Type 1 Diabetes Genetic Risk Score Differentiates Subgroups of Ketosis-Prone Diabetes

Abstract

OBJECTIVE To determine whether genetic risk for type 1 diabetes (T1D) differentiates the four Aβ subgroups of ketosis-prone diabetes (KPD), where A+ and A− define the presence or absence of islet autoantibodies and β+ and β− define the presence or absence of β-cell function. RESEARCH DESIGN AND METHODS We compared T1D genetic risk scores (GRS) of patients with KPD across subgroups, race/ethnicity, β-cell function, and glycemia. RESULTS Among 426 patients with KPD (54% Hispanic, 31% African American, 11% White), rank order of GRS was A+β− > A+β+ = A−β− > A−β+. GRS of A+β− KPD was lower than that of a T1D cohort, and GRS of A−β+ KPD was higher than that of a type 2 diabetes cohort. GRS was lowest among African American patients, with a similar distribution across KPD subgroups. CONCLUSIONS T1D genetic risk delineates etiologic differences among KPD subgroups. Patients with A+β− KPD have the highest and those with A−β+ KPD the lowest GRS.