INTRODUCTION: Recovery of beta cell function (BCF) and mass (BCM) is suggested as an underlying mechanisms in remission of type 2 diabetes (T2D) after gastric bypass surgery (RYGB). Recently, ⁶⁸Ga-exendin-4 (Ex4) PET/CT became available, enabling visualizing beta cells by targeting its glucagon-like peptide-1 (GLP-1) receptor. To increase our understanding of beta cells in T2D remission, we examined BCF and BCM before and after RYGB.

METHODS: We included 13 patients with T2D undergoing RYGB. Oral glucose tolerance test, arginine stimulation (AS) and Ex4 PET/CT were performed before and 1 year post RYGB. Total pancreatic uptake of Ex4 (kBq/ per injected MBq) was measured as marker for BCM. C-peptide response (CPR) after AS was measured as marker for BCF.

RESULTS: One year follow up was completed by 12 patients: 10 females, mean age of 53 (35-65) years, mean duration of T2DM of 10 (1-21) years. Seven patients were insulin dependent (ID) (insulin dose: 99±47 IU/day), six patients had only metformin therapy (1-2 g/day). Complete T2D remission was observed in one ID and all NID patients, others had partial remission (N=1) or improvements (N=5).

Before RYGB, CPR and pancreatic uptake were lower in ID than NID patients (p=0.074 and p=0.035). After RYGB, CPR decreased and pancreatic uptake remained similar in the NID group. Individually, the largest decrease in CPR corresponded with decreased uptake. In the ID group, CPR remained stable and pancreatic uptake increased (p<0.05). Changes in pancreatic uptake and CPR, tends to be related, although several confounders might be present.

CONCLUSION: BCM was lower in ID than NID patients before RYGB. After RYGB, pancreatic uptake and CPR  decreased in NID patients, probably reflecting normalisation of BCF and BCM. In contrast, increased uptake and CPR in ID patients may point towards recovered beta cells or GLP-1R expression. Similar findings were never observed in humans before. Mechanisms behind changes in pancreatic Ex4 uptake and beta cell mass in T2D need further investigation, for which Ex4 PET can be a valuable tool.