Clonal haematopoiesis of indeterminate potential (CHIP) is associated with macrovascular diseases, including coronary artery disease and stroke. However, the effects of CHIP on microvascular complication have not been evaluated in individuals with type 2 diabetes (T2D). This study included 20,712 T2D participants without prevalent diabetic microvascular complication (DMCs) and hematologic malignancy at baseline. CHIP and related phenotypes were identified using whole exome sequencing derived from peripheral blood samples. The incidence of DMCs defined as a composite of diabetic kidney disease, diabetic retinopathy, or diabetic neuropathy. Associations of any CHIP with incident DMCs and subtypes were assessed using Cox regression. Gene-specific analyses also conducted to determine the effect of mutated driver genes with DMCs. During a median follow-up of 13.0 years, 5,673 participants developed DMCs. Any CHIP was associated with high risk of DMCs (HR, 1.23; 95% CI, 1.10-1.38; P<0.001), specifically, diabetic retinopathy (HR, 1.34; 95% CI, 1.13-1.57; P=0.001) and diabetic kidney disease (HR, 1.26; 95% CI, 1.10-1.45; P=0.001), but not diabetic neuropathy. Gene-specific analyses suggested that DNMT3A, TET2, NF1, and Spliceosome genes were associated with risk of developing DMCs. CHIP increases the risk of developing DMCs in individuals with T2D, independently of other risk factors. These findings offered potential implications for the prevention and management of DMCs.
© 2025 by the American Diabetes Association.