Genetic underpinnings of neonatal diabetes: a review of current research

Abstract

Neonatal diabetes mellitus (NDM) is a rare, insulin-dependent diabetes that manifests within the first month of life and requires insulin therapy for management. NDM is categorized into two primary types: transient NDM (TNDM), which typically resolves during infancy or early childhood, and permanent NDM (PNDM), necessitating lifelong insulin treatment. TNDM has an incidence of approximately 1 in 90,000 to 160,000 live births and is characterized by insulin-dependent hyperglycemia that usually resolves within 12 weeks but may relapse in later adolescence or early adulthood. Congenital manifestations often include intrauterine growth restriction (IUGR), macroglossia, and umbilical hernia, with its etiology linked to epigenetic alterations on chromosome 6q24 that affect the transcription factor PLAGL1. In contrast, PNDM occurs with an incidence ranging from 1 in 108,999 to 1 in 1,029,999 live births and presents with persistent hyperglycemia requiring lifelong insulin therapy. It is primarily associated with mutations in over 49 genes, particularly KCNJ11 and ABCC8, which disrupt ATP-sensitive potassium channels, while some cases involve mutations in the insulin gene that affect β-cell function. Treatment mainly consists of insulin therapy, although some patients may transition to oral sulfonylureas. Long-term follow-up by a multidisciplinary pediatric team is crucial, as individuals with NDM may experience recurrent diabetes and neurological or neuropsychological issues. Insulin therapy is an effective approach for managing NDM, necessitating meticulous monitoring of blood glucose levels to reduce the risk of long-term complications. Genetic testing is essential for diagnosing both types of NDM and informing treatment strategies, including the potential use of oral sulfonylureas for PNDM. Ongoing research into the genetic mechanisms and long-term management approaches is vital for enhancing clinical outcomes and monitoring complications in affected individuals.