Evidence map›Paper›PMID 41697557›Full record

ArticleEndocrine2026

How to manage patients with diabetes suffering from unstable blood glucose control due to insulin antibodies.

M Ishihara, N Hattori, N Nishiyama, T Adachi, N Toyoda, T Saito

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Article in Endocrine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

6 authors.

M IshiharaDepartment of Orthopedic Surgery, Kansai Medical University, Osaka, 573-1010, Japan.
N HattoriDepartment of Orthopedic Surgery, Kansai Medical University, Osaka, 573-1010, Japan. hatsutori.nao@kmu.ac.jp.ORCID 0000-0001-9134-3452
N NishiyamaDepartment of Orthopedic Surgery, Kansai Medical University, Osaka, 573-1010, Japan.
T AdachiDepartment of Orthopedic Surgery, Kansai Medical University, Osaka, 573-1010, Japan.
N ToyodaDepartment of Medicine II, Kansai Medical University Hospital, Osaka, 573-1010, Japan.
T SaitoDepartment of Orthopedic Surgery, Kansai Medical University, Osaka, 573-1010, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeWe had a patient with type 2 diabetes (patient A) who suffered from hyperglycemia and frequent episodes of nocturnal hypoglycemia. He had a high titer of insulin antibodies (> 50.0 U/mL) and a very high serum insulin concentration (19,516 µU/mL). The aims of this study were (1) establishing a non-isotopic method to identify insulin analogs that bind less to the antibodies and validating its clinical usage and (2) elucidating the mechanism of his nocturnal hypoglycemia and its management.

methodsThe optimal conditions for binding study were determined using seven exogenous insulin preparations (human insulin, lispro, aspart, glulisine, glargine, degludec, and detemir) via polyethylene glycol method. The effect of pH on binding of endogenous insulin to its antibodies was examined via gel filtration chromatography (GFC) on different pH.

resultsSeveral times higher concentration of exogenous insulin was most appropriate in binding study. It revealed that all seven insulin preparations significantly bound to the insulin antibodies in patient A. Among the other 53 serum samples containing insulin antibodies, about 70% of them had at least one insulin analog that did not significantly bind to their insulin antibodies. GFC revealed that reducing the pH from 7.4 to 7.2 partially dissociated antibody-bound insulin leading to increased unbound insulin.

conclusionWe established and validated a non-isotopic method to identify suitable insulin preparations that bound less to insulin antibodies. Correcting respiratory acidosis during sleep might be effective to prevent nocturnal hypoglycemia in some patients with diabetes having insulin antibodies.

Indexed as

Diabetes Mellitus, Type 2HypoglycemiaHypoglycemic AgentsInsulinInsulin AntibodiesBlood GlucoseGlycemic ControlHumansMaleMiddle AgedBlood GlucoseHypoglycemic AgentsInsulinInsulin AntibodiesHyperglycemiaHyperinsulinemiaHypoglycemiaInsulin analogsInsulin antibodiesType 2 diabetes

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.