Mexican carriers of the HNF1A p. E508K variant do not experiencean enhanced response to sulfonylureas
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© 2018 by the American Diabetes Association. OBJECTIVE: To assess whether an ethnic-specific variant (p. E508K) in the maturity-onset diabetes of the young (MODY) gene hepatocyte nuclear factor-1a (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.