Publications by authors named "Yi-Jen Hung"

150 Publications

Tumor Necrosis Factor-Alpha Exacerbates Viral Entry in SARS-CoV2-Infected iPSC-Derived Cardiomyocytes.

Int J Mol Sci 2021 Sep 13;22(18). Epub 2021 Sep 13.

Institute of Pharmacology, National Yang-Ming University, Taipei 11217, Taiwan.

The coronavirus disease 2019 (COVID-19) pandemic with high infectivity and mortality has caused severe social and economic impacts worldwide. Growing reports of COVID-19 patients with multi-organ damage indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) may also disturb the cardiovascular system. Herein, we used human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) as the in vitro platform to examine the consequence of SARS-CoV2 infection on iCMs. Differentiated iCMs expressed the primary SARS-CoV2 receptor angiotensin-converting enzyme-II (ACE2) and the transmembrane protease serine type 2 (TMPRSS2) receptor suggesting the susceptibility of iCMs to SARS-CoV2. Following the infection of iCMs with SARS-CoV2, the viral nucleocapsid (N) protein was detected in the host cells, demonstrating the successful infection. Bioinformatics analysis revealed that the SARS-CoV2 infection upregulates several inflammation-related genes, including the proinflammatory cytokine tumor necrosis factor-α (TNF-α). The pretreatment of iCMs with TNF-α for 24 h, significantly increased the expression of ACE2 and TMPRSS2, SASR-CoV2 entry receptors. The TNF-α pretreatment enhanced the entry of GFP-expressing SARS-CoV2 pseudovirus into iCMs, and the neutralization of TNF-α ameliorated the TNF-α-enhanced viral entry. Collectively, SARS-CoV2 elevated TNF-α expression, which in turn enhanced the SARS-CoV2 viral entry. Our findings suggest that, TNF-α may participate in the cytokine storm and aggravate the myocardial damage in COVID-19 patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22189869DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470197PMC
September 2021

Nutrition counseling is associated with less sarcopenia in diabetes: A cross-sectional and retrospective cohort study.

Nutrition 2021 Apr 7;91-92:111269. Epub 2021 Apr 7.

School of Public Health, National Defense Medical Center, Taipei, Taiwan, Republic of China. Electronic address:

Objectives: Muscle is crucial for blood glucose regulation. There is a need to prevent and treat sarcopenia in diabetes mellitus (DM). This study aimed to estimate the prevalence of sarcopenia and evaluate the association of nutritional counseling with the development of sarcopenia for people with DM.

Methods: In a cross-sectional and retrospective cohort study, people with type 2 DM were recruited from the Diabetes Shared Care Program of a teaching hospital. Muscle mass, muscle strength, and physical functional performance were evaluated using the Asian Working Group for Sarcopenia criteria. The skeletal muscle mass index was determined by dividing muscle mass by the square of the height. Clinical information, including the nutrition counseling record, was retrospectively obtained from medical records for a 2-y period.

Results: The prevalence of low skeletal muscle mass index (presarcopenia) and sarcopenia were, respectively, 20.4% and 9.6% (including 3.1% severe) among 1292 participants. Specifically, 15.3% of participants age ≥ 65 y were categorized as having sarcopenia. With more frequent nutritional counseling, there was a lesser risk of sarcopenia; the adjusted odds ratio (95% confidence interval) was 0.51 (0.27-0.94) for ≥ 3 times/2 y compared to no counseling. DM duration and age, glycemic status and medication, and body mass index and counseling frequency had no joint effects; however, these variables (except HbA1 c) were independent risk factors for low skeletal muscle mass index and sarcopenia.

Conclusions: People with type 2 DM have a high risk of sarcopenia. Increased nutrition counseling in outpatients was associated with less sarcopenia. Education about sarcopenia-associated risk factors should be encouraged early in the onset of DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nut.2021.111269DOI Listing
April 2021

Perilla (Perilla frutescens) leaf extract inhibits SARS-CoV-2 via direct virus inactivation.

Biomed J 2021 06 28;44(3):293-303. Epub 2021 Jan 28.

Research Center for Emerging Viral Infections, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan; Research Center for Industry of Human Ecology and Research Center for Chinese Herbal Medicine, Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Taoyuan, Taiwan; Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan; Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan. Electronic address:

Background: While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presents with mild or no symptoms in most cases, a significant number of patients become critically ill. Remdesivir has been approved for the treatment of coronavirus disease 2019 (COVID-19) in several countries, but its use as monotherapy has not substantially lowered mortality rates. Because agents from traditional Chinese medicine (TCM) have been successfully utilized to treat pandemic and endemic diseases, we designed the current study to identify novel anti-SARS-CoV-2 agents from TCM.

Methods: We initially used an antivirus-induced cell death assay to screen a panel of herbal extracts. The inhibition of the viral infection step was investigated through a time-of-drug-addition assay, whereas a plaque reduction assay was carried out to validate the antiviral activity. Direct interaction of the candidate TCM compound with viral particles was assessed using a viral inactivation assay. Finally, the potential synergistic efficacy of remdesivir and the TCM compound was examined with a combination assay.

Results: The herbal medicine Perilla leaf extract (PLE, approval number 022427 issued by the Ministry of Health and Welfare, Taiwan) had EC of 0.12 ± 0.06 mg/mL against SARS-CoV-2 in Vero E6 cells - with a selectivity index of 40.65. Non-cytotoxic PLE concentrations were capable of blocking viral RNA and protein synthesis. In addition, they significantly decreased virus-induced cytokine release and viral protein/RNA levels in the human lung epithelial cell line Calu-3. PLE inhibited viral replication by inactivating the virion and showed additive-to-synergistic efficacy against SARS-CoV-2 when used in combination with remdesivir.

