Endocrine Abstracts

Background and Aims: Type 1 diabetes mellitus (T1DM) is characterised by autoimmune destruction of pancreatic beta-cells resulting in insulin deficiency. Evaluation of novel therapies for T1DM requires reliable methods to measure beta-cell function, which is unattainable using traditional non-invasive imaging techniques. A new approach is manganese-enhanced magnetic resonance imaging (MEMRI). As a calcium analogue, manganese is taken up into pancreatic beta-cells during insulin secretion, serving as intracellular contrast. We conducted a proof-of-concept study to investigate whether MEMRI can be used as a measure of beta-cell function in people with T1DM.

Methods: In a prospective case-control study, 20 people with T1DM (age 52 [44-61] years, 6 female; 10 with very low [<50 pmol/l], and 10 with reduced [>50pmol/l] C-peptide concentrations) and 15 healthy volunteers (age 32 [23-36] years, 6 female) underwent MEMRI of the pancreas following a standardised oral glucose load (Fortisip Compact, 125 mL). MEMRI was performed using intravenous manganese dipyridoxyl diphosphate administered over 10 minutes. Pancreatic T1 mapping was performed prior to and every 2.5 min for 30 min after manganese infusion. Quantitative manganese uptake analysis was performed by measuring T1 relaxation times in regions of interest drawn within the pancreas and compared with the left ventricular blood pool. The rate of pancreatic manganese uptake was determined by Patlak modelling [1]. Scan-rescan reproducibility was performed in 10 participants at least 8 weeks apart.

Results: People with T1DM had impaired pancreatic manganese uptake (Ki) in those with reduced (median Ki 24 [interquartile range 21-25] ml/100 g of tissue/min) or very low (15 [8-16] ml/100 g of tissue/min) C-peptide concentrations compared to healthy volunteers (30 [27-34] ml/100 g of tissue/min; p≤0.002 for both). Compared to healthy volunteers, participants with T1DM had visibly lower pancreatic enhancement 30 min after manganese infusion, especially in those with very low C-peptide concentrations. Ki correlated with C-peptide levels in people with T1DM (r=0.73,P=0.0002) but not in healthy volunteers (r=-0.054, P=0.88). There were no correlations between Ki and age, body-mass index or glycated haemoglobin. We found strong intra-observer (0.98[0.96-0.99]) and inter-observer (0.84[0.51-0.95]) repeatability and scan-rescan reproducibility (0.73[0.23-0.92]) for Ki.

Conclsions: MEMRI can provide a non-invasive imaging technique to assess beta-cell function in people with T1DM. This has important implications for investigation of the pathophysiology of T1DM, monitoring disease progression and assessment of novel immunomodulatory interventions.

References: 1 Spath NB et al. Manganese-enhanced MRI of the myocardium. Heart. doi:10.1136/heartjnl-2019-315227