Lack of glycemic control in type two diabetes mellitus patients is associated with reduced serum epidermal growth factor level and increased insulin resistance.

Abstract

The prevalence of type 2 diabetes mellitus (T2DM) is steadily increasing worldwide in an alarming fashion. Importantly, poor glycemic control is associated with development of various health sequalae's due to glucolipotoxicity, oxidative stress and increased inflammatory cytokines. The aim of the present study was to examine the effect of glycemic control on the relative abundance of inflammatory markers in patients with controlled and uncontrolled T2DM, and to test their association with the glycemic status in diabetic patients in Jordan. An observational cross-sectional study design was used. Patients with T2DM with controlled diabetes [glycated hemoglobin (HbA_1c) ≤7.0%, n=110] and age-, sex- and body mass index (BMI)-matched uncontrolled diabetic patients (HbA_1c >7.0%, n=105) were recruited. An antibody membrane array was used to examine the relative abundance of inflammatory cytokines and growth factors in the sera of the study subjects, followed by enzyme-linked immunosorbent assay (ELISA) to confirm the results. Fasting blood glucose, serum insulin, triglyceride and homeostatic model assessment for insulin resistance (HOMA-IR) score were significantly elevated in the uncontrolled T2DM group (P<0.05). Antibody membrane array showed that serum epidermal growth factor (EGF) is significantly decreased in the uncontrolled T2DM group, and this was confirmed by ELISA (158.77±111.7 vs. 95.9±82.7 pg/ml, P=0.002). The binary logistic model was used to predict the likelihood of being uncontrolled diabetic based on EGF levels. After controlling for age, sex and BMI, EGF was statistically associated with diabetes control, where lower EGF levels predicted uncontrolled diabetes. Additionally, Pearson's product-moment correlation showed a statistically significant negative correlation between EGF and HbA_1c (r=-0.25, P<0.0001), and a positive correlation between HOMA-IR and HbA_1c, (r=0.32, P<0.0001). The current data identify a novel link between serum EGF levels and the status of HbA_1c indicative of diabetic control.