| Outcome Measures: |
Primary: Glipizide Response as Measured by Area Over the Glucose Curve Between Time 0 and 240 Minutes According to Genotype, Investigators will measure glucose levels at 0,30,60,90,120,180 and 240 minutes post 5mg Glipizide administration on Visit 1(Day1), and compare them by genotype at selected loci., 0, 30, 60, 90, 120, 180 and 240 minutes post 5mg oral glipizide dose, Day 1 (visit 1)|Glipizide Response as Measured by Area Under the Insulin Curve Between Time 0 and 240 Minutes According to Genotype, Investigators will measure insulin levels at 0,30,60,90,120,180 and 240 minutes post 5mg Glipizide administration on Visit 1(Day1), and compare them by genotype at selected loci., 0,30,60,90,120,180 and 240 minutes on Day 1 (Visit 1)|Metformin Response - Change in Fasting Glucose From Visit 1 to Visit 2, Investigators will measure the change in glycemic measures between Visit 1 (Day 1) and Visit 2 (Day 8) as an index of Metformin response, and compare them by genotype at selected loci. HOMA-IR is calculated from fasting glucose and fasting insulin values at both visit 1 (day 1) and visit 2 (day 8). HOMA-IR was calculated using (fasting glucose\*fasting insulin)/405) formula., Day 1 (Visit 1) and Day 8 (Visit 2)|Metformin Response - Change in HOMA-IR From Visit 1 to Visit 2, Investigators will measure the change in glycemic measures between Visit 1 (Day 1) and Visit 2 (Day 8) as an index of Metformin response, and compare them by genotype at selected loci. HOMA-IR is calculated from fasting glucose and fasting insulin values at both visit 1 (day 1) and visit 2 (day 8). HOMA-IR was calculated using (fasting glucose\*fasting insulin)/405) formula. A bigger difference/drop between visit 1 and visit 2 will show that metformin had an effect on insulin resistance index for these participants. The higher the HOMA-IR, the more insulin resistant you are., Day 1 (Visit 1) and Day 8 (Visit 2) | Secondary: Incretin Levels, Investigators will measure GLP-1 and GIP during the OGTT from 0 to 120 minutes of Visit 2, and compare them by genotype at selected loci., 0, 5, 10, 15, 30, 60 and 120 minutes, Day 8 (Visit 2)|Proinsulin (Fasting) at Visit 1 and Visit 2 by Genotype for rs7903146, Investigators will measure proinsulin levels at regular intervals during Visits 1 and 2, and compare them by genotype at selected loci., Day 1 (Visit 1) and Day 8 (Visit 2)|Metabolomics, Investigators will perform metabolomic profiling of plasma samples at regular intervals during 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 study interventions., Day 1 (Visit 1) and Day 8 (Visit 2)|Vitamin D, Investigators will measure 25-hydroxy vitamin D levels at baseline, and examine its effects on glycemic measures during Visits 1 and 2., Baseline|Fasting Glucagon at Visit 1 and Visit 2 by Genotype for rs7903146, Investigators will measure glucagon levels at regular intervals during Visits 1 and 2, and compare them by genotype at selected loci., Day 1 (Visit 1) and Day 8 (Visit 2)
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| Locations: |
Massachusetts General Hospital, Boston, Massachusetts, 02114, United States|Brigham and Women's Hospital, Boston, Massachusetts, 02116, United States|Joslin Diabetes Center, Boston, Massachusetts, 02116, United States
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