Short‐term changes in pancreatic α‐cell function after the onset of fulminant type 1 diabetes

A 25-year-old unconscious woman was transferred to Center Hospital, National Center for Global Health and Medicine, Tokyo, Japan. She had ketonuria with blood glucose levels, arterial pH, and HCO3 levels of 843 mg/dL, 6.94 and 3.0 mmol/L, respectively, indicating diabetic ketoacidosis. Her glycated hemoglobin, serum C-peptide, and 24-h urinary C-peptide excretion levels were 6.4%, 0.28 ng/mL and 2.4 l/day, respectively. Her islet autoantibodies were negative. She was finally diagnosed with fulminant type 1 diabetes. Pancreatic aand b-cell functions were evaluated using the arginine stimulation test (AST). Basal insulin was changed from a subcutaneous injection to a continuous intravenous injection 24 h before the AST, and was stopped 1 h before the AST. A total of 30 g of arginine was intravenously administered over a 30-min period, and blood samples were collected before and at 15, 30, 60, 90 and 120 min after arginine loading. The serum C-peptide response was almost diminished, and the plasma glucagon response measured using radioimmunoassay (Sceti Medical Labo, Tokyo, Japan) increased to a peak of 415 pg/mL (Figure 1a). Her blood glucose levels fluctuated between 40 and 500 mg/dL after 6 months. Her glycated hemoglobin level increased to 8.6%, and she was readmitted to our hospital. In the repeat AST, although glucose elevation was similar to that at diabetes onset, the serum C-peptide response was completely absent. Interestingly, the peak plasma glucagon level decreased from 415 to 295 pg/mL, plasma glucagon response during the first 15 min diminished from 292 to -10 pg/mL and the incremental area under the curve decreased from 13.0 9 10 to 8.1 9 10 pg/mL/min (Figure 1a,b). Plasma glucagon levels were also measured using sandwich enzyme-linked immunosorbent assay (Mercodia AB, Uppsala, Sweden), and the curve of plasma glucagon was similar to that obtained using radioimmunoassay. AST was carried out after