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

Abstract

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. We compared T1D genetic risk scores (GRS) of patients with KPD across subgroups, race/ethnicity, β-cell function, and glycemia. 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. 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.