Increased Production of Interleukin-10 and Tumor Necrosis Factor-Alpha in Stimulated Peripheral Blood Mononuclear Cells after Inhibition of S100A12.

Sepsis may induce immunosuppression and result in death. S100A12 can bind to the receptor for advanced glycation end-products (RAGE) and Toll-like receptor (TLR)4 following induction of various inflammatory responses. It is unclear whether S100A12 significantly influences the immune system, which may be associated with sepsis-related mortality. We measured plasma S100A12 levels and cytokine responses (mean ± standard error mean) of lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) after S100A12 inhibition in healthy controls and patients with sepsis on days one and seven. Day one plasma soluble RAGE (sRAGE) and S100A12 levels in patients with sepsis were significantly higher than those in controls (2481.3 ± 295.0 vs. 1273.0 ± 108.2 pg/mL, p < 0.001; 530.3 ± 18.2 vs. 310.1 ± 28.1 pg/mL, p < 0.001, respectively). Day seven plasma S100A12 levels in non-survivors were significantly higher than those in survivors (593.1 ± 12.7 vs. 499.3 ± 23.8 pg/mL, p = 0.002, respectively). In survivors, plasma sRAGE levels were significantly decreased after 6 days (2297.3 ± 320.3 vs. 1530.1 ± 219.1 pg/mL, p = 0.009, respectively), but not in non-survivors. Inhibiting S100A12 increased the production of tumor necrosis factor (TNF)-α and interleukin (IL)-10 in stimulated PBMCs for both controls and patients. Therefore, S100A12 plays an important role in sepsis pathogenesis. S100A12 may competitively bind to TLR4 and RAGE, resulting in decreased IL-10 and TNF-α production.

Decreased Monocyte HLA-DR Expression in Patients with Sepsis and Acute Kidney Injury.

Background and objectives: Acute kidney injury (AKI) is common in critically ill patients, especially those with sepsis. Persistently low human leukocyte antigen (HLA)-DR expression in monocytes reflects the decreased function of antigen-presenting cells, contributing to poor outcomes in sepsis. This study aimed to establish an association between AKI and HLA-DR expression in monocytes of patients with sepsis. Materials and Methods: We detected HLA-DR expression in monocytes and measured plasma levels of S100A12, high-mobility group box 1 (HMGB1), advanced glycation end products (AGE), and soluble receptor for AGE (sRAGE) from septic patients and healthy controls. Results: HLA-DR expression in monocytes was decreased in patients with AKI than in those without AKI (29.8 ± 5.0% vs. 53.1 ± 5.8%, p = 0.005). Compared with AKI patients, the mean monocyte HLA-DR expression in patients with end-stage renal disease was increased without statistical significance. There were no differences in the AGE/sRAGE ratio and plasma levels of S100A12, HMGB1, AGE, and sRAGE between patients with and without AKI. Conclusions: Compared with septic patients without AKI, patients with AKI had significantly lower HLA-DR expression in monocytes. The role of hemodialysis in monocyte HLA-DR expression needs further studies to explore.

Mechanical power during extracorporeal membrane oxygenation and hospital mortality in patients with acute respiratory distress syndrome.

