Exocrine Pancreatic Function in Insulin-Dependent Diabetes mellitus

Lankisch, P. G.; Manthey, G.; Otto, J.; Koop, H.; Talaulicar, M; Willms, B.; Creutzfeldt, W.

doi:10.1159/000198833

Cited by 121 publications

(73 citation statements)

References 6 publications

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“…Studies of the pancreatic exocrine gland of IDDM patients have reported an abnormal response to the secretin-pancreozymin test and a decreased output of lipase, amylase and trypsin [16,17]. We propose the following mechanism as a cause of decreased pancreatic exocrine function in IDDM patients: noticeably decreased secretion of insulin, a growth-promoting hormone, in the pancreas may impair the normal growth of the exocrine gland resulting in atrophy, fibrosis and fatty changes in the tissue.…”

Section: Discussionmentioning

confidence: 88%

Histopathologic Study of the Pancreas Shows a Characteristic Lymphocytic Infiltration in Japanese Patients with IDDM.

et al. 1997

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Abstract. We examined at autopsy 47 cases (22 males and 25 females) of insulin-dependent diabetes mellitus (IDDM) from 21 hospitals in Japan to clarify the pathological changes that occur in the pancreas vs. those in control patients. The mean age was 39.7 ± 13.9 (mean ± SD) years, and the duration of IDDM from clinical onset was 13.1 ± 6.5 years. Causes of death included renal complications, infections, acute diabetic complications such as ketoacidosis or hyper-or hypoglycemic coma, and atherosclerotic disease. This study revealed noticeable decreases in the islet area and beta cell area, and a slight decreases in the alpha cell area and preservation of the number of islets. Insulitis was found in only 1 case, representing 25% of the cases with a duration of IDDM of one year or less. Lymphocytic infiltration of the exocrine gland was seen in 22 cases (46.8%). Predominant phenotypes of the lymphocytes were T lymphocytes and macrophages. Fibrosis, fatty change and atrophy were also found. Although this is not a strictly age-and sex-matched study, the high incidence of lymphocytic infiltration of the exocrine pancreas indicates that the exocrine tissue as well as beta cells is the target of immune reactions in Japanese patients with IDDM.

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Section: Discussionmentioning

confidence: 88%

Histopathologic Study of the Pancreas Shows a Characteristic Lymphocytic Infiltration in Japanese Patients with IDDM.

et al. 1997

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“…This conclusion is substantiated by clinical studies on the exocrine secretory capacity of the pancreas in chronic Type I diabetes demonstrating decreased secretion of enzymes [32][33][34][35][36]. Frier et al found that the preservation of pancreatic function correlates with the duration of diabetes [32] and the persistence of B-cell secretory activity measured by C-peptide levels [33].…”

Section: Discussionmentioning

confidence: 91%

Residual insulin positivity and pancreatic atrophy in relation to duration of chronic Type 1 (insulin-dependent) diabetes mellitus and microangiopathy

