Discussion
The current study assessed the clinical implications of a low glucose 180 minutes value at the 3-hour OGTT among women with a single abnormally high OGTT value. It emerged that a suboptimal daily glucose profile was more prevalent among the women in the study group compared to women in the control group.
Insulin sensitivity has been shown to decline during pregnancy, triggering an enhanced insulin release that culminates in euglycemia after consumption of 100 gr glucose during an OGTT16. Kuhl et al. reported that women with GDM have impaired first-phase insulin response which may result in late occurrence of peak plasma insulin concentrations during an OGTT17. Women with overly impaired insulin response may experience a delayed peak in insulin blood levels at 3 hours after glucose consumption and consequent late hypoglycemia. Thus, hypoglycemia at 3 hours may represent exceedingly impaired glucose tolerance.
Delibas et al. found an association between reactive hypoglycemia during an otherwise normal OGTT and adverse perinatal outcome measures, such as low Apgar scores, low birth weights, and prenatal admission to the neonatal intensive care unit. 18 Since only women with a normal OGTT were included, the daily glucose profile was not assessed. Moreover, the sample size of their study group (pregnant women with reactive hypoglycemia) was relatively low. We were able to demonstrate a possible association between late hypoglycemia and compromised glucose control since our study group included women with a daily glucose profile that was investigated due to a single abnormal value.
To the best of our knowledge, this is the first study to describe a possible association between a low glucose result of a 3-hour 100 g diagnostic OGTT and maternal suboptimal glucose control. Daily glucose control is affected by multiple factors that are related to insulin resistance, such as fasting glucose levels during the first trimester, BMI, gestational weight gain, and previous GDM. We carried out a multivariate logistic regression analysis in order to assess the effect of late hypoglycemia evidenced during an OGTT on the glucose profile. As shown in Fig. 1, hypoglycemia at 3 hours was the only parameter associated with suboptimal glucose control with an odds ratio of 3.1 (CI, 1.35-7.83). Earlier studies had found associations between first or second trimester fasting glucose levels and the need for pharmacological intervention to achieve euglycemia in women with gestational diabetes19,20. In contrast to those findings, our study assessed women with a single abnormal value, under strict diet with similar first trimester fasting glucose values in both study and control groups. Moreover, as mentioned above, fasting glucose was not associated with suboptimal glucose control.
We anticipated that suboptimal glucose values would be reflected in the number of women requiring pharmacological treatment to lower their blood glucose levels, but the difference between the study and control groups failed to reach a level of significance. About 10% of the women in the study group needed insulin compared to 4.4% of the control group (P =.1). This may be explained by efficient interventions, such as diet modification and enhanced physical activity, that allowed us to spare many women with suboptimal glucose control from the need for treatment. Our study has some limitations that bear mention. First, its retrospective nature makes it susceptible to selection bias, potential recording errors, and difficulty in controlling for exposures and outcomes. This limitation precluded us from arriving at any definitive conclusion about the impact of late hypoglycemia during the OGTT on perinatal parameters, we found no significant difference between the groups in neonatal outcomes, including Apgar scores at 5 and 10 minutes and prevalence of NICU admission. Additionally, the study was performed in a single center that treats a relatively homogenous population of characteristically young and multiparous women, thus generalization of the findings may be open to question. Finally, the relatively low numbers of participants prevented us from demonstrating the effect of late hypoglycemia on the need for pharmacological treatment.
This study revealed a significant association between hypoglycemia at 3 hours after glucose consumption during an OGTT and suboptimal maternal glycemic control among women with a single abnormally high value in their OGTT. Stringent follow-up and meticulous glucose control may be essential for this subgroup of women.
The authors report no conflict of interest.
Contribution to authorship:
Lee Reicher, Anat Lavie, Larissa Feinmesser - Manuscript writing/editing
Sharon Maslovitz, Yariv Yogev, Lee Reicher, - Protocol/project development
Emmanuel Attali, Relly Reicher, Isca Landesberg - Data collection and management
Guy Kern -Data analysis
Details of ethics approval: IRB TLV 0273-19 Jan 2019
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors