Sex Difference in the Associations among Obesity-Related Indices with Metabolic Syndrome in Patients with Type 2 Diabetes Mellitus.

Background: The aim of this study was to investigate the associations among obesity-related indices and MetS in diabetic patients, and explore sex differences in these associations. Methods: Patients with type 2 DM were included from two hospitals in southern Taiwan. The Adult Treatment Panel III criteria for an Asian population were used to define MetS. In addition, the following obesity-related indices were evaluated: waist-to-height ratio, waist-hip ratio (WHR), conicity index (CI), body mass index (BMI), body roundness index, body adiposity index, lipid accumulation product (LAP), abdominal volume index, visceral adiposity index (VAI), abdominal volume index and triglyceride-glucose index. Results: A total of 1,872 patients with type 2 DM (mean age 64.0 ± 11.3 years, 808 males and 1,064 females) were enrolled. The prevalence rates of MetS were 59.8% and 76.4% in the males and female (p < 0.001), respectively. All of the obesity-related indices were associated with MetS in both sex (all p < 0.001). LAP and BMI had the greatest areas under the receiver operating characteristic curves in both sex. In addition, the interactions between BMI and sex (p = 0.036), WHR and sex (p = 0.016), and CI and sex (p = 0.026) on MetS were statistically significant. Conclusions: In conclusion, this study demonstrated significant relationships between obesity-related indices and MetS among patients with type 2 DM. LAP and VAI were powerful predictors in both sex. The associations of BMI, WHR and CI on MetS were more significant in the men than in the women.

Causes of in-hospital death in patients with type 2 diabetes with microvascular and macrovascular complications in Taiwan.

AIMS: Diabetes mellitus is a major cause of death worldwide, including Taiwan. The mortality data of the subsets of patients who suffered from microvascular or macrovascular complications is limited. The aim of this study was to investigate the causes of in-hospital death of patients with type 2 diabetes, especially the patients with microvascular, macrovascular and both micro-macrovascular complications. METHODS: A total of 12 159 patients with type 2 diabetes were identified from the Taiwan National Health Insurance Research Database (NHIRD) to analyse the causes of death. Type 2 diabetic subjects with microvascular, macrovascular and both micro-macrovascular complications were further classified and compared to patients without microvascular and macrovascular complications in the logistic regression analysis of the risk of death. RESULTS: Pneumonia increased risk of in-hospital death in patients with microvascular, macrovascular and both micro-macrovascular complications, with adjusted odds ratios (AORs) of 2.13 (95% confidence interval [CI] 1.09-4.18), 3.26 (1.71-6.24) and 3.96 (2.17-7.22), respectively. Septicaemia increased risk of in-hospital death in patients with macrovascular (AOR 2.57 [1.31-5.04]) and both micro-macrovascular complications (AOR 4.69 [2.58-8.50]). CONCLUSION: Pneumonia increased risk of in-hospital death among the type 2 diabetic patients with microvascular, macrovascular and both micro-macrovascular complications. Therefore, efforts aim at preventing pneumonia or decreasing its severity may increase survival.

Obesity-related indices are associated with albuminuria and advanced kidney disease in type 2 diabetes mellitus.

Obesity is an important risk factor for the development of diseases including diabetes, hypertension, and cardiovascular disease. However, few reports have investigated the relationships between these obesity-related indices and diabetic nephropathy. The aim of this study was to evaluate associations between obesity-related markers with albuminuria and advanced kidney disease in patients with type 2 diabetes mellitus (DM). Obesity-related indices including body mass index (BMI), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), body roundness index (BRI), conicity index (CI), lipid accumulation product (LAP), visceral adiposity index (VAI), body adiposity index (BAI), abdominal volume index (AVI), body shape index (BSI), and triglyceride glucose (TyG) index were measured. Albuminuria was defined as a urine albumin/creatinine ratio of ≥30 mg/g. Advanced kidney disease was defined as an estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2. A total of 1872 patients with type 2 DM (mean age 64.0 ± 11.3 years, 809 males and 1063 females) were enrolled. In multivariable analysis, 11 high obesity-related indices (BMI, WHR, WHtR, LAP, BRI, CI, VAI, BAI, AVI, ABSI, and TyG index) were significantly associated with albuminuria. In addition, high BMI, WHR, WHtR, LAP, BRI, CI, VAI, and AVI were significantly associated with eGFR <30 ml/min/1.73 m2. The results of this study showed that various obesity-related indices were significantly associated with albuminuria and advanced kidney disease in patients with type 2 DM. Screening may be considered in public health programs to recognize and take appropriate steps to prevent subsequent complications.

