2026-07-23T23:02:15Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/170852024-11-28T15:43:46Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc Walford, Geoffrey A author Colomo, Natalia author Todd, Jennifer N author Billings, Liana K author Fernandez, Marlene author Chamarthi, Bindu author Warner, A Sofia author Davis, Jaclyn author Littleton, Katherine R author Hernandez, Alicia M author Fanelli, Rebecca R author Lanier, Amelia author Barbato, Corinne author Ackerman, Rachel J author Khan, Sabina Q author Bui, Rosa author Garber, Laurel author Stolerman, Elliot S author Moore, Allan F author Huang, Chunmei author Kaur, Varinderpal author Harden, Maegan author Taylor, Andrew author Chen, Ling author Manning, Alisa K author Huang, Paul author Wexler, Deborah author McCarthy, Rita M author Lo, Janet author Thomas, Melissa K author Grant, Richard W author Goldfine, Allison author Hudson, Margo S author Florez, Jose C author 2015-03-26 OBJECTIVE: Genome-wide association studies have uncovered a large number of genetic variants associated with type 2 diabetes or related phenotypes. In many cases the causal gene or polymorphism has not been identified, and its impact on response to anti-hyperglycemic medications is unknown. The Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH, NCT01762046) is a novel resource of genetic and biochemical data following glipizide and metformin administration. We describe recruitment, enrollment, and phenotyping procedures and preliminary results for the first 668 of our planned 1,000 participants enriched for individuals at risk of requiring anti-diabetic therapy in the future. METHODS: All individuals are challenged with 5 mg glipizide × 1; twice daily 500 mg metformin × 2 days; and 75-g oral glucose tolerance test following metformin. Genetic variants associated with glycemic traits and blood glucose, insulin, and other hormones at baseline and following each intervention are measured. RESULTS: Approximately 50% of the cohort is female and 30% belong to an ethnic minority group. Following glipizide administration, peak insulin occurred at 60 minutes and trough glucose at 120 minutes. Thirty percent of participants experienced non-severe symptomatic hypoglycemia and required rescue with oral glucose. Following metformin administration, fasting glucose and insulin were reduced. Common genetic variants were associated with fasting glucose levels. CONCLUSIONS: SUGAR-MGH represents a viable pharmacogenetic resource which, when completed, will serve to characterize genetic influences on pharmacological perturbations, and help establish the functional relevance of newly discovered genetic loci to therapy of type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01762046. 10.1371/journal.pone.0121553 1932-6203 PloS One http://hdl.handle.net/10668/2332 25812009 http://hdl.handle.net/20.500.12105/17085 Alelos Glucosa sanguínea Diabetes Mellitus, Tipo II Predisposición genética a la enfermedad glipicida Prueba de tolerancia a la glucosa Insulina Biomarcadores Hipoglicemiantes Fenotipo Polimorfismo de nucleótido único Proteína 2 similar al factor de transcripción 7 Resultado del tratamiento The study to understand the genetics of the acute response to metformin and glipizide in humans (SUGAR-MGH): design of a pharmacogenetic resource for type 2 diabetes.