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Diabetic kidney disease (DKD) is a critical microvascular complication of diabetes. With the continuous increase in the prevalence of diabetes since 2000, the prevalence of DKD has also been increasing in past years. The prevalence of DKD among individuals with type 2 diabetes in Taiwan increased from 13.32% in 2000 to 17.92% in 2014. The cumulative incidence of DKD among individuals with type 1 diabetes in Taiwan was higher than 30% during 1999–2012. DKD is the leading cause of end‐stage renal disease (ESRD), with a prevalence of approximately 45% in a population on chronic dialysis in Taiwan. Among individuals with type 2 diabetes, the prevalence of ESRD in the receipt of dialysis also increased from 1.32% in 2005 to 1.47% in 2014. Risk factors for DKD development are age, race, family history, hyperglycemia, hypertension, dyslipidemia, dietary patterns, and lifestyles. Prognostic factors that aggravate DKD progression include age, family history, sex, glycemic control, blood pressure (BP), microvascular complications, and atherosclerosis. This review summarizes updated information on the onset and progression of DKD, particularly in the Taiwanese population. Translating these epidemiological features is essential to optimizing the kidney care and improving the prognosis of DKD in Asian populations., This review summarizes updated information on the onset and progression of DKD, particularly in Taiwan. Translating these epidemiological features is essential to optimizing kidney care and improving the prognosis of DKD in Asian populations.

Fatty acid desaturase (FADS) genetic polymorphisms are strongly correlated with the risk of dyslipidemia and cardiovascular disease. In this study, we examined the impact of FADS1 and FADS2 genetic variants on plasma lipid status, and assessed interactions between FADS genetic polymorphisms and plasma n-3/n-6 fatty acids regarding lipid status within a population of 816 Taiwanese patients with type 2 diabetes.Selected tag single-nucleotide polymorphisms (FADS1 rs174546 [T/C]; FADS2 rs174602 [A/G] and rs2072114 [A/G]) were genotyped (n = 816).The distribution of genotypes were compared with reports publicly available in the Genome Aggregation Database for East Asian populations (https://gnomad.broadinstitute.org). In the subgroup of patients not taking lipid-lowering medications (n = 192), we observed that the G allele of FADS2 rs174602 was statistically significantly correlated with lower low-density lipoprotein cholesterol (LDL-C) concentrations (P = 0.001), whereas the G allele of rs2072114 was marginally associated with LDL-C concentrations (P = 0.091). Using a general linear model adjusted for confounding factors, statistically significant interactions (P = 0.016) between single-nucleotide polymorphisms in rs2072114 and a low alpha-linolenic acid (18:3n-3)/linoleic acid (18:2n-6) ratio; the G allele correlated with lower LDL-C levels among individuals with a low alpha-linolenic acid/linoleic acid ratio. Interaction between rs174602 single-nucleotide polymorphisms and low alpha-linolenic acid/linoleic acid values on LDL-C was only marginally significant (P = 0.063).Our results show the role of n-3/n-6 dietary polyunsaturated fatty acids in modifying the effects of genetic susceptibility on lipoprotein concentrations in patients with type 2 diabetes. Our findings highlight the potential of interventions with dietary polyunsaturated fatty acids regarding developing individualized prevention strategies for type 2 diabetes presenting with co-occurring dyslipidemia and cardiovascular diseases.

Background: Subjects with metabolic syndrome (MetS) commonly have atrial remodeling, which indicates a risk for atrial fibrillation. Objective: This study determined MetS-related changes in lipid components in very-low-density lipoprotein (VLDL), which has been shown causing atrial remodeling, and the effect of statins on these changes, and the correlation between atrial remodeling and VLDL lipid compositions. Methods: Blood samples were collected from 12 non-MetS and 27 sex- and age-matched MetS subjects. Fourteen patients with MetS (MetS­–off statin) discontinued statin therapy 14 days before the study, while the remaining 13 remained on it (MetS–on statin). The VLDLs were isolated and processed for mass-based lipid profiling. Lipidomic analyses were performed and associated with atrial remodeling markers measured using standard echocardiography and electrocardiography. Results: Compared with the VLDL components of the non-MetS group, glucosyl/galactosyl ceramide, lyso-phosphatidylcholine, lyso-phosphatidylethanolamine, and triglycerides were enriched in the MetS–off statin group. The statin therapy attenuated all abnormally abundant lipid classes in MetS, except for triglycerides. In addition, lyso-phosphatidylcholine, lyso-phosphatidylethanolamine, and triglycerides were significantly correlated with atrial dilatation, and the latter two were also correlated with the PR interval. Enrichment of double bonds, which indicates unsaturated fatty acids, was also significantly correlated with atrial remodeling, and P-wave duration. Conclusion: This study suggests that the pathological lipid payload of MetS-VLDL may contribute to atrial remodeling in patients.

