CHIP is an age-related phenomenon characterized by somatic mutations in hematopoietic stem cells. These mutations lead to the clonal expansion of mutant blood cells without overt hematologic malignancies. While CHIP is primarily associated with an increased risk of atherosclerotic cardiovascular diseases (ASCVD), emerging evidence suggests a potential role in metabolic disorders, including type 2 diabetes mellitus (T2DM) and related complications. Prior studies on CHIP in relation to T2DM have demonstrated an increased prevalence and incidence of T2DM. Although there have been individual cohort studies on the risk of CHIP on developing diabetic complications, evidence from large cohort studies is lacking. The increased risk and mortality pertaining to ASCVD, we hypothesized microvascular complications, especially diabetic kidney disease and its associated phenotype of albuminuria and proteinuria, to be influenced by the aberrant immunologic response in CHIP carriers with diabetes.
We thus aim to analyze individuals with whole-exome sequencing data to compare the incidence of diabetes-related complications (e.g., nephropathy, retinopathy, neuropathy) between CHIP carrier T2DM individuals with non-CHIP carriers T2DM individuals, and baseline non-diabetics with or without CHIP who developed T2DM during follow-up
