Diva D. De León-Crutchlow, MD, MSCE
Areas of expertise: Congenital Hyperinsulinism, Hyperinsulinism, Monogenic Diabetes (MODY), Neonatal Diabetes, Post-prandial Hypoglycemia after Nissen Fundoplication
Locations: Main Building
About Diva D. De León-Crutchlow, MD, MSCE
Dr. Diva D. De León-Crutchlow is Chief of the Division of Endocrinology and Diabetes, Director of the Congenital Hyperinsulinism Center at Children's Hospital of Philadelphia (CHOP), and professor of pediatrics at the Perelman School of Medicine at the University of Pennsylvania. She specializes in the diagnosis and management of hypoglycemia disorders, particularly, disorders of insulin secretion. She also has expertise in the diagnosis and treatment of familial forms of diabetes.
Dr. De León-Crutchlow is a physician-scientist and directs an active NIH-funded translational research program. Her research focuses on the interactions between gut hormones and pancreatic beta cell function. She is particularly interested in understanding the pathophysiology of disorders of excessive insulin secretion such as congenital hyperinsulinism. Her aim is to improve understanding of these disorders with the goal of developing effective and innovative therapies. She has published numerous papers in prestigious scientific medical journals, including the Journal of Pediatrics, the Journal of Clinical Endocrinology and Metabolism, Diabetes, and Clinical Genetics.
Dr. De León-Crutchlow is a member of numerous professional societies, including the Society for Pediatric Research, the Pediatric Endocrine Society and the American Diabetes Association.
Titles
Pediatric Endocrinologist
Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania
Certifications
Pediatric Endocrinology – American Board of Pediatrics
Pediatrics – American Board of Pediatrics
Leadership and Memberships
CHOP Clinical Trials Research Affinity Group, Advisory committee member
Editorial and Academic Positions
Editorial positions
2013-present, International Journal of Endocrinology, ad hoc reviewer
2012-present, Journal of Pediatrics, ad hoc reviewer
2012-present, Journal of Neonatal-Perinatal Medicine, ad hoc reviewer
2012-present, Endocrinology, ad hoc reviewer
2011-present, Journal of Clinical Endocrinology and Metabolism, ad hoc reviewer
2011-present, Diabetes Care, ad hoc reviewer
2006-present, Pediatric Diabetes, ad hoc reviewer
2006-present, American Journal of Physiology, ad hoc reviewer
2005-present, Diabetes, ad hoc reviewer
2003-present, Physiologic Genomics, ad hoc reviewer
Academic and institutional committees
2009-present, Chair, Division of Endocrinology Scientific Review Committee
2005-present, CHOP Endocrine Fellowship Advisory Committee
Research Interests
Pathophysiology of congenital hyperinsulinism Mechanisms of entero-insulinar axis dysregulation in hypoglycemia Identification and validation of new therapeutic targets for hyperinsulinism Pathophysiology of post-prandial hypoglycemia after fundoplication Neurodevelopmental outcomes in children with congenital hyperinsulinism
Education & training
Graduate Degree
MS in Clinical Epidemiology - Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Medical Degree
MD - University of Panama School of Medicine, Panama City, Panama
Internship
Monmouth Medical Center, Long Branch, NJ
Residency
Monmouth Medical Center, Long Branch, NJ
Fellowship
The Children's Hospital of Philadelphia, Philadelphia, PA
Publications
Publications
2023
Rosenfeld E, Alzahrani O, De Leon DD: Undiagnosed hypoglycemia disorders in children detected when hypoglycemia occurs in the setting of illness: a retrospective study. BMJ Paediatrics Open BMJ, 7(1), February 2023.
Stanley CA, Thornton PS, De Leon DD: New approaches to screening and management of neonatal hypoglycemia based on improved understanding of the molecular mechanisms of hypoglycemia. Front Pediatr11:1071206, March 2023.
