The early bird catches the worm – predicting the onset of gestational diabetes in the first trimester

The ballooning incidence of gestational diabetes is extremely costly both in terms of maternal and neonatal morbidity but also in terms of immediate and long-term cost to the healthcare system. In the short-term, untreated gestational diabetes has been shown to confer a significantly increased risk of stillbirth, macrosomia, neonatal hypoglycemia, erythrocytosis, and hyperbilirubinemia [1]. In the longer-term, the children of diabetic mothers have a 21% risk of developing diabetes in later life compared to a 4% risk in the offspring of non-diabetic mothers. The fetal macrosomia characteristic of GDM is responsible for an increase in maternal morbidity, as evidenced by increased rates of caesarean and operative vaginal delivery, obstetric anal sphincter injury and prolonged parturition. Increased rates of obstetric intervention such as induction of labor and elective caesarean section are observed in the setting of gestational diabetes. The incidence of type II diabetes in mothers diagnosed with GDM is as high as 50% in the decade after the index pregnancy [2]. The development of GDM therefore should be seen as an important window into the future health of the woman and offers a real and timely opportunity to initiate education and lifestyle modifications.

There is undoubtedly a high and increasing prevalence of gestational diabetes among the obstetric population globally and current estimates put it 12.4% in the Irish population [3].

Thankfully it has definitively been shown that intervention and appropriate treatment of gestational diabetes significantly improve peri-natal outcomes [4]. Interventions targeted at preventing the onset of GDM have also been shown to result in significant healthcare cost savings.

The standard screening modality for gestational diabetes is an oral glucose tolerance test (GTT); usually performed at 24 to 28 weeks. The nature and timing of this test has been the subject of controversy but all regimens are somewhat cumbersome and do not allow for timely intervention for abnormal carbohydrate metabolism in pregnancy. It is an unpleasant test for the pregnant patient to endure and costly for the hospital to perform.

We postulate that the ability to accurately predict gestational diabetes in the first trimester of pregnancy would allow for more timely intervention aimed at reducing GDM-related short-term and long-term morbidity. Reserving the formal glucose-tolerance test only for those women deemed to be at high risk on the basis of first trimester biomarkers would have significant resource-saving implications.

Altered secretion of glycoproteins has been described in gestational diabetes [4]. It is postulated that proteins modified by intracellular glycosylation may serve as indicators of a maternal response to metabolic changes in pregnancy. Potential GDM biomarkers that have been evaluated to date include the glycoprotein adiponectin, sex-hormone binding globulin, high-sensitivity CRP (also a glycoprotein), placental lactogen and glycosylated fibronectin [5].

The vast majority of studies to date have been conducted on small case-control cohorts and not in a prospective manner. Such studies have demonstrated the above markers as being significantly associated with GDM status.

Bearing this data in mind we have commenced a large prospective cohort study which aims to examine a panel of biomarkers (high-sensitivity CRP, sex hormone binding globulin, adiponectin and 1,5 Anhydroglucitol) measured in the first trimester in patients deemed to be at risk of developing gestational diabetes to determine their value in predicting a screen positive OGTT late in the second trimester of pregnancy. Should these biomarkers serve as accurate predictive markers for gestational diabetes, major health benefits would be anticipated from early intervention and treatment along with significant savings in healthcare resources in the short-term due to selective screening with GTT and in the longer term by facilitating early intervention and reducing the burden of disease.

Declaration of interest

The authors report no conflicts of interests. The authors alone are responsible for the content and writing of this article.