Endocrine Abstracts

Background: Poor glycemic control in patients with type two diabetes mellitus (T2DM) is a strong risk risk factor for the development of complications and is associated with increased mortality. A growing body of evidence has demonstrated a role of the epidermal growth factor (EGF) in glucose homeostasis. The EGF contributes to the function, survival and proliferation of the β cells of the pancreas. The EGF also influences the action of insulin via the modulation of insulin receptor expression and downstream signaling pathways. The collective effect of these actions regulates glucose uptake, utilization and sensitivity to insulin. Given the above, it is conceivable that the EGF could also be associated with glycemic control in T2DM patients. Variations in the EGF gene, including single nucleotide polymorphisms (SNPs), could affect the level of the coded EGF protein. Hence, this investigation tested the association of rs4444903 SNP in the EGF gene, EGF protein and EGF mRNA levels with glycemic control.

Methods: In this case-control study, a total of 330 patients with T2DM were recruited. Cases were patients with poor glycemic control and controls were patients with good glycemic control. Blood samples were collected for DNA extraction and measurement of the EGF protein. An enzyme-linked immunosorbent assay (ELISA) was used to quantify levels of the EGF. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine EGF rs4444903 genotype. An additional set of 42 patients per group was recruited to determine EGF mRNA expression in peripheral monocytes. mRNA levels were quantified using qPCR.

Results: Patients with poor glycemic control had significantly lower levels of EGF compared to controls (P<0.05). GA genotype of rs4444903 was significantly more frequent among the poor glycemic control group (P<0.05). Multivariate regression analysis confirmed this association and showed that EGF levels significantly lowered the risk of poor glycemic control (OR=0.99, 95%CI:0.98-0.99, P<0.001). In this analysis, the GA genotype was associated with an increased risk of poor glycemic control (OR=1.96, 95%CI:1.02-3.57, P=0.04). Cases had a markedly reduced expression of EGF mRNA (60% of the expression levels observed in the controls).

Conclusion: This study revealed the association between EGF genetic variation, protein and mRNA expression with glycemic control. Future studies should provide more insights into the molecular mechanism(s) of this association and the role of the EGF in the management of poor glycemic in T2DM.]