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Diabetes and Vascular Disease

MON-592 - Associations of Clonal Hematopoiesis with Type 2 Diabetes and Cardiovascular Disease

Monday, June 15, 2026
9:00 AM - 2:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Brooke D'Mello, BHSc: No financial relationships to disclose


Background: Clonal hematopoiesis (CH) is the age-related expansion of hematopoietic stem cells, arising from mosaic chromosomal alterations (mCAs) or somatic mutations in leukemia-driver genes such as DNMT3A, TET2, and ASXL1 (clonal hematopoiesis of indeterminate potential, CHIP). CHIP is typically defined by a variant allele frequency (VAF), the proportion of sequencing reads supporting an acquired somatic mutation in canonical driver genes, of at least 2%. CH has been linked to increased cardiometabolic disease in general, but its associations with type 2 diabetes (T2D) and individual cardiovascular endpoints have been inconsistently reported.

Objective: (1) Determine the associations of CH with incident and prevalent T2D, and with incident myocardial infarction (MI), stroke, and cardiovascular mortality. (2) Determine if observed associations are dependent on VAF and/or driver genes. (3) Determine if baseline T2D status modifies the CH-cardiovascular relationships.

Methods: We performed a systematic review and meta-analysis, searching MEDLINE, Embase, Cochrane, and CENTRAL from inception to June 2025 for cohorts reporting age-adjusted CH estimates for our outcomes of interest in adults without hematologic malignancy. Using random-effects models, we generated odds ratios (ORs) for prevalent T2D and hazard ratios (HRs) for incident outcomes. We performed prespecified subgroup analyses by type of CH (mCA, CHIP), VAF (unselected VAF, VAF ≥10%) and driver gene (DNMT3A, TET2, ASXL1). We used meta-regression to explore whether baseline diabetes prevalence modified CH associations with cardiovascular outcomes.

Results: We included 27 cohorts, encompassing more than 650,000 individuals. CH was associated with incident T2D (HR 1.20, 95% CI 1.02–1.41). mCAs were associated with prevalent T2D (OR 5.26, 2.36–11.74), but CHIP was not (OR 1.26, 0.99–1.60). Association of CHIP with prevalent T2D were stronger in studies reporting unselected VAF (OR 1.57, 1.02–2.43), while no association was observed in studies restricted to VAF ≥10% (OR 1.10, 0.89–1.35). CH was associated with increased incidence of MI (HR 1.14, 1.00–1.29; p=0.047), stroke (HR 1.12, 1.03–1.23), and cardiovascular mortality (HR 1.20, 1.07–1.36). In driver gene analyses, TET2 mutations were associated with a higher risk of stroke (HR 1.41, 1.03–1.93), and ASXL1 mutations with cardiovascular mortality (HR 2.22, 1.37–3.60). Associations with stroke and cardiovascular mortality were consistent across VAF thresholds. In meta-regression, baseline diabetes prevalence did not modify the association between CH and cardiovascular outcomes.

Conclusion: CH is associated with T2D and individual cardiovascular endpoints with the magnitude of association dependent on type of CH, VAF threshold and driver gene. Our findings support a potential role for CH as a somatic genomic predictor of cardiometabolic risk.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*