Sevilay Tokgöz1, Hajime Yamazaki2,3, Katsiaryna Prystupa4,5, Julia Hummel6, Laura Deden1,7, Martin Gotthardt1, Róbert Wagner4,5,8, Martin Heni6,9
1Department of Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands. 2Section of Clinical Epidemiology, Department of Community Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. 3Center for Innovative Research for Communities and Clinical Excellence (CiRC2LE), Fukushima Medical University, Fukushima, Japan. 4Institute for Clinical Diabetology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany. 5German Center for Diabetes Research (DZD), Neuherberg, Germany. 6Division of Endocrinology and Diabetology, Department of Internal Medicine I, University of Ulm, Ulm, Germany. 7Department of surgery, Rijnstate Hospital, Arnhem, the Netherlands. 8Department of Endocrinology and Diabetology, University Hospital Düsseldorf, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany. 9Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen, Germany.
Background: Histological studies suggest that individuals with type 2 diabetes have a smaller pancreas and lower beta cell mass compared to healthy individuals, although considerable individual variation exists. In addition, intrapancreatic fat deposition (IPFD) represents another risk factor of type 2 diabetes. However, whether a small pancreas with high IPFD and lower beta cell mass are causes or consequences of type 2 diabetes is unclear. In this study, we aimed to investigate the interplay between pancreatic volume, IPFD and beta cell mass using [68Ga]Ga-NODAGA-exendin-4 PET/CT imaging in a large variety of individuals either with or without type 2 diabetes or other metabolic disturbances.
Methods: This posthoc analysis included 52 individuals either with type 2 diabetes (n=25), with remission of type 2 diabetes after Roux-en-Y gastric bypass (RYGB) (n=7), without remission of type 2 diabetes after RYGB (n=8), without type 2 diabetes (n=3), and without (a history of) type 2 diabetes who underwent RYGB (n=9). Baseline fasting glucose and C-peptide levels were determined to compute beta cell function (HOMA2-%B) and insulin resistance (HOMA2-IR) using the HOMA2 model. The total pancreatic uptake of [68Ga]Ga-NODAGA-exendin-4 was determined on PET/CT scans as a measure for beta cell mass followed by measurements of the pancreatic volume and pancreas attenuation on CT representing IPFD.
Results: We observed a positive correlation between the total pancreatic tracer uptake, representing overall beta-cell mass, and both pancreatic volume (Spearman r=0.66, p<0.0001) and pancreatic CT attenuation (Spearman r=0.29, p=0.037). In addition, the total pancreatic tracer uptake correlated with HOMA2-%B (Spearman r=0.48, p=0.0006), but did not correlate with HOMA2-IR (Spearman r=0.040, p=0.79).
Discussion/Conclusion: Our data indicate that a smaller pancreas accompanied by pancreatic fat accumulation is associated with lower beta cell mass, which may contribute to impaired beta cell function.