Mexican Carriers of the HNF1A p.E508K Variant Do Not Experience an Enhanced Response to Sulfonylureas
Author:
Martagón Alexandro J.12, Bello-Chavolla Omar Yaxmehen13ORCID, Arellano-Campos Olimpia1, Almeda-Valdés Paloma14ORCID, Walford Geoffrey A.567, Cruz-Bautista Ivette14, Gómez-Velasco Donají V.1, Mehta Roopa14, Muñoz-Hernández Liliana1, Sevilla-González Magdalena1, Viveros-Ruiz Tannia L.1, Ordoñez-Sánchez María Luisa8, Rodríguez-Guillen Rosario8, Florez Jose C.567, Tusié-Luna María Teresa8, Aguilar-Salinas Carlos A.124ORCID, Mercader Josep M., Huerta-Chagoya Alicia, Moreno-Macías Hortensia, García-Ortiz Humberto, Manning Alisa, Caulkins Lizz, Flannick Jason, Patterson Nick, Martínez-Hernández Angélica, Centeno-Cruz Federico, Barajas-Olmos Francisco Martin, Zerrweck Carlos, Contreras-Cubas Cecilia, Mendoza-Caamal Elvia, Revilla-Monsalve Cristina, Islas Andrade Sergio, Córdova Emilio, Soberón Xavier, González-Villalpando María Elena, Wilkens Lynne, Le Marchand Loic, Monroe Kristine, Kolonel Laurence, Arellano-Campos Olimpia, Ordóñez-Sánchez María L., Rodríguez-Torres Maribel, Segura-Kato Yayoi, Rodríguez-Guillén Rosario, Cruz-Bautista Ivette, Muñoz-Hernández Linda Liliana, Martagón Alexandro J., Sevilla Gonzalez Magdalena del Rocio, Gómez Donají, Almeda-Valdés Paloma, Garay Maria Eugenia, Malacara Hernandez Juan Manuel, Burtt Noël P., Cortes Maria L., Altshuler David M., Haiman Christopher A., Aguilar-Salinas Carlos A., González-Villalpando Clicerio, Orozco Lorena, Tusié-Luna Teresa, Florez Jose C.,
Affiliation:
1. Unidad de Investigación de Enfermedades Metabólicas, Instituto Nacional de Ciencias Médicas y Nutrición, Ciudad de México, México 2. Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, Nuevo León, México 3. Plan de Estudios Combinados en Medicina, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, México 4. Departamento de Endocrinología y Metabolismo, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, México 5. Center for Genomic Medicine and Diabetes Unit, Massachusetts General Hospital, Boston, MA 6. Programs in Metabolism and Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 7. Harvard Medical School, Boston, MA 8. Unidad de Biología Molecular y Medicina Genómica, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, México
Abstract
OBJECTIVE
To assess whether an ethnic-specific variant (p.E508K) in the maturity-onset diabetes of the young (MODY) gene hepatocyte nuclear factor-1α (HNF1A) found in Mexicans is associated with higher sensitivity to sulfonylureas, as documented in patients with MODY3.
RESEARCH DESIGN AND METHODS
We recruited 96 participants (46 variant carriers and 50 age- and sex-matched noncarriers). Response to glipizide (one 2.5–5.0-mg dose), metformin (four 500-mg doses), and an oral glucose challenge was evaluated using a previously validated protocol. Glucose and insulin levels and their areas under the curve (AUCs) were compared between groups.
RESULTS
Carriers of the p.E508K variant had a lower maximum insulin peak during the glipizide challenge as compared with noncarriers with diabetes (P < 0.05). Also, carriers had a lower insulin response after the oral glucose challenge. Following an oral glucose tolerance test in the presence of metformin, carriers of the p.E508K variant with diabetes had a lower maximum insulin peak and total and incremental insulin AUC value as compared with noncarriers with diabetes (P < 0.05). A similar but nonsignificant trend was seen in participants without type 2 diabetes.
CONCLUSIONS
Carriers of variant p.E508K in HNF1A have a reduced insulin response rather than the increased sensitivity to sulfonylureas seen in patients with MODY3.
Funder
Consejo Nacional de Ciencia y Tecnología
Publisher
American Diabetes Association
Subject
Advanced and Specialized Nursing,Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
18 articles.
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