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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.

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.

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.

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.

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.

// 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.

Aim Patients with diabetes have higher rates of depression than does the general population, but diabetes management mainly aims to maintain glucose stability. For this reason, our study assessed the relationship between 1-year variations in fasting plasma glucose (FPG) and risk of depression in Chinese patients with type 2 diabetes (T2D). Methods This retrospective cohort study was conducted on 32,829 patients aged ≥ 30 years who were diagnosed with T2D and who participated in the National Diabetes Case Management Program in Taiwan. Their 1-year FPG variation as a predictor was determined by coefficient of variation (CV), whereas depressive events were analyzed by Cox's proportional hazards models. Results During a mean 8.23 years of follow-up, 1041 new cases of depression were diagnosed. When patients were grouped based on quartiles of FPG-CV, incidence rates were 3.23, 3.49, 3.96 and 4.80 per 1000 person-years in the first, second, third and fourth quartile subgroups, respectively. After adjusting for traditional risk factors, baseline fasting glucose and HbA1c levels, and diabetes complications, FPG-CV was independently linked with incident depression. Hazard ratios of depression for FPG-CV in the fourth vs first quartile subgroups was 1.33 (95% CI: 1.11–1.59), respectively. Conclusion Patients whose 1-year FPG variations were > 42.6% had an increased risk of depression, thus suggesting that FPG variations may be a predictor of depression in patients with T2D. Also, glucose variation during outpatient visits may be an indicator for individualized diabetes management in clinical practice.

We investigated the association between fasting plasma glucose variability (FPG-CV) and the risk of hip fracture in elderly diabetic patients. Our finding showed a temporal association between FPG-CV and hip fracture as patients categorized as FPG-CV greater than 25.4 % showed an increased risk in hip fractures. Hip fracture is a major health burden in the population and is associated with high rates of mortality and morbidity especially in elderly. It is evident that diabetes mellitus is a risk factor of osteoporosis which is a significant risk factor of hip fracture. However, epidemiological studies exploring the risks of hip fracture among type 2 diabetic patients are limited. A retrospective study of 26,501 ethnic Chinese older persons enrolled in the National Diabetes Care Management program in Taiwan was conducted; related factors were analyzed with extended Cox proportional hazards regression models to competing risk data on hip fracture incidence. The results show a temporal association between FPG-CV and hip fracture as patients categorized as FPG-CV greater than 25.4 % showed an increased risk in hip fractures, confirming a linear relationship between the two. After multivariate adjustment, the risk of hip fracture increased among patients with FPG-CV of 25.4–42.3 % and >42.3 % compared with patients with FPG-CV of ≦ 14.3 % (hazard ratio, 1.35; 95 % confidence interval 1.14–1.60 and 1.27; 1.07–1.52, respectively). Significant linear trends among various FPG-CV were observed. Thus, the present study demonstrated the importance of glucose stability for fracture prevention in older persons with type 2 diabetes. Future studies should be conducted to explore whether reduction in glucose oscillation in older adults with diabetes mellitus can reduce the risk of hip fracture.

This study aims to develop a risk score system for hepatocellular carcinoma (HCC) in patients with type 2 diabetes using the Taiwan National Diabetes Care Management Program database. This retrospective cohort study included 31,723 Chinese patients who had type 2 diabetes, aged 30-84 years. Participants were randomly grouped into derivation and validation sets in 2:1 ratio. Cox proportional hazard regression models were used to identify the risk factors of HCC in the derivation set. Discrimination ability of the model was assessed by means of a receiver operating characteristic curve and performance was expressed as the c statistic, assessed internally on validation data sets. The average follow-up was 8.33 years with 748 HCC incident cases in the derivation set. The final HCC risk score system included age (-2 to 8 points), gender (0-2 points), smoking (0-2 points), variation in hemoglobin A1c (0-1 point), serum glutamic-pyruvic transaminase (0-6 points), liver cirrhosis (9 points), hepatitis B (4 points), hepatitis C (3 points), antidiabetes medications (0-3 points), and antihyperlipidemia medications and total/high-density lipoprotein cholesterol ratio (-4 to 2 points). The HCC risk score was the sum of these individual scores (range -6 to 40). The area under the receiver operating characteristic curve for 3-, 5-, and 10-year HCC risks was 0.81, 0.80, and 0.77 for the derivation set, respectively. This HCC risk score system has good prediction accuracy and discriminatory ability, and serves a simple tool for HCC risk prediction.

