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Myostatin is a negative regulator of skeletal muscle and myocardial mass. The relationship between myocardial ischemia and scar burden and levels of myostatin has not been established.We enrolled symptomatic patients with heart failure (HF) with a left ventricular ejection fraction (LVEF) 45 % and controls (LVEF ≥ 45 %). Serum levels of myostatin were measured. Single-photon emission computed tomography (SPECT) imaging was interpreted, and summed scores of 17 stress and rest image segments in 5-point scale produced the summed stress score (SSS) and summed rest score (SRS), respectively. The summed difference score (SDS) was calculated as the difference between the SSS and SRS.Ninety-six patients with HF and 103 controls were enrolled. The levels of myostatin were higher in the HF group. In linear regression analysis, myostatin level was positively correlated with SSS (β coefficient = 6.840, p = 0.013) and SRS (β coefficient = 5.557, p = 0.026), but not correlated with SDS. The areas under the receiver operating characteristic curves of myostatin levels for SSS ≥ 8 and SSS ≥ 13 were 0.6813 ± 0.04854 (p 0.001) and 0.7498 ± 0.04402 (p 0.001), respectively.Serum levels of myostatin were correlated with the extent of myocardial scarring as defined by SPECT imaging. Serum levels of myostatin may be a predictor of myocardial scar burden.

The need is growing to create medical big data based on the electronic health records collected from different hospitals. Errors for sure occur and how to correct them should be explored.Electronic health records of 9,197,817 patients and 53,081,148 visits, totaling about 500 million records for 2006-2016, were transmitted from eight hospitals into an integrated database. We randomly selected 10% of patients, accumulated the primary keys for their tabulated data, and compared the key numbers in the transmitted data with those of the raw data. Errors were identified based on statistical testing and clinical reasoning.Data were recorded in 1573 tables. Among these, 58 (3.7%) had different key numbers, with the maximum of 16.34/1000. Statistical differences (P 0.05) were found in 34 (58.6%), of which 15 were caused by changes in diagnostic codes, wrong accounts, or modified orders. For the rest, the differences were related to accumulation of hospital visits over time. In the remaining 24 tables (41.4%) without significant differences, three were revised because of incorrect computer programming or wrong accounts. For the rest, the programming was correct and absolute differences were negligible. The applicability was confirmed using the data of 2,730,883 patients and 15,647,468 patient-visits transmitted during 2017-2018, in which 10 (3.5%) tables were corrected.Significant magnitude of inconsistent data does exist during the transmission of big data from diverse sources. Systematic validation is essential. Comparing the number of data tabulated using the primary keys allow us to rapidly identify and correct these scattered errors.

To explore the complex genetic architecture of common diseases and traits, we conducted comprehensive PheWAS of ten diseases and 34 quantitative traits in the community-based Taiwan Biobank (TWB). We identified 995 significantly associated loci with 135 novel loci specific to Taiwanese population. Further analyses highlighted the genetic pleiotropy of loci related to complex disease and associated quantitative traits. Extensive analysis on glycaemic phenotypes (T2D, fasting glucose and HbA1c) was performed and identified 115 significant loci with four novel genetic variants (HACL1, RAD21, ASH1L and GAK). Transcriptomics data also strengthen the relevancy of the findings to metabolic disorders, thus contributing to better understanding of pathogenesis. In addition, genetic risk scores are constructed and validated for absolute risks prediction of T2D in Taiwanese population. In conclusion, our data-driven approach without a priori hypothesis is useful for novel gene discovery and validation on top of disease risk prediction for unique non-European population.

This pilot, randomized, open-label controlled study compared the basal–bolus regimens of insulin glargine (IG) and neutral protamine Hagedorn (NPH) insulin in stroke patients with hyperglycemia receiving intensive care. The study recruited acute stroke patients requiring intensive care within 72 h (h) of onset and had blood glucose > 200 mg/dL. 50 patients received IG (n = 26) or NPH (n = 24) with added short-acting prandial regular insulin over a 72-h period. The primary end point was the percentage of glucose within 80–180 mg/dL assessed through continuous glucose monitoring. The baseline characteristics were comparable, except the IG had higher glucose pre-randomization than the NPH (290.69 ± 82.31 vs. 246.04 ± 41.76 mg/dL, P = 0.021). The percentage of time with glucose between 80 and 180 mg/dL was 45.88 ± 27.04% in the IG and 53.56 ± 22.89% in the NPH (P = 0.341) and the percentage of glucose reduction was 31.47 ± 17.52% in the IG and 27.28 ± 14.56% in the NPH (P = 0.374). The percentage of time with glucose Trial registration ClinicalTrials.gov, NCT02607943. Registered 18/11/2015, https://clinicaltrials.gov/ct2/show/NCT02607943.

Since bone and fat mass are derived from mesenchyme in early development, adipokines secreted by adipose tissue may have an effect on bone metabolism. The relationship between adiponectin and bone mineral density (BMD) has been inconsistent in previous reports, with results being dependent on age, gender, menopausal status and bone sites. We investigated the relationship between serum adiponectin levels and the BMD of proximal femur and vertebrae bones in a 96-week longitudinal study of post-menopausal women with repeated measures of both. Linear regression models were used to determine the relation between adiponectin and BMD at each time point cross-sectionally, and a generalized estimating equation (GEE) model was used to investigate the longitudinal trends. Among 431 subjects, 376 (87%) provided baseline adiponectin measurements and 373 provided more than two measurements for longitudinal analysis. The means of serum adiponectin and BMD decreased with time. In linear regression models, adiponectin at baseline, the 48th week and the 96th week appeared to be inversely associated with BMD of proximal femur bone, but not lumbar spine after adjusting for age and various confounders. However, they all turn insignificant with further adjustment of body mass index. The inverse association between adiponectin and BMD of proximal femur is substantiated by all generalized equation models. Before adding the BMI in the model, the increase of 1 mg/dL of adiponectin can accelerate the decrease of proximal femur BMD by 0.001 (SE = 0.0004, p = 0.008). With BMI in the model, the drop rate was 0.0008 (SE = 0.0004, p = 0.026) and remained similar with further adjustment of two bone turnover markers. In this longitudinal analysis with both adiponectin and BMD measured at three time points, we demonstrate that with the increase of adiponectin level, the decline of proximal femur BMD in postmenopausal women accelerated during a period of 96 weeks.

Objective Concurrent autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) is being reported more frequently. Several somatic mutations including PRKACA, GNAS, and CTNNB1 were identified in cortisol-producing adenomas (CPAs). The presence of these mutations in unilateral PA (uPA) patients concurrent with ACS (uPA/ACS) is not well known. This study aimed to investigate the prevalence of these mutations and their clinical vs pathological characteristics in uPA/ACS. Design This is a retrospective cohort study. Methods Totally 98 uPA patients from the Taiwan Primary Aldosteronism Investigation registry having overnight 1-mg dexamethasone suppression test (DST) and adrenalectomy from 2016 to 2018 were enrolled. Their adrenal tumors were tested for PRKACA, GNAS, and CTNNB1 mutations. Results 11 patients had CPA-related mutations (7 PRKACA and 4 GNAS). The patients carrying these mutations had higher post-DST cortisol (5.6 vs 2.6 μg/dL, P = 0.003) and larger adenoma (2.2 ± 0.3 vs 1.9 ± 0.7 cm, P = 0.025). Adenomas with these mutations had a higher prevalence of non-classical uPA (72.7% vs 26.3%, P = 0.014). Numerically, slightly more complete clinical success of uPA patients with these mutations was noticed after adrenalectomy, although it was statistically non-significant. Post-DST cortisol levels, adenoma size >1.9 cm, and the interaction of adenoma size >1.9 cm with potassium level were found to be associated with the presence of these mutations. Conclusion Our study showed that CPA-related mutations were detected in 36.7% of uPA/ACS adenomas. The presence of these mutations was associated with higher post-DST cortisol levels, larger adenoma sizes, and a high percentage of non-classical uPA. However, these mutations did not significantly affect the clinical and biochemical outcomes after adrenalectomy of uPA/ACS patients but they showed a better trend.