Aims/Introduction Electronegative low‐density lipoprotein (L5) is the most atherogenic fraction of low‐density lipoprotein and is elevated in people with metabolic syndrome (MetS), whereas the retinol‐binding protein 4 receptor (stimulated by retinoic acid 6 [STRA6]) cascade is disrupted in various organs of patients with obesity‐related diseases. Our objective was to investigate whether L5 from MetS patients capably induces pathogenesis of aorta through disrupting the STRA6 cascade. Material and Methods We examined the in vivo and in vitro effects of L5 on the STRA6 cascade and aortic atherogenic markers. To investigate the role of this cascade on atherosclerotic formation, crbp1 transfection was carried out in vitro. Results This study shows that L5 activates atherogenic markers (p38 mitogen‐activated protein kinases, pSmad2 and matrix metallopeptidase 9) and simultaneously suppresses STRA6 signals (STRA6, cellular retinol‐binding protein 1, lecithin‐retinol acyltransferase, retinoic acid receptor‐α and retinoid X receptor‐α) in aortas of L5‐injected mice and L5‐treated human aortic endothelial cell lines and human aortic smooth muscle cell lines. These L5‐induced changes of the STRA6 cascade and atherogenic markers were reversed in aortas of LOX1−/− mice and in LOX1 ribonucleic acid‐silenced human aortic endothelial cell lines and human aortic smooth muscle cell lines. Furthermore, crbp1 gene transfection reversed the disruption of the STRA6 cascade, the phosphorylation of p38 mitogen‐activated protein kinases and Smad2, and the elevation of matrix metallopeptidase 9 in L5‐treated human aortic endothelial cell lines. Conclusions This study shows that L5 from MetS patients induces atherogenic markers by disrupting STRA6 signaling. Suppression of STRA6 might be one novel pathogenesis of aorta in patients with MetS., Dyslipoproteinemia can cause aortic injuries by utilizing electronegative low‐density lipoprotein caused disruption of stimulated by retinoic acid 6 signaling. The suppression of stimulated by retinoic acid 6 might be one novel pathogenesis of aorta in people with metabolic syndrome.

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

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.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.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 for40 defined daily doses in 90 days or1000 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).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.

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 P 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.

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 left atrial dilatation. Methods: We evaluated 87 MetS and 80 non-MetS individuals between 23 and 74 years old (50.6% men) without overt cardiovascular diseases. Blood samples were collected while fasting and postprandially (at 0.5, 1, 2, and 4 hours 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 atrial 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 Conclusion: Postprandial VLDL-χ is associated with atrial remodeling. VLDL-χ is a novel biomarker for atrial cardiomyopathy in MetS patients and may be a therapeutic target. Trial registration: ISRCTN 69295295. Registered 9 June 2020.

