Type 5 diabetes mellitus: revisiting malnutrition-related diabetes.

Abstract

A distinct form of diabetes occurring in lean, young individuals with a history of undernutrition was first described in the 1950s asa paradoxical combination of severe hyperglycemia, low body weight, and the absence of ketosis. Historically termed malnutrition-relateddiabetes mellitus (MRDM), it was recognized as a separate entity by the World Health Organization (WHO) in 1985 but was removedfrom formal classification in 1999 due to insufficient mechanistic evidence. Over the following two decades, research in low- and middle-income countries revealed unique metabolic traits of malnutrition-associateddiabetes, distinguishing it from type 1 and type 2 diabetes. In 2025, the International Diabetes Federation (IDF) formally endorsed recognitionof type 5 diabetes mellitus (T5DM), which is estimated to affect approximately 20-25 million people worldwide and predominantlyaffects young individuals with low body mass index living in low- and middle-income countries. T5DM is characterized by impaired insulin secretion, preserved insulin sensitivity, resistance to ketosis despite severe hyperglycemia, and absence of autoimmune markers. Early-life undernutrition is increasingly recognized as a factor disrupting pancreatic organogenesisand β-cell development, resulting in persistent structural deficits and limited functional β-cell reserve in adulthood. Effective management necessitates an integrated nutritional and pharmacological approach. Incorrectly classifying the condition as type 1diabetes may lead to unnecessary lifelong intensive insulin therapy, while misclassification as type 2 diabetes may lead to an inappropriatefocus on insulin resistance-targeted therapies. Although T5DM is most commonly reported in low- and middle-income countries, awareness is essential in high-income settings, particularly among migrant populations from regions affected by chronic undernutrition. Further research is needed to develop standardized diagnostic criteria, improve prevention strategies, and establish evidence-based treatment guidelines.