Bromocriptine Improves Central Aortic Stiffness in Adolescents with Type 1 Diabetes: Arterial Health Results from the BCQR-T1D Study

Abstract

Background: The presence of vascular dysfunction is a well-recognized feature in youth with type 1 diabetes (T1D), accentuating their lifetime risk of cardiovascular events. Therapeutic strategies to mitigate vascular dysfunction are a high clinical priority. In the bromocriptine quick release T1D study (BCQR-T1D), we tested the hypothesis that BCQR would improve vascular health in youth with T1D. Methods: BCQR-T1D was a placebo-controlled, random-order, double-blinded, cross-over study investigating the cardiovascular and metabolic impact of BCQR in T1D. Adolescents in the BCQR-T1D study were randomized 1:1 to phase-1: 4 weeks of BCQR or placebo after which blood pressure and central aortic stiffness measurements by pulse wave velocity, relative area change, and distensibility from phase-contrast magnetic resonance imaging were performed. Following a 4-week washout period, phase 2 was performed in identical fashion with the alternate treatment. Results: Thirty-four adolescents (mean age 15.9±2.6 years, hemoglobin A1c 8.6±1.1%, body mass index percentile 71.4±26.1, median T1D duration 5.8 years) with T1D were enrolled and had magnetic resonance imaging data available. Compared with placebo, BCQR therapy decreased systolic (Δ=-5 mmHg [95% CI, -3 to -7]; P<0.001) and diastolic blood pressure (Δ=-2 mmHg [95% CI, -4 to 0]; P=0.039). BCQR reduced ascending aortic pulse wave velocity (Δ=-0.4 m/s; P=0.018) and increased relative area change (Δ=-2.6%, P=0.083) and distensibility (Δ=0.08%/mmHg; P=0.017). In the thoraco-abdominal aorta, BCQR decreased pulse wave velocity (Δ=-0.2 m/s; P=0.007) and increased distensibility (Δ=0.05 %/mmHg; P=0.013). Conclusions: BCQR improved blood pressure and central and peripheral aortic stiffness and pressure hemodynamics in adolescents with T1D over 4 weeks versus placebo. BCQR may improve aortic stiffness in youth with T1D, supporting future longer-term studies.