Metformin protection against cancer risk in Orientals is uncertain. We examined the possible metformin effect on total, esophageal, gastric, colorectal (CRC), hepatocellular (HCC) and pancreatic cancers in a Taiwanese cohort. A representative sample of 800,000 was drawn from the Taiwanese National Health Insurance data of 2000. A cohort of 480,984 participants 20 years or older, diabetes-cancer-free on 1st January 2000 was formed and categorized as four groups by DM and metformin usage status. Eligible incident cancer events had to occur one year after the index date until the end of 2007. The Cox proportional-hazards model evaluated relative risk of cancer for treated DM patients with or without metformin. The covariates included age, gender, other oral anti-hyperglycemic medication, Charlson comorbidity index (CCI) score and metformin exposure dosage and duration. With diabetes but no anti-hyperglycemic medication, cancer incidence density increased at least 2-fold for total, CRC and HCC. On metformin, total, CRC and HCC incidences decreased to near non-diabetic levels but to varying degrees depending on gender and cancer type (CRC in women, liver in men). Adjustment for other oral anti-hyperglycemic agents usage and CCI made the benefit of metformin more evident [hazard ratios (95% confidence intervals): total 0.12 (0.08-0.19), CRC 0.36 (0.13-0.98), liver 0.06 (0.02-0.16), pancreas 0.15 (0.03-0.79)]. There was a significant gender interaction with metformin in CRC which favored women. Metformin dosage for a significant decrease in cancer incidence was ≤500 mg/day. Metformin can reduce the incidences of several gastroenterological cancers in treated diabetes.

To determine incidence of dementia in type 2 diabetic (T2DM) patients, and whether there are adverse or favorable effects of oral agents (OA) in DM, we obtained a representative cohort of 800,000 from Taiwan's National Health Insurance database. Thos

Calcium is a universal secondary messenger that triggers many cellular responses. However, it is unclear how a calcium signal is coordinately decoded by different calcium sensors, which in turn regulate downstream targets to fulfill a specific physiological function. Here we show that SOS2-LIKE PROTEIN KINASE5 (PKS5) can negatively regulate the Salt-Overly-Sensitive signaling pathway in Arabidopsis. PKS5 can interact with and phosphorylate SOS2 at Ser²⁹⁴, promote the interaction between SOS2 and 14-3-3 proteins, and repress SOS2 activity. However, salt stress promotes an interaction between 14-3-3 proteins and PKS5, repressing its kinase activity and releasing inhibition of SOS2. We provide evidence that 14-3-3 proteins bind to Ca²⁺, and that Ca²⁺ modulates 14-3-3-dependent regulation of SOS2 and PKS5 kinase activity. Our results suggest that a salt-induced calcium signal is decoded by 14-3-3 and SOS3/SCaBP8 proteins, which selectively activate/inactivate the downstream protein kinases SOS2 and PKS5 to regulate Na⁺ homeostasis by coordinately mediating plasma membrane Na⁺/H⁺ antiporter and H⁺-ATPase activity.

Inhibition of the renin-angiotensin-aldosterone system with an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) delays the progression of chronic kidney disease (CKD) in patients with and without diabetes mellitus, particularly those with mild to moderate renal insufficiency as reflected by a serum creatinine level of 1.5 to 3.0 mg/dL (to convert to micromoles per liter, multiply by 88.4).^1-4 Two randomized clinical trials in China^5,6 and a post hoc analysis of the Ramipril Efficacy in Nephropathy trial⁷ further demonstrated that the use of ACEIs or ARBs is beneficial in patients with stage 4 CKD, defined by a glomerular filtration rate (GFR) of 15 to 29 mL/min/1.73 m² and a serum creatinine level of approximately 3.0 to 5.0 mg/dL, who do not have diabetes mellitus. However, data focusing on the use of ACEIs and/or ARBs in patients with serum creatinine levels of greater than 5.0 mg/dL or a GFR of less than 15 mL/min/1.73 m² are limited. Because most prospective, large-scale clinical trials of ACEI/ARB use excluded individuals with stage 5 CKD who were not undergoing dialysis (predialysis CKD), whether ACEI/ARB therapy should be used continuously in patients with advanced CKD remains unclear.

Diabetes mellitus (DM) and DM-related complications place a high socioeconomic burden on individuals and society. Updating nationwide information periodically is thus pivotal to preventing DM and improving its management in Taiwan. We used the National Health Insurance Research Database; disease diagnosis codes were assigned according to the International Classification of Diseases, 9th Revision, Clinical Modification. DM was defined as ≥3 outpatient visits or 1 hospitalization within a year. We excluded individuals with gestational DM, those with missing data, and those aged >100 years. Type 1 DM (T1DM) was defined based on information from the catastrophic illness registry. From 2005 to 2014, total population with DM increased by 66% and age-standardized prevalence in patients aged 20-79 years increased by 41%. The DM prevalence was generally higher in men; however, the prevalence was higher in women aged ≥65 years. The prevalence of DM was approximately 50% in those aged >80 years. DM incidence increased by 19%; the increase was most obvious in patients aged 20-39 years (p < 0.001). The standardized incidence of T1DM slightly decreased by 11% (p = 0.118) and standardized prevalence of T1DM increased from 0.04% to 0.05%. Number of T1DM accounted for 0.51-0.59% of the entire diabetic population during the observation period. DM prevalence is continually increasing, but the incidence only marginally increased from 2005 to 2014. Moreover, DM is a major problem in elderly people. The higher incidence of DM in men is consistent with the pandemic of overweight and obesity in men in Taiwan.

Background: Frail older adults are predisposed to multiple comorbidities and adverse events. Recent interventional studies have shown that frailty can be improved and managed. In this study, effective individualized home-based exercise and nutrition interventions were developed for reducing frailty in older adults. Methods: This study was a four-arm, single-blind, randomized controlled trial conducted between October 2015 and June 2017 at Miaoli General Hospital in Taiwan. Overall, 319 pre-frail or frail older adults were randomly assigned into one of the four study groups (control, exercise, nutrition, and exercise plus nutrition [combination]) and followed up during a 3-month intervention period and 3-month self-maintenance period. Improvement in frailty scores was the primary outcome. Secondary outcomes included improvements in physical performance and mental health. The measurements were performed at baseline, 1 month, 3 months, and 6 months. Results: At the 6-month measurement, the exercise (difference in frailty score change from baseline: − 0.23; 95% confidence interval [CI]: − 0.41, − 0.05; p = 0.012), nutrition (− 0.28; 95% CI: − 0.46, − 0.11; p = 0.002), and combination (− 0.34; 95% CI: − 0.52, − 0.16; p < 0.001) groups exhibited significantly greater improvements in the frailty scores than the control group. Significant improvements were also observed in several physical performance parameters in the exercise, nutrition, and combination groups, as well as in the 12-Item Short Form Health Survey mental component summary score for the nutrition group. Conclusions: The designated home-based exercise and nutrition interventions can help pre-frail or frail older adults to improve their frailty score and physical performance. Trial registration: Retrospectively registered at ClinicalTrials.gov (identifier: NCT03477097); registration date: March 26, 2018.