Clinical Characteristics and Antibody Persistence over Time in Youth in the Pediatric Diabetes Consortium (PDC) Type 2 Diabetes (T2D) Cohort
Authors: KLINGENSMITH GEORGEANNA J. , CHENG PEIYAO , GAL ROBIN L. , BEAULIEU LINDSEY C. , TAMBORLANE WILLIAM V. , BACHA FIDA , KELSEY MEGAN M. , KOLLMAN CRAIG , CONSORTIUM PEDIATRIC DIABETES 
Published: June 2018

Objective: To describe the characteristics of youth diagnosed with T2D who have tested positive for ≥1 islet autoantibody (IA) and to examine the persistence of IA over time.
Methods: Youth enrolled in the PDC T2D Registry with ≥2 years follow-up after diagnosis and ≥1 positive IA at any time were identified. T2D was determined using ADA guidelines. IAs were measured at each PDC site according to local practice and included IAA, GADA, IA-2A, ZnT8A, and ICA. Positive IAA tests were excluded if measured after insulin initiation. Clinical characteristics, clinical presentation, and treatment over time were analyzed.
Results: Positive IA is an exclusion for enrollment in the PDC T2D Registry; however, on review of the ∼1,300 youth in the PDC, 38 were found to have IA. A single IA was found in 35 and &gt;1 IA in 3 participants. GADA was most common (N=32); 3 were persistently positive, 13 converted to negative, 8 became positive after a negative GADA, and 8 had only 1 IA determination. Positive IAA (N=5), IA-2A (N=4) and ZnT8 (N=1) were uncommon or rare, no positive ICA were found. At diagnosis, those IA positive were more likely to be treated with insulin (95% vs. 73%) but with similar HbA1c (10.4% vs. 10.0%). At last visit, those IA positive had longer diabetes duration (5.7 years. vs. 4.8 years.) and higher insulin use (71% vs. 59%) compared to the IA negative cohort, but HbA1c levels were similar (8.7% vs. 9.0%). Age at diagnosis, race/ethnicity, percent male, and BMI were not different between those with and without IA.
Conclusion: Most IA positive youth with a T2D phenotype require insulin at diagnosis and more IA positive than IA negative youth require insulin during follow-up treatment. These findings suggest the importance of IA ascertainment at diagnosis and in those failing oral therapy. In T2D youth GADA is the most common IA; yield from ZnT8 and ICA determinations is low; fluctuations in IA positivity are not uncommon. Additional study of youth with T2D phenotype and IA is needed.

Disclosure
G.J. Klingensmith: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Foundation. P. Cheng: None. R.L. Gal: Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Development Center Americas, Inc., Novo Nordisk Inc. L.C. Beaulieu: Research Support; Self; Novo Nordisk Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Development Center Americas, Inc. W.V. Tamborlane: Consultant; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Medtronic MiniMed, Inc., Novo Nordisk Inc., Sanofi, Takeda Pharmaceuticals U.S.A., Inc. F. Bacha: Research Support; Self; AstraZeneca, JAEB Center For Health Research, National Institutes of Health, Pediatric Diabetes Consortium. M.M. Kelsey: Other Relationship; Self; Daiichi Sankyo Company, Limited, Merck Sharp & Dohme Corp. C. Kollman: Research Support; Self; JDRF, Bigfoot Biomedical, Dexcom, Inc., Tandem Diabetes Care, Inc., Medtronic MiniMed, Inc., Helmsley Charitable Trust.