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Mexican Carriers of the HNF1A p.E508K Variant Do Not Experience an Enhanced Response to Sulfonylureas

2018; American Diabetes Association; Volume: 41; Issue: 8 Linguagem: Inglês

10.2337/dc18-0384

1935-5548

Alexandro J. Martagón, Omar Yaxmehen Bello‐Chavolla, Olimpia Arellano‐Campos, Paloma Almeda‐Valdés, Geoffrey Walford, Ivette Cruz‐Bautista, Donají Gómez‐Velasco, Roopa Mehta, L. Hernández, Magdalena Sevilla‐Gonzalez, Tannia Leticia Viveros-Ruiz, María Luisa Ordóñez-Sánchez, Rosario Rodríguez-Guillén, José C. Florez, Marı́a Teresa Tusié-Luna, Carlos A. Aguilar‐Salinas, Josep M. Mercader, Alicia Huerta-Chagoya, Hortensia Moreno-Macías, Humberto Garcia‐Ortíz, Alisa K. Manning, Lizz Caulkins, Jason Flannick, Nick Patterson, Angélica Martínez‐Hernández, Federico Centeno-Cruz, Francisco Barajas‐Olmos, Carlos Zerrweck, Cecilia Contreras-Cubas, Elvia Mendoza‐Caamal, M. Revilla, Sergio Islas Andrade, Emilio J. Córdova, Xavier Soberón, María Elena González-Villalpando, Lynne R. Wilkens, Loı̈c Le Marchand, Kristine R. Monroe, Laurence N. Kolonel, Olimpia Arellano‐Campos, María Luisa Ordóñez-Sánchez, M. Rodríguez‐Torres, Yayoi Segura-Kato, Rosario Rodríguez-Guillén, Ivette Cruz‐Bautista, L. Hernández, Alexandro J. Martagón, Magdalena del Rocio Sevilla Gonzalez, Donají Gómez, Paloma Almeda‐Valdés, Maria Eugenia Garay, Juan Manuel Hernandez, Noël P. Burtt, Maria L. Cortés, David Altshuler, Christopher A. Haiman, Carlos A. Aguilar‐Salinas, Clicerio González‐Villalpando, Lorena Orozco, Teresa Tusié‐Luna, José C. Florez,

Diabetes and associated disorders

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.