Abstract
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is associated with decreased plasma glutamine and increased plasma glucose, but using both measurements together has not been utilised as a diagnostic test for PDAC. Glutamine is used by the tricarboxylic acid cycle during glucose metabolism, and is a substrate for gluconeogenesis during periods of starvation; which might be augmented by insulin resistance associated with PDAC. Our aim was to examine the utility of a plasma glutamine:glucose ratio as a diagnostic test for PDAC, and investigate the influence of fasting on this ratio.
Method: Plasma samples were taken from 50 fasted participants, who were starved for 12 hours, and compared to 50 separate non-fasted participants. The relative abundance of glucose and glutamine from both groups was measured with 1H-NMR spectroscopy. The intensity of the signal on the vertical axis represents the quantity of each metabolite. Mann-Whitney U tests compared the differences between each metabolite, and receiver operator characteristic curves based on the ratios between the groups were generated using Stata 16.
Results: Twenty-six fasted PDAC patients (aged 65.9 ± 11.2, 65.3% male) and 24 fasted controls (aged 68.3 ± 8.2, 54% male) were studied, alongside 40 non-fasted PDAC patients (aged 68.1 ± 9.9, 47.5% male) and 10 non-fasted controls (aged 60.5 ± 14.4, 60% male). The intensity of the glutamine signal was lower in those with PDAC compared to controls in the fasted group (3.64AU, vs 3.94AU, P = 0.025), whereas in the non-fasted there was no significant difference between PDAC and controls (4.39AU, vs 4.02AU, P = 0.22). The intensity of the glucose signal was increased in those with PDAC compared to controls in the fasted state (10.16AU vs 8.59AU, P < 0.001). This was also the case in the non-fasted state (10.60AU vs 7.17AU, P = 0.001). The AUROC for the ratio of glutamine:glucose for a diagnosis of PDAC compared to controls in the fasted state was 0.82 (95% CI: 0.58 – 0.93). In the non-fasted state the AUROC was 0.75 (95% CI: 0.69 – 0.94). There was no significant difference in AUROCs between fasted and non-fasted participants (P = 0.56).
Conclusion: Glutamine uptake is higher in PDAC amongst fasted individuals. The data indicates that the plasma glutamine:glucose ratio has a good diagnostic performance for diagnosing PDAC, and further research is needed to study the utility of this test in PDAC.