Publications by authors named "Chih-Hsueh Lin"

122 Publications

Independent and joint associations of skeletal muscle mass and physical performance with all-cause mortality among older adults: a 12-year prospective cohort study.

BMC Geriatr 2022 07 18;22(1):597. Epub 2022 Jul 18.

School of Medicine, College of Medicine, China Medical UniversityJingmao RdBeitun Dist, No. 100, Sec. 1, 406040, Taichung, Taiwan.

Background: Decreased skeletal muscle mass and low physical performance are independently associated with increased mortality in elderly individuals. However, little is known about the effects of skeletal muscle mass combined with physical performance on the prediction of mortality risk among community-dwelling older adults. This study aimed to determine the combined effects of skeletal muscle mass and physical performance on total mortality.

Methods: A community-based prospective cohort study was conducted among 641 participants aged 65 and older in 2009. The height-adjusted skeletal muscle index (hSMI) and the weight-adjusted SMI (wSMI) were determined by dual-energy X-ray absorptiometry examination. Physical performance tests measured at baseline included gait speed (GS), timed up-and-go (TUG) test, timed chair stand (TCS), weight-adjusted leg press (WaLP), and handgrip strength (HS). Cox proportional hazards regression models were applied to determine the adjusted hazard ratios (HRs) of mortality with 95% confidence intervals (95% CIs) for baseline skeletal muscle mass, physical performance, and traditional risk factors.

Results: During the follow-up of 12 years, 198 (30.89%) participants died. Low hSMI, low GS, high TUG, high TCS, low WaLP, and low HS were associated with high risks of mortality after the adjustment for confounders. The results of receiver operating characteristic (ROC) curve analyses revealed the values of ROC for models with additional consideration for TUG or all indicators significantly improved the discriminatory ability of mortality compared with the model with traditional factors (all P < 0.05). Elders with low hSMI and low GS (HRs = 4.33, 95% CI: 2.76-6.78), high TUG (4.11, 2.60-6.48), high TCS (2.97, 1.92-4.59), low WaLP (3.19, 2.13-4.79), and low HS (4.08, 2.70-6.17) were associated with high risks of mortality compared with those with high hSMI and their corresponding counterparts.

Conclusion: The hSMI and physical performance are significantly associated with increased risks of all-cause mortality. The combined use of hSMI and physical performance can provide improved risk stratification, which may be appropriately used as a screening tool targeting high-risk elders for the effective prevention of sarcopenia-related mortality.
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http://dx.doi.org/10.1186/s12877-022-03292-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295364PMC
July 2022

Predicting frailty in older adults using vocal biomarkers: a cross-sectional study.

BMC Geriatr 2022 07 1;22(1):549. Epub 2022 Jul 1.

Department of Chinese Medicine, China Medical University Hospital, No. 2, Yude Road, North District, 40447, Taichung, Taiwan.

Background: Frailty is a common issue in the aging population. Given that frailty syndrome is little discussed in the literature on the aging voice, the current study aims to examine the relationship between frailty and vocal biomarkers in older people.

Methods: Participants aged ≥ 60 years visiting geriatric outpatient clinics were recruited. They underwent frailty assessment (Cardiovascular Health Study [CHS] index; Study of Osteoporotic Fractures [SOF] index; and Fatigue, Resistance, Ambulation, Illness, and Loss of weight [FRAIL] index) and were asked to pronounce a sustained vowel /a/ for approximately 1 s. Four voice parameters were assessed: average number of zero crossings (A1), variations in local peaks and valleys (A2), variations in first and second formant frequencies (A3), and spectral energy ratio (A4).

Results: Among 277 older adults, increased A1 was associated with a lower likelihood of frailty as defined by SOF (odds ratio [OR] 0.84, 95% confidence interval [CI] 0.74-0.96). Participants with larger A2 values were more likely to be frail, as defined by FRAIL and CHS (FRAIL: OR 1.41, 95% CI 1.12-1.79; CHS: OR 1.38, 95% CI 1.10-1.75). Sex differences were observed across the three frailty indices. In male participants, an increase in A3 by 10 points increased the odds of frailty by almost 7% (SOF: OR 1.07, 95% CI 1.02-1.12), 6% (FRAIL: OR 1.06, 95% CI 1.02-1.11), or 6% (CHS: OR 1.06, 95% CI 1.01-1.11). In female participants, an increase in A4 by 0.1 conferred a significant 2.8-fold (SOF: OR 2.81, 95% CI 1.71-4.62), 2.3-fold (FRAIL: OR 2.31, 95% CI 1.45-3.68), or 2.8-fold (CHS: OR 2.82, 95% CI 1.76-4.51, CHS) increased odds of frailty.

Conclusions: Vocal biomarkers, especially spectral-domain voice parameters, might have potential for estimating frailty, as a non-invasive, instantaneous, objective, and cost-effective estimation tool, and demonstrating sex differences for individualised treatment of frailty.
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http://dx.doi.org/10.1186/s12877-022-03237-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248103PMC
July 2022

Prediction of all-cause and cardiovascular mortality using ankle-brachial index and brachial-ankle pulse wave velocity in patients with type 2 diabetes.

Sci Rep 2022 Jun 30;12(1):11053. Epub 2022 Jun 30.

Department of Public Health, College of Public Health, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung City, 406040, Taiwan R.O.C..

Ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) are used as non-invasive indicators for detecting atherosclerosis and arterial stiffness, two well-known predictors of mortality in patients with type 2 diabetes mellitus (T2DM). ABI and baPWV have independent associations with mortality; however, their joint and interactive effects on mortality have not been assessed in patients with T2DM. This work aims to evaluate the independent, joint, and interactive associations of ABI and baPWV with all-cause and expanded cardiovascular disease (CVD) mortality in patients with T2DM. This observational study included 2160 patients with T2DM enlisted in the Diabetes Care Management Program database of China Medical University Hospital from 2001 to 2016 and then followed their death status until August 2021. Cox proportional hazard models were used to evaluate the independent, joint, and interactive effects of ABI and baPWV on the risk of all-cause and expanded CVD mortality. A total of 474 patient deaths occurred after a mean follow-up of 8.4 years, and 268 of which were attributed to cardiovascular events. Abnormal ABI (≤ 0.9) and highest baPWV quartile were independently associated with increased risks of all-cause [ABI: hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.30-2.11; baPWV: 1.63, 1.16-2.27] and expanded CVD mortality (ABI: 2.21, 1.62-3.02; baPWV: 1.75, 1.09-2.83). The combination of abnormal ABI (≤ 0.9) and highest baPWV quartile was associated with a significantly higher risk of all-cause (4.51, 2.50-8.11) and expanded CVD mortality (9.74, 4.21-22.51) compared with that of the combination of normal ABI and lowest baPWV quartile. Significant interactions were observed between ABI and baPWV in relation to all-cause and expand CVD mortality (both p for interaction < 0.001). Through their independent, joint, and interactive effects, ABI and baPWV are significant parameters that can improve the prediction of all-cause and expanded CVD mortality in patients with T2DM and help identify high-risk patients who may benefit from diabetes care.
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http://dx.doi.org/10.1038/s41598-022-15346-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247028PMC
June 2022

Development of a traditional Chinese medicine-based agent for the treatment of cancer cachexia.

J Cachexia Sarcopenia Muscle 2022 Jun 19. Epub 2022 Jun 19.

School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.

