Hypoglycemia in sulfonylurea‐treated KCNJ11‐neonatal diabetes: Mild‐moderate symptomatic episodes occur infrequently but none involving unconsciousness or seizures

• Published in: Pediatric diabetes Vol. 19; no. 3; pp. 393 - 397
• Main Authors: Lanning, Monica S, Carmody, David, Szczerbiński, Łukasz, Letourneau, Lisa R, Naylor, Rochelle N, Greeley, Siri Atma W
• Format: Journal Article
• Language: English
• Published: Former Munksgaard John Wiley & Sons A/S 01.05.2018; John Wiley & Sons, Inc
• Subjects: Adolescent; Child; Child, Preschool; Diabetes; Diabetes mellitus; Diabetes Mellitus - drug therapy; Diabetes Mellitus - genetics; Female; Glucose monitoring; Humans; Hypoglycemia; Hypoglycemia - chemically induced; KCNJ11; Male; monogenic diabetes; Mutation; neonatal diabetes; Neonates; Newborn babies; Potassium Channels, Inwardly Rectifying - genetics; Registries; Seizures; Sulfonylurea; Sulfonylurea Compounds - therapeutic use; sulfonylurea; neonatal diabetes; KCNJ11; monogenic diabetes; hypoglycemia
• ISSN: 1399-543X; 1399-5448; 1399-5448
• DOI: 10.1111/pedi.12599

Background Neonatal diabetes mellitus (NDM) caused by mutations in KCNJ11 can be successfully treated with high dose oral sulfonylureas; however, little data is available on the risk of hypoglycemia. Objective To determine the frequency, severity, and clinical significance of hypoglycemia in KCNJ11‐related NDM. Methods Utilizing the University of Chicago Monogenic Diabetes Registry, parents completed an online questionnaire addressing hypoglycemia. Continuous glucose monitoring (CGM) data was available for 7 subjects. Results Thirty subjects with KCNJ11‐related permanent NDM (166 patient‐years on sulfonylurea) had median sulfonylurea dose of 0.39 mg/kg/day (0.24‐0.88 IQR, interquartile range) with median HbA1c 5.7% (39 mmol/mol) (5.5‐6.1 IQR, 37‐43 mmol/mol). Hypoglycemia (<70 mg/dL) was reported monthly once or less frequently in 89.3% of individuals, but 3 (10.7%) reported once weekly or more. Of all hypoglycemic episodes reported, none involved seizures or unconsciousness and thus did not meet the current ISPAD definition of severe hypoglycemia. Seven individuals wore a CGM for a total of 912 hours with blood sugars falling below 70 mg/dL for 5.8% of the time recorded, similar to ranges reported for people without diabetes. Conclusions In our cohort of KCNJ11‐related permanent NDM, hypoglycemia is infrequent and mild despite the high doses of sulfonylurea used and near‐normal level of glycemic control. Long‐term follow‐up on larger numbers will be required to clarify the incidence and determinants of hypoglycemia in this unique population.