Immunological Hypoglycemia Associated with Insulin Antibodies Induced by Exogenous Insulin in 11 Chinese Patients with Diabetes

Aims. To investigate the characteristics of immunological hypoglycemia associated with insulin antibodies (IAbs) induced by exogenous insulin in Chinese patients with diabetes.Methods. The clinical data of patients with immunological hypoglycemia due to IAbs were retrospectively analyzed by screening patients with diabetes discharged from West China Hospital from 2007 to 2013.Results. A total of 11 patients (eight men and three women) were identified. Insulin-C-peptide separation was found in all patients via insulin and C-peptide release test. Previous insulin use was ceased after admission and was switched to oral hypoglycemic agents (OHAs) (8/11), lifestyle modification only (2/11), or regular human insulin (1/11). Hypoglycemia was ameliorated after a median of 20 days (interquartile range [IQR], 11–40), while IAbs turned negative after a median of 17 months (IQR, 4–19), and serum immunoreactive insulin (IRI) levels dropped substantially after a median of 22 months (IQR, 9–32) in these cases.Conclusions. In insulin-treated patients with unexpected and refractory hypoglycemia even after insulin therapy was gradually reduced or even withdrawn, IAbs induced by exogenous insulin should be considered, and insulin withdrawal might be promptly needed. The course of immunological hypoglycemia was benign and self-limited.

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Analysis of the clinical characteristics of insulin autoimmune syndrome induced by exogenous insulin in diabetic patients

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00658-z ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Zuojun Li ◽

Dan Yi ◽

Lijuan Zheng ◽

Shiran Li ◽

Weijin Fang ◽

...

Keyword(s):

Clinical Characteristics ◽

Serum Insulin ◽

Insulin Antibodies ◽

Hypoglycemic Agents ◽

Oral Glucose ◽

Diabetic Patients ◽

Exogenous Insulin ◽

Oral Hypoglycemic Agents ◽

Insulin Autoimmune Syndrome ◽

Autoimmune Syndrome

Abstract Background The exact incidence, clinical features and uniform diagnostic criteria of exogenous insulin autoimmune syndrome (EIAS) are still unclear. The purpose of this study is to explore the clinical characteristics of EIAS and to provide a structural approach for clinical diagnosis, treatment and prevention. Methods The literature on EIAS in Chinese and English from 1970 to 2020 was collected for retrospective analysis. Results A total of 122 patients (33 males and 73 females) were included in the study with a median age of 67 years (range 14–86) and a median HbA1c of 7.7%. EIAS mainly occurred in type 2 diabetes mellitus patients using premixed insulin. Symptoms manifested were hypoglycemia in 86.54%, recurrent episodes of symptomatic hypoglycemia in 35.58%, nocturnal hypoglycemia along with daytime hyperglycemia in 21.15% and recurrent hypoglycemia after discontinued insulin in 64.43%. The onset of symptoms occurred at night, in the early morning or during fasting, ranging from a few days to 78 months after the administration of insulin. The mean blood glucose level during the hypoglycemic phase was 2.21 mmol/L (range 1–3.4), and the serum insulin levels were mainly ≥ 100 U/mL and were associated with low C-peptide levels (≤ 10 ng/ml). Insulin autoantibodies (IAAs) were positive in all EIAS patients. The 75-g extended oral glucose tolerance test (OGTT) mainly showed a diabetic curve. Pancreatic imaging was unremarkable. Withdrawal of insulin alone or combination of oral hypoglycemic agents or replacement of insulin formulations or with corticosteroid treatment eliminated hypoglycemia in a few days to 3 months. IAA turned negative in 6 months (median, range 1–12). No hypoglycemia episodes were observed at a median follow-up of 6 months (range 0.5–60). Conclusions EIAS is an autoimmune disease caused by insulin-binding antibodies in susceptible subjects. Insulin antibodies change glucose dynamics and could increase the incidence of hypoglycemic episodes. Detection of insulin antibodies is the diagnostic test. Changing therapeutic modalities reduced the incidence of hypoglycemic episodes.

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