Heart Failure as a Comorbidity of Diabetes: Role of Dipeptidyl Peptidase 4.

Heart failure is a primary cause of death worldwide, and it is notable that heart failure patients exhibit a high incidence of diabetes. On the other hand, comorbid diabetes significantly worsens the prognosis of heart failure, even independently of complicated coronary artery disease.To date, heart failure caused by diabetes has been designated as "diabetic cardiomyopathy (DMC)," and a recent cohort study of the large-scale (1.9 million people) research platform of linked electronic medical records in UK (CALIBER registry) demonstrated that heart failure and peripheral arterial disease are the most common initial manifestations of cardiovascular disease in type 2 diabetes. The underlying pathophysiology has been characterized as microvasculopathy, myocardial hypertrophy, and cardiac fibrosis; however, these evidences are mostly obtained under a preclinical setting, and its clinical application on DMC in terms of its diagnosis and therapeutic intervention yet has reached practical. Our group has focused on and clarified the molecular mechanisms underlying DMC both in preclinical and clinical settings and has found the primary role of "dipeptidyl peptidase-4 (DPP4)" in the pathogenesis of diabetic microvasculopathy in the heart. Moreover, there are evidences implicating the potent role of circulating DPP4 activity in the diagnosis of diastolic heart failure. The present review aimed to review the current comprehension regarding diabetes and heart failure and discuss the therapeutic and diagnostic roles of DPP4.