Rare Cause of Recurrent Hypoglycemia: Insulin Autoimmune Syndrome

We report a case of insulin autoimmune syndrome associated with several autoantibodies, presenting with recurrent hypoglycemia, predominantly in the postprandial period, which improved by dietary management and spontaneously resolved within two months. Differentiation from other causes of hyperinsulinemic hypoglycemia, such as insulinoma, is important to avoid unnecessary invasive procedures or surgical interventions. The 75-gram oral glucose tolerance test (OGTT) and mixed meal test showed a typical pattern, which may be useful indirect evidence of insulin autoimmune syndrome.

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Comparison of Two Autoimmune Dysglycemia Syndromes: Insulin Autoimmune Syndrome (IAS) and Type B Insulin Resistance Syndrome (B-IRS)

Hormone and Metabolic Research ◽

10.1055/a-1005-0071 ◽

2019 ◽

Vol 51 (11) ◽

pp. 723-728 ◽

Cited By ~ 1

Author(s):

Sui Yu ◽

Guoqing Yang ◽

Jingtao Dou ◽

Baoan Wang ◽

Weijun Gu ◽

...

Keyword(s):

Insulin Resistance ◽

Serum Insulin ◽

Insulin Resistance Syndrome ◽

Tolerance Test ◽

White Blood Count ◽

Oral Glucose ◽

Type B ◽

Insulin Autoimmune Syndrome ◽

Autoimmune Syndrome ◽

Clinical Differential Diagnosis

AbstractInsulin autoimmune syndrome (IAS) and type B insulin resistance syndrome (B-IRS) are rare autoimmune dysglycemia syndromes, but their treatment and prognosis are different. This study aimed to provide a basis for the clinical differential diagnosis of IAS and B-IRS. This was a retrospective study of the medical records of all patients diagnosed with IAS or B-IRS between January 2006 and March 2018 at the Chinese PLA General Hospital. Demographic, clinical, biochemistry, treatment, and follow-up data were examined. There were several different biochemical parameters between IAS (n=13) and B-IRS (n=6): white blood count (WBC, 7.05±3.06 vs. 2.70±0.73×109/l, p=0.004), platelet (249±56.6 vs. 111±68.0×109/l, p<0.001), serum creatine (59.0±17.8 vs. 43.1±7.05 μmol/l, p=0.013), serum albumin (42.3±5.17 vs. 33.6±3.40 g/l, p=0.002), triglyceride (median, 1.33 (1.01, 1.93) vs. 0.56 (0.50, 0.79) mmol/l, p=0.002), plasma IgG (1183±201 vs. 1832±469 mg/ml, p=0.018), IgA (328±140 vs. 469±150 mg/ml, p=0.018), and C3 (128±23.4 vs. 45.3±13.5 mg/l, p<0.001). Fasting insulin in the IAS and B-IRS patients was high (299–4708 vs. 118–851 mU/l, p=0.106), and there was a difference in 2 h oral glucose tolerance test insulin (4217–8343 mU/l vs. 274–1143 mU/l, p=0.012). Glycated hemoglobin (HbA1c) in the B-IRS patients was higher than in IAS patients (114±14.4. vs. 40.6±8.89 mmol/mol, p<0.001). Serum insulin-like growth factor-1 (IGF-1) was lower in all B-IRS patients (25±0.00 vs. 132±52.7 ng/ml, p<0.001). Although IAS and B-IRS are autoimmune hyperinsulinemic dysglycemic syndromes, several clinical parameters (body mass index, HbA1c, WBC, platelet, albumin, triglyceride, IgG, C3, and IGF-1) are different between these two syndromes.

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Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog

Endocrinology Diabetes and Metabolism Case Reports ◽

10.1530/edm-16-0079 ◽

2016 ◽

Vol 2016 ◽

Cited By ~ 6

Author(s):

Chih-Ting Su ◽

Yi-Chun Lin

Keyword(s):

High Serum ◽

Insulin Antibodies ◽

Insulin Analog ◽

Hyperinsulinemic Hypoglycemia ◽

Oral Glucose ◽

List Type ◽

Exogenous Insulin ◽

C Peptide ◽

Insulin Autoimmune Syndrome ◽

Autoimmune Syndrome

Summary Insulin 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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Pitfalls in the diagnosis of insulin autoimmune syndrome (Hirata’s disease) in a hypoglycemic child: a case report and review of the literature

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2018-0441 ◽

2019 ◽

Vol 32 (4) ◽

pp. 421-428 ◽

Cited By ~ 1

Author(s):

Tiago Jeronimo Dos Santos ◽

Caroline Gouvêa Buff Passone ◽

Marina Ybarra ◽

Simone Sakura Ito ◽

Milena Gurgel Teles ◽

...