Conclusion: Our results demonstrate for the first time that PLE is capable of inhibiting SARS-CoV-2 replication by inactivating the virion. Our data may prompt additional investigation on the clinical usefulness of PLE for preventing or treating COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bj.2021.01.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840404PMC
June 2021

Effects of a Technology-Assisted Integrated Diabetes Care Program on Cardiometabolic Risk Factors Among Patients With Type 2 Diabetes in the Asia-Pacific Region: The JADE Program Randomized Clinical Trial.

JAMA Netw Open 2021 04 1;4(4):e217557. Epub 2021 Apr 1.

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong Special Administrative Region, China.

Importance: Many health care systems lack the efficiency, preparedness, or resources needed to address the increasing number of patients with type 2 diabetes, especially in low- and middle-income countries.

Objective: To examine the effects of a quality improvement intervention comprising information and communications technology and contact with nonphysician personnel on the care and cardiometabolic risk factors of patients with type 2 diabetes in 8 Asia-Pacific countries.

Design, Setting, And Participants: This 12-month multinational open-label randomized clinical trial was conducted from June 28, 2012, to April 28, 2016, at 50 primary care or hospital-based diabetes centers in 8 Asia-Pacific countries (India, Indonesia, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam). Six countries were low and middle income, and 2 countries were high income. The study was conducted in 2 phases; phase 1 enrolled 7537 participants, and phase 2 enrolled 13 297 participants. Participants in both phases were randomized on a 1:1 ratio to intervention or control groups. Data were analyzed by intention to treat and per protocol from July 3, 2019, to July 21, 2020.

Interventions: In both phases, the intervention group received 3 care components: a nurse-led Joint Asia Diabetes Evaluation (JADE) technology-guided structured evaluation, automated personalized reports to encourage patient empowerment, and 2 or more telephone or face-to-face contacts by nurses to increase patient engagement. In phase 1, the control group received the JADE technology-guided structured evaluation and automated personalized reports. In phase 2, the control group received the JADE technology-guided structured evaluation only.

Main Outcomes And Measures: The primary outcome was the incidence of a composite of diabetes-associated end points, including cardiovascular disease, chronic kidney disease, visual impairment or eye surgery, lower extremity amputation or foot ulcers requiring hospitalization, all-site cancers, and death. The secondary outcomes were the attainment of 2 or more primary diabetes-associated targets (glycated hemoglobin A1c <7.0%, blood pressure <130/80 mm Hg, and low-density lipoprotein cholesterol <100 mg/dL) and/or 2 or more key performance indices (reduction in glycated hemoglobin A1c≥0.5%, reduction in systolic blood pressure ≥5 mm Hg, reduction in low-density lipoprotein cholesterol ≥19 mg/dL, and reduction in body weight ≥3.0%).

Results: A total of 20 834 patients with type 2 diabetes were randomized in phases 1 and 2. In phase 1, 7537 participants (mean [SD] age, 60.0 [11.3] years; 3914 men [51.9%]; 4855 patients [64.4%] from low- and middle-income countries) were randomized, with 3732 patients allocated to the intervention group and 3805 patients allocated to the control group. In phase 2, 13 297 participants (mean [SD] age, 54.0 [11.1] years; 7754 men [58.3%]; 13 297 patients [100%] from low- and middle-income countries) were randomized, with 6645 patients allocated to the intervention group and 6652 patients allocated to the control group. In phase 1, compared with the control group, the intervention group had a similar risk of experiencing any of the primary outcomes (odds ratio [OR], 0.94; 95% CI, 0.74-1.21) but had an increased likelihood of attaining 2 or more primary targets (OR, 1.34; 95% CI, 1.21-1.49) and 2 or more key performance indices (OR, 1.18; 95% CI, 1.04-1.34). In phase 2, the intervention group also had a similar risk of experiencing any of the primary outcomes (OR, 1.02; 95% CI, 0.83-1.25) and had a greater likelihood of attaining 2 or more primary targets (OR, 1.25; 95% CI, 1.14-1.37) and 2 or more key performance indices (OR, 1.50; 95% CI, 1.33-1.68) compared with the control group. For attainment of 2 or more primary targets, larger effects were observed among patients in low- and middle-income countries (OR, 1.50; 95% CI, 1.29-1.74) compared with high-income countries (OR, 1.20; 95% CI, 1.03-1.39) (P = .04).

Conclusions And Relevance: In this 12-month clinical trial, the use of information and communications technology and nurses to empower and engage patients did not change the number of clinical events but did reduce cardiometabolic risk factors among patients with type 2 diabetes, especially those in low- and middle-income countries in the Asia-Pacific region.

Trial Registration: ClinicalTrials.gov Identifier: NCT01631084.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2021.7557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087959PMC
April 2021

Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices.

Nat Commun 2021 04 12;12(1):2182. Epub 2021 Apr 12.

Division of Cardiology, George Washington University School of Medicine and Healthcare Sciences, Washington, DC, USA.

Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-22339-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042019PMC
April 2021

Multi-omics analysis identifies CpGs near G6PC2 mediating the effects of genetic variants on fasting glucose.

Diabetologia 2021 Jul 12;64(7):1613-1625. Epub 2021 Apr 12.

Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan.

Aims/hypothesis: An elevated fasting glucose level in non-diabetic individuals is a key predictor of type 2 diabetes. Genome-wide association studies (GWAS) have identified hundreds of SNPs for fasting glucose but most of their functional roles in influencing the trait are unclear. This study aimed to identify the mediation effects of DNA methylation between SNPs identified as significant from GWAS and fasting glucose using Mendelian randomisation (MR) analyses.