Introduction: Low muscle function determined unfavorable clinical outcome than low muscle mass; nevertheless, comparison of detrimental parameters among dynapenia, presarcopenia and sarcopenia was sparse. We hypothesized that adiposity is implicated in low muscle function related adverse events. Methods: We recruited community elders to measure handgrip strength and walking speed. Using bioelectronics impedance analyzer to examine body compositions. The faller is indicated of having a fall event in the past one year. Associations of different obesity parameters, metabolic syndrome (MetS) and fall among the groups were analyzed. Results: Among 765 participants, the dynapenia group had higher metabolic profiles, body fat percentage (BFP), waist circumference, and fat to muscle ratio (FMR) than the other groups, whereas the presarcopenia subjects had the lowest obesity parameters. The fallers tended to have poorer muscle function than non-fallers (p

The pathogenesis of diabetic gastroparesis due to visceral neuropathy involves multidimensional mechanisms with limited exploration of gastric mucosal innervation. This study aimed to examine quantitatively this topic and its relationship with gastroparesis symptoms and gastric emptying in diabetes.We prospectively enrolled 22 patients with type 2 diabetes and gastroparesis symptoms and 25 age- and gender-matched healthy controls for comparison. The assessments included: (i) neuropathology with quantification of gastric mucosal innervation density (MID) on endoscopic biopsy; (ii) clinical manifestations based on the Gastroparesis Cardinal Symptom Index (GCSI) questionnaire; and (iii) functional tests of gastric emptying scintigraphy (GES).In patients with diabetes, stomach fullness, bloating and feeling excessively full after meals constituted the most common GCSI symptoms. Seven patients with diabetes (32%) had prolonged gastric emptying patterns. In diabetes, gastric MID was significantly lower in all the regions examined compared with the controls: antrum (294.8 ± 237.0 vs. 644.0 ± 222.0 mm/mmIn diabetes, gastric MID was reduced and GES parameters were prolonged. Both were correlated with gastroparesis symptoms and glycemic control. These findings provide pathology and functional biomarkers for diabetic visceral neuropathy of gastroparesis and underlying pathophysiology.

S14 has been identified as a potent stimulator of de novo hepatic lipogenesis (DNL) in rodents. However, it is unclear how S14 is regulated in humans with non-alcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the relationship between serum S14 and liver steatosis in humans with NAFLD. A total of 614 participants were recruited from community. Liver steatosis were evaluated according to the Ultrasonographic Fatty Liver Indicator (US-FLI), which is a semi-quantitative liver ultrasound score. Anthropometric and biochemical indices were collected for further analysis. The risk of liver steatosis severity was estimated by a cumulative logistic regression model. NAFLD was found in 52.2% of the participants. The subjects with NAFLD showed higher levels of waist circumference, body mass index, insulin resistance, aspartate aminotransferase, dyslipidemia, visceral fat, serum S14 and risk of metabolic syndrome (MetS) than those of controls. Compared with the first tertile of serum S14, the odds ratios for the risk of more severe liver steatosis were 1.22 (95% confidence interval [CI]: 0.78–1.92) for those of the second tertile and 2.08 (95% CI: 1.28–3.39) for the third tertile (P for trend

Context Previous cross-sectional studies show diabetes and higher levels of plasma hemoglobin A1c (HbA1c) are associated with a higher prevalence of gastrointestinal (GI) complications. However, whether the glycemic status is associated with incident acid-related upper GI disorders remains unclear. Objective We aimed to determine the effect of hyperglycemia per se, in terms of HbA1c, on the incidence of acid-related disorders. Methods We analyzed consecutive subjects who had undergone repeated upper endoscopies as part of the health examinations at the National Taiwan University Hospital from 2005 to 2011. Acid-related endoscopic abnormalities were defined as erosive esophagitis (EE), Barrett’s esophagus (BE), and peptic ulcer disease (PUD), which included gastric ulcers (GUs) and duodenal ulcers (DUs). All subjects were categorized by 3 tertiles of HbA1c levels. We analyzed the occurrence of respective acid-related disorders during the follow-up period. Results A total of 11 391 participants (mean HbA1c level 5.6 ± 0.7%) were enrolled in this longitudinal study. During the 38 426.3 person-years of follow-up (mean duration 3.37 ± 1.59 years), the incidence of EE, BE, GU, DU, PUD, and any acid-related disorders were 22.1%, 0.5%, 4.5%, 8.6%, 12.3%, and 30.3%, respectively. The higher HbA1c level was associated with higher risk of disease incidents, except BE, during the follow-up (all log-rank P Conclusion Higher HbA1c level was associated with a higher risk of acid-related upper GI endoscopic abnormalities. Efforts toward better glycemic control may help to prevent the development of late GI complications.

Obesity is a significant risk factor for atherosclerotic cardiovascular disease; however, the "obesity paradox", in which obese patients enjoy superior survival, has been observed in various cardiovascular conditions. Whether this phenomenon exists for peripheral artery disease (PAD) remains uncertain. The goal of this study was to evaluate the relationship between body mass index (BMI) and mortality in patients with PAD.A comprehensive literature search identified seven eligible cohort studies that reported the association between BMI and all cause mortality in patients with PAD. A dose response meta-analysis was done for all cause mortality, short term (30 day or in hospital) mortality and long term mortality. The dose response association between BMI and mortality was also assessed in patients who received endovascular therapy (EVT).The non-linear dose response analysis showed that higher BMI values were associated with a lower mortality risk from the range between 15 kg/mThe obesity paradox was evident in the analysis of long term survival among patients with PAD, with the lowest mortality rates observed in obese patients. However, this association was not observed for short term or in hospital mortality.

This study investigated the alterations of mineral metabolism in patients with Graves’ disease (GD) who achieved euthyroidism. They had higher fibroblast growth factor 23 (FGF23) and phosphorus as compared with healthy subjects. Serum FGF23 was negatively correlated with serum phosphorus. These indicated abnormal mineral metabolism even after 1.6 years of euthyroid status. FGF23 is involved in the mineral homeostasis, especially the regulation of serum phosphorus. Graves’ disease (GD) is associated with accelerated bone turnover, hyperphosphatemia, and elevated serum FGF23. Evidence suggested that serum FGF23 decreased after a 3-month treatment of GD. However, it remains unclear whether serum FGF23, serum phosphorus, and other markers of mineral metabolism will be normalized after euthyroid status achieved. A total of 62 patients with euthyroid GD and 62 healthy control subjects were enrolled, and the median duration of euthyroid status was 1.6 years. Endocrine profiles including thyroid function test, autoantibodies, serum FGF23, and bone turnover markers were obtained and compared between the two groups. Euthyroid GD patients had significantly higher serum FGF23 and phosphorus, and lower 25-hydroxyvitamin D (25(OH)D) and intact parathyroid hormone (iPTH) levels as compared with the control group. Serum FGF23 was significantly and negatively correlated with phosphorus level after adjusted for age, gender, calcium, iPTH, and 25(OH)D in the euthyroid GD group. Serum phosphorus and FGF23 levels remain higher in GD patients even after euthyroid status has been achieved for a median of 1.6 years. Serum FGF23 was negatively correlated with serum phosphorus in euthyroid GD patients. Underlying mechanisms warrant further investigations. Registration number: NCT01660308 and NCT02620085

Recent reports have shown that sleeve gastrectomy (SG) accelerates gastric emptying (GE), but the etiology remains unclear. This study aimed to investigate the factors affecting GE before and after SG. We enrolled 35 normal weight healthy subjects and 23 obese patients receiving SG. The normal individuals and obese patients before and 3 months after SG received oatmeal-based scintigraphy to measure GE. Gastrointestinal symptoms and circulating levels of peptide YY (PYY) were also measured. There were no differences in the GE parameters, including simple half-time at 3 h and percentage of gastric retention at 0.5, 1, 2, and 3 h between healthy controls and pre-SG obese subjects. SG led to accelerated GE, more gastrointestinal symptoms, and increased fasting PYY levels postoperatively. Based on our previously established normal GE values, 18 (78.3%) obese patients with rapid postoperative GE had higher levels of preoperative fasting glucose and glycated hemoglobin, and homeostasis model assessment of the insulin resistance index than those with normal postoperative GE. Twelve (52.2%) obese patients had preoperative diabetes mellitus (DM), and only four (17.4%) remained diabetic after SG. The post-SG gastric retention at 0.5 and 1 h was lower in patients with preoperative DM than in those without preoperative DM. Neither severity of gastrointestinal symptoms nor fasting PYY levels were associated with postoperative GE alterations. Most of the obese patients had accelerated GE after SG. A higher preoperative glycemic profile was associated with rapid post-SG GE.