Rosenfeld E, De Leon DD: Bridging the gaps: recent advances in diagnosis, care, and outcomes in congenital hyperinsulinism. Curr Opin Pediatr, Mar 2023.
2022
Thornton PS, Stanley CA, De Leon DD: Congenital hyperinsulinism: a historic perspective. Horm Res Paediatr 95: 631-637, 2022.
Danowitz M, De Leon DD: The role of GLP-1 signaling in hypoglycemia due to hyperinsulinism. Front Endocrinol 13: 863184, Mar 2022.
Sigal WM, Alzahrani O, Guadalupe GM, Guzman H, Radcliffe J, Thomas NH, Jawad AF, De Leon DD: Natural history and neurodevelopment outcomes in perinatal stress induced hyperinsulinism. Front Pediatr Page: doi: 10.3389/fped.2022.999274. Oct 2022.
Cuff H, Lord K, Ballester L, Scully T, Stewart N, De Leon DD: The use of lanreotide in the treatment of congenital hyperinsulinism. J Clin Endocrinol Metab 107(8): e3115-e3120, Jul 2022.
Boodhansingh KE, Yang Z, Li C, Chen P, Lord K, Becker SA, States LJ, Adzick NS, Bhatti T, Show-Ling S, Ganguly A, Stanley CA, De Leon DD: Localized islet nuclear enlargement hyperinsulinism (LINE-HI) due to ABCC8 and GCK mosaic mutations. Eur J Endocrinol Online ahead of print: EJE-21-1095, Jun 2022.
Rosenfeld E, Nanga RPR, Lucas A, Revell AY, Thomas A, Thomas NH, Roalf DR, Shinohara RT, Reddy R, Davis KA, De Leon DD: Characterizing the neurological phenotype of the hyperinsulinism hyperammonemia syndrome. Orphanet J Rare Dis 17(1): 248, Jun 2022.
Stefanovski D, Vajravelu ME, Givler S, De Leon DD: Exendin-(9-39) effects on glucose and insulin in children with congenital hyperinsulinism during fasting and during a meal and a protein challenge Diabetes Care. 45(6): 1381-1390, June 2022.
2021
Rayannavar A, Mitter LM, Balliro CA, El-Khatib FH, Lord KL, Hawkes CP, Ballester LS, Damiano ER, Russel SJ, De Leon DD: The biohormonal bionic pancreas improves glycemic control in individuals with hyperinsulinism and postpancreatectomy diabetes - a pilot study. Diabetes Care 44(11): 2582-5, November (Epub ahead of print] 2021.
Vajravelu ME, Lee JJ, Mitteer L, Zemel BS, Bittinger K, De Leon DD: Gut microbiome profile after pancreatectomy in infants with congenital hyperinsulinism. Pancreas 50(1): 89-92, January 2021.
States LJ, Becker SA, De Leon DD: Congenital hyperinsulinism: localization of a focal lesion with 18F-FDOPA positron emission tomography. Pediatr Radiol Epub ahead of print, Oct 2021.
2020
Soundarapandian MM, Juliana CA, Chai J, Haslett PA, Fitzgerald K, De Leon DD: Activation of protein kinase A (PKA) signaling mitigates congenital hyperinsulinism associated hypoglycemia in the Sur1-/- mouse model. PLoS One 15(7): e0236892, July 2020.
Rayannavar A., Elci O.U., Mitteer L., De Leon D.D: Continuous glucose monitoring systems: are they useful for evaluating glycemic control in children with hyperinsulinism? Horm Res Paediatr 92(5): 319-27, March 2020 Notes: DOI:10.1159/000506230.
States LJ, Saade-Lemus S, De Leon DD: 18-F-L 3,4 Dihydoxyphenylalanine PET/Computed Tomography in the management of Congenital Hyperinsulinism. PET Clin 15(3): 349-59, July 2020.
2019
Rosenfeld E, Ganguly A, De Leon D: Congenital Hyperinsulinism Disorders: genetic and clinical characteristics. Am J Med Gen C Semin Med Genet [Epub ahead of print], August 14 2019.
