Hypoglycemia due to insulin binding antibodies in a patient with insulin-treated type 2 diabetes and Graves’ disease

Abstract

To the Editor, Insulin autoimmune syndrome (IAS) showed hypoglycemia, hyperinsulinemia, positive insulin antibodies without insulin injection history. Some patients with diabetes, treated with insulin, also showed these signs. The first case of IAS was reported in 1970s. [1, 2]. IAS can be induced by autoimmune diseases, some drugs, such as methimazole [3]. Here we report one case of special IAS, who suffered from type 2 diabetes concomitant with Graves’ disease. This an 85-year-old woman diagnosed with type 2 diabetes 30 years ago. She accepted oral antidiabetic drugs initially, and switched to insulin injection therapy (Novolin 30R 12 u/day) 5 years ago. About 1 year ago, she began to experiencing recurrent cold sweat, hunger, palpitation, and other symptoms of hypoglycemia, with her peripheral blood glucose ranged from 3.0–4.0 mmol/L during the night and morning. Hypoglycemia episodes still occurred after insulin treatment was suspended. Meanwhile she appeared weight loss, palpitation, chest tightness, fatigue, and lower extremity edema. One month prior to admission, the patient began to appearing eyelid edema, proptosis, photophobia, tearing, redness and pain of eye, polyphagia, heat intolerance, sweating, irritability, and stool frequency. She has hypertension and dyslipidemia history. Physical examination revealed a thinly built woman, BMI 20.7 kg/m, BP 160/70 mmHg, pulse 106/min. Her skin appeared sweeting and hot. She appeared wider palpebral fissures, proptosis, limited eye movements, conjunctival edema, and hyperemia. The movements of the lids were jerky and spasmodic, and the lightly closed lids tremor. Thyroid examination revealed II degrees of goiter with marked tremor and vascular murmur. Thyroid function tests revealed that TSH 0.01 lU/mL, T4 223.18 nmol/l, FT4 34.8 pmol/l, rT3 0.58 ng/ml, thyroglobulin 27.73 ng/ml, Anti-Tg 906.1 IU/ml, TPO [ 600 IU/ml, TRAB 20.8 IU/ml, ESR 64 mm/h. Serum total insulin concentration was 552.3 uU/ml, free insulin concentration 394.4 uU/ml, and Iab binding rate 70.6 %. Scatchard analysis revealed that the serum Iab constituted by two types binding sites which were high-affinity with low capacity (k1 = 3.125 9 10 mol/l, b1 = 37.5 9 10 mol/l) and low-affinity with high capacity (k2 = 1.0 9 10 mol/l, b2 = 5.918 9 10 mol/l), (Fig. 1). Insulin binding antibodies analysis suggested that it was IgG with k light chains. Ultrasound showed bilateral thyroid swelling, diffuse lesions. Abdominal magnetic resonance imaging revealed no abnormalities. The patient was diagnosed with Grave’s diseases, Grave’s ophthalmopathy and IAS, and start receiving prednisone (20 mg/day) and methimazole (10 mg qd) treatment. The insulin injection treatment (Novolin 30R) continued and the dose increased along with blood glucose change. After treatment for 1 month, symptoms including palpitation, heat intolerance, fatigue relieved, photophobia and tearing relieved, meanwhile hypoglycemia attack disappeared. After 2 months of treatment, her serum insulin levels returned to normal range and insulin antibody became X. Wang X. Xu X. Zhao X. Ma H. Yu H. Gong F. Chen (&) No. 3 People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China 280# MoHe Road, Shanghai 201900, People’s Republic of China e-mail: 903561138@qq.com; fengling_chen@hotmail.com