No abstract

Aims Leukocyte telomere length (LTL), as a biomarker of biological aging, is associated with the prevalence and complications of diabetes. This study aims to investigate the associations between LTL and all‐cause and cause‐specific mortality in patients with type 2 diabetes. Methods All participants with baseline LTL records were included from the National Health and Nutrition Examination Survey 1999–2002. Death status and its causes were ascertained for National Death Index based on International Classification of Diseases, Tenth Revision code. Cox proportional hazards regression models were established to estimate the hazard ratios (HRs) of LTL associating with all‐cause and cause‐specific mortality. Results The study enrolled 804 diabetic patients with the mean follow‐up of 14.9 ± 2.59 years. There were 367 (45.6%) all‐cause deaths, 80 (10.0%) cardiovascular deaths, and 42 (5.2%) cancer‐related deaths. Longer LTL was associated with reduced all‐cause mortality, whereas this association disappeared after adjusting for other variables. Compared with the lowest tertiles of LTL, the multivariable‐adjusted hazard ratio of cardiovascular mortality was 2.11 (95% confidence interval [CI] 1.31–3.39; p < .05) in the highest tertiles. In terms of cancer mortality, the highest tertile was negatively correlated with the risk of cancer mortality (HR 0.58 [95% CI 0.37, 0.91], p < .05). Conclusion In conclusion, LTL was independently associated with the risk of cardiovascular mortality in patients with type 2 diabetes and was negatively correlated with the risk of cancer mortality. Telomere length may be a predictor of cardiovascular mortality in diabetes.

Background: Protein kinase AMP-activated non-catalytic subunit gamma 2 gene (PRKAG2) cardiac syndrome, caused by mutations in PRKAG2, often shows myocardial hypertrophy and abnormal glycogen deposition in cardiomyocytes. However, it remains incurable due to a lack of a management guideline for treatment.Methods: We constructed a fluorescently labeled adenovirus carrying the wild-type or R302Q mutant of the PRKAG2 gene, infected neonatal rat cardiomyocytes (NRCMs) and H9C2 cell lines, and then analyzed changes in AMP-activated protein kinase (AMPK) activity, cell hypertrophy, glycogen storage, and cell proliferation when presence or absence of metoprolol or protein kinase A (PKA) inhibition H89, and then analyzed the changes in AKT-mTOR signal transduction activity.Results: Overexpression of PRKAG2 R302Q in primary cardiomyocytes increased the activity of AMPK, induced cellular hypertrophy and glycogen storage, and promoted the phosphorylation levels of AKT-mTOR signaling pathway. Application of either β1-adrenergic receptor (β1-AR) blocker metoprolol or PKA inhibitor H89 to the cardiomyocytes rescued the hypertrophic cardiomyopathy (HCM)-like phenotypes induced by PRKAG2 R302Q, including suppression of both AKT-mTOR phosphorylation and AMPK activity.Conclusions: The current study not only determined the mechanism regulating HCM induced by PRKAG2 R302Q mutant, but also demonstrated a therapeutic strategy using β1-AR blocker to treat the patients with PRKAG2 cardiac syndrome.