Methods: We first performed GWAS analyses for three cohorts (Taiwan Biobank with 18,122 individuals, the Healthy Aging Longitudinal Study in Taiwan with 1989 individuals and the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance with 416 individuals) with individuals of Han Chinese ancestry in Taiwan, followed by a meta-analysis for combining the three GWAS analysis results to identify significant and independent SNPs for fasting glucose. We determined whether these SNPs were methylation quantitative trait loci (meQTLs) by testing their associations with DNA methylation levels at nearby CpG sites using a subsample of 1775 individuals from the Taiwan Biobank. The MR analysis was performed to identify DNA methylation with causal effects on fasting glucose using meQTLs as instrumental variables based on the 1775 individuals. We also used a two-sample MR strategy to perform replication analysis for CpG sites with significant MR effects based on literature data.

Results: Our meta-analysis identified 18 significant (p < 5 × 10) and independent SNPs for fasting glucose. Interestingly, all 18 SNPs were meQTLs. The MR analysis identified seven CpGs near the G6PC2 gene that mediated the effects of a significant SNP (rs2232326) in the gene on fasting glucose. The MR effects for two CpGs were replicated using summary data based on the European population, using an exonic SNP rs2232328 in G6PC2 as the instrument.

Conclusions/interpretation: Our analysis results suggest that rs2232326 and rs2232328 in G6PC2 may affect DNA methylation at CpGs near the gene and that the methylation may have downstream effects on fasting glucose. Therefore, SNPs in G6PC2 and CpGs near G6PC2 may reside along the pathway that influences fasting glucose levels. This is the first study to report CpGs near G6PC2, an important gene for regulating insulin secretion, mediating the effects of GWAS-significant SNPs on fasting glucose.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00125-021-05449-9DOI Listing
July 2021

Whole genome sequence analyses of eGFR in 23,732 people representing multiple ancestries in the NHLBI trans-omics for precision medicine (TOPMed) consortium.

EBioMedicine 2021 Jan 6;63:103157. Epub 2021 Jan 6.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.

Background: Genetic factors that influence kidney traits have been understudied for low frequency and ancestry-specific variants.

Methods: We combined whole genome sequencing (WGS) data from 23,732 participants from 10 NHLBI Trans-Omics for Precision Medicine (TOPMed) Program multi-ethnic studies to identify novel loci for estimated glomerular filtration rate (eGFR). Participants included European, African, East Asian, and Hispanic ancestries. We applied linear mixed models using a genetic relationship matrix estimated from the WGS data and adjusted for age, sex, study, and ethnicity.

Findings: When testing single variants, we identified three novel loci driven by low frequency variants more commonly observed in non-European ancestry (PRKAA2, rs180996919, minor allele frequency [MAF] 0.04%, P = 6.1 × 10; METTL8, rs116951054, MAF 0.09%, P = 4.5 × 10; and MATK, rs539182790, MAF 0.05%, P = 3.4 × 10). We also replicated two known loci for common variants (rs2461702, MAF=0.49, P = 1.2 × 10, nearest gene GATM, and rs71147340, MAF=0.34, P = 3.3 × 10, CDK12). Testing aggregated variants within a gene identified the MAF gene. A statistical approach based on local ancestry helped to identify replication samples for ancestry-specific variants.

Interpretation: This study highlights challenges in studying variants influencing kidney traits that are low frequency in populations and more common in non-European ancestry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2020.103157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804602PMC
January 2021

Use and effectiveness of dapagliflozin in patients with type 2 diabetes mellitus: a multicenter retrospective study in Taiwan.

PeerJ 2020 17;8:e9998. Epub 2020 Nov 17.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan.

Aims/introduction: To investigate the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) who initiated dapagliflozin in real-world practice in Taiwan.

Materials And Methods: In this multicenter retrospective study, adult patients with T2DM who initiated dapagliflozin after May 1 2016 either as add-on or switch therapy were included. Changes in clinical and laboratory parameters were evaluated at 3 and 6 months. Baseline factors associated with dapagliflozin response in glycated hemoglobin (HbA1c) were analyzed by univariate and multivariate logistic regression.

Results: A total of 1,960 patients were eligible. At 6 months, significant changes were observed: HbA1c by -0.73% (95% confidence interval [CI] -0.80, -0.67), body weight was -1.61 kg (95% CI -1.79, -1.42), and systolic/diastolic blood pressure by -3.6/-1.4 mmHg. Add-on dapagliflozin showed significantly greater HbA1c reduction (-0.82%) than switched therapy (-0.66%) ( = 0.002). The proportion of patients achieving HbA1c <7% target increased from 6% at baseline to 19% at Month 6. Almost 80% of patients experienced at least 1% reduction in HbA1c, and 65% of patients showed both weight loss and reduction in HbA1c. Around 37% of patients had at least 3% weight loss. Multivariate logistic regression analysis indicated patients with higher baseline HbA1c and those who initiated dapagliflozin as add-on therapy were associated with a greater reduction in HbA1c.

Conclusions: In this real-world study with the highest patient number of Chinese population to date, the use of dapagliflozin was associated with significant improvement in glycemic control, body weight, and blood pressure in patients with T2DM. Initiating dapagliflozin as add-on therapy showed better glycemic control than as switch therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.9998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678460PMC
November 2020

Growth arrest-specific 6 modulates adiponectin expression and insulin resistance in adipose tissue.

J Diabetes Investig 2021 Apr 13;12(4):485-492. Epub 2020 Oct 13.

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan.

Aims/introduction: Obesity is characterized by disturbed adipocytokine expression and insulin resistance in adipocytes. Growth arrest-specific 6 (GAS6) is a gene encoding the Gas6 protein, which is expressed in fibroblasts, and its related signaling might be associated with adipose tissue inflammation, glucose intolerance and insulin resistance. The aim of this study was to investigate the associations among Gas6, adipocytokines and insulin resistance in adipocytes.

