Discussion
MetS.Despite, generalised, MetS, diabetes
DIABETES, INSULIN RESISTANCE, LGL
The current study compares the plasma metabolomic responses in postmenopausal women with or without MetS to two carbohydrate-rich meals, differing on the basis of GL. Using an untargeted LC–MS strategy, the results demonstrate a predominance of differences in circulating AAs between the healthy and MetS women. There were far fewer and more subtle differences in the circulating AA response between the HGL and LGL meals. Of the responses evident, these tended to be within the first hour following the meal, with no effect evident over the subsequent 2 h of analysis. The untargeted metabolomic analysis also identified metabolites related to energy utilisation pathways, including lactic acid and carnitine that exhibited a greater post-meal excursion in the women with MetS.Despite the design of the meals to alter the calculated GL, the measured blood glucose concentrations demonstrated only a small transient heightened response in the MetS women, following ingestion of the HGL meal. For all study participants, blood glucose exhibited a bi-phasic response, with a nadir between 45 and 60 min after meal ingestion. Although the bi-phasic nature of blood glucose response to a mixed meal has been previously reported [Increased circulating BCAA has been demonstrated to be predictive of diabetes risk [The dispensable amino acid tyrosine exhibited the tendency for increased abundances from 60 min till the study completion (300 min) in the MetS women, irrespective of the meal. These results are consistent with the observation of greater plasma tyrosine responses following different high protein meals in those individuals exhibiting insulin resistance [In the current study, further two-way associations in the response of several amino acids and energy metabolites was demonstrated. Of the identified AAs, alanine was notable in that the post-meal response tended to be greater in the women with MetS. Alanine provides a physiological balance for glucose and proline via glutamate in the tricarboxylic acid cycle (TCA) [Of particular interest is whether variations in the GL of a meal can be identified to modify the concentration of metabolites indicative of altered oxidative metabolism. Lactic acid is the end product of glycolysis, with plasma concentrations indicative of flux in the Cori cycle, where it is exported from glycolytically active tissues into the plasma for synthesis to glucose in the liver [Fasted creatine has previously been associated with MetS [There are important considerations and limitations of the current study. These investigations are limited to older Caucasian females who are postmenopausal, and hence, caution is required in generalising these results to males, younger adults, or to multiple ethnicities. Furthermore, whilst metabolomics has provided significant insight into the differences between postprandial profiles of healthy and MetS women, it does not provide a detailed understanding of the variations in the either the rate of absorption or the rate of tissue clearances due to breakdown of meals between phenotypes. Additionally, the choice of meal is likely to impact on the extent to which these results can be generalised. Future studies can address this issue by incorporating stable isotopes into the food, enabling the precise analysis of metabolite fluxes. Given that there was no formal estimation of sample size calculation and the untargeted nature of the LC–MS analysis, this study should be viewed as a potential pilot to provide guidance for future investigations.