Insulin Autoimmune Syndrome PossiblyCaused by Alpha Lipoic Acid

Takeuchi, Yuichiro; Miyamoto, Takahide; Kakizawa, Tomoko; Shigematsu, Satoshi; Hashizume, Kiyoshi

doi:10.2169/internalmedicine.46.1893

Cited by 49 publications

(42 citation statements)

References 8 publications

(3 reference statements)

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“…These findings revealed a potential clinical application of LA for other diseases. However, it has been reported that LA induces insulin autoimmune syndrome (33).…”

Section: Discussionmentioning

confidence: 97%

Protective role of α-lipoic acid in hyperuricemia-induced endothelial dysfunction

Zou

Wang

Liu

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. The aim of the current study was to determine the effects of α-lipoic acid (LA) on hyperuricemia and endothelial dysfunction, and to uncover the underlying mechanism of its action. A hyperuricemic rat model was established by administration of uric acid (UA) and the rats were orally fed with 2 g/kg/day LA or phosphate-buffered saline. Primary rat aortic endothelial cells were subsequently isolated, and a cell viability assay, apoptosis assay, enzyme nitric oxide synthase (eNOS) activity assay and mitochondrial function assay were all performed. For the in vitro study, human umbilical vein endothelial cells were used and western blotting was performed to assess Akt signaling activity. The results of the current study indicated that LA inhibited apoptosis, enhanced eNOS activity and production of nitric oxide (NO), and rescued mitochondrial mass and function in uric acid (UA)-treated endothelial cells. LA activated Akt signaling and inhibition of Akt signaling abolished the effects of LA on cell viability, NO production, ROS production and ATP levels in UA-treated endothelial cells. Therefore, the current study demonstrated that LA attenuated oxidant stress and inhibited apoptosis in UA-treated endothelial cells by activating Akt signaling. The results indicate that LA may serve as a therapeutic approach to treat hyperuricemia-induced endothelial dysfunction.

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“…These findings revealed a potential clinical application of LA for other diseases. However, it has been reported that LA induces insulin autoimmune syndrome (33).…”

Section: Discussionmentioning

confidence: 97%

Protective role of α-lipoic acid in hyperuricemia-induced endothelial dysfunction

Zou

Wang

Liu

et al. 2017

Experimental and Therapeutic Medicine

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“…Indeed, up to one half of patients with insulin autoimmune syndrome presented with a history of using drugs containing a sulfhydryl group, which include methimazole, α-mercaptopropionyl glycine, and glutathione within the previous year [13]. More recently, cases of insulin autoimmune syndrome caused by α-lipoic acid have been increasing, which has been attributed to the two sulfur atoms connected by a disulfide bond of α-lipoic acid, which generates a strong reducing power [14]. Based on these observations, insulin autoimmune syndrome is attributed to either methimazole or carbimazole, which is converted to methimazole in the body, in patients with Graves' disease.…”

Section: Discussionmentioning

confidence: 99%

Two Cases of Methimazole-Induced Insulin Autoimmune Syndrome in Graves' Disease

Roh

Kim

et al. 2013

Endocrinol Metab

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We report here the cases of two females with Graves' disease who developed insulin autoimmune syndrome after treatment with methimazole. The patients exhibited a sudden altered mental state after treatment with methimazole for approximately 4 weeks. Patients had hypoglycemia with serum glucose below 70 mg/dL, and laboratory findings showed both high levels of serum insulin and high titers of insulin autoantibodies. The two women had never been exposed to insulin or oral antidiabetic agents, and there was no evidence of insulinoma in imaging studies. After glucose loading, serum glucose, and total insulin levels increased abnormally. One of the patient was found to have HLA-DRB1*0406, which is known to be strongly associated with methimazole-induced insulin autoimmune syndrome. After discontinuation of methimazole, hypoglycemic events disappeared within 1 month. Insulin autoantibody titer and insulin levels decreased within 5 months and there was no further development of hypoglycemic events. We present these cases with a review of the relevant literature.

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“…The risk of hypoglycaemia with the use of ALA has been attributed to an autoimmune process called Insulin Autoimmune Syndrome (IAS), in addition to potentiating the effects of other hypoglycaemic agents like insulin therapy [82,83]. IAS (also known as Hirata's disease) was first described in 1970 and is a relatively rare cause of hypoglycaemia [84].…”

Section: Adverse Effectsmentioning

confidence: 99%

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

Poh¹,

Goh

2009

EMIDDT

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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.

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Insulin Autoimmune Syndrome PossiblyCaused by Alpha Lipoic Acid

Abstract: Abstract

Cited by 49 publications

References 8 publications

Protective role of α-lipoic acid in hyperuricemia-induced endothelial dysfunction

Protective role of α-lipoic acid in hyperuricemia-induced endothelial dysfunction

Two Cases of Methimazole-Induced Insulin Autoimmune Syndrome in Graves' Disease

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

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