Introduction and Objective: Cardiovascular (CV) risk increases with age in T1D, but the role of adiposity in this progression is unclear. We used mediation analysis to determine if rising BMI explains the age-related increase in CV risk.Methods: We analyzed 1,266 patients living with T1D (52.1% male). CV risk was defined as a composite of hypertension, dyslipidemia, obesity, smoking, and microvascular complications. We have used a mediation analysis to extract these findings.Results: The rate of CV risk accumulation remained relatively low during paediatric and young adult age with an inflection point around age 35, when the rate of increase accelerated by approximately 2.5-fold. Age was significantly associated with both BMI (β=0.247 per year, p<0.001) and CV risk count (β=0.0288 per year, p<0.001, Figure 1a). BMI independently predicted CV risk count after adjusting for age (β=0.0618 per unit, p<0.001). Mediation analysis showed that approximately 28.5% of the total effect of age on CV risk accumulation was mediated through increasing BMI, and multiple CV risk factors increased significantly with age (Figure 1b).Conclusion: A substantial portion of the cardiovascular aging process in T1D is mediated by rising adiposity. These data suggest that the “Double Diabetes” is a major driver of CV risk and highlight the need for early weight interventions targeting weight gain throughout the lifespan of T1D.
E. Abdelgadir: None. D. Osborne: None. J.M. Schattenberg: Consultant; Current; 89bio, Inc., Akero Therapeutics, Inc., Alentis Therapeutics, Alexion Pharmaceuticals, Inc., Altimmune, AstraZeneca, Bionorica, Boehringer Ingelheim International GmbH, Boston Therapeutics, Inc., Eli Lilly and Company, Gilead Sciences, Inc., GlaxoSmithKline plc., HistoIndex, Ipsen Biopharmaceuticals, Inc., Inventiva Pharma, Kriya Therapeutics, Madrigal Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novartis AG, Pfizer Inc., Roche Pharmaceuticals, Sanofi, Siemens. Speaker’s Bureau; Current; AbbVie Inc., Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Ipsen Biopharmaceuticals, Inc., Lilly, Madrigal Pharmaceuticals, Inc., Novo Nordisk. Stock/Shareholder; Current; Hepta Bio. K. Hafidh: None. J. Nafach: None. A.H. Khamis: None. B.E. Mohamad: None.
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