Background and aims Familial hypercholesterolemia (FH) is an autosomal dominant disorder with paramount health impacts. However, less than 1% FH patients in Taiwan were formally diagnosed, partly due to the lack of reliable cost-effective genetic testing. We aimed at using a next-generation sequencing (NGS) platform as the clinical genetic testing method for FH. Methods We designed probes to capture the whole LDLR gene and all coding sequences of APOB and PCSK9, and then sequenced with Illumina MiSeq platform (2 × 300 bps). The entire pipeline was tested on 13 DNA samples with known causative variants (including 3 large duplications and 2 large deletions). Then we enrolled a new cohort of 28 unrelated FH patients with Dutch Lipid Clinic Network score ≥5. Relatives were included in the cascade screening. Results From the 13 DNA samples, we correctly identify all the variants, including big duplications and deletions. From the new cohort, we identified the causative variants in 21 of the 28 unrelated probands; five of them carrying a novel splice site variant c.1186+2T>G in LDLR. Among the family members, the concentration of LDL cholesterol was 7.82 ± 2.13 mmol/l in LDLR c.1186+2T>G carrier group (n = 26), and was significantly higher than 3.18 ± 1.36 mmol/l in the non-carrier group (n = 25). Conclusions This is the first capture-based NGS testing for FH to cover the whole LDLR genomic region, and therefore making reliable structural variation detection. This panel can comprehensively detect disease-causing variants in LDLR, APOB, and PCSK9 for FH patients.

Background: Lipopolysaccharide-binding protein (LBP) presents bacterial endotoxin, lipopolysaccharides, to cellular surface pattern receptors for immune responses in the gut-brain axis of Parkinson’s disease (PD). Objective: We investigated whether plasma LBP levels were associated with PD severity and progression. Methods: This study included 397 participants (248 PD patients and 149 controls). We measured participants’ plasma levels of LBP and pro-inflammatory cytokines, including TNF-α, IL-6, andIL-17A. PD patients underwent motor and cognition evaluations at baseline and at a mean follow-up interval of 4.7±2.3 years. We assessed the progression of motor and cognition symptoms based on changes in the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III motor score and Mini-Mental State Examination (MMSE) score, respectively. Results: Plasma LBP levels were lower in PD patients than controls (9.08±2.91 vs. 10.10±3.00μg/ml, p

There are several debates on the association between gastric anatomy and weight loss after laparoscopic sleeve gastrectomy (LSG). There is a paucity of data on the impact of gastric wall volume (GWV) on weight loss. This study therefore aimed to investigate the effect of GWV on weight loss response after LSG.Thirty-two patients with body mass index (BMI) of ≧ 40 kg/mThe mean preoperative GWV was 216.9 ± 47.7 ml in the SGWV group, versus 336.3 ± 24.1 ml in the LGWV group. Patients with LGWV had significantly lower 1-year %TWL (34.9.1% versus 27.9%, p = 0.0439). Multilinear regression identified LGWV as a significant prognostic factor after adjusting for BMI and early weight loss response. Repeated measure mixed effect model showed that the LGWV group had a significantly slower %TWL change, particularly after 3 months postoperatively. No association was found between 1-year %TWL and preoperative and postoperative gastric luminal volume or resected gastric volume.3D-CT disclosed GWV, but not other gastric anatomical characteristics, was an independent predictor of %TWL after 1-year post LSG.

Context The association between arterial stiffness and clinical outcome in lateralized primary aldosteronism (PA) patients after adrenalectomy has not been clearly identified. Objective We hypothesized that arterial stiffness estimated by brachial-ankle pulse wave velocity (baPWV) before adrenalectomy was associated with the clinical outcomes and cardiorenal injury in lateralized PA patients after adrenalectomy. Design and Patients We designed a retrospective observational cohort study. We collected lateralized PA patients who had undergone adrenalectomy between 2013 and 2016 from the Taiwan Primary Aldosteronism Investigation database. The primary outcome was achieving complete clinical success at 1 year after adrenalectomy. The secondary outcome was estimated glomerular filtration rate declining over 20% and improved left ventricular mass index. Results We enrolled 221 patients with lateralized PA (50.7% men; mean age, 51.9 years), of whom 101 patients (45.7%) achieved complete clinical success at the 1-year follow-up assessment after adrenalectomy. Lower baPWV before adrenalectomy (odds ratio = 0.998; 95% confidence interval, 0.996-0.999; P = 0.003) correlated with higher likelihood of complete clinical success by multivariate logistic regression analysis. Multifactorial adjusted generalized additive model demonstrated that preoperative baPWV Conclusions Our study demonstrated that the preoperative severe arterial stiffness was associated with absent complete clinical success in lateralized PA patients after adrenalectomy, and this effect may contribute to cardiorenal injury, which at least partially explains kidney function deterioration and lessened regression of heart mass.

The spread of SARS-CoV-2 since December 2019 has become a pandemic and impacted many aspects of human society. Here, we analyzed genetic variation of SARS-CoV-2 and its related coronavirus and found the evidence of intergenomic recombination. After correction for mutational bias, analysis of 137 SARS-CoV-2 genomes as of 2/23/2020 revealed the excess of low frequency mutations on both synonymous and nonsynonymous sites which is consistent with recent origin of the virus. In contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China was two time higher than those derived from the rest of the world. In addition, in network analysis, haplotypes collected from Wuhan city were at interior and have more mutational connections, both of which are consistent with the observation that the outbreak of cov-19 was originated from China.SUMMARYIn contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated.

Recent studies show brain-derived neurotrophic factor (BDNF) and fibroblast growth factor 21 (FGF21) are neurotrophic factors associated with obesity and diabetes mellitus (DM). Laparoscopic sleeve gastrectomy (LSG) can significantly reduce weight and improve DM. In this study, we enrolled 78 patients with obesity and evaluated the change of BDNF and FGF21 6 months after LSG. At baseline, the BDNF level was similar between the preoperative DM (n = 30) (17.1 ± 7.7 ng/ml) and non-DM (n = 48) (17.0 ± 6.9 ng/ml) patients with obesity, but FGF21 was significantly higher in the DM patients (201.5 ± 204.3 versus 107.6 ± 63.8 pg/ml). At 6 months after LSG, most of the preoperative DM patients (96.7%) had DM either resolved (66.7%) or improved (30%). BDNF increased and FGF21 decreased significantly regardless of the preoperative DM status, while FGF21 decreased more prominently in the preoperative DM patients (−92.6 ± 179.8 versus −4.6 ± 63.4 pg/ml). After adjusted for age, sex, and preoperative DM status, FGF21 became significantly and positively related to C-peptide (β = 18.887), insulin (β = 2.399), and homeostasis model assessment of insulin resistance index (β = 8.566) after surgery. In conclusion, diabetic patients with obesity had higher FGF21 and similar BDNF levels compared to non-diabetic obese patients. BDNF increased and FGF21 decreased significantly after LSG. FGF21 became positively associated with several insulin-related profiles after surgery.

Antithyroid drugs (ATDs) are known to cause various adverse drug reactions (ADRs) that can lead to treatment complexity and unpredictable risks. With the aim of ensuring safer drug use, we assessed whether thyrotropin receptor antibody (TRAb) titers are associated with ATD-induced cutaneous reactions and/or hepatotoxicity, and examined potential genetic predisposition factors.We compared TRAb titers of 37 Graves' disease (GD) patients who had experienced carbimazole/methimazole-induced cutaneous reactions and/or hepatotoxicity with those of 40 normal individuals, or 78 GD patients without the aforementioned ATD-induced ADRs. We performed a genome-wide association study and/or human leukocyte antigen genotyping on GD patients [first stage (chart reviews): 24 cases with ADRs and 423 controls; second stage (actively recruited): 45 cases with ADRs and 137 controls].For patients with Graves' hyperthyroidism, individuals with higher TRAb titers showed a predisposition to carbimazole/methimazole-induced cutaneous reactions and/or hepatotoxicity, with an estimated odds ratio of 5.19 (cut-off value: 64%). Potential associations with the rs144542704 and rs61893841 on chromosomes 17 and 11, respectively, warrant further genetic association analysis.Our findings support the use of carbimazole/methimazole in patients with low TRAb titers to ensure safer drug use. The identified genetic associations warrant further research.

Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, significantly improves cardiovascular outcomes in diabetic patients; however, the mechanism is unclear. We hypothesized that empagliflozin might have beneficial effects on cardiac function, structure, adiposity, and myocardial diffuse fibrosis. This prospective study enrolled 35 patients (48.6% men, age 63.5 ± 9.7 years) with type 2 diabetes mellitus (T2DM) from June 1, 2017, to November 31, 2018. The patients received an SGLT2 inhibitor (empagliflozin 25 or 12.5 mg/d) for 6 months in addition to stable oral hypoglycaemic treatment. All patients underwent cardiac magnetic resonance imaging (CMRI) before and after empagliflozin treatment. Left ventricular (LV) function and structure were quantified using cine CMRI. Cardiac adiposity was defined based on pericardial fat and intracardiac triglyceride contents, whereas myocardial diffuse fibrosis was indicated by extracellular volume (ECV). The statistical significance of parameter changes was assessed using paired t-test and stepwise multiple linear regression. There were no significant differences in LV function and structure changes. Cardiac adiposity and diffuse fibrosis indices were also not different before and after empagliflozin treatment. Concerning clinical parameters, only a significant decrease in systolic blood pressure (by 6.4 mmHg) was observed (p = 0.013). Stepwise multiple linear regression revealed that worse baseline MRI parameters were associated with better improvements. Intracardiac triglyceride content decrease was inversely associated with baseline intracardiac triglyceride content (p

Purpose To evaluate the association between increased pancreatic echogenicity (IPE) and the risk of glycemic progression and incident diabetes. Materials and Methods This retrospective study was approved by the institutional review board, with waiver of informed consent. Consecutive individuals who had undergone abdominal ultrasonography as part of a health examination at a tertiary hospital between January 2005 and December 2011 were included. IPE was defined as increased echogenicity of the pancreas compared with that of the left lobe of liver. Glycemic progression was defined as the development of new prediabetes or diabetes in normoglycemic participants or as new diabetes in prediabetic participants during the follow-up period (median, 3.17 years; interquartile range, 2.01-4.67 years). The occurrence of incident diabetes, defined as a new diagnosis of diabetes during follow-up, was also analyzed. Results Mean age of the 32 346 participants was 50.4 years ± 12.2, and 48% (15 489 of 32 346) were female. The prevalence of IPE and nonalcoholic fatty liver disease (NAFLD) was 8.4% (2720 of 32 346) and 41.4% (13 389 of 32 346), respectively. A total of 8856 participants were included in the follow-up analysis. During the 29 819.2 person-years of follow-up, 1217 (13.7%) and 449 (5.1%) of the 8856 participants developed glycemic progression and new diabetes, respectively. IPE was associated with more glycemic progression (hazard ratio, 1.54; 95% confidence interval: 1.23, 1.92; P.001) and incident diabetes (hazard ratio, 1.49; 95% confidence interval: 1.05, 2.11; P = .024) after adjustment for confounders, HbA

We aimed to investigate the association of difference between observed and predicted glycated hemoglobin (dopHbA1c) and HbA1c reduction after vildagliptin-based oral therapy in patients with type 2 diabetes (T2D).This was a prospective observational study. Adults ≥ 20 years old with T2D and HbA1c ≧7% treated with oral anti-diabetic drugs (OADs) were eligible if their OADs were shifted to vildagliptin-based dual oral therapy. Fasting plasma glucose (FPG) and HbA1c were recorded at baseline, week 12, and week 24. To determine baseline dopHbA1c, a predicted HbA1c was calculated by inserting baseline FPG into a regression equation (HbA1c = FPG ∗ 0.0225 + 4.3806) developed from linear relationship between HbA1c and FPG in an independent cohort of 3239 outpatients with T2D (dopHbA1c = observed HbA1c - predicted HbA1c). Patients were assigned to low (≦0) or high (0) dopHbA1c group according to their baseline dopHbA1c levels. The study endpoint was changes from baseline to week 24 in HbA1c levels.A total of 1224 patients were enrolled. Patients with a dopHbA1c0 had a greater HbA1c reduction after vildagliptin-based dual oral therapy than those with a dopHbA1c ≦0 (-1.5 ± 2.0 vs. -0.4 ± 1.0%, p 0.001). Baseline dopHbA1c was positively associated with HbA1c reduction from baseline to week 24 (β coefficient 0.883, 95% CI 0.811 to 0.955, p 0.001), and the association remained significant after adjustment for confounders.In T2D patients with an HbA1c ≧7%, a higher baseline dopHbA1c was associated with a greater HbA1c reduction after shifting to vildagliptin-based dual oral therapy.

Plasma leucine-Rich α-2-glycoprotein 1 (LRG1) is an innovative biomarker for inflammation and angiogenesis. Many adverse pathophysiological changes including inflammation, atherosclerosis, and premature mortality is associated with End-stage renal disease (ESRD). However, whether levels of plasma LRG1 correlate with the co-morbidities of ESRD patients is unknown. Plasma LRG1 and high-sensitivity C-reactive protein (hsCRP) were analyzed by ELISA in 169 hemodialysis patients from the Immunity in ESRD (iESRD) study. Patient demographics and comorbidities at the time of enrollment were recorded. Peripheral blood monocyte and T cell subsets were assessed by multicolor flow cytometry. In the univariate analysis, a higher level of LRG1 was associated with the presence of cardiovascular disease (CVD) and peripheral arterial occlusive disease (PAOD). In multivariate logistic regression models, higher LRG1 tertile was significantly associated with PAOD (odds ratio = 3.49) and CVD (odds ratio = 1.65), but not with coronary artery disease, history of myocardial infarction, or stroke after adjusting for gender, diabetes, hemoglobin, albumin, calcium-phosphate product, and level of hsCRP. In addition, the level of LRG1 had a positive correlation with IL-6, hsCRP, and also more advanced T cell differentiation. The association suggests that LRG1 participates in the progression of atherosclerosis by inducing inflammation. Therefore, the role of LRG1 in coexisting inflammatory response should be further investigated in the pathogenesis of cardiovascular morbidity and mortality in patients with ESRD.

Purpose: Orbital fibroblasts are involved in pathogenesis of Graves’ orbitopathy (GO). Fibroblast growth factor (FGF) affects fibroblasts of GO. This study aims to investigate the roles of FGF and FGF receptor (FGFR) in GO. Methods: Serum FGF proteins and orbital fibroblast FGFR proteins and mRNAs were measured in GO patients and controls. Orbital fibroblasts of GO were cultured and accessed for changes in proliferation (by nuclei number and MTT), myofibroblastic differentiation (by α-SMA), and adipogenesis (by oil droplets using Oil Red O stain) under FGF1 with or without FGFR inhibitors (FGFRi). Results: Serum FGF1 and FGF2 were increased in GO patients. FGFR1 was the most abundantly expressed FGFR in GO orbital fibroblasts. FGF1 increased GO fibroblast proliferation/adipogenesis and suppressed myofibroblastic differentiation, while FGFRi reversed these effects. Conclusion: FGF signaling may be involved in GO pathogenesis. Manipulation of FGF-FGFR pathway for GO treatment is worthy of further investigation. Registration number on Clinicaltrials.gov: NCT03324022.

