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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.

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.

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.

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.

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 (

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.

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.

Carotid intima&ndash, 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 (&ge, 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&ndash, 2.32). Compared with those with carotid stenosis less than 25%, persons with carotid stenosis of 25&ndash, 36% had a significant increased risk for death (1.57, 1.12&ndash, 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&rsquo, s predictive ability (all p-values &lt, 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.

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.

Additional file 1: Figure S1. Time points of the data collection for the Taichung Community Health Study (TCHS), Taichung Community Health Study-Elder (TCHS-E), and Family Study of TCHS and TCHS-E. Table S1. Multivariate analysis of carotid intima-media thickness for serum cystain C, albumin-to-creatinine ration, and estimated glomerular filtration rate along with traditional risk factors. Table S2. Multivariate analysis of carotid intima-media thickness for serum cystain C, albumin-to-creatinine ration, and serum creatinine along with traditional risk factors.

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 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&ndash, 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 &ge, 1673 Kcal total energy, 43&ndash, 52% carbohydrate intake, and 15&ndash, 16% protein intake among people with T2DM.

Plasma lipids in mid-life are important predictors for cardiovascular events and deaths. However, the association between plasma lipid concentrations and mortality in late life is controversial. Recent studies showed that older people with extremely low total cholesterol (TC) have poor survival outcome, but this conclusion was drawn mostly from Western cohorts. Our study investigated association between plasma lipid concentrations and mortality in Taiwanese elderly population.A retrospective cohort study was conducted among the 69,824 elderly people who participated in the Taipei City Geriatric Health Examination between 2006 and 2010, with a mean follow-up of 3.6 years. The measurements of TC, high density lipoprotein (HDL) and triglycerides were obtained from the records of the participants. Low density lipoprotein (LDL) was calculated using Friedewald formula in 69,088 participants. All lipid components were categorized into quartiles. Males and females were analyzed separately using multivariate Cox proportional hazards models.The elderly with the lowest quartile of TC (

Clustered multinomial responses are common in public health studies. In this situation, the baseline logit random effects model is usually suggested as a general modelling approach. When nonignorable missing outcomes exist, naïve methods such as complete case analysis or likelihood methods ignoring missing information may distort the conclusions that are drawn. While methods to deal with binary and ordinal outcomes have been proposed, no easily implementable method is specifically available for missing clustered nominal responses. Joint modelling is usually one of the available choices but has high complexity in terms of likelihood. The numerical integration of both missing data and random effects is challenging. In this study, we have derived a closed form of likelihood. A simplified likelihood is also proposed, which is an extension of a previous study. One advantage is that both methods are easily implemented with commonly used software. We illustrate our proposed methods using the Global Youth Tobacco Survey and compare the results obtained by naïve methods that ignore missing data with the results obtained using the proposed methods. Our approaches restore the parameter estimates and predicted probability of each category to an acceptable extent. Analysis guidelines for the use of our methods are provided.