Materials And Methods: Mature Simpson Golabi Behmel Syndrome adipocytes were treated with high levels of insulin to mimic insulin resistance, and were examined for the expressions of Gas6, cytokines and adipocytokines from preadipocytes in differentiation. In an animal study, high-fat diet-induced obese mice were used to verify the Gas6 expression in vitro.

Results: During the differentiation of adipocytes, the expression of Gas6 gradually decreased, and was obviously downregulated with adipocyte inflammation and insulin resistance. Gas6 levels were found to be in proportion to the expression of adiponectin, which has been regarded as closely relevant to improved insulin sensitivity after metformin treatment. Similar results were also confirmed in the animal study.

Conclusions: Our results suggest that Gas6 might modulate the expression of adiponectin, and might therefore be associated with insulin resistance in adipose tissues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jdi.13412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015836PMC
April 2021

Metformin Attenuates Osteoporosis in Diabetic Patients with Carcinoma in Situ: A Nationwide, Retrospective, Matched-Cohort Study in Taiwan.

J Clin Med 2020 Sep 2;9(9). Epub 2020 Sep 2.

Department of Medical Research, National Defense Medical Center, Taipei 11490, Taiwan.

Patients with diabetes are at increased risk of cancer development and osteoporosis. Metformin is an effective agent for diabetes management. Epidemiological studies have identified an association between metformin use and cancer prevention. This article outlines the potential for metformin to attenuate the rate of osteoporosis in diabetic patients with carcinoma in situ (CIS). From the National Health Insurance Research Database of Taiwan, 7827 patients with diabetes with CIS who were receiving metformin therapy were selected, along with 23,481 patients as 1:3 sex-, age- and index year-matched controls, who were not receiving metformin therapy. A Cox proportional hazard analysis was used to compare the rate of osteoporosis during an average of 15-year follow-up. Of the subjects who were enrolled, 801 (2.56%) had osteoporosis, including 168 from the metformin group (2.15%) and 633 from the without metformin group (2.70%). The metformin group presented a lower rate of osteoporosis at the end of follow-up ( = 0.009). The Cox proportional hazard regression analysis revealed a lower rate of osteoporosis for the metformin group (adjusted hazard ratio of 0.820; 95% confidence interval = 0.691-0.972, = 0.022). Diabetic patients with CIS under metformin therapy presented lower osteoporosis rate than those who were not receiving metformin therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9092839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565460PMC
September 2020

Identification of type 2 diabetes loci in 433,540 East Asian individuals.

Nature 2020 06 6;582(7811):240-245. Epub 2020 May 6.

Vanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.

Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D); however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes-NKX6-3 and ANK1-in different tissues. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-020-2263-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292783PMC
June 2020

Influence of silk clothing therapy in patients with atopic dermatitis.

Dermatol Reports 2019 Sep 22;11(2):8176. Epub 2019 Dec 22.

Department of Pediatrics, Songshan Branch, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.

The existence of red, inflammatory, and chronic itchy condition in the skin is commonly speculated as the presence of Atopic Dermatitis (AD) in patients. The use of silk clothing as a non-pharmacological approach in the management of AD has been noticed as an effective alternative therapy; however, the evidence based on its usage is poorly served. Hence, we aim to evaluate the effectiveness of using pure silk clothing in the therapy of AD patients. The clinical trial was performed by recruiting 30 patients with AD for up to 8 weeks of observation. They were instructed to wear pure silk clothing for the whole day without any additional medication and were investigated using the AD-related questionnaires. The findings revealed a significant decrease of AD occurrence along with a great improvement of patient's quality of life at each time point. Our investigation demonstrated that this treatment promotes good skin appearance, comfort, and remarkable improvement in the quality of life. This promising preliminary outcome warrants a further study; hence, it can be a potential non-pharmacological treatment choice for controlling the severity of AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4081/dr.2019.8176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137929PMC
September 2019

Piperacillin-tazobactam induced bicytopenia in low cumulative treatment doses.

BMJ Case Rep 2019 Dec 30;12(12). Epub 2019 Dec 30.

Internal Medicine, Tri-Service General Hospital Songshan Branch, Taipei, Taiwan.

We present the case of infected wet gangrene of right foot in the setting of poorly controlled type 2 diabetes in a 71-year-old woman. This patient presented with improved infection condition after intravenous piperacillin-tazobactam (PTZ) 2.25 gm every 6 hours treatment and below knee amputation surgery on day 3. However, neutropenia and thrombocytopenia developed on day 13. We consulted a haematologist and performed a series of examinations. However, no significant findings were noted thereafter. PTZ was suspected to be the most likely cause of neutropenia and thrombocytopenia and was hence terminated on day 14 (cumulative dose of PTZ: 126 g) following stabilisation of the infection condition. A transfusion was performed with two units of single donor platelets on day 14 and treated with intravenous dexamethasone 5 mg every 8 hours from day 14 to 16. Her white blood cell and platelet counts increased on day 15 and continued to recover thereafter.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2019-232944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954770PMC
December 2019

Associations of autozygosity with a broad range of human phenotypes.

Nat Commun 2019 10 31;10(1):4957. Epub 2019 Oct 31.

Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht University, Utrecht, 3584 CX, The Netherlands.

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F) for >1.4 million individuals, we show that F is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F are confirmed within full-sibling pairs, where the variation in F is independent of all environmental confounding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-019-12283-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6823371PMC
October 2019

Combination of COX-2 inhibitor and metformin attenuates rate of admission in patients with rheumatoid arthritis and diabetes in Taiwan.

Medicine (Baltimore) 2019 Oct;98(41):e17371

Department of Medical Research, Tri-Service General Hospital.

