The dissertation provides a new, scientifically based theoretical generalization and the solution of the current problem, which was to establish the basic genetic and metabolic patterns of comorbid course of type 2 diabetes mellitus in combination with obesity and chronic pancreatitis.
It was first established that the combination of type 2 diabetes mellitus (T2DM), obesity and chronic pancreatitis has a mutually aggravating course, which is due to common pathogenetic links, in particular, inflammation, insulin resistance and dyslipidemia, taking into account the polymorphism of IRS1 (rs2943640) and TP53 (rs1042522) genes. A dysfunctional and uncontrolled leukocyte response was shown in the comorbid course of T2DM with overweight/obesity and chronic pancreatitis. At the same time, in patients with T2DM with overweight/obesity without chronic pancreatitis there is a significant negative relationship between the percentage of segmented neutrophils and aminotransferase activity. Unidirectional changes of the lipid profile in patients with T2DM regardless of comorbidity with maximum disturbances in the combination of T2DM with overweight/obesity and chronic pancreatitis were detected. The severity of lipid metabolism disorders is affected by both overweight/obesity and chronic pancreatitis.
It was established that the combined course of type 2 diabetes, obesity and chronic pancreatitis is associated with the C allele (genotypes C/C and C/A) of the IRS1 gene (rs2943640), (p<0.05), as well as with the C allele in both homozygous and heterozygous states of the TP53 gene (rs1042522), (p<0.05). In patients with T2DM, as well as its combined course with obesity, an association was established between the IRS1 gene polymorphism (rs2943640) and lipid profile abnormalities, with maximum changes of the lipid profile recorded in carriers of the C/C genotype. Data of the lipid panel of carriers of the C allele of the TP53 gene (rs1042522) in the heterozygous state (genotype C/G) in patients with T2DM with concomitant obesity and chronic pancreatitis were significantly different from those in patients with T2DM and also in its combination with obesity, p<0.05. Carriers of the C allele of the IRS1 gene (rs2943640), patients with combined course of T2DM, obesity and chronic pancreatitis have the highest indices of insulin resistance, which are significantly higher from the results of patients with T2DM and patients with combined course of T2DM and obesity, which justifies the role of chronic pancreatitis in carriers of the C allele in the progression of insulin resistance at T2DM. Carriers of the A allele of the IRS1 gene (rs2943640) have significantly higher levels of insulin and HOMA-IR in patients with combined course of T2DM, obesity and chronic pancreatitis, as well as in patients with T2DM and obesity, relative to the results of patients with T2DM, indicating a significant contribution of obesity in the progression of insulin resistance at T2DM in these patients.
It was shown that at the comorbid course of T2DM, obesity and chronic pancreatitis in carriers of the C allele of the C/C genotype of the TP53 gene (rs1042522) have significantly higher insulin level in plasma and HOMA-IR compared to patients with T2DM without comorbidities, which indicates an important contribution of both chronic pancreatitis and obesity in the progression of insulin resistance at T2DM. Carriers of the G allele of the C/G genotype of the TP53 gene (rs1042522) with comorbid course of T2DM, obesity and chronic pancreatitis had significantly higher levels of glycemic profile and HOMA-IR values against control, indicating a risk of high resistance to insulin in patients with T2DM with concomitant course.
