Serum neuregulin 1, a potential noninvasive biomarker for detecting cardiometabolic risk in type 2 diabetes

The researchers found a robust relationship between serum NRG-1 levels and hyperglycemia, subclinical atherosclerosis, insulin resistance, and cardiac dysfunction in type 2 diabetes patients.

Neuregulin 1 is one of the members of the members of the epidermal growth factors (EGF) proteins. It was found to be released from the heart endothelial cells. It has antifibrotic and regenerative effects on the myocardium. NRG-1 and the ErbB receptors are expressed in the skeletal muscle, central nervous system, pulmonary cells, liver, kidney, and enterocytes.

There is a significant unmet clinical need for the identification of NRG-1's role in diabetes in humans and its relation to subclinical atherosclerosis, insulin resistance, and cardiovascular disease. To fill this knowledge gap, Emad Gamil Khidr, Al-Azhar University, Cairo, Egypt, and colleagues provide novel insights into the relationship between serum levels of NRG-1 and insulin resistance, subclinical atherosclerosis and cardiac dysfunction that occur in T2D.

The study included 50 patients with type 2 diabetes and 40 healthy gender- and age-matched controls. ELISA was used for measuring serum NRG-1. Lipid profiles, glycemic parameters, and insulin resistance were assessed. Carotid intima-media thickness (CIMT) and trans-thoracic echocardiography were studied for all study subjects.

The researchers reported the following findings:

• Type 2 diabetes patients had significantly lower serum NRG-1 levels than controls.
• Serum NRG-1 was negatively correlated with fasting blood glucose, age, HbA1c, blood urea, insulin resistance, serum creatinine and LDL-C, and positively correlated with HDL-C, eGFR and CIMT.
• Regarding echocardiographic variables, serum NRG-1 correlated positively with left ventricular global longitudinal strain and negatively with the E/Ea ratio.
• NRG-1 predicted subclinical atherosclerosis in type 2 diabetes patients at a cut-off value < 108.5 pg/ml with 78% sensitivity and 80% specificity.

"The findings point to the presence of a robust relationship between serum NRG-1 level and insulin resistance, cardiac dysfunction, and subclinical atherosclerosis in T2D patients," the researchers wrote. "Thus, NRG-1 may be a potential noninvasive biomarker for detecting cardiometabolic risk in T2D."

"Its positive effects on atherosclerosis and glucose metabolism render it a promising therapeutic target that merits further large-scale future studies," they concluded.

The limitation of the study is a relatively small study population sample size.

Reference:

Eldin, A. S., Fawzy, O., Mahmoud, E., Elaziz, O. H. A., Enayet, A. E. A., & Khidr, E. G. (2023). Serum neuregulin 1 in relation to ventricular function and subclinical atherosclerosis in type 2 diabetes patients. Endocrinología, Diabetes y Nutrición, 70(10), 619-627. https://doi.org/10.1016/j.endinu.2023.10.001