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Insulin Resistance as a Shared Pathophysiological Driver in Neurological Disorders: a Narrative Review.

Aslıhan Atar1,2, İrem Nur Şahin Anılgan3,4

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Central insulin resistance is a key factor in neurological disorders, impacting brain function and disease progression. Nutritional and metabolic interventions show promise for managing these conditions.

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Area of Science:

  • Neuroscience
  • Metabolic disorders
  • Neurology

Background:

  • Insulin resistance traditionally viewed as peripheral, but central nervous system (CNS) insulin signaling is critical in neurological disorders.
  • Accumulating evidence links impaired CNS insulin signaling to neurodegenerative, neurological, and neuropsychiatric conditions.

Purpose of the Study:

  • Synthesize evidence for insulin resistance as a shared pathophysiological driver in neurological disorders.
  • Evaluate nutrition- and metabolism-based interventions for modulating CNS insulin resistance.

Main Methods:

  • Narrative review of human and experimental studies.
  • Analysis of neuroimaging, cerebrospinal fluid biomarkers, and molecular profiling data.

Main Results:

  • Central insulin resistance disrupts brain energy metabolism, neuroinflammation, synaptic plasticity, and network stability.
  • Mechanisms contribute to Alzheimer's, Parkinson's, epilepsy, and mood disorders.
  • Dietary patterns, energy restriction, and lifestyle interventions can improve insulin sensitivity and mitigate neurobiological vulnerability.

Conclusions:

  • Insulin resistance is an active disease-modifying factor in neurological disorders, not just a comorbidity.
  • Targeting insulin signaling via nutrition and metabolism offers a promising strategy for prevention and adjunctive management.
  • Future research needs to integrate metabolic phenotyping with neurological outcomes for clinical translation.