Corticosteroid-responsive diabetes mellitus associated with autoimmune pancreatitis

Tanaka, Shoichiro; Kobayashi, Tetsuro; Nakanishi, Kōji; Okubo, Minoru; Murase, Toshio; Hashimoto, Masaji; Takeuchi, Kazuo

doi:10.1016/s0140-6736(00)02684-2

Cited by 131 publications

(74 citation statements)

References 17 publications

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“…In all cases, development of diabetes followed the onset of ACP (duration of ACP 3 Ϯ 3 months [1][2][3][4][5]) with prodrome of mild epigastralgia and weight loss (9 Ϯ 2 kg [7][8][9][10]) before hospitalization. Insulin was required in three patients (cases 1-3), and an oral hypoglycemic agent (gliclazide) in one patient (case 4) for control of hyperglycemia.…”

Section: Subjectsmentioning

confidence: 99%

“…Remarkably, this value was reduced when compared with patients with type 2 diabetes (48 Ϯ 14% , n ϭ 8, P ϭ 0.0015 vs. patients with ACP) and nondiabetic control subjects (58 Ϯ 13% [39 -77], n ϭ 7, P ϭ 0.0002 vs. patients with ACP). Percentage areas of ␣-cells and ␦-cells in islets of pancreata in patients with ACP (9 Ϯ 1% [7][8][9][10] and 7 Ϯ 1% [6 -8], respectively) did not differ when compared with patients with type 2 diabetes (17 Ϯ 8% [8 -30] and 6 Ϯ 2% [4 -9], respectively) and nondiabetic control subjects (10 Ϯ 5% [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] and 6 Ϯ 3% [4 -12], respectively). Cytokeratin 19 -positive ductal cells contained insulin as well as glucagon in all cases (Fig.…”

Section: Clinicalmentioning

confidence: 99%

“…CONCLUSIONS -ACP is characterized by clinical symptoms, including mild abdominal pain and weight loss, the presence of autoantibodies against pancreatic exocrine tissues, radiographic or ultrasonographic findings of pancreatic swelling, and narrowing of the main pancreatic duct (3)(4)(5)(6)(7)(8). The prevalence of ACP is ϳ2% in cases with chronic pancreatitis, as diagnosed by endoscopic retrograde cholangiopancreatography (5).…”

Section: Immunostaining Of Ipf-1mentioning

confidence: 99%

“…The prevalence of ACP is ϳ2% in cases with chronic pancreatitis, as diagnosed by endoscopic retrograde cholangiopancreatography (5). Noteworthy is the finding that most patients with ACP have diabetes (8).…”

Section: Immunostaining Of Ipf-1mentioning

confidence: 99%

“…Patients with ACP are sometimes subjected to pancreatectomy or chemotherapy (6,7). Recently, we have reported that a large proportion of patients with ACP had diabetes and responded well to corticosteroid therapy, and after treatment, those patients had normal or mild glucose intolerance with improved insulin response (8). Current knowledge is limited regarding the changes in both affected endocrine as well as exocrine pancreas.…”

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Evidence of Primary β-Cell Destruction by T-Cells and β-Cell Differentiation From Pancreatic Ductal Cells in Diabetes Associated With Active Autoimmune Chronic Pancreatitis

