Imaging of β-Cell Mass and Insulitis in Insulin-Dependent (Type 1) Diabetes Mellitus

Abstract

Insulin-dependent (type 1) diabetes mellitus is a metabolic disease with a complex multifactorial etiology and a poorly understood pathogenesis. Genetic and environmental factors cause an autoimmune reaction against pancreatic β-cells, called insulitis, confirmed in pancreatic samples obtained at autopsy. The possibility to noninvasively quantify β-cell mass in vivo would provide important biological insights and facilitate aspects of diagnosis and therapy, including follow-up of islet cell transplantation. Moreover, the availability of a noninvasive tool to quantify the extent and severity of pancreatic insulitis could be useful for understanding the natural history of human insulin-dependent (type 1) diabetes mellitus, to early diagnose children at risk to develop overt diabetes, and to select patients to be treated with immunotherapies aimed at blocking the insulitis and monitoring the efficacy of these therapies. In this review, we outline the imaging techniques currently available for in vivo, noninvasive detection of β-cell mass and insulitis. These imaging techniques include magnetic resonance imaging, ultrasound, computed tomography, bioluminescence and fluorescence imaging, and the nuclear medicine techniques positron emission tomography and single-photon emission computed tomography. Several approaches and radiopharmaceuticals for imaging β-cells and lymphocytic insulitis are reviewed in detail.

Pancreatic biopsies in type 1 diabetes: revisiting the myth of Pandora’s box

“…Next, attempts to understand the inner workings of the pancreas in type 1 diabetic patients, living or deceased, should not stop with this setback. Indeed, if anything, this outcome should bolster alternative approaches to evaluate the inner workings of the pancreas, including and especially pancreatic imaging via NMR or PET [10]. These efforts also provide support, albeit indirect, for initiatives designed to collect whole pancreases from organ donors, such as PanFin and the Network for Pancreatic Organ Donors with Diabetes (nPOD) (www.jdrfnpod.org) [11,12].…”

Translational Molecular Imaging of Diabetes

“…Intraoperative US examination can be useful for detecting islets during transplantation in a clinical setting aiding to the evaluation of the safety of the procedure. This clinical modality could also be useful for evaluating and monitoring focal fatty infitration (steatosis) that could accompany islet transplantation [6,96].…”

“…We concentrate mainly on magnetic resonance imaging (MRI) and nuclear imaging, as these are the two modalities with the highest potential for clinical translation as it relates to diabetes imaging. While optical imaging offers excellent possibilities for imaging beta cells and insulitis in vitro or in animal models, translational potential of this approach is hampered by deep location of the pancreas in the body and by the difficulty of detecting fluorescence with the currently available technology [6].…”

Are mast cells important in diabetes?

“…Type 1 diabetes mellitus can occur for genetic and environmental reasons, and presents with destruction of pancreatic β cells due to the infiltration of immune and inflammatory cells, including MCs, in the pancreas (an effect called insulitis) [10]. Therefore, inhibition of activated MCs and their degranulation and/or inflammatory cytokine/chemokine generation might act to protect pancreatic β cells in T1DM [11].…”