Effect of Metformin in Children With Type 1 Diabetes
Condition: Effect of Change in T1DM Glycemic Control
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Cardiovascular disease is the leading cause of mortality in type 1 diabetes mellitus (T1DM).
      Vascular dysfunction is an early and critical event in the development of cardiovascular
      disease. Children with T1DM have vascular dysfunction therefore early interventions to
      improve vascular health are essential to reduce cardiovascular mortality in T1DM. Metformin
      is an insulin sensitising agent which is known to improve vascular health outcomes in type 2
      diabetes mellitus (T2DM) and other individuals with insulin resistance. It has been used
      safely in children and adolescents with T2DM for over 10 years. This study aims to assess the
      effect of metformin on vascular health in children with T1DM.

      This is the first study to study effect of metformin on circulating neuregulin-4 levels as a
      marker for subclinical atherosclerosis.
    

Detailed description: 
      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.
    

Intervention name(s): metformin; Basal/bolus insulin
Intervention type(s): Drug; Drug
Intervention description(s): Oral hypoglycemic drug metformin; Basal/bolus insulin
Other intervention name(s): Glucophage
Intervention MeSH terms: Metformin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Neuregulin-4; metformin; Type 1 diabetes