First trimester prediction of gestational diabetes mellitus using plasma biomarkers: a case-control study
-
Paula J. Correa
, Pia Venegas
, Yasna Palmeiro , Daniela Albers , Gregory Rice , Jaime Roa , Jorge Cortez , Max Monckeberg , Manuel Schepeler , Eduardo Osorio and Sebastian E. Illanes
Abstract
Objectives
To evaluate the first trimester maternal biomarkers for early pregnancy prediction of gestational diabetes mellitus (GDM).
Methods
The study was a case-control study of healthy women with singleton pregnancies at the first trimester carried out at the Obstetrics and Gynecology Unit, Clinica Davila, Santiago, Chile. After obtaining informed consent, peripheral blood samples of pregnant women under 14 weeks of gestation were collected. At 24–28 weeks of pregnancy, women were classified as GDM (n=16) or controls (n=80) based on the results of a 75-g oral glucose tolerance test (OGTT). In all women, we measured concentrations of fasting blood glucose, insulin, glycated hemoglobin, uric acid, cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), triglycerides, aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), alkaline phosphatase (AP), sex hormone-binding globulin (SHBG), adiponectin, tissue plasminogen activator (t-PA), leptin and placental growth factor (PGF).
Results
The GDM group displayed an increased median concentration of cholesterol (P=0.04), triglycerides (P=0.003), insulin (P=0.003), t-PA (P=0.0088) and homeostatic model assessment (HOMA) (P=0.003) and an increased mean concentration of LDL (P=0.009) when compared to the control group. The receiver operating characteristic (ROC) curve for significant variables achieved an area under the curve (AUC) of 0.870, a sensitivity of 81.4% and a specificity of 80.0%. The OGTT was positive for GDM according to the IADPSG (International Diabetes in Pregnancy Study Group) criteria.
Conclusion
Women who subsequently developed GDM showed higher levels of blood-borne biomarkers during the first trimester, compared to women who did not develop GDM. These data warrant validation in a larger cohort.
Acknowledgments
We thank the Clinica Davila and the Obstetrics and Gynecology Department and Laboratory staff for their cooperation and for obtaining, storing and processing blood samples. We specially thank Stephanie Acuña from the Universidad of Los Andes Biology of Reproduction Laboratory for processing all the samples. Finally, we would like to acknowledge the contribution of Conicyt through regular FONDECYT code 1140119.
Author contributions: Sebastian Illanes developed the original idea for the study, participated in the implementation, recruited patients and acquired the grant for funding. Paula Correa designed, coordinated and implemented the project; supervised the follow-up and evaluated the result and also wrote the report and submitted the article. Pia Venegas coordinated recruitment, interviewed and educated patients, recorded patient data, supervised sample extraction and follow-up and cooperated in results analysis. Yasna Palmeiro, Daniela Albers, Max Monckeberg and Gregory Rice participated in statistical analysis. Gregory Rice also supervised the manuscript development. Jorge Cortez, Jaime Roa, Manuel Schepeler and Eduardo Osorio recruited and followed-up patients. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: We acknowledge the funding from Conicyt CONICYT, MINSAL, Funder Id: 10.13039/501100002848. Grant Code FONIS SA133i20154.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Buchanan T, Xiang A. Gestational diabetes mellitus. J Clin Invest 2005;115:485–91.10.1172/JCI200524531Search in Google Scholar
2. Albrecht S, Kuklina E, Bansil P, Jamieson D, Whiteman M, Kourtis A, et al. Diabetes trends among delivery hospitalizations in the U.S., 1994–2004. Diabetes Care 2010;33:768–73.10.2337/dc09-1801Search in Google Scholar PubMed PubMed Central
3. Godfrey K, Barker D. Fetal programming and adult health. Public Health Nutr 2001;4:611–24.10.1079/PHN2001145Search in Google Scholar PubMed
4. Yessoufou A, Moutairou K. Maternal diabetes in pregnancy: early and long-term outcomes on the offspring and the concept of metabolic memory. Exp Diabetes Res 2011;2011:218598.10.1155/2011/218598Search in Google Scholar PubMed PubMed Central
5. Standards of Medical Care in Diabetes 2016: Summary of Revisions. Diabetes Care 2015;39(Suppl 1):S4–5.10.2337/dc16-S003Search in Google Scholar PubMed
