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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
42
10 or 20 mg daily
10 or 20 mg daily
Alfred I duPont Hospital
Wilmington, Delaware, United States
Nemours Children's Clinic
Jacksonville, Florida, United States
Nemours Children's Clinic
Orlando, Florida, United States
Nemours Children's Clinic
Pensacola, Florida, United States
Nemours Children's Clinic-Jefferson
Philadelphia, Pennsylvania, United States
LDL-C Levels Assessed at Randomization and 6 Months
To assess if the use of statins in children with type 1 DM is safe, improves measures of LDL-C. Subjects will have a physical exam, laboratories, nutritional counseling and moderate aerobic exercise recommended. Diabetes management will be intensified. At 3 months fasting lipoprotein fractions (ion mobility)re-drawn and if LDL-C \>100mg/dl patients will be randomized to treatment with statins or placebo for 6 months, randomization stratified by BP and microalbuminuria, duration of diabetes and HgA1C. At 1 month safety labs will be repeated and blood withdrawn again at 3 and 6 months from baseline.
Time frame: Randomization and 6 months
Hs-CRP Levels Assessed at Randomization and 6 Months
To assess if the use of statins in children with type 1 DM decreases the concentration of inflammatory markers.
Time frame: Randomization and 6 months
MAGE
Mean amplitude of glycemic excursion (MAGE) with continuous glucose monitoring (CGM - IPro®, Medtronic Minimed) worn blindly for 6d to assess glucose variability
Time frame: Randomization and 6 months
RAGE
Receptor for Advanced Glycation End Products
Time frame: Randomization and 6 months
Descending Aortic Strain
Subclinical atherosclerosis and arterial stiffness of abdominal aortic MRI
Time frame: Randomization
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