Background: Despite recent advances in understanding the pathophysiology of cancer cachexia, prevention/treatment of this debilitating disease remains an unmet medical need.

Methods: We developed an integrated, multi-tiered strategy involving both in vitro and in vivo muscle atrophy platforms to identify traditional Chinese medicine (TCM)-based anti-cachectic agents. In the initial screening, we used inflammatory cytokine-induced atrophy of C2C12 myotubes as a phenotypic screening platform to assess the protective effects of TCMs. The selected TCMs were then evaluated for their abilities to protect Caenorhabditis elegans from age-related reduction of mobility and contractility, followed by the C-26 colon adenocarcinoma mouse model of cachexia to confirm the anti-muscle atrophy effects (body/skeletal muscle weights, fibre size distribution, grip strengths, and serum IL-6). Transcriptome analysis, quantitative real-time polymerase chain reaction, and immunoblotting were performed to gain understanding of the potential mechanism(s) by which effective TCM protected against C26 tumour-induced muscle atrophy.

Results: Of 29 widely used TCMs, Dioscorea radix (DR) and Mu Dan Pi (MDP) showed a complete protection (all P values, 0.0002) vis-à-vis C26 conditioned medium control in the myotube atrophy platform. MDP exhibited a unique ability to ameliorate age-associated decreases in worm mobility, accompanied by improved total body contractions, relative to control (P < 0.0001 and <0.01, respectively), which, however, was not noted with DR. This differential in vivo protective effect between MDP and DR was also confirmed in the C-26 mouse model. MDP at 1000 mg/kg (MDP-H) was effective in protecting body weight loss (P < 0.05) in C-26 tumour-bearing mice without changing food or water intake, accompanied by the restoration of the fibre size distribution of hindleg skeletal muscles (P < 0.0001) and the forelimb grip strength (P < 0.05). MDP-treated C-26-tumour-bearing mice were alert, showed normal posture and better body conditions, and exhibited lower serum IL-6 levels (P = 0.06) relative to vehicle control. This decreased serum IL-6 was associated with the in vitro suppressive effect of MDP (25 and 50 μg/mL) on IL-6 secretion into culture medium by C26 cells. RNA-seq analysis, followed by quantitative real-time polymerase chain reaction and/or immunoblotting, shows that MDP's anti-cachectic effect was attributable to its ability to reverse the C-26 tumour-induced re-programming of muscle homoeostasis-associated gene expression, including that of two cachexia drivers (MuRF1 and Atrogin-1), in skeletal muscles.

Conclusion: All these findings suggest the translational potential of MDP to foster new strategies for the prevention and/or treatment of cachexia. The protective effect of MDP on other types of muscle atrophy such as sarcopenia might warrant investigations.
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http://dx.doi.org/10.1002/jcsm.13028DOI Listing
June 2022

Novel design of cryptosystems for video/audio streaming via dynamic synchronized chaos-based random keys.

Multimed Syst 2022 May 21:1-16. Epub 2022 May 21.

Department of Electronic Engineering, National Chin-Yi University of Technology, Taichung, 41107 Taiwan.

In this paper, a novel chaos-based cryptosystem is proposed to ensure the communication security of video/audio streaming in the network environment. Firstly, by the proposed synchronization controller for the master and slave chaotic systems, respectively, embedded in the transmitter and receiver, the cryptosystem can generate the synchronized and dynamic chaotic random numbers at the transmitter and receiver simultaneously. Then integrating the chaotic random numbers with SHA3-256 (Secure hash algorithm 3), the design of synchronized dynamic key generators (SDKGs) is completed. Continuously, we can apply the SDKGs to encrypt/decrypt streaming audio/video data. In our design, we introduce the AES CFB (Advanced encryption standard cipher feedback) encryption algorithm with SDKGs to encrypt the video/audio streaming. Then the cipher-text is transmitted to the receiver via the network public channel and it can be fully decrypted with the dynamic random keys synchronously generated at the receiver. A duplex audio/video cryptosystem is realized to illustrate the performance and feasibility of this proposed research. Finally, many tests and comparisons are performed to stress the quality of random sequences generated by proposed SDKGs.
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http://dx.doi.org/10.1007/s00530-022-00950-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9123879PMC
May 2022

Sleep duration predicts subsequent long-term mortality in patients with type 2 diabetes: a large single-center cohort study.

Cardiovasc Diabetol 2022 04 27;21(1):60. Epub 2022 Apr 27.

Department of Public Health, College of Public Health, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung, 406040, Taiwan.

Background: Sleep duration is associated with mortality. However, prior studies exploring whether sleep duration predicts subsequent long-term mortality in patients with diabetes are limited. This study aims to examine whether metabolic factors affect the associations between baseline sleep duration and subsequent risks of all-cause, expanded, and non-expanded cardiovascular disease (CVD) mortalities among patients with type 2 diabetes (T2D).

Methods: A total of 12,526 T2D patients aged 30 years and older, with a follow-up period ≥ 3 years, were identified from the Diabetes Case Management Program of a medical center in Taiwan. Sleep duration was measured using computerized questionnaires by case managers, and the time frame for this question was 1 month prior to the interview date. Sleep duration in relation to subsequent mortality from all causes, expanded CVD, and non-expanded CVD was examined using Cox proportional hazard models.

Results: Within 10 years of follow-up, 2918 deaths (1328 CVD deaths and 1590 non-CVD deaths) were recorded. A J-shaped association was observed for all-cause, expanded CVD, and non-expanded CVD mortalities, and the lowest risks were observed for patients with 5-7 h of sleep. The significant joint effects included sleep duration of more or less than 7 h with age ≥ 65 years [adjusted HRs: 4.00 (3.49-4.60)], diabetes duration ≥ 5 years [1.60 (1.40-1.84)], age at diabetes diagnosis ≤ 45 years [1.69 (1.38-2.07)], insulin use [1.76 (1.54-2.03)], systolic blood pressure/diastolic blood pressure > 130/85 mmHg [1.24 (1.07-1.43)], triglyceride ≥ 150 mg/dL [1.38 (1.22-1.56)], HbA1c ≥ 7% [1.31 (1.13-1.52)], and body mass index < 27 kg/m [1.31 (1.17-1.45)] for all-cause mortality.

Conclusion: A J-shaped association was observed between sleep duration and all-cause and expanded CVD mortality, and a sleep duration of 5-7 h had the lowest mortality risk. Sleep duration also showed significant synergistic interactions with diabetes duration but shared an antagonistic interaction with age and obesity.
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http://dx.doi.org/10.1186/s12933-022-01500-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9045470PMC
April 2022

Immunogenicity and safety of homologous and heterologous ChAdOx1-S and mRNA-1273 vaccinations in healthy adults in Taiwan.

J Clin Virol 2022 Jun 6;150-151:105156. Epub 2022 Apr 6.

Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan,; Department of Laboratory Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan; Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan,; Ph.D Program for Aging, School of Medicine, China Medical University, Taichung, Taiwan. Electronic address:

Background: In Taiwan, the vaccination program started in March 2021, with ChAdOx1-S being the first available WHO-approved COVID-19 vaccine, followed by Moderna vaccine. This study aimed to investigate the immunogenicity and safety of homologous and heterologous prime-boost regimens with ChAdOx1-S and mRNA-1273.

