medwireNews: Study results presented at the virtual ADA 80th Scientific Sessions suggest that a substantial proportion of people with type 2 diabetes have islet autoimmunity, and those with T cell-mediated autoimmunity may represent a distinct subgroup with diminished beta-cell function.
Ashok Balasubramanyam (Baylor College of Medicine, Houston, Texas, USA) and colleagues from the GRADE Research Group used an immunoblotting assay to investigate the frequency of islet autoimmunity in 419 patients with a type 2 diabetes duration of less than 10 years who were taking metformin as their sole diabetes medication. Participants had an average age of 57.2 years and a BMI of 33.5 kg/m2.
In all, 13.5% of patients tested positive for islet autoantibodies, indicating humoral autoimmunity, while 41.4% were found to have T-cell autoreactivity against a broad range of islet antigens, indicating cellular autoimmunity. Balasubramanyam said that this prevalence of cellular autoimmunity was “extremely high,” and there was only a small degree of overlap between humoral and cellular autoimmunity, with 5.4% of patients testing positive for both types.
The researchers identified a significant association between the presence of cellular autoimmunity and diminished beta-cell function, as measured from oral glucose tolerance test samples using two different methods. Specifically, the C-peptide index and the ratio of incremental area under the curve (iAUC) of C-peptide to iAUC of glucose were both significantly lower in patients with cellular autoimmunity than in those without.
Moreover, there was a significant association between cellular autoimmunity and poor glycemic control, with individuals positive for T-cell autoreactivity having higher glycated hemoglobin (HbA1c) and fasting glucose levels than those with a negative result.
These findings indicate that the association between T-cell-mediated islet autoimmunity and diminished beta-cell function “was clinically significant,” said Balasubramanyam.
On the other hand, there were no such associations with humoral autoimmunity; measures of beta-cell function were comparable among patients testing positive versus negative for islet autoantibodies, as were HbA1c levels. The presenter noted that fasting glucose levels were lower in autoantibody-positive versus negative individuals “for unknown reasons.”
Taken together, these findings suggest that autoantibody-positive type 2 diabetes “could be defined as LADA [latent autoimmune diabetes of adulthood],” whereas cellular islet autoimmunity likely represents “a subtype of type 2 diabetes with islet dysfunction accelerated by immune responses to a range of islet antigens,” he concluded.
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