Hawkes CP, De Leon DD, Rickels MR: Novel preparations of glucagon for the prevention and treatment of hypoglycemia. Curr Diab Rep 19(10): 97, Sep 2019.
Adzick NS, De Leon DD, Staley LJ, Lord K, Bhatti TR, Becker SA, Stanley CA: Surgical treatment of congenital hyperinsulinism: results from 500 pancreatectomies in neonates and children. J Ped Surg 54(1): 27-32, Jan 2019.
Yap KL, Knight Johnson AE, Fischer D, Sodadasi P, Deml J, Nelakuditi V, Hallbach S, Jeha GS, Burrage LC, Bodamer O, Benavides VC, Lewis AM, Ellard S, Shah P, Cody D, Diaz A, Devarajan A, Truong L, Greeley SA, De Leon DD, Edmonson AC, Das S, Thornton P, Waggoner D, del Gaudio D. : Congenital hyperinsulinism as the presenting feature of Kabuki syndrome: clinical and molecular characterization of 10 affected individuals Genet Med 21(1): 262-5, Jan 2019.
Grand K, Gonzalez-Gadolfi C, Ackermann AM, Aljeaid D, Bedoukian E, Bird LM, De Leon DD, Diaz J, Hopkin RJ, Kadakia SP, Keena B, Klein KO, Krantz I, Leon E, Lord K, McDougall C, Medne L, Skraban CM, Stanley CA, Tarpinian J, Zackai E, Deardorff MA, Kalish JM: Hyperinsulinemic hypoglycemia in seven patients with de novo NSD1 mutations. Am J Med Genet A 179(4): 542-51, Apr 2019.
Boodhansingh KE, Balamurugan K, Mitteer L M, Givler S, De Leon D, Shyng SL, Ganguly A, Stanley CA: Novel dominant KATP channel mutations in infants with congenital hyperinsulinism: validation by in vitro expression studies and in vivo carrier phenotyping. Am J Med Genet A [Epub ahead of print], Aug 28 2019.
Hawkes CP, Lado JJ, Givler S, De Leon DD: The effect of continuous intravenous glucagon on glucose requirement in infants with congenital hyperinsulinism. JIMD Rep 45: 45-50, 2019.
2018
Gibson CE, Boodhansingh KE, Li C, Conlin L, Chen P, Becker S, Adzick NS, Bamba V, De Leon DD, Ganguly A, Stanley CA: Congenital hyperinsulinism in Infants with Turner Syndrome: Possible association with Monosomy X and KDM6A haploinsufficiency. Hormone Research in Pediatrics 89:413-422, 2018.
Adzick NS, De Leon DD, States LJ, Lord K, Bhatti TR, Becker SA, Stanley CA. Surgical treatment of congenital hyperinsulinism: Results from 500 pancreatectomies in neonates and children. J Pediatr Surg. 2019 Jan;54(1):27-32. doi: 10.1016/j.jpedsurg.2018.10.030. Epub 2018 Oct 5.
2017
Banerjee I, De León D, Dunne MJ. Extreme caution on the use of sirolimus for the congenital hyperinsulinism in infancy. Orphanet J Rare Dis. 2017 Apr 14;12(1):70. doi: 10.1186/s13023-017-0621-5.
Ferrara CT, Boodhansingh KE, Paradies E, Giuseppe F, Steinkrauss LJ, Topor LS, Quintos JB, Ganguly A, De León DD, Palmieri F, Stanley CA. Novel hypoglycemia phenotype in congenital hyperinsulinism due to dominant mutations of uncoupling protein 2. J Clin Endocrinol Metab. 2017 Mar 1;102(3):942-949. doi: 10.1210/jc.2016-3164.
