Changes in Metabolites During an Oral Glucose Tolerance Test in Early and Mid-Pregnancy: Findings from the PEARLS Randomized, Controlled Lifestyle Trial
Abstract
:1. Introduction
2. Results
2.1. Influence of Intervention on Changes in Metabolites during an OGTT Among Pregnant Women
2.2. Changes in Metabolites during an OGTT
2.3. Differences in Changes in Metabolites during OGTT at Early Versus Mid-Pregnancy
2.4. Sensitivity Analyses
3. Discussion
3.1. Changes in Metabolites during an OGTT at Early Versus Mid-Pregnancy
3.2. Influence of Intervention on Changes in Metabolites during OGTT Among Pregnant Women
3.3. Study Strengths and Limitations
4. Materials and Methods
4.1. Study Population
4.2. Metabolomics Profiling
4.3. Participant Characteristics
4.4. Statistical Analysis
5. Conclusions and Future Perspectives
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Characteristic | Intervention (N = 13) | Standard Care (N = 16) |
---|---|---|
Age at randomization, years | * 30.7 ± 5.3 | * 25.6 ± 4.8 |
Body mass index, kg/m2 | 34.2 ± 7.5 | 36.2 ± 6.8 |
Educational level | ||
High school education/diploma or less | 6 (46) | 8 (50) |
College education | 7 (54) | 8 (50) |
Total annual family income | ||
≤$9999 | 5 (38.5) | 8 (50) |
$10,000–$19,999 | 5 (38.5) | 5 (31) |
≥$20,000 | 3 (23) | 3 (19) |
Marital Status | ||
Married/living with a partner | 8 (62) | 14 (87.5) |
Single/separated/divorced/widowed | 5 (38) | 2 (12.5) |
Current Smoking | 0 (0) | 0 (0) |
Any alcohol intake during pregnancy | 1 (7.7) | 0 (0) |
Parous | 9 (69) | 11 (69) |
Gestational Diabetes at 24 weeks | 2 (15) | 3 (19) |
Fasting glucose (mg/dL) | * 95.5 ± 7.6 | * 90.5 ± 4.5 |
Total energy intake, kcal/day 2 | 2501 ± 873 | 2523 ± 945 |
Metabolite | HMDB ID | Biological Description | Early Pregnancy 1 | Mid-Pregnancy 2 | ||||
---|---|---|---|---|---|---|---|---|
Intervention Mean (SD) | Control Mean (SD) | p-Value | Intervention Mean (SD) | Control Mean (SD) | p-Value | |||
myristoleoylcarnitine (C14:1) * | NA | Fatty Acid Metabolism (Acyl Carnitine, Monounsaturated) | −1.7 (0.7) | −1.5 (0.5) | 0.50 | −1.7 (0.4) | −0.9 (0.4) | ** 0.0003 |
palmitoleoylcarnitine (C16:1) * | HMDB00641 | Fatty Acid Metabolism (Acyl Carnitine, Monounsaturated) | −1.6 (0.4) | −1.5 (0.5) | 0.67 | −1.8 (0.4) | −1.0 (0.4) | ** 0.0008 |
leucine | NA | Leucine, Isoleucine and Valine Metabolism | −1.2 (1.0) | −1.6 (0.3) | 0.31 | −1.8 (0.2) | −1.3 (0.3) | 0.004 |
linoleoylcarnitine (C18:2) * | HMDB06469 | Fatty Acid Metabolism (Acyl Carnitine, Polyunsaturated) | −1.0 (0.5) | −1.2 (0.5) | 0.51 | −1.4 (0.6) | −0.6 (0.4) | 0.009 |