The relationship between glycemic control and adverse outcomes found in a population with diabetes has seldom been evaluated in patients with type 2 diabetes. We explored the association between hemoglobin A1c (HbA1c) and hospitalization risks within one-year and eight-year follow-up periods.We conducted a retrospective cohort study on 57,061 patients with type 2 diabetes from National Diabetes Case Management Program during 2002-2004 in Taiwan. HbA1c at baseline and in-hospital mortality, all-cause and cause-specific hospitalization over one year and eight years were analyzed.After multivariate adjustment, one-year risk was higher for cases with HbA1c level6%, 9-10%, ≥10% versus 6-7% for all-cause hospitalization (hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 1.03-1.20; 1.08, 1.01-1.16, and 1.19, 1.12-1.26, respectively) and for ≥10% for diabetes-related hospitalization (1.68, 1.46-1.92). Yet each 1-step increment in HbA1c category (6.0, 6.0-6.9, 7.0-7.9, 8.0-8.9, 9.0-9.9 and ≥10.0%) showed linkage with lower risk of hypoglycemia hospitalization (0.81, 95% CI: 0.74-0.88). For eight-year risk, subjects with HbA1c level6%, and ≥10% were more likely to have in-hospitality mortality (1.16, 1.03-1.31, and 1.23, 1.11-1.35, respectively). Each 1-step increment in HbA1c category showed an association with higher risks of all-cause and diabetes-related hospitalization (1.04, 1.03-1.05, and 1.15, 1.14-1.17, respectively).Higher HbA1c level correlated with lower one-year risk due to hypoglycemia hospitalization but increased one-year and eight-year risks due to all-cause and diabetes-specific hospitalization among Chinese people with type 2 diabetes in Taiwan. Future study must ascertain how to meet HbA1c targets and improve outcome without risk to this population.

Hip fracture, which is associated with substantial morbidity and long-term mortality, imposes a major burden on the healthcare system. Diabetes is a risk factor for osteoporosis, which is a crucial risk factor of hip fracture. However, epidemiological studies investigating the risk of hip fracture among patients with type 2 diabetes are limited. This study explored the association between hemoglobin A1c (HbA1c) and the risk of hip fracture in people with type 2 diabetes aged 65 years and older. We conducted a retrospective cohort study of 20 025 older patients with type 2 diabetes who participated in the National Diabetes Case Management Program in Taiwan. The HbA1c level at the baseline and hip fracture incidence over an average of 7.41 years of follow-up were analyzed (maximum and standard deviation were 10.9 and 2.42 years, respectively). A total of 1514 hip fracture cases were recorded. The incidence rates of hip fracture were 9.15, 8.02, 9.58, 10.61, 12.51, and 13.43 per 1000 person-years in patients with baseline HbA1c levels of < 6%, 6–7%, 7%–8%, 8%–9%, 9%–10%, and ≥ 10%, respectively. After multivariate adjustment, the risk of hip fracture increased among patients with HbA1c levels of 9%–10% and ≥ 10.0% compared with patients with HbA1c levels of 6–7% (hazard ratio, 1.24; 95% confidence interval, 1.02–1.49 and 1.32; 1.09–1.58, respectively). Significant linear trends among various HbA1c levels were observed (P

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 (HbAPatients with T2DM enrolled in the National Diabetes Care Management Program, age ≥60 years, and without diagnosis of AD (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 HbAFPG CV and HbA

