Insulin Autoimmune Syndrome Research Articles

Late Postprandial Hypoglycemia due to Bioactive Insulin Dissociation from Autoantibody Leading to Unconsciousness in a Patient with Insulin Autoimmune Syndrome

We report here the case of an 83-year-old man who was treated for unconsciousness and hypoglycemia (39 mg/dL) accompanied by marked elevation of serum immunoreactive insulin (IRI) (4,760 µIU/mL). We diagnosed his condition as insulin autoimmune syndrome (IAS, Hirata disease) because of a high insulin autoantibody (IAA) titer (>90%: bound/total) and no history of exogenous insulin administration. Reactive hypoglycemia occurred due to immediate association followed by dissociation between insulin and insulin autoantibodies after glucose or food intake. An α-glucosidase inhibitor in combination with frequent small meals reduced the postprandial hyperglycemia (glucose spike) and ameliorated the reactive hypoglycemia.

What We Recently Know from Insulin Autoimmune Syndrome

What We Recently Know from Insulin Autoimmune Syndrome

A Case of Insulin Autoimmune Syndrome Induced by Bucillamine

A Case of Insulin Autoimmune Syndrome Induced by Bucillamine

Insulin autoimmune syndrome (Hirata disease): epidemiology in Asia, including Japan

As populations with a higher prevalence of HLADRB1*0406 have been found to have a higher risk of developing insulin autoimmune syndrome (IAS), we report here the clinical features of Asian and Japanese IAS. There was female dominance in the 20- to 49-year-old age group at the onset of IAS development. Forty-two percent of Japanese IAS patients had received drugs or α-lipoic acid containing the sulfhydryl group, while 81% of Asian IAS patients outside Japan had received methimazole or carbimazole before the development of IAS.

Von der Frau, der das Essen nicht bekam

We report the case of a 59-year-old women with idiopathic insulin auto-immune syndrome, a rare cause of endogenous hyperinsulinemic hypoglycemia. It is characterized by extremely high levels of insulin in the presence of high titers of insulin antibodies despite the absence of previous insulin injections. Early postprandial increase in glucose concentrations due to impaired insulin action resulting from the buffering effect of the antibodies and late postprandial hypoglycemia as a consequence of the dissociation of insulin from the antibodies was observed. A correct diagnosis is important to avoid unnecessary investigations and surgery in these patients who are best treated conservatively - with a good prognosis - by fractionating carbohydrate intake during the day.

A Current Update on the Use of Alpha Lipoic Acid in the Management of Type 2 Diabetes Mellitus

Type 2 Diabetes Mellitus (T2DM) which is characterised by insulin resistance, is closely linked to the triad of glucolipotoxicity, inflammation and oxidative stress. Increased adiposity, leading to increased free fatty acids (FFAs), contributes to insulin resistance by disrupting the signal transduction pathway of insulin mediated glucose disposal, and causes impaired insulin secretion. Hyperglycaemia and dyslipidaemia driven oxidative stress resulting from enhanced free-radical formation and/or defects in antioxidant defence is implicated in the pathogenesis of diabetic neuropathy (DN). This and other inflammatory pathways account for a complex network of interacting metabolic factors responsible for causing diabetes and her complications. There is growing evidence that Alpha Lipoic Acid (ALA) has beneficial effects on the treatment of T2DM and some of its complications. It represents an attractive pharmacological target in the treatment of T2DM by modulating the signal transduction pathways in insulin resistance and antagonizing the oxidative and inflammatory stresses, which are major players in the pathogenesis of this disorder. A potent anti-oxidant and free radical scavenger, ALA also targets cellular signal transduction pathways which increases glucose uptake and utilization, thus providing specific targeted therapy in the treatment of insulin resistance and diabetic neuropathy. Apart from the rare risk of Insulin Autoimmune Syndrome (IAS), ALA has shown to be relatively safe, even in patients with renal and liver failure. This review focuses and summarises the molecular mechanisms of T2DM, and underlines the therapeutic value of ALA in this globally significant disease.

低血糖症状を契機に発見され，健康食品（αリポ酸）が誘因である可能性を否定できなかったインスリン自己免疫症候群の一症例

低血糖症状を契機に発見され，健康食品（αリポ酸）が誘因である可能性を否定できなかったインスリン自己免疫症候群の一症例

Autoimmune Forms of Hypoglycemia

Autoimmune syndromes are a rare cause of hypoglycemia characterized by elevated levels of insulin in the presence of either anti-insulin antibodies (insulin autoimmune syndrome) or anti-insulin receptor antibodies (type B insulin resistance). Insulin autoimmune syndrome is the third leading cause of hypoglycemia in Japan, but has rarely been described in the non-Asian population.In the current study, we report the clinical and biochemical characteristics and clinical course of 2 white patients with insulin autoimmune syndrome, and present a literature review of non-Asian patients reported with insulin autoimmune syndrome. Also, we describe the clinical and biochemical characteristics of patients reported in the literature with type B insulin resistance who manifested hypoglycemia. We compare the clinical and laboratory features of insulin autoimmune syndrome and type B insulin resistance with each other and with other forms of hyperinsulinemic hypoglycemia.Autoimmune forms of hypoglycemia are uncommon. However, they should be considered in any patient with hypoglycemia in the setting of unsuppressed insulin levels associated with anti-insulin or anti-insulin receptor antibodies. Making the correct diagnosis may spare a hypoglycemic patient from an unnecessary pancreatic surgical procedure.

