Pancreatic beta and alpha cells are both decreased in patients with fulminant type 1 diabetes: a morphometrical assessment

Abstract

Aims/hypothesis: We have previously reported that fulminant type 1 diabetes is characterised by an absence of diabetes-related antibodies and a remarkably abrupt onset. However, little is known about the mechanism of beta cell destruction in this diabetes subtype, and to obtain insights into the aetiology of the disease, we investigated residual endocrine cells and the expression of Fas and Fas ligand in fulminant type 1 diabetes. Methods: Residual beta and alpha cells were morphologically assessed in pancreatic tissue obtained by biopsy from five patients with recent-onset fulminant type 1 diabetes and five patients with recent-onset typical autoimmune type 1 diabetes. In addition, the expression of Fas and Fas ligand was evaluated by immunohistochemistry. Results: In fulminant type 1 diabetes, beta and alpha cell areas were decreased significantly, compared with autoimmune type 1 diabetes and control subjects. In contrast, the alpha cell area was not decreased significantly in autoimmune type 1 diabetes, compared with that in control subjects. No Fas expression in islets and Fas ligand expression in CD3 + cells in the exocrine pancreas were found in the fulminant type 1 diabetic patients who underwent this evaluation. Conclusions/ interpretation: Our study showed that beta and alpha cells are damaged in fulminant type 1 diabetes. In addition to the lack of Fas and Fas ligand expression, the results suggest that the mechanism of beta cell destruction in fulminant type 1 diabetes is different from that in autoimmune type 1 diabetes.

Short‐term changes in pancreatic α‐cell function after the onset of fulminant type 1 diabetes

“…According to a previous report, glucagon responses to AST in patients with type 1 diabetes are positively correlated with diabetes duration, which is contrary to our present result1. In another study, the areas of α‐ and β‐cells morphologically decreased in patients with fulminant type 1 diabetes compared with those in patients with acute‐onset type 1 diabetes3. Rodent autoimmune diabetes models have revealed a substantial loss of alpha cells and impaired glucagon response to hypoglycemia 4.…”

Possible Role of α-Cell Insulin Resistance in Exaggerated Glucagon Responses to Arginine in Type 2 Diabetes

“…Autoimmune type 1 diabetes is caused by a ␤-cell-targeted immune reaction and destruction with relatively conserved ␣-cell mass (25). Therefore, the glucagon response to arginine cannot be suppressed by intrinsic insulin in hypoinsulinemic diabetic patients (12).…”

Pathogenesis of Fulminant Type 1 Diabetes

“…We have reported that the pancreatic β-cell area in patients with fulminant type 1 diabetes was 0.4% of that in normal subjects [15]. As shown in Figure 1, pancreatic β-cells were almost completely absent from the sections of patients obtained at 1-5 months after the onset of overt diabetes.…”