Non-invasive imaging of functional pancreatic islet beta-cell mass in people with type 1 diabetes mellitus

Abstract

Aims: To investigate whether manganese-enhanced magnetic resonance imaging can assess functional pancreatic beta-cell mass in people with type 1 diabetes mellitus. Methods: In a prospective case–control study, 20 people with type 1 diabetes mellitus (10 with low (≥50 pmol/L) and 10 with very low (<50 pmol/L) C-peptide concentrations) and 15 healthy volunteers underwent manganese-enhanced magnetic resonance imaging of the pancreas following an oral glucose load. Scan-rescan reproducibility was performed in 10 participants. Results: Mean pancreatic manganese uptake was 31 ± 6 mL/100 g of tissue/min in healthy volunteers (median 32 [interquartile range 23–36] years, 6 women), falling to 23 ± 4 and 13 ± 5 mL/100 g of tissue/min (p ≤ 0.002 for both) in people with type1 diabetes mellitus (52 [44–61] years, 6 women) and low or very low plasma C-peptide concentrations respectively. Pancreatic manganese uptake correlated strongly with plasma C-peptide concentrations in people with type1 diabetes mellitus (r = 0.73, p < 0.001) but not in healthy volunteers (r = −0.054, p = 0.880). There were no statistically significant correlations between manganese uptake and age, body-mass index, or glycated haemoglobin. There was strong intra-observer (mean difference: 0.31 (limits of agreement −1.42 to 2.05) mL/100 g of tissue/min; intra-class correlation, ICC = 0.99), inter-observer (−1.23 (−5.74 to 3.27) mL/100 g of tissue/min; ICC = 0.85) and scan-rescan (−0.72 (−2.9 to 1.6) mL/100 g of tissue/min; ICC = 0.96) agreement for pancreatic manganese uptake. Conclusions: Manganese-enhanced magnetic resonance imaging provides a potential reproducible non-invasive measure of functional beta-cell mass in people with type 1 diabetes mellitus. This holds major promise for investigating type 1 diabetes, monitoring disease progression and assessing novel immunomodulatory interventions.