Age of Diagnosis Does Not Alter the Presentation or Progression of Robustly Defined Adult-Onset Type 1 Diabetes
Authors: Thomas Nicholas J. , Hill Anita V. , Dayan Colin M. , Oram Richard A. , McDonald Timothy J. , Shields Beverley M. , Jones Angus G. ,   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 Francis , 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 Katherine , 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 , Jones Angus , Hill Anita , Bolt Robert , Hammersley Suzanne , Aldred Migaila , Steele Anna , Tippett Peter 
Published: February 2023

OBJECTIVE
To determine whether presentation, progression, and genetic susceptibility of robustly defined adult-onset type 1 diabetes (T1D) are altered by diagnosis age.

RESEARCH DESIGN AND METHODS
We compared the relationship between diagnosis age and presentation, C-peptide loss (annual change in urine C-peptide–creatinine ratio [UCPCR]), and genetic susceptibility (T1D genetic risk score [GRS]) in adults with confirmed T1D in the prospective StartRight study, 1,798 adults with new-onset diabetes. T1D was defined in two ways: two or more positive islet autoantibodies (of GAD antibody, IA-2 antigen, and ZnT8 autoantibody) irrespective of clinical diagnosis (n = 385) or one positive islet autoantibody and a clinical diagnosis of T1D (n = 180).

RESULTS
In continuous analysis, age of diagnosis was not associated with C-peptide loss for either definition of T1D (P &gt; 0.1), with mean (95% CI) annual C-peptide loss in those diagnosed before and after 35 years of age (median age of T1D defined by two or more positive autoantibodies): 39% (31–46) vs. 44% (38–50) with two or more positive islet autoantibodies and 43% (33–51) vs. 39% (31–46) with clinician diagnosis confirmed by one positive islet autoantibody (P &gt; 0.1). Baseline C-peptide and T1D GRS were unaffected by age of diagnosis or T1D definition (P &gt; 0.1). In T1D defined by two or more autoantibodies, presentation severity was similar in those diagnosed before and after 35 years of age: unintentional weight loss, 80% (95% CI 74–85) vs. 82% (76–87); ketoacidosis, 24% (18–30) vs. 19% (14–25); and presentation glucose, 21 mmol/L (19–22) vs. 21 mmol/L (20–22) (all P ≥ 0.1). Despite similar presentation, older adults were less likely to be diagnosed with T1D, insulin-treated, or admitted to hospital.

CONCLUSIONS
When adult-onset T1D is robustly defined, the presentation characteristics, progression, and T1D genetic susceptibility are not altered by age of diagnosis.