5-dodecenoylcarnitine (C12:1) | HMDB13326 | Fatty Acid Metabolism (Acyl Carnitine, Monounsaturated) | −1.7 (0.5) | −1.5 (0.8) | 0.52 | −1.7 (0.7) | −0.8 (0.4) | 0.01 |
myristoylcarnitine (C14) | HMDB05066 | Fatty Acid Metabolism (Acyl Carnitine, Long Chain Saturated) | −1.4 (0.6) | −1.3 (0.6) | 0.68 | −1.6 (0.5) | −0.9 (0.7) | 0.02 |
palmitoylcarnitine (C16) | HMDB00222 | Fatty Acid Metabolism (Acyl Carnitine, Long Chain Saturated) | −1.1 (0.5) | −1.2 (0.7) | 0.60 | −1.4 (0.7) | −0.6 (0.5) | 0.02 |
3-hydroxybutyrate (BHBA) | HMDB00929 | Ketone Bodies | −2.2 (0.6) | −2.0 (0.6) | 0.40 | −2.0 (0.6) | −1.3 (0.5) | 0.02 |
oleoylcarnitine (C18:1) | HMDB05065 | Fatty Acid Metabolism (Acyl Carnitine, Monounsaturated) | −1.2 (0.5) | −1.3 (0.7) | 0.81 | −1.5 (0.8) | −0.6 (0.4) | 0.02 |
asparagine | HMDB00168 | Alanine and Aspartate Metabolism | −0.7 (0.8) | −1.1 (0.6) | 0.31 | −1.4 (0.5) | −0.7 (0.7) | 0.02 |
glycodeoxycholate | HMDB00631 | Secondary Bile Acid Metabolism | 0.5 (1.0) | 0.8 (0.6) | 0.53 | 0.6 (0.4) | −0.04 (0.7) | 0.03 |
tryptophan | HMDB00357 | Tryptophan Metabolism | −0.3 (0.9) | −0.9 (0.7) | 0.23 | −0.5 (0.4) | −0.9 (0.4) | 0.03 |
glutamine | NA | Glutamate Metabolism | −1.2 (0.4) | −1.1 (0.8) | 0.62 | −1.2 (0.4) | −0.7 (0.6) | 0.04 |
adrenate (22:4n6) | HMDB02226 | Long Chain Polyunsaturated Fatty Acid (n3 and n6) | −2.2 (1.3) | −1.6 (0.8) | 0.24 | −1.7 (0.3) | −0.9 (1.2) | 0.07 |
isoleucine | HMDB00172 | Leucine, Isoleucine and Valine Metabolism | −1.4 (0.9) | −1.6 (0.3) | 0.56 | −1.7 (0.3) | −1.4 (0.3) | 0.07 |
linoleate (18:2n6) | HMDB00673 | Long Chain Polyunsaturated Fatty Acid (n3 and n6) | −2.4 (1.3) | −2.2 (0.5) | 0.61 | −2.0 (0.5) | −1.4 (0.8) | 0.08 |
ornithine | HMDB03374 | Urea cycle; Arginine and Proline Metabolism | −0.4 (0.8) | −0.3 (0.5) | 0.85 | −0.7 (0.4) | −0.4 (0.5) | 0.08 |
glycocholate | HMDB00138 | Primary Bile Acid Metabolism | 0.8 (0.6) | 0.6 (0.7) | 0.51 | 0.5 (0.8) | −0.2 (0.6) | 0.09 |
linolenate [alpha or gamma; (18:3n3 or 6)] | HMDB03073 | Long Chain Polyunsaturated Fatty Acid (n3 and n6) | −2.4 (1.1) | −2.1 (0.5) | 0.63 | −1.9 (0.4) | −1.4 (0.8) | 0.09 |
pyruvate | HMDB00243 | Glycolysis, Gluconeogenesis, and Pyruvate Metabolism | 0.7 (1.2) | 0.5 (0.9) | 0.81 | 0.6 (0.6) | 0.1 (0.5) | 0.09 |
hexanoylcarnitine (C6) | HMDB00705 | Fatty Acid Metabolism (Acyl Carnitine, Medium Chain) | −1.5 (0.4) | −1.6 (0.5) | 0.66 | −1.4 (0.5) | −1.0 (0.5) | 0.10 |
oleate/vaccenate (18:1) | NA | Long Chain Monounsaturated Fatty Acid | −2.4 (1.1) | −2.2 (0.6) | 0.66 | −2.0 (0.6) | −1.4 (0.8) | 0.10 |
acetylcarnitine (C2) | HMDB00201 | Fatty Acid Metabolism (Acyl Carnitine, Short Chain) | −1.6 (0.6) | −1.6 (0.6) | 0.93 | −1.5 (0.5) | −1.2 (0.4) | 0.12 |
