Ricerc@Sapienza

To the Editor
The paper by Jones et al. in which they studied the response of a
cohort of 19 patients with adult-onset diabetes who were glutamic
acid decarboxylase autoantibodies (GADA) positive, most with very
low levels of C peptide and multiple autoantibodies, is consistent with
published results studying GLP-1 agonists in patients with established
type 1 diabetes who show little by way of a beneficial response.1,2
Importantly, they note that those with GADA, who were not on insulin
therapy from diagnosis, had a similar response to a GLP-1 agonist
to those who were GADA negative and by implication had type 2 diabetes.
This point is important as the implication is that patients with
GADA, the usual diabetes-associated autoantibodies screening test in
adults, could benefit from GLP-1 agonists as long as they have limited
insulin deficiency, that is, as long as they are not on multiple
insulin injections. By inference, GLP-1 agonists are a reasonable
option in the management of adult-onset autoimmune diabetes
patients who are not on multiple insulin therapy.
Jones and McDonald have misread the assay specificity of our
GADA assay; their assay specificity is 97.5% and ours, based on the
international workshop (DASP), is 99%; therefore, our assay is more
specific than theirs.3 In addition, the positive predictive value of an
assay increases as the population under test is enriched, as with the
adult-onset diabetes cases we studied.4 We found a rate of GADA
positive cases in our cohort (7.6%, 188 GADA+ out of 2466 patients)
comparable to the rate they found with their assay, despite theirs having
only a slightly lower assay specificity: “Eight percent of insulintreated
participants” compared with a lower rate and longer disease
duration at “0.9% of non–insulin-treated participants.”1
Finally, the high titre cut-off is arbitrary in this cohort in order to
make it comparable with other studies in which it was not arbitrary.
Those previous studies used inflections in the Quartile-Quartile plot
to define a second population with a high GADA titre different from
those with a lower GADA titre.
We accept that our study has limitations, despite it comprising
tenfold the number of cases than their analysis. In addition, this is the
first study of a once-weekly as compared to a once-daily GLP-1 agonist
regime, which could be relevant to differences in responses. Large case-controlled cases are awaited, but the data we presented on our
large cohort is compelling, while the combined results from their study
and the study by Jones et al. indicate that GLP-1 agonists are likely to
have a limited role in patients with severe insulin deficiency and frank
clinical type 1 diabetes.