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Background This study aimed to explore trends, in 3 periods, in the intake of energy and macronutrients among Taiwanese older adults. Methods Study subjects were those aged ≥65 years in the Nutrition and Health Survey in Taiwan 1999–2000 as well as the surveys in 2005–2008 and 2013–2016. Twenty-four-hour dietary recall data were obtained. This study used the 3 nutrition survey datasets for 1999–2000, 2005–2008, and 2013–2016, including data on the questionnaire, physical examination, and dietary intakes. Each nutrition survey involved the face-to-face household interview, and individual’s dietary intake of carbohydrate, fat, and protein (% of energy) was estimated. Subsequently, intake statuses of the three macronutrients were classified into below, meeting, and above intake categories. Results In the 2013–2016 survey, approximately 40% of the older adults had a low intake of energy. The prevalence of older adults with a meeting intake of carbohydrate, fat, and protein have increased from the 1999–2000 to 2013–2016 periods. The prevalence of people having a low intake of carbohydrate declined from the 1999–2000 period to the 2013–2016 period. The prevalence of high fat intake in 2013–2016 was approximately 5% higher than that in 1999–2000. In the 2013–2016 period, the prevalence of low intake of carbohydrate, fat, and protein were 25.9, 24.5, and 4.9%, respectively; moreover, the prevalence of high intake of the aforementioned macronutrients were 38.7, 36.2, and 17.6%, respectively. Conclusions Our study provides important evidence on the dietary patterns, as well as their changes over time among Taiwanese older adults. Such information would be useful for health policy makers about the burden of unbalanced diet and for nutrition educators on planning nutrition promotion interventions about well-balanced dietary for the older persons.

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.

Background Obesity and cognitive impairment prevalence increases as age increases. Recent growing evidence finds links between obesity and cognitive impairment in older adults. However, the association between the two is controversial. This study aims to identify obesity marker trajectory patterns, and to assess whether these patterns are associated with cognitive impairment and cognitive decline during a 10-year follow-up period among community-dwelling older adults. Methods A total of 626 older adults aged 65 and older were involved in the study, with at least two repeated measurements at baseline, one-year or 10-year follow-up. Cognitive function was measured through the Mini Mental State Examination. Obesity markers included body mass index, waist circumference, waist-to-hip (WHR), fat mass (FM), and abdominal fat (AF) measured by dual-energy X-ray absorptiometry. Multivariate logistic regression analyses were performed to estimate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of cognitive impairment and cognitive decline for obesity marker trajectory patterns. Results After a 10-year follow-up, 168 older adults with incident cognitive impairment and 156 with rapid cognitive decline were defined as the top 25th percentile of cognitive decline. Four distinct trajectory groups of obesity markers were identified. In multivariate logistic regression analyses, a low likelihood of cognitive impairment was observed in the consistently high-level group from FM trajectory (ORs = 0.41, 95% CI = 0.20–0.85); the high-level U-shaped group from WHR trajectory (0.43, 0.22–0.84); and the median-level flat inverse U-shaped, consistently high-level, and low-level flat U-shaped groups from AF trajectory (0.44, 0.26–0.77; 0.33, 0.18–0.61; 0.39, 0.18–0.82). In addition, a low likelihood of rapid decline was found in the low-level, slightly increasing trend group from WHR trajectory (0.43, 0.22–0.85). Conclusion FM and AF trajectories with consistent high levels and WHR trajectory with high level with U-shaped group are associated with low risks of incident cognitive impairment in older adults. Similarly, WHR trajectory with a low but slowly increasing trend is associated with a decreased risk of cognitive decline.

This study is to estimate the lifetime risks of hip fracture in Chinese patients with type 2 diabetes. The lifetime risks of hip fracture have not been reported across the age spectrum in male adults and female adults with type 2 diabetes. A retrospective cohort study was conducted on 25275 men and 27953 women with type 2 diabetes aged 30–100 years old and participated in the National Diabetes Case Management Program in 2002–2004 in Taiwan. Sociodemographic factors, biomarkers, and comorbidity at the baseline and hip fracture events were analyzed with Cox proportional hazards regression models with age as the time scale. Significant differences in the lifetime risks of hip fracture were observed between men and women with type 2 diabetes. The cumulative lifetime incidences (%) of hip fracture at 50, 60, 65, 70, 75, 80, and 85 years old for men were 0.11, 0.40, 0.84, 1.84, 3.82, 8.53, and 16.72, respectively. The corresponding lifetime incidences (%) for women at 50, 60, 65, 70, 75, 80, and 85 years old were 0.05, 0.50, 1.36, 3.89, 9.56, 21.19, and 35.45, respectively. With competing risks, the significant multivariate-adjusted hazard ratio of developing hip fracture included smoking, alcohol drinking, duration of diabetes, type of oral hypoglycemic drugs use (no medication, sulfonylurea only, thiazolidinediones (TZD) only or TZD plus others, other single or multiple oral agents, insulin use, insulin plus oral hypoglycemic drug use), loop diuretics use, use of corticosteroids, normal weight or underweight, hyperlipidemia, and chronic obstructive pulmonary disease. The gender differences in lifetime hip fracture risk were significant. Thiazolidinediones and insulin use are factors with the greater magnitude of strength of association among those significantly associated with hip fracture.

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

Few studies have explored the association of visit-to-visit variation in blood pressure (BP) and glycemic factors with cardiovascular disease (CVD) morbidity and mortality. This study aimed to examine the independent and joint effect of visit-to-visit BP and glycemic variation on CVD morbidity and mortality in persons with T2DM.The present study consisted of two retrospective cohort studies. The Taiwan Diabetes Study was based on a database of the National Diabetes Care Management Program (DCMP) and linked with cardiovascular morbidity incidence. The Taichung Diabetes Study was based on the DCMP database of a medical center, which can be linked with the National Death Registry dataset. The outcomes were analyzed by using Cox's proportional hazard models.A total of 13,280 and 10,894 persons with T2DM in Taiwan and Taichung Diabetes Study, respectively, were included. SBP-CV, FPG-CV, and HbA1c-CV were significant predictors of stroke, CVD event or death, all-cause mortality, and expanded CVD mortality, whereas DBP-CV was a significant predictor of all-cause mortality and expanded and non-expanded CVD mortality. The joint effect of SBP, FPG, and HbA1c predicted the incidence of stroke and CVD event or death with increased risks of 16 %-35 %. In addition, the joint effect of SBP, DBP, FPG, and HbA1c was associated with all-cause and expanded CVD mortality with increased risks of 29 %-81 %.The joint effect of BP and glucose variation improved the prediction of cardiovascular morbidity and mortality. Moreover, simultaneous measurement of visit-to-visit BP and glycemic variation may stratify persons with cardiovascular risks and may be regarded as important therapeutic goals in the care of T2DM.

