This study tests the hypothesis that non-diabetic individuals with a high genetic risk score for type 2 diabetes have impaired glucose tolerance and insulin resistance compared to those with a low genetic risk score for type 2 diabetes.

The study team will recruit individuals based on genetic risk score for type 2 diabetes from the biobank populations who have agreed to be recontacted for future research. Each participant will undergo a frequently sampled four-hour oral glucose tolerance test and whole body DXA scan (dual-energy X-ray absorptiometry) in addition to baseline laboratory and history assessment.

Inclusion Criteria:

• Age 10-70 years
• Prior participant of the UPenn Biobank or Center for Applied Genomics Biobank and agreed to be recontacted for future research.
• Adults with BMI 25kg/m2 or higher, children and adolescents with BMI 85th percentile or higher

Exclusion Criteria:

• prior diagnosis of type 1, type 2, or secondary diabetes
• use of medications that would impact glucose and insulin response such as steroids, metformin or other anti-diabetic medication
• acute illness that may impact insulin and glucose dynamics
• pregnancy
• hypothalamic obesity or related genetic disorder of metabolism
• recent systemic chemotherapy use
• gastrointestinal impairment or surgery that may impact absorption
• anemia
• major organ system illness or any underlying condition requiring regular medication or treatment that could make implementation of the protocol or interpretation of the study results difficult
• inability to comply with study protocol

Data analyses (including by outcomes assessors and investigators) will be de-identified, and individuals performing laboratory analyses and DXA interpretation will be blinded to polygenic risk score for type 2 diabetes. Participants and nursing staff will not be informed of polygenic risk score at the time of the study.