According to the updated classification of American Diabetes Association (2021), latent autoimmune diabetes in adults (LADA) is classified as type 1 diabetes (T1D), which develops in adulthood and has a slowly progressive course [1].
Together with insulin, b-cells of the islets of Langerhans produce amylin or islet amyloid polypeptide [2]. The effect of amylin levels on the course of diabetes is still controversial and ambiguous, and the role of hyperamylinemia in the development and progression of micro- and macrovascular complications, in particular diabetic kidney disease (DKD), remains unnoticed by researchers. According to this, the objective of our study was to determine the features of the course of chronic kidney disease (CKD) depending on the level of amylinemia in patients with T1D and type 2 diabetes (T2D).
In patients with classical T1D, the level of amylinemia did not change, whereas in T2D group it was 10.8 times significantly higher compared to the control and 8.3 times higher than in the group of patients with classical T1D. In the group of patients with LADA, the amylin content was 9.0 times higher than in control and 6.8 times higher compared to classical T1D. The highest indicator was registered in patients with LADA2 phenotype. The level of amylin was increasing in proportion to the stages of CKD and categories of albuminuria. Positive correlations were found between the content of amylin and insulin, C-peptide, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index and creatinine.
The results of our study indicate the probable role of hyperamylinemia in the development of CKD in patients with diabetes. Kidney damage in this case can occur by binding amylin to procalcitonin and receptor for advance glycation endproducts-22 (RAGE22) on the podocyte membrane. RAGE22 in turn activates p21ras, mitogen-activated protein kinase, nuclear kB-factor and CDC42/Ras pathways. Stimulation of RAGE22 induces the expression of endothelial vascular growth factor, which causes endothelial cell hyperpermeability, disrupts the expression of intracellular adhesion molecule-1, promotes adhesion and inflammation of macrophages, activates nuclear kB-factor and increases the expression of proinflammatory cytokines — TNF-a, IL-1b, IL-6, which leads to podocyte damage and the occurrence of proteinuria [3]. In turn, in CKD, redox stress caused by hyperglycemia, lipotoxicity and glycotoxicity contributes to the accelerated formation of amylin deposits by cross-linking oligomers with each other by the end products of glycation. Thus, strict metabolic control and reduction of insulin resistance significantly inhibit the formation and accumulation of amylin deposits, which is very important for the prevention of CKD development and progression in diabetes.
In patients with T2D and LADA, serum amylin levels significantly increase progrediently with the stages of development of CKD and albuminuria categories. The degree of amylinemia correlates with insulin resistance and renal function, which indicates its role in the development and progression of CKD in this category of patients.
Conflict of interest
None declared.