Background: Global vascular dysfunction is well-recognized in youth with type 1 diabetes (T1D) , accentuating lifetime cardiovascular event risk and making therapeutic strategies to mitigate vascular dysfunction a high priority. In the BCQR-T1D study, we tested the hypothesis that BCQR, a medication used in obese adults with type 2 diabetes, would improve vascular health in T1D youth.

Methods: BCQR-T1D was a placebo-controlled, random-order, double-blinded, cross-over study investigating cardiovascular and metabolic impacts of BCQR in T1D. Youth were randomized 1:1 to phase-1: 4-weeks of BCQR or placebo after which blood pressure (BP) , peripheral vascular stiffness by brachial artery distensibility (BrachD) , and central aortic stiffness by pulse wave velocity (PWV) , relative area change (RAC) and distensibility from phase-contrast MRI, were performed. Following a 4-week washout period, phase 2 was performed in identical fashion with the alternate treatment.

Results: Forty-two adolescents (mean age 15.9 years, HbA1c 8.6%, BMI %ile 71.4, T1D duration 5.8 years) with T1D were enrolled. Compared to placebo, BCQR therapy decreased systolic (∆ = -5 mmHg, p<0.001) and diastolic BP (∆ = -2 mmHg, p=0.039) . BCQR reduced ascending aortic (AA) PWV (∆ = -0.4 m/s, p=0.005) , and increased RAC (∆ = -2.6%, p=0.022) and distensibility (∆ = 0.%/mmHg, p=0.010) . In the thoraco-abdominal aorta, BCQR decreased PWV (∆ = -0.2 m/s, p=0.013) and increased distensibility (∆ = 0.%/mmHg, p=0.032) . Of interest, in the normal-weight participants, BCQR improved systolic BP (∆ = -5 [95.0%CI: -7, -1] mmHg, p= 0.009) , AA PWV (∆ = -0.4 [95.0%CI: -0.7, 0] m/s, p= 0.030) and BrachD (∆ = 0.56 %/mmHg, p=0.023) , and tended to improve AA distensibility (∆ = 0.[95.0%CI: -0.01, 0.19] %/mmHg, p= 0.084) .

Conclusions: BCQR improved BP, central and peripheral aortic stiffness and pressure hemodynamics in T1D adolescents over 4 weeks vs. placebo, even if normal weight, supporting future longer-term studies.


M.Schäfer: None. I.E.Schauer: None. K.J.Nadeau: None. L.Browne: None. U.Truong: None. P.Bjornstad: Advisory Panel; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Horizon Therapeutics plc, LG Chem, Lilly, Novo Nordisk, Consultant; AstraZeneca, Bristol-Myers Squibb Company. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc. A.Baumgartner: None. K.S.Hunter: None. J.Reusch: Advisory Panel; Medtronic. A.J.Barker: None.



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