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.

Targeting the redox system for cardiovascular regeneration in aging

“…Combined relatively low endogenous antioxidant capacity and increased ROS levels in the heart has been also observed in heart failure with preserved ejection fraction (HFpEF), which comprises >50% of all HF cases worldwide (Jasinska‐Piadlo & Campbell, 2023 ; Saeedi Saravi et al., 2023 ). In diabetic patients, circulating high glucose and altered insulin signaling are associated with increased ROS generation and susceptibility to oxidative responses in the heart, leading to tissue remodeling, ventricular hypertrophy, and impaired systolic and diastolic function (Huo et al., 2023 ; Nishio et al., 2004 ). Analysis of heart‐resident CPCs in insulin‐resistant humans and rodents reveal that hyperglycemia‐induced oxidative stress impairs CM formation and growth (Molinaro et al., 2022 ; Rota et al., 2006 ).…”

NF‐κB pathway as a molecular target for curcumin in diabetes mellitus treatment: Focusing on oxidative stress and inflammation

“…131 It significantly influences myocardial fibrosis in DCM by regulating fibroblast function and extracellular matrix accumulation. 132 Additionally, its link to OS and inflammation highlights its involvement in the onset of cardiac fibrosis 130,133 A study conducted by Gbr et al investigated the cardioprotective effects of pioglitazone (a PPAR-γ agonist) and CUR on DCM in a T1DM rat model. The findings showed significant reductions in heart weight, blood glucose levels, lipid and cardiac injury markers, OS, and fibrosis after treatment with pioglitazone and CUR.…”

Potential clinical value of fibrinogen-like protein 1 as a serum biomarker for the identification of diabetic cardiomyopathy

“…Although therapeutic approaches to treat DbCM, including controlling blood glucose and blood lipid levels 7 , are available, there is currently a lack of drugs that can effectively reverse myocardial injury. Peripheral biomarkers such as haemoglobin A1c (HbA1c), cardiac troponin I, adiponectin and inflammatory mediators may serve as feasible indicators for the early diagnosis of DbCM 8 , however, these are not specific biochemical markers to diagnose DbCM. As DbCM often has an asymptomatic presentation in the early stages, the identification of appropriate diagnostic biomarkers that can confirm DbCM in the early stages is an urgent requirement in a clinical setting.…”