PATHOMORPHOGENESIS OF DIABETIC HEPATOPATHY IN PUBERTAL AGE: CLUSTER ANALYSIS OF MORPHOLOGICAL CHANGES

Considering that type 1 diabetes mellitus (DM) is the most common endocrine disorder in childhood and that glycemic control in adolescents often deteriorates under the influence of multiple factors, the aim of this study was to investigate morpho-functional changes in the liver of peripubertal rats with streptozotocin-induced diabetes mellitus (SIDM) using cluster analysis.Material and Methods. The study involved 16 three-month-old male Wistar rats divided into two groups: a diabetic group (SIDM was induced by a single intraperitoneal injection of streptozotocin at a dose of 7 mg/100 g body weight) and a control group. Histological, histochemical, electron microscopic, and statistical methods were conducted.Results. Using Ward’s hierarchical clustering method, three clusters of hepatocytes were identified in the classical hepatic lobule of three-month-old rats. Cluster 1 (C1) hepatocytes accounted for 40.06% of the measured cells, were predominantly localized in the peripheral zone, and exhibited the largest cell area with a low nuclear-to-cytoplasmic ratio (N/C ratio). Cluster 3 (C3) hepatocytes comprised 43% of the cells, were located in the central zone, and were characterized by the smallest cell area. Cluster 2 (C2) hepatocytes constituted 25.71%, were localized in the intermediate zone, and demonstrated the largest nuclear area and the highest N/C ratio.In the early stage of SIDM (day 14), against the background of hyperglycemia, consistent changes in the morphometric parameters of hepatocytes from different clusters were observed, including a decrease in cell area due to glycogenolysis, which was confirmed by histological and ultrastructural findings.By day 70 of SIDM, morphometric parameters of all hepatocyte clusters approached control values. The increase in hepatocyte area occurred due to the emergence of both young hepatocytes and dystrophically altered cells (granular, vacuolar, and ballooning degeneration). The largest proportion of cells belonged to C3 (50.34% and 44%), among which the highest number of young hepatocytes was observed. These cells were characterized by dense cytoplasm, a large number of immature mitochondria and glycogen granules, and hypertrophy of the rough and smooth endoplasmic reticulum.Conclusion. Thus, in the dynamics of morpho-functional changes in the liver of peripubertal rats with SIDM, two stages can be distinguished: stress-reactive changes (day 14) and compensatory-reparative processes (day 70).