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Adult-onset type 1 diabetes has weaker familial aggregation and lower heritability than pediatric-onset diabetes, according to a study published in The Lancet Diabetes & Endocrinology.
Although type 1 diabetes is the most common chronic disease among children, onset can occur at any age. However, no study has compared the heritability of adult- and pediatric-onset type 1 diabetes.
To evaluate the risk for type 1 diabetes at different ages according to family history, researchers from the Karolinska Institutet conducted a register-based cohort study sourcing data from nationwide registers in Sweden. Participants were born in Sweden between 1982 and 2010 and linked with their parents, siblings, and cousins.
The primary outcome was the risk of developing adult-onset and childhood-onset type 1 diabetes, whereas the secondary outcome was the risk for type 1 diabetes up until 30 years of age. The researchers compared the heritability of type 1 diabetes between individuals diagnosed with adult-onset disease at 19 to 30 years of age and those diagnosed with pediatric-onset disease at 0 to 18 years of age.
The pediatric-onset study cohort included 2,832,755 participants and the adult-onset study cohort included 1,805,826 participants. Among the pediatric- and adult-onset cohorts, 54.8% and 59.7% were women, 24.8% and 61.5% were born between 1982 and 1990, and 12.3% and 8.3% had a first-degree relative with type 1 diabetes, respectively. The median age of type 1 diabetes onset was 9.8 years (IQR, 6.2-13.3) among the childhood-onset cohort and 23.4 years (IQR, 21.1-26.2) among the adult-onset cohort.
“[T]his study suggests that the heritability of adult-onset type 1 diabetes is lower than that of childhood-onset type 1 diabetes, suggesting potential variations in the underlying causes of type 1 diabetes based on the age of onset.
The researchers identified 17,914 cases of pediatric-onset diabetes and 3240 cases of adult-onset diabetes. Within 3 months of diagnosis, patients with adult-onset vs pediatric-onset disease had higher glycated hemoglobin (7.9% vs 7.5%) but lower rates of diabetic coma or ketoacidosis (7.1% vs 10.0%).
The risk for pediatric-onset vs adult-onset type 1 diabetes was greater among participants with:
Any first-degree relative with type 1 diabetes (hazard ratio [HR], 9.92 vs 7.21);
At least 2 first-degree relatives with type 1 diabetes (HR, 12.25 vs 8.77);
A full sibling with type 1 diabetes (HR, 11.30 vs 8.12);
A full sister with type 1 diabetes (HR, 11.58 vs 7.77);
Maternal type 1 diabetes (HR, 7.35 vs 5.22);
Paternal type 1 diabetes (HR, 9.75 vs 7.71);
A full brother with type 1 diabetes (HR, 11.16 vs 8.40);
Maternal half siblings with type 1 diabetes (HR, 3.70 vs 2.78); and,
Cousins with type 1 diabetes (HR, 2.08 vs 1.72)
Adult-onset type 1 diabetes risk was higher than pediatric-onset disease only among participants with paternal half siblings with type 1 diabetes (HR, 3.85 vs 3.25).
In all cases, cumulative instances of type 1 diabetes were higher among individuals with a first-degree relative with pediatric-onset disease (range, 6.6%-9.7%) compared with adult-onset disease (range, 5.2%-6.5%) or no type 1 diabetes (range, 0.9%-0.9%).
When grouping pairs of siblings into concordant pairs with type 1 diabetes, discordant pairs, and concordant pairs without type 1 diabetes, the researchers identified concordance rates of:
7.22% for full siblings with pediatric-onset disease (tetrachoric correlation, 0.41);
2.28% for maternal half-siblings with pediatric-onset disease (tetrachoric correlation, 0.19);
1.84% for full siblings with adult-onset disease (tetrachoric correlation, 0.28; and,
0.93% for maternal siblings with adult-onset disease (tetrachoric correlation, 0.20).
The overall heritability of pediatric-onset type 1 diabetes was higher than adult-onset type 1 diabetes (0.81 vs 0.56), whereas the non-shared environmental component of pediatric-onset type 1 diabetes was lower than adult-onset type 1 diabetes (0.19 vs 0.44), respectively.
Study limitations include the small sample size of maternal half-sibling pairs in the adult-onset type 1 diabetes cohort, the inability to follow participants past 30 years of age, and a lack of generalizability beyond non-European populations.
The researchers concluded, “[T]his study suggests that the heritability of adult-onset type 1 diabetes is lower than that of childhood-onset type 1 diabetes, suggesting potential variations in the underlying causes of type 1 diabetes based on the age of onset.”
This article originally appeared on Endocrinology Advisor