Hsin-Hung Chen

Combination Therapy of Metformin and Statin May Decrease Hepatocellular Carcinoma Among Diabetic Patients in Asia

AbstractPrevious studies have shown that metformin or statins may decrease hepatocellular carcinoma (HCC) in diabetic patients. Accordingly, this article evaluates whether combination therapy may further reduce HCC.Newly diagnosed type 2 diabetes mellitus (DM) patients, excluding those with history of malignancy prior to the date of DM diagnosis, were recruited to a DM cohort. DM patients developed HCC as the cancer cohort and the date for HCC diagnosis as index date. Non-cancer cohort was frequency matched with 4:1 according to age, sex, DM-year, and index date as case group from DM cohort.Patients who were treated with statins showed a 63% decreased risk of HCC (odds ratio [OR] = 0.37; 95% confidence interval [CI] = 0.27–0.49). Patients who consumed simvastatin, atorvastatin, or rosuvastatin significantly decreased risk for HCC (OR = 0.32, 0.31, and 0.22; 95% CI = 0.18–0.58, 0.19–0.52, and 0.08–0.61, respectively). Metformin combinations with simvastatin, atorvastatin, or rosuvastatin may decrease HCC (OR = 0.30, 0.30, and 0.24; 95% CI = 0.15–0.59, 0.16–0.54, and 0.08–0.70, respectively). The comorbidities for HCC were decreased by consuming simvastatin and atorvastatin (OR = 0.31 and 0.29; 95% CI = 0.14–0.67 and 0.15–0.57, respectively). Only combination therapy of metformin and simvastatin may significantly decreased HCC comorbidities (OR = 0.26; 95% CI = 0.11–0.60) in our study.In Asia, not all metformin combinations with statins may reduce the incidence of HCC and not all of this kind of combination therapy may decrease the HCC comorbidities.

Increased Risk of Restless Legs Syndrome in Patients With Migraine: A Nationwide Population-Based Cohort Study.

Abstract Previous studies suggest that an association between restless legs syndrome (RLS) and migraine exists. However, population-based data are unavailable in Asian cohorts. Our study thus aims to evaluate the association between migraine and RLS in a nationwide, population-based cohort in Taiwan and to examine the effects of age, sex, migraine subtype, and comorbidities on RLS development. Data from the Taiwan National Health Insurance Research Database were used. Patients aged 20 years or older with newly diagnosed migraine from 2000 to 2008 were included; 23,641 patients with newly diagnosed migraine and 94,564 subjects without migraine were randomly selected and followed until RLS development, withdrawal from the National Health Insurance, or until the end of 2011. A multivariate Cox proportional hazards regression model was used to explore the risk of RLS in patients with migraine after adjustment for demographic characteristics and comorbidities. Both cohorts were followed for a mean of 7.38 years. After adjustment for covariates, the risk of RLS was 1.42-fold higher (95% confidence interval = 1.13–1.79) in the migraine cohort than in the nonmigraine cohort (7.19 versus 3.42 years per 10,000 person-years). The increased risk was more prominent in males in the migraine cohort (1.87-fold increased risk, 95% confidence interval 1.22–2.85). Neither comorbidity status nor migraine subtype influenced the RLS risk. This population-based study demonstrated that migraine is associated with an increased risk of RLS compared with those without migraine, particularly in male patients with migraine and regardless of the comorbidity status.

Association of Herpes Zoster and Type 1 Diabetes Mellitus

Objective The purpose of our study was to determine the association of type 1 diabetes mellitus (T1DM) and the risk of herpes zoster (HZ). Methods In this cohort study, we selected 4736 patients with T1DM registered in the Catastrophic Illness Patient Database who received insulin therapy before 2003 and 18944 participants without DM who were selected by frequency matched based on sex and age. Cox proportional hazard regression analysis was used to measure the hazard ratios (HRs) of HZ in the T1DM group compared with that in the non-T1DM group. Results Cox proportional hazard regression analysis showed that the adjusted HR of HZ was 2.38 times higher for patients in the T1DM group (95% CI = 1.77–3.19) than for those in the non-T1DM group. According to diabetes severity, mild and serious T1DM patients were associated with a higher risk of HZ (adjusted HR = 2.26, 95% CI = 1.67–3.05; and adjusted HR = 5.08, 95% CI = 2.66–9.71, respectively) than subjects without T1DM. Conclusion Patients with T1DM are at a higher risk of HZ than those without T1DM.

Glycemic Control with Thiazolidinedione Is Associated with Fracture of T2DM Patients.

Objective Diabetes is a common diseases and a major problem worldwide. Diabetic osteopathy might be elevated in diabetic patients and is usually caused by bone fracture. Several diabetes medications, such as thiazolidinediones (TZDs), could lead to increased risks of fracture. Methods We used the nationwide database to identified 32466 patients who had developed type 2 diabetes from 2000 to 2010 as the diabetic cohort and, from that group, we selected 3427 diabetic patients who had developed bone fracture to survey the possible risk factors, includng commonly used diabetes medication. Results We found that TZDs might present increased risks for fracture in patients who used it for an extended period (7 to 730 days before the index date), especially in female patients younger than 64 years old, for whom the risk was elevated from a 1.74- to a 2.58-fold odds ratio. Conclusions We recommend that clinics follow up with non-osteoporotic female patients younger than 64 years old who are using TZDs, to avoid the associated risks of fracture.

Short-term dipeptidyl peptidase-4 inhibitor use increases the risk of herpes zoster infection in Asian patients with diabetes.