BACKGROUND: Mechanical power (MP) refers to the energy delivered by a ventilator to the respiratory system per unit of time. MP referenced to predicted body weight (PBW) or respiratory system compliance have better predictive value for mortality than MP alone in acute respiratory distress syndrome (ARDS). Our objective was to assess the potential impact of consecutive changes of MP on hospital mortality among ARDS patients receiving extracorporeal membrane oxygenation (ECMO). METHODS: We performed a retrospective analysis of patients with severe ARDS receiving ECMO in a tertiary care referral center in Taiwan between May 2006 and October 2015. Serial changes of MP during ECMO were recorded. RESULTS: A total of 152 patients with severe ARDS rescued with ECMO were analyzed. Overall hospital mortality was 53.3%. There were no significant differences between survivors and nonsurvivors in terms of baseline values of MP or other ventilator settings. Cox regression models demonstrated that mean MP alone, MP referenced to PBW, and MP referenced to compliance during the first 3 days of ECMO were all independently associated with hospital mortality. Higher MP referenced to compliance (HR 2.289 [95% CI 1.214-4.314], p = 0.010) was associated with a higher risk of death than MP itself (HR 1.060 [95% CI 1.018-1.104], p = 0.005) or MP referenced to PBW (HR 1.004 [95% CI 1.002-1.007], p < 0.001). The 90-day hospital mortality of patients with high MP (> 14.4 J/min) during the first 3 days of ECMO was significantly higher than that of patients with low MP (≦ 14.4 J/min) (70.7% vs. 46.8%, p = 0.004), and the 90-day hospital mortality of patients with high MP referenced to compliance (> 0.53 J/min/ml/cm H2O) during the first 3 days of ECMO was significantly higher than that of patients with low MP referenced to compliance (≦ 0.53 J/min/ml/cm H2O) (63.6% vs. 29.7%, p < 0.001). CONCLUSIONS: MP during the first 3 days of ECMO was the only ventilatory variable independently associated with 90-day hospital mortality, and MP referenced to compliance during ECMO was more predictive for mortality than was MP alone.

Simple obstructive sleep apnea patients without hypertension or diabetes accelerate kidney dysfunction: a population follow-up cohort study from Taiwan.

BACKGROUNDS: Obstructive sleep apnea (OSA) is common in patients on hemodialysis, but its correlation with chronic kidney disease (CKD) is not clear. We aimed to clarify the relationship between OSA without hypertension or diabetes and incidence of CKD in Taiwan. METHODS: This population-based cohort study consisted of patients with newly diagnosed OSA between 2000 and 2009. The comparison cohort was matched for age, sex, diabetes mellitus, and hypertension. All subjects previously diagnosed with acute or chronic kidney disease were excluded. The primary end point was newly diagnosed CKD. RESULTS: We identified 6866 subjects with OSA during the 10-year study period. The median duration until development of CKD in the OSA cohort was 3.2 years, 2.5 months earlier than that in the non-OSA cohort. After exclusion of hypertension and diabetes, 4319 OSA patients was identified and the hazard ratio (HR) of CKD with OSA was 1.37 (95 % confidence interval [CI], 1.05-1.77; p = 0.019). In the subgroup analysis, an increased incidence of CKD in OSA was observed in women (HR, 1.41; 95 % CI, 1.12-1.78; p = 0.0036). CONCLUSIONS: This longitudinal population-based cohort study provides evidence that patients with OSA even without diabetes or hypertension are at higher risk of developing CKD over the next 3 years and nearly 2.5 months earlier than the non-OSA cohort, particularly women.

Obstructive Sleep Apnea Independently Increases the Incidence of Heart Failure and Major Adverse Cardiac Events: A Retrospective Population-Based Follow-Up Study.

BACKGROUND: Obstructive sleep apnea (OSA) is common in heart failure (HF) patients and exacerbates the outcome of this chronic disease. However, the frequency of HF arising from OSA is varied, with little supporting literature. Here, we aimed to clarify the incidence risk of HF and major adverse cardiac events (MACEs) in OSA patients from the Taiwan large database. METHODS AND RESULTS: From 2000-2010, a total of 2699 newly diagnosed OSA patients after polysomnographic study and 13,490 non-OSA patients utilizing 1:5 matching was enrolled and followed to 2011. Compared to the non-OSA cohort, the OSA cohort increased its MACEs incidence 1.95-fold high and HF incidence reached its highest level, up to 2.75-fold [confidential interval (CI): 1.76-4.29; p value < 0.001]. The most common MACE event was stroke, with a 1.75-fold higher risk in the OSA cohort (CI: 1.37-2.20; p value < 0.001). Although the trend is similar, the OSA cohort showed an increased incidence of atrial fibrillation of approximately 1.63-fold high, (CI: 0.78-3.40; p value: 0.193) and 1.44 high, (CI: 0.74-2.79; p value: 0.287) in myocardial infarction. Between genders, HF risk is considerably higher in female OSA cohort than in corresponding males [female: 6.13 (2.68-14.00), p value < 0.01; male: 1.95 (1.11-3.43), p value = 0.020]. CONCLUSIONS: OSA patients have nearly triple the HF incidence risk than the non-OSA population, particularly in female OSA patients.

