Ketotic and Non-Ketotic Hypoglycemia in Infants of Diabetic Mothers: Mechanisms, Clinical Profiles, and Neurodevelopmental Implications

ABSTRACT: Background: Infants of diabetic mothers (IDMs) are at high risk of neonatal hypoglycemia, driven by metabolic adaptations to maternal dysglycemia. Two major phenotypes occur—non-ketotic hyperinsulinemic hypoglycemia and ketotic hypoglycemia—each reflecting distinct intrauterine environments, substrate availability, and endocrine responses. Differentiating these forms is essential because their mechanisms, clinical presentation, severity, and neurodevelopmental outcomes differ substantially. Objectives: Compare biochemical, clinical, and pathophysiological differences between ketotic and non-ketotic hypoglycemia in IDMs. Identify maternal, placental, and neonatal factors distinguishing the two hypoglycemia patterns. Evaluate treatment approaches, monitoring needs, and associated neurodevelopmental risks. Methods: A structured literature review (2000–2025) was performed using PubMed, Scopus, and Web of Science. Eligible studies included observational cohorts, case series, placental pathology studies, mechanistic metabolic research, and neonatal neurodevelopmental follow-up studies involving IDMs. Data were synthesized into comparative tables covering biochemical mechanisms, clinical features, maternal–placental associations, neurodevelopmental outcomes, and treatment pathways. Emphasis was placed on high-quality