Diabetes is a global epidemic and the 8th leading cause of death, induced by its vascular complications. Pulmonary hypertension is a lethal disease if the patients are not treated promptly, and there is no treatment that cures pulmonary hypertension. We previously demonstrated that diabetes worsens the progression of pulmonary hypertension. In this study, we revealed that koningic acid (an inhibitor of GAPDH) ameliorates the progression of pulmonary hypertension in diabetic mice by reducing glycolysis. Our promising preclinical findings, along with glycolytic changes in ECs, provide a strong rationale for clinical testing of GAPDH inhibitors in patients with PH and diabetes.

We identified the critical role of eNAMPT in the development of coronary microvascular disease in diabetes. Chronic administration of eNAMPT antibody or NAMPT inhibitor restored coronary flow velocity reserve by enhancing coronary vascular relaxation in diabetes; eNAMPT inhibition is a novel therapeutic approach to reducing the severity of coronary microvascular disease in type 2 diabetes.