Diabetic nephropathy (DN) is a major healthcare challenge. We developed and internally and externally validated a risk prediction model of DN by integrating clinical factors and SNPs from genes of multiple CKD-related pathways in the Han Chinese population.A total of 1526 patients with type 2 diabetes were randomly allocated into derivation (n = 1019) or validation (n = 507) sets. External validation was performed with 3899 participants from the Taiwan Biobank. We selected 66 SNPs identified from literature review for building our weighted genetic risk score (wGRS). The steps for prediction model development integrating clinical and genetic information were based on the Framingham Heart Study.The AUROC (95% CI) for this DN prediction model with combined clinical factors and wGRS was 0.81 (0.78, 0.84) in the derivation set. Furthermore, by directly using the information of these 66 SNPs, our final prediction model had AUROC values of 0.85 (0.82, 0.87), 0.89 (0.86, 0.91), and 0.77 (0.74, 0.80) in the derivation, internal validation, and external validation sets, respectively. Under the combined model, the results with a cutoff point of 30% showed 70.91% sensitivity, 67.84% specificity, 51.54% positive predictive value, and 82.86% negative predictive value.We developed and internally and externally validated a model with clinical factors and SNPs from genes of multiple CKD-related pathways to predict DN in Taiwan. This model can be used in clinical risk management practice as a screening tool to identify persons who are genetically predisposed to DN for early intervention and prevention.

Hepatocellular carcinoma (HCC) is one of the most frequent and life-threatening human cancers worldwide. Despite curative resection surgery, the high recurrence rate of HCC leads to poor patient survival. Chronic hepatitis B virus (HBV) infection is a major etiological factor for HCC. HBV pre-S2 gene deletion mutation leads to the expression of an important oncoprotein called a pre-S2 mutant. It represents an independent prognostic biomarker for HCC recurrence. This study aimed to identify other independent prognostic biomarkers from clinicopathological characteristics of 75 HBV-related HCC patients receiving resection surgery and to validate their potential to be combined with pre-S2 gene deletion mutation as a combination biomarker for HCC recurrence. Patients with both the presence of pre-S2 gene deletion mutation and tumor-node-metastasis (TNM) stage IIIA–IIIC had a higher HCC recurrence risk than patients with either one or none of these two factors. Moreover, the combination of pre-S2 gene deletion mutation and TNM stage exhibited better performance than either of these two factors alone in discriminating patients from patients without HCC recurrence. Collectively, this study proposed that the TNM stage held significance as a combination biomarker with pre-S2 gene deletion mutation with a greater performance in predicting HCC recurrence after curative surgical resection.

IntroductionObservational studies support the relationship between C-reactive protein (CRP) level and diabetic nephropathy (DN) in patients with diabetes. The research question regarding whether the relationship between serum high-sensitivity C-reactive protein (hsCRP) level and DN is causal lacks experimental evidence. Therefore, this study aimed to evaluate the causality between hsCRP and DN based on Mendelian randomization (MR) analysis.Research design and methodsA total of 2332 participants with type 2 diabetes from the Taiwan Biobank database was analyzed. Genetic risk scores (GRSs), which comprise four validated CRP loci as two instrumental variables, were calculated as unweighted and weighted scores to evaluate the causal relationship of hsCRP with DN risk. The two-stage regression model was used to estimate OR and 95% CI.ResultsThe analyses of the observational study showed that the hsCRP level was significantly associated with DN after multivariate adjustment (adjusted OR 1.15; 95% CI 1.01 to 1.32). Unweighted/weighted GRSs for log-transformed hsCRP satisfied MR assumptions 1 and 3, respectively; that is, a significant association with hsCRP was observed but that with DN was absent (adjusted OR 1.00, 95% CI 0.92 to 1.09; 1.00, 0.72 to 1.39, respectively). The MR analyses demonstrated that a 1-unit increase in the log-transformed genetically predicted hsCRP by unweighted and weighted GRSs was associated with DN, demonstrating ORs of 1.80 (95% CI 1.51 to 2.14) and 1.67 (95% CI 1.40 to 1.98), respectively.ConclusionsThe current study provided experimental evidence that hsCRP level was causally related to DN. These findings suggest that the elevated hsCRP may be a causal risk factor for DN in patients with type 2 diabetes.

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.

Background. Traditional Chinese medicine (TCM) for the treatment of female infertility remains ambiguous. The aim of the present case-control study was to examine the association between TCM treatment and successful pregnancy among infertile women. Methods. This population-based case-control study included the data from 2,627 infertile women with successful pregnancy and 2,627 infertile women without successful pregnancy using datasets from the Longitudinal Health Insurance Database 2000 of the National Health Insurance Research Database during 2000–2010. The odds ratios (ORs) and 95% confidence intervals (CIs) for the relationship between TCM use and successful pregnancy in infertility women were estimated using logistic regression. Results. Patients who received TCM treatment significantly increased in successful pregnancy (OR = 1.48; 95% CI = 1.31–1.66), compared with patients without TCM. Si-Wu-Tang (OR = 4.25; 95% CI = 2.18, 8.30), Gui-Zhi-Fu-Ling-Wan (OR = 3.27; 95% CI = 2.13, 5.02), and Jia-Wei-Xiao-Yao-San (OR = 3.17; 95% CI = 2.35, 4.28) were the TCM agents that were most strongly associated with successful pregnancy among infertile women. Conclusions. Our study findings indicate that TCM is associated with higher likelihood of successful pregnancy in infertile women, which is worthy of further investigation by randomized control trial.

