Identification of β Cell Dysfunction in Relatives of Individuals With Type 1 Diabetes Mellitus

Study Summary

Despite the valuable information derived from older studies evaluating type 1 diabetes, the diabetes research community has, in large part, overlooked potential contributions of baseline abnormalities in β cell function to T1D development. Newer studies focusing on higher risk individuals often exclude family members without evidence of positive islet autoantibodies. New technologies to assay alternative biomarkers of β cell stress and death remain incompletely explored in both Ab negative and Ab positive family members of T1D patients. Specifically, modern biomarkers of β cell dysfunction have not been rigorously tested in combination with metabolic testing to fully understand their association with insulin secretion. The investigator's working hypothesis is that individuals at genetic risk for T1D exhibit baseline β cell dysfunction, even before development of detectable islet autoimmunity (seropositivity for islet Abs).

Primary Outcome

Our primary outcome is to assess if there is a difference in first phase beta call function in those genetically at risk for developing type 1 diabetes (first degree relatives) but who are islet autoantibody negative versus healthy controls with no family history of type 1 diabetes. We will calculate the first phase beta cell function by multiplying the acute c-peptide response to glucose (ACPRg) (nmol/L) by the insulin sensitivity (M/I) (x10-5 mmol/kg/min per pmol/L)

Interventions

• OTHER There is no intervention