Abstract
Background and objectives: HbA1c measurements may be useful not only in optimizing glycemic control but also as a tool for managing overall vascular risk in patients with diabetes. In the present study, we investigate the clinical significance of HbA1c as a biomarker for hyperglycemia-induced vascular damages in type 2 diabetes (T2D) based on the levels of matrix metalloproteinases-2, -9 (MMP-2, MMP-9), anti-collagen IV (ACIV), and anti-elastin (AE) antibodies (Abs) IgM, IgG, and IgA, and CIV-derived peptides (CIV-DP) reflecting collagen and elastin turnover in the vascular wall. The aim is to show the relationship of hyperglycemia with changes in the levels of vascular markers and the dynamics of this relationship at different degrees of glycemic control reported by HbA1c levels. Materials and Methods: To monitor elastin and collagen IV metabolism, we measured serum levels of these immunological markers in 59 patients with T2D and 20 healthy control subjects with an ELISA. Results: MMP-2, MMP-9, and the AEAbs IgA levels were significantly higher in diabetic patients than in control subjects, whereas those of the AEAbs IgM, ACIVAbs IgM, and CIV-DP were significantly lower. MMP-9 levels were significantly lower at HbA1c values >7.5%. Conclusions: A set of three tested markers (MMP-2, MMP-9, and AEAbs IgA) showed that vascular damages from preceding long-term hyperglycemia begin to dominate at HbA1c values ≥7.5%, which is the likely cut-point to predict increased vascular risk.
Highlights
The prevalence of type 2 diabetes (T2D) is increasing worldwide, and it is expected to affect over 500 million adults worldwide by 2030 [1]
In a previous study of patients with hypertension and T2D, we showed that elevated serum levels of matrix metalloproteinases (MMPs)-2 and MMP-9 may reflect early structural changes in the vascular extracellular matrix [14]
We investigate the clinical significance of HbA1c as a predictive biomarker for hyperglycemia-induced vascular damages in T2D, based on the statistical relationships between
Summary
The prevalence of type 2 diabetes (T2D) is increasing worldwide, and it is expected to affect over 500 million adults worldwide by 2030 [1]. Despite the tendency in patients with good metabolic control to have a significantly reduced risk of developing complications, vascular disease can continue to develop and progress even under intensive treatment regimens due to the phenomenon known as “glycemic memory” [5]. Increased glucose levels can lead to metabolic derangements associated with vision loss, peripheral neuropathy, myocardial infarction, strokes, foot ulcers, and end-stage renal disease, which may cause permanent disability [6]. HbA1c measurements may be useful in optimizing glycemic control and as a tool for managing overall vascular risk in patients with diabetes. Results: MMP-2, MMP-9, and the AEAbs IgA levels were significantly higher in diabetic patients than in control subjects, whereas those of the AEAbs IgM, ACIVAbs IgM, and CIV-DP were significantly lower. MMP-9 levels were significantly lower at HbA1c values >7.5%
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