medwireNews: A high BMI may contribute to the risk for progressing from single to multiple islet autoantibodies, especially in children who would otherwise be at relatively low risk, show findings from TrialNet.
The association with BMI occurred only in children aged 9 years or older, who have a lower risk for progression than younger children. But in this older group the effect of excess BMI was equivalent to that of having a high-risk HLA haplotype, report Maria Jose Redondo (Baylor College of Medicine, Houston, Texas, USA) and co-researchers.
The team notes that the development of multiple islet autoantibodies is “a significant milestone” in the progression of type 1 diabetes, with 70% of people being diagnosed with clinical diabetes within 10 years of multiple autoantibodies appearing.
Of 706 TrialNet participants aged 2–18 years with single autoantibodies at baseline, 20% progressed to multiple autoantibodies. As anticipated, older children were less likely to develop multiple autoantibodies, with each additional year of age reducing this risk by a significant 7%.
At baseline, 25% of the children had excess BMI (≥85th percentile for age and sex), and this was not associated with progression to multiple autoantibodies in the cohort overall. However, in children aged 9 years or older, each 1 kg/m2 of excess BMI was associated with a significant 7% increase in the risk for progression.
In the dichotomized analysis, children aged 9 years or older who were overweight or obese were a significant 1.92-fold more likely to develop multiple autoantibodies than those without excess BMI. This was particularly the case if they lacked the high-risk DR3-DQ2 or DR4-DQ8 HLA haplotypes, with the risk increase associated with excess BMI increasing to 7.32-fold, resulting in a risk for progression similar to that of children without excess BMI but with a high-risk HLA haplotype.
“Thus, in this subgroup with lower intrinsic risk (i.e., older and lacking high-risk HLA haplotypes), risk factors such as elevated BMI may play a more critical role in initiating the first preclinical phase of [type 1 diabetes],” write the researchers in Diabetes Care.
They add that “only a minority” of people with single autoantibodies go on to develop type 1 diabetes, meaning that “identifying [excess] BMI as [a] modifiable risk factor, with both genetic and environmental causes, that influences the conversion from single to multiple autoantibodies […] has clinical implications, as it could be targeted to prevent or delay progression to clinical [type 1 diabetes].”
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