Purpose Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC), a leading cause of cancer-related death worldwide. The HCC patients who harbor HBV pre-S2 mutant, an oncoprotein that plays key roles in HCC development, have been closely associated with a worse prognosis after curative surgical resection, suggesting an urgent need for alternative therapeutic options to improve their survival. In this study, we aimed to evaluate the expression profiles of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1), two of the most well-studied immune checkpoint molecules that promote tumor immune evasion, in tumor of the pre-S2 mutant-positive/high HCC patients. Methods We classified 40 HBV-related HCC patients into the pre-S2-positive/high and -negative/low groups by a next-generation sequencing-based approach. The fluorescent immunohistochemistry staining was performed to detect the expression of PD-1 and PD-L1 in HCC tissues of patients. Results We showed that patients with either deletion spanning pre-S2 gene segment or high percentage of pre-S2 plus pre-S1+pre-S2 deletion (the pre-S2 mutant-positive/high group) exhibited a significantly higher density of PD-L1-positive cells in HCC tissues than those without. Moreover, the percentage of pre-S2 plus pre-S1+pre-S2 deletion displayed a high positive correlation with the density of PD-L1-positive cells in HCC tissues. Conclusion The increased expression of PD-L1 in tumor tissues of the pre-S2 mutant-positive HCC patients suggest that pre-S2 mutant may play a potential role in dysregulation of tumor immune microenvironment in the progression of HBV-related HCC, implicating for the development of future therapeutic strategies.

Mycobacterium abscessus infections are notoriously difficult to be treated and newer treatment options are required. Coptis chinensis (C. chinensis) and its main compound berberine are frequently used to treat bacterial and viral infections. In this study, the susceptibility of M. abscessus to C. chinensis extract and berberine was assessed by minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) evaluation. The effects of C. chinensis and berberine on biofilm formation and antibiotic susceptibility in M. abscessus were observed. C. chinensis at concentrations of MIC (1.5 mg/mL) and 2 × MIC (3.0 mg/mL) and berberine at ½ × MIC (0.125 mg/mL) demonstrated a strong inhibition of biofilm formation. Concentration of C. chinensis at ½ × MIC resulted in a significant reduction in MICs of trimethoprim/sulfamethoxazole (TMP/SXT), clarithromycin (CLA), and linezolid (LZD). Similarly, ½ × MIC berberine had a significant effect on the MIC reductions of nine antibiotics including TMP/SXT, CLA, and LZD. Notably, the resistance level MIC of LZD against M. abscessus was reversed to a susceptible level by treatment with either C. chinensis or berberine. Therefore, C. chinensis and berberine have the potential to produce a synergistic antimycobacterial effect, reduce biofilm formation, and decrease antibacterial resistance to LZD in M. abscessus.

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 2 [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.

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 m2) and ACR data greater than or equal to 30 (mg/g); and eGFR data less than 45 (ml/min/1.73 m2). 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.

Aim Diabetes is a primary cause of hospitalization and in-hospital mortality. However, studies exploring the relationships between body mass index (BMI) and hospitalization-related and mortality-related outcomes in patients with type 2 diabetes are lacking. Methods Our data were obtained from two independent retrospective cohort studies, namely, the Taiwan Diabetes Study (Taiwan DS), providing hospitalization outcome measures, and the Taichung Diabetes Study (Taichung DS) that can be linked with the National Death Registry dataset. BMI and hospitalization, in-hospital mortality, and all-cause and cause-specific death events were analyzed by Cox proportional hazard regression model. Results A total of 3,541, 38,779, and 10,399 patients died during hospitalization, hospitalized for all-cause and diabetes-related events, respectively, in the Taiwan DS cohort. Moreover, 685 deaths were identified in the Taichung DS cohort. Compared with patients with increasing-but-acceptable-risk obesity, multivariable-adjusted hazard ratios (HRs) of in-hospital mortality, all-cause hospitalization, hospitalization due to diabetes, hypoglycaemia, and renal failure for patients who were underweight were 2.09 (95% confidence interval 1.73, 2.51), 1.39 (1.28, 1.50), 1.69 (1.49, 1.90), 1.87 (1.34, 2.61), and 1.55 (1.26, 1.91). Adjusted HRs of all-cause mortality and non-expanded CVD-related mortality in patients with underweight were 2.02 (1.28, 3.21), and 2.27 (1.28, 4.03). Conclusions The BMI associated with the best survival and less hospitalization was the higher-high-risk obesity (≥ 27.5 kg/m2) category. We observed obesity paradox for mortality outcomes, which should be addressed by further research, particularly on whether randomized controlled trials of adopting a healthy lifestyle for patients with obesity can improve type 2 diabetes patients’ survival.

Elevated glucose level is one of the risk factors for lower extremity amputation (LEA), but whether glycaemic variability confers independent risks of LEA remains to be elucidated. This study aimed to investigate the association between visit-to-visit glycaemic variability and minor and major LEA risks during 8 years of follow-up in type 2 diabetic individuals aged 50 years and older. This retrospective cohort study included 27,574 ethnic Chinese type 2 diabetic individuals aged ≥50 years from the National Diabetes Care Management Program in Taiwan. Glycaemic variability measures were presented as the CVs of fasting plasma glucose (FPG-CV) and of HbA1c (A1c-CV). The effect of glycaemic variability on the incidence of LEA events was analysed using Cox proportional hazards models. After a median follow-up of 8.9 years, 541 incident cases of LEA with a crude incidence density rate of 2.4 per 1000 person-years were observed. After multivariate adjustment, FPG-CV and A1c-CV were found to be significantly associated with minor LEA, with corresponding HRs of 1.53 (95% CI 1.15, 2.04) and 1.34 (95% CI 1.02, 1.77) for the third tertiles of FPG-CV and A1c-CV, respectively. In addition, these associations were stronger amongst older adults with longer diabetes duration (≥3 years) than amongst those with shorter duration (

BackgroundDyslipidemia 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.MethodsWe 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.ResultsOver 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.ConclusionsBlood lipid variability except for triglyceride variability was associated with all-cause and cardiovascular mortality in patients with type 2 diabetes.

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 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.

