Autoimmune Forms of Hypoglycemia

Abstract

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.

Recurrent Hypoglycemia from Insulin Autoimmune Syndrome

“…Regardless, IAS is also recognized in other countries, including Europe and the United States (US). 6 A compilation of all IAS cases described in the US is shown in Table 2. IAS should be considered in any hypoglycemic patient, especially in those with a suspected insulinoma, so as to avoid any unnecessary, invasive and costly procedures and surgical interventions.…”

“…6 The disease shows no overall predilection to gender. Affected individuals may complain of marked neuroglycopenic symptoms of confusion and an altered level of consciousness, and may even be in a comatose state on initial presentation.…”

“…7 Autoimmune comorbidities-such as Graves' disease, systemic lupus erythematosus, and rheumatoid arthritis-and/or monoclonal gammopathy may be elicited on history. 6 About half of IAS patients report recent exposure to medications, with over 90 % of offending agents containing a sulfhydryl group. 8 Methimazole is the most commonly implicated drug; others include carbimazole, glutathione, tiopronin, tolbutamide, gold thioglucose, interferon-α, captopril, diltiazem, hydralazine, procainamide, isoniazid, D-penicillamine, imipenem and penicillin G. 6,7,9 Alpha-lipoic acid, a popular health supplement for the treatment of diabetic neuropathy and obesity, has been linked to IAS in recent years.…”

“…6 About half of IAS patients report recent exposure to medications, with over 90 % of offending agents containing a sulfhydryl group. 8 Methimazole is the most commonly implicated drug; others include carbimazole, glutathione, tiopronin, tolbutamide, gold thioglucose, interferon-α, captopril, diltiazem, hydralazine, procainamide, isoniazid, D-penicillamine, imipenem and penicillin G. 6,7,9 Alpha-lipoic acid, a popular health supplement for the treatment of diabetic neuropathy and obesity, has been linked to IAS in recent years. 5 Although the precise mechanism for hypoglycemia in IAS is unknown, the most widely accepted hypothesis is a mismatch between blood glucose and free insulin concentration, secondary to the binding and release of secreted insulin by autoantibodies.…”

“…The resultant hyperglycemia not only promotes further insulin release, but may also explain the increased hemoglobin A1c often seen in IAS patients. 6 As glucose concentration eventually falls, insulin secretion also subsides, and the total insulin level decreases. Insulin molecules spontaneously dissociate from the autoantibodies at this time, giving rise to a raised free insulin level inappropriate for the glucose concentration, evoking hypoglycemia.…”