Fasting but not changes of plasma metabolome during oral glucose tolerance tests improves the diagnosis of severe coronary arterial stenosis.

BACKGROUND: Noninvasive stress tests for the diagnosis of significant coronary arterial stenosis requiring intervention are not perfect. We investigated whether plasma metabolome during the oral glucose tolerance test (OGTT) can improve the diagnosis. METHODS: A total of 117 subjects with positive stress test results who received coronary angiography were recruited. After excluding subjects with a history of myocardial infarction and subjects who did not receive OGTT, the 18 subjects without significant stenosis were selected as controls. Another 18 age- and sex-matched subjects with significant stenosis were selected as cases. Plasma metabolome from samples obtained in fasting, 30 and 120 min after OGTT was measured using liquid chromatography combined with time-of-flight mass spectrometry. RESULTS: We found five metabolites which can identify patients with significant stenosis independent to clinical risk factors, including diabetes, hypertension, hypercholesterolaemia, smoking and history of percutaneous coronary intervention (all P < 0·05). The area under the receiver operating characteristic (AUROC) curve of these metabolites was 0·799-0·818 at fasting and 30 min after OGTT. The addition of metabolites to clinical factors increases the AUROC (0·616, 95%CI 0·429-0·803 for model with clinical factors only; 0·824, 95%CI 0·689-0·959 for model with four metabolites and clinical factors). The changes of plasma metabolite levels during OGTT did not significantly improve the diagnostic performance. CONCLUSIONS: Fasting plasma metabolome, but not change of plasma metabolome during OGTT, can improve the diagnosis of significant stenosis in patients with positive noninvasive stress test results.

Chemokine MCP1/CCL2 and RANTES/CCL5 gene polymorphisms influence Henoch-Schönlein purpura susceptibility and severity.

BACKGROUND/PURPOSE: Henoch-Schönlein purpura (HSP) is the most common small vessel vasculitis in children. It is considered to be an IgA-containing immune complex-mediated disease. Chemokines are small secreted proteins that attract leukocytes during inflammation. Our aim was to determine the serum levels of chemokines and investigate the association of chemokine gene polymorphisms with childhood HSP. METHODS: Serum levels of chemokines (interleukin-8/CXCL8, MCP-1/CCL2, RANTES/CCL5, MIG/CXCL9, and IP-10/CXCL10) were determined using cytometric beads arrays. We investigated the association of three single-nucleotide polymorphisms (SNPs) MCP1/CCL2 -2518C/T, RANTES/CCL5 -403C/T, and RANTES/CCL5 -28C/G with HSP in 85 HSP patients and 136 healthy controls. RESULTS: Five serum chemokine levels were significantly elevated in patients with the acute stage of HSP compared to the normal controls (p < 0.05). MCP1/CCL2 -2518 TT genotype and T allele were associated with the risk for HSP with OR (95% CI) 3.32 (1.45-7.59) and 1.78 (1.20-2.64), respectively. The RANTES/CCL5 -28 GG genotype was associated with a significantly lower percentage of corticosteroid usage and lower corticosteroid accumulative dose in HSP patients. RANTES/CCL5 -403 TC and TT genotype were significantly associated with renal manifestations with an OR (95% CI) of 4.33 (1.44-12.99), adjusted for sex and age and the other two SNP genotypes. CONCLUSION: Our results support the fact that chemokines play important roles in the pathogenesis of HSP. MCP1/CCL2 gene polymorphisms were associated with susceptibility for HSP. RANTES/CCL5 gene polymorphisms may be related to disease severity and HSP nephritis.

Lupus women with delivery with higher risk of heart failure compared with those without pregnancy but neutral in major adverse cardiovascular events. A population-based matched cohort study.