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disease associated with increased prevalence of type 2 diabetes mellitus (T2DM). Here, we investigated the effect of the combination of cyclooxygenase (COX)-2 inhibitors and metformin on the rate of admission in patients with RA and T2DM and compared it with that of only COX-2 inhibitors.In total, 1268 subjects with RA and T2DM under COX-2 inhibitor and metformin therapy were selected from the National Health Insurance Research Database of Taiwan, along with 2536 patients as 1:2 sex-, age-, and index year-matched controls without metformin therapy. Cox proportional hazard analysis was used to compare the rate of admission during the 10 years of follow-up.At the end of the follow-up, 72 enrolled subjects (1.89%) had admission, including 9 from the combination group (0.71%) and 63 from the COX-2 inhibitor group (2.48%). The combination group was associated with a lower rate of admission at the end of follow-up (P < .001). Cox proportional hazard regression analysis revealed the lower rate of admission for subjects under combination therapy (adjusted hazard ratio of 0.275; 95% confidence interval = 0.136-0.557, P < .001).Patients with RA and T2DM receiving the combination of COX-2 inhibitors and metformin were associated with lower admission rate than those on COX-2 inhibitors alone, and this effect may be attributed to the decrease in the levels of proinflammatory factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000017371DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6799465PMC
October 2019

Serum E-selectin concentration is associated with risk of metabolic syndrome in females.

PLoS One 2019 24;14(9):e0222815. Epub 2019 Sep 24.

School of Public Health, National Defense Medical Center, Taipei, Taiwan, ROC.

Objectives: Traits of metabolic syndrome (MetS) and biomarkers of inflammation and endothelial dysfunction were examined. We investigated the differences of various biomarkers among individuals with or without Mets in a gender-specific manner. The gender-specific associations between E-selectin and MetS were further evaluated.

Methods: A total of 205 patients were recruited from the outpatient clinics of Tri-Service General Hospital, Taipei, Taiwan. Inclusion criteria were age between 20-75 years and BMI < 35 kg/m2. Demographic, anthropometric and MetS index data were compared between genders. Markers of inflammation and endothelial dysfunction were compared between individuals with or without MetS by gender.

Results: Age-adjusted E-selectin values showed significant positive correlations with BMI, waist-hip ratio, fasting plasma glucose, systolic and diastolic blood pressure, triglycerides, TNF-α, hsCRP and ICAM-1, and inverse correlation with HDL cholesterol. E-selectin levels were positively correlated with numbers of MetS components in females (P < 0.001) but not in males (P = 0.125).

Conclusions: Increased E-selectin levels are significantly associated with increased MetS risk in females, but not in males.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222815PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6759160PMC
April 2020

Prevalence of diabetic macrovascular complications and related factors from 2005 to 2014 in Taiwan: A nationwide survey.

J Formos Med Assoc 2019 Nov 18;118 Suppl 2:S96-S102. Epub 2019 Sep 18.

Division of Biochemistry, National Defense Medical Center, Taipei, Taiwan; Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, Song Shan Branch, National Defense Medical Center, Taipei, Taiwan. Electronic address:

Background/purpose: Diabetic macrovascular complications contribute to nonignorable causes of morbidity and mortality in patients with diabetes mellitus (DM). In this study, the trends of risk factors and macrovascular complications were examined in patients with DM in Taiwan.

Methods: Health care information and International Classification of Diseases, Ninth Revision diagnostic codes were retrieved from the Taiwan Bureau of National Health Insurance claims files between 2005 and 2014. Using these data, the number of cases and annual prevalence of diabetic macrovascular complications in individuals with DM were stratified by age and sex.

Results: The prevalence of DM with either stroke or cardiovascular disease (CVD) showed a decreasing trend in enrolled patients with DM (p for trend < 0.005), but that of DM with peripheral vascular diseases (PVDs) showed an increasing trend (p for trend < 0.001). Notably, the trend of changes in the prevalence of heart failure (HF) was similar to that of changes in the prevalence of stroke, although the decrease in prevalence was not statistically significant (p for trend = 0.053).

Conclusion: From this nationwide study, we observed a decrease in the prevalence of diabetic macrovascular complications, such as stroke, CVD, and HF, but an increase in the prevalence of PVDs in the past decade in Taiwan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jfma.2019.08.035DOI Listing
November 2019

Cilostazol inhibits hyperglucose-induced vascular smooth muscle cell dysfunction by modulating the RAGE/ERK/NF-κB signaling pathways.

J Biomed Sci 2019 Sep 6;26(1):68. Epub 2019 Sep 6.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Background: Increasing evidence suggests that high glucose (HG) causes abnormalities in endothelial and vascular smooth muscle cell function (VSMC) and contributes to atherosclerosis. Receptor for advanced glycation end-products (RAGE) has been linked to the pathogenesis of both the macrovascular and microvascular complications of diabetes. Cilostazol is used to treat diabetic vasculopathy by ameliorating HG-induced vascular dysfunction.

Objectives: In this study, we investigated whether the cilostazol suppression of HG-induced VSMC dysfunction is through RAGE signaling and its possible regulation mechanism.

Method: We investigated the effect of HG and cilostazol on RAGE signaling in A7r5 rat VSMCs. Aortic tissues of streptozotocin (STZ) diabetic mice were also collected.

Results: Aortic tissue samples from the diabetic mice exhibited a significantly decreased RAGE expression after cilostazol treatment. HG increased RAGE, focal adhesion kinase (FAK), matrix metalloproteinase-2 (MMP-2), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expressions, and was accompanied with increased reactive oxygen species (ROS), cell proliferation, adhesion and migration. Cilostazol significantly reversed HG-induced RAGE, ROS, downstream gene expressions and cell functions. RAGE knockdown significantly reversed the expressions of HG-induced vasculopathy related gene expressions and cell functions. Cilostazol with RAGE knockdown had additive effects on downstream ERK/NF-κB signaling pathways, gene expressions and cell functions of A7r5 rat VSMCs in HG culture.

