A 49-year-old male came to our hospital to seek medical advice in May 2020 with frequent episodes of hypoglycemia. Since January 2020, he had experienced recurrent attacks of dizziness, palpitations, tremors, and sweating, both when fasting and after meals, with a documented hypoglycemia (peripheral blood glucose levels were approximately 2.8-3.5 mmol/L). The symptoms were relieved after food intake. He had a history of type 2 diabetes (T2D) for 10 years. His glucose concentration was well controlled initially after diagnosis with metformin. One year ago, metformin was changed to Novolin 30R for weight loss. He denied suffering from hyperthyroidism and other autoimmune diseases, and using glutathione and lipoic acid. Then, he was hospitalized for frequent hypoglycemia. On physical examination, he was healthy, with a Body Mass Index(BMI) of 19.1 kg/m2. A tentative diagnosis of insulinoma prompted a negative abdominal computed tomography (CT) scan. The laboratory findings, the level of growth hormones, thyroid, and adrenal function were all normal except for slightly increased antibodies to a cyclic citrullinated peptide (ACCP) at 17.36 u/mL (average value: < 1 u/mL). The IA test revealed that the class of immunoglobulins was 35.43 U/mL [average value: 0.00-0.40 U/mL, radioligand-binding assay (RBA)]. The HLA allele of this patient was DRB1*0405.
A 300-min oral glucose tolerance test (OGTT) of 82.5g anhydrous glucose was carried out on 07:00 07/06/2020 to investigate reactive hypoglycemia: the basal glucose level was 5.60 mmol/L, with a maximum level of 17.20 mmol/L at 120 min and a nadir of 3.20 mmol/L at 300 min. The plasma insulin ranged from a basal level of 732.10 mIU/L to a peak of 1420.00 mIU/L at 120 min. C-peptide levels (average value: 0.37-1.47mmol/L) were 1.43 nmol/L at the baseline and 3.16 nmol/L at the peak. The islet function of the patient exists, but C-peptide secretion was insufficient after glucose stimulation. The patient underwent 54.9 hours of continuous glucose monitoring (CGM) after admission, which revealed: time in range (TIR) (3.9 mmol/L < PT < 10 mmol/L) of 41.30% (22 h 40 min), time above range (TAR) (PT > 13.9 mmol/L) of 21.67% (11 h 53 min), time below range TBR (PT <3.9 mmol/L) of 6.76% (3 h 42 min). Hypoglycemia occurred between 12 a.m. to 4 a.m. He was treated with acarbose (100 mg three times a day) instead of insulin injections and prescribed to take leflunomide for rheumatoid arthritis. During the subsequent follow-up, the hypoglycemic episodes became less frequent and ceased altogether after a few months. The IAs assay and a 180-min OGTT were repeated at 8 and 15 months after the diagnosis of EIAS (see Table 1 and Figure 1).