OBJECTIVES: Limited data exist regarding the incidence rate and relative risks of major adverse cardiovascular events in women with lupus who have successfully delivered compared to those who have not been pregnant. METHODS: A retrospective, population-based matched cohort study was performed on women with lupus from 2000 to 2006. In total, 149 women with lupus and a successful delivery were enrolled as the study cohort, and 446 women with lupus with no pregnancy, frequency-matched for age, duration of systemic lupus erythematosus, hypertension and diabetes as the comparison cohort. Poisson regression modeling was used to determine the relative risk of a successful delivery on the risk of major adverse cardiovascular events among the women with lupus. RESULTS: Successful delivery for women with lupus had a neutral effect on major adverse cardiovascular events. The incidence rate of any major adverse cardiovascular event was 1,139 per 100,000 person-years, consisting mainly of heart failure, stroke, and all-cause mortality, with incidence rates of 652, 481 and 481 per 100,000 person-years, respectively. The women with lupus and a successful delivery had a higher incidence rate of heart failure (RR=5.4, 95% CI=1.4-21.7, p<0.017). CONCLUSIONS: Major adverse cardiovascular events and mortality were rare events in the women with lupus of reproductive age. Successful delivery had a neutral effect on major adverse cardiovascular events in the women with lupus, although they had a higher incidence of heart failure.

Major adverse cardiovascular events in adult congenital heart disease: a population-based follow-up study from Taiwan.

BACKGROUND: The aim of the present study was to identify the long-term major adverse cardiovascular events (MACE) in adult congenital heart disease (ConHD) patients in Taiwan. METHODS: From the National Health Insurance Research Database (1997-2010), adult patients (≥18 years) with ConHD were identified and compared to non-ConHD control patients. The primary end point was the incidence of MACE. Cox proportional hazards models were used to compute hazard ratios as estimates for multivariate adjusted relative risks with or without adjusting for age and sex. RESULTS: A total of 3,267 adult patients with ConHD were identified between 2000 and 2003 with a median follow-up of 11 years till December 31, 2010. The five most common types of ConHD were atrial septal defects, ventricular septal defects, patent ductus arteriosus, tetralogy of Fallot, and pulmonary stenosis. Overall, the incidence of MACE was 4.0-fold higher in the ConHD group compared with the controls. After adjustment for age and gender, the patients with ConHD had an increased risk of heart failure, malignant dysrhythmia, acute coronary syndrome, and stroke. The adult ConHD patients had a decreased life-long risk of MACE if they received surgical correction, especially in the patients with atrial septal defects. CONCLUSIONS: After a median of 11 years of follow-up, the Taiwanese patients with ConHD were at an increased risk of life-long cardiovascular MACE, including heart failure, stroke, acute coronary syndrome, and malignant dysrhythmia. Surgical correction may help to decrease long-term MACE in ConHD patients, especially those with ASD.

Influence of gestational hypertension and maternal air pollutant exposure on birth outcomes.

The relationship between exposure to air pollutants and fetal growth outcomes has shown inconsistency, and only a limited number of studies have explored the impact of air pollution on gestational hypertension and birth outcomes. This study aimed to evaluate how maternal exposure to air pollutants and blood pressure could influence fetal birth outcomes. A total of 55 women with gestational hypertension and 131 healthy pregnant women were enrolled in this study. Data pertaining to personal characteristics, prenatal examinations, outdoor air pollutant exposure, and fetal birth outcomes were collected. The study revealed that fetal birth weight and abdominal circumference exhibited a significant reduction among women with gestational hypertension compared to healthy pregnant women, even after adjustments for body mass index, gestational age, and exposure to air pollutants had been made. Moreover, maternal exposure to outdoor air pollutants displayed a notable correlation with decreased birth length of fetuses. Consequently, the study concluded that maternal blood pressure and exposure to outdoor air pollutants during pregnancy potentially stand as pivotal factors influencing fetal birth outcomes.

Replication of genome-wide association signals of type 2 diabetes in Han Chinese in a prospective cohort.

