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

Diabetes Care
Alexandro J MartagónSlim Initiative in Genomic Medicine for the Americas (SIGMA) Type 2 Diabetes Consortium

Abstract

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. 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. 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. Carriers of variant p.E508K in HNF1A have a reduced insulin response rather t...Continue Reading

References

Feb 15, 1997·The Journal of Clinical Investigation·M LehtoL Groop
Feb 24, 1998·Diabetic Medicine : a Journal of the British Diabetic Association·A T Hattersley
Jun 17, 1998·Diabetologia·O SøvikG I Bell
Sep 29, 2001·The New England Journal of Medicine·S S FajansK S Polonsky
Oct 25, 2003·Lancet·Ewan R PearsonAndrew T Hattersley
Apr 25, 2009·Diabetic Medicine : a Journal of the British Diabetic Association·M ShepherdA T Hattersley
Jun 11, 2014·JAMA : the Journal of the American Medical Association·UNKNOWN SIGMA Type 2 Diabetes ConsortiumDaniel G MacArthur
Jan 30, 2016·Diabetes Research and Clinical Practice·Souhaïra Ben KhelifaAbdelhedi Miled
Jan 5, 2017·Nutrition Reviews·Omar Y Bello-ChavollaMauricio Hernández-Avila

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Dec 18, 2019·European Journal of Human Genetics : EJHG·Clara S H TanSu Chi Lim
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