A performance guide for major risk factors control in patients with atherosclerotic cardiovascular disease in Taiwan.

Atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease, cerebrovascular disease, and peripheral artery disease, carries a high morbidity and mortality. Risk factor control is especially important for patients with ASCVD to reduce recurrent cardiovascular events. Clinical guidelines have been developed by the Taiwan Society of Cardiology, Taiwan Society of Lipids and Atherosclerosis, and Diabetes Association of Republic of China (Taiwan) to assist health care professionals in Taiwan about the control of hypertension, hypercholesterolemia and diabetes mellitus. This article is to highlight the recommendations about blood pressure, cholesterol, and sugar control for ASCVD. Some medications that are beneficial for ASCVD were also reviewed. We hope the clinical outcomes of ASCVD can be improved in Taiwan through the implementation of these recommendations.

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.

Liraglutide Inhibits Hepatitis C Virus Replication Through an AMP Activated Protein Kinase Dependent Mechanism.

Insulin resistance and diabetes are both associated with chronic hepatitis C virus (HCV) infection, and the glucagon-like peptide-1(GLP-1) receptor agonist, liraglutide, is a common therapy for diabetes. Our aim was to investigate whether liraglutide treatment can inhibit HCV replication. A cell culture-produced HCV infectious system was generated by transfection of in vitro-transcribed genomic JFH-1 ribonucleic acid (RNA) into Huh-7.5 cells. Total RNA samples were extracted to determine the efficiency of HCV replication. The Ava5 cells were treated with liraglutide and cell viability was calculated. A Western blot analysis of the protein expression was performed. The immunoreactive blot signals were also detected. Liraglutide activated GLP-1 receptors in the HCV infectious system, and inhibited subgenomic HCV RNA replication in the HuH-7.5 cells. The Western blot analysis revealed both HCV protein and replicon RNA were reduced after treatment with liraglutide in a dose-dependent manner. Liraglutide decreased the cell viability of HCV RNA at an optimum concentration of 120 µg/mL, activated the 5' adenosine monophosphate-activated protein kinase (AMPK) and the phosphorylated- transducer of regulated cyclic adenosine monophosphate (CAMP) response element-binding protein 2 (TORC2), thereby decreasing the cell viability of phosphoenolpyruvate carboxykinase (PEPCK) and G6pase RNA Therefore, we conclude that liraglutide can inhibit HCV replication via an AMPK/TORC2-dependent pathway.

Glucagon-Like Peptide-1 Receptor Agonist Attenuates Autophagy to Ameliorate Pulmonary Arterial Hypertension through Drp1/NOX- and Atg-5/Atg-7/Beclin-1/LC3ß Pathways.

Mitochondrial dysfunction is associated with cardiovascular diseases and diabetes. Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling, and the abnormal proliferation, apoptosis and migration of pulmonary arterial smooth muscle cells (PASMCs). The glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, has been shown to prevent pulmonary hypertension in monocrotaline-exposed rats. The aim of this study was to investigate the effect of liraglutide on autophagy, mitochondrial stress and apoptosis induced by platelet-derived growth factor BB (PDGF-BB). PASMCs were exposed to PDGF-BB, and changes in mitochondrial morphology, fusion-associated protein markers, and reactive oxygen species (ROS) production were examined. Autophagy was assessed according to the expressions of microtubule-associated protein light chain 3 (LC3)-II, LC3 puncta and Beclin-1. Western blot analysis was used to assess apoptosis, mitochondrial stress and autophagy markers. Liraglutide significantly inhibited PDGF-BB proliferation, migration and motility in PASMCs. PDGF-BB-induced ROS production was mitigated by liraglutide. Liraglutide increased the expression of α-smooth muscle actin (α-SMA) and decreased the expression of p-Yes-associated protein (p-YAP), inhibited autophagy-related protein (Atg)-5, Atg-7, Beclin-1 and the formation of LC3-ß and mitochondrial fusion protein dynamin-related (Drp)1. Therefore, liraglutide can mitigate the proliferation of PASMCs via inhibiting cellular Drp1/nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) pathways and Atg-5/Atg-7/Beclin-1/LC3ß-dependent pathways of autophagy in PAH.