glycochenodeoxycholate | HMDB00637 | Primary Bile Acid Metabolism | 1.0 (1.0) | 0.8 (0.7) | 0.62 | 0.6 (0.5) | 0.1 (0.7) | 0.12 |
palmitoleate (16:1n7) | HMDB03229 | Long Chain Monounsaturated Fatty Acid | −2.4 (1.2) | −2.2 (0.6) | 0.65 | −1.8 (0.5) | −1.4 (0.6) | 0.12 |
laurylcarnitine (C12) | HMDB02250 | Fatty Acid Metabolism (Acyl Carnitine, Medium Chain) | −1.6 (0.6) | −1.5 (0.8) | 0.87 | −1.2 (0.6) | −0.8 (0.4) | 0.13 |
tetradecadienedioate (C14:2-DC) * | NA | Fatty Acid, Dicarboxylate | −1.7 (0.5) | −1.1 (0.4) | 0.02 | −1.0 (0.2) | −0.7 (0.5) | 0.13 |
myristoleate (14:1n5) | HMDB02000 | Long Chain Monounsaturated Fatty Acid | −2.3 (0.9) | −2.2 (0.7) | 0.77 | −1.8 (0.6) | −1.3 (0.7) | 0.17 |
valine | HMDB00883 | Leucine, Isoleucine and Valine Metabolism | −0.5 (0.8) | −1.1 (0.6) | 0.15 | −1.1 (0.4) | −0.8 (0.6) | 0.18 |
methionine | HMDB00696 | Methionine, Cysteine, SAM and Taurine Metabolism | −1.3 (1.0) | −1.7 (0.6) | 0.27 | −1.7 (0.4) | −1.4 (0.4) | 0.19 |
lactate | HMDB00190 | Glycolysis, Gluconeogenesis, and Pyruvate Metabolism | 0.9 (1.2) | 0.7 (1.4) | 0.70 | 0.3 (0.8) | 0.8 (1.0) | 0.21 |
decanoylcarnitine (C10) | HMDB00651 | Fatty Acid Metabolism (Acyl Carnitine, Medium Chain) | −1.3 (0.4) | −1.3 (0.5) | 0.92 | −1.1 (0.7) | −0.7 (0.6) | 0.21 |
dimethylarginine (SDMA + ADMA) | HMDB01539 | Urea cycle; Arginine and Proline Metabolism | −0.3 (0.8) | −0.6 (0.8) | 0.57 | −1.2 (0.3) | −0.9 (0.5) | 0.22 |
octanoylcarnitine (C8) | HMDB00791 | Fatty Acid Metabolism (Acyl Carnitine, Medium Chain) | −1.3 (0.4) | −1.3 (0.5) | 0.98 | −1.1 (0.6) | −0.7 (0.5) | 0.23 |
alanine | HMDB00161 | Alanine and Aspartate Metabolism | 0.3 (0.8) | −0.3 (0.7) | 0.11 | 0.1 (0.6) | −0.2 (0.5) | 0.24 |
arginine | HMDB00517 | Urea cycle; Arginine and Proline Metabolism | −0.2 (1.4) | −0.9 (0.6) | 0.27 | −0.4 (0.7) | −0.8 (0.6) | 0.25 |
phenylalanine | HMDB00159 | Phenylalanine Metabolism | −0.7 (1.4) | −1.2 (0.6) | 0.45 | −1.4 (0.4) | −1.1 (0.6) | 0.25 |
docosapentaenoate (n6 DPA; 22:5n6) | HMDB01976 | Long Chain Polyunsaturated Fatty Acid (n3 and n6) | −2.0 (0.7) | −1.3 (0.5) | 0.06 | −1.3 (0.5) | −1.0 (0.8) | 0.33 |
isocitrate | HMDB00193 | TCA Cycle | −0.6 (0.6) | −0.6 (0.5) | 0.89 | −0.2 (0.4) | 0.2 (1.1) | 0.35 |
threonine | HMDB00167 | Glycine, Serine and Threonine Metabolism | −0.6 (0.8) | −1.1 (0.4) | 0.21 | −0.9 (0.3) | −0.8 (0.2) | 0.37 |
eicosapentaenoate (EPA; 20:5n3) | HMDB01999 | Long Chain Polyunsaturated Fatty Acid (n3 and n6) | −1.7 (0.7) | −1.3 (0.6) | 0.32 | −1.5 (0.5) | −1.2 (0.9) | 0.37 |
lysine | HMDB00182 | Lysine Metabolism | −0.5 (0.6) | −0.5 (0.6) | 0.90 | −0.8 (0.3) | −0.7 (0.4) | 0.39 |
