Relationship between islet autoantibody status and the clinical characteristics of children and adults with incident type 1 diabetes in a UK cohort

Abstract

Objectives: To describe the characteristics of children and adults with incident type 1 diabetes in contemporary, multiethnic UK, focusing on differences between the islet autoantibody negative and positive.

Design: Observational cohort study.

Setting: 146 mainly secondary care centres across England and Wales.

Participants: 3312 people aged ≥5 years were recruited within 6 months of a clinical diagnosis of type 1 diabetes via the National Institute for Health Research Clinical Research Network. 3021 were of white European ethnicity and 291 (9%) were non-white. There was a small male predominance (57%). Young people <17 years comprised 59%.

Main outcome measures: Autoantibody status and characteristics at presentation.

Results: The majority presented with classical osmotic symptoms, weight loss and fatigue. Ketoacidosis was common (42%), especially in adults, and irrespective of ethnicity. 35% were overweight or obese. Of the 1778 participants who donated a blood sample, 85% were positive for one or more autoantibodies against glutamate decarboxylase, islet antigen-2 and zinc transporter 8. Presenting symptoms were similar in the autoantibody-positive and autoantibody-negative participants, as was the frequency of ketoacidosis (43%vs40%, P=0.3). Autoantibody positivity was less common with increasing age (P=0.0001), in males compared with females (82%vs90%, P<0.0001) and in people of non-white compared with white ethnicity (73%vs86%, P<0.0001). Body mass index was higher in autoantibody-negative adults than autoantibody-positive adults (median, IQR 25.5, 23.1-29.2vs23.9, 21.4-26.7 kg/m²; P=0.0001). Autoantibody-negative participants were more likely to have a parent with diabetes (28%vs16%, P<0.0001) and less likely to have another autoimmune disease (4%vs8%, P=0.01).

Conclusions: Most people assigned a diagnosis of type 1 diabetes presented with classical clinical features and islet autoantibodies. Although indistinguishable at an individual level, autoantibody-negative participants as a group demonstrated features more typically associated with other diabetes subtypes.

Trial registration number: ISRCTN66496918; Pre-results.

Keywords: epidemiology; general diabetes; immunology; paediatric endocrinology.

Figure 1

Individual characteristics as predictors of diabetes presentation and autoantibody status. Univariate logistic regression ORs or linear regression coefficients (circles), 95% CIs (horizontal lines)^# and statistical significances are shown. Red circles signify that a significant univariate relationship was sustained on multivariable analysis with all individual characteristics included as predictor variables (participants with complete data: n=2911–3312) and in the subgroup with antibodies measured (participants with complete data including antibody status: n=1610–1778). *Not significant in subgroup with antibodies measured on multivariable analysis. **Significant in subgroup with antibodies measured on multivariable analysis. †Not significant on multivariable analysis. ††Significant on multivariable analysis. #For ‘Age’, ORs or coefficients and 95% CIs were derived from standardised data. DM, diabetes mellitus.

Figure 2

The percentage of participants exhibiting islet autoantibodies (any and individual) in relation to age at diagnosis. GAD, glutamate decarboxylase; IA2, islet antigen-2; ZnT8, zinc transporter 8.