Walford, Geoffrey AColomo, NataliaTodd, Jennifer NBillings, Liana KFernandez, MarleneChamarthi, BinduWarner, A SofiaDavis, JaclynLittleton, Katherine RHernandez, Alicia MFanelli, Rebecca RLanier, AmeliaBarbato, CorinneAckerman, Rachel JKhan, Sabina QBui, RosaGarber, LaurelStolerman, Elliot SMoore, Allan FHuang, ChunmeiKaur, VarinderpalHarden, MaeganTaylor, AndrewChen, LingManning, Alisa KHuang, PaulWexler, DeborahMcCarthy, Rita MLo, JanetThomas, Melissa KGrant, Richard WGoldfine, AllisonHudson, Margo SFlorez, Jose C2016-08-092016-08-092015-03-26Walford GA, Colomo N, Todd JN, Billings LK, Fernandez M, Chamarthi B, et al. 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. PLoS ONE. 2015; 10(3):e0121553http://hdl.handle.net/10668/2332ClinicalTrials.gov NCT01762046; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't;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.enAlelosGlucosa sanguíneaDiabetes Mellitus, Tipo IIPredisposición genética a la enfermedadglipicidaPrueba de tolerancia a la glucosaInsulinaBiomarcadoresHipoglicemiantesFenotipoPolimorfismo de nucleótido únicoProteína 2 similar al factor de transcripción 7Resultado del tratamientoMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::AgedMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Structures::Genome::Genome Components::Genes::AllelesMedical Subject Headings::Chemicals and Drugs::Biological Factors::Biological MarkersMedical Subject Headings::Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Glucose::Blood GlucoseMedical Subject Headings::Diseases::Endocrine System Diseases::Diabetes Mellitus::Diabetes Mellitus, Type 2Medical Subject Headings::Check Tags::FemaleMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genotype::Genetic Predisposition to DiseaseMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Sulfur Compounds::Sulfones::Sulfonylurea Compounds::GlipizideMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Clinical Laboratory Techniques::Clinical Chemistry Tests::Blood Chemical Analysis::Glucose Tolerance TestMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Hypoglycemic AgentsMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Pancreatic Hormones::InsulinsMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amidines::Guanidines::Biguanides::MetforminMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Biological Science Disciplines::Pharmacology::PharmacogeneticsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::PhenotypeMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single NucleotideMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::TCF Transcription Factors::Transcription Factor 7-Like 2 ProteinMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment OutcomeMedical Subject Headings::Named Groups::Persons::Age Groups::Adultresearch article25812009open access10.1371/journal.pone.01215531932-6203PMC4374872