Methods: From March to November 2021, homologous or heterologous regimens with ChAdOx1-S and mRNA-1273 vaccination (ChAdOx1-S/ChAdOx1-S, mRNA-1273/mRNA-1273, ChAdOx1-S/mRNA-1273) were given to 945 healthy participants. Serum samples were collected at designated time points. The anti-RBD/S1 antibody titers and neutralizing ability were measured by three different immunoassays: Elecsys® Anti-SARS-CoV-2 S (Roche Diagnostics, Mannheim, Germany), AdviseDx SARS-CoV-2 IgG II (Abbott Diagnostics Division, Sligo, Ireland), and cPass™ SARS-CoV-2 Neutralization Antibody Detection Kit (GenScript, New Jersey, USA).

Results: We found that heterologous vaccination with ChAdOx1-S/mRNA-1273 had an acceptable safety profile and induced higher total anti-RBD/S1 antibody production (p < 0.0001), yet lower anti-RBD/S1 IgG titer (p < 0.0001) and neutralizing ability (p = 0.0101) than mRNA-1273/mRNA-1273 group. Both regimens showed higher antibody titers and superior neutralizing abilities than ChAdOx1-S/ChAdOx1-S. An age-dependent antibody response to ChAdOx1-S/mRNA-1273 was shown after both the priming and the booster doses. Younger age was associated with higher antibody production and neutralizing ability.

Conclusions: Heterologous ChAdOx1-S/mRNA-1273 vaccination regimen is generally safe and induces a robust humoral immune response that is non-inferior to that of mRNA-1273/mRNA-1273.
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http://dx.doi.org/10.1016/j.jcv.2022.105156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986279PMC
June 2022

Development and validation of a risk prediction model for chronic kidney disease among individuals with type 2 diabetes.

Sci Rep 2022 03 21;12(1):4794. Epub 2022 Mar 21.

Department of Public Health, College of Public Health, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung City, 406040, Taiwan.

Many studies had established the chronic kidney disease (CKD) prediction models, but most of them were conducted on the general population and not on patients with type 2 diabetes, especially in Asian populations. This study aimed to develop a risk prediction model for CKD in patients with type 2 diabetes from the Diabetes Care Management Program (DCMP) in Taiwan. This research was a retrospective cohort study. We used the DCMP database to set up a cohort of 4,601 patients with type 2 diabetes without CKD aged 40-92 years enrolled in the DCMP program of a Taichung medical center in 2002-2016. All patients were followed up until incidences of CKD, death, and loss to follow-up or 2016. The dataset for participants of national DCMP in 2002-2004 was used as external validation. The incident CKD cases were defined as having one of the following three conditions: ACR data greater than or equal to 300 (mg/g); both eGFR data less than 60 (ml/min/1.73 m) and ACR data greater than or equal to 30 (mg/g); and eGFR data less than 45 (ml/min/1.73 m). The study subjects were randomly allocated to derivation and validation sets at a 2:1 ratio. Cox proportional hazards regression model was used to identify the risk factors of CKD in the derivation set. Time-varying area under receiver operating characteristics curve (AUC) was used to evaluate the performance of the risk model. After an average of 3.8 years of follow-up period, 3,067 study subjects were included in the derivation set, and 786 (25.63%) were newly diagnosed CKD cases. A total of 1,534 participants were designated to the validation set, and 378 (24.64%) were newly diagnosed CKD cases. The final CKD risk factors consisted of age, duration of diabetes, insulin use, estimated glomerular filtration rate, albumin-to-creatinine ratio, high-density lipoprotein cholesterol, triglyceride, diabetes retinopathy, variation in HbA1c, variation in FPG, and hypertension drug use. The AUC values of 1-, 3-, and 5-year CKD risks were 0.74, 0.76, and 0.77 in the validation set, respectively, and were 0.76, 0.77, and 0.76 in the sample for external validation, respectively. The value of Harrell's c-statistics was 0.76 (0.74, 0.78). The proposed model is the first CKD risk prediction model for type 2 diabetes patients in Taiwan. The 1-, 3-, and 5-year CKD risk prediction models showed good prediction accuracy. The model can be used as a guide for clinicians to develop medical plans for future CKD preventive intervention in Chinese patients with type 2 diabetes.
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http://dx.doi.org/10.1038/s41598-022-08284-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8938464PMC
March 2022

Effect of blood pressure trajectory and variability on new-onset chronic kidney disease in patients with type 2 diabetes.

Hypertens Res 2022 05 3;45(5):876-886. Epub 2022 Mar 3.

Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan, ROC.

This study aimed to evaluate the effects of BP trajectory and variability on chronic kidney disease (CKD) incidence in patients with type 2 diabetes. This retrospective longitudinal study included 4,560 participants with type 2 diabetes, aged ≥30 years, free of CKD, with ≥3 years of follow-up, and who attended the Diabetes Care Management Program in 2001-2013. The follow-up period ended in 2016. The adverse outcome was a new-onset CKD event, which was determined using eGFR and albuminuria. Cox proportional hazards models were used to assess the associations. At the end of the follow-up, 1255 participants had developed CKD, with a mean follow-up of 4.3 ± 3.2 years. Three trajectory subgroups of BP, i.e., Cluster 1: "moderate-stable" for SBP and "moderate-downward" for DBP, Cluster 2: "low-upward-downward" for both SBP and DBP, and Cluster 3: "high-downward-upward" for both SBP and DBP, were generated. The BP variability was grouped into three classes on the basis of tertiles. For the BP trajectory, patients in Cluster 3 of DBP had a higher CKD risk than those in Cluster 1 (HR = 1.24, 95% CI = 1.03-1.50). For the BP variability, patients in Tertile 3 had a significantly higher CKD risk than those in Tertile 1 (SBP: 1.28, 1.11-1.47; DBP: 1.17, 1.02-1.34). Persons with type 2 diabetes who achieved a small reduction in DBP after participating in the education program but rebounded and those who had the highest variation in both SBP and DBP faced the highest increase in CKD risk.
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http://dx.doi.org/10.1038/s41440-022-00882-8DOI Listing
May 2022

Applying Machine Learning to Carotid Sonographic Features for Recurrent Stroke in Patients With Acute Stroke.

Front Cardiovasc Med 2022 28;9:804410. Epub 2022 Jan 28.

Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan.

Background: Although carotid sonographic features have been used as predictors of recurrent stroke, few large-scale studies have explored the use of machine learning analysis of carotid sonographic features for the prediction of recurrent stroke.

Methods: We retrospectively collected electronic medical records of enrolled patients from the data warehouse of China Medical University Hospital, a tertiary medical center in central Taiwan, from January 2012 to November 2018. We included patients who underwent a documented carotid ultrasound within 30 days of experiencing an acute first stroke during the study period. We classified these participants into two groups: those with non-recurrent stroke (those who has not been diagnosed with acute stroke again during the study period) and those with recurrent stoke (those who has been diagnosed with acute stroke during the study period). A total of 1,235 carotid sonographic parameters were analyzed. Data on the patients' demographic characteristics and comorbidities were also collected. Python 3.7 was used as the programming language, and the scikit-learn toolkit was used to complete the derivation and verification of the machine learning methods.

