OR11-2 Atorvastatin Safely Reduces Non-HDL Cholesterol in Children with Type I Diabetes (T1DM) and High LDL-C: Preliminary Results

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR11-Pediatric Endocrinology
Clinical
Saturday, June 15, 2013: 11:30 AM-1:00 PM
Presentation Start Time: 11:45 AM
Room 104 (Moscone Center)
Jose Atilio Canas*1, Judith L Ross2, Martha V Taboada3, Kaitlin Sikes1, Ligeia Damaso3, Jobayer Hossain4, Michael Phillip Caulfield5, Samuel Gidding6 and Nelly Mauras1
1Nemours Children's Clinic, Jacksonville, FL, 2Thomas Jefferson University, Philadelphia, PA, 3Nemours Children's Hospital, Orlando, FL, 4Alfred I duPont Hospital for Children, Willmington, DE, 5Quest Diagnostics Nichols Inst, San Juan Capistrano, CA, 6Alfred I duPont Hospital for Children, Wilmington, DE
Background: Dysglycemia, inflammation, and elevations in LDL-C and small dense lipoprotein (Lp) fractions increase the risk for early development of atheromatous plaque and micro- and macrovascular disease. These factors are especially concerning in children with T1DM.

Specific Aim: To investigate whether statin use in children with T1DM and elevated LDL-C has an acceptable safety profile and whether statins improve LDL-C and other atherogenic Lp concentrations.

 

Methods: Children with T1DM were recruited after appropriate consent for a multiarm study of cardiovascular risk: 80 children with LDL-C >90 mg/dl were targeted for a randomized clinical trial (RCT) and 28 non-diabetic, normal LDL-C, age-matched, lean children studied as controls. A 3-month run-in phase of intensification of diabetes and dietary management was followed by randomization to atorvastatin (Lipitor®, 10 mg titrated up to 20 mg) or placebo (PL) for 6 months. Safety parameters and adverse events (AEs) were monitored and Lp subfractions measured by a novel ion mobility assay (Quest Diagnostics).

 

Results: 82 children were recruited (39M/43F, mean age 15 ± 0.3 (SE) yr, mean diabetes duration 6.9 ± 0.4 yr, HbA1C 8.7 ± 0.2%, BMI 22.9 ± 0.4 kg/m2, with normal BP, and mean LDL-C 110 ± 3.0 mg/dl).  After a 3 month run-in, 40 dropped out - 49% due to improved LDL-C (<90 mg/dl) and others for miscellaneous reasons; none due to AEs. Lp subfractions were significantly higher in T1DM than in controls, particularly for most non-HDL subfractions. Mixed model analysis showed a significant decrease in total mean non HDL-C (nmol/L) at 6 months in the statins group (-554 ± 258) vs. PL (+529 ± 265, p=0.007). Lp subparticles (LDL-Large & Total, VLDL-Small & Medium, and ApoB) and the ApoB/A1 ratio significantly decreased in the statins group and remained the same or increased in PL. HbA1C was constant at 3 and 6 months post-randomization in both groups (p=NS). Both groups had a small, comparable number of AEs, with 1 SAE unrelated to statins. Creatine kinase and liver function tests were unchanged in both groups.

Conclusion: Atorvastatin significantly lowered LDL-C and atherogenic Lp subparticles in children with T1DM and elevated LDL-C. The drug was well tolerated and safe for 6 months. Ongoing studies on the relationship of Lp subparticles and dysglycemia measures will provide insight into the early development of cardiovascular disease in childhood T1DM.

 

Disclosure: MPC: Employee, Quest Diagnostics. Nothing to Disclose: JAC, JLR, MVT, KS, LD, JH, SG, NM

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Supported by Nemours Research Programs, with grant support from Quest Diagnostics and drug supply from Pfizer.