The Potential Diabetic and Her Treatment in Pregnancy

The purpose of this study was to examine pregnancy outcome in women with abnormal oral glucose tolerance tests, in relation to treatment with diet and insulin. Glucose tolerance tests, done because of well-known historical risk factors, were considered abnormal if two or more readings exceeded the following: fasting, 110; 1 hour, 170; 2 hours, 120; and 3 hours, 110 (all in mg/100 mL, measured as total reducing substances in whole venous blood). Those with positive tests were divided randomly into a “positive-control” group (n 308) that received standard prenatal care or a “positive-treated” group (n 307) that received dietary instructions (30 kcal/kg ideal body weight, 40% as carbohydrate, and 1.5–2 g protein/kg body weight) and insulin (initial dose 10 U per day of intermediate-acting insulin, adjusted subsequently as directed by blood and urine studies), beginning at usually about 32 weeks. A third group (n 328), termed “negative controls,” had exhibited normal glucose tolerance testing. The three groups were similar, except that those with abnormal glucose tolerance tended to be older and heavier, as expected. With respect to outcome, infants with birth weights exceeding 9 lb were three times as frequent in positive-control subjects as in either positive-treated subjects or negative controls (13.1%, 4.3%, and 3.7%, respectively). Perinatal deaths (28 weeks’ gestation through 14 days after birth) were similar in the two positive groups (4.9% in control and 4.3% in treated) and significantly higher than in negative controls (1.9%), with the increase involving both fetal and neonatal components. The conclusions were 1) abnormal glucose tolerance during pregnancy leads to larger infants and higher perinatal mortality and 2) treatment with diet and insulin ameliorates the former but not the latter. This study concerned what O’Sullivan called potential diabetes and others at the time termed latent or chemical diabetes or prediabetes, but what today we refer to as gestational diabetes. Acceptance of it as a pathologic entity was far from unanimous in 1966. O’Sullivan resolved the controversy with this large, well-designed, and well-analyzed clinical trial. The immediate influence was two-fold. In the first place, it settled the existing disagreement as to whether or not impaired glucose tolerance adversely influences pregnancy outcome; large infants occurred three times as frequently and perinatal deaths were more than doubled in women with abnormal carbohydrate metabolism. Second, the findings of the intervention trial indicated clearly that treatment of gestational diabetes with diet and insulin in late gestation normalizes birth weight (although it did not seem to influence perinatal mortality), a finding confirmed a number of times by subsequent investigators. Incidentally, the frequencies of both fetal and neonatal deaths may seem high, but it needs to be remembered that this experience antedated the advent of modern fetal surveillance and neonatal intensive care. John B. O’Sullivan, a pioneer in clinical research in gestational diabetes, was an internist. He defined standards for the oral glucose tolerance test in pregnancy that, though modified slightly by subsequent investigators, are basically those in use today. Born in 1926, he received his medical education in his native Ireland before immigrating to the United States in 1955. After further training in internal medicine at the Lahey Clinic, he took a faculty position at the Boston University School of Medicine, where he did his original work on early diabetes as medical director of the Prenatal Metabolism Clinic at Boston City Hospital and chief of medicine at St. Margaret’s Hospital. In addition to his position as Associate Professor at Boston University, he also served on the faculties of the Harvard and Yale medical schools. Later he was director of employee health for the Liberty Mutual Insurance Company. He died of cancer in August 2001.