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.

Association of HbA1C Variability and Renal Progression in Patients with Type 2 Diabetes with Chronic Kidney Disease Stages 3⁻4.

Little is known about the predictive value of glycosylated hemoglobin (HbA1C) variability in patients with advanced chronic kidney disease (CKD). The aim of this study was to investigate whether HbA1C variability is associated with progression to end-stage renal disease in diabetic patients with stages 3⁻5 CKD, and whether different stages of CKD affect these associations. Three hundred and eighty-eight patients with diabetes and stages 3⁻5 CKD were enrolled in this longitudinal study. Intra-individual HbA1C variability was defined as the standard deviation (SD) of HbA1C, and the renal endpoint was defined as commencing dialysis. The results indicated that, during a median follow-up period of 3.5 years, 108 patients started dialysis. Adjusted Cox analysis showed an association between the highest tertile of HbA1C SD (tertile 3 vs. tertile 1) and a lower risk of the renal endpoint (hazard ratio = 0.175; 95% confidence interval = 0.059⁻0.518; p = 0.002) in the patients with an HbA1C level ≥ 7% and stages 3⁻4 CKD, but not in stage 5 CKD. Further subgroup analysis showed that the highest two tertiles of HbA1C SD were associated with a lower risk of the renal endpoint in the group with a decreasing trend of HbA1C. Our results demonstrated that greater HbA1C variability and a decreasing trend of HbA1C, which may be related to intensive diabetes control, was associated with a lower risk of progression to dialysis in the patients with stages 3⁻4 CKD and poor glycemic control (HbA1c ≥ 7%).

Exogenous Heat Shock Cognate Protein 70 Suppresses LPS-Induced Inflammation by Down-Regulating NF-κB through MAPK and MMP-2/-9 Pathways in Macrophages.

Heat shock cognate protein 70 (HSC70), a molecular chaperone, is constitutively expressed by mammalian cells to regulate various cellular functions. It is associated with many diseases and is a potential therapeutic target. Although HSC70 also possesses an anti-inflammatory action, the mechanism of this action remains unclear. This current study aimed to assess the anti-inflammatory effects of HSC70 in murine macrophages RAW 264.7 exposed to lipopolysaccharides (LPS) and to explain its pathways. Mouse macrophages (RAW 264.7) in 0.1 µg/mL LPS incubation were pretreated with recombinant HSC70 (rHSC70) and different assays (Griess assay, enzyme-linked immune assay/ELISA, electrophoretic mobility shift assay/EMSA, gelatin zymography, and Western blotting) were performed to determine whether rHSC70 blocks pro-inflammatory mediators. The findings showed that rHSC70 attenuated the nitric oxide (NO) generation, tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) expressions in LPS-stimulated RAW264.7 cells. In addition, rHSC70 preconditioning suppressed the activities and expressions of matrix metalloproteinase-2 (MMP-2) and MMP-9. Finally, rHSC70 diminished the nuclear translocation of nuclear factor-κB (NF-κB) and reduced the phosphorylation of extracellular-signal regulated kinases 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (MAPK), and phosphatidylinositol-3-kinase (PI3K/Akt). We demonstrate that rHSC70 preconditioning exerts its anti-inflammatory effects through NO production constriction; TNF-α, and IL-6 suppression following down-regulation of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), and MMP-2/MMP-9. Accordingly, it ameliorated the signal transduction of MAPKs, Akt/IκBα, and NF-κB pathways. Therefore, extracellular HSC70 plays a critical role in the innate immunity modulation and mechanisms of endogenous protective stimulation.