Background Retinol-binding protein 4 (RBP4) is elevated and associated with inflammation in metabolic diseases. Disruption of the retinol cascade and O-GlcNAcylation of the RBP4 receptor (STRA6) are found in diabetic kidneys. Objectives We investigated whether the disruption of the retinol cascade induces RBP4 overproduction and if O-linked GlcNAc modification targets RBPR2 and contributes to the disruption of retinol cascades in diabetic livers. Methods Western blot or immunohistochemistry for RBPR2, CRBP1, LRAT, RALDH, RARα, RARγ, RXRα, RBP4, GFAT, OGT, OGA and inflammatory markers, as well as ELISA for RBP4, were performed in livers of db/db and ob/ob mice and high glucose-cultured hepatocytes. Immunoprecipitation and dual fluorescence staining were used to explore O-GlcNAc-modified RBPR2 and RBP4 binding activity on RBPR2. Transfection of the CRBP1 gene was done to verify whether a disrupted retinol cascade induces RBP4 overproduction. OGT silencing was done to investigate the association of O-GlcNAcylation with the disruption of retinol cascade. Results Disruption of retinol cascade, RBP4 overproduction, O-GlcNAcylation of RBPR2, decreased RBP4 binding activity on RBPR2 and inflammation were found in livers of db/db and ob/ob mice and high glucose-cultured hepatocytes. CRBP1 gene transfection reversed the suppression of the cellular retinol cascade and simultaneously attenuated the RBP4 overproduction and inflammation in high glucose-treated hepatocytes. The silencing of OGT reversed the disruption of the cellular retinol cascade, RBP4 overproduction and inflammation induced by high glucose in hepatocytes. Conclusions This study indicates that the disruption of cellular retinol cascade is strongly associated with RBP4 overproduction and inflammation in diabetic livers. RBPR2 is one target for high glucose-mediated O-linked GlcNAc modification, which causes liver retinol dyshomeostasis.

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.

Additional file 1: Table S1. Univariate and multivariable linear regression of determining factors of LA diameter in the matched groups (n = 94). Table S2. Multivariable linear regression of determining factors of LA diameter by metabolic syndrome (MetS). Table S3. Multivariable linear regression of determining factors of LA diameter by metabolic syndrome (MetS) in the matched groups (n = 94). Figure S1. Correlation between left atrial (LA) diameter and plasma concentration of glucose before (fasting) and after the unified meal (postprandial 0.5, 1, 2, and 4 h) in participants without MetS (in blue, A-E) and with MetS (in orange, F-J). Figure S2. Correlation between left atrial (LA) diameter and plasma concentration of triglyceride before (fasting) and after the unified meal (postprandial 0.5, 1, 2, and 4 h) in participants without MetS (in blue, A-E) and with MetS (in orange, F-J). Figure S3. Correlation between left atrial (LA) diameter and plasma concentration of very-low-density lipoprotein cholesterol (VLDL-C) before (fasting) and after the unified meal (postprandial 0.5, 1, 2, and 4 h) in participants without MetS (in blue, A-E) and with MetS (in orange, F-J). Figure S4. Correlation between left atrial (LA) diameter and plasma concentration of negative-charged low-density lipoprotein cholesterol (LDL-χ) before (fasting) and after the unified meal (postprandial 0.5, 1, 2, and 4 h) in participants without MetS (in blue, A-E) and with MetS (in orange, F-J).

Context Although α-glucosidase inhibitors (AGIs) have been shown to reduce the risk of myocardial infarction in patients with impaired glucose tolerance, the cardiovascular benefits of AGIs in those with type 2 diabetes (T2D) remains unclear. Objective We compared the clinical outcomes of adding acarbose vs sulfonylureas to metformin therapy in patients with T2D. Design, setting, and participants The study population was drawn from the database of the Diabetes Pay-for-Performance program in Taiwan. Sulfonylureas and acarbose were prescribed to 196,143 and 14,306 patients with T2D, respectively, from 2004 to 2015, who had been treated with metformin. A propensity score-matched cohort study was conducted. The patients were followed up for clinical adverse events of all-cause mortality and hospitalizations of major atherosclerotic events (i.e., myocardial infarction and ischemic stroke), heart failure, or hypoglycemia. Results A total of 14,306 propensity score-matched pairs (age, 55.8 ± 13.1 years; 47.8% men) were enrolled in the present analysis. Compared with sulfonylureas as the add-on therapy to metformin, the use of acarbose was associated with significantly lower risks of hospitalizations for major atherosclerotic events [hazard ratio (HR), 0.69; 95% CI, 0.52 to 0.91], ischemic stroke (HR, 0.68; 95% CI, 0.49 to 0.94), and hypoglycemia (HR, 0.23; 95% CI, 0.08 to 0.71), after accounting for major confounding factors. Conclusions In T2D treatment, the use of acarbose as an add-on remedy to metformin was associated with lower risks of major atherosclerotic events, ischemic stroke, and hypoglycemia compared with the use of sulfonylurea as an add-on remedy.

