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Chaitanya Dutt,1 Joao Eduardo Nunes Salles,2 Shashank Joshi,3 Tiny Nair,4 Subhankar Chowdhury,5 Ambrish Mithal,6 Viswanathan Mohan,7 Ravi Kasliwal,8 Satyawan Sharma,9 Jan Tijssen,10 Nikhil Tandon11 1Research and Development, Torrent Pharmaceuticals Ltd, Ahmedabad, Gujarat, India; 2Discipline of Endocrinology, Medical Sciences of Santa Casa de São Paulo, São Paulo, Brazil; 3Department of Endocrinology, Lilavati Hospital, Mumbai, Maharashtra, India; 4Department of Cardiology, PRS Hospital, Thiruvananthapuram, Kerala, India; 5Department of Endocrinology, Institute of Post-Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital, Kolkata, West Bengal, India; 6Department of Endocrinology & Diabetes, Max Healthcare, New Delhi, India; 7Madras Diabetes Research Foundation, Chennai, Tamil Nadu, India; 8Medanta- The Medicity, Gurgaon, Haryana, India; 9Department of Cardiology, Bombay Hospital and Medical Research Center, Mumbai, Maharashtra, India; 10Academic Medical Center - University of Amsterdam, Amsterdam, the Netherlands; 11Department of Endocrinology, All India Institute of Medical Sciences, New Delhi, IndiaCorrespondence: Chaitanya Dutt, Research & Development, Torrent Pharmaceuticals Ltd., Ahmedabad, Gujarat, India, Tel +91 9825606901, Email Cdutt@torrentpharma.comAbstract: 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.Keywords: mitochondrial modulator, insulin resistance, diabetes mellitus, dyslipidemia hypertension, non-high-density lipoprotein-cholesterol, triglycerides, apolipoprotein B |
