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 (X2 = 5.09, p = 0.023) in T2DM patients with severe/acute hyperglycemia. IRS2 polymorphisms were not associated with insulin resistance (X2 = 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.Keywords: Insulin receptor substrate, Genetic, Polymorphism, Diabetes, Insulin resistance, Hyperglycemia, IRS1, IRS

Fatty acids composition of microalgae Chlorella vulgaris can be modulated by varying carbon dioxide concentration in outdoor culture

Varying culture methods of Chlorella vulgaris (CV) has been associated with different nutrient composition. The aim of this study was to investigate the fatty acid contents and other nutrients of CV subjected to various culturing conditions. We found that CV cultured under 24 h light and 10% CO2 showed the best growth rates and contained higher lipid, protein and moisture contents compared to other culture conditions. Interestingly, the content of fatty acids of CV was dependent on the amount of CO2. Fatty acid analysis of CV by gas chromatography-mass spectrometry (GC-MS) showed the presence of cis-10-pentadecanoic acid (C15:1), palmitic acid (C16:0), palmitoleic acid (C16:1), heptadecanoic acid (C17:0), stearic acid (C18:0), oleic acid (C18:1n9c), linoleic acid (C18:2n6c), linolenic acids (C18:3n3) and arachidic acid (C20:0). Remarkably, polyunsaturated fatty acids (linoleic and linolenic acids) are found in abundance compared to other fatty acids in CV. The concentrations of palmitic, oleic, linoleic and linolenic acids increased when the amount of carbon dioxide was raised from 1 to 10% under both culture conditions (12 and 24 h light). This study shows the possibility of modifying lipid contents in freshwater microalgae by varying the amount of carbon dioxide and light.Key words: Chlorella vulgaris, microalgae, fatty acids, vitamins, minerals, carbon dioxide

Effect of Interaction between Polymorphisms in Insulin Receptor Substrate Genes in Type 2 Diabetes Mellitus Patients with Severe/Acute Hyperglycemia

Purpose: To investigate whether there are interactions between insulin receptor substrate 1 (IRS1) and insulin receptor substrate 2 (IRS2) that are associated with increased insulin resistance during such episodes.Methods: Testing Haplotype EffectS in Association Studies (THESIAS) software was used to investigate allelic and haplotype interactions between the polymorphisms in 156 T2DM patients with severe or acute hyperglycemia.Results: Binary analysis showed there were significant differences in the haplotype frequencies for the IRS1 and IRS2 polymorphisms based on the insulin resistance status. Nevertheless, estimation of haplotype effects by equality analysis showed no significant interactions (likelihood ratio tests: all p > 0.05) in increased insulin resistance in T2DM patients with severe/acute hyperglycemia.Conclusion: There are no interactions between IRS1 rs1801278 (p.Gly972Arg) and IRS2 rs1805097 (p.Gly1057Asp) polymorphisms that would affect insulin resistance in T2DM patients with severe/acute hyperglycemia.Keywords: Insulin receptor substrate, Proteins, Insulin resistance, Diabetes mellitus, Hyperglycemia, Haplotype, Genetic polymorphis

A Prospective Cohort Study of IRS Genes Polymorphisms in Type 2 Diabetes Mellitus Patients during Severe/Acute Hyperglycemia Phase. 2: Association with Glycemic Control

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