Diabetic cardiomyopathy: Early diagnostic biomarkers, pathogenetic mechanisms, and therapeutic interventions

Abstract

Diabetic cardiomyopathy (DCM) mainly refers to myocardial metabolic dysfunction caused by high glucose, and hyperglycemia is an independent risk factor for cardiac function in the absence of coronary atherosclerosis and hypertension. DCM, which is a severe complication of diabetes, has become the leading cause of heart failure in diabetic patients. The initial symptoms are inconspicuous, and patients gradually exhibit left ventricular dysfunction and eventually develop total heart failure, which brings a great challenge to the early diagnosis of DCM. To date, the underlying pathological mechanisms of DCM are complicated and have not been fully elucidated. Although there are therapeutic strategies available for DCM, the treatment is mainly focused on controlling blood glucose and blood lipids, and there is a lack of effective drugs targeting myocardial injury. Thus, a large percentage of patients with DCM inevitably develop heart failure. Given the neglected initial symptoms, the intricate cellular and molecular mechanisms, and the lack of available drugs, it is necessary to explore early diagnostic biomarkers, further understand the signaling pathways involved in the pathogenesis of DCM, summarize the current therapeutic strategies, and develop new targeted interventions.

Fig. 1. Pathogenetic mechanisms of DCM.

Persistent hyperglycemia induces hyperinsulinemia and insulin resistance and then causes abnormal glucose metabolism, cardiomyocyte apoptosis, and myocardial fibrosis. Lipids and lipid intermediate metabolites, advanced glycation end products (AGEs), endoplasmic reticulum stress (ERS), oxidative stress, inflammation, impaired Ca²⁺ handling, autophagy, mitophagy, renin–angiotensin–aldosterone system (RAAS) activation, imbalance between MMPs and TIMPs and TGFβ-mediated signaling pathways are all involved in the progression of DCM.

Fig. 2

Key pathogenetic mechanisms involved in DCM progression.

Fig. 3

Targeted interventions for DCM.