No abstract

Weight change over 4 years showed a reverse J-shaped all-cause mortality curve, independent of BMI status. Weight loss was associated with a greater risk of mortality than was weight gain.

One of the histopathologic hallmarks of early diabetic retinopathy is the loss of pericytes. Evidences suggest that the pericyte loss in vivo is mediated by apoptosis. However, the underlying cause of pericyte apoptosis is not fully understood. This study investigated the influence of methylglyoxal (MGO), a reactive α-dicarbonyl compound of glucose metabolism, on apoptotic cell death in bovine retinal pericytes. Analysis of internucleosomal DNA fragmentation by ELISA showed that MGO (200 to 800 µM) induced apoptosis in a concentration-dependent manner. Intracellular reactive oxygen species were generated earlier and the antioxidant, N-acetyl cysteine, inhibited the MGO-induced apoptosis. NF-κB activation and increased caspase-3 activity were detected. Apoptosis was also inhibited by the caspase-3 inhibitor, Z-DEVD-fmk, or the NF-κB inhibitor, pyrrolidine dithiocarbamate. These data suggest that elevated MGO levels observed in diabetes may cause apoptosis in bovine retinal pericytes through an oxidative stress mechanism and suggests that the nuclear activation of NF-κB are involved in the apoptotic process.

Background:The global public health burden of obesity has increased with socio-economic development. The Korean Society for the Study of Obesity released the 2021 Obesity Fact Sheet to address trends in obesity prevalence and comorbid conditions by different age groups. Methods: Individuals ≥20 years old who underwent a health checkup provided by the Korean National Health Insurance Service between 2009 and 2019 were included. The prevalence of obesity and abdominal obesity was standardized by age and sex based on the 2010 population and housing census. The incidence of obesity-related comorbidities was tracked from 2009 to 2019, and the incidence per 1,000 person-years was calculated using Poisson regression adjusted for age and sex. Results: Obesity and abdominal obesity prevalence has increased for the entire population over the past 11 years. Obesity prevalence has risen rapidly in individuals in their 20s and 80s compared with other age groups. Additionally, class III obesity prevalence in both men and women has significantly increased by nearly threefold. The relative risk of developing type 2 diabetes, myocardial infarction, ischemic stroke, and cancers in people with obesity or abdominal obesity is greater than in people without obesity or abdominal obesity. The relative risk was higher in young and middle-aged individuals than in the older population. Conclusion:The findings based on the 2021 Obesity Fact Sheet suggest the need to better understand obesity characteristics according to age and sex and to establish individualized treatment strategies.

Dipeptidyl peptidase 4 (DPP4) inhibitors have been touted as promising antihyperglycemic agents due to their beneficial effects on glycemia without inducing hypoglycemia or body weight gain and their good tolerability. Beyond their glucose-lowering effects, numerous clinical trials and experimental studies have suggested that DPP4 inhibitors may exert cardioprotective effects through their pleiotropic actions via glucagon-like peptide 1-dependent mechanisms or involving other substrates. Since 2008, regulatory agencies have required an assessment of cardiovascular disease (CVD) safety for the approval of all new anti-hyperglycemic agents, including incretin-based therapies. Three large prospective DPP4 inhibitor trials with cardiovascular (CV) outcomes have recently been published. According to the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR-TIMI 53) and EXamination of cArdiovascular outcoMes with alogliptIN versus standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome (EXAMINE) trials, DPP4 inhibitors, including saxagliptin and alogliptin, did not appear to increase the risk of CV events in patients with type 2 diabetes and established CVD or high risk factors. Unexpectedly, saxagliptin significantly increased the risk of hospitalization for heart failure by 27%, a finding that has not been explained and that requires further exploration. More recently, the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) trial demonstrated the CV safety of sitagliptin, including assessments of the primary composite CV endpoint and hospitalization for heart failure in patients with type 2 diabetes and established CVD. The CV outcomes of an ongoing linagliptin trial are expected to provide new evidence about the CV effects of a DPP4-inhibitor in patients with type 2 diabetes.