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. 2 vs. ≥ 90 mL/min/1.73 m2), 1.55 (1.25–1.92) for UACR (≥ 30 mg/g vs. 2 vs. ≥ 90 mL/min/1.73 m2), 2.13 (1.52–2.99) for UACR (≥ 25 mg/g vs.

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.

Aim To explore the effectiveness of a clinical reasoning teaching workshop (CRTW) in preceptors' teaching ability, self-efficacy of clinical reasoning teaching. Background Preceptors' teaching skills are crucial for training novice nurses. How to enhance preceptors' teaching ability is a pertinent concern in clinical practice. Methods This study comprised two stages. At stage I, we administered a pre- to post-test single group with 33 participants to investigate the changes in preceptors' knowledge and self-efficacy in clinical reasoning teaching after clinical reasoning teaching workshop. At stage II, a quasi-experimental design was adopted to assess the effectiveness of the clinical reasoning teaching workshop by comparing the preceptors' teaching ability by novice nurses. There were 22 nurses' preceptors who underwent the clinical reasoning teaching workshop and 70 nurses with preceptors who did not undergo clinical reasoning teaching workshop and matched with preceptors' age and working experience. Results After clinical reasoning teaching workshop, preceptors' knowledge and self-efficacy of clinical reasoning teaching ware increased significantly. Novice nurses (study group) scored their preceptors' teaching ability significantly higher than nurses' (control group). Conclusion The clinical reasoning teaching workshop can enhance preceptors' teaching ability and confidence, thereby improving their teaching ability. Implications for nursing management A well-designed workshop with appropriated teaching method can allow preceptors to learn effectiveness. Clinical reasoning teaching workshop can be used in the training of preceptors.

We investigated the association between blood pressure variability measured by the coefficient of variation (CV) of blood pressure and hip fracture in older persons with diabetes. After excluding patients with acute complications and comorbidities, a positive association with similar magnitude of strength was found between BP variability and hip fracture, compared with that in the original analysis. Hypertension is a risk factor of osteoporosis and hip fracture, but studies have yet to investigate whether blood pressure variability measured by the CV of blood pressure can predict hip fracture in older persons with diabetes. We conducted a retrospective cohort study on 21,160 patients who suffered from type 2 diabetes (age ≥ 50 years) and participated in the National Diabetes Care Management Program in Taiwan. The patients’ 1-year variability in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the baseline and subsequent hip fracture incidence for 8.2 years were analyzed. There were 937 recorded incident hip fractures. SBP-CV and DBP-CV were classified based on their tertiles. After multivariate adjustment was conducted, SBP-CV found to be a predictor of hip fracture, and its hazard ratio was 1.18 (95% CI 1.00–1.40) for the third tertile compared with the first tertile. Our study suggests SBP stability is a predictor for hip fracture incidence in older persons with type 2 diabetes.

The purposes of this study were to develop the Chinese-version betel quid dependence instrument (BQDI) and to test its reliability and validity. An item pool relevant to betel quid dependence was generated. A panel of three experts assessed content validity including content relevance, clarity, and domain coverage. A cross-sectional study was conducted, consisting of 113 participants from a construction site, betel quid stalls, and a teaching hospital in Taichung, Taiwan. Construct validity was assessed by hypothesizing a significant correlation between the BQDI score and number of pieces-years for betel quid chewing and betel quid biomarkers. The overall Cronbach's alpha coefficient was 0.94. Factor analysis indicated the BQDI consisted of a three-factor structure, including physical and psychological cravings, lack of resistance to betel quid, and maladaptive use. We observed significant associations of BQDI total and factor scores with arecaidine (adjusted odds ratio [OR] for medium total BQDI score: 12.87, 95% CI: 1.45–114.5; high total BQDI score: 28.9, 3.53–236.6) and N-methylnipecotate (medium total BQDI score: 6.18, 1.21–31.62; high total BQDI score: 13.10, 2.72–63.03, respectively). Our results provide preliminary good internal consistency and construct validation of the Chinese-version BQDI as a measure of betel quid dependence in community adults.

Background The incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP) has rapidly increased. This study aimed to assess the effect of Coptis chinensis and its compounds on the minimal inhibitory concentrations (MICs) of eight antibiotics against CRKP. Methods Cell cultures were used to investigate the effects of C. chinensis and its compounds on the MICs of eight antibiotics against CRKP. The MICs for antibiotics alone and antibiotics with C. chinensis or compounds were measured and compared. Furthermore, the effects of C. chinensis on cell membrane injury and intracellular adenosine triphosphate (ATP) CRKP concentration were also measured. The Mann–Whitney rank-sum test was used to analyze the differences between means. Results C. chinensis exhibits a notable MIC bacteriostatic effect at 5 mg/mL on CRKP. A significant MIC reduction against CRKP exists when C. chinensis was added to colistin and colistin-containing two-antibiotic combinations. Moreover, C. chinensis could damage cell membrane integrity and decrease intracellular ATP concentration in CRKP. Thus, C. chinensis exhibits antimicrobial activity superiority with colistin against CRKP. Furthermore, the effects of identified compounds in C. chinensis on the MICs of colistin, four-to eight-, two-to four-, and one-to two-fold reductions were found in ferulic acid, magnoflorine, and jatrorrhizine hydrochloride, respectively. Among these compounds, ferulic acid destroys membrane integrity and decreases intracellular ATP concentration. Conclusion C. chinensis and ferulic acid can potentiate the antimicrobial activity of colistin and may represent a promising component of combination therapy against CRKP infections in a clinical setting.