Characteristics of the antibodies of two patients who developed daytime hyperglycemia and morning hypoglycemia because of insulin antibodies

We encountered two patients who developed daytime hyperglycemia and early morning hypoglycemia because of insulin antibody (IA) that the affinity was extremely lower and the capacity extremely higher than those of IA in the insulin autoimmune syndrome, after their insulin treatment were changed from human insulin to analog insulin.

Glucose Counterregulatory Hormone Response During Hypoglycemia due to Endogenous Hyperinsulinemia

Background: In patients with hypoglycemia due to endogenous hyperinsulinemia such as insulinoma or insulin autoimmune syndrome, little is known about the counterregulatory hormone response to spontaneous hypoglycemia. We therefore compared hormone responses during spontaneous hypoglycemia due to endogenous hyperinsulinemia with those at the end of a 72-hour fast. Methods: We measured glucagon, epinephrine, cortisol, and growth hormone responses during spontaneous hypoglycemia in 8 patients with insulinoma and 18 patients with insulin autoimmune syndrome. We also assessed these responses in 13 normal control subjects who underwent a 72-hour fast. Results: In patients with insulinoma (median serum glucose level, 35.0 mg/dL), plasma glucagon levels (median, 42.9 vs. 76.2 pg/mL, respectively; P < 0.05) were lower than those in control subjects (serum glucose level, 62.5 mg/dL), whereas, there were no statistically significant differences in the other hormone responses between the two groups. In contrast, in the patients with insulin autoimmune syndrome (median serum glucose level, 34.5 mg/dL), plasma glucagon levels (median, 73.7 vs. 76.2 pg/mL, respectively) were lower than those in the control subjects, but there was no statistically significant difference between the two groups. There were no statistically significant differences in counterregulatory hormone responses during spontaneous hypoglycemia between patients with insulinoma and patients with insulin autoimmune syndrome. Conclusion: Our results suggest that defective glucagon secretion in patients with insulinoma rather than insulin autoimmune syndrome may contribute to hypoglycemia in addition to hyperinsulinemia. (J Korean

Severe insulin resistance due to anti‐insulin antibodies: response to plasma exchange and immunosuppressive therapy

Anti-insulin antibodies have been described in two contexts: in insulin-naive individuals (so-called 'insulin autoimmune syndrome') and in patients with insulin-treated diabetes, in whom antibodies are rarely of clinical significance. We report the case of an 68-year-old woman who exhibited a local allergic reaction to subcutaneous insulin followed by severe insulin resistance, evidenced by poor glycaemic control despite treatment with > 3.5 U/kg of insulin per day. She was found to have circulating polyclonal anti-insulin antibodies of the IgG subtype and responded clinically to a course of plasma exchange and immunosuppression with mycophenolate mofetil and, subsequently, intravenous immunoglobulin. Falling titres of antibodies on this regimen correlated with improved glycaemic control. This case suggests that clinicians should be alert to the possibility of insulin resistance due to anti-insulin antibodies and that immunosuppression in this situation may be a valuable therapeutic option.

A Case of Insulin Autoimmune Syndrome in a Patient with Partial Hypopituitarism

Insulin autoimmune syndrome is one of the rare causes of hypoglycemia, and characterized by hyperinsulinemic hypoglycemia associated with high titer of antibodies to endogenous insulin. We report a case of insulin autoimmune syndrome in a 57-year-old woman, presenting with mental changes due to hypoglycemia. She had no history of diabetes or insulin administration. The serum C-peptide level was 4.69 ng/mL and the insulin concentration was 229.55 μ U/mL, when fasting plasma glucose level was 32 mg/dL. The insulin-to-glucose ratio was 7.17, while there was no radiologic evidence of insulinoma. The insulin antibody level was over 100 μU/mL, resulting in the diagnosis of insulin autoimmune syndrome. Hormonal studies revealed partial hypopituitarism and a lack of glucagon-response to hypoglycemia. Hypoglycemia disappeared with replacement of prednisolone with levothyroxine therapy. Under secretion of growth hormone and of adrenocorticotropic hormone due to hypopituitarism were associated with insufficient counterregulation to hypoglycemia. One should keep in mind that insulin autoimmune syndrome or hypopituitarism is one cause of hypoglycemia in patients with no history of diabetes, and corticosteroid can be an effective treatment for

