Association between large detectable clonal mosaicism and type 2 diabetes with vascular complications

Philippe Froguel and colleagues report an analysis of large chromosomal clonal mosaic events in individuals with type 2 diabetes. They find a significant association between CME occurrence and T2D with vascular complications. Large chromosomal clonal mosaic events (CMEs) have been suggested to be linked to aging 1 , 2 , 3 and to predict cancer 2 , 3 . Type 2 diabetes (T2D) has been conceptualized as an accelerated-aging disease 4 , 5 , 6 and is associated with higher prevalence of cancers 7 , 8 , 9 , 10 , 11 . Here we aimed to assess the association between T2D and CME occurrence in blood. We evaluated the presence of CMEs in 7,659 individuals (including 2,208 with T2D) using DNA arrays. A significant association between CME occurrence and T2D was found (odds ratio (OR) = 5.3; P = 5.1 × 10 −5 ) and was stronger when we only considered non-obese individuals with T2D (OR = 5.6; P = 4.9 × 10 −5 ). Notably, CME carriers with T2D had higher prevalence of vascular complications than non-carriers with T2D (71.4% versus 37.1%, respectively; P = 7.7 × 10 −4 ). In CME carriers, we found an increase in the percentage of abnormal cells over 6 years ( P = 8.60 × 10 −3 ). In conclusion, given the increased risk of cancer in CME carriers 2 , 3 , our results may have profound clinical implications in patients with severe T2D.