Hepatocellular carcinoma (HCC) is a frequent and deadly human cancer worldwide that is intimately associated with chronic hepatitis B virus (HBV) infection. Pre-S2 mutant is a HBV oncoprotein that plays important roles in HCC development and is linked to poor prognosis in HCC patients. However, the profiles of tumor-infiltrating lymphocytes in HCC tissues of pre-S2 mutant-positive patients remain unknown. In this study, we performed fluorescent immunohistochemistry staining to detect the infiltration of ‘anti-tumor’ cytotoxic T lymphocytes (CTLs) and ‘pro-tumor’ regulatory T cells (Tregs) in pre-S2 mutant-positive and -negative HCC patients. We showed that pre-S2 mutant-positive patients had a significantly higher infiltration of CD4+CD25+ cells and forkhead box P3 (Foxp3)-expressing cells but similar CTLs and lower granzyme B-expressing cells in HCC tissues compared with pre-S2 mutant-negative patients. Moreover, the percentage of pre-S2 plus pre-S1 + pre-S2 deletion (pre-S2 mutant) was positively correlated with the density of CD4+CD25+ cells and Foxp3-expressing cells but negatively with granzyme B-expressing cells in HCC tissues. Considering that increased intratumoral Tregs have been shown to promote tumor immune evasion, our data may provide new insights into the pathogenesis of HBV pre-S2 mutant-induced HCC and suggest that therapeutics targeting Tregs may be a promising strategy for treating pre-S2 mutant-positive high-risk patient population.

Additional file 1: Table A1. Medical utilization in 2 months at baseline, 1 year follow-up, and difference among the elderly with different change in frailty status after 1 year follow-up. Table A2. Change in frailty status and medical utilization via the multivariate logistic regression models after adjusting for baseline age, gender, cognitive impairment, regular exercise, smoking, drinking status and co-morbidity (hypertension and diabetes). Table A3. Independent effects of change in frailty status and the utilization of 2-month outpatient clinic on 9-years mortality via Cox proportional hazard model. Table A4. Combined effects of change in frailty status and the utilization of 2 months outpatient clinic on 9 years mortality via Cox proportional hazard model with additional adjustment for co-morbidity. Fig. A1. Sensitivity analysis for association between frailty status and the number of outpatient visits in 2 months. Negative binomial regression models with inverse probability weighting approach for controlling potential drop-out bias were adjusted for baseline age, gender, education, cognitive impairment, regular exercise, smoking and drinking status. Table A5. Sensitivity analysis of change in frailty status and medical utilization via the multivariate logistic regression models with inverse probability weighting approach for controlling potential drop-out bias. Table A6. Sensitivity analysis of combined effects of change in frailty status and utilization of 2-month outpatient clinic on 9-year mortality via the Cox proportional hazard models with inverse probability weighting approach for controlling potential drop-out bias.

Our study used data collected in Chung-Hsing Village in Taiwan in May 1998 to evaluate the distribution of triglycerides and the association between hypertriglyceridemia and its correlates in elderly people. All individuals aged 65 and over were recruited as study subjects. A total of 1093 persons, out of 1774 registered residents, were contacted in face-to-face interviews. The response rate was 61.6%. However, only 586 respondents had blood tests and completed questionnaires. Analysis in this study was based on these 586 subjects. To study the significant correlates of hypertriglyceridemia, t-tests, ANOVAs, chi-square analysis and multivariate logistic regression were used. Among the study population, 66.0% were men and 34.0% were women. The mean age was 73.1 ± 5.3 years. The mean triglyceride values were 1.65 ± 0.93 mmol/L in men and 2.02 ± 1.44 mmol/L in women (p < 0.01). The proportions of hypertriglyceridemia were 18.7% in men and 27.6% in women (p < 0.05). After controlling the other covariates, analysis by multivariate logistic regression showed that the factors significantly related to hypertriglyceridemia were high systolic pressure, abnormal glutamic pyruvic transaminase, hypercholesterolemia and hyperglycemia. Thus, these results support the hypothesis that it is important to examine the other cardiovascular risk factors if one cardiovascular risk factor is observed. The data also suggest one should determine the triglyceride level when abnormal glutamic pyruvic transaminase is identified in an elderly subject.

AIM To explore the relationships between nurses' quality of life, personal quality of life, intention to stay (ITS) and resign and factors related to resignation. DESIGN Prospective cohort design. METHODS The participants were recruited from three different levels of hospital in central Taiwan. The survey instruments were structured questionnaires including demographics, Professional Quality of Life Scale, Short Form Health Survey (SF-36) and the Scale of ITS. The survey data were collected from December 2017-August 2018. Data on nurses' resignation were collected from the hospital systems 3 months after the survey. Descriptive analysis and multiple logistic regression were used to analyse the factors predicting participants' resignation. RESULTS Five hundred and fifty-three participants were recruited. Forty-nine out of 553 participants resigned (8.9%). Higher scores in compassion satisfaction were related to a greater ITS (p

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.

Aims A model has yet to be developed for predicting mortality in relation to the effect of glycemic and blood pressure variabilities, which are important clinical predictors of the mortality of patients, especially those with diabetes. This study aimed to develop and validate risk score systems by examining the effects of glycemic and blood pressure variabilities on the all-cause and expanded cardiovascular-specific mortality of persons with type 2 diabetes. Materials and methods This retrospective cohort study consisted of 9,692 patients aged 30-85 years, diagnosed with type 2 diabetes, and enrolled in a managed care program of a medical center from 2002 to 2016. All the patients were randomly allocated into two groups, namely, training and validation sets (2:1 ratio), and followed up until death or August 2019. Cox's proportional hazard regression was performed to develop all-cause and expanded cardiovascular-specific mortality prediction models. The performance of the prediction model was assessed by using the area under the receiver operating characteristic curve (AUROC). Results Overall, 2,036 deaths were identified after a mean of 8.6 years of follow-up. The AUROC-measured prediction accuracies of 3-, 5-, 10-, and 15-year all-cause mortalities based on a model containing the identified traditional risk factors, biomarkers, and variabilities in fasting plasma glucose, HbA1c, and blood pressure in the validation set were 0.79 (0.76-0.83), 0.78 (0.76--0.81), 0.80 (0.78--0.82), and 0.80 (0.78--0.82), respectively. The corresponding values of the expanded cardiovascular-specific mortalities were 0.85 (0.80--0.90), 0.83 (0.79--0.86), 0.80 (0.77--0.83), and 0.79 (0.77--0.82), respectively. Conclusions Our prediction models considering glycemic and blood pressure variabilities had good prediction accuracy for the expanded cardiovascular-specific and all-cause mortalities of patients with type 2 diabetes. This article is protected by copyright. All rights reserved.

