Pathologic Anatomy of the Pancreas in Juvenile Diabetes Mellitus

Abstract

1. Quantitative study of insular tissue has revealed that the number of B cells is greatly diminished in Patients with acute juvenile diabetes from the time of clinical onset of the disease. The number of these cells is as a rule less than 10 per cent of normal. Such B cells as are still present show the cytological signs of marked activity. 2. The normal or supranormal insular activity that is usually found in juvenile diabetics in this stage of the disease cannot therefore be due to the presence of a normal insular tissue, but is produced by a small number of hyperactive B cells. 3. On the basis of histological findings (presence of islets of large size, signs of new islet formation), it may be assumed that during the preclinical phase of juvenile diabetes, an extrapancreatic factor has exerted a strong stimulant action on the insular tissue. In the long run this must lead to exhaustion of the islet-forming capacity on the pancreatic parenchyma and to a decrease in the number of the B cells. By the time the disease becomes clinically manifest only the latter stage of this process can be observed and the majority of islets consist of A cells or of atrophic tissue devoid of B cells. 4. Peri- and intra-insular inflaminatory infiltrates have been found in 68 per cent of those patients with juvenile diabetes who died soon after the clinical onset of their disease. In other words, and contrary to the generally held view, this lesion is not uncommon. It is specific for diabetes and has never been observed in the chronic cases 5. In patients with chronic juvenile diabetes, the B cells are completely absent, except in occasional cases. The islets consist of small, atrophic cells. 6. A valid assessment of the functional capacity of insular tissue can only be achieved if as much use as pos sible is made of quantitative technics and of cytological examination

Four-year metabolic outcome of a randomised controlled CD3-antibody trial in recent-onset type 1 diabetic patients depends on their age and baseline residual beta cell mass

“…It is conceivable that residual beta cells are lost because the autoimmune reactivity had only been transiently suppressed; their survival and/or function may also have been affected by the chronic state of hyperglycaemia. Since the beta cell mass is already markedly reduced at clinical onset of type 1 diabetes [18,19], it is likely that any immune-modulating intervention will have to be associated with, or followed by, a beta cell replacement therapy, as recently tested in rodents [20]; a combination with other methods for tolerance-induction should also be considered [21,22].…”

Treg cells in pancreatic lymph nodes: the possible role in diabetogenesis and β cell regeneration in a T1D model

“…7 The finding that insulin-secreting cells could fully recover under conditions that restrain their devastation inspired exploration of the immunomodulatory approaches for therapy of T1D. [8][9][10][11][12][13][14] To further explore the concept that suppression of autoimmunity could become an adequate condition for recovery of the autologous insulin-secreting tissue, we established a model in which recovery of the physiological function of the autologous b cells was achieved in nonobese diabetic (NOD) mice by induction of allogeneic hemopoietic chimerism after the onset of hyperglycemia.…”

Risk for developing Type 1 (insulin-dependent) diabetes mellitus and the presence of islet 64K antibodies

“…An immunological pathogenesis for Type 1 (insulin-dependent) diabetes mellitus is supported by the presence of inflammatory cells in the islets of Langerhans at onset [1][2][3] and of autoantibodies, reacting with pancreatic islet cells [4][5][6], insulin [7], or a Beta-cell Mr 64,000 (64K) protein [8], as early as several years prior to clinical onset [9][10][11][12].…”