Objective:To examine whether variations in fasting plasma glucose (FPG), as measured by the coefficient of variation (CV), is a predictor of diabetic polyneuropathy (DPN) risk, considering glycated hemoglobin (HbA1c) and other traditional risk factors.Methods:Type 2 diabetic patients enrolled in the National Diabetes Care Management Program were ≥30 years of age and free of DPN (n = 36,152). They were enrolled in 2002–2004 and were monitored until 2011. The related factors were analyzed using Cox proportional hazards regression models.Results:During an average 7.23 years of follow-up, a total of 7,219 incident cases of DPN were identified, with a crude incidence rate of 27.62/1,000 person-years (25.83 for men and 29.31 for women). After multivariate adjustment, both FPG-CV and HbA1c were significant predictors of DPN, with corresponding hazard ratios of 1.14 (95% confidence interval [CI] 1.05–1.23) and 1.15 (95% CI 1.06–1.24) for FPG-CV in the fourth to fifth quintiles and 1.13 (95% CI 1.07–1.20) for HbA1c ≥7%. This finding maintained consistency after excluding potential confounders in the sensitivity analysis, further validating the results.Conclusions:FPG-CV and HbA1c ≥7% were potent predictors of DPN in type 2 diabetic patients. The associations among HbA1c, glycemic variability, and DPN suggest a linked pathophysiologic mechanism, which may play a crucial role in clinical risk assessments.

OBJECTIVE To examine whether combined lifestyle behaviors have an impact on all-cause and cause-specific mortality in patients aged 30–94 years with type 2 diabetes (T2DM). RESEARCH DESIGN AND METHODS Participants included 5,686 patients >30 years old with T2DM who were enrolled in a Diabetes Care Management Program at a medical center in central Taiwan before 2007. Lifestyle behaviors consisted of smoking, alcohol drinking, physical inactivity, and carbohydrate intake. The main outcomes were all-cause and cause-specific mortality. Cox proportional hazards models were used to examine the association between combined lifestyle behaviors and mortality. RESULTS The mortality rate among men was 24.10 per 1,000 person-years, and that among women was 17.25 per 1,000 person-years. After adjusting for the traditional risk factors, we found that combined lifestyle behavior was independently associated with all-cause mortality and mortality due to diabetes, cardiovascular disease, and cancer. Patients with three or more points were at a 3.50-fold greater risk of all-cause mortality (95% CI 2.06–5.96) and a 4.94-fold (1.62–15.06), 4.24-fold (1.20–14.95), and 1.31-fold (0.39–4.41) greater risk of diabetes-specific, CVD-specific, and cancer-specific mortality, respectively, compared with patients with zero points. Among these associations, the combined lifestyle behavior was not significantly associated with cancer mortality. CONCLUSIONS Combined lifestyle behavior is a strong predictor of all-cause and cause-specific mortality in patients with T2DM.

Background The aim of this study was to determine the annual trends of traditional Chinese medicine (TCM) use for prevalent and incident asthmatic adults in Taiwan from 2000 to 2011. The annual prevalence and incidence of asthma in adults among subgroups of sociodemographic factors were also investigated. Methods A population-based study was conducted using a random sample with one million beneficiaries of all residents aged ≥18 years enrolled in the National Health Insurance program. Adults diagnosed with asthma were identified from the National Health Insurance Research Database. The annual prevalence and incidence of asthma in the adult population were estimated by using International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic codes to identify relevant cases from 2000 to 2011. Results The number of annual prevalent cases of diagnosed asthma increased from 56,885 in 2000 to 101,535 in 2011. The prevalence increased significantly on annual basis, whereas the incidence rate fluctuated over time. The prevalence of TCM use by adults with asthma decreased significantly (p

Background Glycemic variation as an independent predictor of ischemic stroke in type 2 diabetic patients remains unclear. This study examined visit-to-visit variations in fasting plasma glucose (FPG), as represented by the coefficient of variation (CV), for predicting ischemic stroke independently, regardless of glycated hemoglobin (HbA1c) and other conventional risk factors in such patients. Methods Type 2 diabetic patients enrolled in the National Diabetes Care Management Program, ≥30 years old and free of ischemic stroke (n = 28,354) in 2002 to 2004 were included, and related factors were analyzed with extended Cox proportional hazards regression models of competing risk data on stroke incidence. Results After an average 7.5 years of follow-up, there were 2,250 incident cases of ischemic stroke, giving a crude incidence rate of 10.56/1,000 person-years (11.64 for men, 9.63 for women). After multivariate adjustment, hazard ratios for the second, third and fourth versus first FPG-CV quartile were 1.11 (0.98, 1.25), 1.22 (1.08, 1.38) and 1.27 (1.12, 1.43), respectively, without considering HbA1c, and 1.09 (0.96, 1.23), 1.16 (1.03, 1.31) and 1.17 (1.03, 1.32), respectively, after considering HbA1c. Conclusions Besides HbA1c, FPG-CV was a potent predictor of ischemic stroke in type 2 diabetic patients, suggesting that different therapeutic strategies now in use be rated for their potential to (1) minimize glucose fluctuations and (2) reduce HbA1c level in type 2 diabetic patients to prevent ischemic stroke.