Background Cognitive impairment is accompanied with high rates of comorbid conditions, leading ultimately to death. Few studies examine the relation between cognitive transition and mortality, especially in Asian population. This study evaluated baseline cognition and cognitive transition in relation to all-cause mortality among community-dwelling older adults. Methods We conducted a community-based prospective cohort study among 921 participants of Taichung Community Health Study for Elders in 2009. Cognitive function was evaluated by the Mini-Mental State Examination. Cognitive impairment was considered if the total score is less than 27, 24, and 21 for a participant’s educational level of more than 6 years, equal or less than 6 years, and illiteracy, respectively. One-year transition in cognitive function was obtained among 517 individuals who were assessed in both 2009 and 2010. Mortality was followed up until 2016. Cox proportional hazards models were applied to estimate the adjusted hazard ratios of mortality for baseline cognitive impairment and one-year transition in cognitive status. Results After a follow-up of 6.62 years, 160 deaths were recorded. The multivariate adjusted hazard ratio (95% confidence interval) for baseline cognitive impairment was 2.08 (1.43, 3.01). Significantly increased mortality risk was observed for cognitively impaired–normal and impaired–impaired subgroups over 1 year as compared with those who remained normal [2.87 (1.25, 6.56) and 3.79 (1.64, 8.73), respectively]. The area under the receiver operating characteristic curves demonstrated that baseline cognition and one-year cognitive transition had no differential predictive ability for mortality. Besides, there was an interaction of cognitive impairment and frailty, with an additive mortality risk [5.41 (3.14, 9.35)] for the elders who presented with both. Conclusion Baseline cognitive impairment rather than one-year progression is associated with mortality in a six-year follow-up on older adults.

Aims To test the reliability and validity of the Chinese version of the Insulin Treatment Appraisal Scale (ITAS) questionnaire in patients with type 2 diabetes mellitus (T2DM). Methods A total of 200 patients with T2DM were consecutively recruited from the outpatient clinic in Taiwan. The World Health Organization guideline was followed to translate the questionnaire. The internal consistency was assessed by Cronbach’s α coefficient and item-total correlations. The construct validity was evaluated by using confirmatory factor analysis, convergent validity, and discriminate validity. Results The Cronbach’s α coefficient for estimates of internal consistency of the total scale was 0.72, and ranged from 0.76 to 0.77 for the subscales. A value of ≥0.40 was considered being substantial. The item-total correlation values were 14 out of 20 items having substantial correlations (4 out of 4 items on the positive appraisal scale and 10 out of 16 items on the negative appraisal scale). The confirmatory factor analysis confirmed both positive and negative factors with total explained variance 33.9% (12.2% for positive subscale and 21.7% for negative subscale). The success rate, calculated from the item-total correlation values, was 70% for the convergent validity (100% for positive subscale and 63% for negative subscale) and 90% for discriminate validity (100% for positive subscale and 88% for negative subscale), respectively. Both the ceiling effect and floor effect were 0%. Conclusions The Chinese version of the ITAS questionnaire is a valid and reliable instrument for measuring the perceptions of insulin injection in patients with T2DM.

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 1,000 person-years), bypass surgery (incidence rate 8.15 vs. 5.15 per 1,000 person-years), all-cause mortality (incidence rate 6.20 vs. 4.72 per 1,000 person-years), and the composite measure of MI, repeat PCI, bypass surgery, all-cause mortality (incidence rate 37.31 vs. 28.14 per 1,000 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 1,000 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.

Background This study investigated whether visit-to-visit fasting plasma glucose (FPG) variability, as measured by the coefficient of variation (CV), increased peripheral artery disease (PAD) risk. Methods Individuals with type 2 diabetes from the National Diabetes Care Management Program during the period 2002–2004, ≥ 30 years of age, and free of PAD (n = 30,932) were included and monitored until 2011. Cox proportional hazards regression models were implemented to analyze related determinants of PAD. Results A total of 894 incident cases of PAD were identified during an average 8.2 years of follow-up, resulting in a crude incidence rate of 3.53 per 1000 person-years. Both FPG-CV and HbA1c were significantly associated with PAD after multivariate adjustment, with corresponding hazard ratios of 1.24 [95% confidence interval (CI) 1.04–1.47] for FPG-CV in the third tertile and 1.50 (95% CI 1.10–2.04) for HbA1c ≥ 10%. The findings of the sensitivity analysis remained consistent after excluding potential confounders, demonstrating the consistency of the results. Conclusions The associations between HbA1c, variability in FPG-CV, and PAD suggest a linked pathophysiological mechanism, suggesting the crucial role of glycemic variability in clinical management and therapeutic goals in preventing PAD in type 2 diabetes.

Additional file 1: Figure S1. Flow chart of recruitment procedures for the study. Table S1. Hazard ratios (HRs) of peripheral vascular disease based on HbA1c and FPG-CV levels in persons with diabetes enrolled in the National Diabetes Care Management Program, Taiwan (n=30,932).

Aim This study aims to develop and validate a lower extremity amputation (LEA) risk score system in persons with type 2 diabetes. Methods A retrospective population-based cohort study was conducted among eligible 21,484 participants in the derivation set and 10,742 participants in the validation set who were enrolled in the Taiwan National Diabetes Care Management Program. The risk score system was developed following the steps proposed by the Framingham Heart Study with a Cox proportional hazards model algorithm. Discrimination ability was assessed by the receiver operating characteristic curve, and calibration was performed by Hosmer–Lemeshow test. Results A total of 504 patients developed LEA at an average follow-up of 7.4 years. The point scores were derived from 15 predictors as follows: age, gender, duration of type 2 diabetes, body mass index, HbA1c, triglyceride, eGFR, variation of fasting blood glucose, comorbidities of stroke, diabetes retinopathy, hypoglycemia and foot ulcer, anti-diabetes medication, and use of diuretics and nitrates. The c-statistics for predicting 3-, 5-, and 8-year LEA risks were 0.80 [95% confidence interval (CI) 0.76–0.83], 0.78 (0.75–0.81), and 0.76 (0.74–0.79) in the derivation set, respectively, and 0.81 (0.76–0.85), 0.77 (0.73–0.81), and 0.74 (0.71–0.77) in the validation set, respectively. Conclusions A new risk score for LEA was developed and validated in the clinical setting with good discriminatory ability. Poor glycemic control, glucose variation, comorbidities, and medication use were identified as predictive factors for LEA in patients with type 2 diabetes.

