Phenotyping Genetic Risk for Type 2 Diabetes

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Phenotyping Children and Adults With Possible High or Low Genetic Risk for Type 2 Diabetes

Conditions
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Diabetes Mellitus, Type 2, Genetics

Intervention / Treatment
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* Other: 75g glucose beverage (Glucola, Trutol, or similar brand)
* Other: DXA, whole body


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Interventional Model Description: cross sectional
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Phenotyping<br>All participants will undergo a four-hour frequently sampled oral glucose tolerance test in which they will ingest a 75g glucose beverage (intervention) within five minutes and have samples collected at baseline and for four hours after. They will also undergo a whole body DXA (intervention) during the study day. | Other: 75g glucose beverage (Glucola, Trutol, or similar brand)<br>* Subjects will present fasting to the study day and ingest the glucose beverage during the oral glucose tolerance test.<br>Other: DXA, whole body<br>* Subjects will undergo a whole body DXA scan for assessment of adiposity index and body fat distribution.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose response to an oral glucose load | Glucose area under the curve after the 75g glucose beverage | samples will be collected over four hours and these results will be used to calculate area under the curve | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visceral adiposity index | DXA whole body scan visceral adiposity index | DXA scan will be obtained on the same day as the oral glucose test and will be completed in less than 30 minutes | 
| HOMA-IR | Insulin resistance estimate | calculated from baseline fasting insulin and glucose levels | 
| Disposition index | product of insulin sensitivity and amount of insulin released; calculated using mixed modeling techniques | samples will be collected over four hours after the 75g glucose beverage and these results will be used for mixed modeling | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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polygenic risk for type 2 diabetes