Importance of beta cell mass for glycaemic control in people with type 1 diabetes

Abstract

Aims/hypothesis: The role of beta cell mass in the balance of glucose control and hypoglycaemic burden in people with type 1 diabetes is unclear. We applied positron emission tomography (PET) imaging with radiolabelled exendin to compare beta cell mass among people with type 1 diabetes and either low glucose variability (LGV) or high glucose variability (HGV).

Methods: All participants with either LGV (n=9) or HGV (n=7) underwent a mixed-meal tolerance test to determine beta cell function and wore a blinded continuous glucose monitor for a week. After an i.v. injection with [⁶⁸Ga]Ga-NODAGA-exendin-4, PET images were acquired for the quantification of pancreatic uptake of radiolabelled exendin. The mean standardised uptake value (SUVmean) of the pancreas was used to determine the amount of beta cell mass.

Results: Participants with LGV had lower HbA_1c (46.0 mmol/mol [44.5-52.5] [6.4% (6.3-7)] vs 80 mmol/mol [69.0-110] [9.5% (8.5-12.2)], p=0.001) and higher time in range (TIR) (75.6% [73.5-90.3] vs 38.7% [25.1-48.5], p=0.002) than those with HGV. The SUVmean of the pancreas was higher for the LGV than for the HGV group (5.1 [3.6-5.6] vs 2.9 [2.1-3.4], p=0.008). The AUC_C-peptide:AUC_glucose ratio was numerically, but not statistically, higher in the LGV compared with the HGV group (2.7×10^-2 [6.2×10^-4-5.3×10^-2] vs 9.3×10^-4 [4.7×10^-4-5.2×10^-3], p=0.21). SUVmean correlated with the AUC_C-peptide:AUC_glucose ratio (Pearson r=0.64, p=0.01), as well as with the TIR (r=0.64, p=0.01) and the SD of interstitial glucose levels (r=-0.66, p=0.007).

Conclusion/interpretation: Our data show higher beta cell mass in people with type 1 diabetes and LGV than in those with HGV, independent of beta cell function.

Keywords: Beta cell mass; Exendin; Glucose control; Glucose variability; Hypoglycaemic burden; PET imaging; Pancreatic beta cell; Type 1 diabetes.