Expression of CD4+ CD28null T lymphocytes in children and adolescents with type 1 diabetes mellitus: Relation to microvascular complications, aortic elastic properties, and carotid intima media thickness

Abstract

Background: Cardiovascular risk in type 1 diabetes mellitus (T1DM) is associated with endothelial dysfunction, inflammation, and altered immunity. CD4⁺ CD28^null T-cells are a subset of long-lived cytotoxic CD4⁺ T-lymphocytes with proatherogenic and plaque-destabilizing properties. We hypothesized that the frequency of CD4⁺ CD28^null T-cells may be altered in T1DM and related to vascular complications.

Aim: To assess the percentage of CD4⁺ CD28^null T-lymphocytes in children and adolescents with T1DM and their relation to vascular structure and glycemic control.

Methods: Totally 100 patients with T1DM were divided into 2 groups according to the presence of microvascular complications and compared with 50 healthy controls. CD4⁺ CD28^null T-lymphocytes were analyzed using flow cytometry. Aortic elastic properties and carotid intima media thickness (CIMT) were assessed.

Results: Aortic stiffness index and CIMT were significantly higher among patients compared with healthy controls while aortic strain and distensibility were decreased. The percentage of CD4⁺ CD28^null T-cells was significantly higher in patients with and without microvascular complications compared with controls. High frequency of CD4⁺ CD28^null T-cells was found among patients with microalbuminuria or peripheral neuropathy. Patients with CD4⁺ CD28^null T-cells ≥10% had higher HbA1c, urinary albumin creatinine ratio, aortic stiffness, and CIMT. CD4⁺ CD28^null T-cells were positively correlated to HbA1c, aortic stiffness index, and CIMT.

Conclusions: Changes in aortic elastic properties and increased CIMT among young patients with T1DM may enable the recognition of preclinical cardiac impairment. The correlation between CD4⁺ CD28^null T-cells and assessed parameters of vascular structure highlights the role of altered immune response in the occurrence of diabetic vascular complications.

Keywords: CD4+CD28null T lymphocytes; aortic stiffness; carotid intima media thickness; microvascular complications; type 1 diabetes.