Conclusions: Both in vitro and in vivo experimental diabetes models showed novel signal transduction of cilostazol-mediated protection against HG-related VSMC dysfunction, and highlighted the involvement of RAGE signaling and downstream pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12929-019-0550-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6731603PMC
September 2019

Effects of a 12-week moderate-intensity exercise training on blood glucose response in patients with type 2 diabetes: A prospective longitudinal study.

Medicine (Baltimore) 2019 Sep;98(36):e16860

School of Nursing & School of Medicine, National Defense Medical Center; Department of Nursing, Tri-Service General Hospital Songshan Branch, Taipei, Taiwan, ROC.

Background: The blood glucose response to moderate-intensity exercise remains unclear for patients with type 2 diabetes (T2DM). In addition, little is known about determinants of blood glucose response to a 12-week moderate-intensity exercise training. Therefore, this study aimed to explore trends in blood glucose in response to a 12-week moderate-intensity exercise training in patients with T2DM and to explore the predictors of post-exercise blood glucose (PEBG) and exercise-induced glucose response (EIGR).

Methods: A prospective longitudinal study was conducted. Of the 66 participants with T2DM recruited from outpatient clinics of a medical center, 20 were eligible to enroll in a 12-week moderate-intensity exercise training. Participants were randomly assigned to 1 of 3 exercise times (morning, afternoon, or evening). Blood glucose were measured pre- and post-exercise. The EIGR was calculated by subtracting the PEBG from the before-exercise blood glucose (BEBG). Generalized estimating equations were used to examine the trends and predictors of PEBG and EIGR.

Results: The BEBG declined progressively (β = -1.69, P < .001); while the PEBG (β = -0.18, P = .08) remained stable over time during the 12-week exercise training. Higher BEBG predicted higher (β = 0.53, P < .001) PEBG. Higher baseline maximum oxygen uptake (VO2max) contributed to a larger magnitude of EIGR; higher HgbA1c and BEBG predicted higher EIGR (β = 0.27, P = .02; β = 0.45, P < .001); afternoon or evening exercise predicted lower (β = -13.2, P = .04; β = -5.96, P = .005) EIGR than did morning exercise.

Conclusions: A 12-week moderate-intensity exercise training appears safe for patients with T2DM. Time of day for exercise, baseline VO2max, and baseline metabolic control may influence the impact of exercise for individuals with T2DM. These findings provide considerations for design of optimal exercise training for T2DM patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000016860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739009PMC
September 2019

Active Physical Activity Patterns Are Associated With Improved Quality of Life and Depression Status in Taiwanese Women With Metabolic Syndrome.

J Cardiovasc Nurs 2019 Nov/Dec;34(6):491-502

Li-Chi Chiang, PhD, RN Professor, School of Nursing, National Defense Medical Center, Taipei; and School of Nursing, China Medical University, Taichung, Taiwan, ROC. Shang-Lin Chiang, MD, PhD Assistant Professor, School of Medicine, National Defense Medical Center; and Director, Department of Physical Medicine and Rehabilitation, Tri-Service General Hospital, Taipei, Taiwan, ROC. Wen-Chii Tzeng, PhD, RN Associate Professor, School of Nursing, National Defense Medical Center, Taipei, Taiwan, ROC. Meei-Shyuan Lee, PhD Professor, School of Public Health and Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, ROC. Yi-Jen Hung, MD Professor, School of Medicine, National Defense Medical Center; Superintendent, Songshan Branch of Tri-Service General Hospital; Taipei, Taiwan, ROC. Chia-Huei Lin, PhD, RN Assistant Professor, Schools of Nursing and Medicine, National Defense Medical Center; and Supervisor, Department of Nursing, Songshan Branch of Tri-Service General Hospital, Taipei, Taiwan, ROC.

Background: Metabolic syndrome (MetS), health-related quality of life (HRQL), and depression status are independently associated with cardiac health. Therefore, understanding the associations between MetS, HRQL, and depression status and determining factors related to improved HRQL and depression status in people with MetS may help in cardiovascular disease prevention.

Objective: The aim of this study was to examine whether there are differences in HRQL and depression status between Taiwanese women with and without MetS and whether physical activity patterns are associated with HRQL and depression status in this population.

Methods: A cross-sectional study of 326 Taiwanese middle-aged and older women (≥40 years) was conducted. Metabolic syndrome was determined based on the National Cholesterol Education Program Adult Treatment Panel III definition. Health-related quality of life and depression status were collected using the Short Form 36 Health Survey and Beck Depression Inventory. Univariate and multivariate linear regression analyses were conducted.

Results: Women with MetS had lower HRQL (P < .001) and higher depression status (P = .002) than those without MetS. Participants with active physical activity patterns had higher HRQL (P < .001) and lower depression status (P = .046) than those with sedentary patterns. Among women with MetS, those with active physical activity patterns had higher HRQL (P = .001) and lower depression status (P = .007) than those with sedentary patterns.

Conclusions: Metabolic syndrome is related to lower HRQL and higher depression status in women 40 years and older. Active physical activity patterns are associated with better HRQL and reduced depression status in middle-aged and older women (≥40 years) with MetS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JCN.0000000000000602DOI Listing
September 2020

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure.

Hum Mol Genet 2019 08;28(15):2615-2633

Icelandic Heart Association, Kopavogur, Iceland.

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P < 5 × 10-8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddz070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644157PMC
August 2019

Multi-ancestry genome-wide gene-smoking interaction study of 387,272 individuals identifies new loci associated with serum lipids.

Nat Genet 2019 04 29;51(4):636-648. Epub 2019 Mar 29.

Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.

