Department of Clinical Biochemistry and Immunology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
The University of Cambridge MRC Metabolic Disease Unit, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK.
Diabet Med. 2023 Nov;40(11):e15194. doi: 10.1111/dme.15194. Epub 2023 Sep 1.
Anti-insulin antibodies in insulin-treated diabetes can derange glycaemia, but are under-recognised. Detection of significant antibodies is complicated by antigenically distinct insulin analogues. We evaluated a pragmatic biochemical approach to identifying actionable antibodies, and assessed its utility in therapeutic decision making.
Forty people with insulin-treated diabetes and combinations of insulin resistance, nocturnal/matutinal hypoglycaemia, and unexplained ketoacidosis were studied using broad-specificity insulin immunoassays, polyethylene glycol (PEG) precipitation and gel filtration chromatography (GFC) with or without ex vivo insulin preincubation.
Twenty-seven people had insulin immunoreactivity (IIR) below 3000 pmol/L that fell less than 50% after PEG precipitation. Insulin binding by antibodies in this group was low and judged insignificant. In 8 people IIR was above 3000 pmol/L and fell by more than 50% after PEG precipitation. GFC demonstrated substantial high molecular weight (HMW) IIR in 7 of these 8. In this group antibodies were judged likely significant. In 2 people immunosuppression was introduced, with a good clinical result in one but only a biochemical response in another. In 6 people adjustment of insulin delivery was subsequently informed by knowledge of underlying antibody. In a final group of 5 participants IIR was below 3000 pmol/L but fell by more than 50% after PEG precipitation. In 4 of these GFC demonstrated low levels of HMW IIR and antibody significance was judged indeterminate.
Anti-insulin antibodies should be considered in insulin-treated diabetes with unexplained glycaemic lability. Combining immunoassays with PEG precipitation can stratify their significance. Antibody depletion may be beneficial, but conservative measures often suffice.
在接受胰岛素治疗的糖尿病患者中，抗胰岛素抗体可扰乱血糖水平，但未得到充分认识。由于具有不同抗原性的胰岛素类似物的存在，检测到显著的抗体变得复杂。我们评估了一种实用的生化方法来识别有作用的抗体，并评估其在治疗决策中的效用。
研究了 40 名接受胰岛素治疗的糖尿病患者，这些患者存在胰岛素抵抗、夜间/清晨低血糖和不明原因酮症酸中毒等情况，使用广谱胰岛素免疫测定法、聚乙二醇（PEG）沉淀和凝胶过滤色谱（GFC），并在有或没有体外胰岛素预孵育的情况下进行检测。
27 人的胰岛素免疫反应性（IIR）低于 3000pmol/L，PEG 沉淀后下降不到 50%。该组中抗体的胰岛素结合力较低，被认为不重要。8 人的 IIR 高于 3000pmol/L，PEG 沉淀后下降超过 50%。GFC 在这 8 人中的 7 人显示出大量高分子量（HMW）IIR。在该组中，抗体被判断为可能具有重要意义。在 2 人引入免疫抑制后，其中 1 人的临床结果良好，但另 1 人的仅为生化反应。在 6 人随后根据对潜在抗体的了解调整了胰岛素的输送。在最后一组的 5 名参与者中，IIR 低于 3000pmol/L，但 PEG 沉淀后下降超过 50%。在这 4 人中，GFC 显示出低水平的 HMW IIR，抗体意义被判断为不确定。
在不明原因血糖不稳定的接受胰岛素治疗的糖尿病患者中应考虑抗胰岛素抗体。将免疫测定与 PEG 沉淀相结合可以对其意义进行分层。抗体耗竭可能有益，但保守措施通常就足够了。
