We show that plasma levels of APOC3 predict the progression of DKD in people with type 2 diabetes and, using mechanistic mouse models that have elevated levels of TRLs, demonstrate that silencing APOC3 reduces atherosclerosis and kidney disease via reduced accumulation of TRLs in the glomerulus and artery wall. The gene discussed is APOC3; the disease is type 2 diabetes mellitus.