The concentrations of high- and low-density-lipoprotein cholesterol and triglycerides are influenced by smoking, but it is unknown whether genetic associations with lipids may be modified by smoking. We conducted a multi-ancestry genome-wide gene-smoking interaction study in 133,805 individuals with follow-up in an additional 253,467 individuals. Combined meta-analyses identified 13 new loci associated with lipids, some of which were detected only because association differed by smoking status. Additionally, we demonstrate the importance of including diverse populations, particularly in studies of interactions with lifestyle factors, where genomic and lifestyle differences by ancestry may contribute to novel findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-019-0378-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6467258PMC
April 2019

Motivational Counseling to Reduce Sedentary Behaviors and Depressive Symptoms and Improve Health-Related Quality of Life Among Women With Metabolic Syndrome.

J Cardiovasc Nurs 2019 Jul/Aug;34(4):327-335

Li-Chi Chiang, PhD, RN Professor, School of Nursing, China Medical University, Taichung; and School of Nursing & Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan, R.O.C. Margaret McLean Heitkemper, PhD, RN, FAAN Professor and Chairperson, Department of Biobehavioral Nursing and Health Systems, and Adjunct Professor, Division of Gastroenterology, School of Medicine, University of Washington, Seattle. Shang-Lin Chiang, MD, PhD Assistant Professor, School of Medicine, National Defense Medical Center; and Director, Department of Physical Medicine and Rehabilitation, Tri-Service General Hospital, Taipei, Taiwan, ROC. Wen-Chii Tzeng, PhD, RN Associate Professor, School of Nursing, National Defense Medical Center, Taipei, Taiwan, R.O.C. Meei-Shyuan Lee, PhD Professor, School of Public Health & Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan, R.O.C. Yi-Jen Hung, MD Professor, School of Medicine, National Defense Medical Center; and Superintendent, Songshan Branch of Tri-Service General Hospital, Taipei, Taiwan, R.O.C. Chia-Huei Lin, PhD, RN Assistant Professor, Schools of Nursing and Medicine, National Defense Medical Center; and Supervisor, Department of Nursing, Songshan Branch of Tri-Service General Hospital, Taipei, Taiwan, R.O.C.

Background: Motivational interviewing, as a counseling approach, could promote not only behavioral changes but also individuals' psychological adaptation. Previous studies provide evidence that motivational interviewing focused on increasing physical activity decreases the risk of metabolic syndrome in women. Its effects on sedentary behaviors, depressive symptoms, and health-related quality of life (HRQL) remain unknown.

Objectives: The aim of this study was to evaluate whether a 12-week motivational counseling program reduces sedentary behaviors and depressive symptoms and improves HRQL in Taiwanese women.

Methods: A randomized controlled study was conducted. Participants (n = 115) were randomly assigned into 3 groups: experimental group (received a brochure on lifestyle modification combined with 12 weeks of motivational counseling), comparison group (received a lifestyle modification brochure), and usual care group (UCG). Outcome variables were measured at baseline and at 12 weeks post intervention by the International Physical Activity Questionnaire, Beck Depression Inventory, and Medical Outcomes Short Form-36 Health Survey. Generalized estimating equations were applied to analyze the intervention effects of groups by interaction of group and time.

Results: Women in the experimental group not only reduced (P < .001) weekly sitting time by 374 minutes but also decreased (P < .05) depressive symptoms, as well as had greater overall HRQL including 8 subscales as compared with the UCG. As compared with the UCG, the women in the comparison group had no change in sedentary behaviors, but they had reduced depressive symptoms and improvement on some HRQL subscales.

Conclusions: Motivational counseling that incorporates behavioral change principles is effective in reducing sedentary behaviors and depressive symptoms and improving HRQL for women with metabolic syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JCN.0000000000000573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581294PMC
October 2020

Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution.

Nat Genet 2019 03 18;51(3):452-469. Epub 2019 Feb 18.

Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.

Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-018-0334-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560635PMC
March 2019

Basal insulin therapy: Unmet medical needs in Asia and the new insulin glargine in diabetes treatment.

J Diabetes Investig 2019 May 18;10(3):560-570. Epub 2019 Jan 18.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.

Diabetes remains a global epidemic and a tremendous health challenge, especially in the Asian population. Dramatic increases in the prevalence of diabetes across different countries or areas in Asia have been reported in recent epidemiological studies. Although clinical guidelines have strengthened appropriate antihyperglycemic medications and lifestyle modifications for optimal diabetes management, inadequate glycemic control still occurs in many patients with an increased risk of developing microvascular and macrovascular complications. Insulin administration is the main therapy for diabetes in response to the inability to secrete insulin, and is recommended in current guidelines to treat patients with type 2 diabetes after failure of oral antidiabetic drugs. Clinical studies have shown that long-acting insulin analogs improve basal glycemic control with reduced risk of hypoglycemia. In the present review, we discuss previous challenges with basal insulin therapy in Asia, the pharmacological development of insulin analogs to overcome the unmet medical needs and recent clinical studies of the new ultra-long-acting insulin analog, insulin glargine U300. Furthermore, relevant findings of current real-world evidence are also included for the comparison of the efficacy and safety of different insulin formulations. Based on the accumulating evidence showing a low incidence of hypoglycemia and technical benefits of dose titration, treatment with glargine U300 can be a promising strategy for Asian diabetes patients to achieve glycemic targets with favorable safety.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jdi.12984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497775PMC
May 2019

Author Correction: Predictive Value of Serum Gamma-glutamyltranspeptidase for Future Cardiometabolic Dysregulation in Adolescents- a 10-year longitudinal study.

Sci Rep 2018 Nov 13;8(1):16934. Epub 2018 Nov 13.

Department of Pathology, Cardinal Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-34497-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233213PMC
November 2018

Plasma Growth Arrest-Specific 6 Protein and Genetic Variations in the GAS6 Gene in Patients with Metabolic Syndrome.

Metab Syndr Relat Disord 2019 02 20;17(1):22-28. Epub 2018 Oct 20.

