Fulminant Type 1 Diabetes

Abstract

OBJECTIVE -To describe the clinical and immunologic characteristics of fulminant type 1 diabetes, a novel subtype of type 1 diabetes, we conducted a nationwide survey.RESEARCH DESIGN AND METHODS -History and laboratory data, including isletrelated autoantibodies, were examined in 222 patients with fulminant and nonfulminant type 1 diabetes in our hospitals in addition to another 118 patients with fulminant type 1 diabetes located outside our hospitals in Japan.RESULTS -In our hospitals, of the 222 patients studied, 43 (19.4%) were diagnosed with fulminant type 1 diabetes, 137 (61.7%) were classified as having autoimmune type 1 diabetes, and 42 were type 1 diabetic subjects who were not fulminant and did not have anti-islet antibodies. An additional 118 fulminant patients outside our hospitals were enrolled, making a total of 161 fulminant type 1 diabetic subjects (83 male and 78 female subjects; 14 children/ adolescents and 147 adults) identified from all over Japan. (In 2000, the average incidence was three cases per month.) Flu-like symptoms and pregnancy were more frequently observed in the fulminant than in the autoimmune group (P Ͻ 0.001). In the fulminant patients, 4.8% were positive for anti-GAD antibodies and none were positive for anti-islet antigen 2 antibodies.CONCLUSIONS -Fulminant type 1 diabetes is a distinct subtype and accounts for ϳ20% of the ketosis-onset type 1 diabetes cases in Japan. Flu-like symptoms are characteristic of disease onset. Metabolic derangement is more severe in this subtype than in autoimmune type 1 diabetes. Diabetes Care 26:2345-2352, 2003T ype 1 (insulin-dependent) diabetes is characterized by insulin deficiency from the destruction of pancreatic ␤-cells. According to the recently proposed classification of diabetes by the American Diabetes Association (ADA) and the World Health Organization (WHO), type 1 diabetes is divided into two subtypes: autoimmune type 1 (immune-mediated; type 1A) diabetes and idiopathic (type 1B) diabetes (1,2).Since 1974, when Bottazzo et al. (3) reported the presence of islet cell antibodies (ICAs) in the sera of type 1 diabetic patients, several autoantibodies to pancreatic islet cells have been recognized as a marker of type 1 diabetes. These isletrelated autoantibodies are anti-GAD antibodies (GADAb), insulin autoantibodies (IAA), and anti-islet antigen 2 (IA-2)/ IA-2␤ antibodies (4,5).However, type 1 diabetic patients are not always positive for these autoantibodies, even at the onset of overt diabetes (6,7). Patients with type 1 diabetes who do not have islet autoantibodies at the time of diagnosis are classified as having idiopathic or type 1B diabetes. In Japan, several cases have been reported in which islet-related autoantibodies were negative and the onset of diabetes was acute (8 -12). Imagawa and colleagues (13,14) have proposed that these cases are "nonautoimmune fulminant" type 1 diabetes. The clinical characteristics of this subtype of type 1 diabetes are 1) remarkably abrupt onset of disease; 2) very short (Ͻ1 week) duration of di...

Endogenous insulin secretion even at a very low level contributes to the stability of blood glucose control in fulminant type 1 diabetes

“…We used 5.6 mmol/L (100 mg/dL) as the selected standard. The deviation index (δ) of each individual glucose value (γ) is first calculated as δ = (10 × log[γ/5.0]) 3 . M ‐value is the average of all the individually calculated deviation indices (∑δ/ n ) 6 .…”

“…We previously reported a novel subtype of type 1B diabetes that we referred to fulminant type 1 diabetes 2 . In fulminant type 1 diabetes, remarkably acute and almost complete β‐cell destruction occurs and nearly no insulin secretion remains, even just after the disease onset 3 .…”

A case of fulminant type 1 diabetes masquerading acute pancreatitis

“…As the name suggests, this subtype is characterized by its markedly abrupt onset with ketosis or ketoacidosis, but unlike other forms of ketosis‐prone diabetes, it is also characterized by hyperglycemia with a relatively low glycated hemoglobin level at the onset 2. According to its characteristics,3 fulminant type 1 diabetes is thought to meet the ADA/WHO criteria for type 1B diabetes. Although the pathogenesis of fulminant type 1 diabetes has not yet been elucidated, recent studies indicate the causes as either viral infection or genetic background, such as human leukocyte antigens 4…”

“…As the majority of the cases have been reported from Asia, especially from Japan, a nationwide survey was conducted in Japan which revealed some unique manifestations 3. First, 98% of the patients with this subtype showed increased levels of serum exocrine pancreatic enzymes.…”

“…Histological analyses revealed mononuclear infiltration of both the exocrine and endocrine pancreas,5 and it indicates the presence of both “microscopic” pancreatitis and insulitis as pathogenesis. Second, 72.5% of the patients with this subtype had abdominal symptoms such as nausea, vomiting, or abdominal pain 3. With these symptoms and elevated pancreatic enzymes, typical fulminant type 1 diabetes artfully masquerades as acute pancreatitis.…”