Results: In total, 2,411 patients were enrolled in this study, of whom 1,896 and 515 had non-recurrent and recurrent stroke, respectively. After extraction, 43 features of carotid sonography (36 carotid sonographic parameters and seven transcranial color Doppler sonographic parameter) were analyzed. For predicting recurrent stroke, CatBoost achieved the highest area under the curve (0.844, CIs 95% 0.824-0.868), followed by the Light Gradient Boosting Machine (0.832, CIs 95% 0.813-0.851), random forest (0.819, CIs 95% 0.802-0.846), support-vector machine (0.759, CIs 95% 0.739-0.781), logistic regression (0.781, CIs 95% 0.764-0.800), and decision tree (0.735, CIs 95% 0.717-0.755) models.

Conclusion: When using the CatBoost model, the top three features for predicting recurrent stroke were determined to be the use of anticoagulation medications, the use of NSAID medications, and the resistive index of the left subclavian artery. The CatBoost model demonstrated efficiency and achieved optimal performance in the predictive classification of non-recurrent and recurrent stroke.
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http://dx.doi.org/10.3389/fcvm.2022.804410DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8833232PMC
January 2022

Effect of blood lipid variability on mortality in patients with type 2 diabetes: a large single-center cohort study.

Cardiovasc Diabetol 2021 11 25;20(1):228. Epub 2021 Nov 25.

Department of Family Medicine, China Medical University Hospital, No. 2, Yude Rd., North Dist., Taichung, 404332, Taiwan (R.O.C.).

Background: Dyslipidemia is a major cardiovascular risk factor and common in diabetes patients. Most guidelines focus on optimal lipid levels, while variation of lipid profiles is far less discussed. This study aims to investigate the association of visit-to-visit variability in blood lipids with all-cause, cardiovascular, and non-cardiovascular mortality in patients with type 2 diabetes.

Methods: We identified 10,583 type 2 diabetes patients aged ≥ 30 years with follow-up ≥ 3 years and who participated in the Diabetes Care Management Program at a medical center in Taiwan. Variability in lipid profiles within 3 years after entry was calculated using coefficient of variation. Cox proportional hazard models were used to evaluate lipid variability in relation to subsequent mortality.

Results: Over a mean follow-up of 6.4 years, 1838 all-cause deaths (809 cardiovascular deaths) were observed. For each 10% increase in variability in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total cholesterol, the hazard ratios (95% confidence intervals) of all-cause mortality were 1.30 (1.22-1.37), 1.05 (1.01-1.09), and 1.10 (1.03-1.16), respectively; those of cardiovascular mortality were 1.27 (1.16-1.39), 1.08 (1.02-1.15), and 1.16 (1.07-1.27), respectively. Each 10% increase in high-density lipoprotein cholesterol variability conveyed 31% greater risk of non-cardiovascular mortality. High variability in total cholesterol and low-density lipoprotein cholesterol increased all-cause mortality in subgroups of nonsmoking, regular exercising, non-dyslipidemia, and more severe status of diabetes at baseline.

Conclusions: Blood lipid variability except for triglyceride variability was associated with all-cause and cardiovascular mortality in patients with type 2 diabetes.
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http://dx.doi.org/10.1186/s12933-021-01421-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620132PMC
November 2021

Corrigendum to 'Risk of sarcopenia among older persons with Type 2 diabetes mellitus with different status of albuminuria: A dose-responsive association' [Archives Gerontology Geriatrics volume 95C (July/August 2021) 104338].

Arch Gerontol Geriatr 2022 Jan-Feb;98:104574. Epub 2021 Nov 16.

Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan; Aging and Health Research Center, National Yang Ming University, Taipei, Taiwan; Department of Geriatric Medicine, National Yang Ming University School of Medicine, Taipei, Taiwan.

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http://dx.doi.org/10.1016/j.archger.2021.104574DOI Listing
November 2021

Derivation and validation of a clinical prediction model for risks of venous thromboembolism in diabetic and general populations.

Medicine (Baltimore) 2021 Oct;100(39):e27367

Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan.

Abstract: Most studies on the prediction of venous thromboembolism (VTE) focused on hospitalized, surgery, and cancer patients or women receiving hormonal contraceptives or menopausal hormone therapy. No study considered diabetic and general populations to establish a VTE prediction model, especially in Asia. We developed a predictive model for VTE among type 2 diabetic patients and the general population.This study considered 2 nationwide retrospective cohort studies consisting of 52,427 diabetic participants and 508,664 participants from the general population aged 30 to 85 years during 2001 to 2004 in Taiwan. All participants were followed up until VTE event, death, or December 2011. The outcome event was VTE, including deep venous thrombosis and pulmonary embolism. Candidate predictors consisted of socio-demographic factors, diabetes-related factors and biomarkers, comorbidities, and medicine use. Our study followed the procedures proposed by the Framingham Heart Study to develop prediction models by using a Cox regression model. The predictive accuracy and performance characteristics were assessed using the area under curve of receiver operating characteristics curve and calibration of a risk score were performed by Hosmer-Lemeshow goodness-of-fit test.The common factors for persons with type 2 diabetes and general population included age, hospitalization status 1 year before the baseline, hypertension, chronic kidney disease, chronic obstructive pulmonary disease, and anti-diabetes medications; the specific factors for persons with type 2 diabetes consisted of body mass index, glycosylated hemoglobin A1C, and creatinine; and the factors for general population included gender, peripheral vascular disease, cancer, hypertension medication, cardiovascular medication, and non-steroidal anti-inflammatory drug. The area under curve of 3-, 5-, and 8-year VTE prediction models were 0.74, 0.71, and 0.69 in the diabetic population and 0.77, 0.76, and 0.75 in the general population, respectively.The new clinical prediction models can help identify a high risk of VTE and provide medical intervention in diabetic and general populations.
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http://dx.doi.org/10.1097/MD.0000000000027367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483831PMC
October 2021

Three-year trajectories of metabolic risk factors predict subsequent long-term mortality in patients with type 2 diabetes.

Diabetes Res Clin Pract 2021 Sep 4;179:108995. Epub 2021 Aug 4.

Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan; Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan. Electronic address:

Aim: This study aims to evaluate the associations between 3-year trajectories of metabolic risk factors and subsequent mortality in patients with type 2 diabetes.

Methods: A total of 6400 persons aged ≥ 30 years with type 2 diabetes and ≥ 3 years of follow-up period were included. The cluster analysis determined the patterns of 3-year trajectories, and Cox proportional hazards models evaluated the associations between patterns and mortality.

Results: Three trajectory subgroups of metabolic risk factors, namely, cluster 1, normal; cluster 2, high-stable or reducing with high level at baseline; and cluster 3, fluctuation: elevated and decreasing, were generated. The clusters 2 and 3 of body mass index (BMI), fasting plasma glucose (FPG), HbA1c, and triglyceride (TG) trajectories were associated with increased risks of all-cause mortality compared with cluster 1 (hazard ratio = 1.27, 95% confidence interval = 1.06-1.51 and 1.45, 1.19-1.78 for BMI; 1.41, 1.22-1.62 and 1.81, 1.38-2.38 for FPG; 1.42, 1.23-1.64 and 1.47, 1.23-1.75 for HbA1c; 1.34, 1.10-1.63 and 2.40, 1.30-4.37 for TG, respectively). For the systolic blood pressure trajectory, only cluster 3 was associated with an increased mortality risk relative to cluster 1 (1.76, 1.13-2.77).

Conclusions: Long-term metabolic risk factor trajectories may be associated with subsequent mortality.
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http://dx.doi.org/10.1016/j.diabres.2021.108995DOI Listing
September 2021

A risk scoring system to predict the risk of new-onset hypertension among patients with type 2 diabetes.

