The Impact of Calpain-10 Gene Polymorphisms on Therapeutic Response to Metformin at the crossroad Type Two Diabetes Mellitus Patients

Abstract

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 plasma membrane and the mitochondria, respectively. G homozygous for the recessive model SNP-43, who had a 19% increased risk of type 2 diabetes mellitus. This prospective cohort study included one hundred patients who were recently diagnosed with type 2 diabetes mellitus. The research was conducted in Al Diwaniyah Teaching Hospital, located in Diwaniya Governorate, Iraq. The ages exhibited variation, with an average age of 55.25 and a standard deviation of 9.88. Each patient had a 12-week period between the first blood sample, which was collected at the time of diagnosis before treatment had started, and the second blood sample, which was taken 12 weeks later. Following the administration of metformin medicine, there was a significant reduction in the average 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 average lipid profile levels (p< 0.001), with the exception of an increase in the average HDL level. Gender disparities 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). After three months of using metformin, we discovered a significant deterioration of glycemic control as measured by HbA1c (threshold of < 7%) (p = 0.01) and CAPN 10 gene SNP-43. Metformin has demonstrated efficacy in enhancing 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. A significant correlation was found between the lower response to metformin treatment and the CAPN-10 gene SNP-43.