January 16, 2020
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Pediatric islet autoimmunity risk rises with BMI gains

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Children who have a relative with type 1 diabetes and a single islet autoantibody may be more likely to develop multiple autoantibodies if they have excess weight, according to findings published in Diabetes Care.

“Type 1 diabetes is now recognized as a spectrum of diseases with heterogenous preclinical stages prior to the onset of symptomatic hyperglycemia,” Maria Jose Redondo, MD, PhD, MPH, associate professor of pediatrics-diabetes and endocrinology at Baylor College of Medicine in Houston, and colleagues wrote. “While type 1 diabetes prevention trials focus on halting the development of clinical onset of type 1 diabetes (stage 3), there is also great interest in arresting the development of multiple autoantibody positivity, which marks entry into stage 1 of type 1 diabetes.”

Redondo and colleagues assessed BMI and islet autoimmunity via multiple positive autoantibody development among 706 children who tested positive at baseline for a single autoantibody (median age, 9.8 years; 50.8% girls) from the TrialNet PTP study. The researchers categorized children as having overweight if they were in the 85th percentile or higher in BMI based on 2000 growth charts from the CDC. The researchers determined cumulative excess BMI as the amount of kilograms per square meter a participant was above the 85th percentile.

The researchers identified multiple positive autoantibodies in 144 participants and cumulative excess BMI in 189 participants. Multiple positive autoantibody risk was greater for those with HLA DR3-DQ2 or DR4-DQ8 vs. those without what the researchers called “high-risk HLA haplotypes” (HR = 1.86; 955 CI, 1.23-2.82). In addition, there was a decrease in multiple positive autoantibody risk for every year of age (HR = 0.93; 95% CI, 0.89-0.97).

Type 1 diabetes diagnosis 2019 
Children who have a relative with type 1 diabetes and a single islet autoantibody may be more likely to develop multiple autoantibodies if they have excess weight.
Source: Adobe Stock

Despite these findings, the researchers observed heightened multiple positive autoantibody risk in participants aged at least 9 years with cumulative excess BMI vs. participants with no excess BMI (HR = 1.92; 95% CI, 1.12-3.29). The HR for multiple positive autoantibodies when adding 1 kg/m2 of cumulative excess BMI was 1.07 (95% CI, 1.01-1.13). Additionally, there was a rise in multiple positive autoantibody risk for participants aged at least 9 years who did not have HLA DRE-DQ2 or DR4-DQ8 (HR = 7.32; 95% CI, 1.88-28.5).

“We provide evidence that sustained elevation in BMI may at least in part contribute to type 1 diabetes pathophysiology through an acceleration of the autoimmune process, particularly in those without high-risk factors,” the researchers wrote. “Targeted lifestyle interventions to maintain BMI < 85th percentile may help prevent or delay the progression to multiple autoantibody positivity and could halt the growing incidence of clinical stage 3 type 1 diabetes.” – by Phil Neuffer

Disclosures: The authors report no relevant financial disclosures.