American Diabetes Association
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Type 1 diabetes genetic risk score differentiates subgroups of Ketosis-Prone Diabetes

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posted on 2023-07-28, 20:05 authored by Deborah Osafehinti, Surya N Mulukutla, Christiane S Hampe, Ruchi Gaba, Nalini Ram, Michael N Weedon, Richard A Oram, Ashok Balasubramanyam

Objective: To determine if genetic risk for type 1 diabetes (T1D) differentiates the four “Ab” subgroups of Ketosis-Prone Diabetes (KPD), where “A+” and “A-” define presence or absence of islet autoantibodies and “b+” and “b-” define presence or absence of beta cell function.

Research Design and Methods: We compared T1D genetic risk scores (GRS) of KPD patients across subgroups, race/ethnicity, beta cell function and glycemia. 

Results: Among 426 KPD patients (54% Hispanic, 31% African American, 11% White), rank-order of GRS was A+b- > A+b+ = A-b- > A-b+. GRS of A+b- KPD was lower than that of a T1D cohort and GRS of A-b+ KPD was higher than that of a T2D cohort. GRS was lowest among African American patients with a similar distribution across KPD subgroups.

Conclusions: T1D genetic risk delineates etiological differences between KPD subgroups. A+b- KPD patients have the highest and A-b+ KPD patients the lowest GRS. 


This work was supported by funds from NIH R01-DK056689 and the Rutherford Chair, Baylor-St. Luke’s Medical Center / Baylor College of Medicine (to AB), and a Diabetes UK Harry Keen Fellowship (16/0005529) (to RAO).