Disorders of Proteoglycan and Collagen Metabolism in the Kidneys in Diabetes Mellitus: Clinical and Pathogenetic Mechanisms and Laboratory Markers
Authors:   National University of Pharmacy. 53, Pushkinska St., Kharkiv 61002, Ukraine, Morozenko D. V. ,   Sytenko Institute of Spine and joint Pathology, Academy of Medical Science, Ukraine. 80, Pushkinskaya St., Kharkiv 61024, Ukraine, Yeromenko R. F. ,   National University of Pharmacy. 53, Pushkinska St., Kharkiv 61002, Ukraine, Gliebova K. V. ,   National University of Pharmacy. 53, Pushkinska St., Kharkiv 61002, Ukraine, Timoshenko O. P. ,   Kharkiv State Zooveterinary Academy. 1, Akademichna St., Mala Danylivka 62342, Dergachivs’kiy district, Kharkiv region, Ukraine, Zakharyev A. V. ,   National University of Pharmacy. 53, Pushkinska St., Kharkiv 61002, Ukraine
Published: December 2020

The article considers the issue of disorders of connective tissue metabolism in diabetes mellitus. Glycosylation of structural components of connective tissue and glucose toxicity have been found to determine the pathogenesis of late complications of diabetes mellitus. The most common concept of the pathogenesis of diabetes is metabolic, according to which all variants of diabetes mellitus, including blood vessels, their basement membrane, are associated with primary disorders of lipid, glycoprotein, protein and carbohydrate metabolism due to complete or partial insufficiency. It has been found that the formation of interstitial fibrosis in the kidneys of patients with diabetes begins in the preclinical stages of diabetic nephropathy. The leading cause of interstitial fibrogenesis is hyperglycemia; exacerbate proteinuria fibrosis, activation of the renin-angiotensin system, chronic inflammation and the formation of myofibroblasts in the interstitium. According to the results of the study of aspects of early diagnosis of kidney damage in type 1 diabetes mellitus, it was found that the development of diabetic nephrosclerosis is characterized by qualitative and quantitative changes in collagen composition in the glomeruli and interstitium, rebalance between collagen synthesis and breakdown, glycosaminoglycans, increased synthesis of fibrogenic growth factors and oxidative modification of proteins. The formation of diabetic nephropathy in patients with diabetes is also characterized by the accumulation of collagen types IV and VI, the appearance of interstitial collagen types III and I in the glomeruli, as well as the accumulation of collagen of all types in tubulointerstitium. Quantitative and qualitative characteristics of sulfated glycosaminoglycans of urine in human diabetes indicated different degrees of development of diabetic nephropathy. Glycosaminoglycans hyperexcretion was observed in patients with diabetes mellitus without proteinuria. In patients with microalbuminuria, glycosaminoglycans hyperexcretion was even more pronounced. It was also found that in diabetes, the total excretion of sulfated glycosaminoglycans in the urine doubles. Conclusion. Thus, in diabetes mellitus, an important pathogenetic link in the violation of the morpho-functional state of the kidneys is the degradation of collagen and proteoglycans of the basement membranes of the glomeruli, as well as interstitial fibrosis. This is reflected in changes in urinary glycosaminoglycans excretion, in particular heparansulfate and chondroitin sulfate, which may serve as a marker of proteoglycan metabolism disorders in the kidneys. Patients with diabetes also have an increase in the urine of hydroxyproline, which indicates an increase in the intensity of collagen metabolism in patients