Liu Wei Di Huang Wan and the Delay of Insulin Use in Patients with Type 2 Diabetes in Taiwan: A Nationwide Study.

INTRODUCTION: Patients with type 2 diabetes are widely prescribed metformin for controlling blood glucose levels to avoid related comorbidities. In Taiwan, traditional Chinese medicine (TCM) is also commonly used, especially Liu Wei Di Huang Wan (LWDHW), which has been reported to delay the occurrence of kidney failure. However, the effect of combinational therapy of TCM and oral antidiabetic drugs is still unclear. This study aims to estimate their efficacy in delaying insulin use. MATERIALS AND METHODS: This case-control study was conducted using one million randomized samples from the National Health Insurance Research Database in Taiwan. The effects of TCM and LWDHW were estimated using the Cox proportional hazards model. RESULTS: In this study, 70,036 diabetic patients were enrolled; of them, 17,451 (24.9%) used insulin, while the rest (52,585, 75.1%) did not. TCM users had a lower risk for insulin use (HR: 0.58, 95% CI: 0.56-0.60). LWDHW users had a lower risk compared with patients who used other TCM (HR: 0.86, 95% CI: 0.82-0.90) and presented a dose-dependent effect. CONCLUSION: The use of LWDHW and oral antidiabetic drugs is highly associated with the delay in the use of insulin. Clinical practitioners may take them into consideration when treating patients with type 2 diabetes.

Pyogenic Liver Abscess Risk in Patients With Newly Diagnosed Type 2 Diabetes Mellitus: A Nationwide, Population-Based Cohort Study.

Background: To date, no comprehensive epidemiological study exists on pyogenic liver abscess (PLA) risk in patients with newly diagnosed type 2 diabetes mellitus (T2DM) worldwide. Methods: We conducted a retrospective cohort study by using data from Taiwan National Health Insurance Research Database (NHIRD) to examine the association between newly diagnosed T2DM and PLA. The T2DM cohort included patients newly diagnosed as having T2DM (ICD-9-CM:250) from 2000 to 2009, with follow-up until December 31, 2011. The comparison cohort was then recruited through 1:4 random frequency matching with the T2DM cohort. Finally, the adjusted hazard ratios for PLA were compared between the T2DM and comparison cohorts, which included 44,728 patients with T2DM and 178,912 patients without DM respectively. Results: In T2DM cohort, 166 patients were diagnosed as having PLA (incidence rate = 5.87 per 10,000 person-years) and in comparison cohort, 238 patients were diagnosed as having PLA (incidence rate = 2.06 per 10,000 person-years). The T2DM cohort exhibited higher PLA risk than did the comparison cohort (hazard ratio = 2.83, 95% confidence interval = 2.32-3.46). Furthermore, the adjusted hazard ratio for PLA risk in T2DM cohort was the highest in those who were younger, man and with duration of DM <2 years. In the T2DM cohort, the most common PLA causative agent was Klebsiella pneumonia (KP). In addition, PLA risk was high in T2DM patients with gallstone and cholecystitis. Compared with comparison cohort, patients with T2DM prescribed acarbose has a lower PLA risk, however glyburide significantly increased PLA risk in T2DM cohort. Conclusion: In patients with newly diagnosed T2DM, PLA risk was high and acarbose might reduce PLA risk.

The Association Between Pleural Empyema and Peripheral Arterial Disease in Younger Patients: A Retrospective National Population-Based Cohort Study.