uridine | HMDB00296 | Pyrimidine Metabolism, Uracil containing | −0.2 (0.7) | 0.6 (0.6) | 0.03 | 0.4 (0.5) | 0.1 (0.7) | 0.39 |
palmitate (16:0) | HMDB00220 | Long Chain Saturated Fatty Acid | −2.4 (1.2) | −2.1 (0.6) | 0.58 | −1.8 (0.7) | −1.5 (0.9) | 0.41 |
glycine | HMDB00123 | Glycine, Serine and Threonine Metabolism | −0.4 (0.8) | −0.8 (0.5) | 0.28 | −0.9 (0.6) | −0.7 (0.8) | 0.45 |
stearoylcarnitine (C18) | HMDB00848 | Fatty Acid Metabolism (Acyl Carnitine, Long Chain Saturated) | −0.5 (0.8) | −0.6 (1.2) | 0.78 | −0.6 (0.8) | −0.3 (0.7) | 0.46 |
betaine | HMDB00043 | Glycine, Serine and Threonine Metabolism | 1.1 (0.7) | 0.5 (0.6) | 0.08 | 0.1 (0.4) | 0.3 (0.6) | 0.46 |
stearate (18:0) | HMDB00827 | Long Chain Saturated Fatty Acid | −2.1 (1.1) | −1.9 (0.5) | 0.80 | −1.7 (1.1) | −1.3 (1.0) | 0.47 |
2-aminoadipate | HMDB00510 | Lysine Metabolism | −0.7 (0.7) | −0.1 (1.1) | 0.20 | −0.6 (1.0) | −0.2 (0.9) | 0.50 |
aspartate | HMDB00191 | Alanine and Aspartate Metabolism | 0.3 (1.4) | 0.001 (0.8) | 0.60 | −0.3 (0.8) | −0.1 (0.8) | 0.51 |
quinolinate | HMDB00232 | Nicotinate and Nicotinamide Metabolism | −0.1 (0.6) | −0.3 (0.6) | 0.54 | −0.4 (0.3) | −0.3 (0.4) | 0.52 |
histidine | HMDB00177 | Histidine Metabolism | −0.8 (0.7) | −1.0 (0.8) | 0.51 | −1.1 (0.7) | −0.9 (0.3) | 0.54 |
docosapentaenoate (n3 DPA; 22:5n3) | HMDB06528 | Long Chain Polyunsaturated Fatty Acid (n3 and n6) | −2.4 (0.9) | −1.8 (0.6) | 0.18 | −1.6 (0.6) | −1.4 (0.8) | 0.55 |
citrulline | HMDB00094 | Urea cycle; Arginine and Proline Metabolism | −1.5 (0.4) | −1.4 (0.7) | 0.78 | −1.6 (0.7) | −1.4 (0.5) | 0.59 |
urate | HMDB00289 | Purine Metabolism, (Hypo)Xanthine/Inosine containing | −0.1 (0.4) | −0.3 (0.6) | 0.35 | −0.1 (0.7) | −0.2 (0.6) | 0.64 |
fructose | HMDB00660 | Fructose, Mannose and Galactose Metabolism | 1.1 (1.3) | 0.2 (1.8) | 0.21 | 0.8 (0.8) | 0.6 (1.0) | 0.64 |
tyrosine | HMDB00158 | Tyrosine Metabolism | −1.0 (1.4) | −1.0 (0.8) | 0.98 | −0.9 (1.1) | −1.1 (1.0) | 0.66 |
proline | HMDB00162 | Urea cycle; Arginine and Proline Metabolism | −0.2 (1.0) | −0.8 (0.5) | 0.17 | −0.7 (0.3) | −0.7 (0.2) | 0.68 |
hypoxanthine | HMDB00157 | Purine Metabolism, (Hypo)Xanthine/Inosine containing | 1.4 (1.7) | 0.5 (1.5) | 0.30 | 0.2 (0.8) | 0.02 (1,0) | 0.69 |
arachidonate (20:4n6) | HMDB01043 | Long Chain Polyunsaturated Fatty Acid (n3 and n6) | −1.4 (1.1) | −1.0 (0.7) | 0.37 | −1.1 (0.8) | −0.9 (1.0) | 0.75 |
taurine | HMDB00251 | Methionine, Cysteine, SAM and Taurine Metabolism | 0.4 (1.3) | 0.3 (0.8) | 0.85 | −0.1 (1.2) | 0.1 (1.1) | 0.78 |
trans-4-hydroxyproline | HMDB00725 | Urea cycle; Arginine and Proline Metabolism | −0.8 (0.3) | −0.9 (0.4) | 0.65 | −0.4 (0.6) | −0.4 (0.5) | 0.80 |
