Cytokines Are Promising Diagnostic and Prognostic Biomarkers of Microvascular Complications of Diabetes Mellitus

In recent years, the classical knowledge about the pathogenesis of diabetes mellitus (DM) and its complications has been supplemented by ideas about the role of chronic inflammation. It has been established that inflammatory reactions play a role in beta cell dysfunction, the formation of insulin resistance, and vascular wall remodeling. Cytokines—soluble low-molecular proteins and peptides that perform information and regulatory functions—play a central role in the development of inflammation. A wide range of biological activity and involvement in many aspects of pathogenesis allow us to consider cytokines as promising molecules for the diagnosis and prognosis of complications of diabetes. In this review, we systematized data from studies that assessed the role of cytokines as diagnostic and prognostic markers for the development of microvascular complications of diabetes. Available evidence indicates that angiogenic and pro-inflammatory cytokines (VEGF, TNF-α, IL-6, IL-8, IL-15, IL-17, MCP-1, IP-10, INF-γ, PEDF, etc.) are promising biomarkers of proliferative diabetic retinopathy, especially when studying their local production (in the vitreous humor, aqueous humor, and tear fluid). The role of these molecules as indicators of nonproliferative diabetic retinopathy and diabetic macular edema merits further research. Serum pro-inflammatory and fibrogenic cytokines (primarily, MCP-1, IL-6, TNF-α, YKL-40, TGF-β, and bFGF) and cytokine receptors (sTNFR1, sTNFR2) are considered as promising diagnostic and prognostic markers of diabetic kidney damage. Urinary excretion of IL-6 and MCP-1 is a predictor of progression of diabetic nephropathy. Multiplex analysis and mass spectrometry make it possible to study panels of cytokines in small-volume samples of biological material. Combination biomarkers including multiple cytokines may improve the reliability of predicting diabetic complications.