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.

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.

Association of Far-Infrared Radiation Therapy and Ankle-Brachial Index of Patients on Hemodialysis with Peripheral Artery Occlusive Disease.

Background and Aim: The ankle-brachial index (ABI) is recognized to be a good marker for atherosclerosis, and is useful in the diagnosis of peripheral artery occlusive disease (PAOD) which is prevalent among patients on hemodialysis (HD). Methods: This randomized trial aimed to evaluate the effect of far-infrared radiation (FIR) therapy on ABI in HD patients with PAOD. PAOD was defined as patients with ABI < 0.95. One hundred and eight HD patients were enrolled, including 50 in the control group and 58 in the FIR group. A WS TY101 FIR emitter was applied for 40 minutes during each HD session, three times per week for six months. The ABI was measured before and after the FIR therapy. Results: Regardless of FIR therapy, the bilateral ABI decreased (in the FIR group, left: 0.88±0.22 to 0.85±0.24, p = 0.188; right: 0.92±0.20 to 0.90±0.23, p = 0.372; in control group, left: 0.91±0.23 to 0.88±0.21, p = 0144; right: 0.93±0.17 to 0.89±0.21, p = 0.082). Multivariate logistic analysis of the FIR group revealed that high uric acid (odds ratio [OR]: 2.335; 95% confidence interval [CI]: 1.117-4.882; p=0.024) and aspirin use (OR: 16.463; 95% CI: 1.787-151.638; p=0.013) were independently associated with increased bilateral ABI after FIR therapy. Conclusions: This study demonstrates that ABI is not increased after FIR therapy in HD patients with PAOD. However, in the FIR group, patients with higher uric acid level or those who used aspirin have increased bilateral ABI after FIR therapy.

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.

MTTP-297H polymorphism reduced serum cholesterol but increased risk of non-alcoholic fatty liver disease-a cross-sectional study.

BACKGROUND: Microsomal triglyceride transfer protein (MTP) works to lipidate and assemble the apoB-containing lipoproteins in liver. It closely links up the hepatic secretion of lipid to regulate serum lipid and atherosclerosis. Cases of MTTP gene mutation is characterized by abetalipoproteinemia and remarkable hepatic steatosis or cirrhosis. Several MTTP polymorphisms have been reported relating to metabolic syndrome, hyperlipidemia and steatohepatitis. We supposed the regulation of serum lipids and risk of non-alcoholic fatty liver disease (NAFLD) formation may be modified by individual susceptibility related to the MTTP polymorphisms. METHODS AND RESULTS: A cross-sectional population of 1193 subjects, 1087 males and 106 females mean aged 45.9 ± 8.9 years, were enrolled without recognized secondary hyperlipidemia. Fasting serum lipid, insulin, and non-esterified fatty acid were assessed and transformed to insulin resistance index, HOMA-IR and Adipo-IR. After ruling out alcohol abuser, non-alcoholic fatty liver disease (NAFLD) was diagnosed by abdominal ultrasound. Five common MTTP polymorphisms (promoter -493 G/T, E98D, I128T, N166S, and Q297H) were conducted by TaqMan assay. Multivariate regression analysis was used to estimate their impact on serum lipid and NAFLD risk. Assessment revealed a differential impact on LDL-C and non-HDL-C, which were sequentially determined by the Q297H polymorphism, insulin resistance, body mass index and age. Carriers of homozygous minor allele (297 H) had significantly lower LDL-C and non-HDL-C but higher risk for NAFLD. Molecular modeling of the 297 H variant demonstrated higher free energy, potentially referring to an unstable structure and functional sequence. CONCLUSION: These results evidenced the MTTP polymorphisms could modulate the lipid homeostasis to determine the serum lipids and risk of NAFLD. The MTTP 297 H polymorphism interacted with age, insulin resistance and BMI to decrease serum apoB containing lipoproteins (LDL-C and non-HDL-C) but increase the risk of NAFLD formation.

Statin, calcium channel blocker and Beta blocker therapy may decrease the incidence of tuberculosis infection in elderly Taiwanese patients with type 2 diabetes.