The α-eleostearic acid (α-ESA) in bitter melon seed oil (BMSO) is efficiently converted by the body into rumenic acid. The objective of this study was to investigate effects of BMSO on skeletal muscle fiber-type switch and endurance capacity in mice, with or without exercise training. In a 3×2 factorial design, C57BL/6J mice were fed a 30% high-fat diet composed of soybean oil, butter or a 1:1 mixture of BMSO and soybean oil, i.e., SB, BT and BM diets, respectively, and were allocated to be sedentary or undergo exercise (Ex). The Ex groups received a 15-min training regimen on a motorized treadmill 5 times a week. After 3-week intervention, endurance capacity was evaluated (total running time and distance until exhaustion). Mice fed a BM diet had significantly less body fat, with increased muscle percentage and improved endurance capacity. Combining sedentary and Ex groups, mice fed a BM diet ran 33% longer and 50% further than those fed SB, or 25% longer and 36% further than those fed BT (P

Objectives Diabetes is a major cause of hospitalization and in-hospital mortality. However, a scoring system that can be used to identify diabetic patients at risk of diabetes-related hospitalization and in-hospital mortality is lacking. Methods We included 32,653 patients in this retrospective cohort study. All recruited patients had type 2 diabetes, were 30–84 years of age, and were enrolled in the National Diabetes Care Management Program over the period of 2001–2003. We used the Cox proportional hazard regression model to derive risk scores. The predictive accuracy of the models was evaluated using receiver operating characteristic curves. We conducted the Hosmer–Lemeshow test to assess the agreement between predicted and observed risks. Results Over a follow-up period of eight years, 6243 patients were hospitalized for diabetes-related events, and 2048 deaths were registered in hospital records. For the one-, three-, five-, and eight-year periods, the areas under the curve (AUC) for diabetes-related hospitalization in the validation set were 0.80, 077, 0.76, and 0.74, respectively. The corresponding values for in-hospital mortality in the validation set were 0.87, 080, 0.77, and 0.76. The goodness-of-fit test showed that the predicted and observed probabilities in the one-, three-, five-, and eight-year periods were similar for diabetes-related hospitalization and in-hospital mortality in the validation set (all p values > 0.05). Conclusion We developed models for the estimation of the risks of diabetes-related hospitalization and in-hospital mortality in patients with type 2 diabetes. The models may be used to identify diabetic patients who are at high risk for hospital admission and in-hospital mortality.

Aims The study evaluated associations between 3-year eGFR trajectory patterns and adverse renal event in diabetic patients. Methods Adverse renal event was defined as sustained eGFR 300 mg/g creatinine. Cox proportional hazards models evaluated association between eGFR trajectory patterns and adverse renal event. Results We detected six clusters. Cluster 1 had a stable but relatively low baseline eGFR level (n = 823, 20.52%), cluster 2 had a high baseline eGFR level, but slightly decreased afterwards (n = 1708, 42.59%), cluster 3 had an increasing eGFR during the first 15-month follow-up and then a decline rate (n = 505, 12.59%), cluster 4 decreased during the first 9-month follow-up and then remained stable (n = 774, 19.30%), cluster 5 had a sharp decline and then was elevated after 21 months until the end of follow-up (n = 135, 3.37%), and cluster 6 had an extremely fluctuating eGFR and then a sharp increase at the last 12-month period (n = 65, 1.62%). Clusters 1, 3, and 4 show increased adverse renal risks compared with cluster 2 (2.24, 1.69–2.97; 2.70, 2.02–3.61; and 2.15, 1.64–2.83, respectively). Conclusions Patients with sustained low-level renal function, renal decline, or increasing trend in eGFR trajectory encountered an increased CKD risk.

Objective The purpose of this study was to investigate the effectiveness of preterm infant learning portfolios in enabling mothers to develop infant care knowledge and skills, as well as confidence in their abilities. Design This study used a quasi-experimental design. Setting and participants The sample consisted of 52 mothers with preterm infants recruited at a neonatal intermediate unit of a medical centre in central Taiwan. Among those, 26 participants in the control group received regular health education and 26 participants in the experimental group received learning portfolios and regular care. Intervention The Preterm Infant Care Learning Portfolio (PICLP) is a semi-structured learning portfolio which was provided by nurses. Intervention started with 15 min of instructions on how to use PICLP, including a list of learning task and methods of self-assessment. Follow-up sessions of 5–10 min were conducted after each learning task. The frequency of learning skills could be adjusted depending on participants' learning needs. Measurements Self-administered questionnaires regarding knowledge of and skills in preterm infant care and maternal confidence were used to evaluate the effectiveness of the intervention; the questionnaires were conducted before the intervention, 1 day before discharge and 1 month after discharge. We also tracked the frequency with which participants attended instructional sessions before discharged. Findings Mothers' preterm infant care knowledge and skills and confidence improved in both groups after the intervention. The experimental group showed greater improvement than the control group by post-test 2; there was no statistical difference between groups at 1 day before discharge and 1 month after discharge. However, participants in the experimental group came for instructional sessions on baby care for more frequently than the control group. The frequency of learning sessions attended was a predictor of improved scores of the skill assessment before discharge. Conclusions Both programmes led to improvements in preterm infant care knowledge and skills and maternal confidence. Giving mothers learning portfolios appears to stimulate significantly greater participation in hospital-based instructional programmes, which should in turn lead to greater long-term retention of learning. The learning portfolios may have an additional benefit in promoting acquisition of care abilities for mothers with preterm infant before hospital discharge and application of these abilities at home. Implication for practice At-home care for preterm infants requires specialized care skills and confidence. Learning portfolios can be used as an effective learner-centred strategy for teaching these health care abilities.

