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 μ/day, respectively. Her islet autoantibodies were negative. She was finally diagnosed with fulminant type 1 diabetes. Pancreatic α‐ and β‐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 loading1. 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 × 103 to 8.1 × 103 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 achieving glycemic control without any hypoglycemia (<70 mg/dL), as confirmed by continuous glucose monitoring at diabetes onset and 6 months later.

Figure 1

Glucose, C‐peptide and glucagon responses to arginine stimulation in a patient with fulminant type 1 diabetes. Thirty grams of arginine was intravenously administered over 30 min, and the levels of plasma glucose, serum C‐peptide, and plasma glucagon were measured before and 15, 30, 60, 90, and 120 min after arginine loading1 at the (a) onset of fulminant type 1 diabetes and (b) 6 months later.

Fulminant type 1 diabetes has recently been reported as a novel subtype of type 1 diabetes, and is characterized by a remarkably abrupt disease onset and rapidly depleted insulin secretion2. To our knowledge, this is the first case report describing changes in plasma glucagon response to AST in a patient with fulminant type 1 diabetes. According to a previous report, glucagon responses to AST in patients with type 1 diabetes are positively correlated with diabetes duration, which is contrary to our present result1. In another study, the areas of α‐ and β‐cells morphologically decreased in patients with fulminant type 1 diabetes compared with those in patients with acute‐onset type 1 diabetes3. Rodent autoimmune diabetes models have revealed a substantial loss of alpha cells and impaired glucagon response to hypoglycemia.4 We have considered that the loss of alpha cells is correlated with the early‐phase attenuation of glucagon response and appears to be delayed in the present case.

In conclusion, we report the short‐term changes in the plasma glucagon response to AST in a patient with fulminant type 1 diabetes. Further research with multiple participants is desirable to confirm the pancreatic endocrinological functions in patients with fulminant type 1 diabetes.

Disclosure

The authors declare no conflict of interest.