For the first time, it was established that the frequency of astheno-vegetative syndrome, the intensity of hepatomegaly, steatosis of hepatocytes, and the stage of fibrosis (p<0.05) in patients with NASH prevailed among comorbidities with DM2 and DKD in patients with NASH compared to the course of DM2 without DKD, as well as the frequency of manifestation mesenchymal inflammation, higher activity of enzymatic markers of cholestasis, deeper disorders of pigment metabolism, decrease in the protein-synthetic function of the liver, which depended on the stage of DKD (р<0.05).
For the first time, it was investigated that the course of NASH with concomitant DM2 under the conditions of DKD is characterized by a higher level of fasting glycemia, postprandial hyperglycemia, the content of glycosylated hemoglobin in the blood, insulin, HOMA IR, deepening of the lipid distress syndrome with a probable increase in the content of total lipids in the blood, total cholesterol.
For the first time, it was established that the course of NASH with DM2 is characterized by an increase in the activity of collagen synthesis with a simultaneous inhibition of its breakdown due to a decrease in the activity of collagenolysis with an increase in the stage of DKD (p<0.05). For the first time, a higher degree of degradation of fucoglycoproteins was registered in NASH with DM2 and DKD compared to NASH and DM2 without DKD and maximum activation of hexosamine synthesis in the ЕCM of the liver (p<0.05).
For the first time, the negative influence of comorbidity with NASH on indicators of the functional state of the kidneys in patients with DM2 with DKD was established, in which hypoalbuminemia, blood creatinine and urea content were probably higher; lower GFR, higher level of albuminuria; creatinine content in urine, A/C ratio (р<0.05) than without NASH.
For the first time, the pathogenetic concept of the mutual burden of comorbid conditions - NASH with DM2 and DKD, which consists in significantly higher activation of the lipid distress syndrome, insulin resistance, oxidative stress, endogenous intoxication, systemic proteolysis against the background of insufficient factors of the glutathione system, compared to the course without DKD, which contributes to the progression of endothelial dysfunction, the formation of a hypercoagulation syndrome with the activation of primary platelet hemostasis against the background of inhibition of fibrinolysis (p<0.05), which depended on the stage of DKD (p<0.05), and contributed to an increase in the degree of steatosis of hepatocytes, the intensity of their apoptosis , increasing the activity of clinical and biochemical NASH syndromes and the intensity of liver fibrosis (p<0.05).
For the first time in the complex therapy of NASH, DM2, and DKD, the effectiveness of the use of EРL and quercetin as part of complex therapy was proposed and proven, which contributed to a significant reduction in the frequency and intensity of clinical and biochemical syndromes of NASH, a decrease in the degree of steatosis of hepatocytes, optimization of the blood lipid spectrum with a decrease in the atherogenic index, degree IR, endogenous intoxication, oxidative stress as a result of the restoration of the content of RG in the blood (p<0.05), as well as the restoration of the functional state of the endothelium and the elimination of manifestations of hypercoagulation syndrome. The maximum nephroprotective ability in DKD according to indicators of increased GFR, decreased albuminuria and achievement of positive dynamics of the A/C ratio was established with the use of the EPL complex with quercetin (р<0.05).
For the first time in the treatment of patients with NASH, DM2, and DKD, the effectiveness of the use of bicyclol as part of complex therapy was proposed and proven, which contributed to a significant reduction in the intensity of manifestations of astheno-vegetative syndrome, dyspepsia, elimination of hepatomegaly, splenomegaly, abdominal discomfort, and cholestasis (р<0.05), the activity of biochemical syndromes of NASH, elimination of endotoxicosis, reduction of the degree of steatosis of hepatocytes, liver fibrosis index (p<0.05) due to optimization of the spectrum of ECM connective tissue components with a decrease in the blood content of collagen anabolism markers (protein-bound oxyproline), an increase in blood content markers of collagen catabolism (free oxyproline) due to the activation of blood CLA, a decrease in the blood content of hexosamines and carbohydrate-protein markers of degradation of fucoglycoproteins of ECM of the liver (p<0.05), as well as a decrease in the intensity of lipid distress syndrome, the degree of IR, restoration of antioxidant protection, inhibition of systemic proteolysis, reduction of ED manifestations, but to a lesser extent than EPL and quercetin therapy (p<0.05).
