The SUGAR-MGH investigators are studying the influence of inherited gene variants on the response to two commonly prescribed type 2 diabetes medications, metformin and glipizide. They hypothesize that variants in genes that are associated with type 2 diabetes or related traits may impact the effect of anti-diabetic medications. In addition, physiological responses to an insulin secretagogue or an insulin sensitizer may shed light on the mechanism of action of reported genetic associations.
Name: Glipizide
Name: Metformin
Name: Oral Glucose Tolerance Test
Description: Investigators will measure insulin and glucose levels for 240 minutes after Glipizide administration on Visit 1, and compare them by genotype at selected loci.
Measure: Glipizide response Time: Between 0-240 minutes, Visit 1Description: Investigators will measure the change in glycemic measures between Visit 1 and Visit 2 as an index of Metformin response, and compare them by genotype at selected loci.
Measure: Metformin response Time: 7 daysDescription: Investigators will measure GLP-1 and GIP during the 120 minutes of Visit 2, and compare them by genotype at selected loci.
Measure: Incretin levels Time: 120 minutes, Visit 2Description: Investigators will measure proinsulin and glucagon levels at regular intervals during Visits 1 and 2, and compare them by genotype at selected loci.
Measure: Proinsulin, glucagon Time: 7 daysDescription: Investigators will perform metabolomic profiling of plasma samples at regular intervals in Visits 1 and 2, by using initially a targeted approach on an existing platform that measures ~400 metabolites (both polar and non-polar); they will compare their relative concentrations by genotype at selected loci before and after the interventions.
Measure: Metabolomics Time: 7 daysDescription: Investigators will measure 25-hydroxy vitamin D levels at baseline, and examine its effects on glycemic measures during Visits 1 and 2.
Measure: Vitamin D Time: BaselineAllocation: N/A
Single Group Assignment
There is one SNP
In particular, sulfonylureas may have differential effects on individuals depending on the allelic variant they carry at KCNJ11 E23K; conversely, because TCF7L2 is postulated to influence insulin secretion by regulating the action of glucagon-like peptide 1 (GLP-1), and sulfonylureas act at a different step in the insulin secretion pathway, the effect of sulfonylureas on insulin secretion could be independent of genetic variation at TCF7L2. --- E23K ---