BACKGROUND: It is well known that diabetes mellitus impairs immunity and therefore is an independent risk factor for tuberculosis. However, the influence of associated metabolic factors, such as hypertension, dyslipidemia and gout has yet to be confirmed. This study aimed to investigate whether the strong association between tuberculosis and diabetes mellitus is independent from the influence of hypertension and dyslipidemia, and its treatment in elderly Taiwanese patients. METHODS: A total of 27,958 patients aged more than 65 years were identified from the National Health Insurance Research Database (NIHRD) in 1997 and were followed from 1998 to 2009. The demographic characteristics between the patients with and without diabetes were analyzed using the χ2 test. A total of 13,981 patients with type 2 diabetes were included in this study. Cox proportional hazard regression models were used to determine the independent effects of diabetes on the risk of tuberculosis. RESULTS: After adjusting for age, sex, other co-morbidities and medications, calcium channel blocker, beta blocker and statin users had a lower independent association, with risk ratios of 0.76 (95% CI, 0.58-0.98), 0.72 (95% CI, 0.58-0.91) and 0.76 (95% CI, 0.60-0.97), respectively. CONCLUSION: Calcium channel blocker, beta blocker and statin therapy may decrease the incidence of tuberculosis infection in elderly Taiwanese patients with type 2 diabetes.

Diabetes mellitus increases severity of thrombocytopenia in dengue-infected patients.

BACKGROUND: Diabetes mellitus is known to exacerbate bacterial infection, but its effect on the severity of viral infection has not been well studied. The severity of thrombocytopenia is an indicator of the severity of dengue virus infection. We investigated whether diabetes is associated with thrombocytopenia in dengue-infected patients. METHODS: We studied clinical characteristics of 644 patients with dengue infection at a university hospital during the epidemic on 1 June 2002 to 31 December 2002 in Taiwan. Platelet counts and biochemical data were compared between patients with and without diabetes. Potential risk factors associated with thrombocytopenia were explored using regression analyses. RESULTS: Dengue-infected patients with diabetes had lower platelet counts than patients without diabetes during the first three days (54.54±51.69 vs. 86.58±63.4 (p≤0.001), 43.98±44.09 vs. 64.52±45.06 (p=0.002), 43.86±35.75 vs. 62.72±51.2 (p=0.012)). Diabetes mellitus, death, dengue shock syndrome (DSS) and dengue hemorrhagic fever (DHF) and increased glutamic-pyruvate transaminase (GPT) levels were significantly associated with lower platelet counts during the first day of hospitalization for dengue fever with regression ß of -13.981 (95% confidence interval (CI) -27.587, -0.374), -26.847 (95% CI -37.562, -16.132), and 0.054 (95% CI 0.015, 0.094) respectively. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients with or without diabetes with regression ß of -2.947 (p=0.004), 2.801 (p=0.005), and -3.568 (p≤0.001), respectively. Diabetic patients with dengue had a higher rate of dengue hemorrhagic fever (DHF)/dengue shock syndrome (DSS) than non-diabetic patients. They also had lower blood albumin, were older, and higher triglyceride levels. Older age, hypoalbuminemia, and hypertriglyceridemia were independently correlated with thrombocytopenia in dengue patients. CONCLUSIONS: Dengue patients with diabetes tended to have more severe thrombocytopenia and were more likely to have DHF/DSS. Older age, hypoalbuminemia, and hypertriglyceridemia were independently associated with more severe thrombocytopenia in dengue patients.

Increased unbound retinol-binding protein 4 concentration induces apoptosis through receptor-mediated signaling.

