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 genetic determinant for glycemic control in T2DM patients during severe/acute phase hyperglycemia.Keywords: Insulin receptor substrate, Gene, Polymorphism, Diabetes, Insulin resistance,Hyperglycemia, IRS 1, IRS 2

Highlights

  • Primary acute illnesses or diseases are a major threat for hospitalisation in severe or acute hyperglycemic attacks in type 2 diabetes mellitus (T2DM) patients. [1,2]

  • Insulin Receptor Substrate (IRS) genes mainly Insulin Receptor Substrate 1 (IRS1) and Insulin Receptor Substrate 2 (IRS2) are the most speculated genes to influence the glycemic control based on their key roles to maintain the basic functions of cell growth, survival, and metabolism [4]

  • This study found that neither IRS1 nor IRS2 gene polymorphisms correlated with glycemic control during severe hyperglycemia or acute phase

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Summary

INTRODUCTION

Primary acute illnesses or diseases are a major threat for hospitalisation in severe or acute hyperglycemic attacks in type 2 diabetes mellitus (T2DM) patients. [1,2]. This study aims to identify IRS 1 and IRS2 gene polymorphisms that could possibly influence the management and treatment of T2DM during severe/acute phase hyperglycemia. Centrifuge (Eppendorf, Hamburg, Germany), Water bath (Memmert, Schwabach, Germany), UV-160A spectrophotometer (Shimadzu, Kyoto, Japan), PTC-100TM thermocycler (MJ Research Inc., Watertown, MA, USA), Fluorchem FC2 gel documentation system (Alpha Innotech, MultimageTM, USA), were used in this study. This was a prospective study carried out in the medical wards in which 156 patients at National University of Malaysia (UKMMC) were recruited as earlier described [5]. SNP and its association with glycemic control in T2DM patients with severe/acute phase hyperglycemia were studied. This situation proves that the results of the PCRRFLP method are applicable

RESULTS
DISCUSSION
American Diabetes Association
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