1987

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Summary.The relationship of residual insulin positivity in chronic Type I (insulin-dependent) diabetes and atrophy of the exocrine pancreas to duration of diabetes, age at onset and microangiopathy was studied in 26 patients (disease duration 2 to 54 years, mean 26 years). Islets containing insulin cells were found in 13/26 pancreata. In 5/13 pancreata insulin positive cells were detected in only one lobule, while in 8/13 insulin positivity was multifocal. All patients with diabetes duration less than 11 years had residual insulin cells; whereas, the rate of insulin positivity was near 40% with diabetes duration of more than 11 and 21 years, respectively. Survival of insulin cells was not clearly related to age at onset. HLA-DR expression on insulin cells was seen in one case. lnsulitis was lacking. Pancreatic volume determined in 18 patients ranged from 14-110ml (age adjusted mean 56.3 ml) and was significantly less than that of control subjects (age adjusted, mean 89.9 ml, p < 0.0001). Computerized morphometry of the exocrine pancreas revealed severe acinat atrophy due to a reduction in size of acinar cells. Acinar atrophy correlated neither with the degree of insulin positivity, disease duration nor severity of microangiopathy. The findings suggest that in about 40% of patients with Type 1 diabetes a small population of insulin cells may escape autoimmune destruction, irrespective of disease duration or age at onset. Though exocrine atrophy and insulin deficiency are associated, the variable extent of pancreatic atrophy could not to be related to such factors as amount of surviving insulin cells, duration of diabetes or microangiopathy.Key words: Chronic Type 1 (insulin-dependent) diabetes, residual insulin cells, exocrine atrophy, HLA-DR expression, diabetic microangiopathy.Loss of insulin cells characterises the islet lesions in patients with Type 1 (insulin-dependent) diabetes mellitus [1][2][3][4]. This loss, however, need not to be complete, since B cells, though severely reduced, have been demonstrated even in patients with a diabetes duration up to 37 years [1,3], The mechanisms which may protect some insulin cells from destruction by the autoimmune process underlying Type I diabetes are largely unkrlown.Another finding that characterises the pancreas in chronic Type 1 diabetes is a reduction in weight and volume [3,[5][6][7][8]. The pancreatic atrophy is attributed to the lacking trophic effect of insulin on the acinar cells [2,3,[9][10][11][12][13]. The extent of the exocrine atrophy, however, appears to vary considerably from patient to patient and has not yet been related to the remaining insulin positivity in the pancreas, to diabetes duration or to the degree of microangiopathy. * Presented in part at the 22 nd EASD meeting in Rome, 1986 ** Present address: Department of Pathology, Free University of Brussels, BelgiumThe aim of the present study was to investigate the degree and distribution of residual insulin positivity in the pancreas of patients with long-standing Type 1 diabetes by immunocyt...

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“…It has previously been reported that the pancreas of people with type 1 diabetes is characterised by increased fibrosis, small size and impaired exocrine function [3,7,8,33,34]. This has led to speculation that this might be due to a separate autoimmune process affecting the exocrine pancreas [35].…”

Section: Discussionmentioning

confidence: 99%

Sustained beta cell apoptosis in patients with long-standing type 1 diabetes: indirect evidence for islet regeneration?

Meier¹,

Bhushan²,

Butler³

et al. 2005

Diabetologia

456

383

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Aims/hypothesis: Type 1 diabetes is widely held to result from an irreversible loss of insulin-secreting beta cells. However, insulin secretion is detectable in some people with long-standing type 1 diabetes, indicating either a small population of surviving beta cells or continued renewal of beta cells subject to ongoing autoimmune destruction. The aim of the present study was to evaluate these possibilities. Materials and methods: Pancreatic sections from 42 individuals with type 1 diabetes and 14 non-diabetic individuals were evaluated for the presence of beta cells, beta cell apoptosis and replication, T lymphocytes and macrophages. The presence and extent of periductal fibrosis was also quantified. Results: Beta cells were identified in 88% of individuals with type 1 diabetes. The number of beta cells was unrelated to duration of disease (range 4-67 years) or age at death (range 14-77 years), but was higher (p<0.05) in individuals with lower mean blood glucose. Beta cell apoptosis was twice as frequent in type 1 diabetes as in control subjects (p<0.001), but beta cell replication was rare in both groups. The increased beta cell apoptosis in type 1 diabetes was accompanied by both increased macrophages and T lymphocytes and a marked increase in periductal fibrosis (p<0.001), implying chronic inflammation over many years, consistent with an ongoing supply of beta cells. Conclusions/interpretation: Most people with long-standing type 1 diabetes have beta cells that continue to be destroyed. The mechanisms underlying increased beta cell death may involve both ongoing autoimmunity and glucose toxicity. The presence of beta cells despite ongoing apoptosis implies, by definition, that concomitant new beta cell formation must be occurring, even after long-standing type 1 diabetes. We conclude that type 1 diabetes may be reversed by targeted inhibition of beta cell destruction.

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Exocrine Pancreatic Function in Insulin-Dependent Diabetes mellitus

Cited by 121 publications

References 6 publications

Histopathologic Study of the Pancreas Shows a Characteristic Lymphocytic Infiltration in Japanese Patients with IDDM.

Histopathologic Study of the Pancreas Shows a Characteristic Lymphocytic Infiltration in Japanese Patients with IDDM.

Residual insulin positivity and pancreatic atrophy in relation to duration of chronic Type 1 (insulin-dependent) diabetes mellitus and microangiopathy

Sustained beta cell apoptosis in patients with long-standing type 1 diabetes: indirect evidence for islet regeneration?

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