Cardiovascular biomarkers in clinical studies of type 2 diabetes

Abstract

When planning cardiovascular (CV) studies in type 2 diabetes (T2D), selection of CV biomarkers is a complex issue. Because the pathophysiology of CV disease (CVD) in T2D is multifactorial, ideally, the selected CV biomarkers should cover all aspects of the known pathophysiology of the disease. This will allow the researcher to distinguish between effects on different aspects of the pathophysiology. To this end, we discuss a host of biomarkers grouped according to their role in the pathogenesis of CVD, namely: (1) cardiac damage biomarkers; (2) inflammatory biomarkers; and (3) novel biomarkers (oxidative stress and endothelial dysfunction biomarkers). Within each category we present the best currently validated biomarkers, with special focus on the population of interest (people with T2D). For each individual biomarker, we discuss the physiological role, validation in the general population and in people with T2D, analytical methodology, modifying factors, effects of glucose-lowering drugs, and interpretation. This approach will provide clinical researchers with the information necessary for planning, conducting and interpreting results from clinical trials. Furthermore, a systematic approach to selection of CV biomarkers in T2D research will improve the quality of future research.

Changes in arginine are inversely associated with type 2 diabetes: A case‐cohort study in the PREDIMED trial

“…We also considered a pre-hypothesized arginine/ADMA ratio, 6 as well as the global arginine bioavailability ratio (GABR) defined as arginine/ (citrulline + ornithine) in our primary analysis. 7 We fitted Cox regression models, stratified by recruitment centre, using inverse probability weights and employing a sandwich variance estimator.…”

“…For example, a 2.00 HR per 1‐SD increase would mean that an individual with a plasma concentration of a given metabolite that is 1 SD above that of another individual would have twice the relative rate of T2D incidence of that individual. We also considered a pre‐hypothesized arginine/ADMA ratio, as well as the global arginine bioavailability ratio (GABR) defined as arginine/(citrulline + ornithine) in our primary analysis …”

Advanced Glycation End Products: Potential Mechanism and Therapeutic Target in Cardiovascular Complications under Diabetes

“…The expression of inflammatory factors such as tumor necrosis factor- α (TNF- α ) and interleukin-6 (IL-6) was demonstrated to promote cardiac fibroblast proliferation, thereby increasing collagen synthesis and ultimately leading to myocardial fibrosis [35]. Inflammatory factors are in turn considered to increase ROS [36]. NF- κ B can increase the expression of inducible nitric oxide synthase (iNOS), which promotes the generation of nitric oxide.…”

Adenylate Kinase: A Ubiquitous Enzyme Correlated with Medical Conditions

“…A diminished activity of 5′-AMP activated kinase (AMPK) followed by accumulation of misfolded proteins along with decreased mitochondrial biogenesis could explain the molecular mechanisms of these diseases [63,64]. Further, besides of the constellation of metabolites modified in these disorders, the antioxidant defenses mechanisms are also reduced, brain is one of the most vulnerable tissue when face to oxidative damage [65,66]. A big picture of dysregulation of different enzymes expressed in the neurons suggests that the dynamic of some enzymes in different stage of Parkinson disease are distinctive.…”