Pathophysiological Links Between Stroke and Prediabetes: A Systematic Review.

Area of Science:

• Endocrinology and Neurology
• Biomarker Research
• Cardiovascular Health

Background:

• Prediabetes represents a critical stage preceding type 2 diabetes mellitus (T2DM), impacting over 425 million globally.
• This stage is associated with vascular damage and elevated stroke risk, yet the link remains under-investigated.
• Understanding stroke biomarkers in prediabetes is crucial for early intervention.

Purpose of the Study:

• To systematically review and synthesize existing literature on stroke-related biomarkers in normoglycaemia, prediabetes, and T2DM.
• To identify potential associations between prediabetes and stroke through biomarker analysis.
• To explore early pathophysiological changes indicative of increased stroke risk in prediabetic individuals.

Main Methods:

• A systematic literature search was conducted across major databases (PubMed, Google Scholar, Scopus, Web of Science, Science Direct) from 2003-2023.
• Eligible studies included original human research with defined glycaemic diagnostic criteria (ADA or WHO) and reported biomarker associations or stroke risk.
• Eight studies (n=3003) were included after excluding those with major comorbidities; bias was assessed using the Newcastle-Ottawa Scale.

Main Results:

• Elevated levels of Neuron-Specific Enolase (NSE) were consistently reported in hyperglycaemic individuals.
• Interleukin-6 (IL-6) showed mixed results, with one study indicating a significant increase in diabetes and another a non-significant upward trend in prediabetes.
• Single studies reported significant elevations in D-dimer and GFAP in hyperglycaemic individuals with stroke or cognitive impairment, while S100B findings were divergent.

Conclusions:

• Biomarker alterations observed in T2DM may originate in the prediabetic stage.
• Individuals with prediabetes may exhibit altered inflammatory (IL-6), coagulation (D-dimer), and neurovascular (S100B, GFAP, NSE) markers.
• Further robust studies are essential to validate these associations and develop biomarker-based tools for early stroke risk detection and prevention in prediabetes.