Description and purpose
The loss of functional β-cell capacity [BCFxM = β-cell mass (BCM) × β-cell function (BCF)] is the key mechanism underlying the development of diabetes. We have previously developed a PET-CT method using 68Ga-exendin-4 to quantify BCM, combined with advanced modeling for BCFxM. After validation in subjects with type 1 diabetes and obesity, the objectives are: 1)to complete its validation by comparing the BCM estimated by imaging with histology and GLP-1 receptor expression; 2) to reconstruct the natural history of BCM and BCF in type 2 diabetes (T2D).
Purpose
The first objective is to validate PET-CT with 68Ga-exendin-4 by comparing the BCM estimated with histological analysis of GLP-1 receptor expression in patients undergoing pancreatectomy (7 normo-tolerant, 7 with impaired glucose tolerance, and 7 patients with T2D), a study conducted at the Gemelli Hospital (Rome). The second objective, currently ongoing in Parma, assesses BCM and BCF in subjects with newly diagnosed T2D (n=20), long-standing T2D (n=20), and normo-tolerant subjects (n=20).
Expected results
1) Further validation of PET-CT through detection of pancreatic GLP-1 receptor occupancy; 2) cross-sectional assessment of BCM and BCF trajectories in the transition from normo-tolerant subjects to short-duration T2D and then to long-duration T2D, providing missing key elements of the natural history of the disease.
Achieved results
To date, in Parma, 10 subjects with short-duration T2D, 5 with long-duration T2D, 5 with impaired glucose tolerance, and 23 normo-tolerant subjects have been recruited. All these subjects have undergone testing for the evaluation of β-cell functionality (BCFxM), and PET scans with 68Ga-exendin-4 for BCM estimation are ongoing. Preliminary analyses appear to show that PET with 68 Ga-exendin-4 is capable of discriminating subjects with different functional β-cell mass.
