Assessment and Management of Anti-insulin Autoantibodies in Varying Presentations of Insulin Autoimmune Syndrome

Context: Insulin autoimmune syndrome (IAS), spontaneous hyperinsulinemic hypoglycemia due to insulin-binding autoantibodies, may be difficult to distinguish from tumoral or other forms of hyperinsulinemic hypoglycemia including surreptitious insulin administration. No standardized treatment regimen exists. Objectives: To evaluate an analytic approach to IAS and responses to different treatments. Design and Setting: Observational study in the UK Severe Insulin Resistance Service. Patients: 6 patients with hyperinsulinemic hypoglycemia and detectable circulating anti-insulin antibody (IA). Main outcome measures: Glycemia, plasma insulin and C-peptide concentrations by immunoassay or mass spectrometry (MS). Immunoreactive insulin was determined in the context of polyethylene glycol (PEG) precipitation and gel filtration chromatography (GFC). IA quantification using enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA), and IA were further characterized using radioligand binding studies. Results: All patients were diagnosed with IAS (5 IgG, 1 IgA) based on high insulin:C-peptide ratio, low insulin recovery after PEG precipitation, and GFC evidence of antibody-bound insulin. Neither ELISA nor RIA result proved diagnostic for every case. MS provided a more robust quantification of insulin in the context of IA. 1 patient was managed conservatively, 4 were treated with diazoxide without sustained benefit, and 4 were treated with immunosuppression with highly variable responses. IA affinity did not appear to influence presentation or prognosis. Conclusions: IAS should be considered in patients with hyperinsulinemic hypoglycemia and a high insulin:C-peptide ratio. Low insulin recovery on PEG precipitation supports the presence of insulin-binding antibodies, with GFC providing definitive confirmation. Immunomodulatory therapy should be customized according to individual needs and clinical response

Exploring the Surge in Paediatric Type 2 Diabetes in an Inner-City London Centre—A Decade-Long Analysis of Incidence, Outcomes, and Transition

The rising prevalence of paediatric type 2 diabetes (T2D) is concerning, particularly with limited medical intervention despite evidence of accelerated disease progression. This study of a Barts Health NHS Trust cohort from 2008 to 2022 aims to elucidate the incidence, clinical outcomes, and complications associated with paediatric T2D. A retrospective analysis utilising electronic and paper records identified 40 patients with T2D. The incidence doubled from 2.6/year in 2008–2013 to 5.4/year in 2014–2018. Sixty-eight percent exhibited co-morbidities, notably learning disabilities. At diagnosis, the mean BMI was 32.4 ± 6.71 kg/m2, with no gender-based disparity and no significant change over a two-year follow-up. The initial HbA1c was 75.2 ± 21.0 mmol/mol, decreasing to 55.0 ± 17.4 mmol/mol after three months (p = 0.001) and then rising to 63.0 ± 25.5 mmol/mol at one year (p = 0.07). While 22/37 patients achieved HbA1c p = 0.34). This study highlights substantial therapeutic failure, with current management falling short in achieving a sustained reduction in BMI or HbA1c. Novel treatment approaches are needed to improve clinical outcomes and address the high burden of co-morbidities and complications