Keyword(s):

Differential Diagnosis ◽

Previous History ◽

Human Leukocyte ◽

Hyperinsulinemic Hypoglycemia ◽

Insulin Levels ◽

Insulin Autoimmune Syndrome ◽

Endogenous Insulin ◽

Autoimmune Syndrome ◽

Insulin Autoantibody ◽

Control Food Intake

Abstract Background Insulin autoimmune syndrome (IAS) is a rare cause of hyperinsulinemic hypoglycemia (HH) not addressed as a potential differential diagnosis in current pediatric guidelines. We present a case of IAS in a child with no previous history of autoimmune disease, no previous intake of triggering medications and absence of genetic predisposition. Case presentation A 6-year-old boy presented with recurrent HH (blood glucose of 26 mg/dL [1.4 mmol/L] and insulin of 686 μU/mL). Abdominal imaging was normal. After multiple therapeutic failures, we hypothesized misuse of exogenous insulin and factitious hypoglycemia. Council of Guardianship had the child separated from his mother, but insulin levels remained high. A chromatography test was then performed which showed high titers of endogenous insulin autoantibody (IAA) with early dissociation from the insulin molecule. The human leukocyte antigen (HLA) test showed a DRB1 *13:01/*08:02 genotype. The patient was advised to control food intake and physical activity routines. During a 5-year follow-up, hypoglycemic episodes were sparse, despite high insulin levels. Conclusions Misdiagnosis of IAS with factitious hypoglycemia may happen if IAS is not considered as a differential diagnosis, leading to potential traumatic consequences. Further efforts should be made to increase awareness of IAS as a differential diagnosis of hypoglycemia and to include it in pediatric guidelines.

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FGF21 Is an Insulin-Dependent Postprandial Hormone in Adult Humans

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2017-01257 ◽

2017 ◽

Vol 102 (10) ◽

pp. 3806-3813 ◽

Cited By ~ 25

Author(s):

Ricardo J Samms ◽

Jo E Lewis ◽

Luke Norton ◽

Francis B Stephens ◽

Christopher J Gaffney ◽

...

Keyword(s):

Dietary Intervention ◽

Insulin Response ◽

Tolerance Test ◽

Fibroblast Growth Factor 21 ◽

Oral Glucose ◽

High Fat ◽

Postprandial Period ◽

Carbohydrate Consumption ◽

Adult Humans ◽

The Impact

Abstract Context Fibroblast growth factor 21 (FGF21) secretion has been shown to respond directly to carbohydrate consumption, with glucose, fructose, and sucrose all reported to increase plasma levels of FGF21 in rodents and humans. However, carbohydrate consumption also results in secretion of insulin. Objective The aim of this study was to examine the combined and independent effects of hyperglycemia and hyperinsulinemia on total and bioactive FGF21 in the postprandial period in humans, and determine whether this effect is attenuated in conditions of altered insulin secretion and action. Methods Circulating glucose, insulin, total and bioactive FGF21, and fibroblast activation protein were measured in adults with and without type 2 diabetes (T2D) following an oral glucose tolerance test (OGTT), and under a series of insulin and glucose clamp conditions and following high-fat diet in healthy adults. Results Circulating total and bioactive FGF21 levels responded acutely to OGTT, and their ratio was attenuated in T2D patients with reduced postprandial insulin response. The clamp studies revealed that insulin but not glucose accounts for the postprandial rise in FGF21. Finally, there was an attenuated rise in FGF21 in response to a high-fat dietary intervention that is known to alter insulin-stimulated substrate utilization in metabolically active tissues. Conclusions Insulin rather than glucose per se increases total and bioactive FGF21 in the postprandial period in adult humans. Understanding the impact of T2D on bioactive FGF21 will have a significant effect upon the efficacy of therapeutic agents designed to target the FGF21 pathway.