J Clin Hypertens (Greenwich) 2021 08 12;23(8):1570-1580. Epub 2021 Jul 12.

Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan.

Hypertension (HTN), which frequently co-exists with diabetes mellitus, is the leading major cause of cardiovascular disease and death globally. This study aimed to develop and validate a risk scoring system considering the effects of glycemic and blood pressure (BP) variabilities to predict HTN incidence in patients with type 2 diabetes. This research is a retrospective cohort study that included 3416 patients with type 2 diabetes without HTN and who were enrolled in a managed care program in 2001-2015. The patients were followed up until April 2016, new-onset HTN event, or death. HTN was defined as diastolic BP (DBP) ≥ 90 mm Hg, systolic BP (SBP) ≥ 140 mm Hg, or the initiation of antihypertensive medication. Cox proportional hazard regression model was used to develop the risk scoring system for HTN. Of the patients, 1738 experienced new-onset HTN during an average follow-up period of 3.40 years. Age, sex, physical activity, body mass index, type of DM treatment, family history of HTN, baseline SBP and DBP, variabilities of fasting plasma glucose, SBP, and DBP and macroalbuminuria were significant variables for the prediction of new-onset HTN. Using these predictors, the prediction models for 1-, 3-, and 5-year periods demonstrated good discrimination, with AUC values of 0.70-0.76. Our HTN scoring system for patients with type 2 DM, which involves innovative predictors of glycemic and BP variabilities, has good classification accuracy and identifies risk factors available in clinical settings for prevention of the progression to new-onset HTN.
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http://dx.doi.org/10.1111/jch.14322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8678759PMC
August 2021

Renal markers and risks of all cause and cardiovascular mortality from the Taichung community based cohort study.

Sci Rep 2021 07 8;11(1):14143. Epub 2021 Jul 8.

Department of Public Health, College of Public Health, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist., Taichung, 406040, Taiwan, ROC.

This study aimed to explore the associations between renal-related and arterial stiffness biomarkers with all-cause and expanded cardiovascular disease (CVD) mortality in a general Taiwanese population. This prospective community-based cohort study included 4883 subjects aged ≥ 20 years who were followed up until December 31, 2016. Renal-related biomarkers consisted of blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and urine albumin-to-creatinine ratio (UACR). Arterial stiffness biomarker consisted of brachial-ankle pulse wave velocity (baPWV). The death status of the subjects was ascertained by matching information from death records with the identification number and date of birth of the subjects. Cox proportional hazard models with restricted cubic splines estimated the hazard ratios and 95% confidence intervals for all-cause mortality and expanded CVD mortality. During a mean 8.3 years of follow up, 456 deaths were recorded, 146 of which were due to expanded CVD mortality. The multivariable-adjusted hazard ratios of all-cause mortality was 1.53 (95% CI 1.21-1.94) for BUN (≥ 20 mg/dL vs. < 20 mg/dL), 1.57 (1.15-2.14) for eGFR (< 90 mL/min/1.73 m vs. ≥ 90 mL/min/1.73 m), 1.55 (1.25-1.92) for UACR (≥ 30 mg/g vs. < 30 mg/g), and 1.75 (1.14-2.67) for baPWV (≥ 1400 cm/s vs. < 1400 cm/s). The expanded CVD mortality was 1.89 (95% CI 1.30-2.73) for BUN (≥ 20 mg/dL vs. < 20 mg/dL), 2.28 (1.13-4.57) for eGFR (< 90 mL/min/1.73 m vs. ≥ 90 mL/min/1.73 m), 2.13 (1.52-2.99) for UACR (≥ 25 mg/g vs. < 25 mg/g), and 15.73 (2.14-115.61) for baPWV (≥ 1400 cm/s vs. < 1400 cm/s). High levels of BUN, UACR, and baPWV and low levels of eGFR showed high risks with all-cause and expanded CVD mortality. Our study provides insights into screening tests to target populations at high risk of premature death due to CVD.
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http://dx.doi.org/10.1038/s41598-021-93627-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266842PMC
July 2021

Efficacy of intratracheal budesonide-surfactant combined therapy in surfactant-insufficient rat lungs with lipopolysaccharide insult.

J Chin Med Assoc 2021 08;84(8):783-790

Department and Institute of Physiology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.

Background: Intratracheal steroid therapy for lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains challenging particularly in surfactant-insufficient lungs, a common problem of neonatal or pediatric ALI. Surfactant has been used as a vehicle for intratracheal steroid in the treatment of other types of ALI. This study investigated the efficacy of intratracheal budesonide (BUD) delivered by two concentrations of surfactant in the treatment of LPS-induced ALI in surfactant-insufficient rat lungs.

Methods: Male adult rats were anesthetized and ventilated. Our ALI model was established by repeated saline lavage to produce surfactant insufficiency, followed by intratracheal LPS instillation. Five study groups (n = 5 for each) with different intratracheal treatments following ALI were used: control (no treatment), BUD (NS-BUD; BUD in saline), DS-BUD (BUD in diluted surfactant), FS-BUD (BUD in full-strength surfactant), FS (full-strength surfactant). Cardiopulmonary variables were monitored 4 hours post injury. Histological and immunohistochemical assessments of the lungs were performed.

Results: The FS-BUD and FS groups presented better gas exchange, less metabolic acidosis, less oxygen index, and more stable hemodynamic changes than the DS-BUD, NS-BUD, and control groups. The total lung injury scores assessed by histological examination were ordered as follows: FS-BUD < DS-BUD or FS < NS-BUD < control. The immunostaining intensities of lung myeloperoxidase showed the following order: NS-BUD, DS-BUD, or FS-BUD < control or FS. Only the FS-BUD group displayed a smaller immunostaining intensity of lung tumor necrosis factor (TNF)-α than the control group.

Conclusion: Among our therapeutic strategies, intratracheal BUD delivered by full-strength surfactant confers an optimal protection against LPS-induced ALI in surfactant-insufficient rat lungs.
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http://dx.doi.org/10.1097/JCMA.0000000000000567DOI Listing
August 2021

Association between Parkinson's disease and proton pump inhibitors therapy in older people.

Biomedicine (Taipei) 2020 1;10(3):1-4. Epub 2020 Sep 1.

College of Medicine, China Medical University, Taichung, Taiwan.

Objectives: The study was to explore the association between Parkinson's disease and proton pump inhibitors use.

Methods: A population-based case-control study was conducted to analyze the 2000-2013 database of Taiwan National Health Insurance Program. In total, there were 4280 participants aged ≥65 years with newly diagnosed Parkinson's disease as the case group and 4280 sex- and age-matched participants without Parkinson's disease as the control group. Ever use of proton pump inhibitors was defined as participants who had at least a prescription for proton pump inhibitors before the index date. Never use of proton pump inhibitors was defined as participants who did not have a prescription for proton pump inhibitors before the index date. The odds ratio and 95% confidence interval were used to estimate the association between Parkinson's disease and proton pump inhibitors use by the logistic regression model.

Results: A significant association was detected between Parkinson's disease and proton pump inhibitors use (odds ratio 1.15, 95% confidence interval 1.04-1.27).