Spot 14 (S14) protein is primarily expressed in adipogenic tissues. Compared to wild type, S14 knockout mice had better resistance to diet-induced obesity and glucose tolerance. However, the association between serum S14 level and metabolic variables in humans has never been investigated. The objectives of this study were to evaluate the associations between serum S14 concentrations with components of metabolic syndrome (MetS). A total of 327 subjects were recruited in this cross-sectional study and categorized by presence of MetS. The mean serum levels of S14 were significantly lower in subjects with MetS than those without (87.1±26.3 μg/L vs. 107.3±40.2 μg/L, p

Fetuin-A is a protein with various biological functions. It plays a role in insulin resistance and arterial calcium deposition. Thyroid dysfunction may affect energy expenditure, glucose metabolism, and the risk of cardiovascular diseases. In the present study, we compared the serum fetuin-A concentrations in hyperthyroid patients with those in euthyroid patients.We recruited 30 newly-diagnosed hyperthyroid patients (the HY group) and treated them with anti-thyroid regimens as clinically indicated. We recruited 30 euthyroid individuals (the EU group) as controls. We compared laboratory parameters at the baseline and at 6 months. We then determined the associations between the levels of fetuin-A and free thyroxine (fT4), thyroid-stimulating hormone (TSH), or log transformation of TSH (logTSH).At the baseline, the HY patients had significantly higher serum fetuin-A levels than the EU patients (median [Q1, Q3]: 735.4 [537.9, 843.4] ng/mL vs 561.1[449.2, 670.5] ng/mL, P = .010). At 6 months, the serum fetuin-A levels of the HY patients decreased but were still higher than those of the EU patients (698.4 [627.6, 924.3] ng/mL vs 616.5 [498.2, 727.7] ng/mL, P = .002). At baseline, the serum levels of fetuin-A were negatively associated with logTSH (β = -53.79, P = .010). At 6 months, the levels of fetuin-A were positively associated with fT4 (β = 86.91, P = .039), and negatively associated with logTSH (β = -104.28, P < .001). Changes to the levels of fetuin-A within 6 months were negatively associated with changes to logTSH (β = -57.80, P = .019). The negative associations between fetuin-A levels and logTSH at baseline and at 6 months, and the changes during the 6 months remained significant after adjustment for sex and age (β = -51.72, P = .016; β = -103.11, P < .001; and β = -59.36, P = .020, respectively).The patients with hyperthyroidism had higher serum fetuin-A levels than the patients with euthyroidism. In patients with hyperthyroidism, the serum fetuin-A concentrations decreased after the anti-thyroid treatment. In the present study, serum fetuin-A concentrations were negatively associated with logTSH.

Aims Patients with diabetes are predisposed to develop a variety of complications, including lower urinary tract (LUT) dysfunction. We aimed to examine the associations between glycemic control and LUT dysfunction in women with type 2 diabetes (T2D). Methods We included 400 women with T2D (age range, 48–75 years) in this cross-sectional analysis. The participants were divided into tertiles according to glycosylated hemoglobin (Hb A1c ) measurements. The mean Hb A1c levels for tertiles 1, 2, and 3 were 6.2% (N=132), 7.1% (N=132), and 8.4% (N=136), respectively. We evaluated LUT dysfunction with the American Urological Association Symptom Index (AUA-SI) questionnaire, uroflowmetry (UFM), and post-void residual (PVR). Results No significant differences were found among Hb A1c tertiles regarding storage, voiding and total AUA-SI scores, and prevalence of LUT symptoms. However, women in tertile 3 had higher prevalences of severe LUT symptoms (AUA-SI≥20) and clinically significant PVR (≥100mL) compared to women in the other tertiles. Multivariate analysis revealed that diabetic neuropathy, but not Hb A1c , significantly predicted LUT symptoms in women with T2D after adjustment for age, body mass index (BMI) and hypertension. However, Hb A1c was associated with an increased risk of developing clinically significant PVR. Conclusions Our findings do not support significant associations between glycemic control and LUT symptoms in women with T2D. However, women with poor glycemic control are more likely to develop urinary retention than women with proper glycemic control. Clinicians should, therefore, be aware of and educate patients about the association between urinary retention and glycemic control.

BACKGROUND Low gait speed is associated with inflammation and muscle strength. Follistatin, a glycosylated plasma protein, is involved in inflammatory diseases, bone metabolism, muscle strength and cognition. However, research regarding the relationship between follistatin and gait speed in elderly individuals is limited. In this study, we aimed to examine the association between follistatin and gait speed in older adults. METHODS This cross-sectional, observational study included 205 ambulatory individuals aged ≥ 65 years. The baseline measures included 15-foot walking time, a structured questionnaire, grip strength and biomarkers, including follistatin and myostatin levels. Multiple linear regression was used to determine the change in gait speed for each 1 pg/mL increase in serum follistatin level. An extended model approach with a quartile-based analysis of serum follistatin levels was conducted. RESULTS In the linear regression model, the β coefficient, representing the change in gait speed for each 1 pg/mL increase in serum follistatin level, was -0·308 (P < 0·001). After additional adjustment for relevant covariates, the β coefficient changed slightly, although the negative correlation remained (all P ≤ 0·001). After controlling for multiple covariates, participants in the highest serum follistatin level quartile had a significantly lower gait speed than those in the lowest quartile (all P for trend < 0·001). CONCLUSIONS A higher follistatin level was independently associated with lower gait speed in community-dwelling elderly individuals; this suggests that serum follistatin level may be an indicator of mobility in elderly persons and may more particularly represent lower extremity function.

To investigate the expression patterns of 2 soluble isoforms of receptor for advanced glycation end-product (RAGE), including endogenous secretory RAGE (esRAGE) and cleaved RAGE (cRAGE), and their associations with outcome in acute ischemic stroke (IS).Acute IS patients (n = 106) and age- and sex-matched controls (n = 150) were recruited. Plasma levels of total soluble RAGE (sRAGE) and esRAGE in patients at48 hours and 48-72 hours after IS and in controls were measured by ELISA. The level of cRAGE was calculated by subtracting the level of sRAGE from that of esRAGE. Poor outcome was defined as modified Rankin Scale score2 at 3 months after stroke.The plasma levels of cRAGE were significantly higher and correlated to those of esRAGE (p0.001). The plasma levels of esRAGE and cRAGE were both significantly higher in IS patients48 hours and 48-72 hours after onset than in controls, but only level of cRAGE at48 hours was independently associated with poor outcome after adjusting for clinical variables (odds ratio 2.44; 95% confidence interval 1.16-5.16; p = 0.019).The plasma level of cRAGE at48 hours after IS, rather than esRAGE, is a significant predictor of acute IS outcome.

The global incidence and prevalence of type 2 diabetes have been escalating in recent decades. Patients with type 2 diabetes have an increased risk of atherosclerotic cardiovascular disease (ASCVD). About two-thirds of death in type 2 diabetes are due to ASCVD, including 40% from coronary heart disease (CHD), 15% from heart failure (HF), and 10% from stroke. The association between hyperglycemia and elevated CV risk has been demonstrated in multiple cohort studies. However, clinical trials of intensive glucose reduction did not significantly reduce macrovascular outcomes. It remains unclear whether the absence of demonstrable benefits is attributed to the inclusion of patients with far advanced ASCVD in whom a short treatment period is barely enough for CV protective effects to be shown, or complications associated with the treatment such as hypoglycemia hamper the beneficial effects to manifest, or simply glucose-lowering per se is ineffective. Since the US FDA issued a mandate in December 2008 that every new anti-diabetic agent requires rigorous assessments of its CV safety, there have been more than 200,000 patients enrolled in a number of randomized controlled trials (RCTs), and around half of them have been completed and published. The results of these CV outcome trials are important for clinicians in their clinical practice, and also provide an opportunity for academic society to formulate treatment guidelines or consensus to provide specific recommendations for glucose control in various CV diseases. The Taiwan Society of Cardiology (TSOC) and the Diabetes Association of Republic of China (DAROC), aiming to formulate a treatment consensus in type 2 diabetic patients with CVD, have appointed a jointed consensus group for the 2018 Consensus of TSOC/DAROC (Taiwan) on the Pharmacological Management of Patients with Type 2 Diabetes and CV Diseases. The consensus is comprised of 5 major parts: 1) Treatment of diabetes in patients with hypertension, 2) Treatment of diabetes in patients with CHD, 3) Treatment of diabetes in patients with stage 3 chronic kidney disease, 4) Treatment of diabetes in patients with a history of stroke, and 5) Treatment of diabetes in patients with HF. The members of the consensus group comprehensively reviewed all the evidence, mainly RCTs, and also included meta-analyses, cohort studies, and studies using claim data. The treatment targets of HbA1c were provided. The anti-diabetic agents were ranked according to their clinical evidence. The consensus is not mandatory. The final decision may need to be individualized and based on clinicians' discretion.