et al. 2001

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OBJECTIVE -Diabetes associated with autoimmune chronic pancreatitis (ACP) is a subtype of diabetes that is responsive to corticosteroid treatment of progressive endocrine and exocrine dysfunction. However, little is known about pathological changes of islet and exocrine pancreas in ACP. RESULTS -The pancreatic specimens in all cases exhibited inflammatory cell infiltration surrounding ductal cells and extensive fibrosis. Some islets were infiltrated with mononuclear cells with disrupted ␤-cells. The subsets of T-cells infiltrated to the islets were mainly CD8 ϩ . Islet ␤-cell volume was decreased; the mean percentage area of ␤-cells in the islets in four cases with ACP were 16% (range 13-20) (P ϭ 0.0015 vs. type 2 diabetic patients, 48% , n ϭ 8; P ϭ 0.0002 vs. nondiabetic control subjects, 58% [39 -77], n ϭ 7). Preserved ductal cells were surrounded predominantly by CD8 ϩ or CD4 ϩ T-cells. Some cytokeratin 19 -positive ductal cells contained insulin and glucagon, representing upregulated differentiation of islet cells from ductal cells. Insulin promoter factor-1 (IPF-1) was hyperexpressed in insulin-containing ductal cells. RESEARCH DESIGN AND METHODSCONCLUSIONS -Diabetes associated with ACP is caused by T-cell-mediated mechanisms primarily involving islet ␤-cells as well as pancreatic ductal cells. In ACP, ductal islet precursor cells were associated with IPF-1 hyperexpression, suggesting a critical role of IPF-1 on islet cell differentiation and eventual ␤-cell restoration. Diabetes Care 24:1661-1667, 2001D iabetes occurs in ϳ50% of patients with chronic pancreatitis (1,2). Although chronic pancreatitis is often related to excessive alcohol consumption, in Ͼ25% of patients with chronic pancreatitis, the disorder is not related to alcohol (1,2). Autoimmune-mediated mechanisms often underlie such nonalcoholic impairment of the pancreas, so-called "autoimmune chronic pancreatitis" (ACP) (3-7). ACP is characterized by diffuse swelling and severe fibrosis associated with mononuclear cell infiltration involving the exocrine pancreas (3-7). The disorder can induce severe pancreatic swelling or tumor formation, with malabsorption and often cholestasis, and is sometimes misdiagnosed as pancreatic carcinoma or lymphoma. Patients with ACP are sometimes subjected to pancreatectomy or chemotherapy (6,7). Recently, we have reported that a large proportion of patients with ACP had diabetes and responded well to corticosteroid therapy, and after treatment, those patients had normal or mild glucose intolerance with improved insulin response (8). Current knowledge is limited regarding the changes in both affected endocrine as well as exocrine pancreas. In this study, we report the findings of the affected pancreas of patients with diabetes associated with ACP on a morphological, immunological, and morphometric bases. RESEARCH DESIGN AND METHODS SubjectsOur cohort study of ACP was performed between 1993 and 1999 and included 2,483 Japanese patients with suspected chronic pancreatitis and symptoms of abdominal and/or back pain, m...

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Section: Subjectsmentioning

confidence: 99%

Section: Clinicalmentioning

confidence: 99%

Section: Immunostaining Of Ipf-1mentioning

confidence: 99%

Section: Immunostaining Of Ipf-1mentioning

confidence: 99%

mentioning

confidence: 99%

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Evidence of Primary β-Cell Destruction by T-Cells and β-Cell Differentiation From Pancreatic Ductal Cells in Diabetes Associated With Active Autoimmune Chronic Pancreatitis

et al. 2001

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Diabetes Secondary to Acquired Disease to the Pancreas

Prato¹,

Coppelli²,

Tiengo³

2004

International Textbook of Diabetes Mellitus

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Secondary diabetes is a condition of hyperglycemia which develops after the destruction of the pancreatic tissue by an acquired disease with subsequent impairment of exocrine and endocrine pancreatic functions. In general, any pathologic process of the pancreatic acinar tissue may results in an insult to its endocrine component, leading to some degree of hormone insufficiency. This condition was first described in 1788 by Sir Thomas Cawley, but it was soon appreciated that hyperglycemia can ensues acute and chronic pancreatitis, partial and total pancreatectomy, neoplasia as well as systemic processes involving the pancreas, such as hemochromatosis and cystic fibrosis. The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus of the American Diabetes Association has identified these forms of diabetes as “diabetes secondary to diseases of the exocrine pancreas.” The new diagnostic criteria for diabetes introduced by the ADA and WHO Expert Committees are likely to influence the prevalence of diabetes in patients with diseases of the exocrine pancreas, but direct assessment using the new criteria is still too scanty. When the 1979 NDDG and 1985 WHO criteria are used, it can be calculated that diabetes secondary to disease of the exocrine pancreas represents, approximately, 0.5% of all cases of diabetes mellitus. Its frequency is likely to be twice as high in populations with heavy alcohol consumption. In the tropics, the prevalence of diabetes secondary to fibrocalculous pancreatitis can be as high as 10–20%. At variance with the selective B‐cell destruction occurring in type 1 diabetes, pancreatic diabetes is characterized by concomitant destruction of all endocrine cells of the islet of Langherans. The dual insulin–glucagon deficit is responsible for many of the metabolic and clinical manifestation of this form of diabetes, including lower risk for ketoacidosis and more frequent and severe hypoglycemic episodes. Since the late 1950s, the general idea has been that secondary diabetes was not associated with vascular complications. However, with the improved life expectancy of these patients during the past few years, a similar prevalence of retinopathy and microalbuminuria has been described in pancreatic and type 1 diabetes mellitus. The knowledge of the hormonal, metabolic, and clinical features of these forms of diabetes is essential in defining the most appropriate therapeutic strategies.

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