Endocrine Abstracts

Introduction: Diabetes mellitus (DM) is a complex chronic metabolic disease characterized by elevated blood glucose levels due to insulin resistance and the failure of pancreatic beta cells to compensate. T2D and its complications have reached epidemic proportions worldwide over the past four decades [1]. A very rare condition known as Type B Insulin Resistance (TBIR) is characterized by severe insulin resistance and the presence of circulating autoantibodies (autoAb) directed against the insulin receptor (InsR). TBIR usually manifests in adulthood and is associated with a high risk of mortality. Insulin receptor autoAb are associated with higher fasting insulin levels in patients with TBIR [2]. Current methods for the diagnosis of TBIR have several limitations, most importantly they cannot be used for routine applications or for the analysis of large sample cohorts. There for it has been suggested that Type 1 Diabetes (T1D) and T2D patients with severe insulin resistance may be underdiagnosed of InsR-autoAb.

Objectivee: The pilot study aimed to determine the prevalence of InsR-autoAb in healthy controls and patients with DM.

Subjects and Methods: An in-house developed and validated fluorescence immunoprecipitation assay [2] was used to quantify InsR autoAb in sera from a small commercial cohort of (n=443 participants, including (n=296 self-reported healthy subjects, (n=111 T2D patients, and (n=36 patients with T1D.

Results: The group of T2D subjects showed an InsR autoAb prevalence of 4.5% compared to 0% in T1D and 2% in healthy subjects. In a more rigorous analysis using a stricter cut-off of BI >20, the prevalence in the T2D group is 2.7% compared to 0% in healthy subjects.

Conclusion: The pilot study supports the hypothesis that there are patients with T2D with undiagnosed InsR autoAb. None of the T1D patients showed InsR autoAb, suggesting that this is associated with acquired insulin resistance rather than insulin deficiency. This raises the question of the clinical relevance of these autoAb in the pathogenesis, which needs to be tested in sufficiently large prospective clinical trials. References1. Tomic, D., J.E. Shaw, and D.J. Magliano, The burden and risks of emerging complications of diabetes mellitus. Nature Reviews Endocrinology, 2022. 18(9): p. 525-539. 2. Minich, W.B., et al., A Novel in vitro Assay Correlates Insulin Receptor Autoantibodies With Fasting Insulin in Type B Insulin Resistance. The Journal of Clinical Endocrinology & Metabolism, 2023. 108(9): p. 2324-2329.