Barrosse-Antle M, Su C, Chen P, Boodhansingh KE, Smith TJ, Stanley CA, De León DD, Li C. A severe case of hyperinsulinism due to hemizygous activating mutation of glutamate dehydrogenase. Pediatr Diabetes. 2017 Feb 6. doi: 10.1111/pedi.12507.
De León DD, Stanley CA. Congenital hypoglycemia disorders: new aspects of etiology, diagnosis, treatment and outcomes: Highlights of the Proceedings of the Congenital Hypoglycemia Disorders Symposium, Philadelphia April 2016. Pediatr Diabetes. 2017 Feb;18(1):3-9. doi: 10.1111/pedi.12453. Epub 2016 Oct 18.
McMahon AW, Wharton GT, Thornton P, De León DD. Octreotide use and safety in infants with hyperinsulinism. Pharmacoepidemiol Drug Saf. 2017 Jan;26(1):26-31. doi: 10.1002/pds.4144. Epub 2016 Dec 2.
2016
Martin GM, Rex EA, Devaraneni P, Denton JS, Boodhansingh KE, De León DD, Stanley CA, Shyng SL. Pharmacological Correction of Trafficking Defects in ATP-sensitive Potassium Channels Caused by Sulfonylurea Receptor 1 Mutations. J Biol Chem. 2016 Oct 14;291(42):21971-21983. Epub 2016 Aug 29.
Yang TB, McMahon P, De Léon DD, Treat JR. Use of propranolol for treating hemangiomas in infants with previously diagnosed hypoglycemic conditions. Pediatr Dermatol. 2016 Nov;33(6):e381-e384. doi: 10.1111/pde.12975. Epub 2016 Aug 30.
Wong SY, Beamer LJ, Gadomski T, Honzik T, Mohamed M, Wortmann SB, Brocke Holmefjord KS, Mork M, Bowling F, Sykut-Cegielska J, Koch D, Ackermann A, Stanley CA, Rymen D, Zeharia A, Al-Sayed M, Marquardt T, Jaeken J, Lefeber D, Conrad DF, Kozicz T, Morava E. Defining the phenotype and assessing severity in phosphoglucomutase-1 deficiency. J Pediatr. 2016 Aug;175:130-136.e8. doi: 10.1016/j.jpeds.2016.04.021. Epub 2016 May 17.
Coughlin CC, Roy SM, Arkin LM, Adzick NS, Yan AC, De León DD, Rubin AI. Iatrogenic necrolytic migratory erythema in an infant with congenital hyperinsulinism. Pediatr Dermatol. 2016 Mar-Apr;33(2):e43-7. doi: 10.1111/pde.12741. Epub 2015 Dec 9.
Hawkes CP, Grimberg A, Dzata VE, De León DD. Adding Glucagon-Stimulated GH Testing to the Diagnostic Fast Increases the Detection of GH-Sufficient Children. Horm Res Paediatr. 2016;85(4):265-72. doi: 10.1159/000444678. Epub 2016 Mar 17.
Kalish JM, Boodhansingh KE, Bhatti TR, Ganguly A, Conlin LK, Becker SA, Givler S, Mighion L, Palladino AA, Adzick NS, De León DD, Stanley CA, Deardorff MA. Congenital hyperinsulinism in children with paternal 11p uniparental isodisomy and Beckwith-Wiedemann syndrome. J Med Genet. 2016 Jan;53(1):53-61. doi: 10.1136/jmedgenet-2015-103394. Epub 2015 Nov 6.
Hawkes CP, Adzick NS, Palladino AA, DeLeon DD: Late presentation of fulminant necrotizing enterocolitis in a child with hyperinsulinism on octreotide therapy. Horm Res Paediatr 86:131-136, 2016.