BACKGROUND We aimed to evaluate whether patients with diabetes who use dipeptidyl peptidase (DPP)-4 inhibitors are at a higher risk of developing a herpes zoster (HZ) infection. METHODS We used a subset of the Longitudinal Health Insurance Database 2000 containing all inpatient and outpatient medical claims of ∼1 million people who were randomly sampled from the National Health Insurance Research Database. Patients who were newly diagnosed with Type 2 diabetes International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM 250.x0 and 250.x2) who used antidiabetic medications were divided into two cohorts based on their use of DPP-4 inhibitors between 2009 and 2011. Cox proportion hazard regression models were used to assess the effects of DPP-4 inhibitors on the incidence of HZ compared with the non-DPP-4-inhibitor-exposed cohort. RESULTS Patients in DPP-4-inhibitor-exposed cohort with diabetes and HZ infections revealed an incidence density of 4.20 per 1000 person-years compared with 3.50 per 1000 person-years for the non-DPP-4-inhibitor-exposed cohort (adjusted hazard ratio [HR] = 1.19, 95% confidence interval [CI] = 0.70-1.99). Furthermore, high-dose DPP-4-inhibitor treatment was associated with a significantly higher risk of HZ (adjusted HR = 2.46, 95% CI = 1.16-5.19 for a defined daily dose [DDD] ≥ 360). In addition, short-term DPP-4-inhibitor treatment was associated with a significantly higher risk of HZ (adjusted HR = 2.04, 95% CI = 1.03-4.04 for a DDD ≥ 360 days). CONCLUSION These results suggest that Asian patients with diabetes who use short-term DPP-4 inhibitors might be at a higher risk of developing HZ.

Risk of Depression, Chronic Morbidities, and l-Thyroxine Treatment in Hashimoto Thyroiditis in Taiwan: A Nationwide Cohort Study.

AbstractThe aim of this study was to evaluate the risk of depression in and effect of L-thyroxine therapy on patients with Hashimoto thyroiditis (HT) in Taiwan.In this retrospective, nationwide cohort study, we retrieved data from the Longitudinal Health Insurance Database 2000. We collected data of 1220 patients with HT and 4880 patients without HT for the period 2000 to 2011. The mean follow-up period for the HT cohort was 5.77 years. Univariate and multivariate Cox proportional hazards regression models were used to estimate the risk of depression in the HT cohort.In the HT cohort, 89.6% of the patients were women. Compared with the non-HT cohort, the HT cohort exhibited a higher prevalence of diabetes mellitus, hyperlipidemia, and coronary artery disease. Furthermore, the HT cohort showed a higher overall incidence of depression compared with the non-HT cohort (8.67 and 5.49 per 1000 person-year; crude hazard ratio [HR] = 1.58, 95% confidence interval [CI] = 1.18–2.13). The risk of depression decreased after administration of L-thyroxine treatment for more than 1 year (adjusted HR = 1.02; 95% CI = 0.66–1.59).In Taiwan, the overall incidence of depression was greater in the young HT cohort. L-thyroxine treatment reduced the risk of depression.

Statins Can Delay Insulin Use and Reduce Diabetes-related Diseases in Asian Patients With Type 2 Diabetes

AbstractWe evaluated the role of statins in delaying insulin use and diabetes-related diseases in Asian patients with type 2 diabetes mellitus (T2DM) because statins can cause new-onset diabetes.We used data from the Longitudinal Health Insurance Database in this retrospective cohort study. The 12,470 T2DM patients were categorized into 2 cohorts: a statin cohort comprising 2545 patients who received statin therapy for at least 6 months (180 days) before the index date and a nonstatin cohort comprising 9925 patients who did not receive statin therapy. The control-to-case ratio was set at approximately 4:1. Univariable and multivariable Cox proportional hazards regression analyses were performed to evaluate the risk of diabetes-related events and insulin use on receiving statin treatment.Patients in the statin cohort had a 48% lower risk of diabetes-related coma than those in the nonstatin cohort (95% confidence interval = 0.29–0.92). Patients with >730 days of statin therapy had a significantly lower risk of insulin use, diabetes-related disorders of the eye and neurons, and peripheral circulatory disorders. Compared with patients in the nonstatin cohort, the risk of insulin use, diabetes-related coma, and diabetes-related disorders of the eye and neurons was lower in patients on a cumulative defined daily dose (cDDD) of statins for >475 days.These results suggest that longer duration of statin use and higher cDDD of statins can delay insulin use in Asian patients with T2DM.

Association of Tramadol and Hypoglycemia in Diabetic Asians

To evaluate the association between tramadol and hypoglycemia in diabetic Asians. The data adopted in this study were derived from a subset of the National Health Insurance (NHI) Research Database, which comprises data on one million randomly sampled beneficiaries enrolled in the NHI program. Patients diagnosed with diabetes (according to the International Classification of Diseases, Ninth Revision, Clinical Modification code 250) were identified from claims data between 1998 and 2011. Diabetic patients aged 20 years or older and prescribed tramadol constituted the tramadol group and other diabetic patients without tramadol use constituted the non-tramadol group. For each tramadol case, one non-tramadol control frequency matched according to age (every 5 years), sex and the year of tramadol use was identified. The tramadol group comprised 12,446 patients and non-tramadol group comprised 11,982 patients. During a mean follow-up of 2 years for the patients in the tramadol group and 2.79 years for those in the non-tramadol group, the overall incidences of hypoglycemia (per 1000 person-years) were 7.37 and 3.77, respectively. According to the multivariable analyses, after baseline characteristics were controlled, the tramadol group exhibited a significantly greater risk of hypoglycemia (hazard ratio (HR) = 1.34, 95% confidence interval (CI) = 1.05–1.71) compared with the non-tramadol group. Tramadol use increases hypoglycemia in diabetic Asians. Greater attention must be paid to diabetic Asians with tramadol use.