The Inflammatory Bridge Between Type 2 Diabetes and Neurodegeneration: A Molecular Perspective

Int J Mol Sci. 2025 Aug 5;26(15):7566. doi: 10.3390/ijms26157566.

Abstract

Chronic low-grade inflammation is a hallmark of both metabolic and neurodegenerative diseases. In recent years, several studies have highlighted the pivotal role of systemic metabolic dysfunction, particularly insulin resistance, in shaping neuroinflammatory processes and contributing to impaired cognitive performance. Among metabolic disorders, type 2 diabetes mellitus has emerged as a major risk factor for the development of age-related neurodegenerative conditions, suggesting a complex and bidirectional crosstalk between peripheral metabolic imbalance and central nervous system function. This review aims to explore the cellular and molecular mechanisms underlying the interaction between metabolic dysregulation and brain inflammation. By integrating current findings from endocrinology, immunology, and neuroscience, this work provides a comprehensive overview of how chronic metabolic inflammation may contribute to the onset and progression of neurodegenerative conditions. This interdisciplinary approach could offer novel insights into potential therapeutic strategies targeting both metabolic and neuroinflammatory pathways.

Keywords: aging; insulin resistance; neuroinflammaging; neuroinflammation; type 2 diabetes mellitus.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / metabolism
  • Diabetes Mellitus, Type 2* / pathology
  • Humans
  • Inflammation* / metabolism
  • Insulin Resistance
  • Neurodegenerative Diseases* / etiology
  • Neurodegenerative Diseases* / metabolism
  • Neurodegenerative Diseases* / pathology
  • Neuroinflammatory Diseases* / metabolism