A randomized, double blind, placebo-controlled pilot trial of the safety and efficacy of atorvastatin in children with elevated low-density lipoprotein cholesterol (LDL-C) and type 1 diabetes

Background: Children with type 1 diabetes (T1D) and elevated LDL-C have an increased risk for cardiovascular disease, a process that can begin in childhood. Objective: To assess the safety and efficacy of atorvastatin improving lipid profiles in children with T1D and elevated LDL-C. Subjects: Sixty children (31M/29F) with T1D, mean age: 15 +/- 0.3 yr, mean diabetes duration: 6.8 +/- 0.5 yr, HbA(1c): 8.8 +/- 0.2%, with mean LDL-C 124 +/- 4.0mg/dl were recruited. Methods: After a 3-month run-in period, subjects were randomized double-blindly to atorvastatin or placebo for 6 months. Lipoprotein subfractions were measured by ion mobility and glucose control by HbA1C; continuous glucose monitors were worn quarterly. Results: After a run-in period, 42 subjects were randomized. There were decreases in total cholesterol (-21%), LDL-C (-32%), non-HDL-C (-31%) and apoB (-26%) in the atorvastatin group versus placebo (p < 0.001). Lipoprotein subparticles (LDL-large 1 and 2A, IDL-large and small, VLDL- medium and small) decreased with statins (p < 0.03 all). Insulin sensitivity scores remained constant in both groups and correlated inversely with apoB (r = -0.312 p = 0.039) and small LDL 3A (r = -0.404 p = 0.007). One subject had asymptomatic elevation of creatinine kinase which normalized after atorvastatin discontinuation. Conclusions: Atorvastatin lowered LDL-C, apoB, and atherogenic lipoprotein subparticles in children with T1D and elevated LDL-C without worsening insulin resistance. The drug was well tolerated and safe. Long-term studies would provide better insight on the impact of these interventions in the development of cardiovascular disease in children with diabetes.