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

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Genetic risk for type 1 diabetes (T1D) helps distinguish ketosis-prone diabetes (KPD) subgroups. Patients with islet autoantibodies and absent beta-cell function (A+β-) had the highest T1D genetic risk.

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Area of Science:

  • Endocrinology
  • Genetics
  • Immunology

Background:

  • Ketosis-prone diabetes (KPD) is a heterogeneous condition.
  • KPD is characterized by four subgroups based on islet autoantibodies (A+ or A-) and beta-cell function (β+ or β-).
  • Understanding the distinct etiologies of KPD subgroups is crucial for effective management.

Purpose of the Study:

  • To investigate if genetic risk for type 1 diabetes (T1D) differentiates the four KPD subgroups.
  • To compare T1D genetic risk scores (GRS) across KPD subgroups, considering race/ethnicity, beta-cell function, and glycemic control.

Main Methods:

  • Retrospective analysis of 426 KPD patients.
  • Comparison of T1D genetic risk scores (GRS) among KPD subgroups (A+β-, A+β+, A-β-, A-β+).
  • Analysis of GRS in relation to race/ethnicity, beta-cell function, and glycemia.

Main Results:

  • The rank order of GRS in KPD subgroups was A+β- > A+β+ = A-β- > A-β+.
  • A+β- KPD patients had a lower GRS compared to a T1D cohort.
  • A-β+ KPD patients had a higher GRS compared to a type 2 diabetes cohort.
  • African American patients exhibited the lowest GRS across all subgroups.

Conclusions:

  • T1D genetic risk effectively delineates etiologic differences among KPD subgroups.
  • Patients with A+β- KPD demonstrate the highest T1D genetic risk.
  • Patients with A-β+ KPD exhibit the lowest T1D genetic risk.