Kyoto, Japan -- In type 1 diabetes, the immune system starts to destroy insulin-producing beta cells in the pancreas. Progressive loss of these cells destabilizes the body's glucose levels and drives the course of the disease, so preserving or restoring beta cell mass is a central treatment goal.
New therapies aimed at preserving or increasing beta cell mass are advancing rapidly, but a noninvasive, direct measurement of this mass, and how much has been preserved or restored in interventions, is still lacking in routine clinical settings. Assessment of beta cell loss has largely relied on indirect blood-based markers that can be influenced by glucose conditions, making it difficult to assess as the condition advances.
This motivated a team of researchers at Kyoto University to evaluate an 18F-labeled PET tracer targeting the GLP-1 receptor, which they hypothesized could provide a noninvasive assessment of residual beta cell mass.
"Our study was driven by a key gap in type 1 diabetes research and care," says first author Kentaro Sakaki. "We hope this approach can help fill that gap by providing an objective readout for therapeutic evaluation."
The research team conducted a prospective study at Kyoto University Hospital, first intravenously administering [18F]FB(ePEG12)12-exendin-4, a GLP-1 receptor-targeted PET tracer, to adults with type 1 diabetes, who then underwent PET and CT imaging. The researchers then used standardized PET measures to quantify the pancreatic uptake, comparing it with data from participants without diabetes. Finally, the team examined the imaging results in relation to clinical and laboratory measures linked to beta cell function and glucose levels.
The results revealed that the pancreatic imaging measurement was lower in participants with type 1 diabetes than in participants without diabetes, and that this measurement was inversely related to hemoglobin A1c, a measure of average blood glucose levels over the previous two to three months, and the total daily insulin dose used for treatment. The researchers also observed no serious side effects among the participants.
Larger and longitudinal studies, and studies with more diverse participants, are needed to confirm the utility of the PET tracer in measuring beta cell mass. But if substantiated in future studies, beta cell-targeted PET/CT could complement existing assessments by providing a direct, imaging-based readout of residual beta cell mass.
This method may potentially help define stages of the disease, track changes over time, and offer an objective endpoint for clinical studies that aim to preserve or restore beta cells. It may be especially useful when beta cell function temporarily declines and does not mirror residual beta cell mass.
"Many decisions in type 1 diabetes treatment would benefit from a clearer picture of how much beta cell mass remains," says team leader Takaaki Murakami. "Our findings suggest that this tracer may provide a noninvasive, quantitative readout that could support disease staging and treatment monitoring."
