A Novel Approach to the Management of Neonatal Diabetes Using Sensor-Augmented Insulin Pump Therapy With Threshold Suspend Technology at Diagnosis

Neonatal diabetes mellitus (NDM) is a rare genetic condition with an incidence of 1 in 100,000 (1) that presents before 1 year of age (2). There are two main clinical forms of NDM: permanent NDM (PNDM), which requires lifelong treatment with insulin, and transient NDM (TNDM), which may spontaneously remit and sometimes recurs in the second to third decade of life. In most cases, TNDM and PNDM cannot be distinguished clinically at the time of diagnosis, and genetic analysis needs to be performed. The genetic origin for >90% of TNDM cases has been established. In TNDM, 68% of the cases have abnormalities in an imprinted region on chromosome 6q24; 10% have KCNJ11 gene mutations; and 13% have an ABCC8 gene mutation (3). Multiple genes involved in pancreatic development, β-cell apoptosis, or dysfunction cause PNDM (4). The most common mutations are in the KATP channel genes KCNJ11 (30%) and ABCC8 (11%) or the insulin (INS) gene (13%) (3). Insulin is acutely required in most infants to establish metabolic control in NDM (5). Early initiation of sulfonylurea treatment is also recommended (6) as a treatment option in selected cases of NDM caused by ABCC8 and KCNJ11 mutations, and, in responsive cases, sulfonylurea therapy provides better long-term metabolic control (7,8) and could even improve neurodevelopmental outcomes (9). The MiniMed 530G (Medtronic, Inc., Northridge, CA) is a firstgeneration artificial pancreas system approved by the U.S. Food and Drug Administration (FDA) on 26 September 2013 for the management of diabetes in people ≥16 years of age. The system includes an external glucose sensor and insulin pump, transmitter, glucose meter, and therapy management software. Sensor signals are transmitted to the MiniMed 530G insulin pump and converted into glucose values every 5 minutes. Fingerstick blood glucose testing is still required for both device calibration and management decisions. The unique feature of this system is that it can be programmed to automatically suspend delivery of insulin when sensor glucose values fall below a predefined threshold between 60 and 90 mg/dL. The system is not designed to treat hypoglycemia, but rather to detect severe hypoglycemia, alerting the user to immediately check blood glucose to determine appropriate treatment. The ASPIRE (CArfilzomib, Lenalidomide, and DexamethaSone versus Lenalidomide and Dexamethasone for the treatment of PatIents with Relapsed Multiple MyEloma) study showed reduced nocturnal hypoglycemia without significant differences in A1C when using sensor-augmented insulin pump therapy (SAPT) with a thresholdsuspend feature compared to SAPT without threshold suspend (10). A Novel Approach to the Management of Neonatal Diabetes Using Sensor-Augmented Insulin Pump Therapy With Threshold Suspend Technology at Diagnosis