Prevalence of anti-insulin antibodies and its relation to severe hypoglycaemia in insulin-treated diabetic patients

Wredling, Regina; Lins, Per‐Eric; Adamson, Ulf

doi:10.1080/00365519009089170

Cited by 22 publications

(4 citation statements)

References 32 publications

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“…IAs could prevent insulin from binding its receptor, possibly resulting in the deterioration of the physiological effects of insulin; thereafter, insulin is released from the complexes irrespective of blood glucose concentrations, thus inducing hypoglycemia ( 14 – 18 ). However, the relationship between IAs and hypoglycemia was not determined in previous large-scale studies ( 13 , 19 , 20 ). One of the most important reasons for discrepancy among these findings may be the uncertainty of collecting information related to mild hypoglycemia based on subjects’ retrospective memory.…”

Section: Discussionmentioning

confidence: 91%

The clinical implications of fasting serum insulin levels in patients with insulin-treated type 2 diabetes: a cross-sectional survey

Zhou

Luo

Wang

et al. 2023

Front. Clin. Diabetes Healthc.

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ObjectiveThis study aimed to investigate the clinical implications of fasting serum insulin (FINS) levels in subjects with type 2 diabetes who were receiving insulin therapy.MethodsA total of 1,553 subjects with type 2 diabetes [774 subjects who had never received insulin treatment (N-INS) and 779 subjects who were receiving insulin therapy (constant insulin treatment, C-INS)] admitted to the Department of Endocrinology and Metabolism of Peking University People’s Hospital were enrolled in this study. Their FINS levels were measured and those with hyperinsulinemia were identified. The underlying mechanisms of hyperinsulinemia were revealed by measuring insulin antibodies (IAs) and analyzing changes in FINS levels before and after polyethylene glycol (PEG) precipitation. In addition, the clinical characteristics of patients with different types of hyperinsulinemia were compared.ResultsHigher FINS levels and a higher incidence (43.8%, 341/779) of hyperinsulinemia (FINS > 15μIU/mL) were observed in subjects with C-INS than in subjects with N-INS. Among subjects with C-INS and hyperinsulinemia, 66.9% (228/341) were IAs positive, and the incidence of IAs was found to be positively associated with FINS level. By performing PEG precipitation, we found that all subjects without IAs (i.e., those with real hyperinsulinemia) and 31.1% of subjects (71/228) with IAs (i.e., those with both real and IAs-related hyperinsulinemia) still had hyperinsulinemia after PEG precipitation, whereas FINS levels in the other 68.9% of subjects (157/228) with IAs were normal (IAs-related hyperinsulinemia) after PEG precipitation. Comparisons between the groups showed that subjects with real hyperinsulinemia showed more obvious insulin resistance characteristics, including higher lipid levels, BMIs, and homoeostasis model assessment2-estimated insulin resistance (HOMA2-IR) index, and were more likely to have hypertension, obesity, and metabolic syndromes (p < 0.05). However, the risk of hypoglycemia and glucose variability increased significantly in subjects with IAs compared with those without IAs. A cutoff of FINS to serum C-peptide ratio (≥ 9.3μIU/ng) could be used to screen IAs in clinical practice with 83.3% sensitivity and 70% specificity.ConclusionsIt is necessary to measure FINS in subjects with C-INS to distinguish between types of hyperinsulinemia, which should help to tailor treatment regimens.

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Section: Discussionmentioning

confidence: 91%

The clinical implications of fasting serum insulin levels in patients with insulin-treated type 2 diabetes: a cross-sectional survey

Zhou

Luo

Wang

et al. 2023

Front. Clin. Diabetes Healthc.

