Metabolomic analysis reveals amino-acid responses to an oral glucose tolerance test in women with prior history of gestational diabetes mellitus

Abstract

Objective Although gestational diabetes mellitus (GDM) is associated with an increased risk of type 2 diabetes mellitus (T2DM) compared to normoglycemic pregnancies, the biochemical pathways underlying the progression of GDM to T2DM are not fully elucidated. The purpose of this exploratory study was to utilize metabolomics with an oral glucose tolerance test (OGTT) to examine the amino acid response in women with prior GDM to determine if a relationship between these metabolites and established risk factors for T2DM exists. Materials/Methods Thirty-eight non-pregnant women without diabetes but with prior GDM within the previous 3 years were recruited from a community-based population. A 75 g-OGTT was administered; fasting and 2-hr plasma samples were obtained. Metabolite profiles of 23 amino acids or amino acid derivatives were measured with gas chromatography-mass spectrometry. Measures of insulin resistance were derived from the OGTT and risk factors for T2DM were obtained by self-report. Results Twenty-two metabolite levels decreased significantly in response to the OGTT (p<0.05). The clinical covariates most powerfully associated with metabolite level changes included race, body mass index (BMI), and duration of prior breastfeeding, (mean ± SD of standardized β-coefficients, β = −0.38 ± 0.05, 0.25 ± 0.08, and 0.44 ± 0.03, respectively, all p<0.05). Notably, a prior history of breastfeeding was associated with the greatest number of metabolite changes. Conclusions Greater change in metabolite levels after a glucose challenge was significantly associated with a longer duration of breastfeeding and higher BMI. Further exploration of these preliminary observations and closer examination of the specific pathways implicated are warranted.

A systematic review of metabolite profiling in gestational diabetes mellitus

“…For example, Ho et al [15] studied a community-based population of 377 men and women with diabetes using LC-MS and found significant blunted changes after OGTT for β-hydroxybutyrate, isoleucine, lactate and pyridoxate in participants with insulin resistance compared with non-insulin-resistant individuals. Also, a pilot study of women with a history of GDM by Bentley-Lewis et al [17] reported metabolite decreases after an OGTT of similar magnitude to those found by Ho et al [15]. Moreover, Bentley-Lewis et al identified that the greatest changes in metabolite levels after an OGTT in women with a history of GDM was significantly associated with a longer duration of breastfeeding, higher BMI, increasing fasting glucose levels, race, adiponectin and parity, suggesting a relationship between metabolite profiles and behavioural and clinical characteristics [17].…”

“…Also, a pilot study of women with a history of GDM by Bentley-Lewis et al [17] reported metabolite decreases after an OGTT of similar magnitude to those found by Ho et al [15]. Moreover, Bentley-Lewis et al identified that the greatest changes in metabolite levels after an OGTT in women with a history of GDM was significantly associated with a longer duration of breastfeeding, higher BMI, increasing fasting glucose levels, race, adiponectin and parity, suggesting a relationship between metabolite profiles and behavioural and clinical characteristics [17]. Because the investigation of women with GDM often incorporates an OGTT to biochemically diagnose GDM at 24-28 weeks of gestation, future studies could include biological fluid collection for metabolomic analyses.…”

“…Because the investigation of women with GDM often incorporates an OGTT to biochemically diagnose GDM at 24-28 weeks of gestation, future studies could include biological fluid collection for metabolomic analyses. In addition, consideration of clinical and behavioural factors of the population is critical to maximally characterise the impact of metabolite profile data [17]. …”

“…Recent investigations have also suggested combining metabolomics and the OGTT as an effective method of revealing unique metabolic phenotypes [15-17]. Metabolomic analyses of samples from participants before and after an OGTT have been used to detect early shifts in metabolism during the progression from early insulin resistance to type 2 diabetes [15].…”

Lactation is associated with altered metabolomic signatures in women with gestational diabetes

“…Glycerophospholipid and BCAA levels are reported to be related to insulin resistance, type 2 diabetes and obesity [29][30][31][32][33]. Moreover, population-based studies of previously healthy adults revealed that low lyso-PC C18:2 concentrations were associated with an increased risk of pre-type 2 diabetes and type 2 diabetes [30,34], while high concentrations of several diacyl-PCs (C32:1, C36:1, C38:3 and C40:5) were associated with a risk of type 2 diabetes independent of dietary, lifestyle and anthropometric factors.…”