2014
Stanescu DE, Hughes N, Patel P, De León DD: A novel mutation in GATA6 causes pancreatic agenesis. Pediatr Diabetes Jan 17 2014 [Epub ahead of print]
Browning E, Wang H, Hong N, Yu K, Buerk DG, DeBolt K, Gonder D, Sorokina EM, Patel P, De León DD, Feinstein SI, Fisher AB and Chatterjee S: Mechanotransduction drives post ischemic revascularization through KATP channel closure and production of reactive oxygen species. Antioxidants & Redox Signaling 20(6): 872-86, Feb 2014.
Lasaosa M, Patel P, Givler S, De León DD, Seeholzer SH: A liquid chromatography-mass spectrometry assay for quantification of exendin [9-39] in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci 947-948: 186-91, Feb 2014.
2013
Lord K, Dzata E, Snider KE, Gallagher PR, De León DD: Clinical presentation and management of children with diffuse and focal hyperinsulinism: a review of 223 cases. J Clin Endocrinol Metab 98(11): E1786-9, Nov 2013.
Lord K, De León DD: Monogenic hyperinsulinemic hypoglycemia: current insights into the pathogenesis and management. Int J Pediatr Endocrinol 1: 3, Feb 2013.
2012
Lin YW, Akrouh A, Hsu YC, Hughes N, Nichols CG, De León DD: Compound heterozygous mutations in the SUR1 (ABCC 8) subunit of pancreatic K(ATP) channels cause neonatal diabetes by perturbing the coupling between Kir6.2 and SUR1 subunits. Channels (Austin) 6(2): 133-8, March-April 2012.
Calabria AC, Li C, Gallagher PR, Stanley CA, De León DD: GLP-1 receptor antagonist exendin-(9-39) elevates fasting blood glucose levels in congenital hyperinsulinism due to inactivating mutations in the ATP-sensitive K+ channel. Diabetes 61(10): 2585-91, Oct 2012.
Stanescu DE, Hughes N, Kaplan B, Stanley CA, De León DD: Novel presentations of congenital hyperinsulinism due to mutations in the MODY genes: HNF1A and HNF4A. J Clin Endocrinol Metab 97(10): E2026-30, Oct 2012.
Books
Volume Editors: De Leon DD, Stanley CA: Monogenic Hyperinsulinemic Hypoglycemia Disorders. Frontiers in Diabetes. Karger, Basel, Switzerland, 12, Feb 2012.
Editorials, Reviews, Chapters
2013
Alves C, Constança J, De León DD, Snider K, Stanley C: A novel atypical presentation of insulin autoimmune syndrome (Hirata's disease) in a child. J Pediatr Endocrinol Metab 26(11-12): 1163-6, Jul 2013.
De León DD and Stanley CA: Hypoglycemia. Pediatric Endocrinology: A Practical Clinical Guide. Radovick S and MacGillivray MH (eds.). Springer, New York, NY. 2013.
De León DD, Stanley CA: Determination of insulin for the diagnosis of hyperinsulinemic hypoglycemia. Best Pract Res Clin Endocrinol Metab 27(6): 763-9, Dec 2013.
2012
De León DD: Role of Incretin Hormones in Hyperinsulinemic Hypoglycemia Frontiers in Diabetes: Monogenic Hyperinsulinemic Hypoglycemia Disorders. Stanley CA and De León DD (eds.). Karger, Basel, Switzerland, 21, Feb 2012.
De León DD, Stanley CA: Pathophysiology of Diffuse ATP-Sensitive Potassium Channel Hyperinsulinism. Frontiers in Diabetes: Monogenic Hyperinsulinemic Hypoglycemia Disorders. Stanley CA and De León DD (eds.). Karger, Basel, Switzerland, 21, Feb 2012.
2011
Palladino AA and De León DD: Hypoglycemia. Netter's Pediatrics (Netter Clinical Science). Florin T and Ludwig S (eds.). Saunders, Jun 2011.
2010
Weaver LA, De León DD, Borgmann-Winter K: Use of metformin to control clozapine-associated weight gain in an adolescent with schizoaffective disorder. J Child and Adolesc Psychopharmacol 20(2): 153-7, Apr 2010.
