Tokgöz S¹, Deden L^1,2, Hofboer A², Hazebroek E², Meijer RI³, de Galan BE^3,4, Tack CJ³, Boss M¹, Gotthardt M¹

¹Department of Medical Imaging, Radboud University Medical Center, Nijmegen, The Netherlands. ²Department of Surgery, Rijnstate Hospital, Arnhem. ³Department of Internal Medicine, Radboud University Medical Center Nijmegen, The Netherlands. ⁴Department of internal medicine, Maastricht University Medical Center, CARIM School for cardiovascular diseases, Maastricht university.

Contact: Sevilay.Tokgoz@radboudumc.nl

Background: In people with type 2 diabetes (T2D) and obesity, persistent weight loss can be obtained by bariatric surgery, such as Roux-en-Y Gastric Bypass (RYGB), with potential remission of diabetes through restoration of insulin sensitivity and -secretion. RYGB has been reported to improve beta cell function in individuals with T2D, but the effects on beta cell mass are still unclear. In this study, we aimed to compare the differences in beta cell mass in individuals with and without remission of T2D after RYGB using [⁶⁸Ga]Ga-NODAGA-exendin-4 PET/CT imaging.

Methods: Age- and BMI-matched individuals with (n=8) and without (n=9) remission of type 2 diabetes up to 4 years after RYGB underwent a combined arginine stimulation test (AST) and oral glucose tolerance test (OGTT) to determine beta cell function. Subsequently, beta cell mass was quantified using PET/CT imaging after infusion with 100±5.6 MBq of [⁶⁸Ga]Ga-NODAGA-exendin-4.

Results: Individuals without remission of T2D after RYGB had a longer T2D duration before RYGB compared to individuals with remission (18±8 vs 8±6 years; p=0.0096). Beta cell function was lower in individuals without remission of T2D after RYGB compared to individuals with remission (AST: AUC_C-peptide:AUC_glucose 0.053 (0.037-0.096) vs 0.16 (0.11-0.24), p=0.0016; OGTT: AUC_C-peptide:AUC_glucose 0.032 (0.023-0.054) vs 0.15 (0.11-0.24), p=0.0052). In contrast, our data show similar beta cell mass in individuals with and without remission of T2D (SUV_mean 3.8±0.9 vs 3.6±1.1, p=0.80). Beta cell mass did not significantly correlate to beta cell function (AST r=-0.20, p=0.45; OGTT r=0.058, p=0.83), BMI (r=-0.35, p=0.17) or diabetes duration (r=0.11, p=0.69).

Discussion/Conclusion: Individuals with T2D who show remission after RYGB have better beta cell function compared to those not achieving remission, but do not differ with respect to beta cell mass. Our data argue against a stimulating effect of RYGB on beta cell mass, although reviving of nonfunctional beta cells cannot be excluded.