Does metformin improve vascular heath in children with type 1 diabetes? Protocol for a one year, double blind, randomised, placebo controlled trial

BACKGROUND: Cardiovascular disease is the leading cause of mortality in Type 1 diabetes (T1D). Vascular dysfunction is an early and critical event in the development of cardiovascular disease. Children with T1D have vascular dysfunction therefore early interventions to improve vascular health are essential to reduce cardiovascular mortality in T1D. Metformin is an insulin sensitising agent which is known to improve vascular health outcomes in type 2 diabetes (T2D) and other individuals with insulin resistance. It has been used safely in children and adolescents with T2D for over 10 years. This study aims to assess the effect of metformin on vascular health in children with T1D. METHODS/DESIGN: This study is a 12 month, double blind, randomised, placebo controlled trial to determine the effect of metformin on vascular health in children (age 8–18) with T1D. The sample size is 76 with 38 children in the metformin group and 38 children in the placebo group. Vascular health and biochemical markers will be measured at baseline, 3, 6 and 12 months. Vascular function will be measured using flow mediated dilatation and glyceryl trinitrate mediated dilatation of the brachial artery and vascular structure will be measured with carotid and aortic intima media thickness, using standardised protocols. DISCUSSION: This study will be the first to investigate the effect of metformin on vascular health in children with T1D. It will provide important information on a potential intervention to improve cardiovascular morbidity and mortality in this population at high risk from cardiovascular disease. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTRN12611000148976