Changes in Metabolites During an Oral Glucose Tolerance Test in Early and Mid-Pregnancy: Findings from the PEARLS Randomized, Controlled Lifestyle Trial

Abstract

<jats:p>The oral glucose tolerance test (OGTT) is used to diagnose gestational and other types of diabetes. We examined metabolite changes during an OGTT, and how a comprehensive diet and physical activity intervention may influence these changes in a population of overweight/obese Hispanic pregnant women. Integration of changes in metabolites during an OGTT may help us gain preliminary insights into how glucose metabolism changes during pregnancy. Among women from the Pregnancy and EARly Lifestyle improvement Study (PEARLS), we measured metabolites during a multipoint OGTT (fasting, 30, 60 and 120 min) at early and mid-pregnancy. Metabolite levels were measured by liquid chromatography–mass spectrometry in plasma samples in the lifestyle intervention (n = 13) and control (n = 16) arms of the study. A total of 65 candidate metabolites were selected that displayed changes during an OGTT in previous studies. Paired and unpaired t-tests were used to examine differences in Δfast-120 min: (1) at early and mid-pregnancy; and (2) by intervention assignment. We applied principal component analysis (PCA) to identify those metabolites that differed by intervention assignment and OGTT time points. Most of the characteristic changes in metabolites post-OGTT were similar at both gestational time points. PCA identified characteristic metabolite patterns associated with OGTT time points at both early and mid-pregnancy. These metabolites included ketone bodies, tryptophan, acyl carnitines, polyunsaturated fatty acids, and biomarkers related to bile acid, urea cycle, arginine, and proline metabolism. PCA identified distinct Δfast-120 min in fatty acid, acyl carnitine, bile acid, ketone body, and amino acid levels at mid- compared to early pregnancy. Participants in the intervention group did not display mean decreases in Δfast-120 min of several long-chain acyl carnitines that were observed in the control group. These findings provide preliminary insight into metabolites, whose role in increased insulin resistance during pregnancy, should be explored further in future studies.</jats:p>

Metabolic Responses to an Acute Glucose Challenge: The Differential Effects of Eight Weeks of Almond vs. Cracker Consumption in Young Adults

“…This study characterized changes in the human metabolome following an acute glucose challenge and investigated variations in these responses between individuals consuming almonds versus graham crackers for 8 weeks. As shown previously [9,[13][14][15][16], a progressive temporal shift in response to a glucose challenge was observed with alterations across amino acid, carbohydrate, and lipid metabolism pathways. Findings also exhibit a notable biphasic lipid response distinguished by higher levels of certain lipids such as unsaturated triglycerides in the earlier periods of a glucose challenge followed by lower levels in the latter period in the almond versus the cracker group.…”

Human metabolic chambers reveal a coordinated metabolic-physiologic response to nutrition

“…While the precise dietary exposures were different in nature and duration from our study, some metabolites were shared, including carnitines, select amino acids, ketones, and microbially products. Moreover, while we did not have access to long-term outcomes in the present report, acute metabolic responses to select substrates (e.g., oral glucose 11,[29][30][31] or mixed meal tolerance testing 32 ) may map to longerterm cardiometabolic outcomes 33 . Indeed, in the present report, we observed dynamic changes in metabolites (glycine 34 , glutamine 35 , DMGV [36][37][38] ) linked to cardiometabolic states in select dietary interventions (e.g., high-fat, fasting, high-protein), opening the potential for individualizing metabolic risk mitigation strategies by precision metabolic response to nutrition.…”

Human Milk Oligosaccharides in Maternal Serum Respond to Oral Glucose Load and Are Associated with Insulin Sensitivity

“…Few studies so far have investigated changes in metabolites during an OGTT in pregnant women [ 21 , 22 ], and none have investigated HMOs. Most metabolites decrease upon glucose challenges such as acyl carnitines, amino acids and fatty acids [ 23 ]. Our findings that HMOs are affected by glucose fluctuation highlight the need to consider the fasting/fed status in future HMO studies.…”