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

Pediatr Diabetes. 2015 Mar;16(2):79-89. doi: 10.1111/pedi.12245. Epub 2014 Nov 22.

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.

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.

Trial registration: ClinicalTrials.gov NCT01236365.

Keywords: Adolescents; Cardiovascular Disease; HMG-CoA; Statins.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Atorvastatin
  • Child
  • Cholesterol, LDL / blood
  • Combined Modality Therapy / adverse effects
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / diet therapy
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / therapy
  • Diet, Diabetic
  • Diet, Fat-Restricted
  • Double-Blind Method
  • Drug Monitoring
  • Exercise
  • Female
  • Glycated Hemoglobin / analysis
  • Heptanoic Acids / administration & dosage
  • Heptanoic Acids / adverse effects
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / complications
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / therapy
  • Hyperglycemia / prevention & control
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use
  • Insulin / administration & dosage
  • Insulin / therapeutic use
  • Insulin Resistance
  • Male
  • Pilot Projects
  • Pyrroles / administration & dosage
  • Pyrroles / adverse effects
  • Pyrroles / therapeutic use*

Substances

  • Cholesterol, LDL
  • Glycated Hemoglobin A
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypoglycemic Agents
  • Insulin
  • Pyrroles
  • hemoglobin A1c protein, human
  • Atorvastatin

Associated data

  • ClinicalTrials.gov/NCT01236365