Diabetes Mellitus and Malaria Co‐Existence as Deadly Burden in Sub‐Saharan Africa: A Review of Clinical Outcomes and Molecular Interactions

Diabetes and malaria co-morbidity in malaria-endemic areas has significant therapeutic implications. Evidence suggests that diabetes mellitus promotes malaria pathogenicity while malaria exposure is thought to modulate blood glucose and insulin levels in diabetes mellitus. Here, we extensively reviewed clinical studies and molecular interactions underlying the diabetes mellitus and malaria coexistence. Malaria-related inflammation, oxidative stress, and immune activation disrupt insulin signaling and beta-cell function, resulting in increased hyperglycemia in diabetics. On the other hand, chronic hyperglycemia in diabetics damages the endothelium, raises oxidative stress, and impairs immunity, all of which contribute to an environment that facilitates malaria parasite survival and growth. Tumor necrosis factor-alpha (TNF-α) and insulin signaling pathways emerge as a pivotal link between malaria and diabetes, orchestrating inflammatory responses that contribute to both disease pathogenesis and metabolic dysregulation. These observations were related to higher subclinical infection rates and prolonged parasitemia links among diabetic patients in malaria-endemic areas. This bidirectional relationship could be exploited in the development of novel therapeutic strategy against both malaria and diabetes in tandem, particularly in sub-Saharan Africa, where the two diseases co-exist and are endemic.