A Prospective Cohort Study on IRS Gene Polymorphisms in Type 2 Diabetes Mellitus Patients during Severe/Acute Hyperglycemia Phase 1: Association with Insulin Resistance

Purpose: To investigate the genetic polymorphisms that may contribute to the worsening of insulin resistance in type 2 diabetes mellitus (T2DM) with severe or acute hyperglycemia. Methods: This is a prospective cohort study involving 156 T2DM patients with severe or acute hyperglycemia from all medical wards of the National University of Malaysia Medical Centre (UKMMC) that were placed on insulin therapy. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the genetic association of insulin receptor substrate (IRS) gene with insulin resistance. Insulin resistance status was determined using the homeostatic model assessment for insulin resistance (HOMA-IR) index. Results: IRS1 polymorphisms were associated with increased insulin resistance (X = 5.09, p = 0.023) in T2DM patients with severe/acute hyperglycemia. IRS2 polymorphisms were not associated with insulin resistance (X = 0.69, p = 0.406) in this group of patients. Conclusion: IRS1 genetic factor alone may be a significant genetic determinant for insulin resistance in T2DM patients during severe/acute phase hyperglycemia.