Electronegative L5 low-density lipoprotein (LDL) level may be a useful biomarker for predicting cardiovascular disease. We determined the range of plasma L5 levels in healthy adults (n = 35) and examined the power of L5 levels to differentiate patients with coronary artery disease (CAD; n = 40) or patients with hyperlipidemia (HLP) without evidence of CAD (n = 35) from healthy adults. The percent L5 in total LDL (L5%) was quantified by using fast-protein liquid chromatography with an anion-exchange column. Receiver operating characteristic curve analysis was performed to determine cut-off values for L5 levels. The mean L5% and plasma concentration of L5 (ie, [L5]) were significantly higher in patients with HLP or CAD than in healthy adults (P 1.6%, the odds ratio was 9.636 for HLP or CAD. In individuals with [L5] >1.7 mg/dL, the odds ratio was 17.684 for HLP or CAD. The power of L5% or [L5] to differentiate patients with HLP or CAD from healthy adults was superior to that of the LDL/high-density lipoprotein ratio. The ranges of L5% and [L5] in healthy adults determined here may be clinically useful in preventing and treating cardiovascular disease.

The prevalence of metabolic syndrome (MetS) in patients with type 2 diabetes mellitus is high. The aim of this study was to investigate the association between MetS and micro- and macrovascular disease in patients with diabetes and the associated risk factors.The study enrolled 1,986 (854 men and 1,132 women) patients with type 2 diabetes mellitus from outpatient clinics. MetS was defined according to the Adult Treatment Panel III for Asians.Of the enrolled patients, 1,363 had MetS and 623 did not. The patients with MetS had significantly higher rates of albuminuria (40.8% vs. 21.8%, P0.001), retinopathy (37.9% vs. 28.6%, P0.001), coronary artery disease (19.4% vs. 11.6%, P0.001), cerebrovascular disease (5.8% vs. 3.2%, P = 0.014), and an ankle-brachial index0.9 or ≥ 1.3 (6.1% vs. 3.0%, P = 0.015). Moreover, there were significant trends for stepwise increases in albuminuria, retinopathy, coronary artery disease, cerebrovascular disease and peripheral artery disease corresponding to the number of MetS components (all P for trend0.05). Risk factors including MetS, old age, sex, wide pulse pressure, increased hemoglobin AMetS and the number of its components were significantly associated with micro- and macrovascular disease in the study patients with diabetes and this resulted in a higher risk of cardiovascular disease. Screening programs to allow for early detection and interventions should be established to lower the risk of cardiovascular disease.

Although some studies have reported an association between peripheral artery disease (PAD) and diabetic retinopathy (DR) in patients with diabetes, whether or not a causal relationship exists is unknown. The aim of this study was to investigate whether PAD, as indicated by an abnormally low or high ankle-brachial index (ABI), is associated with the development of DR in patients with type 2 diabetes mellitus (DM) without DR. We enrolled 414 (221 men and 193 women) patients with type 2 DM who underwent ABI measurements at our outpatient clinic. PAD was defined as an abnormally low (vs. ABI ≥0.9 to p = 0.005). An abnormal ABI was associated with the development of DR in our patients with type 2 DM without DR.

