The dissertation presents a new, scientifically established theoretical generalization and solution of the current problem, which was to establish the main pathogenetic features of the comorbid course of type 2 diabetes mellitus combined with obesity and arterial hypertension.
Significantly higher values of insulin and HOMA index were found in the combined course of type 2 diabetes mellitus (T2DM) with overweight and arterial hypertension against the data in T2DM and normal body weight (p<0.05). It was shown that carbohydrate metabolism in T2DM is affected by both arterial hypertension and body mass index, which is confirmed by the established significant changes of carbohydrate metabolism indices.
It was noted that both overweight/obesity and arterial hypertension affect the severity of lipid metabolism disorders, but as the body mass index increases, the number of T2DM patients with dyslipidemia increases too, characterized by exceeding the target levels of triacylglycerols (TG) and non-high-density lipoprotein cholesterol (non-HDL-C), while in most patients with T2DM and arterial hypertension, only the concentration of TG exceeds the target values. Optimal cut-off points of a ROC curve for lipid profile values were proposed, which determine the relative risk of macrovascular complications in patients with T2DM in combination with subclinical hypothyroidism: TG > 1.65 mmol/L, non-HDL-C > 3.74 mmol/L and remnant cholesterol (RC)>0.74 mmol/L.
It was established that the presence of the C allele of the IRS1 gene (rs2943640) in both homozygous and heterozygous states may increase the risk of comorbid course of T2DM, obesity and arterial hypertension. It was shown that in T2DM patients, regardless of the presence of C or A allele of the IRS1 gene (rs2943640), carbohydrate metabolism indices are affected by comorbidity, in particular, obesity and arterial hypertension. Analysis of lipid profile indices, depending on the presence of C/A alleles of the IRS1 gene (rs2943640) in patients, included in the study, showed a significantly lower concentration of HDL-C (by 20.3 %, p = 0.029) and higher concentration of non-HDL-C (by 39.4 %, p = 0.042) in carriers of the C allele, in relation to carriers of the A allele of the IRS1 gene (rs2943640). The carriers of the C allele of the IRS1 gene were found to have significantly higher concentrations of TG (by 164.6 %) and RC (by 161.4 %) in T2DM patients and obesity in relation to patients with T2DM. At the same time, the carriers of CC genotype have the highest concentration of TC, LDL-C, TG, non-HDL-C and RC, and the lowest levels of HDL-C, relative to carriers of CA and AA genotypes of the IRS1 gene (rs2943640). Patients with comorbid course of T2DM, obesity and hypertension, carriers of the AA genotype, compared to patients with T2DM have significantly higher concentrations of TC (by 27.5 %), LDL-C (by 36.3 %), TG (by 119.6 %), non-LDL-C (by 49.8 %) and RC (by 119.6 %), significantly lower - the concentration of HDL-C (by 29.1 %).
