Abstract
Due to many adverse effects of gestational diabetes mellitus (GDM) on the mother and fetus, its diagnosis is crucial. The presence of GDM can be confirmed by an abnormal fasting plasma glucose level (aFPG) and/or oral glucose tolerance test (OGTT) performed mostly between 24 and 28 gestational week. Both aFPG and abnormal glucose tolerance (aGT) are used to diagnose GDM. In comparison to measurement of FPG, OGTT is time-consuming, usually inconvenient for the patient, and very often needs to be repeated. Therefore, it is necessary to seek tests that will be helpful and convenient to diagnose GDM. For this reason, we investigated the differences in fasting serum metabolites between GDM women with abnGM and normal FPG (aGT-GDM group), with aFPG and normal glucose metabolism (aFPG-GDM group) as well as pregnant women with normal glucose tolerance (NGT) being a control group. Serum metabolites were measured by an untargeted approach using gas chromatography–mass spectrometry (GC–MS). In the discovery phase, fasting serum samples collected from 79 pregnant women (aFPG-GDM, n = 24; aGT-GDM, n = 26; NGT, n = 29) between 24 and 28 weeks of gestation (gwk) were fingerprinted. A set of metabolites (α–hydroxybutyric acid (α–HB), β–hydroxybutyric acid (β–HB), and several fatty acids) significant in aGT-GDM vs NGT but not significant in aFPG-GDM vs NGT comparison in the discovery phase was selected for validation. These metabolites were quantified by a targeted GC–MS method in a validation cohort consisted of 163 pregnant women (aFPG-GDM, n = 51; aGT-GDM, n = 44; and NGT, n = 68). Targeted analyses were also performed on the serum collected from 92 healthy women in the first trimester (8–14 gwk) who were NGT at this time, but in the second trimester (24–28 gwk) they were diagnosed with GDM. It was found that α–HB, β–HB, and several fatty acids were associated with aGT-GDM. A combination of α–HB, β–HB, and myristic acid was found highly specific and sensitive for the diagnosis of GDM manifested by aGT-GDM (AUC = 0.828) or to select women at a risk of aGT-GDM in the first trimester (AUC = 0.791). Our findings provide new potential markers of GDM and may have implications for its early diagnosis.
Highlights
Gestational diabetes mellitus (GDM), the most common form of metabolic complication in pregnancy (Tenenbaum-Gavish et al, 2020), is defined as any degree of glucose intolerance with the onset or first recognition during pregnancy (Sweeting et al, 2019)
Another noticeable group of compounds increased in the subjects with abnormal glucose tolerance (aGT)-gestational diabetes mellitus (GDM) compared to normal glucose tolerance (NGT) consisted of hydroxy acids and derivatives, with α–hydroxybutyric acid (α–HB) and β–hydroxybutyric acid (β–HB) as the most represented (1.28–fold and 1.76–fold change, respectively)
In the first part of the study, we identified and confirmed a set of metabolites representative for GDM women with abnormal glucose tolerance but a normal fasting plasma glucose (FPG) level
Summary
Gestational diabetes mellitus (GDM), the most common form of metabolic complication in pregnancy (Tenenbaum-Gavish et al, 2020), is defined as any degree of glucose intolerance with the onset or first recognition during pregnancy (Sweeting et al, 2019). In 2017, GDM affected about 204 million women worldwide, with a projection to increase to 308 million by 2045, mostly in developing countries (Yahaya et al, 2020). Several factors can impact the onset of GDM, including immune function disorder, heredity, gene mutations, and especially the effect of hormones (Mdoe et al, 2021). Women who had GDM have an elevated risk to develop diabetes mellitus type 2 (T2DM) or cardiovascular diseases, as well as obesity or hyperlipidemia in later life (Plows et al, 2018). The early diagnosis of GDM could be crucial to prevent abovementioned disorders (Buchanan et al, 2012)
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