BACKGROUND: A recent genome-wide association study for type 2 diabetes in Han Chinese identified several novel genetic variants. We investigated their associations with quantitative measures to explore the mechanism by which these variants influence glucose homoeostasis. We also examined whether these variants predict progression to diabetes in a large prospective family based Chinese cohort. METHODS: Five single nucleotide polymorphisms (SNPs) near the protein tyrosine phosphatase, receptor type, D (PTPRD), SRR, MAF/WWOX, and KCNQ1 genes were genotyped in 1138 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance study. RESULTS: At baseline, the risk-conferring rs7192960 C allele near the MAF/WWOX genes was associated with lower homoeostasis model assessment of ß-cell (HOMA-ß) (P = 0·01) and second-phase insulin response in oral glucose tolerance test (OGTT) (P = 0·04). The risk-conferring rs2237897 C alleles in the KCNQ1 gene were associated with higher fasting glucose (P = 0·009), lower HOMA-ß (P = 0·03), and lower first-phase insulin response in OGTT (P = 0·03). Over an average follow-up period of 5·43 years, participants with the risk-conferring rs17584499 TT genotype in the PTPRD gene were more likely to progress from nondiabetes to diabetes than were noncarriers (hazard ratio: 8·82, P = 4 × 10(-5) ). The risk-conferring T allele in the PTPRD gene was associated with greater increase in homoeostasis model assessment of insulin resistance (HOMA-IR) (P = 0·04) over time. PTPRD gene expression in human adipose tissues was negatively associated with fasting insulin levels and HOMA-IR. CONCLUSION: Genetic variants near the KCNQ1 and MAF/WWOX genes are associated with reduced insulin secretion. The PTPRD genetic variant appears to be associated with progression to diabetes in Han Chinese, most likely through increased insulin resistance.

Common sequence variants in CD36 gene and the levels of triglyceride and high-density lipoprotein cholesterol among ethnic Chinese in Taiwan.

BACKGROUND: Evidence of the genetic association between CD36 candidate gene and the risk of metabolic syndrome and its components has been inconsistent. This case-control study assessed the haplotype-tagged SNPs from CD36 on the risk of metabolic syndrome and components. METHODS AND RESULTS: We recruited 1,000 cases and age, gender-matched controls were randomly selected from the participants with metabolic syndrome defined by International Diabetes Federation. Overall, the haplotype tagged SNPs of CD36 gene were not related to the risk of metabolic syndrome. For individuals with normal lipid levels, several SNPs were significantly associated with the triglycerides and HDL-cholesterol levels: Subjects with rs3211848 homozygote had a higher triglyceride level (99.16 ± 2.61 mg/dL), compared with non-carriers (89.27 ± 1.45 mg/dL, P = 0.001). In addition, compared with non-carriers, individuals with rs1054516 heterozygous and homozygous genotypes had a significantly lower HDL-cholesterol (46.6 ± 0.46 mg/dL for non-carrier, 44.6 ± 0.36 mg/dL for heterozygous, and 44.3 ± 0.56 mg/dL for homozygous, P = 0.0008). CONCLUSION: The CD36 gene variants were significantly associated with triglycerides and HDL-cholesterol concentrations among ethnic Chinese in Taiwan.

Biosignatures: comparative effectiveness research in biomarker clinical studies.

Due to increased healthcare expenditure and the need for evidence-supported clinical decision-making, clinical evaluation using comparative effectiveness research (CER) was initially proposed in the US. CER consists of generating and synthesizing evidence in relative benefits, harms, and costs of different alternatives through direct head-to-head comparisons. CER studies can help identify the most effective interventions for patients under specific circumstances, and therefore improve the efficiency of the healthcare system. A Biosignatures project newly launched in Taiwan was inspired by CER, aiming at using discovered biomarkers panel as tools in early detection of disease and prediction of treatment effectiveness.

OSA Treatment on Cardio- and Cerebrovascular Comorbidities: A Long-term Nationwide Cohort Study.

