244-OR: Toward Improved Identification of Adult-Onset Type 1 Diabetes (T1D): Clinical Characteristics Associated with T1D Polygenic Risk Scores in the Million Veteran Program (MVP)
Authors: YANG PETER K. , JACKSON SANDRA , CHAREST BRIAN R. , WEEDON MICHAEL N. , CHENG YILING J. , SUN YAN V. , RAGHAVAN SRIDHARAN , LITKOWSKI ELIZABETH M. , LEGVOLD BRIAN T. , RHEE MARY K. , MERCADO CARLA , ORAM RICHARD A. , VUJKOVIC MARIJANA , REAVEN PETER , CHO KELLY , PHILLIPS LAWRENCE S. , LEONG AARON 
Published: June 2021

Adult onset T1D is often misdiagnosed as T2D, leading to poor metabolic control and increased risk of microvascular complications and cardiovascular morbidity and mortality. We examined characteristics associated with a T1D genetic risk score in Veterans, a population where new diagnoses are generally presumed to be T2D, since persons with typical juvenile-onset T1D are excluded from military service. A 30 SNP T1D genetic risk score (GRS), previously validated with the Wellcome Trust Case Control Consortium (WTCCC), was applied to 111,663 Veterans with diabetes in the MVP. Patients were stratified by T1D GRS centile groups (≤5th, &gt;5th-≤36th, &gt;36th-≤50th, and &gt;50th) which corresponded to T1D specificity in the WTCCC of 29%, 53%, 90%, and 95%, respectively. Typical T1D clinical characteristics were significantly more common (p&lt;0.001) across increasing GRS centile groups: diabetic ketoacidosis 1.07%, 1.34%, 1.95%, 3.55%; hypoglycemia prompting an emergency department visit 3.95%, 3.84%, 4.45%, 5.45%; random plasma glucose &lt;50 mg/dl at a primary care visit 8.05%, 7.99%, 9.01%, 12.43%; years to starting outpatient insulin Rx 4.40, 4.31, 3.97, 3.38; any use of a T1D ICD code 16.56%, 17.76%, 20.90%, 27.62%; low C-peptide if tested 2.91%, 9.75%, 18.96%, 32.55%; and GAD antibody (+) if tested 8.80%, 23.39%, 32.73%, 45.00%. Among the 5% tested, years to starting insulin fell significantly (p&lt;0.001) in lowest to highest centile groups, from 2.59 to 1.28 yr for GAD(-), and from 1.77 vs. 0.90 yr for GAD(+).

Conclusions: The 10% of US Veterans with diabetes in MVP in the two highest T1D GRS centile groups have characteristics suggestive of T1D, although only 5% were tested for GAD antibodies, and most had no use of T1D diagnosis codes. Since adult-onset T1D may be misdiagnosed as T2D in settings where T2D is more common, genetic analyses and/or clinical characteristics may warrant definitive testing and appropriate management.

Disclosure

P. K. Yang: None. M. K. Rhee: None. C. Mercado: None. R. A. Oram: Consultant; Self; Janssen Research & Development, LLC. M. Vujkovic: None. P. Reaven: Research Support; Self; AstraZeneca, Dexcom, Inc. K. Cho: None. L. S. Phillips: Other Relationship; Self; Diasyst Inc., Research Support; Self; AbbVie Inc., Eli Lilly and Company, GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc., Kowa Pharmaceuticals America, Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Pharma Ltd., Pfizer Inc., Sanofi-Aventis. A. Leong: None. S. Jackson: None. B. R. Charest: None. M. N. Weedon: None. Y. J. Cheng: None. Y. V. Sun: None. S. Raghavan: None. E. M. Litkowski: None. B. T. Legvold: None.

Funding

U.S. Department of Veterans Affairs (CSP2008, I01CX001899, I01CX001737); National Institutes of Health (R18DK066204, R21AI156161, U01DK091958, U01DK098246, UL1TR002378)