Circulating anti-insulin receptor antibodies in a patient suffering from lupus nephritis and hypoinsulinemic hypoglycaemia

A 46-year-old female patient suffering from Lupus Nephritis came to our attention in 1981 for severe recurrent hypoglycaemia; she was obliged to eat every 5-7 hr to maintain glucose values not below 1.3-1.6 mM. All known causes of hypoglycaemia were excluded by performing selective angiography of the pancreas and skull, chest and abdominal computerized tomography, as well as stimulation and suppression tests. Oral glucose tolerance, tolbutamide and intravenous insulin (0.4 U/Kg b.w.) tests demonstrated that the patient was highly insulin resistant; furthermore, studies on the patient's red blood cells suggested that her insulin receptors were completely unable to bind insulin. Studies carried out to reveal the reason for this binding inhibition demonstrated that red blood cells from normal subjects as well as adipocytes from normal rats incubated with the patient's serum did not bind insulin (50% inhibition occurring at about 1:30 serum dilution). Insulin binding inhibitors were found in the fraction of the serum precipitated by ammonium sulphate. The serum cleared of IgG fraction was unable to affect insulin binding. These data demonstrate that the serum from the female patient investigated contained anti-insulin receptor antibodies blocking the binding of insulin to its receptors. Plasmaphaeresis improved the patient's metabolic status. The clinical picture would suggest that recurrent hypoglycaemia was caused by anti-insulin receptor antibodies acting as insulin on target cells.