6. Landon M, Spong C, Thom E, Carpenter M, Ramin S, Casey B, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 2009;361:1339–48.10.1056/NEJMoa0902430Search in Google Scholar PubMed PubMed Central
7. Monteiro L, Norman J, Rice G, Illanes S. Fetal programming and gestational diabetes mellitus. Placenta 2016;48:S54–60.10.1016/j.placenta.2015.11.015Search in Google Scholar PubMed
8. Simmons D, Jelsma JG, Galjaard S, Devlieger R, van Assche A, Jans G, et al. Results from a European multicentre randomized trial of physical activity and/or healthy eating to reduce the risk of gestational diabetes mellitus: the DALI Lifestyle Pilot. Diabetes Care 2015;38:1650–6.10.2337/dc15-0360Search in Google Scholar PubMed
9. Ainuddin JA, Kazi S, Aftab S, Kamran A. Metformin for preventing gestational diabetes in women with polycystic ovarian syndrome. J Coll Physicians Surg Pak 2015;25:237–41.Search in Google Scholar
10. Riskin-Mashiah S, Damti A, Younes G, Auslender R. First trimester fasting hyperglycemia as a predictor for the development of gestational diabetes mellitus. Eur J Obstet Gynecol Reprod Biol 2010;152:163–7.10.1016/j.ejogrb.2010.05.036Search in Google Scholar PubMed
11. Georgiou H, Illanes S, Rice G. Novel screening approaches for the early detection of gestational diabetes mellitus. In: Radenkovic M, editor. Gestational diabetes. Chapter 1. Rijeka, Croatia: In-Tech; 2011. p. 1–20.Search in Google Scholar
12. Bito T, Foldesi I, Nyari T, Pal A. Prediction of gestational diabetes mellitus in a high-risk group by insulin measurement in early pregnancy. Diabet Med 2005;22:1434–9.10.1111/j.1464-5491.2005.01634.xSearch in Google Scholar PubMed
13. Beneventi F, Simonetta M, Lovati E, Albonico G, Tinelli C, Locatelli E, et al. First trimester pregnancy-associated plasma protein-A in pregnancies complicated by subsequent gestational diabetes. Prenat Diagn 2011;31:523–8.10.1002/pd.2733Search in Google Scholar PubMed
14. Caglar G, Ozdemir E, Cengiz S, Demirta S. Sex-hormone-binding globulin early in pregnancy for the prediction of severe gestational diabetes mellitus and related complications. J Obstet Gynaecol Res 2012;38:1286–93.10.1111/j.1447-0756.2012.01870.xSearch in Google Scholar PubMed
15. Savvidou M, Nelson S, Makgoba M, Messow C, Sattar N, Nicolaides K. First-trimester prediction of gestational diabetes mellitus: examining the potential of combining maternal characteristics and laboratory measures. Diabetes 2010;59:3017–22.10.2337/db10-0688Search in Google Scholar PubMed PubMed Central
16. Nanda S, Savvidou M, Syngelaki A, Akolekar R, Nicolaides K. Prediction of gestational diabetes mellitus by maternal factors and biomarkers at 11 to 13 weeks. Prenat Diagn 2010;31:135–41.10.1002/pd.2636Search in Google Scholar PubMed
17. International Association of Diabetes and Pregnancy Study Groups Consensus Panel. International Association of Diabetes and Pregnancy Study Groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy. Diabetes Care 2010;33:676–82.10.2337/dc09-1848Search in Google Scholar PubMed PubMed Central
18. Matthews D, Hosker J, Rudenski A, Naylor B, Treacher D, Turner R. Homeostasis model assessment: insulin resistance and B-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–9.10.1007/BF00280883Search in Google Scholar PubMed
19. Gabbay-Benziv R, Doyle LE, Blitzer M, Baschat AA. First trimester prediction of maternal glycemic status. J Perinat Med 2015;43:283–9.10.1515/jpm-2014-0149Search in Google Scholar PubMed
20. van Leeuwen M, Opmeer B, Zweers E, van Ballegooie E, ter Brugge H, de Valk H, et al. Estimating the risk of gestational diabetes mellitus: a clinical prediction model based on patient characteristics and medical history. Br J Obstet Gynecol 2010;117:69–75.10.1111/j.1471-0528.2009.02425.xSearch in Google Scholar PubMed
21. Li G, Kong L, Zhang L, Fan L, Su Y, Rose J, et al. Early pregnancy maternal lipid profiles and the risk of gestational diabetes mellitus stratified for body mass index. Reprod Sci 2014;22:712–7.10.1177/1933719114557896Search in Google Scholar PubMed PubMed Central
22. Fahami F, Torabi S, Abdoli S. Prediction of glucose intolerance at 24–28 weeks of gestation by glucose and insulin level measurements in the first trimester. Iran J Nurs Midwifery Res 2015;20:81–6.Search in Google Scholar
