Interplay between MASLD, obesity and type 2 diabetes: epidemiology, shared pathways and clinical implications.

Area of Science:

• Hepatology
• Endocrinology
• Cardiology

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global epidemic and a hepatic manifestation of systemic metabolic dysfunction.
• MASLD frequently coexists with obesity and type 2 diabetes mellitus (T2DM), forming a triad that accelerates disease progression and increases cardiometabolic risk.
• Limited data exist on the combined overlap and shared mechanisms of MASLD, obesity, and T2DM.

Purpose of the Study:

• To synthesize current evidence on the epidemiological overlap and shared risk architecture of MASLD, obesity, and T2DM.
• To examine the integrated pathophysiological and molecular mechanisms underlying this triad.
• To discuss clinical implications, including screening strategies, non-invasive fibrosis identification, and evidence-based therapeutic approaches.

Main Methods:

• Systematic review of epidemiological and mechanistic evidence.
• Analysis of pathophysiological pathways including insulin resistance, lipotoxicity, and gut-liver axis perturbations.
• Review of clinical implications, screening algorithms, and therapeutic strategies.

Main Results:

• The triad of MASLD, obesity, and T2DM markedly accelerates liver disease progression and heightens cardiometabolic risk.
• Shared mechanisms include insulin resistance, lipotoxicity, mitochondrial dysfunction, and gut-liver axis dysregulation.
• Integrated screening and therapeutic approaches show promise for managing this complex metabolic interplay.

Conclusions:

• MASLD, obesity, and T2DM share a common risk architecture and interconnected pathophysiological mechanisms.
• Integrated hepatic-cardiometabolic care is essential for improving clinical outcomes in patients with this metabolic triad.
• Further research is needed to refine screening and therapeutic strategies for comprehensive management.