glutamate | HMDB00148 | Glutamate Metabolism | 0.1 (1.3) | −0.2 (0.9) | 0.59 | −0.3 (0.9) | −0.3 (0.8) | 0.87 |
serine | HMDB00187 | Glycine, Serine and Threonine Metabolism | −0.6 (1.1) | −0.8 (0.7) | 0.64 | −0.9 (1.0) | −1.0 (0.6) | 0.89 |
arachidonoylcarnitine (C20:4) | NA | Fatty Acid Metabolism (Acyl Carnitine, Polyunsaturated) | −0.6 (0.4) | −0.9 (0.9) | 0.39 | −0.8 (1.0) | −0.7 (0.6) | 0.91 |
Fasting | 30 min | 60 min | 120 min | ||||
---|---|---|---|---|---|---|---|
β (SE) | p Value | β (SE) | p Value | β (SE) | p Value | ||
Early pregnancy | |||||||
PC1 | Ref. | −1.9 (0.7) | 0.005 | −5.8 (0.7) | <0.001 | −9.4 (0.7) | <0.001 |
PC2 | Ref. | −0.9 (0.7) | 0.24 | −1.8 (0.7) | 0.02 | −1.4 (0.7) | 0.05 |
Mid-Pregnancy | |||||||
PC1 | Ref. | - | - | −4.7 (1.0) | <0.001 | −7.7 (1.0) | <0.001 |
PC2 | Ref. | - | - | 0.9 (0.8) | 0.29 | 1.6 (0.8) | 0.06 |
Early and Mid-Pregnancy | |||||||
PC1 | Ref. | −1.2 (0.6) | 0.04 | −5.4 (0.5) | <0.001 | −8.8 (0.5) | <0.001 |
PC2 | Ref. | 0.1 (0.6) | 0.85 | 0.8 (0.5) | 0.10 | 0.3 (0.5) | 0.60 |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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Haslam, D.E.; Li, J.; Liang, L.; Martinez, M.; Palacios, C.; Trak-Fellermeier, M.A.; Franks, P.W.; Joshipura, K.; Bhupathiraju, S.N. Changes in Metabolites During an Oral Glucose Tolerance Test in Early and Mid-Pregnancy: Findings from the PEARLS Randomized, Controlled Lifestyle Trial. Metabolites 2020, 10, 284. https://doi.org/10.3390/metabo10070284
Haslam DE, Li J, Liang L, Martinez M, Palacios C, Trak-Fellermeier MA, Franks PW, Joshipura K, Bhupathiraju SN. Changes in Metabolites During an Oral Glucose Tolerance Test in Early and Mid-Pregnancy: Findings from the PEARLS Randomized, Controlled Lifestyle Trial. Metabolites. 2020; 10(7):284. https://doi.org/10.3390/metabo10070284
Chicago/Turabian StyleHaslam, Danielle E., Jun Li, Liming Liang, Marijulie Martinez, Cristina Palacios, Maria A. Trak-Fellermeier, Paul W. Franks, Kaumudi Joshipura, and Shilpa N. Bhupathiraju. 2020. "Changes in Metabolites During an Oral Glucose Tolerance Test in Early and Mid-Pregnancy: Findings from the PEARLS Randomized, Controlled Lifestyle Trial" Metabolites 10, no. 7: 284. https://doi.org/10.3390/metabo10070284
APA StyleHaslam, D. E., Li, J., Liang, L., Martinez, M., Palacios, C., Trak-Fellermeier, M. A., Franks, P. W., Joshipura, K., & Bhupathiraju, S. N. (2020). Changes in Metabolites During an Oral Glucose Tolerance Test in Early and Mid-Pregnancy: Findings from the PEARLS Randomized, Controlled Lifestyle Trial. Metabolites, 10(7), 284. https://doi.org/10.3390/metabo10070284