1 Division of Endocrinology and Metabolism, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Background: Growth arrest-specific 6 (Gas6) is a vitamin K-dependent protein secreted by immune cells, endothelial cells, vascular smooth muscle cells, and adipocytes. Recent studies indicate that Gas6 and receptors of the TAM (Tyro3, Axl, and Mer) family may be involved in the pathogenesis of obesity, systemic inflammation, and insulin resistance. The aim of this study was to investigate the association between plasma Gas6 protein and the c.843 + 7G>A Gas6 polymorphism in metabolic syndrome (MetS).

Methods: Two hundred five adults (88 men and 117 women) were recruited in this study. Plasma Gas6 concentration, general, and biochemical data were measured. All subjects were genotyped for the c.843 + 7G>A Gas6 polymorphism.

Results: Plasma Gas6 concentrations decreased in parallel with various MetS components in all groups (P = 0.017 for trend). Patients in the second and third tertiles of Gas6 level had higher high-density lipoprotein cholesterol (HDL-C) levels than those in the first tertile overall and in the female group. Plasma Gas6 levels were significantly positively correlated with HDL-C level and negatively with fasting glucose level in the female patients. The A allele and genotype AA in single nucleotide polymorphism c.843 + 7G>A were less frequent in the subjects with MetS compared to those without MetS.

Conclusions: Our results demonstrated a positive correlation between Gas6 protein values and HDL-C and reinforce the association with fasting glucose. In addition, the presence of c.843 + 7G>A Gas6 polymorphisms, especially the AA genotype, had an association with MetS. The potential role of the Gas6/TAM system in MetS deserves further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/met.2017.0143DOI Listing
February 2019

[Diabetic Foot Neuropathy and Related Factors in Patients With Type 2 Diabetes Mellitus].

Hu Li Za Zhi 2018 06;65(3):28-37

PhD, RN, Associate Professor, School of Nursing, National Defense Medical Center, and Consultant, Department of Nursing, Taiwan, ROC.

Background: Patients with type 2 diabetes mellitus (T2DM) face a higher risk of diabetic foot neuropathy, which increases the risk of death. The early detection of factors that influence diabetic neuropathy reduces the risk of foot lesions, including foot ulcerations, lower extremity amputation, and mortality.

Purpose: To explore the demographic, disease-characteristic, health-literacy, and foot-self-care-behavior factors that affect diabetic foot neuropathy in patients with T2DM.

Methods: A case-control study design was employed in which cases (Michigan Neuropathy Screening Instrument, MNSI) ≥ 2 were matched to controls based on age and gender in a medical center. A total of 114 patients diagnosed with T2DM in a medical center were recruited as participants. Data were collected using a structured questionnaire. The collected data were analyzed using Fisher's exact test, Mann-Whitney U test, and logistic regression.

Results: The results of multiple logistic regression showed that glycated hemoglobin (B = 1.696, p = .041) and communication and critical health literacy (B = -0.082, p = .034) were significant factors of diabetic foot neuropathy.

Conclusions / Implications For Practice: The findings of this study suggest that nurses should assess the health literacy of patients with T2DM before providing health education and should develop a specific foot-care intervention for individuals with poor glycemic control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.6224/JN.201806_65(3).06DOI Listing
June 2018

Long-term effect of statins on the risk of new-onset osteoporosis: A nationwide population-based cohort study.

PLoS One 2018 3;13(5):e0196713. Epub 2018 May 3.

Division of Internal Cardiology, Chung Shan Medical University Hospital and Chung Shan Medical University, Taichung, Taiwan, ROC.

Background: Several observational cohort and meta-analytical studies in humans have shown that statin users have a lower risk of fractures or greater bone mineral densities (BMD) than nonusers. However, some studies including randomized clinical trials have the opposite results, particularly in Asian populations.

Objective: This study investigates the impacts of statins on new-onset osteoporosis in Taiwan.

Methods: In a nationwide retrospective population-based cohort study, 45,342 subjects aged between 50-90 years having received statin therapy (statin-users) since January 1 2001, and observed through December 31 2013 were selected from the National Health Insurance Research Database of Taiwan. Likewise, 115,594 patients had no statin therapy (statin-non-users) were included as controls in this study. Multivariable Cox proportional hazards analysis for drug exposures was employed to evaluate the association between statin treatment and new-onset of osteoporosis risk. We also used the long-rank test to evaluate the difference of probability of osteoporosis-free survival.

Results: During the 13-year follow-up period, 16,146 of all enrolled subjects (10.03%) developed osteoporosis, including 3097 statin-users (6.83%) and 13,049 statin-non-users (11.29%). Overall, statin therapy reduced the risk of new-onset osteoporosis by 48% (adjusted hazard ratio [HR] 0.52; 95% CI 0.50 to 0.54). A dose-response relationship between statin treatment and the risk of new-onset osteoporosis was observed. The adjusted hazard ratios for new-onset osteoporosis were 0.84 (95% CI, 0.78 to 0.90), 0.56 (95% CI, 0.52 to 0.60) and 0.23 (95% CI, 0.21 to 0.25) when cumulative defined daily doses (cDDDs) ranged from 28 to 90, 91 to 365, and more than 365, respectively, relative to nonusers. Otherwise, high-potency statins (rosuvastatin and atorvastatin) and moderate-potency statin (simvastatin) seemed to have a potential protective effect for osteoporosis.

Conclusions: In this population-based cohort study, we found that statin use is associated with a decreased risk of osteoporosis in both genders. The osteoprotective effect of statins seemed to be more prominent with a dependency on the cumulative dosage and statin intensity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196713PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5933736PMC
August 2018

A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure.

Am J Hum Genet 2018 03 15;102(3):375-400. Epub 2018 Feb 15.

Health Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIH, Baltimore, MD 21224, USA.

Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 × 10) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 × 10). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajhg.2018.01.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985266PMC
March 2018
-->