Background Studies showed that the endotoxemia-related biomarker, lipopolysaccharide-binding protein (LBP), is associated with obesity and fatty liver. The level of LBP is reduced after surgical weight loss. This study aimed to verify the change of serum LBP levels after one-year medical weight management in subjects with obesity. Methods and findings A total of 62 subjects with obesity, 39 subjects with overweight, and 21 subjects with normal body mass index were enrolled for a one-year weight management program. Basic information, body composition analysis, clinical data, serum LBP level, and abdominal ultrasonography findings were collected. At baseline, the serum LBP levels of the obese and overweight subjects were significantly higher than that of the normal group (30.9±7.4 and 29.6±6.3 versus 23.1±5.6 μg/mL, respectively, p

Background Although bisphosphonate-related osteonecrosis of the jaw (ONJ) develops mainly after tooth extractions (TEs), the strength of the association between them and how the existence of the disease among bisphosphonate (BP)-treated osteoporotic patients exposed to TE remain uncertain. Methods A nationwide retrospective cohort study investigated the influence of alendronate and TE on the development of ONJ. Results Incidence of ONJ following long-term alendronate therapy was 262/100,000 person-years, while no event developed in the control group on raloxifene. Overall prevalence of ONJ in osteoporotic subjects receiving alendronate was estimated at 0.34% which rose to 2.16% after TE. Multiple logistic regression analysis, adjusted for the potential confounders, showed TE (adjusted odds ratio, 9.60 [4.33–21.29]), drug duration exceeding 3 years (3.00 [1.33–6.76]), and concomitant rheumatoid arthritis (4.94 [1.64–14.90]) were independent predictors of ONJ. Conclusions This article strengthens the relationship between ONJ and BPs. Among osteoporotic patients exposed to alendronate, TE confers a 9.6-fold increased risk for ONJ and it should be performed with caution irrespective of drug duration.

Age-related hearing impairment (ARHI) is a complex neurodegenerative disorder caused by a combination of environmental and genetic factors. We have reported previously that obesity increases the risk for ARHI, and that plasma levels of adiponectin are associated with ARHI. In the present study, we further explored the role of adiponectin in the pathophysiology of ARHI by investigating the genotypes of ADIPOQ and ADIPOR1, the genes of adiponectin and its type 1 receptor, respectively. A total of 1682 volunteers were enrolled, and their audiological phenotypes were determined according to the z scores converted from their original frequency-specific hearing thresholds. A total of 9 tag-single nucleotide polymorphisms (tagSNPs) in ADIPOQ and 4 tagSNPs in ADIPOR1 were genotyped, and the genotypes were correlated to the audiological phenotypes under the assumption of various inheritance models. Significant associations were identified between certain ADIPOQ tagSNPs and z scores under dominant, codominant, or additive models, whereas no association was identified between ADIPOR1 tagSNPs and z scores. The associations between ADIPOQ tagSNPs and z scores appear to exist only in subjects with specific ADIPOR1 genotypes, indicating an interaction between adiponectin and AdipoR1. Measurement of plasma adiponectin in 736 subjects revealed that ADIPOQ genotypes might exert their effects on hearing levels via modulation of plasma adiponectin levels. Subsequently, we confirmed the expression of AdipoR1 in the inner ear of mice, and demonstrated antiapoptotic effects of adiponectin in cochlear explant cultures. These results provide insights into the physiological function and potential clinical implications of adiponectin against ARHI.

Study question Can the use of whole-exome sequencing (WES) together with single nucleotide polymorphism (SNP) array help to identify novel causative genes of isolated Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome? Summary answer OR4M2 (olfactory receptor, family 4, subfamily M, member 2) and PDE11A (phosphodiesterase 11A) gene loss-of-function variants as well as deletions at 15q11.2, 19q13.31, 1p36.21, and 1q44 were identified as possible commonly altered regions in patients with type 1 MRKH. What is known already The isolated form of Mullerian aplasia is the most common subtype of MRKH syndrome, which invariably leads to difficulties producing offspring in affected women. However, there is little information currently available to allow for genetic testing and counseling to be performed for those affected by this syndrome. Study design, size and duration This was a case-series genetic study. A total of seven consecutive unrelated women with type 1 MRKH were enrolled. The enrollment and experimental procedures were performed over a 2-year period. Participants/materials, setting, methods Whole exome-targeted next-generation sequencing and SNP array (Affymetrix Genome-Wide Human SNP Array 6.0) were performed on the first five unrelated women with type 1 MRKH syndrome. The data were combined, and the '3-hit principal' was applied on a genome-wide scale to search for the common causative genes. Quantitative PCR (qPCR) and Sanger sequencing were used to validate the identified genomic copy number losses and variants. Replication tests using direct Sanger sequencing and qPCR were performed on the remaining two women with type 1 MRKH syndrome to support the credibility of the potential candidate genes and deletions. Main results and the role of chance A total of 3443 damaging variants based on WES were shown to intersect with 1336 copy number variations (deletions) derived from the SNP array. Four highly recurrent deletions at 15q11.2 (80%), 19q13.31 (40%), 1p36.21 (40%) and 1q44 (40%) were identified in the first five women with type 1 MRKH syndrome and were considered to be novel candidate aberrations. A previously reported 1q21.1 deletion was also recurrent in two of the first five women with type 1 MRKH syndrome. The 1q44 and 19q13.31 deletions were present in at least one of the two additional patients. Damaging variants were detected in HNRNPCL1 (heterogeneous nuclear ribonucleoprotein C-like 1), OR2T2 (olfactory receptor, family 2, subfamily T, member 2), OR4M2, ZNF816 (zinc finger protein 816), and PDE11A in several of the initial five patients. Among these, the damaging variants of OR4M2 (located at 15q11.2) and PDE11A were found in at least one of the two additional patients with type 1 MRKH. Limitations, reasons for caution In this study, we only searched for the deletions or damaging variants causing loss-of-function of genes in at least three of the initial five patients (3-hit criteria). Therefore, the study was designed to only detect common causative genes. Genomic duplications and/or rare individual mutations that may have also contributed to MRKH syndrome were not investigated. Wider implications of the findings This study demonstrated the feasibility of the use of combined data from both WES and SNP arrays for the identification of possible common causative genetic aberrations in patients with type 1 MRKH syndrome on a genome-wide scale. Further validation of our found causative genes is required before applying on genetic testing and counseling. Study funding/competing interests The study was supported by grants from the National Science Council of Taiwan (NSC98-2314-B002-105-MY3 and NSC 100-2314-B002-027-MY3). The funding sources had no involvement in the design or analysis of the study. The authors have no competing interests to declare. Trial registration number Not applicable.

Supplemental Digital Content is available in the text, Patients with coronary heart disease or acute myocardial infarction after cardiac catheterization with stenting referred for phase II cardiac rehabilitation (CR) were grouped according to their preference. Cardio-pulmonary exercise testing (CPET) was used to determine oxygen uptake () at peak exercise and anaerobic threshold (AT). The control patients received counseling only while the experiment group received 36 sessions of CR in 3 to 6 months. Exercise physiology parameters and serum myokines (myostatin, insulin-like growth factor-1 (IGF-1), and interleukin-6 (IL-6) were measured pre- and postrehabilitation. There were 29 patients in the experiment group and 10 in the control group, with no significant differences in baseline parameters. The experiment group had prominent progress in aerobic capacity and body composition after CR, but their serum myokine concentrations did not change significantly. Serum myostatin is positively correlated to peak pre- and post-training, and pretraining AT , after adjusting for age, sex, and body composition. Serum IGF-1 is positively correlated with grip strength before training. Serum myostatin level is positively correlated to aerobic capacity, and IGF-1 level is positively correlated to grip strength in cardiac patients receiving CR.

Background Ribonuclease-L (RNase-L) was known to be a ubiquitous enzyme involved in several cellular functions, especially innate immunity. It was recently shown to participate in adipogenesis in rodents. Here, we developed a method to measure serum levels of RNase-L and analyzed the relationship between RNase-L and metabolic syndrome (MetS). Methods A total of 396 subjects were recruited from a health check-up program. An in-house RNase-L immunoassay was developed. The serum RNase-L levels of these subjects were measured, and the association of MetS-related factors with RNase-L levels was assessed. Results The mean serum level of RNase-L of the subjects with MetS were lower than those without (16.5 ± 6.4 vs. 18.4 ± 8.0 μg/ml, P = 0.018). The subjects with central obesity, elevated blood pressure, or impaired fasting glucose also had lower serum RNase-L levels in comparison to those without. In multivariate linear regression analysis, diastolic blood pressure (β = −0.129, P = 0.024) and high-density lipoprotein cholesterol (HDL-C) (β = 0.127, P = 0.036) were related to serum RNase-L. For every 5 μg/ml increase in serum RNase-L levels, it is associated with a reduced risk of MetS (OR 0.83, 95% CI 0.71–0.98, P = 0.028), central obesity (OR 0.82, 95% CI 0.71–0.94, P = 0.005), or low HDL-C (OR 0.86, 95% CI 0.74–1.00, P = 0.042). Moreover, age is inversely related to serum RNase-L levels in various analyses. Conclusions The serum RNase-L levels were inversely associated with MetS, unfavorable metabolic profiles, and age.

