Sevilay Tokgöz1, Pleun de Groen 2, Tom Jansen1, Coco Fuhri-Snethlage2, Marti Boss1, Hajime Yamazaki3,4, Max Nieuwdorp2,5, Martin Gotthardt1, Nordin Hanssen2,5, Rick Meijer6
1Department of Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands. 2Department of Internal and Vascular Medicine, Amsterdam University Medical Center, Amsterdam, the Netherlands.3Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 4Center for Innovative Research for Communities and Clinical Excellence (CiRC2LE), Fukushima Medical University, Fukushima, Japan. 5Diabeter (Center Amsterdam), the Netherlands.6Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
Background: C-peptide decline in type 1 diabetes (T1D) is associated with disease duration as it declines during the first 7 years and stabilizes thereafter. It is unclear whether this process entails loss of beta cell function or also loss of beta cell mass. Additionally, pancreatic volume is reported to decrease prior to the diagnosis. In this pooled post-hoc analysis, we aimed to investigate beta cell mass, function, pancreatic volume and intrapancreatic fat deposition (IPFD) in individuals with short-duration (<7 years) and long-duration (≥7 years) T1D.
Methods: Data of 16 individuals with short-duration (<7 years) and 10 with long-duration T1D (≥7 years), who underwent [68Ga]Ga-NODAGA-exendin-4 PET/CT scan and mixed-meal tolerance test were used to assess beta cell mass and function, respectively. The CT scan was used to determine IPFD and pancreatic volume.
Results: Individuals with short-duration T1D had higher beta cell mass compared to those with long-duration T1D (4.4±1.8 vs 2.8±1.3 kBq/MBq, p=0.012). In addition, beta cell function was significantly higher in short-duration T1D compared to long-duration (AUCC-peptide 47.7(29.0-99.0) vs 1.2(1.2-15.7) nmol/L/min-1, p=0.0047). A larger pancreatic volume (61.2±16.4 vs 45.3±9.1 ml, p=0.0041) and lower IPFD (CT attenuation as inverse marker; 47.9±8.7 vs 38.8±11.3 HU, p=0.047) were observed in short-duration T1D. These results did not change after correcting for age and sex. Beta cell mass correlated with beta cell function (r=0.46, p=0.019) and pancreatic volume (r=0.91, p<0.0001), and correlated with BMI inversely (r=-0.61, p=0.0009).
Discussion/Conclusion: These results offer promising insights in the decline of beta cell mass during the course of T1D and shows the potential of imaging markers together with function tests to monitor disease progression. This may offer valuable information for timing to restore beta cell function or to slow down beta cell destruction.