Conclusions: An association is found between Parkinson's disease and proton pump inhibitors use in older people. Other real-world data are required to confirm the clinical impact of proton pump inhibitors therapy on the risk of Parkinson's disease.
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http://dx.doi.org/10.37796/2211-8039.1048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721474PMC
September 2020

Longitudinal data of multimorbidity and polypharmacy in older adults in Taiwan from 2000 to 2013.

Biomedicine (Taipei) 2020 5;10(2):1-4. Epub 2020 Jun 5.

College of Medicine, China Medical University, Taichung, Taiwan.

Objective: The objective of the study was to evaluate the prevalences and trends of multimorbidity and polypharmacy in older adults in Taiwan.

Methods: An observational study was performed using the 2000-2013 database of the Taiwan National Health Insurance Program (analysis in 2018). Participants ≥65 years were included in the study. Multimorbidity was defined as participants having two or more chronic diseases annually. Polypharmacy was defined as the average daily number of prescribed medications ≥5.

Results: The prevalences of multimorbidity were 42.4% in 2000 and 56% in 2013. The prevalences of polypharmacy were 22.9% in 2000 and 32.1% in 2013.

Conclusions: From 2000 to 2013, multimorbidity and polypharmacy were prevalent among older adults in Taiwan. Public health efforts to intervene the primary prevention for chronic diseases should be considered in older adults.
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http://dx.doi.org/10.37796/2211-8039.1013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608846PMC
June 2020

Frailty status changes are associated with healthcare utilization and subsequent mortality in the elderly population.

BMC Public Health 2021 04 1;21(1):645. Epub 2021 Apr 1.

School of Medicine, College of Medicine, China Medical University, No. 100, Sec. 1, Jingmao Rd., Beitun Dist, Taichung City, 406040, Taiwan ROC.

Background: This study determined (1) whether a change in frailty status after a 1 year follow up is associated with healthcare utilization and evaluated (2) whether a change in frailty status after a 1 year follow up and health care utilization are associated with all-cause mortality in a sample of Taiwan population.

Methods: This work is a population-based prospective cohort study involving residents aged ≥65 years in 2009. A total of 548 elderly patients who received follow-ups in the subsequent year were included in the current data analysis. Fried frailty phenotype was measured at baseline and 1 year. Information on the outpatient visits of each specialty doctor, emergency care utilization, and hospital admission during the 2 month period before the second interview was collected through standardized questionnaires administered by an interviewer. Deaths were verified by indexing to the national database of deaths.

Results: At the subsequent 1 year follow-up, 73 (13.3%), 356 (64.9%), and 119 (21.7%) elderly participants exhibited deterioration, no change in status, and improvement in frailty states, respectively. Multivariate logistic analysis showed the high risk of any type of outpatient use (odds ratios [OR] 1.94, 95% confidence interval [CI] 1.02-3.71) among older adults with worse frailty status compared with those who were robust at baseline and had unchanged frailty status after 1 year. After multivariate adjustment, participants with high outpatient clinic utilization had significantly higher mortality than those with low outpatient clinic visits among unchanged pre-frail or frail (hazard ratios [HR] 2.79, 95% CI: 1.46-5.33) and frail to pre-frail/robust group (HR 9.32, 95% CI: 3.82-22.73) if the unchanged robustness and low outpatient clinic visits group was used as the reference group.

Conclusions: The conditions associated with frailty status, either after 1 year or at baseline, significantly affected the outpatient visits and may have increased medical expenditures. Combined change in frailty status and number of outpatient visits is related to increased mortality.
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http://dx.doi.org/10.1186/s12889-021-10688-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017879PMC
April 2021

Risk of sarcopenia among older persons with Type 2 diabetes mellitus with different status of albuminuria: A dose-responsive association.

Arch Gerontol Geriatr 2021 Jul-Aug;95:104338. Epub 2021 Feb 5.

Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan; Aging and Health Research Center, National Yang Ming University, Taipei, Taiwan; Department of Geriatric Medicine, National Yang Ming University School of Medicine, Taipei, Taiwan.

Background: The association between type 2 diabetes mellitus (T2DM) and sarcopenia has been reported before, but little was known regarding associations between albuminuria status in the development of sarcopenia. This study aimed to explore the associations between albuminuria status and sarcopenia among older patients with T2DM.

Methods: This cross-sectional study recruited T2DM patients aged 65 years and older from the DM shared care center in a regional hospital who were grossly absent from functional impairment. Demographic characteristics were collected and functional assessments were performed for all participants. Urinary albumin-to-creatinine ratio (UACR) was obtained by spot urine exams, whereas UACR ≥ 30 mg/g was defined as microalbuminuria, and UACR > 300 mg/g as macroalbuminuria. Appendicular lean mass (ASM) was measured by the dual X-ray absorptiometry, and the relative appendicular muscle mass (RASM) was calculated as the ASM divided by height square (kg/m).The definition of sarcopenia was made according to the Asian Working Group for Sarcopenia and muscle quality was defined as handgrip strength (kg) divided by RASM.

Results: Overall, 180 participants (mean age: 72.5±5.3 years, 53.3% males) were enrolled for study. Higher HbA1c levels and poorer renal function were significantly associated with more severe albuminuria status.Besides, sarcopenia and low handgrip strength also showed dose-responsive associations with albuminuria status, which was similar in muscle quality.The receiver operating characteristic curve determine that the UACR of 13.7 mg/g was the optimal cutoff for sarcopenia diagnosis, which was lower than the conventionally definition of microalbuminuria (<30 mg/g).

Conclusions: Albuminuria status was dose-responsively associated with sarcopenia among older persons with T2DM, and the risk started to escalate from minimal albuminuria (UACR 9.18 mg/g in men and 18.4 mg/g in women). Further intervention studies are needed to evaluate potential benefits of better diabetes control in preventing sarcopenia and its outcomes.
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http://dx.doi.org/10.1016/j.archger.2021.104338DOI Listing
June 2021

Mitochondrial DNA haplogroups affect physical performances in Han older adults: an 8-year follow-up prospective cohort study.

Geriatr Gerontol Int 2021 Feb 14;21(2):166-171. Epub 2020 Dec 14.

Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.

Aim: The objective of this study was to explore the association between mitochondrial DNA (mtDNA) haplogroups and physical performances in Han older adults.

Methods: This study was an 8-year follow-up prospective cohort study. A total of 104 Han older adults completed the measurements of the 6-min walk test, grip strength and mitochondrial DNA sequencing. The mtDNA haplogroups were classified by using HaploGrep2 software. We used the mixed model to analyze the longitudinal effect of mtDNA haplogroups on physical performance tests among three waves of data.

Results: The mean age at wave 3 among men and women were 78.3 and 77.2 years, respectively. The overall proportions of mtDNA haplogroups in this study population was 26.9% F, 21.2% M, 15.4% R, 14.4% D, 8.7% B and others. After adjusted for age, sex, ethnicity, body mass index and exercise, the interaction of mtDNA haplogroup M and waves significantly affected the 6-min walk distance. Notably, the adjusted mean of the 6-min walk distance among the group of mtDNA haplogroup M was significantly lower than other haplogroups at wave 3. The adjusted mean of grip strength among the group of mtDNA haplogroup R was significantly higher than other haplogroups at wave 3.

Conclusions: This finding suggests that mtDNA haplogroups might have effects on the 6-min walk test and grip strength in Han older adults, although studies of the physical performance of older adults with larger sample sizes are necessary to further substantiate these findings. Geriatr Gerontol Int 2021; 21: 166-171.
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http://dx.doi.org/10.1111/ggi.14105DOI Listing
February 2021

Independent associations of urinary albumin-to-creatinine ratio and serum cystatin C with carotid intima-media thickness in community-living Taiwanese adults.

