Pathophysiological hallmarks in type 2 diabetes heterogeneity (review).

Area of Science:

• Endocrinology and Metabolism
• Pathophysiology
• Precision Medicine

Background:

• Type 2 diabetes (T2DM) presents significant heterogeneity, complicating patient classification and treatment.
• Current classification strategies fail to fully capture the diverse pathophysiological mechanisms in T2DM.
• Understanding T2DM complexity is crucial for developing effective precision medicine approaches.

Purpose of the Study:

• To propose nine key pathophysiological hallmarks of T2DM.
• To mechanistically explain the complexities and features of diabetes-associated pathophysiological events.
• To provide a framework for advancing precision medicine in diabetes care.

Main Methods:

• Review of existing literature on T2DM pathophysiology.
• Identification and synthesis of key pathophysiological events contributing to T2DM heterogeneity.
• Proposal of nine distinct pathophysiological hallmarks.

Main Results:

• Identified nine core pathophysiological hallmarks of T2DM: pancreatic beta cell dysfunction, insulin sensitivity, insulin resistance, obesity, aging, subclinical inflammation, metabolic dysregulation, prothrombotic state induction, and hypertension.
• Detailed the molecular mediators, influencing factors, clinical biomarkers, and assessment methodologies for each hallmark.
• Established a mechanistic understanding of diabetes-associated pathophysiological events.

Conclusions:

• The proposed nine pathophysiological hallmarks offer a comprehensive framework for understanding T2DM complexity and heterogeneity.
• Detailed knowledge of these hallmarks supports precision medicine strategies, including patient stratification, subtype diagnosis, and tailored treatment.
• This approach aims to improve clinical outcomes for individuals with T2DM.