Effect of Metformin in Children With Type 1 Diabetes

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by T-cell mediated destruction of the pancreatic b-cells, resulting in insulin deficiency and elevated blood glucose levels.

The increasing incidence of type 1 diabetes mellitus in many countries challenges health systems because the disease is presently incurable with no known method of prevention. Around 490,100 children live with the disease worldwide, with incidence estimated to be increasing in children under 15 years by 2.8% per year .This trend is particularly worrying because type 1 diabetes increases mortality and morbidity population-wide.

Vascular co-morbid diseases include retinopathy, which may cause reduced vision and blindness, and nephropathy, which may result in renal failure and require dialysis or kidney transplantation. This is in addition to hypertension, which is linked to peripheral, cardio- and cerebrovascular disease, the end points of which are limb amputations, cardiac failure, stroke and sudden death. As vascular complications curtail both life expectancy and quality of life development at younger ages when people are typically establishing Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by T-cell mediated destruction of the pancreatic b-cells, resulting in insulin deficiency and elevated blood glucose levels.

The increasing incidence of type 1 diabetes mellitus in many countries challenges health systems because the disease is presently incurable with no known method of prevention . Around 490,100 children live with the disease worldwide, with incidence estimated to be increasing in children under 15 years by 2.8% per year .This trend is particularly worrying because type 1 diabetes increases mortality and morbidity population-wide.

Vascular co-morbid diseases include retinopathy, which may cause reduced vision and blindness, and nephropathy, which may result in renal failure and require dialysis or kidney transplantation. This is in addition to hypertension, which is linked to peripheral, cardio- and cerebrovascular disease, the end points of which are limb amputations, cardiac failure, stroke and sudden death. As vascular complications curtail both life expectancy and quality of life development at younger ages when people are typically establishing careers and families is particularly detrimental .

Neuregulin 4 (Nrg4), a recently identified adipokine, has been found in multiple organs, in particular brown adipose tissue (BAT), and belongs to the epidermal growth factor (EGF) family of extracellular ligands. Overexpression of Nrg4 can reduce chronic inflammation through inhibiting the gene expression of macrophage marker monocyte chemotactic protein 1 (Mcp1) and enhancing the expression of M2 macrophage marker gene Cd163, demonstrating that Nrg4 may possess anti-inflammatory and anti-atherogenic properties. Lower Nrg4 levels have been reported to be associated with the percentage of body fat mass, liver fat content, obesity, IR, impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) .

Moreover, serum Nrg4 levels have been reported to be inversely associated with subclinical cardiovascular disease (CVD) in obese adults.

Recent studies reveal that neuregulin.4 may be closely associated with non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS). Many lines of evidence indicate that inflammation is closely associated with atherosclerosis and plays a crucial role in the development of CVD.

Biguanides sensitize body cells to insulin, which may cause a reduction of atherogenic lipid fractions in patients with type 2 diabetes.

Inclusion criteria

• Patients with type 1 diabetes mellitus (5 years duration at least) and with micro-vascular complications.
• Patients on regular visits to clinic.
• Patients on regular insulin therapy.

Exclusion criteria

• Any clinical evidence of infection, hematological diseases, tumors, liver dysfunction, urinary tract disorders, connective tissue disease, or other autoimmune diseases.