Clinical Characteristics in
Swedish Children With and
Without Autoantibodies at the
Time of Type 1 Diabetes
Diagnosis
Diab Care
Emma Hedlund,1,2 Marlena Maziarz,3
Tomas Lindahl,1 Helena Elding-Larsen,3,4
Gun Forsander,5 Martina Persson,6
Auste Pundziute-Lyckå,5,7 Karin Åkesson,8
Johnny Ludvigsson,9,10 and
Annelie Carlsson
Swedish children diagnosed with type 1 diabetes (T1D) show different clinical characteristics depending on their autoantibody status at the time of diagnosis
Children who are negative for autoantibodies are more often male and have a higher HbA1c level, and are less likely to present with diabetic ketoacidosis (DKA) than children who are autoantibody-positive.
Research from the Swedish National Diabetes Register and studies like TEDDY (The Environmental Determinants of Diabetes in the Young) have highlighted the heterogeneity in T1D, finding distinct differences between these two groups.
Clinical characteristics of autoantibody-negative children
In comparison to autoantibody-positive children at the time of diagnosis, Swedish children without detectable autoantibodies displayed the following traits:
- Sex: Autoantibody-negative children were more likely to be boys.
- HbA1c: They had a higher average glycated hemoglobin (HbA1c) level at diagnosis.
- Diabetic ketoacidosis (DKA): They were less likely to present with DKA.
- Family history: They were more likely to have a parental history of type 2 diabetes (T2D).
- Pathogenesis: These differences suggest a potentially distinct disease mechanism in autoantibody-negative T1D, highlighting the heterogeneous nature of the condition.
Clinical characteristics of autoantibody-positive children
Swedish children who were positive for autoantibodies at diagnosis presented with the following:
- Sex: They were more likely to be girls.
- HbA1c: Their average HbA1c level at diagnosis was lower.
- Diabetic ketoacidosis (DKA): They were more likely to present with DKA, which indicates more rapid beta-cell destruction.
- Early seroconversion: In some cases, the presence of autoantibodies (seroconversion) was detected months or years before the clinical diagnosis of T1D.
Other related findings from Swedish research
- Age-related differences in autoantibodies: Younger children (under 2 years) more often produce insulin autoantibodies (IAA) first, while older children are more likely to have glutamic acid decarboxylase autoantibodies (GADA) as the first autoantibody to appear.
- Genetic factors: The autoantibody profile can also be linked to specific HLA genotypes, with high-risk HLA genotypes more commonly associated with IAA-initiated autoimmunity.
- Associated autoimmune diseases: A significant portion of children with T1D have other autoimmune conditions, such as celiac disease and thyroiditis.
- Family history of diabetes: A parental history of T1D is associated with a younger age at diagnosis and lower HbA1c levels in the child.
ARTICLE HIGHLIGHTS
- Why did we undertake this study?
To study the phenotypic and genetic heterogeneity in children with and without autoantibodies at type 1 diabetes diagnosis.
- What is the specific question we wanted to answer?
Are there differences in clinical characteristics at diagnosis of type 1 diabetes between those with and without antibodies in the Swedish national
cohort?
- What did we find?
We found that children without autoantibodies at type 1 diabetes diagnosis were more likely boys, with a higher HbA1c, less likely to present with
diabetic ketoacidosis at diagnosis, and were more likely to have parents with type 2 diabetes.
These findings suggest potential heterogeneity in the disease’s pathogenesis across subgroups of type 1 diabetes.
______________________
ABSTRACT
OBJECTIVE
Autoantibodies have long been recognized as biomarkers of islet autoimmunity
in type 1 diabetes, but their role in the pathogenesis is not fully understood. The
aim of this study was to analyze clinical and hereditary characteristics of children
presenting with and without autoantibodies at type 1 diabetes diagnosis.
RESEARCH DESIGN AND METHODS
Data were collected from children (<18 years) at the time of diabetes diagnosis
as part of Sweden’s national Better Diabetes Diagnosis study. Participants were
categorized based on the presence or absence of autoantibodies. Variables com-
pared were age at diagnosis, sex, HbA1c, diabetic ketoacidosis (DKA), parental he-
redity of type 1 and type 2 diabetes, level of C-peptide, BMI SD score (SDS), and
HLA genotype. We used t tests, χ2 tests, and logistic regression for comparisons.
RESULTS
Of the 2,753, children, 169 (6.1%) were autoantibody-negative at type 1 diabetes di-
agnosis. Of those, 66% were boys compared with 56% of children with autoantibod-
ies (P = 0.009). Also, children without autoantibodies had higher HbA1c at diagnosis
(11.3 vs. 10.8% [100 vs. 94 mmol/mol], P = 0.003), were less likely to present with
DKA (9 vs. 15%, P = 0.039), and more likely to have parental history of type 2 diabetes
(8 vs. 2%, P < 0.001) compared with children with autoantibodies. We did not ob-
serve differences for age at diagnosis, C-peptide levels, BMI-SDS, or HLA genotype
between the children with and without autoantibodies.
CONCLUSIONS
We identified differences in clinical characteristics when comparing children with
and without autoantibodies at type 1 diabetes diagnosis, highlighting potential
heterogeneity in the disease’s pathogenesis across subgroups
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”Clinical Characteristics in
Swedish Children With and
Without Autoantibodies at the
Time of Type 1 Diabetes
Diagnosis”
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