OBJECTIVE: To compare the cardio- and cerebrovascular outcomes and survival rates of surgical and nonsurgical interventions for patients with obstructive sleep apnea (OSA) based on a national population-based database. STUDY DESIGN: Retrospective cohort study. SETTING: Taiwan National Health Insurance Research Database. METHODS: We analyzed all cases of OSA among adults (age >20 years and confirmed with ICD-9-CM) from January 2001 to December 2013. We compared the patients with OSA who received upper airway surgery with age-, sex-, and comorbidity index-matched controls with continuous positive airway pressure (CPAP) treatment. The risk of myocardial infarction (MI) or stroke after treatment of OSA-related surgery versus CPAP was investigated. RESULTS: During follow-up, 112 and 92 incident cases of MI occurred in the OSA surgery and CPAP treatment groups, respectively (rates of 327 and 298 per 100,000 person-years). Furthermore, 50 and 39 cases were newly diagnosed with stroke in the OSA surgery and CPAP treatment groups (rates of 144 and 125 per 100,000 person-years). Cox proportional hazard regressions showed that the OSA treatment groups (OSA surgery vs CPAP) were not significantly related to MI (hazard ratio, 1.03 [95% CI, 0.781-1.359]; P = .833) and stroke (hazard ratio, 1.12 [95% CI, 0.736-1.706]; P = .596) at follow-up, after adjustment for sex, age at index date, days from diagnosis to treatment, and comorbidities. CONCLUSION: Our study demonstrated that there was no difference of cardio- and cerebrovascular results between CPAP and surgery for patients with OSA in a 13-year follow-up. LEVEL OF EVIDENCE: 3.

Diabetic foot disease in subjects with End-stage renal Disease: A nationwide study over 14 years highlighting an emerging threat.

AIMS: To disclose prevalence, demographic, foot characteristics as well as management and lower-extremity amputations (LEAs) of subjects with end-stage renal disease (ESRD) on diabetic foot diseases (DFDs). METHODS: Data were derived from the Taiwan National Health Insurance Research Database between 2004 and 2017. DFDs were defined as ulcers, infections, or severe peripheral arterial diseases (PADs) in patients with type 2 diabetes. Clinical characteristics were analyzed between subjects with and without ESRD. RESULTS: Subjects with ESRD have increased impacts on the DFD population either from annual prevalence (2.7 % to 10.42 %, P for trend < 0.001), or proportional representation in LEAs (7.91 % to 26.37 %, P < 0.001) over 14 years. The annual trends for major-LEAs rates have decreased in both subjects with and without ESRD (13.67 % to 5.82 % and 3.48 % to 1.47 %, both P < 0.001). Notably, the concomitant increase of endovascular treatments (EVTs) (7.09 % to 29.41 %, P < 0.001) was associated with the decrease of major-LEAs (P for interaction < 0.001) in subjects with ESRD. CONCLUSIONS: As the annual prevalence of subjects with ESRD has increased 3.9-fold over years, they now account for more than 30% of annual major-LEA of the total DFD population. Interdisciplinary team approach and aggressive EVTs might reduce major-LEAs in these patients.

A genome-wide association study for melatonin secretion.

Melatonin exerts a wide range of effects among various tissues and organs. However, there is currently no study to investigate the genetic determinants of melatonin secretion. Here, we conducted a genome-wide association study (GWAS) for melatonin secretion using morning urine 6-hydroxymelatonin sulfate-to-creatinine ratio (UMCR). We initially enrolled 5000 participants from Taiwan Biobank in this study. After excluding individuals that did not have their urine collected in the morning, those who had history of neurological or psychiatric disorder, and those who failed to pass quality control, association of single nucleotide polymorphisms with log-transformed UMCR adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for estimated glomerular filtration rate (eGFR). A total of 2373 participants underwent the genome-wide analysis. Five candidate loci associated with log UMCR (P value ranging from 6.83 × 10-7 to 3.44 × 10-6) encompassing ZFHX3, GALNT15, GALNT13, LDLRAD3 and intergenic between SEPP1 and FLJ32255 were identified. Similar results were yielded with further adjustment for eGFR. Interestingly, the identified genes are associated with circadian behavior, neuronal differentiation, motor disorders, anxiety, and neurodegenerative diseases. We conducted the first GWAS for melatonin secretion and identified five candidate genetic loci associated with melatonin level. Replication and functional studies are needed in the future.

Genetic predisposition and nongenetic risk factors of thiazolidinedione-related edema in patients with type 2 diabetes.