BMC Nephrol 2020 10 31;21(1):454. Epub 2020 Oct 31.

School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.

Background: Renal function is a key factor of cardiovascular disease. Carotid intima-media thickness (IMT) has been widely used as a marker of early subclinical atherosclerosis. The determinants of cystatin C, a novel marker of renal function, have not been extensively studied in the Asian population. This study aimed to assess the determinants of cystatin C and explore whether carotid thickening was associated with urinary albumin-creatinine ratio and cystatin C in community-living Taiwanese adults.

Methods: A cross-sectional study was conducted on participants from Taichung City, Taiwan. All the participants underwent carotid ultrasonography. Carotid IMT-mean and IMT-maximum were derived. Kidney biomarkers were measured on the basis of urinary albumin-to-creatinine ratio (ACR) and cystatin C. Multiple linear regression analysis was used.

Results: A total of 1032 individuals were recruited, and 469 (45.44%) of them were men. An increased cystatin C level was significantly associated with older age, male gender, lack of physical activity, low HDL cholesterol, abdominal obesity, high hs-CRP, and high ACR. The multivariate-adjusted mean carotid IMT-mean and IMT-maximum values significantly increased by 80.49 and 195.23 μm for every one unit of increase in cystatin C level and by 0.07 and 0.14 μm for every one unit of increase in ACR, respectively (all p < 0.001 except ACR on IMT-maximum with p < 0.01). Lack of physical activity, low HDL, abdominal obesity, high hs-CRP, and high ACR were the determinants of cystatin C.

Conclusion: Cystatin C and ACR were strongly and linearly associated with carotid thickening, a marker of subclinical atherosclerosis.
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http://dx.doi.org/10.1186/s12882-020-02123-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603773PMC
October 2020

Interactions among IGF-1, AKT2, FOXO1, and FOXO3 variations and between genes and physical activities on physical performance in community-dwelling elders.

PLoS One 2020 28;15(9):e0239530. Epub 2020 Sep 28.

School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.

This study assessed the interactions among IGF-1, AKT2, FOXO1, and FOXO3 variations and the interactions of gene and physical activity on handgrip strength, arm muscle mass-adjusted handgrip (armGrip), gait speed (GS), timed up and go (TUG), and leg press strength (LPS). Nine single nucleotide polymorphisms (SNPs) containing three IGF-1 SNPs (rs6214, rs5742692, and rs35767), two AKT2 SNPs (rs892119 and rs35817154), two FOXO1 SNPs (rs17446593 and rs10507486), and two FOXO3 SNPs (rs9480865 and rs2153960) were genotyped in 472 unrelated elders with a mean age of 73.8 years. We observed significant interactions of IGF-1 SNP rs6214 and rs35767 with regular physical activity on TUG and GS; and AKT2 SNP rs892119 and FOXO3 SNP rs9480865 with regular physical activity on armGrip. Genotype GG of IGF-1 rs6214 and rs35767 in individuals without regular physical activity had poor performance in TUG and GS, as well as GG of AKT2 rs892119 decreased armGrip in individuals without regular physical activity. After FDR adjustment, no significant gene-gene interactions were found. A sedentary lifestyle may increase the risk of impairing physical performance and regular physical activity is a remedy for sarcopenia, even a little regular physical activity can overcome carrying some risk alleles in this pathway.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239530PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521683PMC
November 2020

Derivation and validation of 10-year all-cause and cardiovascular disease mortality prediction model for middle-aged and elderly community-dwelling adults in Taiwan.

PLoS One 2020 14;15(9):e0239063. Epub 2020 Sep 14.

School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.

Prediction model mainly focused on specific diseases, such as diabetes, hypertension, cardiovascular disease, or patients with cancer, or populations of Europe and America, thereby limiting its generalization. This study aimed to develop and validate a 10-year mortality risk score by using data from a population-representative sample of adults. Data were collected from 2,221 Taichung Community Health study participants aged ≥40 years. The baseline period of the study was 2004, and all participants were followed up until death or in 2016. Cox's proportional hazards regression analyses were used to develop the prediction model. A total of 262 deaths were ascertained during the 10-year follow-up. The all-cause mortality prediction model calculated the significant risk factors, namely, age, sex, marital status, physical activity, tobacco use, estimated glomerular filtration rate, and albumin-to-creatinine ratio, among the baseline risk factors. The expanded cardiovascular disease (CVD) mortality prediction model consisted of six variables: age, sex, body mass index, heart disease plus heart disease medication use, stroke plus medication use, and ankle-brachial index. The areas under receiver operating curves of the 3-, 5- and 10-year predictive models varied between 0.97, 0.96, and 0.88 for all-cause mortality, and between 0.97, 0.98, and 0.84 for expanded CVD mortality. These mortality prediction models are valid and can be used as tools to identify the increased risk for mortality.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239063PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489508PMC
November 2020

Diabetes mellitus associated with an increased risk of percutaneous coronary intervention long-term adverse outcomes in Taiwan: A nationwide population-based cohort study.

J Diabetes Complications 2020 11 23;34(11):107689. Epub 2020 Jul 23.

School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan. Electronic address:

Aims: This study compared the incidence rates of patients with diabetes mellitus (DM) and patients without DM with percutaneous coronary intervention (PCI) in a national population-based cohort to determine if the patients with DM have an increased risk of adverse outcomes.

Methods: We performed a retrospective cohort study among 92,624 patients with and without DM, who underwent PCI for the first time in 2000-2008. The patients were identified from National Health Insurance Program Database through propensity score matching. Endpoints were the occurrence of PCI adverse outcomes, including myocardial infarction (MI), need for target vessel revascularization by either bypass surgery or repeat PCI, all-cause mortality or 2011/12/31. Incidence rate was calculated and hazard ratios of PCI adverse events were estimated using Cox's proportional hazard regression model.

Results: During the mean six-year follow up, the rates of MI (incidence rate 20.96 vs. 15.59 per 1000 person-years), bypass surgery (incidence rate 8.15 vs. 5.15 per 1000 person-years), all-cause mortality (incidence rate 6.20 vs. 4.72 per 1000 person-years), and the composite measure of MI, repeat PCI, bypass surgery, all-cause mortality (incidence rate 37.31 vs. 28.14 per 1000 person-years) were higher in patients with DM. The corresponding hazard ratios (HRs) and their 95% confidence intervals (CIs) were 1.34 (95% CI: 1.29, 1.39), 1.46 (1.38, 1.56), 1.34 (1.25, 1.44), and 1.31 (1.27, 1.35). However, the repeat PCI rate (incidence rate 2.65 vs. 2.70 per 1000 person-years); with an adjusted HR of 0.97 (0.88, 1.07) was not statistically different.

Conclusions: This nationwide retrospective cohort study determined a positive correlation between PCI adverse events and DM. As the prevalence of DM and PCI continues to increase, novel treatments and intensified surveillance coronary angiography for high risk patients are needed.
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http://dx.doi.org/10.1016/j.jdiacomp.2020.107689DOI Listing
November 2020

Effects of concurrent aerobic and resistance exercise in frail and pre-frail older adults: A randomized trial of supervised versus home-based programs.

