Conventional insulin pump therapy in two neonatal diabetes patients harboring the homozygous PTF1A enhancer mutation: Need for a novel approach for the management of neonatal diabetes

Abstract

Kurnaz E, Aycan Z, Yıldırım N, Çetinkaya S. Conventional insulin pump therapy in two neonatal diabetes patients harboring the homozygous PTF1A enhancer mutation: Need for a novel approach for the management of neonatal diabetes. Turk J Pediatr 2017; 59: 458-462. The enhancer of PTF1A mutation causes developmental defects of the pancreas. This condition can result in insulin-requiring diabetes and exocrine pancreatic insufficiency. We report two patients with diabetes mellitus harboring the homozygous PTF1A enhancer mutation. The patients had hyperglycemia in the first month of life and were started with subcutaneous insulin injections with NPH insulin. When blood glucose (BG) exceeded 250 mg/dl, a conservative dose of rapid-acting insulin was administered to restore BG to the target range. In cases with documented poor control (persistent hypoglycemia and rebound hyperglycemia), it was decided that the baby would benefit from a continuous subcutaneous insulin infusion pump. But our experience shows that wide fluctuations in BG concentrations despite the strict follow-up was probably due to the absence of circulating glucagon. Further treatment options would overcome this problem, especially for children with pancreas agenesis. We could say theoretically that using diluted insulin, a sensor-augmented insulin pump system and single-hormone (insulin alone) and dual-hormone (insulin and glucagon) artificial pancreas systems may mitigate the severity of hypogylcemia.

Clinical Characteristics and Long-term Follow-up of Patients with Diabetes Due To PTF1A Enhancer Mutations

“…This phenotype and epigenetic data suggested that this enhancer is pancreas specific and functional analysis demonstrated that the base substitutions disrupted enhancer activity by abolishing transcription factor (FOXA2 and PDX1) binding ( 15 ). After the initial report, 8 further cases have been published ( 16-18 , 26 , 27 ). Overall these cases appear to be more common than those with biallelic truncating PTF1A variants, likely due to the higher survival rate resulting from the lack of severe neurological features.…”

“…Data on the long-term growth outcome in patients with distal enhancer PTF1A mutations have so far been scarce. In some case reports of patients with enhancer mutations, catch-up growth in the infancy period has been reported ( 16 , 17 , 26 , 27 ). Nevertheless, the majority of these reports did not provide a long-term follow-up.…”

Transient Neonatal Diabetes Mellitus Managed with Continuous Subcutaneous Insulin Infusion (CSII) and Continuous Glucose Monitoring

“…Among the subgroups of NDM, TNDM is characterized by self limited hyperglycemia, which lasts for a median of 12 weeks and completely resolves by the age of 18 months 13,14) . TNDM accounts for approximately 45% of all NDM cases, PNDM accounts for most of the remaining 55%, and syndromic NDM constitutes 10,15) . Overexpression of the imprinted genes at chromosome 6q24 as well as mutations in ZFP57 and HNF1B have been re ported to be responsible for TNDM.…”

“…It rapidly switches off when the risk of hypoglycemic episodes is anticipated. Never theless, inconsistencies of appetite and feeding schedule and fre quent infection of the needle insertion sites are factors that pose difficulties in treating diabetes during the neonatal period 10) .…”

ISPAD Clinical Practice Consensus Guidelines 2022: Insulin treatment in children and adolescents with diabetes

“…Rapid‐acting insulin can be diluted to 1/10 (U10) or U50 with sterile NPH diluent and stored for 1 month 67 for use in pumps for infants or very young children. Insulin diluted in a 1/5 ratio (U20 insulin; 20 units/ml) has been used successfully during automated insulin treatment in young children (3–6 years old) with T1D 68–72 . Dosing errors with unconventional insulin concentrations can be serious.…”