OBJECTIVE: This study aimed to analyze the association of thiazolidinedione (TZD)-related edema with genetic and clinical variables and develop a simple points system to predict the risk of developing TZD-related edema. METHODS: Fifty-eight (21.6%) of 268 individuals who received TZD for type 2 diabetes developed peripheral edema. Twenty-eight tag single nucleotide polymorphisms (SNPs) from candidate genes involved in sodium and water reabsorption were genotyped. Cox regression and logistic regression models were used to analyze the associations of different genotypes and weighted genotypic scores with TZD-related edema risk. RESULTS: Individuals with edema were older, predominantly female, and had greater weight gain. The AQP2 rs296766 T allele was associated with TZD-related edema [allelic P=0.0059; odds ratio (OR), 2.89; 95% confidence interval (CI), 1.61-5.17]. The SLC12A rs12904216 G allele had borderline significance (allelic P=0.049), which disappeared after correction for multiple testing. Patients with two SNP-based (AQP2 rs296766 and SLC12A1 rs12904216), who weighted genotypic scores within the top quartile, had a higher risk of developing TZD-related edema (OR, 16.45; 95% CI, 3.05-88.76). Combining the weighted genetic scores of two SNPs or all SNPs with age and sex information significantly improved the predictive power for TZD-related edema. We also developed a simple risk factor-based points system to predict an individual's risk of developing TZD-related edema. CONCLUSION: A clinically applicable prediction model including age, sex, and genetic information from AQP2 rs296766 and/or SLC12A rs12904216 SNPs can be developed to estimate the risk of TZD-related edema in type 2 diabetes patients.

Multilevel analysis of habitual physical activity and metabolic syndrome in Northern Taiwan.

OBJECTIVE: This study examines the relationship between the availability of public facilities for habitual physical activity in the community and metabolic syndrome in northern Taiwan, one of most densely populated countries in the world. METHODS: Subjects consisted of 14,658 participants (43.3% men and 56.7% women) ≥40 years old (mean=59.5) from 10 districts of Taoyuan County in a health check-up program in 2004-2005. Public facilities for habitual physical activity included school campuses and parks, and the density of such facilities was categorized into four levels. Multilevel logistic regression models were created to examine the effect on metabolic syndrome at both the individual and the contextual level using MLwiN software. RESULTS: The addition of the contextual variable to the model that included individual characteristics led to a further reduction of 7.2% in the variance. Using the facility density level I as the reference, the odds ratios (95% confidence interval) of metabolic syndrome for levels II, III, and IV were 0.87 (0.71-1.07), 0.87 (0.68-1.12), and 0.78 (0.61-0.99), respectively, with the trend test reaching significance. CONCLUSION: Greater availability of free facilities for habitual physical activity in a district was associated with a lower risk of metabolic syndrome among its residents.

Plasma fatty acids and the risk of metabolic syndrome in ethnic Chinese adults in Taiwan.

BACKGROUND: Evidence of predictive power of various fatty acids on the risk of metabolic syndrome was scanty. We evaluated the role of various fatty acids, including saturated fat, monounsaturated fat, transfat, n-6 fatty acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for the risk of the metabolic syndrome in Taiwan. RESULTS: A nested case-control study based on 1000 cases of metabolic syndrome and 1:1 matched control subjects. For saturated fat, monounsaturated fat and transfat, the higher the concentration the higher the risk for metabolic syndrome: participants in the highest quintile had a 2.22-fold (95% confidence interval [CI], 1.66 to 2.97) higher risk of metabolic syndrome. In addition, the participants in higher EPA quintiles were less likely to have the risk of metabolic syndrome (adjusted risk, 0.46 [0.34 to 0.61] for the fifth quintile). Participants in the highest risk group (low EPA and high transfat) had a 2.36-fold higher risk of metabolic syndrome (95% CI, 1.38 to 4.03), compared with those in the lowest risk group (high EPA and low transfat). For prediction power, the area under ROC curves increased from 0.926 in the baseline model to 0.928 after adding fatty acids. The net reclassification improvement for metabolic syndrome risk was substantial for saturated fat (2.1%, P = 0.05). CONCLUSIONS: Plasma fatty acid components improved the prediction of the metabolic syndrome risk in Taiwan.