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

Abstract

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.

Diabetes Mellitus Is Associated With an Exocrine Pancreatopathy

“…We identified 7 studies 10,11,27–31 encompassing 1272 subjects with DM who commented on the changes in exocrine pancreas (see Supplementary Table 1, http://links.lww.com/MPA/A487, for details on individual studies and summary of all studies in Supplementary Table 2, http://links.lww.com/MPA/A487). Four studies included controls 27–30 ; however, only in 2 studies were findings in the exocrine pancreas compared between DM versus non-DM controls 28,29 (Table 2).…”

“…We identified 7 studies 10,11,27–31 encompassing 1272 subjects with DM who commented on the changes in exocrine pancreas (see Supplementary Table 1, http://links.lww.com/MPA/A487, for details on individual studies and summary of all studies in Supplementary Table 2, http://links.lww.com/MPA/A487). Four studies included controls 27–30 ; however, only in 2 studies were findings in the exocrine pancreas compared between DM versus non-DM controls 28,29 (Table 2). Collectively in all 7 studies, 10,11,27–31 255 (59.4%) of 429 patients had pancreatic fibrosis, with all studies reporting greater than 50% prevalence of fibrosis in those with long-standing DM; Gepts 30 reported 18% prevalence of fibrosis in those with juvenile-onset DM dying less than 2 years of onset of disease.…”

Deciphering the Pathogenesis of Human Type 1 Diabetes (T1D) by Interrogating T Cells from the “Scene of the Crime”

“…In addition to observation of rare insulitis and frequent lymphocytic infiltrate in the exocrine tissue in the pancreas from donors with T1D [43, 44], researchers from Osaka University Medical School recovered by pancreas tissue by biopsy from patients with newly diagnosed T1D and found detectable insulitis in approximately 50% of donors [45, 46]. The insulitis was composed of CD4 + and CD8 + T cells, B cells, and macrophages with noted HLA class I molecule hyperexpression in islets, intercellular adhesion molecule-1 (ICAM-1) expression on endothelial cells [47], and markers of an activated and pro-inflammatory environment were detected on infiltrating immune cells.…”

α-cell role in β-cell generation and regeneration

“…Although α-cells are plentiful in the islets of diabetic individuals and mice and rats, β-cells are reduced in numbers and secretion of insulin in response to nutrient signals is impaired. [90][91][92][93][94] Given these circumstances the question arises as to why β-cell mass and function is impaired in diabetes if α-cells are progenitors of β-cells? It seems that hyperplastic α-cells are poised to become β-cells but the environmental cues required to make this happen are missing.…”

“…An extensive study of pancreases from 47 donors with type 1 diabetes showed over all a slight reduction in total α-cell mass per pancreas with some pancreases showing either no change or a marked increase in α-cell mass compared with non-diabetic, agematched controls. 91 In pancreases from type 2 diabetes donors α-cell mass appears to be maintained on average. 92 In another study islets composed nearly entirely of α-cells are described.…”