Associations of a Preconception Biomarker Risk Score with Future Gestational Diabetes

Abstract

Individual preconception biomarkers have been associated with future gestational diabetes mellitus (GDM) risk. Creating a biomarker risk score incorporating several biomarkers may enhance identification of women at high risk for GDM before pregnancy. The objective of this study was to develop a preconception biomarker risk score and assess its association with subsequent GDM. We conducted a nested case-control study within a cohort of 4,098 women with serum and questionnaire data collected as part of a health checkup (1984-1996) and a subsequent pregnancy (1984-2009) in northern California. Two controls were matched to each GDM case (N=256 cases) on year and age at serum collection, age at pregnancy, and number of pregnancies between serum collection and index pregnancy. Biomarkers associated with GDM in univariable models were dichotomized into high/low risk using quartiles. A biomarker risk score was created by summing the number of high risk biomarkers that were significantly associated with GDM in a multivariable model. Receiver-operating-characteristic curve analyses were used to assess the incremental predictive value of the biomarker risk score beyond conventional GDM risk factors obtained from medical records (age, race/ethnicity, BMI, family history, previous GDM). Compared to low risk, high risk levels of total adiponectin (<7.2 μg/mL), SHBG (<44.2 nmol/L), and HOMA-IR (>3.9) were each independently associated with 2.03 (95% CI: 1.37, 3.02), 2.78 (95% CI: 1.87, 4.13), and 2.07 (95% CI: 1.40, 3.06) times the odds of GDM and thus included in the biomarker risk score. For each one unit increase in the biomarker risk score, odds of GDM were 2.04 times greater (95% CI: 1.62, 2.56). The biomarker risk score had relative incremental predictive value beyond conventional GDM risk factors (AUC= 0.73 vs. 0.67, P<0.0001). Our results suggest the biomarker risk score has potential clinical utility in preconception risk assessment for GDM beyond conventional clinical risk factors. Disclosure S.E. Badon: None. A. Ferrara: None. Y. Zhu: None. S.B. Sridhar: None. C. Lee: None. S. Ehrlich: None. C. Quesenberry: None. M. Hedderson: None.