Background Myostatin negatively regulates muscle growth, and its inhibition by suitable proteins can increase muscle bulk and exercise performance. However, the reference values of serum myostatin in athletes performing strength training are still lacking. Methods A cross-sectional study recruiting28 male collegiate athletes performing strength training and 29 age-matched normal controls was conducted. The serum concentration of myostatin and insulin-like growth factor 1 (IGF-1), grip strength, and body composition were the main outcome measures. We used regression models to analyze the correlation between serum markers and the physiological parameters. The athlete group had greater height, weight, body mass index (BMI), fat mass percentage, fat-free mass, muscle mass, waist girth, grip strength, and estimated daily energy expenditure. Results The IGF-1 concentration was higher in the athlete group (324 ± 80 vs. 263 ± 134 ng/ml), but the myostatin levels did not differ (12.1 ± 3.7 vs. 12.4 ± 3.5 ng/ml). The reference value for IGF-1 among the healthy young males was 293 ± 114 ng/ml, correlated with age and height; the value for myostatin was 12.3 ± 3.6 ng/ml, correlated negatively with BMI, fat mass percentage, and waist girth after adjustment for age. Conclusion Myostatin level is negatively related to fat percentage, and serum IGF-1 is positively related to height. The reference values could provide a basis for future doping-related study.

Adiponectin might play a protective role in cardiometabolic and peripheral auditory disorders, but its role on central auditory function was still unclear. The aim of this study was to examine whether there is an association between plasma adiponectin levels and central auditory function in adults. We recruited 297 adults, with normal or symmetrical sensorineural hearing loss and normal cognitive functions. Multivariate linear regression was performed to assess the association between plasma adiponectin concentrations and pitch pattern sequence (PPS) score, which was one of central auditory tests. The results showed that there were 224 (75.4 %) women and 73 (24.6 %) men in this study. The mean age was 58.1 ± 8.4 years, the mean waist circumference (WC) was 81.1 ± 8.3 cm, and the mean body mass index (BMI) was 24.0 ± 3.0 kg/m2. The mean PPS score was 71.5 ± 14.1 %, and plasma adiponectin concentration was 12.7 ± 5.5 g/mL. After adjusting for age, gender, WC, coronary artery disease, hypertension, diabetes mellitus, chronic kidney disease, smoking and drinking, plasma adiponectin concentrations (coefficient ± standard error, β ± SE = −0.09 ± 0.16, p = 0.563) were found to have no significant associations with PPS score. When WC was excluded from these variables in the multivariate linear regression model, plasma adiponectin concentrations (β ± SE = −0.03 ± 0.15, p = 0.855) were still not significantly associated with PPS score. In conclusion, plasma adiponectin levels were not significantly associated with PPS score, which was one of central auditory function tests. More studies should be conducted for the underlying mechanisms of obesity-related central auditory dysfunction.

Background: This study aimed to explore the possible association between osteonecrosis of the jaws (ONJ) and oral alendronate or raloxifene used for osteoporosis and to estimate its absolute and attributable risks in the Taiwanese population. Methods: Using an electronic medical records system and manual confirmation of ONJ, we identified patients who began taking alendronate or raloxifene for osteoporosis and developed ONJ between January 2000 and April 2012. Results: The incidence of ONJ associated with oral alendronate for the management of osteoporosis began after 1 year of drug exposure and progressively increased with longer durations of therapy, specifically from 0.23% to 0.92% as the duration of treatment went from 2 years to 10 years. The overall frequency of ONJ related to oral alendronate over a 12-year period was 0.55%. The incidence rate of ONJ attributed to alendronate exposure was 283 per 100 000 persons per year. On multivariate Cox proportional analysis, adjusting for the potential confounders, alendronate remains an independent predictor for ONJ occurrence [hazard ratio 7.42 (1.02–54.09)] compared with raloxifene. Advanced age, drug duration, and coexisting diabetes and rheumatoid arthritis are contributing factors to the development of oral alendronate-related ONJ. Conclusion: We provided the evidence to support the association of ONJ with oral alendronate used in the treatment or prevention of osteoporosis.

Background: Obesity is considered a risk factor for hepatocellular carcinoma (HCC). The relationship between adipocytokine and HCC in hepatitis B virus (HBV) carriers remains unclear. We prospectively investigated the association of adiponectin, leptin, and visfatin levels with HCC. Methods: We conducted a nested case–control study in a community-based cohort with 187 incident HCC and 374 HCC-free HBV carriers. Unconditional logistic regression was conducted to estimate the ORs and 95% confidence intervals (CI). Results: Adiponectin, but not leptin and visfatin, levels were associated with an increased risk of HCC after adjustment for other metabolic factors and HBV-related factors. The risk was increased [OR = 0.51; 95% CI, 0.12–2.11; OR = 4.88 (1.46–16.3); OR = 3.79 (1.10–13.0); OR = 4.13 (1.13–15.1) with each additional quintiles, respectively] with a significant dose–response trend (Ptrend = 0.003). HCC risk associated with higher adiponectin level was higher in HBV carriers with ultrasonographic fatty liver, genotype C infection, higher viral load, and with elevated alanine aminotransferase. Longitudinally, participants with higher adiponectin were less likely to achieve surface antigen of hepatitis B virus (HBsAg) seroclearance and more likely to have persistently higher HBV DNA. Eventually, they were more likely to develop liver cirrhosis [OR = 1.65 (0.62–4.39); OR = 3.85 (1.47–10.1); OR = 2.56 (0.96–6.84); OR = 3.76 (1.33–10.7) for the second, third, fourth, and fifth quintiles, respectively; Ptrend = 0.017] before HCC. Conclusions: Elevated adiponectin levels were independently associated with an increased risk of HCC. Impact: Adiponectin may play different roles in the virus-induced and metabolic-related liver diseases, but the underlying mechanism remains unknown. Cancer Epidemiol Biomarkers Prev; 23(8); 1659–71. ©2014 AACR.

Background and purpose In older people with type 2 diabetes mellitus (T2DM), the effects of aging and T2DM may compromise the function of skeletal muscle, deteriorate metabolic status, and jeopardize physical performance, aerobic capacity, and quality of life (QoL). The purpose of this study was to investigate the effects of 12 weeks of resistance training (RT) on muscle function, physical performance, cardiometabolic risks, and QoL in older people with T2DM. Methods This study was a randomized controlled trial that employed block randomization, assessor blinding, and the intention-to-treat principle. Thirty people 65 years or older with a diagnosis of T2DM were randomly assigned to either an exercise group or a control group and were further stratified by gender. The exercise group performed 8 RT exercises in 3 sets of 8 to 12 repetitions at 75% 1-repetition maximum (1-RM) 3 times per week for 12 weeks. The control group received usual care and maintained their daily activities and lifestyle. Muscle function (1-RM and muscle oxygenation responses), physical performance (5-repetition sit-to-stand test and Timed Up and Go test), cardiometabolic risks (aerobic capacity, blood pressure, body composition, glycemic control, lipids levels, and high-sensitivity C-reactive protein levels), and QoL (Audit of Diabetes-Dependent Quality of Life 19) were assessed at baseline (week 0) and after the 12-week interventions (week 12). Results The 1-RM chest-press and leg-press strength and physical performance in 5-repetition sit-to-stand test were significantly improved in the exercise group compared with the controls after the interventions. The exercise group had significantly lower resting systolic blood pressure (by -12.1 mm Hg, P = 0.036) than did the controls after 12 weeks of RT, without any significant within-group change in either group after intervention. The waist circumference, fasting glucose levels, and peak diastolic blood pressure tended to favor RT over usual care after the interventions. Conclusion Twelve weeks of RT increased the maximal strength in chest-press and leg-press tests, and improved 5-repetition sit-to-stand performance in older people with T2DM. Our study demonstrated that supervised, structured RT was able to promote muscle function and alleviate cardiometabolic risks in people with T2DM 65 years or older.

