Detection of Insulitis by Pancreatic Scintigraphy With 99mTc-Labeled IL-2 and MRI in Patients With LADA (Action LADA 10)

Abstract

OBJECTIVEPancreatic scintigraphy with interleukin-2 radiolabeled with 99m Tc ( 99m Tc-IL-2) is a technique used to image chronic inflammatory-mediated disorders. We used this method to detect a signal consistent with the presence of insulitis in patients with autoimmune diabetes. Positive and negative controls (patients with pancreatic carcinoma and type 2 diabetes, respectively) also were studied. RESEARCH DESIGN AND METHODSWe examined 25 patients with autoimmune diabetes (16 with recently diagnosed type 1 diabetes, 9 with latent autoimmune diabetes in adults [LADA]), 6 with type 2 diabetes, and 7 with pancreatic carcinoma (the latter two groups were used as negative and positive controls, respectively). All patients underwent 99m Tc-IL-2 scintigraphy and contrast-enhanced MRI of the pancreas. To validate positive controls, samples were taken from patients with pancreatic carcinoma during surgery for histological and immunohistochemical investigations. RESULTS Pancreatic accumulation of99m Tc-IL-2 was detected in patients with autoimmune diabetes (61% positive) and, notably, in 6 of 9 patients with LADA; semiquantitative evaluation of pancreatic uptake of 99m Tc-IL-2 showed higher values in patients with autoimmune diabetes (both childhood and LADA) and pancreatic carcinoma than in those with type 2 diabetes (4.45 6 1.99, 4.79 6 1.1, and 4.54 6 1.62 vs. 2.81 6 0.63; P = 0.06, P = 0.01, and P = 0.04, respectively). In patients with pancreatic carcinoma, pancreatic interleukin-2 receptor expression correlated with pancreatic 99m Tc-IL-2 uptake (r = 0.8; P = 0.01). In patients with LADA, 99m Tc-IL-2 uptake inversely correlated with duration of disease (r = 0.7; P = 0.03). CONCLUSIONSAutoimmune diabetes in adults is associated with increased pancreatic 99m Tc-IL-2 uptake, indicating the presence of insulitis, particularly within 1 year of the beginning of insulin therapy, similar to type 1 diabetes at diagnosis.Type 1 diabetes (T1D) is a T-cell-mediated autoimmune disease derived from the selective destruction of insulin-secreting b-cells. Several studies have shown that lymphomononuclear cell infiltration of the endocrine pancreas (insulitis) is present for months or even years before the clinical diagnosis and is associated with residual b-cell mass (1-3).

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