Division of Endocrinology, Diabetes and Hypertension, Brigham and Women's Hospital, 221 Longwood Ave, Office 381, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Curr Diab Rep. 2021 Sep 27;21(10):41. doi: 10.1007/s11892-021-01407-2.
Type 2 diabetes (T2D) is associated with an increased risk of heart failure (HF), with diabetic cardiomyopathy (DbCM) referring to abnormal heart structure in the absence of other driving cardiac factors such as hypertension, coronary artery disease (CAD), and valvular heart disease. Stage B DbCM is commonly asymptomatic and represents a form of stage B HF; DbCM thus represents a transitional phenotype prior to onset of symptomatic HF. The pathogenesis of DbCM is not fully elucidated but involves hyperglycemia, insulin resistance, increased free fatty acids (FFA), lipotoxicity, oxidative stress, advanced glycation end product (AGE) formation, activation of the renin-angiotensin-aldosterone system (RAAS) with an increase in angiotensin II, and dyshomeostasis of calcium, which all contribute to left ventricular hypertrophy (LVH) and cardiac systolic and diastolic dysfunction. Although DbCM is an established pathogenic process, it is underrecognized clinically due to its commonly asymptomatic nature. Raising awareness to identify high-risk individuals with stage B HF due to DbCM, who may subsequently progress to overt HF (stage C/D HF), as well as identifying new pharmacological agents and approaches to prevent functional decline, may help reduce this global health problem. The aim of this review is to focus on stage B DbCM; provide data on diagnostic approaches, current therapies, and potential therapies under investigation; and highlight the need to raise awareness and interdisciplinary dialogue among clinicians and researchers.
There are no currently approved therapeutic strategies to treat or prevent progression of stage B DbCM, but multiple attempts are being made to target different pathogenic mechanisms involved in the development of DbCM. Recent cardiovascular (CV) outcome trials (CVOTs) have identified newer therapeutic agents with CV benefit, such as sodium-glucose cotransporter-2 (SGLT-2) inhibitors that reduce hospitalization for HF and glucagon-like peptide-1 (GLP-1) receptor agonists that reduce major adverse CV events (MACE), though without consistent effect on HF outcomes. Recent clinical practice guidelines recommend screening patients at high risk for HF. Further definition and interdisciplinary discussion of high-yield populations to screen, appropriate subsequent evaluation and intervention are needed to advance this area. DbCM is a complex entity that results from multiple pathogenic mechanisms triggered by impairment of glucose and lipid metabolism over many years. DbCM is commonly asymptomatic and represents a form of stage B HF. It is an underrecognized process that may progress to functional decline and overt HF. Although newer medications approved for the treatment of T2D may play an important role in reducing the risk of HF complications, less focus has been placed on earlier recognition and treatment of DbCM while asymptomatic. Additional efforts should be made to further study and target this stage in order to decrease the overall burden of HF.
2 型糖尿病（T2D）与心力衰竭（HF）风险增加相关，糖尿病心肌病（DbCM）是指在没有其他驱动性心脏因素（如高血压、冠状动脉疾病 [CAD] 和瓣膜性心脏病）的情况下，心脏结构异常。B 期 DbCM 通常无症状，代表 B 期 HF 的一种形式；因此，DbCM 是在出现有症状 HF 之前的一种过渡表型。DbCM 的发病机制尚未完全阐明，但涉及高血糖、胰岛素抵抗、游离脂肪酸（FFA）增加、脂毒性、氧化应激、晚期糖基化终产物（AGE）形成、肾素-血管紧张素-醛固酮系统（RAAS）激活导致血管紧张素 II 增加以及钙代谢失衡，所有这些都导致左心室肥厚（LVH）和心脏收缩和舒张功能障碍。尽管 DbCM 是一种已确立的致病过程，但由于其通常无症状的性质，临床上对其认识不足。提高对因 DbCM 导致 B 期 HF 的高危个体的认识，这些个体可能随后进展为显性 HF（C/D 期 HF），以及确定新的药理学方法和预防功能下降的方法，可能有助于减少这一全球健康问题。本综述的目的是重点关注 B 期 DbCM；提供关于诊断方法、现有治疗方法和正在研究的潜在治疗方法的数据；并强调需要提高临床医生和研究人员的认识和跨学科对话。
目前尚无治疗或预防 B 期 DbCM 进展的治疗方法，但正在尝试针对 DbCM 发展涉及的不同致病机制进行治疗。最近的心血管（CV）结局试验（CVOT）发现了具有 CV 益处的新型治疗药物，例如钠-葡萄糖共转运蛋白 2（SGLT-2）抑制剂可降低 HF 住院率，胰高血糖素样肽-1（GLP-1）受体激动剂可降低主要不良心血管事件（MACE），尽管对 HF 结局没有一致的影响。最近的临床实践指南建议筛查 HF 高危患者。需要进一步明确和跨学科讨论要筛查的高收益人群、适当的后续评估和干预，以推进这一领域。DbCM 是一种复杂的实体，是由多年来葡萄糖和脂质代谢受损引发的多种致病机制导致的。DbCM 通常无症状，代表 B 期 HF 的一种形式。它是一种认识不足的过程，可能会进展为功能下降和显性 HF。尽管新批准用于治疗 T2D 的药物可能在降低 HF 并发症风险方面发挥重要作用，但在无症状时，对 DbCM 的早期识别和治疗关注较少。应进一步努力进一步研究和针对这一阶段，以降低 HF 的总体负担。
