Changes of the plasma metabolome during an oral glucose tolerance test: is there more than glucose to look at?

Abstract

The oral glucose tolerance test (oGTT) is a common tool to provoke a metabolic challenge for scientific purposes, as well as for diagnostic reasons, to monitor the kinetics of glucose and insulin. Here, we aimed to follow the variety of physiological changes of the whole metabolic pattern in plasma during an oGTT in healthy subjects in a nontargeted reversed-phase ultra performance liquid chromatography coupled to electrospray ionization quadrupole time of flight mass spectrometric metabolomics approach. We detected 11,500 metabolite ion masses/individual. Applying multivariate data analysis, four major groups of metabolites have been detected as the most discriminating oGTT biomarkers: free fatty acids (FFA), acylcarnitines, bile acids, and lysophosphatidylcholines. We found in detail 1) a strong decrease of all saturated and monounsaturated FFA studied during the oGTT; 2) a significant faster decline of palmitoleate (C16:1) and oleate (C18:1) FFA levels than their saturated counterparts; 3) a strong relative increase of polyunsaturated fatty acids in the fatty acid pattern at 120 min; and 4) a clear decrease in plasma C10:0, C12:0, and C14:1 acylcarnitine levels. These data reflect the switch from beta-oxidation to glycolysis and fat storage during the oGTT. Moreover, the bile acids glycocholic acid, glycochenodeoxycholic acid, and glycodeoxycholic acid were highly discriminative, showing a biphasic kinetic with a maximum of a 4.5- to 6-fold increase at 30 min after glucose ingestion, a significant decrease over the next 60 min followed by an increase until the end of the oGTT. Lysophosphatidylcholines were also increased significantly. The findings of our metabolomics study reveal detailed insights in the complex physiological regulation of the metabolism during an oGTT offering novel perspectives of this widely used procedure.

Metabolomics in diabetes research

“…However, this study demonstrated novel changes in the levels of bile acids following the OGTT; the levels of three bile acids, glycocholic acid, glycochenodeoxycholic acid (GCDCA) and taurochenodeoxycholic acid, were increased within the first 30 min following glucose ingestion and remained stable thereafter. Another study (Zhao et al 2009) examining healthy individuals revealed similar results concerning these bile acids and reported as much as a sixfold increase in these levels after 30 min (followed by a subsequent decrease). Both findings were confirmed by a third study (Matysik et al 2011) that investigated bile acid signalling during the course of an OGTT in relation to 15 conjugated and unconjugated bile acids.…”

“…Moreover, the levels of free carnitine were increased in both groups, although differences between groups were observed for short-and medium-chain acylcarnitine species as well as hydroxyacylcarnitines, where higher levels were observed in T2DM patients. Similar to an OGTT-induced reduction in acylcarnitines (Zhao et al 2009), an insulin-stimulated euglycaemic clamp led to a decrease in all acylcarnitine species for all three of the investigated groups, although this reduction was blunted in patients with T2DM (Mihalik et al 2010). All the investigated fatty acids and acylcarnitines are listed in Table 2.…”

“…In fact, increases in lysophosphatidylcholine (Zhao et al 2009) and decreases in amino acids (Table 1; Shaham et al 2008, Spegel et al 2010, acylcarnitines (Zhao et al 2009) and fatty acids (Table 2; Zhao et al 2009, Spegel et al 2010 were reported. The study by Zhao et al (2009) provided a more systematic overview of fatty acid plasma changes during an OGTT; although the levels of fatty acids declined during an OGTT, the levels of saturated (SFA) and monounsaturated fatty acids (MUFA) were more significantly decreased than those of polyunsaturated fatty acids (PUFA). Moreover, a substantial reduction in the SFA/MUFA ratio was observed, consisting of a shift from MUFA towards SFA.…”

“…Several studies have investigated changes in the metabolic profile in relation to glucose ingestion (Shaham et al 2008, Zhao et al 2009, Spegel et al 2010, Matysik et al 2011). An investigation (Shaham et al 2008) among participants in the Metabolic Abnormalities in College Students (MACS) study, who demonstrated normal glucose tolerance, revealed significant kinetic alterations in 21 out of 191 plasma metabolites, measured by LC-MS, in response to an OGTT.…”

Symposium 2: Modern approaches to nutritional research challenges Targeted and non-targeted approaches for metabolite profiling in nutritional research

“…GC-MS Exercise and influence of different CHO drinks: cross-over design, single dose; 90 min exercise followed by either water, low-CHO drink, high-CHO drink or low-CHO and protein drink, 1-week washout (n 24; men) Serum Zhao et al (51) LC-MS Changes to metabolome following oral glucose tolerance test: samples from subjects undergoing an oral glucose tolerance test (n 16; not specified) Plasma LC, liquid chromatography; CHO, carbohydrate.…”