Medicine (Baltimore) 2020 Jul;99(29):e21187

School of Medicine, College of Medicine, China Medical University.

Background: This study aimed to investigate the effects of supervised and home-based exercise programs on older people with frailty or pre-frailty.

Methods: A total of 146 community-dwelling participants aged 65 and older who were prefrail or frail were randomly allocated into supervised exercise (N = 74) and home exercise (N = 72) groups. The 3-month supervised exercise training consisted of 3 exercise sessions per week, was performed at a hospital and supervised by a physical therapist. Home exercise participants took instructions on exercise and illustrated exercise handouts. The baseline and 3-month follow-up measurements included body composition, strength of selected upper and lower limb muscle groups, grip and leg press strengths, and five physical performance tests. Mixed-model repeated-measures analysis was applied to determine whether two groups differ in terms of changes before and after the intervention and to compare within-group improvements.

Results: After 3 months of supervised or home-based exercise, the average number of frailty criteria met and fat percentage decreased significantly. Strength of knee extensors, knee flexors and leg press improved significantly in supervised exercise group. In home-based exercise group, the strength of all muscle groups tested improved significantly, except for leg press strength. Walking speed improved in both groups, and timed-up-and-go and timed chair rise tests improved significantly only in supervised exercise group.

Conclusions: Three-month supervised or home-based exercise improved walking speed and strength of the limb muscles. Supervised group showed more improvements in the physical performance tests compared with home-based exercise group.
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http://dx.doi.org/10.1097/MD.0000000000021187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7373606PMC
July 2020

Subclinical Atherosclerosis Markers of Carotid Intima-Media Thickness, Carotid Plaques, Carotid Stenosis, and Mortality in Community-Dwelling Adults.

Int J Environ Res Public Health 2020 07 1;17(13). Epub 2020 Jul 1.

School of Medicine, College of Medicine, China Medical University, Taichung 404, Taiwan.

Carotid intima-media thickness (IMT), plaque, and stenosis are widely used as early surrogate markers of subclinical atherosclerosis and strong predictors of future deaths and cardiovascular events. Albuminuria is an indicator of generalized endothelial dysfunction that speeds up atherosclerosis. However, previous studies reporting these associations cannot rule out the confounding effect of albuminuria. We aimed to examine the independent and joint relationships between IMT markers and 10-year mortality in community-dwelling Taiwanese adults. This work was a community-based prospective cohort study consisting of 2956 adults aged at least 30 years recruited in 2007 and followed up through 2019. Cox proportional hazard regression models were used to examine associations of these subclinical atherosclerosis markers with mortality. During an average of 9.41 years of follow up, 242 deaths occurred. The mortality rate was 8.70 per 1000 person-years. Compared with those with carotid IMT less than 1.0 mm, persons with severely increased carotid IMT (≥2.0 mm) had an increased risk for death (hazard ratio (HR): 1.79; 95% confidence interval (CI): 1.07, 3.00). Compared with those without carotid plaque, persons with carotid plaque were more likely to have an increased risk for death (1.65; 1.21-2.32). Compared with those with carotid stenosis less than 25%, persons with carotid stenosis of 25-36% had a significant increased risk for death (1.57; 1.12-2.22). Considering these three IMT markers along with the traditional risk factors (c-statistic: 0.85) significantly increased their predictive ability of mortality compared with any individual variable's predictive ability (all -values < 0.001 for comparisons of c-statistic values). Carotid IMT measures, including IMT thickness, carotid plaque, and carotid stenosis were significant independent predictors of mortality. Our study supports evidence of blood pressure-related media thickening markers to assess future mortality risks in Chinese adults of general population.
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http://dx.doi.org/10.3390/ijerph17134745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369727PMC
July 2020

Dietary Macronutrient Intakes and Mortality among Patients with Type 2 Diabetes.

Nutrients 2020 Jun 3;12(6). Epub 2020 Jun 3.

Department of Public Health, College of Public Health, China Medical University, Taichung 404, Taiwan.

The best macronutrient percentages of dietary intake supporting longevity remains unclear. The strength of association between dietary intake and mortality in patients with type 2 diabetes (T2DM) should be quantified as a basis for dietary recommendations. Our study cohort consisted of 15,289 type 2 diabetic patients aged 30 years and older in Taiwan during 2001-2014 and was followed up through 2016. Percentages of macronutrient intakes were calculated as dietary energy intake contributed by carbohydrate, protein, and fat, divided by the total energy intake using a 24 h food diary recall approach. Cox proportional hazard models were applied to examine the temporal relation of macronutrient intakes with all-cause and cause-specific mortality. The average follow-up time was 7.4 years, during which 2,784 adults with T2DM died. After multivariable adjustment, people with fourth and fifth quintiles of total energy, second and third quintiles of carbohydrate, and fourth quintiles of protein intakes were likely to have lower risks of all-cause and expanded cardiovascular disease (CVD) mortality. People with fifth quintiles of total energy intake were likely to have decreased non-expanded CVD mortality. We found a significant interaction between gender and fat intake on all-cause and expanded CVD mortality. Fat intake was associated with all-cause, expanded and non-expanded CVD mortality among males with T2DM. Total energy, carbohydrate, and protein intakes were associated with lower risks of all-cause and expanded CVD mortality, with minimal risks observed at ≥1673 Kcal total energy, 43-52% carbohydrate intake, and 15-16% protein intake among people with T2DM.
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http://dx.doi.org/10.3390/nu12061665DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352168PMC
June 2020

Pathophysiological effects of intravenous phosphodiesterase type 4 inhibitor in addition to surfactant lavage in meconium-injured newborn piglet lungs.

Pediatr Pulmonol 2020 09 19;55(9):2272-2282. Epub 2020 Jun 19.

Department of Pediatrics, Children's Medical Center, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Nonsteroidal anti-inflammatory drugs, such as selective phosphodiesterase type 4 (PDE4) inhibitors have potential anti-inflammatory and respiratory smooth muscle relaxation effects. This study aimed to investigate the pathophysiological effects of an intravenous PDE4 inhibitor (rolipram) and surfactant lavage (SL) in a newborn piglet model of meconium aspiration syndrome (MAS).

Methods: MAS was induced in 25 newborn piglets, which were randomly divided into control and four SL treatment groups administered with different doses of intravenous rolipram (0, 0.1, 0.5, and 1 mg/kg). Cardiopulmonary variables were monitored and recorded. The experimental time was 4 hours. Serial blood was drawn for blood gas and biomarker analyses. Lung tissue was examined for histological analysis.

Results: All SL-treated groups revealed improved oxygenation during the 4-hour experiments and had significantly lower peak inspiratory pressure levels than the control group at the end of experiments. All SL plus rolipram-treated groups exhibited significantly higher lung compliance than the control group. However, the animals receiving high-dose (0.5 and 1.0 mg/kg) rolipram demonstrated significantly elevated heart rates. Lung histology of the nondependent sites revealed significantly lower lung injury scores in all SL-treated groups compared with that in the control group, but there were no differences among the rolipram-treated groups.

Conclusions: In addition to SL, intravenous PDE4 inhibitors may further improve lung compliance in treating MAS; however, it is necessary to consider cardiovascular adverse effects, primarily tachycardia. Further investigations are required before the clinical application of intravenous PDE4 inhibitor as an anti-inflammatory agent to treat severe MAS.
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September 2020
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