Carotid Artery Disease in Subjects with Type 2 Diabetes: Risk Factors and Biomarkers

Abstract

Carotid atherosclerosis (CA) and, especially, carotid artery stenosis (CAS), are associated with a high risk of cardiovascular events in subjects with type 2 diabetes (T2D). In this study, we aimed to identify risk factors and biomarkers of subclinical CA and CAS in T2D individuals. High-resolution ultrasonography of carotid arteries was performed in 389 patients. Ninety-five clinical parameters were evaluated, including diabetic complications and comorbidities; antihyperglycemic, hypolipidemic, and antihypertensive therapy; indices of glycemic control and glucose variability (GV); lipid panels; estimated glomerular filtration rate (eGFR); albuminuria; blood cell count; and coagulation. Additionally, serum levels of calponin-1, relaxin, L-citrulline, and matrix metalloproteinase-2 and -3 (MMP-2, -3) were measured by ELISA. In univariate analysis, older age, male sex, diabetes duration, GV, diabetic retinopathy, chronic kidney disease, coronary artery disease, peripheral artery disease, and MMP-3 were associated with subclinical CA. In addition to these factors, long-term arterial hypertension, high daily insulin doses, eGFR, and L-citrulline were associated with CAS. In multivariate logistic regression, age, male sex, BMI, GV, and eGFR predicted CA independently; male sex, BMI, diabetes duration, eGFR, and L-citrulline were predictors of CAS. These results can be used to develop screening and prevention programs for CA and CAS in T2D subjects.

Evaluation of Subclinical Vascular Disease in Diabetic Kidney Disease: A Tool for Personalization of Management of a High-Risk Population

“…Several previous reports observed greater atherosclerotic burden in the carotid arteries of patients with DKD than in diabetic patients with preserved renal function [32][33][34][35]. However, most of these studies were performed in non-Caucasians and none evaluated multiple indices of carotid atherosclerosis (i.e., cIMT, degree of stenosis and plaque thickness) [32][33][34][35]. Interestingly, prospective studies suggest that carotid atherosclerosis predicts, not only cardiovascular events, but also renal function decline in patients with DKD [36,37].…”

“…Recently, sterol-O-acyltransferase-1, an enzyme that esterifies free cholesterol, the NLRP3 inflammasome pathway and the interleukin-33/ST2 pathway have also been implicated in the atherogenetic process in these patients [25][26][27][28][29][30][31]. Several previous reports observed greater atherosclerotic burden in the carotid arteries of patients with DKD than in diabetic patients with preserved renal function [32][33][34][35]. However, most of these studies were performed in non-Caucasians and none evaluated multiple indices of carotid atherosclerosis (i.e., cIMT, degree of stenosis and plaque thickness) [32][33][34][35].…”

Relaxin-2 as a Potential Biomarker in Cardiovascular Diseases

“…Tissue relaxin-2 mRNA levels are inversely correlated with MMP-2 in mild atherosclerosis and positively correlated with eNOS in moderate atherosclerosis, which supports the beneficial effect of relaxin-2 in this pathology [ 170 ]. Recently, Klimontov et al (2022) found no associations between serum levels of relaxin-2 and carotid atherosclerosis in patients with type 2 diabetes (T2D) [ 171 ]. A feasible explanation of these results could be that some confounders, such as insulin sensitivity, may modify the relationship between relaxin-2 and atherosclerosis in diabetes [ 171 ].…”

“…Recently, Klimontov et al (2022) found no associations between serum levels of relaxin-2 and carotid atherosclerosis in patients with type 2 diabetes (T2D) [ 171 ]. A feasible explanation of these results could be that some confounders, such as insulin sensitivity, may modify the relationship between relaxin-2 and atherosclerosis in diabetes [ 171 ].…”

Assessment of Compatibility Between Cardiologists and Radiologists for Interpreting and Reporting Carotid Duplex Ultrasound Images

“…Thus, they can notice subclinical carotid artery stenosis without developing a stroke or having an idea of the severity of the concomitant coronary artery disease. 24,25 In addition, interventional cardiologists who perform carotid artery stenting will more easily perform pre-and post-procedure followups of patients with carotid artery USG without the need for radiologists. 26,27 Performing carotid ultrasonography and echocardiography will increase time and labor intensity.…”