Thornton PS, Stanley CA, De Leon D, Kelly A, Sperling MA, Wolfsdorf JI, Haymond M: Research initiatives in neonatal hypoglycemia. J Pediatr 156(5): 862-3, May 2010.
Pinney SE, De León DD: Hypoglycemia. The Inpatient Pediatrics Work-Up. Shah and Frank (eds.). Lippincott Williams & Wilkins, 2010.
2008
De León DD, Stanley CA: Permanent Neonatal Diabetes Mellitus GeneReviews™ [Internet] Pagon RA, Adam MP, Bird TD, Dolan CR, Fong CT, Smith RJH, Stephens K (eds.). Copyright, University of Washington, Seattle, 1993-2014. Feb 2008 [Updated 2014 Jan 23] Notes: Available at http://www.ncbi.nlm.nih.gov/books/NBK1447/
Bamba V and De León DD: Hyperinsulinism. The 5-Minute Pediatric Consult. Schwartz, MW (eds.). Lippincott Williams & Wilkins, Philadelphia, PA, 5th edition, 2008.
De León DD, Stanley CA, Sperling MA: Hypoglycemia in Neonates and Infants. Pediatric Endocrinology Sperling, MA (eds.). Saunders, 3rd edition, 2008.
2007
Hoffman TL, Blanco E, Lane A, Galvin-Parton P, Gadi I, Santer R, De León DD, Stanley C, Wilson TA: Glucose metabolism and insulin secretion in a patient with ABCC8 mutation and Fanconi-Bickel syndrome caused by maternal isodisomy of chromosome 3. Clin Genet 71(6): 551-7, Jun 2007.
De León D, Ham N, Katz LEL: Growth Factor Regulation of Fetal Development. Fetal and Neonatal Physiology. Polin R and Fox (eds.). 4th Edition, 2007.
2006
De León D: Hyperinsulinism. The 5 Minute Pediatric Consult. Schwartz, MW (eds.). Lippincott Williams & Wilkins, Philadelphia, PA, 4th edition, 2006.
De León DD and Stanley CA: Screening for Hypoglycemia in Newborns. When to Screen in Obstetrics and Gynecology. Wildschut, Weiner and Peters (eds.). Elsevier, Philadelphia, PA, 2nd edition, 2006.
2004
De León DD and Grimberg A: Disorders of Growth. Requites in Pediatrics - Endocrinology. Moshang T Jr (eds.). Mosby Publishing, St. Louis, MO, 2004.
2003
De León DD, Cohen P, and Katz L: Growth Factor Regulation of Fetal Growth. Fetal and Neonatal Physiology. Polin, Fox and Abman (eds.). Saunders, 3rd edition, 2003.
2002
De León DD, Lange BJ, Walterhouse D, Moshang T: Long-term (15 years) outcome in an infant with metastatic adrenocortical carcinoma. J Clin Endocrinol Metab 87(10): 4452-6, Oct 2002.
Ng D (De León DD), Weinzimer S: Hyperinsulinism. The 5 Minute Pediatric Consult. Schwartz MW (eds.). Lippincott Williams & Wilkins, Philadelphia, PA 3: 1057, 2002.
2001
Stephens M, Batres LA, Ng D (De León DD), Baldassano R: Growth failure in the child with inflammatory bowel disease. Semin in Gastrointes Dis 12(4): 253-62, Oct 2001.
1994
Rivas de La Lastra E, Lasso Bonilla M, De León DD: Cellulitis periorbiaria por Dermatobia Hominis [Periorbital cellulitis caused by Dermatobis Hominis] Boletin de al Sociedad Panameña de Pediatria 23(1): 43-8, 1994.
1991
De León DD, De León F, De León S, et al. : Aterosclerosis: Detección de los factores de riesgo en la edad pediátrica Aterosclerosis:Detection of risk factors in pediatrics]. Revista Medico-Cientifica 6(1): 46-53, 1991.