The letter by Dr. Robert Fraser (1) adds to the article by Paretti et al. (2) and to my editorial entitled, “What is so bad about a big baby?” (3). Fraser underscores the fact that the peak postprandial glucose response in normal healthy pregnant women is at the 1-h postprandial time point. I appreciate that he combined his two studies into one table for reference. He showed that the highest blood glucose levels in normal pregnant women are <105 mg/dl, similar to the findings in the paper by Parretti et al., and in his table the peak appears 1 h after eating (lunch at 12 noon and peak response at 1:00 p.m.). The American Diabetes Association’s treatment guidelines for pregnant diabetic women suggest that glucose levels can be as high as 140 mg/dl at the 1-h and 120 mg/dl at the 2-h postprandial time point, clearly recommending action only when the glucose is in hyperglycemic ranges, in comparison with the Parretti et al. study, our Diabetes in Early Pregnancy Trial (4), and the table presented in Dr. Fraser’s letter. Perhaps maintaining such high thresholds for action in the treatment of diabetic pregnant women may have contributed to our sustained increased prevalence of macrosomia in infants of diabetic mothers, despite “good glucose control.” It is time to reconsider our guidelines.
In addition, Dr. Fraser reminds us of his three theories as causative factors for macrosomia seen in pregnancies complicated by diabetes. Although his theories are all plausible, I would like to emphasize my belief that postprandial glucose may play the most important role by suggesting an additional theory that explains the significance of a transient postprandial elevation of maternal glucose. The renal threshold for glucose in the fetus is probably <110 mg/dl. We know this fact from the studies (5) of the renal threshold for glucose in premature neonates (<30 weeks gestation). When the maternal glucose level is >110 mg/dl, the intravenous glucose load for the fetus causes fetal glycosyria. Therefore, maternal diabetes out of control is associated with polyhydramios from fetal polyuria. After 20 weeks gestation, the fetus begins to swallow the amniotic fluid. Minor, transient elevations of blood glucose on the maternal side not only result in elevations of blood glucose on the fetal side, but also result in glucose-enriched amniotic fluid ingested by the fetus for hours. The gut stimulus for insulin production in the fetus may be more potent than the transient intravenous hyperglycemia. Thus, hyperglycemia for less than an hour once a day in the mother may produce a fetal insulin stimulus, through the oral route, for hours. Elevations of maternal glucose levels more frequently (after every meal, for example) may produce a more prolonged oral glucose load for the fetus. The “over-nutrition” of extra glucose provided to the fetus by both the intravenous route and the oral route produces an overfed, fat fetus.
I repeat: it is time to revise our guidelines for care of pregnant diabetic women to allow us to provide optimal nutrition for the fetus by taking action when the peak postprandial glucose level is elevated above the normal range. The normal range is now defined as a 1-h postprandial glucose level <105 mg/dl.
References
Address correspondence to Lois Jovanovic, Sansum Medical Research Institute, 2219 Bath St., Santa Barbara, California 93105. E-mail: [email protected].