Background: To investigate the relationship between pleural empyema (PE) and peripheral arterial disease (PAD). Methods: We conducted a retrospective cohort study using data from the National Health Institute Research Database. Univariable and multivariable Cox's proportional hazard regressions were performed to investigate the association between PE and the risk of PAD. Kaplan-Meier method and the differences were assessed using a log-rank test. Results: The overall incidence of PAD was higher in the PE cohort than in the non-PE cohort (2.76 vs. 1.72 per 1,000 person-years) with a crude hazard ratio (HR) of 1.61 [95% confidence interval (CI) = 1.41-1.83]. After adjustment for age, gender, and comorbidities, patients with PE were noted to be associated with an increased risk of PAD compared with those without PE [adjusted HR (aHR) = 1.18, 95% CI = 1.03-1.35]. Regarding the age-specific comparison between the PE and non-PE cohorts, PAD was noted to be significantly high in the ≤ 49 years age group (aHR = 5.34, 95% CI = 2.34-10.1). The incidence of PAD was higher in the first 2 years, with an aHR of 1.35 (95% CI = 1.09-1.68) for patients with PE compared with those without PE. Conclusion: The risk of PAD was higher if patients with PE were younger than 49 years and within the 2-year diagnosis of PE.

Association of Hemorrhoids With Hashimoto's Thyroiditis and Associated Comorbidities: A Nationwide Population-Based Cohort Study.

Background: To evaluate the relationship between hemorrhoids and Hashimoto's thyroiditis (HT). Methods: Using Taiwan's Longitudinal Health Insurance Database, we compared the incident risk of HT between the study cohort (comprising patients with hemorrhoids) and the comparison cohort (comprising patients without hemorrhoids). Both cohorts were followed from index date until the date of HT diagnosis, withdrawal from the National Health Insurance program, or the end of 2015. Results: The study cohort and comparison cohort comprised 6,486 patients with hemorrhoids and 25,944 patients without, respectively. The mean follow-up time was ~3 years. The incidence rate of HT in the study cohort was 5.37 per 1,000 person-years, which was higher than that of the control cohort (2.46 per 1,000 person-years). The risk of developing HT in the study cohort was 2.06 times (95% confidence interval [CI] = 1.02, 4.19) higher than that in the comparison cohort. Conclusion: In our study, patients with hemorrhoids could be at increased risk of HT compared with patients with other comorbidities of HT, such as cardiovascular disease.

Effects of dipeptidyl peptidase-4 inhibitor treatment doses on tuberculosis in patients with diabetes: a long-term nationwide population-based cohort study.

BACKGROUND: To investigate the association of dipeptidyl peptidase-4 inhibitors (DPP4is) treatment doses and tuberculosis (TB) in patients with diabetes. METHODS: We allocated participants into DPP4i users and non-users from the Longitudinal Health Insurance Database. A chi-square test and Wilcoxon's rank-sum test were used to analyze the baseline discrete variables and continuous variable, respectively. The incidence rate was calculated in 1,000 personyears. The hazard ratios (HRs) were adjusted using a multivariate Cox regression model. The effect of DDP4i dosage on TB was analyzed. The Kaplan-Meier method was used to assess the cumulative incidence curves with a log-rank test. RESULTS: We identified 6,399 DPP4i users and 6,399 non-users. The incidence rate of TB in DPP4i users and non-users was 22.2 and 16.2 per 1,000 person-years, respectively. The HR of TB for DPP4i users relative to non-users was 1.04 (P=0.89). Most of the analysis of factors such as the incidence rate, gender and diabetic comorbidities in our study were non-significant. The risk of developing TB in patients with over 20 average defined daily doses (DDDs) per year was increased by 2.19 times (P=0.048). CONCLUSIONS: In our long-term nationwide population-based cohort study, higher doses of DPP4i (20 average DDDs) could increase TB infection risk in patients with diabetes. To pay more attention to this kind of diabetic patients with DPP4i treatment will be more important for the public health issue of TB prevention.

Hashimoto's thyroiditis might increase polycystic ovary syndrome and associated comorbidities risks in Asia.

