Glycosylated Fibronectin as a First-Trimester Biomarker for Prediction of Gestational Diabetes

OBJECTIVE: To evaluate the potential clinical utility of serum biomarkers for first-trimester prediction of gestational diabetes mellitus (GDM). METHODS: Maternal serum concentrations of glycosylated (Sambucus nigra lectin–reactive) fibronectin, adiponectin, sex hormone–binding globulin, placental lactogen, and high-sensitivity C-reactive protein (CRP) were measured at 5–13 weeks of gestation in a case-control study of 90 pregnant women with subsequent development of GDM and in 92 control group participants. Ability to detect GDM was assessed using logistic regression modeling and receiver operating characteristic (ROC) curves. Classification performance and positive and negative predictive values were reported at specific thresholds. Glycosylated fibronectin variation across trimesters was evaluated using a serial-measures analysis of 35 nondiabetic control group participants. RESULTS: First-trimester serum concentrations of glycosylated fibronectin, adiponectin, high-sensitivity CRP, and placental lactogen were significantly associated (P<.001) with GDM. After adjustment for maternal factors and other biomarkers, glycosylated fibronectin demonstrated an independent association with GDM (P<.001). Adiponectin, high-sensitivity CRP, and placental lactogen demonstrated modest classification performance compared with glycosylated fibronectin (respectively: area under the curve [AUC] 0.63; 95% confidence interval [CI] 0.53–0.71; AUC 0.68; 95% CI 0.60–0.76; and AUC 0.67, 95% CI 0.59–0.75; compared with AUC 0.91; 95% CI 0.87–0.96). Glycosylated fibronectin levels above a threshold of 120 mg/L correctly identified 57 GDM case group participants with a positive predictive value of 63% (95% CI 53–72%) and a negative predictive value of 95% (95% CI 94–95%) at a population prevalence of 12%. There was no association between sex hormone–binding globulin and GDM. CONCLUSION: First-trimester glycosylated fibronectin is a potential pregnancy-specific biomarker for early identification of women at risk for GDM. LEVEL OF EVIDENCE: II

[1]  E. Keely,et al.  [Table, International Association of Diabetes and Pregnancy Study Groups (IADPSG) and ADA Recommendations on the Diagnosis and Classification of Hyperglycemia in Pregnancy: 2010]. , 2014 .

[2]  T. Fujiwara,et al.  Prediction of gestational diabetes mellitus by soluble (pro)renin receptor during the first trimester. , 2013, The Journal of clinical endocrinology and metabolism.

[3]  J. Cullinan,et al.  Modeling the Independent Effects of Gestational Diabetes Mellitus on Maternity Care and Costs , 2013, Diabetes Care.

[4]  R. Khadgawat,et al.  Prediction of gestational diabetes mellitus at 24 to 28 weeks of gestation by using first-trimester insulin sensitivity indices in Asian Indian subjects. , 2012, Metabolism: clinical and experimental.

[5]  J. Limpens,et al.  Glucose challenge test for detecting gestational diabetes mellitus: a systematic review , 2012, BJOG : an international journal of obstetrics and gynaecology.

[6]  A. Morisset,et al.  Sex hormone-binding globulin levels and obesity in women with gestational diabetes: relationship with infant birthweight , 2011, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[7]  M. S. Kirkman,et al.  Response to Comment on: American Diabetes Association. Standards of Medical Care in Diabetes—2011. Diabetes Care 2011;34(Suppl. 1):S11–S61 , 2011, Diabetes Care.

[8]  K. Nicolaides,et al.  Maternal serum visfatin at 11-13 weeks of gestation in gestational diabetes mellitus. , 2011, Clinical chemistry.

[9]  A. Dell,et al.  Glycosylation Failure Extends to Glycoproteins in Gestational Diabetes Mellitus , 2011, Diabetes.

[10]  Surabhi Nanda,et al.  Prediction of gestational diabetes mellitus by maternal factors and biomarkers at 11 to 13 weeks , 2011, Prenatal diagnosis.

[11]  V. Basevi.  Standards of Medical Care in Diabetes—2011 , 2011, Diabetes Care.

[12]  D. Mitanchez.  Foetal and neonatal complications in gestational diabetes: perinatal mortality, congenital malformations, macrosomia, shoulder dystocia, birth injuries, neonatal complications. , 2010, Diabetes & metabolism.

