A new study1 provides the first evidence of a direct effect of maternal metabolism on fetal brain activity, suggesting that insulin resistance, the precursor to type 2 diabetes, begins its formation prenatally.
Dr. Katarzyna Linder from the University Hospital Tübingen in Germany and colleagues included in their study 13 healthy pregnant women with normal, singleton pregnancies of between 27 and 36 weeks. All of the women underwent an oral glucose tolerance test, meaning that after a 5-hour overnight fast, each woman drank a solution containing 75 g glucose. The investigators ascertained blood glucose and plasma insulin levels from blood samples taken at 0, 60, and 120 minutes.
At approximately the same time points, but before they drew each blood sample, the authors obtained a fetal magnetoencephalography (fMEG) measurement in an effort to noninvasively record brain activity in utero. During each measurement, they presented an auditory sequence to the fetus. Most (75%) of the time, the sound presented had a frequency of 500 Hz, but 25% of the time the researchers presented a deviant tone with a frequency of 750 Hz to prevent habituation.
The researchers found that maternal insulin sensitivity significantly correlated with response latency of the fetus at the 60-minute time point, so that the higher the insulin sensitivity of the mother, the shorter the response time of the fetus to the sound. The association remained significant even after the investigators controlled for relative maternal weight gain, gestational age, and the child’s birth weight. No significant correlation existed at baseline or at 120 minutes.
The investigators then split the women into 2 groups: those who were insulin-resistant and those who were insulin-sensitive. They found that the fetuses of the insulin-resistant moms were almost 40% slower to respond to the auditory stimuli than those of the insulin-sensitive moms (mean [SD], 283 [79] ms vs 178 [46] ms; P=.03).
According to the US Centers for Disease Control and Prevention, almost one-third (30.3%) of US adults between the ages of 20 and 39 years—the primary child-bearing years—are obese,2 as are 17% of our children and adolescents—triple the rate of 1 generation previous.3 Furthermore, 25.8 million people in the United States have diabetes, including 1 in every 400 children and adolescents.4
Experts know that the children of obese or diabetic mothers are at increased risk for obesity and type 2 diabetes as adults, and that the connection is not purely genetic; environmental and epigenetic (environmental elements that affect genetics) factors also play key roles. The latter is the basis for the fetal or developmental origins hypothesis,5 which posits that a pregnant woman’s exposure to certain environmental factors can affect the programming of her unborn child and impact adult health.
The authors of the current study demonstrate that the metabolism of a pregnant woman after a sugar load directly affects the response time and brain activity of her developing fetus. They suggest as a mechanism for the effect that “insulin-resistant mothers have higher glucose levels accompanied by increased insulin levels in the postprandial state. As glucose passes the placenta, these postprandially increased glucose levels induce hyperinsulinaemia in the fetus.” The resulting chronic hyperinsulinemia “might induce insulin resistance in the fetal brain.”
