Beta cell function and mass in individuals with and without remission of type 2 diabetes after Roux-en-Y gastric bypass

Aims/hypothesis: In people with type 2 diabetes and obesity, Roux-en-Y gastric bypass (RYGB) can induce remission of diabetes. While RYGB has been reported to improve beta cell function in individuals with type 2 diabetes, it is unclear whether this is accompanied by changes in beta cell mass. In this explorative proof-of-concept study, we compared beta cell mass, measured by [ ⁶⁸Ga]Ga-NODAGA-exendin-4 positron emission tomography/computed tomography (PET/CT) imaging, between individuals achieving remission of type 2 diabetes following RYGB and those not achieving remission. Methods: Individuals with (n=8) and without (n=9) remission of type 2 diabetes up to 4 years after RYGB were injected with 100 ± 5.6 MBq of [ ⁶⁸Ga]Ga-NODAGA-exendin-4 to quantify beta cell mass using PET/CT imaging. Beta cell function was determined by the AUC for C-peptide and the ratio between the AUC for C-peptide and AUC for glucose obtained from a combined arginine stimulation test (ARGT) and OGTT. Acquired variables are expressed as mean ± SD or median (IQR) based on normality. Results: Individuals with remission of type 2 diabetes had a shorter diabetes duration than those without remission. After RYGB, beta cell function was higher in individuals with remission of type 2 diabetes than individuals without remission, based on both ARGTs (AUC _C-peptide/fasting glucose 1.1 ± 0.41 vs 0.32 ± 0.16 nmol × min/mmol, p=0.001) and OGTTs (AUC _C-peptide:AUC _glucose 0.15 [0.11–0.24] vs 0.032 [0.023–0.054], p=0.005). In contrast, beta cell mass did not differ between individuals with or without remission of type 2 diabetes (3.6 [3.4–5.4] vs 3.8 [1.9–4.5] kBq/MBq, p=0.87) and did not correlate with beta cell function or body weight parameters. HOMA2-%B, also representing beta cell function, was better in the remission group and significantly improved in these individuals after RYGB, whereas it remained unchanged in non-remitters. Conclusions/interpretation: Individuals with remission of type 2 diabetes after RYGB have better beta cell function than those not achieving remission, but the groups did not differ with respect to beta cell mass. Our preliminary data argue against a stimulating effect of RYGB on beta cell mass, although revival of non-functional (so-called dormant) beta cells is a possible explanation for remission. Trial registration: ClinicalTrials.gov