Biomarker Risk Score May Identify Women at Risk for Gestational Diabetes

The predictive ability of a biomarker risk score beyond established risk factors may help identify women at risk of developing gestational diabetes (GDM) before conception and help with tailoring targeted prevention strategies, according to a study recently published in the Journal of the Endocrine Society.

Researchers led by Sylvia E. Badon, PhD, of the Division of Research at Kaiser Permanente Northern California in Oakland, point out that GDM is a common complication during pregnancy, occurring in 5% to 9% of pregnancies, and that GDM carries with it a number of long- and short-term consequences for mother and child, including increased risk of diabetes and cardiovascular disease in the mother and increased risk of diabetes in the child.

The authors write that several biomarkers measure before pregnancy have been individually associated with the risk of GDM, but “previous studies have not examined the ability of multiple preconception biomarkers considered together, beyond established risk factors, to improve prediction of GDM. To the best of our knowledge, a preconception biomarker risk score has not yet been developed and assessed.” So the researchers aimed to develop a preconception biomarker risk score and test it to see how well it predicted GDM.

From 1984 to 1996, female Kaiser Permanente Northern California members were invited to complete a comprehensive health examination [multiphasic health checkup (MHC)] upon enrollment. The researchers conducted a nested case-control study within the larger cohort of women who participated in the MHC. “Of the 27,743 women, 15- to 45-year-olds who participated in the MHC from 1984 to 1996, 4,098 subsequently became pregnant and gave birth before 31 December 2010; had questionnaire and clinical data, including serum samples, available; and were free of recognized diabetes,” the authors write. “Women diagnosed with GDM were considered cases. Two controls were selected for each case from among women who did not meet the GDM case definition during the study period.” For this study, 256 confirmed cases of GDM with valid biomarker measurements were included.

High-risk levels of sex hormone-binding globulin (SHBG; <44.2 nM), glucose (>90 mg/dL), total adiponectin (<7.2 μg/mL), and homeostasis model assessment-estimated insulin resistance (HOMA-IR) (>3.9) were independently associated greater odds of GDM. “For each unit increase in the biomarker risk score, odds of GDM were 1.94 times greater (95% CI: 1.59, 2.36),” the authors write. “A biomarker risk score including only SHBG and glucose was sufficient to improve prediction beyond established risk factors (age, race/ethnicity, body mass index, family history of diabetes, previous GDM; area under the curve = 0.73 vs 0.67, P = 0.002).”

Based on these results, the authors conclude that a preconception biomarker risk score, including SHBG, glucose, adiponectin, and HOMA-IR—measured, on average, 7 years before pregnancy—was associated with future GDM risk; however, a biomarker score, including only SHBG and glucose, may be sufficient to improve substantially the predictive ability for GDM beyond established GDM risk factors. The authors also note that lifestyle interventions have limited success in early pregnancy to prevent GDM, because the processes leading to GDM begin before pregnancy, as this study shows.

“Identification of women at high risk for future GDM before pregnancy would allow for preconception interventions to attempt to alter the modifiable pathophysiologic pathways underlying the altered biomarker levels that we identified here,” the authors write.

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