The increase of apo-/holo-retinol-binding protein 4 (RBP4) concentrations has been found in subjects with renal dysfunction and even in diabetic patients with microalbuminuria. Holo-RBP4 is recognized to possess cytoprotective function. Therefore, we supposed that the relative increase in apo-RBP4 might induce cell damage. In this study, we investigated the signal transduction that activated apoptosis in response to the increase of apo-/holo-RBP4 concentration. We found that increase of apo-/holo-RBP4 concentration ratio delayed the displacement of RBP4 with "stimulated by retinoic acid 6" (STRA6), enhanced Janus kinase 2 (JAK2)/STAT5 cascade, up-regulated adenylate cyclase 6 (AC6), increased cAMP, enhanced JNK1/p38 cascade, suppressed CRBP-I/RARα (cellular retinol-binding protein/retinoic acid receptor α) expression, and led to apoptosis in HK-2 and human umbilical vein endothelial cells. Furthermore, STRA6, JAK2, STAT5, JNK1, or p38 siRNA and cAMP-PKA inhibitor reversed the repression of CRBP-I/RARα and apoptosis in apo-RBP4 stimulation. In conclusion, this study indicates that the increase of apo-/holo-RBP4 concentration may influence STRA6 signaling, finally causing apoptosis.

Risk interaction of obesity, insulin resistance and hormone-sensitive lipase promoter polymorphisms (LIPE-60 C > G) in the development of fatty liver.

BACKGROUND: Hormone sensitive lipase (HSL) promoter (LIPE-60 C > G) polymorphism has been found to be involved in hepatic steatosis, obesity, diabetes and dyslipidemia. The precise interactions between these risk factors and genetic susceptibility that may affect non-alcoholic fatty liver disease (NAFLD) are still not fully determined. METHODS: A cross-sectional study was conducted in 1056 men. To avoid the confounding effect of plasma glucose, the study population was classified into normal glucose tolerance (NGT, n = 729) and glucose intolerance (GI, n = 299) groups. NAFLD was diagnosed by abdominal ultrasound after ruling out any history of alcohol abuse. A multivariate regression model was used to estimate the impact of these factors on NAFLD. RESULTS: In the NGT group, subjects with NAFLD often have complicated metabolic abnormalities. The coexistence of NAFLD and GI has been demonstrated to have a synergistic effect raising BMI, serum insulin and HOMA-insulin resistance (HOMA-IR). BMI and adipose-insulin resistance (Adipo-IR), but not HOMA-IR, significantly contributed to a greater risk of developing NAFLD. Serum triglyceride was significantly up-regulated in men with the (CG + GG) genotype of HSL promoter polymorphism, NAFLD and Adiopo-IR in sequence. CONCLUSION: Adipo-IR, rather than HOMA-IR, appears to be a consistent insulin resistance index in the study of NAFLD. G allele of the HSL promoter polymorphism may contribute the greatest impact raising serum triglyceride in a state of glucose intolerance.

Better Detection of Peripheral Arterial Disease with Toe-Brachial Index Compared to Ankle-Brachial Index among Taiwanese Patients with Diabetic Kidney Disease.

BACKGROUND: Ankle-brachial index (ABI) is a simple method for diagnosing peripheral artery disease (PAD) but has limited reliability in patients with diabetes mellitus (DM) because of medial artery calcification. Our study aims to investigate whether the toe brachial index (TBI) or the cardio-ankle vascular index (CAVI) has a better detection over the ABI for diagnosing PAD in diabetic kidney disease (DKD). MATERIALS AND METHODS: A cohort of 368 patients (mean age 68.59 ± 13.14 years, 190 males and 178 females) with type 2 DM underwent ABI, TBI, and CAVI measurements at our outpatient clinic. RESULTS: Of all enrolled patients, the TBI is significant in evaluating PAD, especially in patients whose chronic kidney disease (CKD) stage 3a with adjusted odds ratio (AOR) = 6.50, 95% confidence interval (CI) 1.63-25.97, p = 0.0080, stage 3b AOR = 7.47, 95% CI 1.52-36.81, p = 0.0135, and stage 4-5 AOR = 20.13, 95% CI 1.34-94.24, p = 0.0116. CAVI is also significant in CKD stage 1 with AOR = 0.16, 95% CI 0.03-0.77, p = 0.0223, stage 2 with AOR = 0.18, 95% CI 0.04-0.74, p = 0.0180, and stage 3a AOR = 0.31, 95% CI 0.10-0.93, p = 0.0375. CONCLUSION: TBI has a better yield of detection of PAD compared to ABI among Taiwanese patients with DKD. CAVI may play a role in the early stage of DKD.