[13]  N. Sattar,et al.  First-Trimester Prediction of Gestational Diabetes Mellitus: Examining the Potential of Combining Maternal Characteristics and Laboratory Measures , 2010, Diabetes.

[14]  A. Pouta,et al.  Comprehensive maternal serum proteomic profiles of preclinical and clinical preeclampsia. , 2010, Journal of proteome research.

[15]  Bengt Persson,et al.  International Association of Diabetes and Pregnancy Study Groups Recommendations on the Diagnosis and Classification of Hyperglycemia in Pregnancy , 2010, Diabetes Care.

[16]  C. Zera,et al.  Diabetes: Treatment of gestational diabetes reduces obstetric morbidity , 2010, Nature Reviews Endocrinology.

[17]  Dwight J Rouse,et al.  A multicenter, randomized trial of treatment for mild gestational diabetes. , 2009, The New England journal of medicine.

[18]  R. Moses,et al.  Point: Universal Screening for Gestational Diabetes Mellitus , 2009, Diabetes Care.

[19]  A. Hingorani,et al.  Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis , 2009, The Lancet.

[20]  P. Damm.  Future risk of diabetes in mother and child after gestational diabetes mellitus , 2009, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[21]  N. Vitoratos,et al.  Pre- and early post-partum adiponectin and Interleukin-1beta levels in women with and without gestational diabetes , 2008, Hormones.

[22]  A. Ferrara.  Increasing Prevalence of Gestational Diabetes Mellitus , 2007, Diabetes Care.

[23]  Xiao-Hua Zhou,et al.  Confidence intervals for predictive values with an emphasis to case–control studies , 2007, Statistics in medicine.

[24]  B. Zinman,et al.  Decreased high‐molecular‐weight adiponectin in gestational diabetes: implications for the pathophysiology of Type 2 diabetes , 2007, Diabetic medicine : a journal of the British Diabetic Association.

[25]  J. Hiller,et al.  Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. , 2005, The New England journal of medicine.

[26]  P. Qiu.  The Statistical Evaluation of Medical Tests for Classification and Prediction , 2005 .

[27]  G. Dohm,et al.  Gestational Diabetes is Associated with Depressed Adiponectin Levels , 2005, The Journal of the Society for Gynecologic Investigation: JSGI.

[28]  M. Pepe,et al.  Limitations of the odds ratio in gauging the performance of a diagnostic, prognostic, or screening marker. , 2004, American journal of epidemiology.

[29]  H. Martikainen,et al.  Maternal midtrimester free β‐HCG and AFP serum levels in spontaneous singleton pregnancies complicated by gestational diabetes mellitus, pregnancy‐induced hypertension or obstetric cholestasis , 2003 .

[30]  B. Zinman,et al.  C-reactive protein and gestational diabetes: the central role of maternal obesity. , 2003, The Journal of clinical endocrinology and metabolism.

[31]  T. Kempf,et al.  Induction of glycosylation in human C-reactive protein under different pathological conditions. , 2003, Biochemical Journal.

[32]  M. Wolf,et al.  First-trimester sex hormone binding globulin and subsequent gestational diabetes mellitus. , 2003, American journal of obstetrics and gynecology.

[33]  M. Pepe.  The Statistical Evaluation of Medical Tests for Classification and Prediction , 2003 .

[34]  M. Wolf,et al.  First-trimester C-reactive protein and subsequent gestational diabetes. , 2003, Diabetes care.

[35]  J. Bartha,et al.  Sex hormone‐binding globulin in gestational diabetes , 2000, Acta obstetricia et gynecologica Scandinavica.

[36]  C. Wójcikowski,et al.  [Changes in levels of human placenta lactogen (hPL), progesterone, and estriol in blood serum and estrogens in urine during gestational diabetes mellitus]. , 1995, Ginekologia polska.

[37]  G. Cooney,et al.  Sialic acid modification of adiponectin is not required for multimerization or secretion but determines half-life in circulation. , 2010, Molecular endocrinology.

[38]  Y. Jang,et al.  Standards of Medical Care in Diabetes-2010 by the American Diabetes Association: Prevention and Management of Cardiovascular Disease , 2010 .