title: 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.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Pediatric Endocrinology, Diabetes & Metabolism, Nemours Children's Clinic, Jacksonville, FL, USA.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Canas
authors.forename: Judith L
authors.initials: JL
authors.lastname: Ross
authors.forename: Martha V
authors.initials: MV
authors.lastname: Taboada
authors.forename: Kaitlin M
authors.initials: KM
authors.lastname: Sikes
authors.forename: Ligeia C
authors.initials: LC
authors.lastname: Damaso
authors.forename: Jobayer
authors.initials: J
authors.lastname: Hossain
authors.forename: Michael P
authors.initials: MP
authors.lastname: Caulfield
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Gidding
authors.forename: Nelly
authors.initials: N
authors.lastname: Mauras
mesh_terms: D000293:Adolescent; D000069059:Atorvastatin; D002648:Child; D008078:Cholesterol, LDL / Q000097:blood; D003131:Combined Modality Therapy / Q000009:adverse effects; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000178:diet therapy / Q000188:drug therapy / Q000628:therapy; D003927:Diet, Diabetic; D018752:Diet, Fat-Restricted; D004311:Double-Blind Method; D016903:Drug Monitoring; D015444:Exercise; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000628:therapy; D006943:Hyperglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D007333:Insulin Resistance; D008297:Male; D010865:Pilot Projects; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000069059:Atorvastatin; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D011758:Pyrroles; C517652:hemoglobin A1c protein, human
keywords: Adolescents; Cardiovascular Disease; HMG-CoA; Statins