Background and purpose No study has established a prediction dementia model in the Asian populations. This study aimed to develop a prediction model for dementia in Chinese type 2 diabetes patients. Methods The retrospective cohort study included 27 540 Chinese type 2 diabetes patients (aged 50-94 years) enrolled in the Taiwan National Diabetes Care Management Program. Participants were randomly allocated into derivation and validation sets at a 2:1 ratio. Cox proportional hazards regression models were used to identify risk factors for dementia in the derivation set. Steps proposed by the Framingham Heart Study were used to establish a prediction model with a scoring system. Results The average follow-up was 8.09 years, with a total of 853 incident dementia cases in the derivation set. The dementia risk score summed up the individual scores (from 0 to 20). The areas under the curve of 3-, 5- and 10-year dementia risks were 0.82, 0.79 and 0.76 in the derivation set and 0.84, 0.80 and 0.75 in the validation set, respectively. Conclusions The proposed score system is the first dementia risk prediction model for Chinese type 2 diabetes patients in Taiwan.

Aims A risk scoring system for predicting ischemic stroke incidence may identify type 2 diabetes patients at high risk for ischemic stroke who can benefit from preventive intervention programs. Such a risk scoring system can serve as a benchmark to test novel putative risk factors. Methods The study adopted a retrospective cohort, including 28,124 Chinese patients with type 2 diabetes aged 30–84 years during 2001–2004. Participants were randomly assigned to the derivation and validation sets at a 2:1 ratio. Cox’s proportional hazard regression model was used to identify risk factors of ischemic stroke incidence in the derivation set. And then the steps proposed by the Framingham Heart Study for establishing an ischemic stroke prediction model with a scoring system was used. Results Among 9374 patients in the validation set, 1076 subjects (11.48%) developed ischemic stroke with a mean follow up period of 8.0 years. We identified the following risk factors: age, gender, smoking habit, duration of type 2 diabetes, blood pressure, HbA1c level, total cholesterol to high-density lipoprotein ratio, creatinine, fasting plasma glucose variation (FPG-CV), arterial embolism and thrombosis, diabetes retinopathy, hypoglycemia, anti-diabetes medication use, and cardiovascular medication. The area under receiver operating characteristic curve of the 3-year, 5-year, and 8-year ischemic stroke incidence risks were 0.72, 0.71, and 0.68 for the validation set, respectively. Conclusions This proposed ischemic stroke incidence risk prediction model is the first model established for Chinese patients with type 2 diabetes recruited from nationwide clinical settings.

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.

// Tsai-Chung Li 1, 2, * , Chia-Ing Li 3, 4, * , Chiu-Shong Liu 3, 4, 5 , Pao-Hsuan Lin 1 , Wen-Yuan Lin 3, 5 , Chih-Hsueh Lin 3, 5 , Sing-Yu Yang 1 , Jen-Huai Chiang 6 and Cheng-Chieh Lin 3, 4, 5 1 Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan 2 Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan 3 School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan 4 Department of Medical Research, China Medical University Hospital, Taichung, Taiwan 5 Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan 6 Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan * These authors equally contributed as first author Correspondence to: Cheng-Chieh Lin, email: cclin@mail.cmuh.org.tw Keywords: alanine transaminase, cohort study, hepatocellular carcinoma, type 2 diabetes Received: April 05, 2017 Accepted: September 20, 2017 Published: October 10, 2017 ABSTRACT Background: This study examined whether serum alanine transaminase (ALT) and chronic liver diseases were interactively, jointly, or independently associated with hepatocellular carcinoma (HCC) risk in type 2 diabetic patients. Materials and Methods: A retrospective cohort study was conducted in 46,369 Chinese type 2 diabetic patients, aged 30 and older, in National Diabetes Care Management Program in 2002-2004. These data were analyzed by multivariate Cox proportional hazards models. Results: Mean follow-up period was 8.20 years. Multivariate-adjusted hazard ratios of HCC were 2.85 (95% confidence interval, CI: 2.45–3.31), 3.80 (3.04–4.76), and 3.89 (3.08–4.91) for patients with a level of ALT 40–80, 80–120, and >120 U/L, respectively, compared with patients with a level of ALT < 40 U/L after multivariable adjustment. Significant hazard ratios of HCC for patients with a level of ALT ≥ 40 U/L and alcoholic liver damage, nonalcoholic fatty liver disease, liver cirrhosis, hepatitis B virus and hepatitis C virus infection, or any one of these chronic liver diseases compared with patients with ALT level < 40 U/L and no counterpart comorbidity were observed. Significant effect modifications were observed between ALT level with liver cirrhosis and HBV. Conclusions: Results suggest significant effect modification and joint associations of ALT ≥ 40 U/L and chronic liver diseases. Diabetes care should provide lifestyle or treatment interventions to manage ALT level, liver cirrhosis and hepatitis B virus infection for reducing burden of HCC.

OBJECTIVE The relationship between glycemic variability and the incidence of Alzheimer disease (AD) in patients with type 2 diabetes mellitus (T2DM) is unclear. The aim of this study was to examine visit-to-visit variations in fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) represented by the coefficient of variation (CV) and to determine whether they were independently associated with AD, irrespective of HbA1c and other traditional risk factors in such patients. RESEARCH DESIGN AND METHODS Patients with T2DM enrolled in the National Diabetes Care Management Program, age ≥60 years, and without diagnosis of AD (n = 16,706) were included in the study. Potential risk factors were analyzed using extended Cox proportional hazards regression models for competing risk of mortality on AD incidence. RESULTS During a median follow-up of 8.88 years, 831 incident cases of AD were identified, with a crude incidence rate of 3.5/1,000 person-years. After adjustment for sociodemographic factors, lifestyle behaviors, diabetes-related variables, FPG and HbA1c, drug-related variables, and comorbidities, both FPG CV and HbA1c CV were found to be significant predictors of AD, with corresponding hazard ratios of 1.27 (95% CI 1.06–1.52) for the third tertile in FPG CV and 1.32 (95% CI 1.11–1.58) for the third tertile in HbA1c CV. CONCLUSIONS FPG CV and HbA1c CV are independently associated with AD. The associations between glycemic variability and AD demonstrated in this study suggest a linked pathophysiological mechanism, which is worthy of further investigation. Further research is required to confirm our results and to evaluate whether FPG CV and HbA1c CV can be valuable therapeutic targets for patients with T2DM at risk.