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A Prospective Cohort Study of IRS Genes Polymorphisms in Type 2 Diabetes Mellitus Patients during Severe/Acute Hyperglycemia Phase. 2: Association with Glycemic Control Huri, Hasniza Zaman; Makmor-Bakry, Mohd; Hashim, Rosnani; Mustafa, Norlaila & Ngah, Wan Zurinah Wan Abstract Purpose: To investigate the genetic polymorphisms that may contribute to the worsening of glycemic control in type 2 diabetes mellitus (T2DM) with severe or acute hyperglycemia. Methods: The prospective cohort study included 156 T2DM patients with severe or acute hyperglycemia from all medical wards of the National University of Malaysia Medical Centre (UKMMC) that were treated with insulin therapy. For the genetic association study, we used the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The glycemic control assessment during the acute phase was based on the degree to which the patient achieved the targeted glucose levels. The primary outcome was the influence of IRS gene on glycemic control in T2DM patients with severe/acute phase hyperglycemia. Results: Insulin Receptor Substrate 1 (IRS1) (R2 = -0.023, p = 0.771) and Insulin Receptor Substrate 2 (IRS2) gene polymorphisms (R2 = -0.160, p = 0.046) were not associated with glycemic control in T2DM patients with severe/acute hyperglycemia. Conclusion: The IRS1 and IRS2 genetic factors may not be significant Keywords Insulin receptor substrate; Gene; Polymorphism; Diabetes; Insulin resistance; Hyperglycemia; IRS 1; IRS 2

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