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“…Since the introduction of purified insulins and human insulin, the prevalence of anti-insulin autoantibodies in patients previously treated with insulin has declined; however, prevalence remains high. Wredling et al found that among individuals with prior insulin treatment, up to 78% had insulin autoantibodies, particularly prevalent in type 1 DM patients and those with prolonged insulin use ( 21 ). Although rarely clinically significant, anti-insulin IgG autoantibodies can bind to exogenous insulin and form ICs that can deposit in various tissues, triggering the classical complement pathway and causing inflammation.…”

Section: Discussionmentioning

confidence: 99%

A case report and systematic literature review: insulin-induced type III hypersensitivity reaction

Meredith,

Patel,

Huang

et al. 2024

Front. Allergy

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Insulin-induced type III hypersensitivity reactions (HSRs) are exceedingly rare and pose complex diagnostic and management challenges. We describe a case of a 43-year-old woman with type 1 diabetes mellitus (DM), severe insulin resistance, and subcutaneous nodules at injection sites, accompanied by elevated anti-insulin IgG autoantibodies. Treatment involved therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIg) as bridge therapy, followed by long-term immunosuppression, which reduced autoantibody levels and improved insulin tolerance. Given the limited treatment guidelines, we conducted a comprehensive literature review, identifying 16 similar cases. Most patients were females with a median age of 36.5 years; 63% had type 1 DM, and 44% had concurrent insulin resistance (56% with elevated autoantibodies). Treatment approaches varied, with glucocorticoids used in 67% of cases. Patients with Type 1 DM were less responsive to steroids than those with type 1 DM, and had a more severe course. Of those patients with severe disease necessitating immunosuppression, 66% had poor responses or experienced relapses. The underlying mechanism of insulin-induced type III HSRs remains poorly understood. Immunosuppressive therapy reduces anti-insulin IgG autoantibodies, leading to short-term clinical improvement and improved insulin resistance, emphasizing their crucial role in the condition. However, the long-term efficacy of immunosuppression remains uncertain and necessitates continuous evaluation and further research.

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“…These antibodies had the characteristics of low capacity and high affinity, which seldom cause hypoglycemia or hyperglycemia (5). From the literature, incidence of 0.16% of exogenous insulin-induced insulin antibodies in patients with diabetes had been reported (6).…”

Section: Discussionmentioning

confidence: 99%

Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog

Lin

2016

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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SummaryInsulin antibodies (IA) associated with exogenous insulin administration seldom caused hypoglycemia and had different characteristics from insulin autoantibodies (IAA) found in insulin autoimmune syndrome (IAS), which was first described by Dr Hirata in 1970. The characteristic of IAS is the presence of insulin-binding autoantibodies and related fasting or late postprandial hypoglycemia. Here, we report a patient with type 1 diabetes mellitus under insulin glargine and insulin aspart treatment who developed recurrent spontaneous post-absorptive hyperinsulinemic hypoglycemia with the cause probably being insulin antibodies induced by exogenous injected insulin. Examinations of serial sera disclosed a high titre of insulin antibodies (33%, normal <5%), high insulin concentration (111.9 IU/mL) and undetectable C-peptide when hypoglycemia occurred. An oral glucose tolerance test revealed persistent high serum levels of total insulin and undetectable C-peptide. Image studies of the pancreas were unremarkable, which excluded the diagnosis of insulinoma. The patient does not take any of the medications containing sulfhydryl compounds, which had been reported to cause IAS. After administering oral prednisolone for 3 weeks, hypoglycemic episodes markedly improved, and he was discharged smoothly.Learning points:Insulin autoimmune syndrome (IAS) or IAS-like situation should be one of the differential diagnosis in patients with hyperinsulinemic hypoglycemia.Although less reported, insulin antibodies (IA) caused by exogenous insulin analog should be considered as the cause of hypoglycemia.Patients with suspected insulin autoimmune syndrome (IAS) should be screened for drugs related to autoimmunity to endogenous insulin.

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Prevalence of anti-insulin antibodies and its relation to severe hypoglycaemia in insulin-treated diabetic patients

Cited by 22 publications

References 32 publications

The clinical implications of fasting serum insulin levels in patients with insulin-treated type 2 diabetes: a cross-sectional survey

The clinical implications of fasting serum insulin levels in patients with insulin-treated type 2 diabetes: a cross-sectional survey

A case report and systematic literature review: insulin-induced type III hypersensitivity reaction

Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog

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