Pharmacogenetic Influence of Calpain-10 Gene SNP-43 Polymorphism on Response to Metformin in Type Two Diabetes Mellitus Patients

Abstract

Abstract

Background: Diabetes is a complex and multifaceted metabolic disorder characterized by elevated blood glucose levels resulting from either insulin resistance, insufficient insulin synthesis, or both. Metformin is often administered as one of the first oral hypoglycemic medications. The first diabetes gene to be discovered via a genome scan is the Calpain-10 (CAPN10) gene, which is linked to the onset of type 2 diabetes mellitus and insulin resistance as well as glucose metabolism and pancreatic beta- cell function. It makes the translocation of GLUT4 easier. Within the beta-cell, CAPN10 is most likely a sensor and an insulin exocytosis that acts at the mitochondria and the plasma membrane, respectively.

Methods: This prospective cohort study included one hundred five patients who were recently diagnosed with type 2 diabetes mellitus. The ages exhibited variation, with an average age of 55.33 and a standard deviation of 9.79. Each patient had a three months period between the first blood sample, which was collected at the time of diagnosis prior treatment had started, and the second sample, which was taken 12 weeks later.

Results: Following the administration of metformin medicine, there was a significant reduction in the mean BMI (p < 0.01). The fasting plasma glucose, plasma insulin, HbA1c, and insulin resistance (measured by the HOMA-IR index) showed a substantial drop (p< 0.001), whereas insulin sensitivity (measured by the QUICKI) exhibited a significant rise (p< 0.001). There was a significant reduction in the lipid profile (p< 0.001), with the exception of an increase in the mean HDL level. Gender variations in glycemic control measurements suggest that males exhibit higher average values compared to women, while women demonstrate superior management of lipid profiles in comparison to men. However, it is important to note that these differences do not reach statistical significance (p<0.05). Post-treatment HbA1c differed significantly across genotypes (p = 0.01), with carriers of the A variant exhibiting poorer metabolic responses compared with the GG genotype.

Conclusion: Metformin has demonstrated significant improvements in serum lipid profiles, insulin levels, fasting plasma glucose, HbA1c, the insulin resistant index (HOMA-IR), and the insulin sensitivity index (QUICKI) in individuals recently diagnosed with type 2 diabetes mellitus. However, the CAPN10 rs3792267 (SNP-43) polymorphism was associated with variability in treatment response. Carriers of the A allele showed higher post-treatment HbA1c levels and less favorable metabolic outcomes compared with GG homozygotes, suggesting a potential pharmacogenetic influence of CAPN10 on metformin efficacy.