Routine Islet Autoantibody Testing in Clinically Diagnosed Adult-Onset Type 1 Diabetes Can Help Identify Misclassification and the Possibility of Successful Insulin Cessation
Authors: Eason Russell J. , Thomas Nicholas J. , Hill Anita V. , Knight Bridget A. , Carr Alice , Hattersley Andrew T. , McDonald Timothy J. , Shields Beverley M. , Jones Angus G. ,   for the StartRight Study Group, Simon Godwin , Ramos Angelo , Norris Andrea , Tan Kai , Narendran Parth , Ramtoola Shenaz , Ali Amar , Banerjee Moulinath , Brooks Augustin , Chakera Ali , Johnson Andrew , Tatovic Danijela , Ballav Chitrabhanu , Dayan Colin , Nair Sunil , Game Frances , Jones Angus , Beames Susan , Rayman Gerry , Snell Marie , Butler Susie , Beck Sarah , Beecham Janet , Wilding John , Rice Sam , Chen Mimi , Thiraviaraj Athinyaa , Sivappriyan Siva , Issa Basil , Humayun Asif , Hinch Rebecca , Krishnan Leena , Myint Khin Swe , Fox Charles , Prouten Jennifer , Sampson Mike , Mansell Peter , Chee Carolyn , Owen Katharine , Dimitropoulis Ioannis , Cummings Michael , Kavourra Foteini , Heald Adrian , Heller Simon , Sihota Sarbpreet , Muraleedharan Vakkat , Watson Tara , Price Hermione , Whittaker Roger , Orme Sarah , Field Ben , Bain Stephen , Battacharya Beas , Haxton Lesley , Pegler Suzannah , Thompson Catherine , Andrew Rob , Smith Jamie , Browne Duncan , Creely Steve , Yadav Rahul , Kakad Rakhi , Laji Ken , Kumar Mohit , Mohammadi Alirezi , Young James , Pramodh Seshadri , Jayagopal Vijay 
Published: October 2022

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 &lt;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 &lt; 0.001] [type 2 diabetes 10.12]) and lower annual change in C-peptide (UCPCR), −24% vs. −43% (P &lt; 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.