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

Area of Science:

• Endocrinology and Metabolism
• Nutritional Science
• Developmental Biology

Background:

• Type 5 Diabetes Mellitus (T5DM) is an emerging diabetes phenotype associated with chronic undernutrition, primarily affecting young, lean individuals in low- and middle-income countries.
• Formally recognized in 2025, T5DM is now understood as a distinct insulin-deficient phenotype, separate from autoimmune (Type 1) and insulin-resistant (Type 2) diabetes.

Purpose of the Study:

• To synthesize recent evidence on the epidemiology, pathophysiology, clinical characteristics, and management of Type 5 Diabetes Mellitus.
• To highlight the distinct nature of T5DM and the challenges in its diagnosis and management.

Main Methods:

• Review of recent scientific literature on T5DM.
• Analysis of studies focusing on early-life nutritional deprivation and its impact on pancreatic development (DOHaD framework).
• Evaluation of clinical features, diagnostic criteria, and management strategies for T5DM.

Main Results:

• T5DM is strongly influenced by early-life nutritional deprivation, leading to reduced functional beta-cell mass via epigenetic programming.
• Clinical presentation includes low BMI, sarcopenia, marked insulinopenia, absence of autoantibodies, and ketosis resistance despite hyperglycemia.
• Diagnostic challenges persist, with frequent misclassification as Type 1 or Type 2 diabetes; multidimensional assessment is crucial.

Conclusions:

• Type 5 Diabetes Mellitus is a distinct insulin-deficient phenotype resulting from chronic undernutrition.
• Effective management necessitates nutritional rehabilitation, including adequate energy, protein, and micronutrient correction, alongside cautious insulin use.
• Improved recognition and tailored management strategies are essential for optimal clinical outcomes in T5DM patients.