Pathogenesis of Fulminant Type 1 Diabetes

Imagawa, Akihisa; Hanafusa, Toshiaki

doi:10.1900/rds.2006.3.169

Cited by 60 publications

(56 citation statements)

References 43 publications

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“…Clinical characteristics of this subtype of type 1 diabetes are 1) remarkably abrupt onset of disease; 2) very short (Ͻ1 week) duration of diabetic symptoms; 3) severe ketoacidosis at diagnosis; 4) negative status of islet-related autoantibodies, such as GADAb and anti-IA-2 antibody; 5) virtually no C-peptide secretion (10 g/day in urine); and 6) elevated serum pancreatic enzyme levels (26). These features and the absence of insulitis in patients' pancreases have led some to hypothesize that an autoimmune mechanism does not contribute to the development of fulminant type 1 diabetes, but rather that viral infection plays a central role in the pathogenesis of the disease (27). However, we previously demonstrated CD4…”

Section: Discussionmentioning

confidence: 99%

Amylase α-2A Autoantibodies

et al. 2009

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OBJECTIVE-The pathogenesis of autoimmune pancreatitis (AIP) and fulminant type 1 diabetes remains unclear, although it is known that immune-mediated processes severely compromise the endocrine and exocrine functions in both diseases. RESEARCH DESIGN AND METHODS-We have screened aTriplEx2 human pancreas cDNA library with serum from a patient with AIP and obtained positive clones. Sequence analysis revealed that 7 of 10 clones were identical to human amylase ␣-2A. Using a recombinant COOH-terminal amylase ␣-2A protein, we developed an enzyme-linked immunosorbent assay system to detect autoantibodies against human amylase ␣-2A.RESULTS-All 15 serum samples from patients with AIP recognized the recombinant protein, whereas sera from 25 patients with chronic alcoholic pancreatitis and sera from 25 patients with a pancreas tumor did not. Interestingly, 88% (15/17) of patients with fulminant type 1 diabetes were positive for an autoantibody against amylase ␣-2A. These antibodies were detected in 21% of patients with acute-onset type 1 diabetes (9 of 42) and 6% of type 2 diabetic patients (4 of 67).CONCLUSIONS-These results suggest that an autoantibody against amylase ␣-2A is a novel diagnostic marker for both AIP and fulminant type 1 diabetes and that, clinically and immunologically, AIP and fulminant type 1 diabetes are closely related. Diabetes 58:732-737, 2009 R ecently, autoimmune pancreatitis (AIP), a unique form of chronic pancreatitis, has been reported as a discrete disease entity (1). It is characterized by 1) irregular narrowing of the main pancreatic duct and swelling of the pancreas, both of which are due to abundant lymphoplasmacytic inflammation to the exocrine pancreas (2); 2) the increased serum level of IgG and IgG4; 3) positive autoantibodies such as lactoferrin autoantibody or carbonic anhydrase II (CAII) autoantibody (3,4); and 4) a high prevalence of diabetes with complications (5).We recently reported that a high proportion of pancreatic islets and exocrine pancreatic tissues were infiltrated by CD4 ϩ or CD8 ϩ T-cells in the inflammatory process, which might induce diabetes in AIP (6). In addition, treatment with prednisolone improved insulin secretion and glycemic control in AIP patients (5). These data support the concept that autoimmune mechanism(s) plays a pivotal role in the destruction of the endocrine and exocrine pancreas in AIP patients with diabetes.Clinically, the most common initial symptom of AIP is jaundice, but in some patients, no symptoms or only mild symptoms, frequently without acute attacks of pancreatitis, may be present (7). It is difficult to distinguish AIP from other types of chronic pancreatitis or cancer of the pancreatic head (8). In such cases, detection of autoantibodies is useful for diagnosing AIP, but a proportion of patients with AIP are negative for autoantibodies against lactoferrin and CAII (3,4).We encountered an AIP patient whose serum IgG and IgG4 levels were 3,498 and 2,430 mg/dl, respectively. It has been reported that median levels (5th and 95th percentile...

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Section: Discussionmentioning

confidence: 99%

Amylase α-2A Autoantibodies

et al. 2009

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“…Class II HLA has been reported to be associated not only with acute-onset type 1 diabetes, but also with fulminant and slowly progressive type 1 diabetes [2,3,18]. The alleles and haplotypes associated with the disease, however, appear to differ among different subtypes.…”

Section: Hla: a Major Susceptibility Genementioning

confidence: 99%

“…The etiology and pathogenesis of the latter subtype are still unknown, but recent studies suggest that fulminant type 1 diabetes may belong to this subtype [1][2][3]. Type 1A diabetes is caused by autoimmune destruction of insulin-producing beta-cells in the pancreas in genetically susceptible individuals.…”

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confidence: 99%

Genetic Basis of Type 1 Diabetes: Similarities and Differences between East and West

Ikegami

Noso²,

Babaya³

et al. 2008

Rev Diabet Stud

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“…Although the patient had normal pancreatic enzymes levels and did not have previous flu-like or gastrointestinal symptoms, these were minor additional findings for diagnosis (1).…”

Section: Discussionmentioning

confidence: 87%

“…Fulminant type 1 diabetes (FTD) has been defined as a new subtype of type 1 diabetes in which pancreatic islet cell failure rapidly leads to hyperglycemia and ketoacidosis (1). While FTD is frequently reported in far eastern Asia, patients from other areas or ethnic groups are very rare (2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

The First Vietnamese Patient with Fulminant Type 1 Diabetes Mellitus

Kim

Hahm

et al. 2012

Intern. Med.

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A 23-year-old pregnant woman had a stillbirth at 30 weeks gestation due to abrupt diabetic ketoacidosis. The patient had a normal HbA1c, severe hyperglycemia, negative islet cell autoantibodies, and very low insulin secretion capacity. The viral markers associated with fulminant type 1 diabetes were negative. The patient's human leukocyte antigen genotypes were DRB1*04:06 and DQB1*03:01/05:02, not common subtypes for fulminant type 1 diabetes. This is the first Vietnamese patient with fulminant type 1 diabetes mellitus.

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Pathogenesis of Fulminant Type 1 Diabetes

Cited by 60 publications

References 43 publications

Amylase α-2A Autoantibodies

Amylase α-2A Autoantibodies

Genetic Basis of Type 1 Diabetes: Similarities and Differences between East and West

The First Vietnamese Patient with Fulminant Type 1 Diabetes Mellitus

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