration of serum uric acid in the patients with more severe albuminuria and DR. In conclusion, an increased serum uric acid level was significantly correlated with the severity of albuminuria and DR in Taiwanese patients with type 2 DM.

VLDL from Metabolic Syndrome Individuals Enhanced Lipid Accumulation in Atria with Association of Susceptibility to Atrial Fibrillation.

Metabolic syndrome (MetS) represents a cluster of metabolic derangements. Dyslipidemia is an important factor in MetS and is related to atrial fibrillation (AF). We hypothesized that very low density lipoproteins (VLDL) in MetS (MetS-VLDL) may induce atrial dilatation and vulnerability to AF. VLDL was therefore separated from normal (normal-VLDL) and MetS individuals. Wild type C57BL/6 male mice were divided into control, normal-VLDL (nVLDL), and MetS-VLDL (msVLDL) groups. VLDL (15 µg/g) and equivalent volumes of saline were injected via tail vein three times a week for six consecutive weeks. Cardiac chamber size and function were measured by echocardiography. MetS-VLDL significantly caused left atrial dilation (control, n = 10, 1.64 ± 0.23 mm; nVLDL, n = 7, 1.84 ± 0.13 mm; msVLDL, n = 10, 2.18 ± 0.24 mm; p < 0.0001) at week 6, associated with decreased ejection fraction (control, n = 10, 62.5% ± 7.7%, vs. msVLDL, n = 10, 52.9% ± 9.6%; p < 0.05). Isoproterenol-challenge experiment resulted in AF in young msVLDL mice. Unprovoked AF occurred only in elderly msVLDL mice. Immunohistochemistry showed excess lipid accumulation and apoptosis in msVLDL mice atria. These findings suggest a pivotal role of VLDL in AF pathogenesis for MetS individuals.