23. Ozcimen EE, Uckuyu A, Ciftci FC, Yanik FF, Bakar C. Diagnosis of gestational diabetes mellitus by use of the homeostasis model assessment-insulin resistance index in the first trimester. Gynecol Endocrinol 2008;24:224–9.10.1080/09513590801948416Search in Google Scholar PubMed
24. Kumru P, Arisoy R, Erdogdu E, Demirci O, Kavrut M, Ard C, et al. Prediction of gestational diabetes mellitus at first trimester in low-risk pregnancies. Taiwan J Obstet Gynecol 2016;55: 815–20.10.1016/j.tjog.2016.04.032Search in Google Scholar PubMed
25. Alptekin H, Çizmecioğlu A, Işık H, Cengiz T, Yildiz M, Iyisoy M. Predicting gestational diabetes mellitus during the first trimester using anthropometric measurements and HOMA-IR. J Endocrinol Invest 2016;39:577–83.10.1007/s40618-015-0427-zSearch in Google Scholar PubMed
26. Eliasson MC, Jansson J-H, Lindahl B, Stegmayr B. High levels of tissue plasminogen activator (tPA) antigen precede the development of type 2 diabetes in a longitudinal population study. The Northern Sweden MONICA Study. Cardiovasc Diabetol 2003;2:19.10.1186/1475-2840-2-19Search in Google Scholar PubMed PubMed Central
©2019 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Editorial
- Ultrasound Doppler waveform assessment: the story continues
- Review
- Association between increased antenatal vaginal pH and preterm birth rate: a systematic review
- Mini Review
- Update on uterine tachysystole
- Research Articles – Obstetrics
- First trimester prediction of gestational diabetes mellitus using plasma biomarkers: a case-control study
- Emergency peripartal hysterectomy – a single-center analysis of the last 13 years at a tertiary perinatal care unit
- Efficacy and safety of misoprostol vaginal insert vs. oral misoprostol for induction of labor
- Vitamin A and β-carotene in pregnant and breastfeeding post-bariatric women in an urban population
- Effect of dual tocolysis with fenoterol and atosiban in human myometrium
- Antecedents of red cell transfusion in a large contemporary obstetric cohort
- Effect of n-3 long-chain polyunsaturated fatty acids supplementation in healthy mothers on DHA and EPA profiles in maternal and umbilical blood: a randomized controlled trial
- Research Articles – Fetus
- Effect of psychotropic drugs on fetal behavior in the third trimester of pregnancy
- Prognostic value of the aortic isthmus Doppler assessment on late onset fetal growth restriction
- Doppler evaluation of the fetal pulmonary artery pressure
- Mechanisms of death in structurally normal stillbirths
- The diagnostic value of a detailed first trimester anomaly scan in fetuses with increased nuchal translucency thickness
- Research Articles – Newborn
- Small for gestational age and extremely low birth weight infant outcomes
- Does heart rate variability improve prediction of failed extubation in preterm infants?
Articles in the same Issue
- Frontmatter
- Editorial
- Ultrasound Doppler waveform assessment: the story continues
- Review
- Association between increased antenatal vaginal pH and preterm birth rate: a systematic review
- Mini Review
- Update on uterine tachysystole
- Research Articles – Obstetrics
- First trimester prediction of gestational diabetes mellitus using plasma biomarkers: a case-control study
- Emergency peripartal hysterectomy – a single-center analysis of the last 13 years at a tertiary perinatal care unit
- Efficacy and safety of misoprostol vaginal insert vs. oral misoprostol for induction of labor
- Vitamin A and β-carotene in pregnant and breastfeeding post-bariatric women in an urban population
- Effect of dual tocolysis with fenoterol and atosiban in human myometrium
- Antecedents of red cell transfusion in a large contemporary obstetric cohort
- Effect of n-3 long-chain polyunsaturated fatty acids supplementation in healthy mothers on DHA and EPA profiles in maternal and umbilical blood: a randomized controlled trial
- Research Articles – Fetus
- Effect of psychotropic drugs on fetal behavior in the third trimester of pregnancy
- Prognostic value of the aortic isthmus Doppler assessment on late onset fetal growth restriction
- Doppler evaluation of the fetal pulmonary artery pressure
- Mechanisms of death in structurally normal stillbirths
- The diagnostic value of a detailed first trimester anomaly scan in fetuses with increased nuchal translucency thickness
- Research Articles – Newborn
- Small for gestational age and extremely low birth weight infant outcomes
- Does heart rate variability improve prediction of failed extubation in preterm infants?