BACKGROUND: To investigate whether increased the comorbidities such as coronary artery disease (CAD) and risks between Hashimoto's thyroiditis (HT) and polycystic ovary syndrome (PCOS) in Taiwanese women. METHODS: Patients newly diagnosed as having HT during 2000-2012 were assigned to the case group. Cases and controls were matched for age and comorbidities at a 1:2 ratio using propensity score matching. Incidence was calculated in the unit of 1000 person-year. Univariate and multivariate Cox proportional hazard regression, multivariate Cox, logistic regression, and Kaplan-Meier analyses were performed. RESULTS: Among 3,996 participants, 2,664 constituted the control group and 1,332 constituted the case group. The PCOS risk in patients with HT increased by 2.37 times [95% confidence interval (CI): 1.22-4.62] compared with the controls. Hypertension (HTN) [adjusted odds ratio (OR): 1.31, 95% CI: 1.03-1.66] and hyperlipidemia (adjusted OR: 1.55, 95% CI: 1.2-1.9) were more common in HT patients without PCOS than in other patients. The adjusted OR for CAD in patients with HT was 1.51 (95% CI: 1.11-2.06), whereas that in patients with HT and PCOS was 5.92 (95% CI: 1.32-26.53). CONCLUSIONS: In our study, the PCOS risk in patients with HT increased by 2.37 times, which is lower than the increase in HT risk in Asian patients with PCOS (4.56 times). The proportion of CAD increased significantly by 5.92 times in patients with HT and PCOS compared with patients with HT only.

Dipeptidyl peptidase-4 inhibitor treatment could decrease Klebsiella pneumoniae pneumonia in patients with type 2 diabetes.

OBJECTIVES: To investigate the effect of dipeptidyl peptidase-4 inhibitor (DPP4i) for Klebsiella pneumoniae (KP) pneumonia in patients with diabetes. PATIENTS AND METHODS: Patients newly diagnosed with type 2 diabetes from 2009 to 2012 were recruited for this population-based and observational study. Diabetes complications severity index (DCSI) score and defined daily dose (DDD) were used for analysis. The multivariable Cox proportional hazards models were used to estimate the risk of KP pneumonia by DPP4i use, with adjustments for propensity score. The Kaplan-Meier method with the log-rank test was used to estimate the risk of KP pneumonia for DPP4i users. RESULTS: 34774 patients were included. The incidence rate of KP pneumonia in DDP4i users was 1.51 per 1000 person-years and that for the comparison was 2.25 per 1000 person-years. DDP4i users also had a significantly lower cumulative incidence of KP pneumonia (log-rank test p-value = 0.03). DDP4i users had a significantly lower risk of developing KP pneumonia compared with nonusers (adjusted HR = 0.67, 95% CI = 0.48-0.95). CONCLUSIONS: For public health issue with type2 diabetes and infection, DPP4i use decreased KP pneumonia. Male gender, patients with co-morbidities, patients with higher DSCI score and higher DDD of DPP4i were observed to decrease KP pneumonia infection in our analysis. The possible role of DPP4i causing immunological disturbances should be considered.

Increased the risk of heart failure and comorbidities in patients with gout treatment: a population-based cohort study.

BACKGROUND: To investigate the association between gout treatment and heart failure (HF). METHODS: Patients with gout between 2000 and 2010 constituted the gout cohort. The main outcome was a new diagnosis of HF. Multivariable Cox proportional hazard regression models were used to measure the effect of gout on the risk of developing HF. The Kaplan-Meier method was used to estimate the cumulative HF incidence curve for the gout and nongout cohorts. RESULTS: The cohort study included 50,166 patients with gout. The incidence of HF was 1.96 times higher in the gout cohort than the non-gout cohort (7.11 vs. 3.63 per 10,000 person-years). The adjusted HR of developing HF was a 1.06-fold increase (95% CI: 1.06-1.07) with age and a 1.08-fold increase for women compared with men (95% CI: 1.02-1.14). HF incidence was higher in patients with receiving any two or more types of anti-gout drug treatment. CONCLUSIONS: Our study revealed that gout could increase the risk of HF. Gout treatment in Taiwan cannot improve HF and actually increase the risk for HF after combination therapy for gout. The public health burden of gout should be resolved in the future.

