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People with type 1 diabetes (T1D) have been considered to have lost all pancreatic insulin-producing beta cells, leaving the control of their blood glucose levels dependent on insulin injections. There is growing evidence that this dogma may not completely be true as residual beta cells, although not functional, are even found in autopsy pancreata of people having suffered from T1D for several decennia.
To date, it has not been possible to measure beta cell mass in living humans, as pancreas biopsies cause potentially lethal side effects. At Radboudumc, an advanced imaging modality has been developed, called Ga-68-NODAGA-Exendin-4 PET (positron emission tomography), which allows sensitive and specific measurement of the amount of beta cells in the human pancreas.
This technique has been used to measure beta cell mass in people with T1D who have a stable glucose control, compared to a group of people who have difficulties to keep their blood glucose levels stable. The research team demonstrated that in the group with stable glucose control, there are more beta cells present in the pancreata than in the group of people with unstable glucose control. Furthermore, they found a correlation between the beta cell mass and stimulated residual endogenous insulin production.
Abdominal PET/CT images with pancreatic uptake of radiolabelled exendin. Transversal fused PET/CT images (a–c) and PET images (d–f) of three individuals showing pancreatic uptake of 68Ga-exendin as measure for beta cell mass (green arrows). Other regions with exendin uptake are the proximal duodenum (red arrows) and the kidneys (indicated with the letter ‘K’). Pancreatic exendin uptake of individuals with LGV (Low Glucose Variability, ie stable glucose control) were in the same range for individual 1 (a, d) (AUC for C-peptide 122 nmol min/l) and individual 2 (b, e) (no detectable C-peptide), despite differences in C-peptide response, and much greater than in individual 3 (c, f) (no detectable C-peptide)
These results are highly significant in several respects. Firstly, they underline the importance of presence of beta cells in people with T1D, even when these beta cells are dysfunctional and produce only negligible amounts of insulin. Secondly, these results confirm previous hypotheses of presence of residual dysfunctional beta cells in people with long-standing T1D. And finally, this study demonstrates the feasibility of imaging beta cells in living humans non-invasively, an achievement which has been considered the “holy grail” of molecular imaging in diabetes. In the future, because of its very low radiation exposure, this ground breaking technology can be used for longitudinal assessment of beta cell mass in people with diabetes.
Publication
Read the clinical study here: https://pubmed.ncbi.nlm.nih.gov/36394644/
Jansen TJP, Brom M, Boss M, Buitinga M, Tack CJ, van Meijel LA, de Galan BE, Gotthardt M. Importance of beta cell mass for glycaemic control in people with type 1 diabetes. Diabetologia. 2023 Feb;66(2):367-375. doi: 10.1007/s00125-022-05830-2. Epub 2022 Nov 17. PMID: 36394644; PMCID: PMC9669532.
Departments involved: Department of Medical Imaging (Nuclear Medicine) and Department of Internal Medicine (Diabetology)
