Dutt Chaitanya, Nunes Salles Joao Eduardo, Joshi Shashank, Nair Tiny, Chowdhury Subhankar, Mithal Ambrish, Mohan Viswanathan, Kasliwal Ravi, Sharma Satyawan, Tijssen Jan, Tandon Nikhil
Research and Development, Torrent Pharmaceuticals Ltd, Ahmedabad, Gujarat, India.
Discipline of Endocrinology, Medical Sciences of Santa Casa de São Paulo, São Paulo, Brazil.
Diabetes Metab Syndr Obes. 2022 Feb 16;15:451-465. doi: 10.2147/DMSO.S333787. eCollection 2022.
The epidemic of obesity or adiposity-based chronic diseases presents a significant challenge with the rising prevalence of morbidities and mortality due to atherosclerotic cardiovascular diseases (ASCVD), especially in low- and middle-income countries (LMIC). The underlying pathophysiology of metabolic inflexibility is a common thread linking insulin resistance to cardiometabolic-based chronic disease (CMBCD), including dysglycemia, hypertension, and dyslipidemia progressing to downstream ASCVD events. The complex CMBCD paradigm in the LMIC population within the socio-economic and cultural context highlights considerable heterogeneity of disease predisposition, clinical patterns, and socio-medical needs. This review intends to summarize the current knowledge of CMBCD. We describe recently established or emerging trends for managing risk factors, assessment tools for evaluating ASCVD risk, and various pharmacological and non-pharmacological measures particularly relevant for LMICs. A CMBCD model positions insulin resistance and β-cell dysfunction at the summit of the disease spectrum may improve outcomes at a lower cost in LMICs. Despite identifying multiple pathophysiologic disturbances constituting CMBCD, a large percentage of the patient at risk for ASCVD remains undefined. Targeting dysglycemia, dyslipidemia, and hypertension using antihypertensive, statins, anti-glycemic, and antiplatelet agents has reduced the incidence of ASCVD. Thus, primordial prevention targeting pathophysiological changes that cause abnormalities in adiposity and primary prevention by detecting and managing risk factors remains the foundation for CMBCD management. Therefore, targeting pathways that address mitochondrial dysfunction would exert a beneficial effect on metabolic inflexibility that may potentially correct insulin resistance, β cell dysfunction and, consequently, would be therapeutically effective across the entire continuum of CMBCD.
肥胖或基于肥胖的慢性疾病的流行带来了重大挑战，尤其是在低收入和中等收入国家（LMIC），因动脉粥样硬化性心血管疾病（ASCVD）导致的发病率和死亡率不断上升。代谢灵活性受损的潜在病理生理学是将胰岛素抵抗与基于心脏代谢的慢性疾病（CMBCD）联系起来的共同线索，CMBCD包括血糖异常、高血压和血脂异常，并进展为下游的ASCVD事件。在社会经济和文化背景下，LMIC人群中复杂的CMBCD模式凸显了疾病易感性、临床模式和社会医疗需求的显著异质性。本综述旨在总结CMBCD的现有知识。我们描述了最近确立的或新出现的危险因素管理趋势、评估ASCVD风险的工具，以及对LMIC特别相关的各种药物和非药物措施。一个将胰岛素抵抗和β细胞功能障碍置于疾病谱顶端的CMBCD模型可能会以较低成本改善LMIC的治疗效果。尽管已确定构成CMBCD的多种病理生理紊乱，但仍有很大比例的ASCVD风险患者未被明确。使用抗高血压药、他汀类药物、抗血糖药和抗血小板药物针对血糖异常、血脂异常和高血压进行治疗，已降低了ASCVD的发病率。因此，针对导致肥胖异常的病理生理变化进行一级预防，以及通过检测和管理危险因素进行初级预防，仍然是CMBCD管理的基础。因此，针对解决线粒体功能障碍问题的途径，可能会对代谢灵活性产生有益影响，这可能潜在地纠正胰岛素抵抗、β细胞功能障碍，从而在CMBCD的整个连续过程中具有治疗效果。
