Routine Islet Autoantibody Testing in Clinically Diagnosed Adult-Onset Type 1 Diabetes Can Help Identify Misclassification and the Possibility of Successful Insulin Cessation
Russell J. Eason, Nicholas J. Thomas, Anita Hill, Bridget Knight, Alice L. J. Carr, Andrew T. Hattersley, Timothy J. McDonald, Beverley M. Shields, Angus G. Jones, for the StartRight Study Group, Godwin Simon, Angelo Ramos, Andrea R. Norris, Kai Tan, Parth Narendran, Shenaz Ramtoola, Amar Ali, Moulinath Banerjee, Augustin Brooks, Ali Chakera, Andrew Johnson, Danijela Tatović, Chitrabhanu Ballav, Colin Dayan, Sunil Nair, Frances L. Game, Angus G. Jones, Susan Beames, Gerry Rayman, Marie Snell, Susie Butler, Sarah R. Beck, Janet Beecham, John Wilding, Sam Rice, Mimi Chen, Athinyaa Thiraviaraj, Siva Sivappriyan, Basil Issa, Asif Humayun, Rebecca Hinch, Leena Krishnan, Khin Swe Myint, Charles J. Fox, Jennifer Prouten, Mike Sampson, Peter Mansell, Carolyn Chee, Katharine R. Owen, Ioannis Dimitropoulis, Michael P. Cummings, Foteini Kavourra, Adrian Heald, Simon Heller, Sarbpreet Sihota, Vakkat Muraleedharan, Tara Marie Watson, Hermione Price, Roger G. Whittaker, Sarah Orme, Benjamin C. T. Field, Stephen C. Bain, Beas Battacharya, Lesley Haxton, Suzannah Pegler, Catherine Thompson, Rob Andrew, Jamie Smith, Duncan L. Browne, Steve Creely, Rahul Yadav, Rakhi Kakad, Ken Laji, Mahesh Kumar, Alirezi Mohammadi, John K. Young, Seshadri Pramodh, Vijay Jayagopal
Abstract
OBJECTIVE: Recent joint American Diabetes Association and European Association for the Study of Diabetes guidelines recommend routine islet autoantibody testing in all adults newly diagnosed with type 1 diabetes. We aimed to assess the impact of routine islet autoantibody testing in this population. RESEARCH DESIGN AND METHODS: We prospectively assessed the relationship between islet autoantibody status (GADA, IA-2A, and ZNT8A), clinical and genetic characteristics, and progression (annual change in urine C-peptide-to-creatinine ratio [UCPCR]) in 722 adults (≥18 years old at diagnosis) with clinically diagnosed type 1 diabetes and diabetes duration <12 months. We also evaluated changes in treatment and glycemia over 2 years after informing participants and their clinicians of autoantibody results. RESULTS: Of 722 participants diagnosed with type 1 diabetes, 24.8% (179) were autoantibody negative. This group had genetic and C-peptide characteristics suggestive of a high prevalence of nonautoimmune diabetes: lower mean type 1 diabetes genetic risk score (islet autoantibody negative vs. positive: 10.85 vs. 13.09 [P < 0.001] [type 2 diabetes 10.12]) and lower annual change in C-peptide (UCPCR), -24% vs. -43% (P < 0.001).After median 24 months of follow-up, treatment change occurred in 36.6% (60 of 164) of autoantibody-negative participants: 22.6% (37 of 164) discontinued insulin, with HbA1c similar to that of participants continuing insulin (57.5 vs. 60.8 mmol/mol [7.4 vs. 7.7%], P = 0.4), and 14.0% (23 of 164) added adjuvant agents to insulin. CONCLUSIONS: In adult-onset clinically diagnosed type 1 diabetes, negative islet autoantibodies should prompt careful consideration of other diabetes subtypes. When routinely measured, negative antibodies are associated with successful insulin cessation. These findings support recent recommendations for routine islet autoantibody assessment in adult-onset type 1 diabetes.