Role of glycemic variability in gestational diabetes mellitus (GDM): still an uphill climb

Abstract

Insulin resistance tends to increase in physiological pregnancy because of the gradually rising levels of feto-placental hormones such as progesterone, cortisol, growth hormone, prolactin, and human placental lactogen. In response to this imbalance, the pancreas normally compensates with a higher insulin secretion. When this compensatory mechanism fails, glucose intolerance develops and, in pregnancy, this is called gestational diabetes mellitus (GDM) [1]. The resulting maternal hyperglycemia gives rise to a concomitant fetal hyperinsulinemia via the placenta, leading primarily to fetal macrosomia, which is the main cause of well-known complications relating to the fetus’s development (e.g., shoulder dystocia, Erb’s paralysis, hypoxia, and acidosis) and to the course of labor (e.g., perineal laceration, cesarean section) [2]. Clinical evidence has confirmed that the main goal of glycemic management in GDM is to keep the mother’s blood glucose levels as close as possible to the normal range. A number of studies have demonstrated that macrosomia correlate with glycemic control in pregnancy complicated by diabetes [3]. It has recently been suggested that glucose variability, characterized by significant glucose excursions, may overlap with HbA1c levels in determining the risk of diabetes-related complications [4]. Oscillating blood sugar levels have been shown to increase free radicals and endothelial dysfunction, which are the links between hyperglycemia and the activation of pathological pathways that lead to tissue damage [5], and it has been reported that containing these hyperglycemic spikes coincides with a reduction in some markers of oxidative stress. In pregnancy complicated by diabetes even transient periods of hyperglycemia may lead to accelerated fetal growth, resulting in macrosomic infants. These peaks are difficult to capture using common glucose monitoring methods based on six to eight glucose measurements a day, whereas continuous glucose monitoring (CGM) systems are more revealing because they enable glucose levels to be monitored constantly throughout the day [6]. Despite recent opportunities to shed further light on the subject, glucose variability is still a poorly understood factor in GDM patients, especially its link with maternal and fetal complications. In one study, 48-h CGM was performed in all three trimesters in 31 women with GDM, and showed a close relationship between babies’ ponderal index and their mothers’ glucose variability indicators and mean glycemia in the 2nd trimester, irrespective of their HbA1c levels. This study emphasized that fetal growth in the early stages of gestation could be affected even in patients whose glycemic variability indices were only slightly higher than in controls [7]. In this issue of Endocrine, Su et al. [8] set out to use 72-h CGM to analyze several glycemic variability parameters in 30 patients with GDM, as compared with 20 healthy pregnant women and 20 healthy non-pregnant women, seeking a possible association with markers of beta-cell function. As indicators of glucose variability, they took into account the mean amplitude of glycemic excursion (MAGE), the mean of daily differences (MODD), and the standard deviation of blood glucose (SDBG); the HOMA-IR index was calculated to assess insulin resistance. The early insulinogenic index (DI30/DG30) and the area under the curve of insulin (AUCI 180) derived from 75 g oral glucose tolerance test (OGTT) were calculated to A. Lapolla (&) N. C. Chilelli Department of Medicine (DIMED), University of Padua, Via Giustiniani n 2, 35128 Padua, Italy e-mail: annunziata.lapolla@unipd.it