Statins in Children With Type 1 Diabetes and Hypercholesterolemia
Summary
Children with type1 diabetes (T1DM) have increased risk for cardiovascular disease (CVD) due to chronic increase in the blood sugars and inflammation. If there is also increased in cholesterol, it creates a highly abnormal environment not fully corrected by improved control of the blood sugars. CVD remains the principal risk of mortality in T1DM, and its prevention and treatment, compelling in children. This grant proposal encompasses 3 separate, yet interrelated projects addressing different aspects of CVD risk in children with T1DM. Project #1: a randomized controlled trial on the safety and efficacy of a class of drugs called "statins", which lower bad cholesterol in the body, in children with diabetes and elevated bad cholesterol. We will measure changes in concentration of blood inflammatory markers and for the 1st time, correlate levels of these markers with changes in blood sugar as measured by continuous glucose sensors, instruments that measure the blood sugar continuously through a small needle under the skin. Project #2: is a laboratory study to investigate the genetics and concentration of key molecules that participate in the inflammatory cascade and atheromatous plaque formation that causes CVD. Expression levels in children with T1DM will be compared with those in healthy controls for the 1st time. Project #3: examines the use of abdominal aortic MRI to measure damage to the arteries in children with T1DM and healthy age-matched controls. The results of these studies will likely provide important new data on the use of statins in children with diabetes.
Timeline
- Start
- 2010-10
- Primary completion
- 2013-10
- Completion
- 2014-11
Outcome
Mixed primary results
paper 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). PMID 25418907 ↗
registry analysis (superiority or other test); Atorvastatin LDL-C at Randomization vs Atorvastatin LDL-C at 6 Months; p <0.0001; NCT01236365 ↗
registry analysis (superiority or other test); Atorvastatin hsCRP at Randomization vs Atorvastatin hsCRP at 6 Months vs Placebo hsCRP at Randomization vs Placebo hsCRP at 6 Months; p = 0.913; NCT01236365 ↗
registry Change in hsCRP (6months minus 0months) between Atorvastatin and Placebo NCT01236365 ↗
Publications
- Results Canas JA, Ross JL, Taboada MV, Sikes KM, Damaso LC, Hossain J, Caulfield MP, Gidding SS, Mauras N. 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.
- Results McCulloch MA, Mauras N, Canas JA, Hossain J, Sikes KM, Damaso LC, Redheuil A, Ross JL, Gidding SS. Magnetic resonance imaging measures of decreased aortic strain and distensibility are proportionate to insulin resistance in adolescents with type 1 diabetes mellitus. Pediatr Diabetes. 2015 Mar;16(2):90-7. doi: 10.1111/pedi.12241. Epub 2014 Dec 18.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Atorvastatin | Small molecule | 10 mg | — |
| Subject | Atorvastatin | Small molecule | 20 mg | — |