This nationwide population-based study investigated the risk of Parkinson disease (PD) in relation to diabetes mellitus (DM) through the National Health Insurance Research Database in Taiwan.A retrospective study was conducted, consisting of 36,294 patients who were newly diagnosed with DM between January 1, 2000 and December 31, 2006 and 108,882 individuals without DM as healthy controls from insurance claims data from Taiwan's National Health Research Institutes Dataset. The subjects were followed up until December 31, 2011 or until the first manifestation of PD. The hazard ratio (HR) of DM for PD incidence was estimated by Cox proportional hazard regression model.Compared with the non-DM cohort, the incidence density rate of PD was 1.36-fold higher in the DM cohort (1.53 vs 2.08 per 1000 person-years) with an adjusted HR of 1.19 (95% confidence interval = 1.08–1.32) after adjusting for age, sex, comorbidities, and medication use. The adjusted HR of PD for DM with a larger magnitude was observed in females (1.29, 1.12–1.49); individuals age 65 years and older (1.20, 1.06–1.35); those without schizophrenia (1.20, 1.08–1.33), bipolar disorder (1.20, 1.08–1.33), hypertension (1.18, 1.06–1.32), hyperlipidemia (1.21, 1.09–1.34), chronic obstructive pulmonary disease (1.19, 1.06–1.32), coronary artery disease (1.22, 1.09–1.36), stroke (1.23, 1.10–1.37), asthma (1.20, 1.08–1.34), flunarizine use (1.21, 1.08–1.35), zolpidem use (1.16, 1.04–1.30), Charlson comorbidity index score of 0 (1.23, 1.08–1.40), and those using metoclopramide (1.35, 1.14–1.60) and zolpidem (1.46, 1.12–1.90).DM increased the risk of PD during a mean follow-up of 7.3 years. Further mechanistic research on the effect of DM on PD is needed.

BackgroundThis study aims to determine cancer risks among patients with type 2 diabetes through a follow-up study on a nationwide population-based cohort that included Taiwanese diabetic patients and general population in Taiwan as well as to estimate the population attributable fraction (PAF) of site-specific cancer risks that can be attributed to type 2 diabetes in Taiwanese population by using standardized incidence ratios (SIRs, 95% CI).MethodsSubjects with type 2 diabetes consisted of 472,979 patients aged ≥20 years, whereas general population consisted of 9,411,249 individuals of the same age limit but are not diabetic. Subjects were identified from 1997 to 1998 and followed up until December 31, 2007 or until the first manifestation of any cancer.ResultsCancer sites with increased risks in men, which were consistent with the main and sensitivity analyses, included pancreas (SIR = 1.62; 95% CI = 1.53 to 1.72), liver (1.61; 1.57 to 1.64), kidney (1.32; 1.25 to 1.40), oral (1.16, 1.12 to 1.21), and colorectal (1.19, 1.15 to 1.22). Cancer sites with increased risks in women included liver (1.55; 1.51 to 1.60), pancreas (1.44; 1.34 to 1.55), kidney (1.38; 1.30 to 1.46), endometrium (1.36; 1.26 to 1.47), bladder (1.19; 1.11 to 1.27), colorectal (1.16; 1.13 to 1.20), and breast (1.14; 1.09 to 1.18). Overall, PAFs were highest for liver cancer in men (4.0%) and women (3.7%), followed by pancreas (3.4%) and kidney (1.6%) cancers in men, and then for endometrium (1.8%) and kidney (1.8%) cancers in women.ConclusionOur data suggested that increased cancer risks are associated with type 2 diabetes.

Background/Aims: Radix Angelica Sinensis (danggui in Chinese) is widely used in traditional chinese medicine (TCM). N-butylidenephthalide (BP), a bioactive compound in danggui, is a potential antitumor agent for various cancer types. However, its clinical effect and mechanism in the treatment of gastric cancer remain undetermined. Methods: The in vivo protective effect of danggui in patients with gastric cancer were validated using data from Taiwan’s National Health Insurance Research Database (NHIRD). The genes induced by BP-treatment were analyzed by whole transcriptome RNA sequencing (RNA-seq) and validated by real-time PCR, western blot and siRNA transfection. The effect of BP on AGS cell migration and invasion was evaluated in transwell assays. The antitumor effects of BP were evaluated in vivo in an AGS xenograft animal model. Results: Danggui users were found to have an increased survival rate when compared with danggui nonusers (log-rank test p = 0.002) . The use of danggui highly associated with decreased mortality (the adjusted hazard ratio (HR) of danggui user was 0.72 [95 % CI, 0.57-0.92] (p = 0.009). The in vitro results showed that BP inhibited gastric cancer cell proliferation, and triggered cellular apoptosis depending on the activation of mitochondrial apoptotic pathway. Using RNA-seq analysis we found that REDD1 was the highest transcript induced by BP in gastric cancer cells. BP induce an increase of REDD1 expression that inhibits mTOR signaling, thus inhibiting gastric cancer growth. We used RNA interference to demonstrate that the knock-down of REDD1 attenuated the BP-induced mTORC1 activation and growth inhibition. BP suppressed the growth of AGS xenografts tumor in vivo. Conclusion: Danggui can prolong the survival rate of gastric cancer patients in Taiwan. BP caused gastric cancer cell death through the activation of mitochondria-intrinsic pathway and induced the REDD1 expression leading to mTOR signal pathway inhibition in gastric cancer cells. BP inhibited the in vivo growth of AGS xenograft tumors. These results may provide the basis for a new therapeutic approach toward the treatment of gastric cancer progression.