Graves' disease could increase polycystic ovary syndrome and comorbidities in Taiwan.

Background: To investigate the association between Graves' disease (GD) and polycystic ovary syndrome (PCOS) and its comorbidities.Methods: Logistic regression was performed to determine the association between the two conditions. Cumulative incidence curves were obtained using the Kaplan-Meier method and log-rank test. Hazard ratios were determined using the Cox proportional hazards regression model.Results: We included 5399 patients with GD as the study group and 10,798 patients without GD as the control group. The cumulative incidence curve of PCOS in patients with GD was significantly higher than that in patients without GD (p = .02). The adjusted hazard ratio for PCOS in patients with GD compared with patients without GD was 1.47 (95%CI = 1.09-1.98). The adjusted odds ratio of hyperlipidemia in patients with GD and PCOS was 2.18 (95%CI = 1.14-4.17) higher than that in patients with GD only.Conclusion: Our study demonstrated that women with GD could be at risk of developing PCOS; additionally, a higher incidence of comorbidities, including hyperlipidemia, was noted in women with GD and PCOS.

Gout can increase the risk of periodontal disease in Taiwan.

Objectives: To evaluate the risk of periodontal disease (PD) in gout patients. Methods: This retrospective cohort study was conducted using data from the Longitudinal Health Insurance Database 2000. The gout cohort included 31,759 patients newly diagnosed with gout from 2000 to 2012, and the comparison (nongout) cohort included 63,517 patients. Univariate and multivariable adjusted hazard ratios (aHRs), with corresponding 95% confidence intervals (CIs), were estimated using the Cox proportional hazard model for determining the occurrence of PD in both cohorts. We also measured the cumulative incidence of PD in these two cohorts using the Kaplan-Meier method and assessed the curve difference using the log-rank test. Results: The mean follow-up time was more than 6 years for both cohorts. The overall incidence rate of PD was significantly higher in the gout cohort than in the comparison cohort (5.04 vs 4.16 per 10,000 person-years; aHR = 1.13, 95% CI = 1.10-1.16). Only patients using colchicine had a significantly lower risk of PD (aHR = 0.85, 95% CI = 0.79-0.91). Conclusion: In our study, patients with gout showed an increased risk of PD, and treatment with colchicine could decrease the risk. Abbreviations: PD: periodontal disease; LHID: Longitudinal Health Insurance Research Database; NHIRD, National Health Insurance Research Database; ICD-9-CM: International Classification of Diseases, Ninth Revision, Clinical Modification; CI: confidence interval; HR: hazard ratio.

Increased Risk of Polycystic Ovary Syndrome and It's Comorbidities in Women with Autoimmune Thyroid Disease.

OBJECTIVE: To investigate the prevalence of polycystic ovary syndrome (PCOS) and its comorbidities in patients with autoimmune thyroid disease (AITD). POPULATION: In this cohort study, patients newly diagnosed as having Hashimoto thyroiditis (HT) or Grave disease (GD) were recruited into the AITD group. METHOD: The logistic regression model was used to investigate the association between exposure, endpoint, later diseases and treatment. MAIN OUTCOME MEASURES: We assessed the cumulative incidence using the Kaplan-Meier method and verified the difference by the log-rank test. RESULTS: The AITD group included 3599 GD patients and 1332 HT patients. PCOS risk in patients with AITD was higher than that in the control group (adjusted hazard ratio = 1.39; 95% confidence interval = 1.07-1.71). In patients with both AITD and PCOS, the odds ratios of diabetes, hyperlipidemia and coronary artery disease were 2.48, 2.05 and 2.63, respectively. CONCLUSIONS: The risks of PCOS and its comorbidities such as diabetes, dyslipidemia and cardiac artery disease are high in patients with AITD in Taiwan.