Clinical, immunogenetic and metabolic characteristics of autoantibody-negative and autoantibody-positive type 1...

Autoantibody-negative type 1 diabetes is an idiopathic subtype with unclear aetiology. We aimed to characterise and compare the clinical, immune, genetic and metabolic characteristics of individuals with autoantibody-negative vs autoantibody-positive type 1 diabetes.

Clinical features and deep immune phenotyping of 26 individuals with autoantibody-negative type 1 diabetes were analysed and compared with 30 individuals with autoantibody-positive type 1 diabetes and 25 normoglycaemic control participants. Genetic risk was assessed using the type 1 diabetes genetic risk score 2 (GRS2) and compared with individuals with autoantibody-positive type 1 diabetes and latent autoimmune diabetes in adults. Beta cell function was longitudinally assessed in 29 participants with recent-onset type 1 diabetes using glucagon stimulation tests. Mixed meal tests were performed on a subset of participants.

Participants with autoantibody-negative and autoantibody-positive type 1 diabetes had similar age at diagnosis (33.5 ± 11.6 vs 31.6 ± 9.3 years, p=0.78), disease duration (median 3 [IQR 1-6] years for both) and BMI (24.1 ± 3.4 vs 23.4 ± 2.9 kg/m², p=0.82). Immune phenotyping revealed no significant differences. Mean GRS2 scores were comparable (19.6 in autoantibody-negative type 1 diabetes vs 19.4 in autoantibody-positive type 1 diabetes). Beta cell function was also similar in response to glucagon (peak C-peptide 0.25 [0.13-0.38] vs 0.30 [0.20-0.55] nmol/l, respectively, p=0.27) and mixed meal stimuli (C-peptide AUC 1.46 ± 0.29 vs 1.45 ± 0.31 nmol/l × min, respectively, p>0.99).

Adults with autoantibody-negative type 1 diabetes share similar clinical, immunologic, genetic and metabolic features with those who are autoantibody-positive.