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Effect of Cinnamon Tea on Postprandial Glucose Concentration

Journal of Diabetes Research ◽

10.1155/2015/913651 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 13

Author(s):

Maria Alexandra Bernardo ◽

Maria Leonor Silva ◽

Elisabeth Santos ◽

Margarida Maria Moncada ◽

José Brito ◽

...

Keyword(s):

Blood Glucose ◽

Glucose Concentration ◽

Postprandial Glucose ◽

Tolerance Test ◽

Oral Glucose ◽

High Blood Glucose ◽

Postprandial Period ◽

Glucose Levels ◽

Blood Glucose Levels ◽

Oxidative Stress Status

Glycaemic control, in particular at postprandial period, has a key role in prevention of different diseases, including diabetes and cardiovascular events. Previous studies suggest that postprandial high blood glucose levels (BGL) can lead to an oxidative stress status, which is associated with metabolic alterations. Cinnamon powder has demonstrated a beneficial effect on postprandial glucose homeostasis in animals and human models. The purpose of this study is to investigate the effect of cinnamon tea (C. burmannii) on postprandial capillary blood glucose level on nondiabetic adults. Participants were given oral glucose tolerance test either with or without cinnamon tea in a randomized clinical trial. The data revealed that cinnamon tea administration slightly decreased postprandial BGL. Cinnamon tea ingestion also results in a significantly lower postprandial maximum glucose concentration and variation of maximum glucose concentration (p< 0.05). Chemical analysis showed that cinnamon tea has a high antioxidant capacity, which may be due to its polyphenol content. The present study provides evidence that cinnamon tea, obtained fromC. burmannii, could be beneficial for controlling glucose metabolism in nondiabetic adults during postprandial period.

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Recurrent Hypoglycemia from Insulin Autoimmune Syndrome

Journal of General Internal Medicine ◽

10.1007/s11606-013-2588-9 ◽

2013 ◽

Vol 29 (1) ◽

pp. 250-254 ◽

Cited By ~ 22

Author(s):

Sophia L. Wong ◽

Anne Priestman ◽

Daniel T. Holmes

Keyword(s):

Insulin Autoimmune Syndrome ◽

Autoimmune Syndrome ◽

Recurrent Hypoglycemia

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Hypoglycemia due to insulin autoimmune syndrome (Hirata’s disease): a rare cause of hypoglycaemia

International Journal of Advances in Medicine ◽

10.18203/2349-3933.ijam20212871 ◽

2021 ◽

Vol 8 (8) ◽

pp. 1220

Author(s):

Het V. Patel ◽

Sunil Kumar ◽

Kalpesh Moradiya ◽

Vidhi Shah

Keyword(s):

Nutrition Therapy ◽

Serum Glucose ◽

Insulin Antibodies ◽

Laboratory Evaluation ◽

Hyperinsulinemic Hypoglycemia ◽

Lifestyle Modifications ◽

Glucose Levels ◽

Insulin Autoimmune Syndrome ◽

Autoimmune Syndrome ◽

Recurrent Hypoglycaemia

Although the most common cause of recurrent hypoglycaemia is diabetes mellitus as patient is on antidiabetic medications which can be prevented by modification of antidiabetic doses, nutrition therapy and lifestyle modifications. Some endogenous hyperinsulinemic conditions like insulinoma, functional beta cell disorders and insulin autoimmune syndromes, hormonal deficiencies can cause serious and sometimes life threatening hypoglycaemia. So further laboratory evaluation like plasma/serum glucose levels, c-peptide levels, insulin levels, insulin antibodies and imaging studies are needed to evaluate unexplained hypoglycaemia. Here we report a case of insulin autoimmune syndrome in a 67 year old Indian male who had presented to us with multiple episodes of spontaneous hypoglycaemia. On further workup, the patient was found to have endogenous hyperinsulinemic hypoglycemia. As the patient’s abdominal imaging revealed no apparent cause of EHH, on further evaluation he came positive for insulin antibodies. Patient was diagnosed as IAS and he was given frequent small meals and complex carbohydrate diet and he had improved symptomatically. The incidence of IAS is most common in Japan and very few cases have been reported from India, so it should be kept in differential diagnosis of recurrent hypoglycaemia.

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