Phenotyping Genetic Risk for Type 2 Diabetes

Not Applicable

Recruiting

Interventions: Other: 75g glucose beverage (Glucola, Trutol, or similar brand)
Other: DXA, whole body

Brief Summary: 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: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Phenotyping	75g glucose beverage (Glucola, Trutol, or similar brand)	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.
Phenotyping	DXA, whole body	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.

Primary Outcome Measures

Name	Time	Method
Glucose response to an oral glucose load	samples will be collected over four hours and these results will be used to calculate area under the curve	Glucose area under the curve after the 75g glucose beverage

Secondary Outcome Measures

Name	Time	Method
Disposition index	samples will be collected over four hours after the 75g glucose beverage and these results will be used for mixed modeling	product of insulin sensitivity and amount of insulin released; calculated using mixed modeling techniques
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	DXA whole body scan visceral adiposity index
HOMA-IR	calculated from baseline fasting insulin and glucose levels	Insulin resistance estimate

Locations (2): University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
Childrens Hospital of Philadelphia
🇺🇸
Philadelphia, Pennsylvania, United States

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