IMPE Abstracts

Background: Neuregulin-4 (Nrg4), a recently identified adipokine, has been found in multiple organs, in particular brown adipose tissue. Lower Nrg4 levels have been associated with obesity, insulin resistance, impaired glucose tolerance and type 2 diabetes mellitus (T2DM). Metformin is widely utilized for treatment of T2DM due to its ability to improve glycemic control. It has shown some potential in preclinical studies to improve diabetic nephropathy, decrease advanced glycation end products, which mediate some diabetic complications, decrease oxidative stress in endothelial cells and tends to reduce cardiovascular morbidity and mortality. However, no enough data as regards metformin effect on vascular health and microvascular complications in pediatric patients with T1DM.

Objectives: Therefore, we performed a randomized-controlled trial to assess the effect of oral supplementation with metformin on glycemic control, lipid profile, Nrg4 levels and carotid intima media thickness (CIMT) as a marker for subclinical atherosclerosis in pediatric T1DM patients with micro-vascular complications.

Methods: This study included 100 children and adolescents with T1DM. Enrolled patients aged 12-20 years with disease duration ≥ 5 years and have microvascular complications. Patients were randomly assigned into two groups; intervention group who received oral metformin tablets 500 mg once daily. The other group did not receive any supplementation and served as a control group. Both groups were followed-up for 6 months with assessment of fasting blood glucose (FBG), HbA1c, Nrg4 levels, lipid profile, c-reactive protein (CRP), urinary albumin creatinine ratio (UACR) and CIMT.

Results: Both groups were well-matched as regards baseline clinical characteristics and laboratory parameters (P>0.05). After 6 months, metformin therapy for intervention group resulted in a significant decrease of FBG, HbA1c, total cholesterol, C-reactive protein (CRP), urinary albumin creatinine ratio (UACR) and CIMT while Nrg4 levels were increased compared with baseline levels (P<0.001) and compared with control group (P<0.001). Metformin therapy was well-tolerated with minor gastrointestinal disturbances (nausea, heartburn, flatulence and diarrhea). Baseline Nrg4 levels were negatively correlated to FBG, HbA1c, total cholesterol, CRP and CIMT (P<0.001 for all).

Conclusions: Metformin therapy improved blood glucose levels, glycemic control, dyslipidemia and elevated Nrg4 levels and hence, decreased inflammation, microvascular complications and subclinical atherosclerosis in pediatric patients with T1DM.