BACKGROUND፡ Genetic variants that affect insulin signaling play an important role in insulin resistance (IR) in type 2 diabetes mellitus (T2DM). This study aimed to evaluate changes of the glycemic profile and IR in T2DM with comorbid obesity and chronic pancreatitis (CP) considering the allele status of the IRS1 gene (rs2943640).METHODS: The study involved 33 type-2 diabetic patients and 10 healthy individuals. The IRS-1 gene rs2943640 C>A polymorphism was genotyped using the TaqMan real-time PCR method.RESULTS: In type 2 diabetic patients regardless of the presence/absence of comorbid obesity and CP glycemic profile parameters significantly did not differ between carriers of allele С or allele A of the IRS1 gene (rs2943640). At the same time significantly higher HOMA-IR (by 2.25 times) was established in carriers of the C allele. In type 2 diabetic patients with both comorbidities (carriers of the C allele) the maximum HOMA-IR was established, which significantly differed from the data of patients with only T2DM and patients with comorbid obesity. In carriers of the A allele significantly higher level of HOMA-IR was found in patients with comorbid obesity and CP vs patients with only T2DM, and also in patients with comorbid obesity vs patients with only T2DM.CONCLUSIONS: Presence of the C allele of the IRS1 gene (rs2943640) may indicate risk of high IR in type 2 diabetic patients regardless of the presence/absence of comorbid obesity and CP; here with CP is a more important factor in IR progression then obesity.KEYWORDS: Type 2 diabetes mellitus, comorbidities, insulin resistance, IRS1 gene