// Wei-Hao Hsu 1, 2 , Pi-Jung Hsiao 1, 3 , Pi-Chen Lin 1 , Szu-Chia Chen 2, 3, 4, 5 , Mei-Yueh Lee 1, 2, 3, 4 and Shyi-Jang Shin 1, 3, 6 1 Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 2 Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 3 Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 4 Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 5 Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 6 Center for Lipid and Glycomedicine Research, Kaohsiung Medical University, Kaohsiung, Taiwan Correspondence to: Mei-Yueh Lee, email: lovellelee@hotmail.com Keywords: metformin; diabetes mellitus; chronic kidney disease; renal function decline; estimated glomerular filtration rate Received: September 12, 2017 Accepted: December 04, 2017 Published: December 17, 2017 ABSTRACT Background: Impaired renal function can lead to the accumulation of metformin, and elevated concentrations of metformin have been associated with lactic acidosis. The aim of this study was to evaluate the effect of continuous metformin treatment in patients with type 2 diabetes mellitus (DM) and moderate chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) 30–0 ml/min/1.73 m 2 ) on renal function. Methods: A total of the 616 patients were enrolled from the research database of Kaohsiung Medical University Hospital from January 1 to 2009 and December 31, 2013. The patients were divided into two groups: those who continued metformin treatment (continuation group; n = 484), and those who discontinued metformin treatment for at least 100 days (interruption group; n = 132). Results: The slope of eGFR in the metformin interruption group was statistically lower than that in the metformin continuation group (0.75 ± 0.76 vs. –1.32 ± 0.24 mL/min/1.73 m 2 /year, p = 0.0007). After adjusting for baseline covariates in the multivariate linear regression analysis, the continuation of metformin (unstandardized coefficient β, –2.072; 95% confidence interval, –3.268– –0.876) was a risk factor for the patients with DM and moderate CKD. Conclusions: Metformin may have an adverse effect on renal function in patients with type 2 DM and moderate CKD.

The mortality prediction models for the general diabetic population have been well established, but the corresponding elderly-specific model is still lacking. This study aims to develop a mortality prediction model for the elderly with diabetes. The data used for model establishment were derived from the nationwide adult health screening program in Taiwan in 2007–2010, from which we applied a 10-fold cross-validation method for model construction and internal validation. The external validation was tested on the MJ health screening database collected in 2004–2007. Multivariable Cox proportional hazards models were used to predict five-year mortality for diabetic patients ≥65 years. A total of 220,832 older subjects with diabetes were selected for model construction, of whom 23,241 (10.5%) died by the end of follow-up (December 31, 2011). The significant predictors retained in the final model included age, gender, smoking status, body mass index (BMI), fasting glucose, systolic and diastolic blood pressure, leukocyte count, liver and renal function, total cholesterol, hemoglobin, albumin, and uric acid. The Harrell’s C in the development, internal-, and external-validation datasets were 0.737, 0.746, and 0.685, respectively. We established an easy-to-use point-based model that could accurately predict five-year mortality risk in older adults with diabetes.

Context Electronegative low-density lipoprotein (LDL) L5 is a naturally occurring, atherogenic entity found at elevated levels in the plasma of patients with metabolic syndrome (MetS) in the absence of elevated plasma LDL levels. Objective To investigate the role of L5 in the mechanism of adipose tissue inflammation associated with MetS. Patients/Setting Plasma LDL isolated from patients with MetS (n = 29) and controls (n = 29) with similar plasma LDL levels was separated into five subfractions, L1 to L5, with increasing electronegativity. Design We examined the invivo effects of L5 on adipose tissue in mice and the in vitro effects of L5 on adipocytokine signaling and monocytes. Results Tail-vein injection of human L5 but not L1 into C57BL/6 mice induced the accumulation of F4/80+ and CD11c+ M1 macrophages. The effects of L5 were attenuated in mice deficient for L5's receptor, lectin-like oxidized LDL receptor 1 (LOX-1). L5 but not L1 induced human adipocytes to release inflammatory adipocytokines. Incubating human THP-1 monocytes with LDL-free culture media from L5-treated adipocytes enhanced the migration of monocytes by 300-fold (P < 0.001 vs L1-treated adipocyte media)-effects that were attenuated by LOX-1 neutralizing antibody. Migrated cells were positive for mature macrophage marker PM-2K, indicating the transformation of monocytes into macrophages. The infiltration of M1 macrophages in adipose tissue was also observed in a previously established hamster model of endogenously elevated L5. Conclusions L5 induces adipose inflammation through LOX-1 by promoting macrophage maturation and infiltration into adipose tissue. Elevated plasma L5 levels may be a novel etiology of adipose tissue inflammation in patients with MetS.

BackgroundThe aim of the present study was to investigate relationships between the risk of chronic kidney disease (CKD) and obesity and weight changes in Asian patients with type 2 diabetes.

