In This Section

Contact
E-mail
deleon [at] email.chop.edu
Phone
Location - People View
Room 804G

3615 Civic Center Blvd
Philadelphia, PA 19104
United States

Research Topics
Diva D. De León-Crutchlow, MD, MSCE
Diva D. De León-Crutchlow
Chief, Division of Endocrinology and Diabetes

Dr. De Leon-Crutchlow’s translational research program focuses on examining the pathophysiology of disorders of insulin regulation, identifying novel therapeutic targets, and developing new therapies for these conditions. The program approach includes patient-oriented research and bench research employing mouse models and primary islet cultures.

AddtoAny
Share:

Bio

Dr. De León-Crutchlow’s research focuses on the pathophysiology of monogenic disorders of insulin regulation resulting in hyper- and hypoglycemia, the role of the entero-insular axis, and how these mechanisms can be applied toward developing novel therapies.

The laboratory contributions from the examination of human islets isolated from surgical specimens from infants with congenital hyperinsulinism provide novel pathophysiological insights. A particular interest of Dr. De León-Crutchlow involves examining the interactions between the gut and pancreatic beta cell under pathologic conditions.

She demonstrated that the GLP-1 receptor is constitutively active in pancreatic islets isolated from a mouse model of hyperinsulinism (SUR-1-/-), and that pharmacologic antagonism of the GLP-1 receptor (GLP-1R) ameliorates hypoglycemia in SUR-1-/- mice and blunts abnormalities of insulin secretion in cultured mouse and human hyperinsulinism islets.

Dr. De León-Crutchlow is the lead investigator of several clinical studies on exendin-(9-39) as a novel therapy for congenital hyperinsulinism. From examining the phenotype of affected patients and human islets, she has provided novel insights into the pathophysiology of hyperinsulinism. Particularly important findings have been the functional, genomics, and metabolomics characterization of hyperinsulinism islets; the description of a novel syndrome of hyperinsulinism and hypopituitarism caused by a mutation in FOXA2; and the association of hyperinsulinism with mutations in the transcription factors HNF1A and HNF4A, which were previously known to cause monogenic diabetes and with Beckwith Wiedemann Syndrome caused by paternal uniparental disomy of 11p15.5. A better understanding of the pathophysiology and the molecular mechanisms of disease will facilitate the development of new therapeutics and a personalized approach to treatment of children with hyperinsulinism.

Dr. De León-Crutchlow also examines novel mechanisms of disease affecting insulin regulation and resulting in diabetes. Contributions from her laboratory include describing neonatal diabetes due to inactivating mutations in neurogenin-3, activating KATP channel mutations, and inactivating mutations of GATA6.

Education and Training

MD, University of Panama (1992)

MSCE, University of Pennsylvania (Clinical Epidemiology/Clinical Trials), 2012

Titles and Academic Titles

Chief of the Division of Endocrinology and Diabetes

Director, Congenital Hyperinsulinism Center

Distinguished Chair in the Department of Pediatrics

Attending Physician

Associate Professor of Pediatrics

Professional Memberships

American Diabetes Association, 2002-

The Endocrine Society, 2002-

Pediatric Endocrine Society, 2003-

Society for Pediatric Research, 2010-

Professional Awards

Center of Excellence Faculty Scholar, University of Pennsylvania, 2003

Fellow, Arab-American Frontiers of Science, Engineering, and Medicine Symposium. Kuwait Institute for Scientific Research, Kuwait, U.S. National Academies, 2011

Fellow, Japanese-American Kavil Frontiers of Science Symposium. Irvine, California, U.S. National Academies and the Japan Society for the Promotion of Science, 2012

Publication Highlights

Herrera A, Vajravelu ME, Givler S, Mitteer L, Avitabile CM, Lord K, De Leon DD. Prevalence of adverse events in children with congenital hyperinsulinism treated with diazoxide. J Clin Endocrinol Metab. 2018 Dec; 103(12):4365-4372. PMID: 30247666
Vajravelu ME, Chai J, Krock B, Baker S, Langdon D, Alter C, De León DD. Congenital Hyperinsulinism and Hypopituitarism Attributable to a Mutation in FOXA2. J Clin Endocrinol Metab. 2018 Mar; 103(3):1042-1047. PMID: 29329447
Li C, Ackermann AM, Boodhansingh KE, Bhatti TR, Liu C, Schug J, Doliba N, Han B, Cosgrove KE, Banerjee I, Matschinsky FM, Nissim I, Kaestner KH, Naji A, Adzick NS, Dunne MJ, Stanley CA, De León DD. Functional and Metabolomic Consequences of K(ATP) Channel Inactivation in Human Islets. Diabetes. 2017 Jul; 66(7):1901-1913. PMID: 28442472
Lord K, Radcliffe J, Gallagher PR, Adzick NS, Stanley CA, De León DD. High Risk of Diabetes and Neurobehavioral Deficits in Individuals With Surgically Treated Hyperinsulinism. J Clin Endocrinol Metab. 2015 Nov; 100(11):4133-9. PMID: 26327482
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 owing to inactivating mutations in the ATP-sensitive K+ channel. Diabetes. 2012 Oct; 61(10):2585-91. PubMed PMID: 22855730

Links of Interest