Aim:
Background: Lifelong exogenous insulin is cornerstone of treatment type 1 diabetes mellitus (T1DM). The efficacy of insulin in achieving glycemic control depends on its binding affinity to the insulin receptor (INSR). Insulin sensitivity can be influenced by various factors, including genetic polymorphisms. Single nucleotide polymorphisms (SNPs) in the INSR gene may affect the efficacy of exogenous insulin in achieving glycemic control in T1DM, potentially leading to insulin resistance. Genetic mapping of the INSR gene aims to identify the precise loci of SNPs, offering deeper insights into the diminished therapeutic response. Aims: this cross-sectional pharmacokinetic study is of significant interest, as it presents innovative approaches in precision medicine. Novel applications of genome engineering technologies for targeted gene corrections may have substantial therapeutic implications.

Material and methods:
Method: The effect of the SNP rs2229429 G>A have been investigated in 99 T1D individuals, with a mean age of 12.3 years. These patients were managed with exogenous insulin through a basal-bolus monotherapy regimen. Genotyping was performed using an allele-specific polymerase chain reaction technique, and the data were statistically analyzed.

Results:
Results: Results revealed the prevalence of the minor allele frequency is 12% in a sample of Iraqi population. Homozygous mutant carriers of rs2229429 G>A were 10.479 times at higher risk for developing poor glycemic control (HbA1c >86 mmol/mol) compared to wild genotype in T1DM (p=0.008). Ultimately poor responders to exogenous insulin, demonstrating significantly higher plasma insulin receptors levels (p<0.001).

Conclusions:
Conclusion: The investigated SNP is firmly correlated with hyperglycemia in T1DM and contributes to the development of double diabetes.