Abstract

Severe Plasmodium falciparum malaria constituted a life-threatening parasitic infection characterized by widespread 
endothelial activation, microvascular sequestration, and systemic inflammation. Type 1 diabetes mellitus is 
associated with baseline endothelial dysfunction, chronic hyperglycemia-induced vascular damage, and altered 
immune responses. The convergence of these two pathophysiological states in comorbid patients may amplify 
endothelial injury and modify disease severity. This review critically evaluated current evidence regarding 
endothelial activation biomarkers in adults and children with severe P. falciparum malaria who have pre-existing 
type 1 diabetes, examining how diabetic endothelial dysfunction influences malaria pathogenesis, biomarker profiles, 
and clinical outcomes. A comprehensive literature search of PubMed, EMBASE, and Cochrane databases was 
conducted for peer-reviewed studies published between 2010 and 2025 examining endothelial biomarkers in malaria
diabetes comorbidity. Type 1 diabetes potentiated malaria-induced endothelial activation through synergistic 
mechanisms, including advanced glycation end-product accumulation, enhanced cytoadherence receptor expression, 
exaggerated inflammatory responses, and impaired endothelial repair capacity. Biomarkers, including angiopoietin
2, soluble intercellular adhesion molecule-1, von Willebrand factor, and endothelial microparticles, demonstrated 
significantly elevated levels in diabetic patients with severe malaria compared to non-diabetic malaria patients. 
Diabetic comorbidity correlated with increased cerebral malaria risk, prolonged parasite clearance, and higher 
mortality rates. However, evidence derives predominantly from small observational studies with significant 
methodological heterogeneity. Pre-existing type 1 diabetes substantially modified endothelial responses to severe 
malaria, with biomarker elevations reflecting additive pathophysiological burden and predicting worse clinical 
outcomes, though robust prospective studies are needed to establish definitive risk stratification tools.