Aims/hypothesis <p>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.</p> Methods <p>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.</p> Results <p>Participants with autoantibody-negative and autoantibody-positive type 1 diabetes had similar age at diagnosis (33.5&#xa0;±&#xa0;11.6 vs 31.6&#xa0;±&#xa0;9.3 years, <i>p</i>=0.78), disease duration (median 3 [IQR 1–6] years for both) and BMI (24.1&#xa0;±&#xa0;3.4 vs 23.4&#xa0;±&#xa0;2.9 kg/m<sup>2</sup>, <i>p</i>=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, <i>p</i>=0.27) and mixed meal stimuli (C-peptide AUC 1.46&#xa0;±&#xa0;0.29 vs 1.45&#xa0;±&#xa0;0.31 nmol/l × min, respectively, <i>p</i>&gt;0.99).</p> Conclusions/interpretation <p>Adults with autoantibody-negative type 1 diabetes share similar clinical, immunologic, genetic and metabolic features with those who are autoantibody-positive.</p> Graphical Abstract <p></p>

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

  • Shivani K. Patel,
  • Cindy S. Ma,
  • Spiros Fourlanos,
  • Jerry R. Greenfield

摘要

Aims/hypothesis

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.

Methods

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.

Results

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).

Conclusions/interpretation

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

Graphical Abstract