In vivo relationship between bound and free insulin in patients with diabetes having anti-insulin antibodies.

IF 1.3 Q4 ENDOCRINOLOGY & METABOLISM

Diabetology International Pub Date : 2023-06-20 eCollection Date: 2023-10-01 DOI:10.1007/s13340-023-00641-1

Hiroyuki Asaka, Shigehiro Karashima, Daisuke Chujo, Mitsuhiro Kometani, Mikiya Usukura, Kunimasa Yagi, Ko Aiga, Takashi Yoneda

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Abstract

Objective: The Scatchard plot of anti-insulin antibodies is curvilinear, indicating heterogeneity in binding sites. However, the relationship between bound insulin (B) and free insulin (F) in patients with anti-insulin antibodies has not yet been elucidated. This study aimed to determine this relationship.

Methods: We studied two insulin-treated patients with diabetes who had high titers of anti-insulin antibodies. The B and F levels were measured using daily blood samples. Assuming that the law of mass action is applicable to the reactions between insulin and anti-insulin antibody forms, we plotted the bound-to-free ratio (B/F) vs. B using patient data. We also performed an equilibrium binding assay in vitro.

Results: Some of the B/F vs. B plots of the daily variation showed an approximately linear relationship, while the Scatchard plots of in vitro data became curvilinear.

Conclusion: Our study suggests that the one-site (high-affinity site) of anti-insulin antibodies accounts, for the most part, for insulin pharmacokinetics within physiological insulin concentrations.

Supplementary information: The online version contains supplementary material available at 10.1007/s13340-023-00641-1.

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具有抗胰岛素抗体的糖尿病患者体内结合胰岛素和游离胰岛素之间的关系。

目的：抗胰岛素抗体的Scatchard图是曲线图，表明结合位点的异质性。然而，抗胰岛素抗体患者的结合胰岛素（B）和游离胰岛素（F）之间的关系尚未阐明。本研究旨在确定这种关系。方法：我们研究了两名胰岛素治疗的糖尿病患者，他们具有高滴度的抗胰岛素抗体。使用每日血液样本测量B和F水平。假设质量作用定律适用于胰岛素和抗胰岛素抗体形式之间的反应，我们使用患者数据绘制了结合自由比（B/F）与B的关系图。我们还在体外进行了平衡结合测定。结果：一些每日变化的B/F与B图显示出近似线性关系，而体外数据的Scatchard图则变为曲线。结论：我们的研究表明，抗胰岛素抗体的一个位点（高亲和力位点）在很大程度上解释了生理胰岛素浓度下的胰岛素药代动力学。补充信息：在线版本包含补充材料，可访问10.1007/s13340-023-00641-1。

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来源期刊

Diabetology International ENDOCRINOLOGY & METABOLISM-

CiteScore

3.90

自引率

4.50%

发文量

期刊介绍： Diabetology International, the official journal of the Japan Diabetes Society, publishes original research articles about experimental research and clinical studies in diabetes and related areas. The journal also presents editorials, reviews, commentaries, reports of expert committees, and case reports on any aspect of diabetes. Diabetology International welcomes submissions from researchers, clinicians, and health professionals throughout the world who are interested in research, treatment, and care of patients with diabetes. All manuscripts are peer-reviewed to assure that high-quality information in the field of diabetes is made available to readers. Manuscripts are reviewed with due respect for the author''s confidentiality. At the same time, reviewers also have rights to confidentiality, which are respected by the editors. The journal follows a single-blind review procedure, where the reviewers are aware of the names and affiliations of the authors, but the reviewer reports provided to authors are anonymous. Single-blind peer review is the traditional model of peer review that many reviewers are comfortable with, and it facilitates a dispassionate critique of a manuscript.