Progression to type 1 diabetes is highly variable in people with multiple autoantibodies and a family history of the disease, according to researchers exploring preventive agents.

An analysis of 1,815 participants  in the Type 1 Diabetes TrialNet Pathway to Prevention (PTP) study found progression can be as low as 8% depending on the individual’s age and the number and type of autoantibodies.

The investigators – including Dr John Wentworth of the Walter and Eliza Hall Institute of Medical Research, Melbourne –  found there was an inverse relationship between diabetes and age in participants with multiple autoantibodies (mAb). 

“Specifically, participants who were <12.0 years of age at mAb determination (n = 1145) had an estimated 5 year type 1 diabetes rate of 35% (95% CI 31%, 40%) vs those who were ≥12.0 years of age (n = 670), who had an estimated 5-year type 1 diabetes rate of 22% (95% CI 17%, 28%) (HR 0.62 [95% CI 0.48, 0.80]; p = 0.0002),” the study authors said in Diabetologia

The  5-year type 1 diabetes rate was 15% in people over 18 years.

The study found GADA positivity conferred a lower risk of type 1 diabetes relative to the presence of other autoantibodies (HR 0.60; p = 0.0038) while IA-2A positivity conferred a higher risk.

When paired, a combination of IAA/GADA positivity was associated with a 17% risk of diabetes, GADA/ZnT8A with a 26% risk and IAA/ZnT8A with a 33% risk. Higher risk was seen with GADA/IA-2A (40%) and ZnT8A/IA-2A (54%).

And metabolic index was another variable influencing risk of progression to diabetes. 

“For Index60 values <1.0 vs ≥1.0, the 5 year estimated type 1 diabetes risk in those with 2 autoantibodies was 20% vs 68%, respectively, and in those with >2 autoantibodies, it was 22% vs 53%, respectively.”

“Our findings of marked variation in risk among those with mAbs in the TrialNet PTP population is consistent with the heterogeneity of type 1 diabetes,” the study authors said. 

“For each of the characteristics studied (age, autoantibody number, autoantibody type and Index60), there were appreciable proportions of individuals who appeared unlikely to progress to type 1 diabetes.”

“Importantly, our findings not only show that type 1 diabetes risk varies substantially in a population with mAbs, but that appreciable numbers of individuals who appear unlikely to progress to type 1 diabetes can be identified.” 

“With this knowledge, prevention clinical trials can better target those most likely to progress to type 1 diabetes and enrolment criteria can be designed with these features in mind.”

The TrialNet group recently reported that the immunotherapy drug teplizumab could delay type 1 diabetes diagnosis by two years in children and adults at high risk.