TY - JOUR
T1 - Long-term follow-up of glycemic and neurological outcomes in an international series of patients with sulfonylurea-treated abcc8 permanent neonatal diabetes
AU - The Neonatal Diabetes International Collaborative Group
AU - Bowman, Pamela
AU - Mathews, Frances
AU - Barbetti, Fabrizio
AU - Shepherd, Maggie H.
AU - Sanchez, Janine
AU - Piccini, Barbara
AU - Beltrand, Jacques
AU - Letourneau-Freiberg, Lisa R.
AU - Polak, Michel
AU - Greeley, Siri Atma W.
AU - Rawlins, Eamon
AU - Babiker, Tarig
AU - Thomas, Nicholas J.
AU - De Franco, Elisa
AU - Ellard, Sian
AU - Flanagan, Sarah E.
AU - Hattersley, Andrew T.
N1 - Funding Information:
P.B. has a Sir George Alberti Clinical Research Training Fellowship funded by Diabetes UK (grant number 16/0005407). M.H.S. is a National Institute for Health Research (NIHR) Senior Nurse and Midwife Research Leader (NIHR4-SNMRL058) and is also supported by the Exeter NIHR Clinical Research Facility at the University of Exeter. N.J.T. is funded by a Wellcome Trust?funded GW4 PhD. E.D.F. has an RD Lawrence Fellowship funded by Diabetes UK (19/005971). S.E.F. has a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (grant number 105636/Z/14/Z). A.T.H. is supported by a Wellcome Trust Senior Investigator award (grant number 098395/Z/12/ Z). The University of Chicago Monogenic Diabetes Registry is supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK-104942 and P30-DK-020595). The views expressed in this article are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.
Publisher Copyright:
© 2020 by the American Diabetes Association.
PY - 2021/1
Y1 - 2021/1
N2 - ABCC8 mutations cause neonatal diabetes mellitus that can be transient (TNDM) or, less commonly, permanent (PNDM); ∼90% of individuals can be treated with oral sulfonylureas instead of insulin. Previous studies suggested that people with ABCC8-PNDM require lower sulfonylurea doses and have milder neurological features than those with KCNJ11-PNDM. However, these studies were short term and included combinations of ABCC8-PNDMand ABCC8-TNDM. We aimed to assess the long-term glycemic and neurological outcomes in sulfonylurea-treated ABCC8-PNDM. RESEARCH DESIGN AND METHODS We studied all 24 individuals with ABCC8-PNDM diagnosed in the U.K., Italy, France, and U.S. known to transfer from insulin to sulfonylureas before May 2010. Data on glycemic control; sulfonylurea dose; adverse effects, including hypoglycemia; and neurological features were analyzed using nonparametric statistical methods. RESULTS Long-term data were obtained for 21 of 24 individuals (median follow-up 10.0 [range 4.1–13.2] years). Eighteen of 21 remained on sulfonylureas without insulin at the most recent follow-up. Glycemic control improved on sulfonylureas (presulfony-lurea vs. 1-year posttransfer HbA1c 7.2% vs. 5.7%, P 5 0.0004) and remained excellent long term (1-year vs. 10-year HbA1c 5.7% vs. 6.5%, P 5 0.04), n 5 16. Relatively high doses were used (1-year vs. 10-year dose 0.37 vs. 0.25 mg/kg/day glyburide, P 5 0.50) without any severe hypoglycemia. Neurological features were reported in 13 of 21 individuals; these improved following sulfonylurea transfer in 7 of 13. The most common features were learning difficulties (52%), developmental delay (48%), and attention deficit hyperactivity disorder (38%). CONCLUSIONS Sulfonylurea treatment of ABCC8-PNDM results in excellent long-term glycemic control. Overt neurological features frequently occur and may improve with sulfonylureas, supporting early, rapid genetic testing to guide appropriate treatment and neurodevelopmental assessment.
AB - ABCC8 mutations cause neonatal diabetes mellitus that can be transient (TNDM) or, less commonly, permanent (PNDM); ∼90% of individuals can be treated with oral sulfonylureas instead of insulin. Previous studies suggested that people with ABCC8-PNDM require lower sulfonylurea doses and have milder neurological features than those with KCNJ11-PNDM. However, these studies were short term and included combinations of ABCC8-PNDMand ABCC8-TNDM. We aimed to assess the long-term glycemic and neurological outcomes in sulfonylurea-treated ABCC8-PNDM. RESEARCH DESIGN AND METHODS We studied all 24 individuals with ABCC8-PNDM diagnosed in the U.K., Italy, France, and U.S. known to transfer from insulin to sulfonylureas before May 2010. Data on glycemic control; sulfonylurea dose; adverse effects, including hypoglycemia; and neurological features were analyzed using nonparametric statistical methods. RESULTS Long-term data were obtained for 21 of 24 individuals (median follow-up 10.0 [range 4.1–13.2] years). Eighteen of 21 remained on sulfonylureas without insulin at the most recent follow-up. Glycemic control improved on sulfonylureas (presulfony-lurea vs. 1-year posttransfer HbA1c 7.2% vs. 5.7%, P 5 0.0004) and remained excellent long term (1-year vs. 10-year HbA1c 5.7% vs. 6.5%, P 5 0.04), n 5 16. Relatively high doses were used (1-year vs. 10-year dose 0.37 vs. 0.25 mg/kg/day glyburide, P 5 0.50) without any severe hypoglycemia. Neurological features were reported in 13 of 21 individuals; these improved following sulfonylurea transfer in 7 of 13. The most common features were learning difficulties (52%), developmental delay (48%), and attention deficit hyperactivity disorder (38%). CONCLUSIONS Sulfonylurea treatment of ABCC8-PNDM results in excellent long-term glycemic control. Overt neurological features frequently occur and may improve with sulfonylureas, supporting early, rapid genetic testing to guide appropriate treatment and neurodevelopmental assessment.
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U2 - 10.2337/dc20-1520
DO - 10.2337/dc20-1520
M3 - Article
C2 - 33184150
AN - SCOPUS:85100070636
VL - 44
SP - 35
EP - 42
JO - Diabetes Care
JF - Diabetes Care
SN - 1935-5548
IS - 1
ER -