What is the clinical evidence from this study?

Study design: Cohort. Population: Type 1 Diabetes (n=1266). Intervention: Rising BMI. Primary outcome: Cardiovascular risk accumulation (composite of hypertension, dyslipidemia, obesity, smoking, and microvascular complications) (β=0.0618 per unit, p=<0.001).

What question did this study set out to answer?

The aim is to assess if rising BMI explains the increase in cardiovascular risk associated with age in individuals with type 1 diabetes (T1D).

June 7, 2026

2961-LB: Double Diabetes: A Mediator of Age-Related Cardiovascular Risk in Type 1 Diabetes: A Mediation Analysis of a Large T1D Cohort

Q: What are the key findings of this study?

Rising BMI mediated approximately 28.5% of the total effect of age on cardiovascular risk accumulation in patients with Type 1 Diabetes.

Q: What does this research mean for the field?

Rising adiposity mediates approximately 28.5% of the age-related increase in cardiovascular risk among patients with Type 1 diabetes. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

The aim is to assess if rising BMI explains the increase in cardiovascular risk associated with age in individuals with type 1 diabetes (T1D).

Key Result

Rising BMI mediated approximately 28.5% of the total effect of age on cardiovascular risk accumulation in patients with Type 1 Diabetes.

Key Points

The aim is to assess if rising BMI explains the increase in cardiovascular risk associated with age in individuals with type 1 diabetes (T1D).
Analyzed data from 1,266 patients with T1D, including 52.1% males.
Defined cardiovascular risk as a combination of hypertension, dyslipidemia, obesity, smoking, and microvascular complications.
Employed mediation analysis to evaluate the relationship between age, BMI, and cardiovascular risk.
Observed a 2.5-fold increase in CV risk accumulation rate after age 35.
Age showed significant relationships with both BMI (β=0.247, p<0.001) and CV risk count (β=0.0288, p<0.001).
Approximately 28.5% of the age effect on CV risk was mediated through BMI increases.

Study Design

Type

Cohort (n=1,266)

Structured PICO

Does rising BMI mediate the age-related increase in cardiovascular risk in patients with Type 1 Diabetes?

Population

1,266 patients living with Type 1 Diabetes analyzed to assess the mediating role of BMI on age-related cardiovascular risk.

Exposure

Rising BMI / Age (observational exposure)

Outcome

Cardiovascular risk count (composite of hypertension, dyslipidemia, obesity, smoking, and microvascular complications)composite

Rising adiposity mediates a substantial portion (28.5%) of the age-related increase in cardiovascular risk among patients with Type 1 Diabetes, highlighting the importance of weight management.

Main Result

Effect estimate: β=0.0618 per unit

p-value: p=<0.001

Abstract

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, p0.001) and CV risk count (β=0.0288 per year, p0.001, Figure 1a). BMI independently predicted CV risk count after adjusting for age (β=0.0618 per unit, p0.001). 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. Disclosure 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 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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