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. Keywords: Hospitalization, National Health Insurance, Taiwan, Type 2 diabetes mellitus

Background: Metabolic alterations correlate with adverse outcomes in type 2 diabetes. Dietary modification serves as an integral part in its treatment. Objective: We examined the relationships among dietary patterns, dietary biomarkers, and metabolic indicators in type 2 diabetes (n = 871). Design: Diabetic patients (n = 871) who provided complete clinical and dietary data in both 2008 and 2009 were selected from a cohort participating in a diabetic control study in Taiwan. Dietary data were obtained using a short, semiquantitative food frequency questionnaires, and dietary pattern identified by factor analysis. Multiple linear regressions were used to analyze the association between dietary biomarkers (ferritin, folate, and erythrocyte n-3 polyunsaturated fatty acids [n-3 PUFAs]) and metabolic control upon adjusting for confounders. Results: Three dietary patterns (high-fat meat, traditional Chinese food–snack, and fish–vegetable) were identified. Ferritin correlated positively with high-fat meat factor scores (P for trend

Sodium glucose co-transporter 2 (SGLT2) inhibitors have been proved to be beneficial for cardiovascular and renal outcome in diabetic patients. Our study demonstrated that disruption of intracellular retinol signaling is associated with diabetic nephropathy. Retinoid homeostasis, regulated by RBP4/STRA6/CRBP1/LRAT/RARs pathway, is also very crucial in cell biological function of pancreas and islets. This study aimed to demonstrate whether SGLT2 inhibitor or sulfonylurea could protect pancreas and kidney from diabetes-related injury. Diabetic db/db mice were treated with empagliflozin or glibenclamide for 4 weeks at their age of 8 weeks. This study analyzed RBP4/STRA6/CRBP1/LRAT/RARs signals and p-JNK, caspase in both pancreas and kidney, and functional markers of pancreatic β-cells (insulin, MafA, Pdx1, and NKX6.1) in pancreas of wild type, db/db, glibenclamide-treated db/db and empagliflozin-treated db/db mice. Significant reduction of insulin, MafA, Pdx1 and NKX6.1 protein and mRNA in pancreas of db/db mice were found and could be rescued in empagliflozin-treated db/db mice, but not in glibenclamide-treated db/db mice. STRA6, CRBP1, LRAT and RARβ protein and mRNA levels were reduced, while p-JNK and caspase expression increased in pancreas and kidneys of db/db mice. These changes were recovered in empagliflozin-treated db/db mice, but not in glibenclamide-treated db/db mice. The concentration of retinol, and retinoic acid, measured by HPLC, were also conserved in pancreas of empagliflozin-treated db/db mice, not in glibenclamide-treated db/db mice. In conclusion, this study indicates that empagliflozin, but not glibenclamide, exerts protective effects on pancreas and kidneys from diabetes through retrieving the disruption of STRA6-retinol signals in db/db mice. Disclosure S. Shin: None. Funding Taiwan Ministry of Science and Technology

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. Keywords: Diabetic foot, Diabetic kidney disease, Diabetic nephropathy, Diabetic retinopathy, End-stage kidney disease

Aims: This study investigated whether there is a link between severe hypoglycemia and progression into end-stage renal disease (ESRD) in patients with type 2 diabetes. Methods: Tapping into Taiwan&rsquo, s Health Insurance Research Database, we identified all type 2 diabetes patients between 1996 and 2013 and identified those diagnosed with a severe hypoglycemia episode during an emergency department visit and those who were not. Controls were then matched 1:1 for age, sex, index year, and medication. Results: We identified 468,421 type 2 diabetes patients diagnosed as having severe hypoglycemia in an emergency department visit. Compared with controls, these patients with SH had a higher risk of all-cause mortality (Hazard Ratio (HR), 1.76, 95% confidence interval, 1.61&ndash, 1.94) and progressed into ESRD within a shorter period of time. Results were similar after controlling for competing risk. Conclusion: Severe hypoglycemia is significantly associated with worsening renal dysfunction in patients with type 2 diabetes and hastened progression into ESRD.

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.

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.

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 2 years 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.