medwireNews: Among individuals with multiple autoantibodies detected by screening, type 1 diabetes risk varies according to age, autoantibody type, and metabolic impairment, researchers report.
Moreover, it is possible to identify an “appreciable number” of autoantibody-positive people “who appear unlikely to progress to type 1 diabetes,” say Laura Jacobsen, from the University of Florida in Gainesville, USA, and co-authors.
The researchers analyzed data from the Type 1 Diabetes TrialNet Pathway to Prevention cohort, which included 1815 relatives of people with diabetes who were found to have at least two autoantibodies following screening. Participants were aged an average of 12.35 years, had a mean BMI of 19.66 kg/m2, and were followed up for an average of 2.40 years.
As reported in Diabetologia, there was a significant inverse association between age and type 1 diabetes risk, such that individuals aged less than 12 years at the time of screening had an estimated 5-year risk of 35%, while those aged 12 years and older had an estimated risk of 22%, decreasing further to 15% for those aged 18 years or older.
“These arbitrary categories were used to roughly [distinguish] pre-/peri-pubertal from post-pubertal age groups,” explain Jacobsen et al.
The team found that patients with two versus more than two autoantibodies had a comparable 5-year risk for developing diabetes (29% and 31%, respectively), but the type of autoantibodies present influenced progression.
The presence of insulinoma-associated antigen-2 autoantibodies (IA-2A) was associated with the highest risk for diabetes (hazard ratio [HR]=1.97 relative to other autoantibodies), whereas glutamic acid decarboxylase autoantibody (GADA) positivity was associated with the lowest risk (HR=0.60 relative to other autoantibodies). There was no significant association between the presence of multiple insulin autoantibodies or zinc transporter 8 autoantibodies and diabetes risk after adjustment for the number of autoantibodies.
When the researchers focused on the autoantibodies conferring the highest and lowest risk, estimated 5-year rates of diabetes were 60% for individuals who were IA-2A positive and GADA negative, compared with just 21% for those who were GADA positive and IA-2A negative.
Metabolic status, assessed by Index60 (a composite of fasting C-peptide, 60-minute glucose and 60-minute C-peptide measurements), was also significantly associated with diabetes risk. Among individuals with two autoantibodies, the estimated 5-year rates were 68% for those with Index60 values of 1 or more (indicating metabolic impairment) compared with 20% for those with no metabolic impairment. The corresponding rates were 53% versus 22% for patients with more than two autoantibodies.
Together, these findings indicate that “type 1 diabetes risk varies substantially” among people with screen-detected autoantibodies, which “is consistent with the heterogeneity of type 1 diabetes,” say Jacobsen and colleagues.
And the team concludes: “With this knowledge, prevention clinical trials can better target those most likely to progress to type 1 diabetes.”
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Diabetologia 2019; doi:10.1007/s00125-019-05047-w