Magnetic resonance imaging measures of decreased aortic strain and distensibility are proportionate to insulin resistance in adolescents with type 1 diabetes mellitus.

OBJECTIVES: To determine whether children with type 1 diabetes mellitus (T1DM) have evidence of increased aortic stiffness or early atherosclerosis as measured by magnetic resonance imaging (MRI). BACKGROUND: T1DM increases risk for cardiovascular disease in adults but whether this process starts in childhood is unknown. SUBJECTS: A total of 54 T1DM patients (15.4 ± 2.6 yr) and 30 age-matched controls (14.8 ± 2.7 yr) participated. METHODS: MRI was performed to assess aortic arch pulse wave velocity (PWV), strain, and distensibility of the ascending and descending thoracic aorta and measures of atherosclerosis. RESULTS: Groups were well-matched for age, pulse pressure, and gender. Low-density lipoprotein-cholesterol (LDL-C) was higher in T1DM (119.3 ± 50 vs. 76.1 ± 13.5 mg/dL, p < 0.0001). There was a trend toward decreased strain and distensibility in T1DM vs. controls in the ascending (distensibility: T1DM 62.2 ± 19.9 kPa⁻¹ × 10⁻³, control 71.6 ± 26.4 kPa⁻¹ × 10⁻³, p = 0.08) and descending aorta (strain: T1DM 25.8 ± 6.2% vs. control 28.3 ± 6.8%, p = 0.09). There was no difference in arch PWV. Advancing age and male gender was negatively associated with aortic stiffness. Hemoglobin A1c (HbA1c) was inversely related to descending aorta strain and distensibility (p < 0.05). Children with diabetes in the lowest two tertiles of insulin sensitivity demonstrated thoracic descending aortas with significantly lower strain (p = 0.027) and distensibility (p = 0.039) and increased measures of wall irregularity (p = 0.005). There were no differences in measurements of atherosclerosis between the two groups. CONCLUSIONS: Adolescents with T1DM, especially those with lower insulin sensitivity, demonstrated a trend toward stiffer, less compliant thoracic aortas, which was inversely associated with diabetes control. These data suggest large vessel aortopathy starts early in T1DM.

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.

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.