Insulin Autoimmune Syndrome in a Patient with Myasthenia Gravis and Graves' Disease

Insulin Autoimmune Syndrome in a Patient with Myasthenia Gravis and Graves' Disease

A Case of Insulin Autoimmune Syndrome Suspected of Showing False Positive Results for Insulin Receptor Antibody

A Case of Insulin Autoimmune Syndrome Suspected of Showing False Positive Results for Insulin Receptor Antibody

Drug-induced insulin autoimmune syndrome

Although insulin autoimmune syndrome (IAS) was found to be strongly related with methimazole, rapidly increasing numbers of cases with alpha lipoic acid-induced IAS have been confirmed to be reported since 2003. As alpha lipoic acid has gained popularity as a supplement for dieting and anti-aging, a warning should be issued.

Insulin autoimmune syndrome in a patient with ANCA-associated glomerulonephritis

The patient, a 66-year-old woman, who has been under hemodialysis due to antineutrophil cytoplasm autoantibody (ANCA)-associated glomerulonephritis since 2003, was hospitalized because of cold sweating, general fatigue, and somnolence. Hypoglycemia (43 mg/dL) with markedly elevated insulin level (1410 μU/mL) and insulin antibody was found in her serum. She was diagnosed as having insulin autoimmune syndrome. She has not taken any medication that might cause insulin autoimmune syndrome. The possible association of ANCA-associated glomerulonephritis with insulin autoimmune syndrome is discussed.

Binding characteristics and crossreactivity of insulin autoantibodies and insulin antibodies directed to three different insulin molecules

To evaluate ex vivo/in vitro the binding and dissociation characteristics and the level of crossreactivity of insulin antibodies and insulin autoantibodies directed to three different insulin molecules (human, bovine and porcine insulin). In this study sera from 17 diabetic patients were included, who were exclusively treated with s.c. human insulin, but presenting with severe insulin antibody mediated, immunological insulin resistance (i.e., insulin antibodies, IA). In addition, we included serum from one female patient, previously diagnosed with insulin autoimmune syndrome (no exposure to exogenous insulin treatment, i.e., insulin autoantibodies, IAA). Antibody concentrations and a binding/dissociation analysis was performed by using J(125)-labelled (position: A-14) human, porcine and bovine insulin according to the protocol described recently. In the patient with insulin autoimmune syndrome (IAA) we observed total crossreactivity between human, bovine and porcine insulin. By contrast, in the group of s.c. insulin treated diabetic patients with antibody-mediated insulin resistance (IA) we detected only partial crossreactivity. In these patients, there was a significantly higher level in the inital insulin binding (P < 0.05) directed to human insulin (median: 34%, IQR: 21.0-62.0), compared to porcine (median: 29.5%, IQR: 18.3-61.0) and bovine insulin (29%, IQR: 20.3-61.5), respectively. Here, we demonstrate different binding characteristics between IAA and IA, suggesting different epitope specificities. The observation of a significantly lower insulin binding to the "natural insulin analogs" (bovine and porcine insulin) compared to human insulin in the IA-group is in support of the concept that insulin analogs are eventually less immunogenic.

A Case of Insulin Autoimmune Syndrome Probably Induced by Ingestion of &alpha;-Lipoic Acid Associated with Diabetic Ketoacidosis

A Case of Insulin Autoimmune Syndrome Probably Induced by Ingestion of &alpha;-Lipoic Acid Associated with Diabetic Ketoacidosis

Possible Relevance of HLA-DRB1*0403 Haplotype in Insulin Autoimmune Syndrome Induced by α-Lipoic Acid, Used as a Dietary Supplement

Insulin autoimmune syndrome (IAS) is characterized by frequent hypoglycemic attacks associated with the presence of autoantibodies to insulin in patients who have not received insulin injections. Approximately half of IAS patients have a medication history before onset, and over 90% of the agents are sulfydryl compounds such as methimazole, mercaptopropionyl glycine, or glutathione. In addition to these compounds, α-lipoic acid (ALA), which is widely used as a health supplement, …

Severe hypoglycaemia in a person with insulin autoimmune syndrome accompanied by insulin receptor anomaly type B

A rare case of the insulin autoimmune syndrome (IAS) accompanied by insulin receptor anomaly is reported. Antibodies to insulin and insulin receptor were determined in the patient with severe hypoglycaemia before and after the treatment with prednisolone. Titers of antibody to insulin and insulin receptors were 73.0% and 41.5%, respectively. Drug-induced lymphocyte stimulation tests were all negative for the suspicious drugs. Her HLA-DR was DRB1*0403/04051. Following steroid therapy, the formation of antibodies was suppressed and alleviated her symptoms. Scatchard analysis yielded findings specific to polyclonal antibodies. The changes in autoantibodies resulted in alleviation of the hypoglycemic symptoms as a result of steroid therapy.