Spot 14 (S14) is a protein involved in fatty acid synthesis and was shown to be induced by thyroid hormone in rat liver. However, the presence of S14 in human serum and its relations with thyroid function status have not been investigated. The objectives of this study were to compare serum S14 concentrations in patients with hyperthyroidism or euthyroidism and to evaluate the associations between serum S14 and free thyroxine (fT4) or thyroid-stimulating hormone (TSH) levels. We set up an immunoassay for human serum S14 concentrations and compared its levels between hyperthyroid and euthyroid subjects. Twenty-six hyperthyroid patients and 29 euthyroid individuals were recruited. Data of all patients were pooled for the analysis of the associations between the levels of S14 and fT4, TSH, or quartile of TSH. The hyperthyroid patients had significantly higher serum S14 levels than the euthyroid subjects (median [Q1, Q3]: 975 [669, 1612] ng/mL vs 436 [347, 638] ng/mL, P

Insulin-like growth factor 1 (IGF-1) has a molecular structure similar to that of insulin. As an essential mediator of growth hormone, IGF-1 plays a vital role in growth of children and anabolic effects of adults. We evaluated the serum levels of IGF-1 in patients with hyperthyroidism or euthyroidism. In this study, 30 patients each of Graves’ disease with hyperthyroidism (HY group) and euthyroid individuals (EU group) were recruited. The HY patients were treated with antithyroid regimens as clinically indicated. No medications were given to EU patients. The demographic characteristics and anthropometric and laboratory data of both groups at baseline and 6 months were compared. Associations between levels of IGF-1 and free thyroxine (fT4), thyroid-stimulating hormone (TSH), or log transformation of TSH (logTSH) were analyzed. At baseline, the HY patients had significantly higher serum IGF-1 levels than EU patients (median [Q1, Q3]: 305.4 [257.4, 368.1] vs. 236.7 [184.6, 318.8] ng/mL, P = .007). At 6 months, the HY patients still had higher serum levels of IGF-1 than EU patients (299.5 [249.9, 397.9] vs 222.1 [190.2, 305.4] ng/mL, P = .003). At baseline, the serum levels of IGF-1 in the HY and EU patients were positively associated with fT4 (β = 29.02, P = .002) and negatively associated with TSH (β = −31.46, P = .042) and logTSH (β = −29.04, P = .007). The associations between serum levels of IGF-1 with fT4 or TSH became insignificant at 6 months. However, the serum IGF-1 levels had persistent negative associations with logTSH at 6 months (β = −26.65, P = .021). The negative associations between IGF-1 and logTSH at baseline and 6 months remained significant even after adjustment with sex and age (β = −20.22, P = .023 and β = −20.51, P = .024, respectively). The HY patients had higher serum IGF-1 levels than EU patients. The serum IGF-1 concentrations were negatively associated with logTSH in patients with hyperthyroidism or euthyroidism.

OBJECTIVE In mice, a lack of cryptochrome results in up-regulation of aldosterone production due to high expression of the 3β-hydroxysteroid dehydrogenases (HSD3β) gene. The HSD3β pathway might play a pivotal role in aldosterone synthesis. This study aimed to determine the association of HSD3β and HSD3β2 gene variations with primary aldosteronism in a Taiwanese population. METHOD In this case-control cohort, 688 consecutive ethnically matched unrelated individuals including 362 primary aldosteronism and 326 essential hypertension cases were recruited. Nineteen tag single-nucleotide polymorphisms (SNPs) across HSD3β1, HSD3β2, and CYP11β2 were genotyped. Expression of HSD3β mRNA and immunohistochemical stain of HSD3β in the specimens of aldosterone-producing adenoma (APA) was compared with that in nonfunctional incidentaloma. RESULTS The SNPs of rs12410453 A allele in HSD3β2 gene [odds ratio (OR) 1.92, 95% confidence interval (CI) 1.13-3.32, P=0.018] and rs6203 C allele in the HSD3β1 gene (OR 2.21, 95% CI 1.28-3.95, P=0.006) showed significant association with primary aldosteronism, with corresponding population attributable risk of 6.7 and 30.7%, respectively. Primary aldosteronism patients of non-CC in rs6203 and non-GA in rs12401453 had lower plasma aldosterone-to-renin ratio. A haplotype in a linkage disequilibrium block containing rs6203 associated significantly with serum potassium level (OR 1.24, 95% CI 1.02-1.24, P=0.026). The expressions of HSD3β1 mRNA, HSD3β2 mRNA and HSD3β protein were increased in APA, as compared to incidentaloma. CONCLUSION Risk-conferring genetic variations in the HSD3β gene influenced susceptibility of primary aldosteronism. Concomitant presence of rs6203 CC and rs12410453 GA genotypes synergistically increased aldosterone-to-renin ratio.

Objective: Adiponectin plays a role in obesity, lipid metabolism, and anti-inflammation. Women with polycystic ovary syndrome (PCOS) are also at risk for dyslipidemia. Therefore, we investigated the association between adiponectin levels and the lipid profile including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TGs) in women with PCOS and contemplated what role adiponectin might play in dyslipidemia with PCOS. Materials and Methods: We recruited 118 young Taiwanese women with PCOS. The women enrolled were not taking any medication and those with other systemic diseases of nonovarian origin, which could have affected the hypothalamic–pituitary–ovarian axis, were excluded. The serum lipid profile, metabolic and hormonal parameters, and adiponectin were measured. The lipid profile and adiponectin were analyzed and adjusted for age, body mass index (BMI), homeostasis model assessment-insulin resistance (HOMA-IR), and sex hormone-binding globulin (SHBG). Results: In a simple linear regression, adiponectin was significantly inversely related to LDL-C and TGs, but positively related to HDL-C (all p

We aim to determine the cerebrospinal fluid levels of high mobility group box 1 in subarachnoid hemorrhage patients and to investigate the involvement of the receptor for advanced glycation end products and high mobility group box 1 in the pathogenesis of post-subarachnoid hemorrhage neuronal death. The study included 40 patients (mean age, 59 ± 19 years) with Fisher's grade ≥ III aneurysmal subarachnoid hemorrhage. Cerebrospinal fluid was collected on the seventh day post-hemorrhage. Receptor for advanced glycation end products expression was examined in rat brain tissue following subarachnoid hemorrhage and in cultured neurons exposed to post-subarachnoid hemorrhage cerebrospinal fluid. Therapeutic effects of the recombinant soluble form of RAGE on subarachnoid hemorrhage models were also investigated. The results indicated that a higher level of cerebrospinal fluid high mobility group box 1 was independently associated with unfavorable outcome at three months post-subarachnoid hemorrhage (OR = 1.061, 95% CI: 1.005–1.121). Expression of RAGE increased in post-subarachnoid hemorrhage rat brain cells and in cultured neuron with stimulation of post-subarachnoid hemorrhage cerebrospinal fluid. Administration of recombinant soluble form of RAGE significantly reduced the number of positive TUNEL staining cells in subarachnoid hemorrhage rat and improved cell viability in post-subarachnoid hemorrhage cerebrospinal fluid-treated cultured neurons. Thus, the level of cerebrospinal fluid high mobility group box 1 can be a prognostic indicator for patients with Fisher's grade ≥ III aneurysmal subarachnoid hemorrhage and that treatment with soluble form of RAGE is a novel approach for subarachnoid hemorrhage.

Sarcopenia, characterized by low muscle mass and function, results in frailty, comorbidities and mortality. However, its prevalence varies according to the different criteria used in its diagnosis. This cross-sectional study investigated the difference in the number of sarcopenia cases recorded by two different measurement methods of low muscle mass to determine which measurement was better. We recruited 878 (54.2% female) individuals aged over 65 years and obtained their body composition and functional parameters. Low muscle mass was defined as two standard deviations below either the mean height-adjusted (hSMI) or weight-adjusted (wSMI) muscle mass of a young reference group. The prevalence of sarcopenia was 6.7% vs. 0.4% (male/female) by hSMI and 4.0% vs. 10.7% (male/female) by wSMI. The κ coefficients for these two criteria were 0.39 vs. 0.03 (male/female) and 0.17 in all subjects. Serum myostatin levels correlated positively with gait speed (r = 0.142, p = 0.007) after adjustment for gender. hSMI correlated with grip strength, cardiopulmonary endurance, leg endurance, gait speed and flexibility. wSMI correlated with grip strength, leg endurance, gait speed and flexibility. Since hSMI correlated more closely with grip strength and more muscular functions, we recommend hSMI in the diagnosis of low muscle mass.