Hip fracture, which is associated with substantial morbidity and long-term mortality, imposes a major burden on the healthcare system. Diabetes is a risk factor for osteoporosis, which is a crucial risk factor of hip fracture. However, epidemiological studies investigating the risk of hip fracture among patients with type 2 diabetes are limited. This study explored the association between hemoglobin A1c (HbA1c) and the risk of hip fracture in people with type 2 diabetes aged 65 years and older. We conducted a retrospective cohort study of 20,025 older patients with type 2 diabetes who participated in the National Diabetes Case Management Program in Taiwan. The HbA1c level at the baseline and hip fracture incidence over an average of 7.41 years of follow-up were analyzed (maximum and standard deviation were 10.9 and 2.42 years, respectively). A total of 1514 hip fracture cases were recorded. The incidence rates of hip fracture were 9.15, 8.02, 9.58, 10.61, 12.51, and 13.43 per 1000 person-years in patients with baseline HbA1c levels of6%, 6-7%, 7%-8%, 8%-9%, 9%-10%, and ≥ 10%, respectively. After multivariate adjustment, the risk of hip fracture increased among patients with HbA1c levels of 9%-10% and ≥ 10.0% compared with patients with HbA1c levels of 6-7% (hazard ratio, 1.24; 95% confidence interval, 1.02-1.49 and 1.32; 1.09-1.58, respectively). Significant linear trends among various HbA1c levels were observed (P 0.05). Patients with type 2 diabetes whose HbA1c levels exceeded 9.0% exhibited an increased risk of hip fracture, confirming a linear relationship. Our study's findings demonstrated the importance of glycemic control for fracture prevention in older adults with type 2 diabetes.

Background This study examined whether annual variation in glycosylated hemoglobin A 1c (HbA 1c ) and fasting plasma glucose (FPG), as represented by the coefficient of variation (CV), can predict diabetic nephropathy independently of mean FPG, mean HbA 1c , and other risk factors in patients with type 2 diabetes. Methods A computerized database of patients with type 2 diabetes aged ≥30 years and free of diabetic nephropathy (n = 3220) who were enrolled in the Diabetes Care Management Program of China Medical University Hospital before 2007 was used in a time-dependent Cox proportional hazards regression model. Results The incidence rates of diabetic nephropathy were 16.11, 22.95, and 28.86 per 1000 person-years in the first, second, and third tertiles of baseline HbA 1c -CV, respectively; the corresponding incidence rates for FPG-CV were 9.46, 21.23, and 37.51 per 1000 person-years, respectively. After multivariate adjustment, the corresponding hazard ratios for the second and third tertiles versus the first tertile of annual HbA 1c -CV were 1.18 (95% confidence interval [CI], 0.88-1.58) and 1.58 (95% CI, 1.19-2.11), respectively, and 1.55 (95% CI, 0.99-2.41) and 4.75 (95% CI, 3.22-7.01) for FPG-CV, respectively. The risks of diabetic nephropathy for HbA 1c -CV and FPG-CV stratified according to age, gender, renal function, and hypertension status were provided. Conclusions Annual FPG and HbA 1c variations have a strong association with diabetic nephropathy in patients with type 2 diabetes. Whether intervention for reducing glucose variation should be administered needs to be examined in a future study.

