Decoding type 5 diabetes using spatial omics: microarchitectural and molecular mechanisms of malnutrition-associated diabetes

This review advocates for the formal recognition of Type 5 Diabetes Mellitus, a distinct, neglected form of non-autoimmune, lean diabetes predominantly affecting low-income and middle-income populations with a history of early-life malnutrition. Characterized by impaired insulin secretion amid preserved insulin sensitivity, this phenotype exhibits unique microarchitectural alterations within pancreatic islets and is strongly linked to malnutrition-induced epigenetic reprogramming and gut microbiota dysbiosis. Recent advancements in spatial omics technologies have illuminated region-specific gene expression, inflammatory pathways, and cellular remodeling in pancreatic tissue, offering novel insights into its pathophysiology. Despite its global prevalence, especially in resource-constrained settings, Type 5 diabetes remains underdiagnosed and poorly understood, hindering the development of tailored diagnostic criteria and therapeutic strategies. This review synthesizes current epidemiological, mechanistic, and molecular evidence, emphasizing the imperative for establishing standardized classification, research collaborations-including the formation of the IDF Type 5 Diabetes Working Group-and region-specific management protocols. Recognizing this disease entity is critical for advancing health equity, improving clinical outcomes, and guiding future research in metabolic disease frameworks.