Type 5 Diabetes Mellitus: Pathophysiology, Clinical Phenotype, and Nutritional Management.

Type 5 Diabetes Mellitus (T5DM) is an emerging diabetes phenotype linked to chronic undernutrition. It predominantly affects young, lean individuals in low- and middle-income countries. After its formal recognition by the International Diabetes Federation in 2025, T5DM resurfaced as a clinically relevant insulin-deficient phenotype. It is now viewed as distinct from classical autoimmune and insulin-resistant forms of diabetes. This review synthesises recent evidence on the epidemiology, pathophysiology, clinical characteristics, and management of T5DM. Recent studies show that T5DM is influenced by early-life nutritional deprivation. This fits within the Developmental Origins of Health and Disease (DOHaD) framework. Undernutrition during key developmental periods harms pancreatic morphogenesis. It creates a permanent reduction of functional beta-cell mass through epigenetic programming. Clinically, T5DM often appears before age 30. Patients have low body mass index, sarcopenia, marked insulinopenia, absence of diabetes-associated autoantibodies, and resistance to ketosis, despite significant hyperglycemia. Diagnostic challenges remain, as patients are frequently misclassified as type 1 or type 2 diabetes. Relying only on body mass index is insufficient. Accurate diagnosis requires a multidimensional assessment including nutritional history, metabolic features, and exclusion of monogenic diabetes. T5DM is a distinct insulin-deficient phenotype caused by chronic undernutrition. Effective management requires more than glycaemic control. Nutritional rehabilitation is key, with a focus on adequate energy intake, high-biological-value protein supplementation, and correction of key micronutrient deficiencies. Given preserved insulin sensitivity, low-dose insulin should be used cautiously to avoid iatrogenic hypoglycemia. Better recognition and tailored management strategies are needed for optimal clinical outcomes.

© 2026 The Author(s). Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.