ADMA (asymmetric dimethylarginine) and angiogenic potential in patients with type 2 diabetes and prediabetes

Abstract

Asymmetric dimethylarginine is an endogenous competitive inhibitor of nitric oxide synthase and marker of endothelial dysfunction, but the question remains as to whether asymmetric dimethylarginine is a marker of cardiovascular episodes or their independent risk factor. ADMA/DDAH (dimethylaminohydrolase) pathway regulates vascular endothelial growth factor (VEGF)-mediated angiogenesis due to its impact on the NO formation. The aim of the study was to assess the concentrations of asymmetric dimethylarginine and the angiogenic potential in the blood of subjects with type 2 diabetes (T2DM, n = 33) and patients with prediabetes ( n = 32)—impaired fasting glycemia and/or impaired glucose tolerance (WHO criteria). The study found that both the prediabetes group and subjects with T2DM had significantly elevated concentrations of asymmetric dimethylarginine, significantly high levels of VEGF-A, low ratio of sVEGF-R1/VEGF-A, and sVEGF-R2/VEGF-A. This may suggest endothelial damage at early stages of carbohydrate metabolism dysfunction—before T2DM is diagnosed. Higher proangiogenic potential in prediabetes and T2DM patients than in healthy subjects, is not only the effect of an increase in VEGF-A levels, but also reduced inhibition of circulating receptors. Impact statement Our research provided new insight into the mechanisms governing vascular complications in prediabetes and type 2 diabetes. Unfortunately, most studies focus on angiogenesis markers (VEGF-A, sVEGF-R1, sVEGF-R2) and endothelial dysfunction marker (ADMA) separately. Our findings reported for the first time that endothelial damage and angiogenic potential at early stage of carbohydrate dysfunction appear in prediabetes before type 2 diabetes is diagnosed.

Oxidative Stress and Arginine/Nitric Oxide Pathway in Red Blood Cells Derived from Patients with Prediabetes

“…In contrast, at T8 the ADMA levels were similar to that measured at T0. An increase of ADMA following OGTT has been shown both in subjects with normal glycemia and with impaired glucose tolerance [ 48 ] and high levels of ADMA have been detected not only in patients with diabetes, but also in prediabetics [ 57 ]. In this context, it has been suggested that the high ADMA levels may be an epiphenomenon associated with high glucose levels, a documented cause for the increase of ADMA via inhibition of intracellular oxidative stress-dependent dimethylarginine dimethylaminohydrolase activity [ 58 ].…”

Advances and Perspectives in Relation to the Molecular Basis of Diabetic Retinopathy—A Review

“…High levels of ADMA have been identified not only in advanced DR but also in individuals at the prediabetic and diabetic stages. This observation suggests that ADMA likely plays a crucial role in both the initiation and advancement of DR [81,97]. Further studies that involve larger patient populations to better understand the role of plasma ADMA levels in the development and progression of DR are needed.…”

Functional AGXT2 SNP rs37369 Variant Is a Risk Factor for Diabetes Mellitus: Baseline Data From the Aidai Cohort Study in Japan

“…ADMA and its enantiomer, symmetric N G ,N 0G -dimethyl-L-arginine (SDMA), are strong predictors of cardiovascular events and death in a range of illnesses (3,4). Not only individuals with type 2 diabetes mellitus (DM), but also those with prediabetes, have been shown to have significantly elevated concentrations of ADMA compared with healthy controls (5).…”