Type 1 diabetes is divided into two subtypes: autoimmune and idiopathic diabetes (1). Recently, fulminant type 1 diabetes was identified as a novel subtype of idiopathic diabetes (2). Imagawa et al. (2), who first identified this subtype, hypothesized that the disorder is caused by nonautoimmune mechanisms, including viral infection of exocrine pancreatic tissue. This hypothesis was generated from the negative test results for diabetes-related antibodies in patients with fulminant type 1 diabetes.
Additional pieces of supporting evidence were the absence of hyperexpression of major histocompatibility complex class I molecules in islets and the presence of lymphocyte infiltration in exocrine pancreatic tissue without insulitis in biopsy specimens. Consequently, high serum amylase levels were the primary characteristics of patients with fulminant type 1 diabetes. However, the hypothesis mentioned above has not been universally accepted (3). We report a case of fulminant type 1 diabetes in a patient who had a normal level of serum amylase at the time of diagnosis along with increased rheumatoid factor and thyroid-stimulating hormone (TSH) receptor antibody levels.
A 22-year-old woman was admitted to our hospital with diabetic ketoacidosis. She suffered from a sore throat and headache 7 days before admission. Nausea, vomiting, and slight fever started 2 days before admission. She visited the emergency room with epigastric pain and thirst and was found to have a high glucose level. She was transferred to our hospital the next day for admission.
The patient was comatose when she arrived. Her plasma glucose level was 59.6 mmol/l. Her HbA1c was 5.3%, within normal range. Urinary ketone was strongly positive. Arterial pH was 6.922, and bicarbonate was 1.9 mmol/l. Serum and urinary C-peptide levels were low, 0.24 ng/ml and 5.6 μg/day, respectively. She had no diabetes-related antibodies (GAD antibody, tyrosine phosphatase–like protein [IA-2] antibody, islet cell antibody, or insulin autoantibody). These findings were consistent with the characteristics of fulminant type 1 diabetes.
The patient’s serum amylase level was 71 IU/l in the emergency room and 135 IU/l at the time of her admission to our hospital, but it rose to 761 IU/l the next day. The serum levels of other exocrine pancreatic enzymes lipase and trypsin also rose, although the levels of these two enzymes were not measured on the day of admission. These findings suggested that injury to exocrine pancreatic tissue indeed occurred in this subject. However, we considered this injury to be secondary, based on the initially normal amylase level and its subsequent rise.
This patient had HLA-DRB1*0405/*0405, DQA1*0303/*0303, DQB1*0405/*0405, the haplotype associated with type 1 diabetes in Japanese people. Furthermore, her immunological examinations after admission showed elevated rheumatoid factor and the temporal presence of TSH receptor antibody. These findings suggested that her disease had the immunogenetic characteristics of an autoimmune disease but not against the endocrine pancreas.
Unlike previous cases of fulminant type 1 diabetes (4), this case was characterized by a late increase in serum amylase level and autoimmune characteristics. Therefore, although fulminant type 1 diabetes has been clinically identified, its etiology remains in question.
References
Address correspondence to Shinji Sakaue, MD, First Department of Medicine, Hokkaido University School of Medicine, Sapporo 060-8638, Japan. E-mail: [email protected].