Background Patients with non-small cell lung cancer (NSCLC) have a poor prognosis. The objective of this study was to examine the relationship of EORTC QLQ-C30 and QLQ-LC13 and survival in patients with NSCLC undergoing different treatments. Methods Investigators conducted a health-related quality of life (HRQOL) survey of 488 patients with NSCLC: 162 patients undergoing surgery, 312 patients without surgery, and their survival status was prospectively followed up. EORTC QLQ-C30 and QLQ-LC13 scores and clinical variables at baseline were analyzed using Cox’s proportional hazard regression to identify factors that influenced survival. Results Median survival of these 474 patients was 9.82 months. After adjustment, emotional functioning scale, and symptom scales of pain and nausea/vomiting are associated with survival in NSCLC patients with surgery whereas social functioning scale, and symptom scales for fatigue, appetite loss, and financial problems had a significant impact on survival in NSCLC patients without surgery. The results of multivariate analysis showed that none of QLQ-LC13 scales are significant predictors of survival. After simultaneously considering these scales, we found significant independent predictors of survival were nausea/vomiting (HR = 0.11, 95% CI = 0.02-0.63 for score >0 compared with =0) in NSCLC patients with surgery and appetite loss (HR = 1.77, 95% CI = 1.26-2.49 for score >0 compared with =0) in NSCLC patients without surgery. Conclusions HRQOL provides additional predictive information that supplements traditional clinical factors, and is a new prognostic indicator for survival of NSCLC patients under different treatments.

Background Estimated glomerular filtration rate (eGFR) is a powerful predictor of mortality in diabetic patients with limited proteinuria data. In this study, we tested whether concomitant proteinuria increases the risk of mortality among patients with type 2 diabetes. Methods Participants included 6523 patients > 30 years with type 2 diabetes who were enrolled in a management program of a medical center before 2007. Renal function was assessed by eGFR according to the Modification of Diet in Renal Disease Study equation for Chinese. Proteinuria was assessed by urine dipstick. Results A total of 573 patients (8.8%) died over a median follow-up time of 4.91 years (ranging from 0.01 year to 6.42 years). The adjusted expanded cardiovascular disease (CVD)-related mortality rates among patients with proteinuria were more than three folds higher for those with an eGFR of 60 mL/min/1.73 m2 or less compared with those with an eGFR of 90 mL/min/1.73 m2 or greater [hazard ratio, HR, 3.15 (95% confidence interval, CI, 2.0–5.1)]. The magnitude of adjusted HR was smaller in patients without proteinuria [1.98 (95% CI, 1.1–3.7)]. An eGFR of 60 mL/min/1.73 m2 to 89 mL/min/1.73 m2 significantly affected all-cause mortality and mortality from expanded CVD-related causes only in patients with proteinuria. Similarly, proteinuria affected all outcomes only in patients with an eGFR of 2. Conclusion The risks of all-cause mortality, as well as expanded and non-expanded mortality from CVD-related causes associated with proteinuria or an eGFR of 90 mL/min/1.73 m2 or greater are independently increased. Therefore, the use of proteinuria measurements with eGFR increases the precision of risk stratification for mortality.

The study aims to examine whether the annual variations in fasting plasma glucose (FPG) measurements, represented by the coefficient of variation (CV), predict cancer incidence and mortality in the subsequent years independent of traditional risk factors of type 2 diabetic patients. A computerized database of patients with type 2 diabetes of 30 years old and older (n=4805) enrolled in the Diabetes Care Management Program of a medical center before 2006 was analyzed using a time-dependent Cox's proportional hazards regression model. The mortality rates for the first, second, and third tertiles of the first annual FPG-CV were 8.64, 12.71, and 30.82 per 1000 person-years respectively. After adjusting for mean FPG, HbA1c, and other risk factors, the annual FPG-CV was independently associated with cancer incidence, cancer mortality, and cancer incidence or mortality, and the corresponding hazard ratios for the third vs first tertile of the annual FPG-CV were 3.03 (1.98, 4.65), 5.04 (2.32, 10.94), and 2.86 (1.91, 4.29) respectively. The annual variation in FPG was a strong predictor of cancer incidence and mortality in type 2 diabetic patients; therefore, glucose variation may be important in the clinical practice of care management and cancer prevention.

The purpose of this study was to examine the association of glucose variability using coefficient of variation of fasting plasma glucose (FPG-CV) and coefficient of variation of glycated hemoglobin (HbA1c-CV) to end-stage renal disease (ESRD) in 31,841 Chinese patients with type 2 diabetes. Patients with type 2 diabetes enrolled in National Diabetes Care Management Program, aged ≧30 years, and free of ESRD (n = 31,841) in January 1, 2002 to December 31, 2004 were included. Extended Cox proportional hazards regression models with competing risk of all-cause mortality were used to evaluate risk factors on ESRD incidence. Patients were followed till 2012. After a median follow-up period of 8.23 years, 1642 patients developed ESRD, giving a crude incidence rate of 6.27/1000 person-years (6.36 for men, 6.19 for women). After the multivariate adjustment, both FPG-CV and HbA1c-CV were independent predictors of ESRD with corresponding hazard ratios of 1.20 (95% confidence interval [CI] 1.01, 1.41), 1.24 (95% CI 1.05, 1.46) in HbA1c-CV from fourth to fifth quintile and 1.23 (95% CI 1.03, 1.47) in FPG-CV from fifth quintile. One-year visit-to-visit glucose variability expressed by FPG-CV and HbA1c-CV predicted development of ESRD in patients with type 2 diabetes, suggesting therapeutic strategies toward a goal to minimize glucose fluctuation.

Background The aim of this study was to examine whether time-dependent annual fasting plasma glucose (FPG) variation, as represented by coefficient of variation (CV), can predict mortality in subsequent all-cause, expanded, and nonexpanded cardiovascular disease-related mortality independent of mean FPG, renal function, mean hemoglobin A 1 C (HbA 1C ), HbA 1C variation, and other risk factors in patients with type 2 diabetes. Methods A computerized database of all patients with type 2 diabetes aged 30 years and over (n = 5008) enrolled in the Diabetes Care Management Program of China Medical University Hospital before 2007 was used in a time-dependent Cox proportional hazard regression model. Results The mortality rates were 8.64, 12.71, and 30.82 per 1000 person-years in groups of first, second, and third tertiles of baseline FPG-CV, respectively. Among these patients with type 2 diabetes, 336, 1191, 914, 585, and 1979 patients provided 1, 2, 3, 4, and 5 or more years of annual FPG-CV measurements, respectively. After adjusting for mean FPG, mean HbA 1C , HbA 1C variation, and other risk factors, annual FPG-CV was independently associated with all-cause mortality and mortality due to expanded and nonexpanded cardiovascular disease, and the corresponding hazard ratios for third versus first tertile of annual FPG-CV were 5.53 (95% confidence interval [CI], 3.85-7.94), 3.21 (95% CI, 2.00-5.15), and 9.45 (95% CI, 5.37-16.63), respectively. Conclusions Time-dependent variation of FPG was a strong predictor of all-cause, expanded, and nonexpanded cardiovascular disease-related mortality in patients with type 2 diabetes, suggesting that glucose variation may become a measure in clinical practice for the goal in the management of these patients.

This study aimed to examine whether poor glycemic control, measured by glycated hemoglobin A1C (HbA1c) and other cardiovascular risk factors, can predict diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (DM).Patients aged ≥30 years with type 2 DM, enrolled in the National Diabetes Care Management Program, and free of DPN (n = 37,375) in the period 2002 to 2004 were included and followed up until 2011. The related factors were analyzed using Cox proportional hazards regression models.For an average follow-up of 7.00 years, 8379 cases of DPN were identified, with a crude incidence rate of 32.04/1000 person-years. After multivariate adjustment, patients with HbA1c levels 7 to 8%, 8 to 9%, 9 to 10%, and ≥10% exhibited higher risk of DPN (adjusted HR: 1.11 [1.04-1.20], 1.30 [1.21-1.40], 1.32 [1.22-1.43], and 1.62 [1.51-1.74], respectively) compared with patients with HbA1c level 6 to 7%. There was a significant linear trend in DPN incidence with increasing HbA1c (P < 0.001) and significant HRs of DPN for patients with HbA1c level ≥7%, blood pressure ≥130/85 mm Hg, triglycerides (TG) ≥150 mg/dL, high density of lipoprotein-cholesterol (HDL-C)

The purpose of this study was to evaluate the relationship between glycated hemoglobin (HbA1c) and chronic obstructive pulmonary disease (COPD) in patients with type 2 diabetes. We conducted a retrospective cohort study involving 45,753 patients with type 2 diabetes, who participated in the National Diabetes Case Management Program in Taiwan. HbA1c at baseline and COPD events over the subsequent years were analyzed. After multivariate adjustment, the COPD risk increased among patients with HbA1c levels