Gestational Diabetes

Since the 1979 publication on “classification and diagnosis of diabetes mellitus and other categories of glucose intolerance” by the National Diabetes Data Group, gestational diabetes has been defined as “carbohydrate intolerance of variable severity with onset or recognition during pregnancy.” The diagnosis and treatment of gestational diabetes focus on the prevention or reduction of adverse outcomes. However, the criteria that were proposed in 1964 by O’Sullivan and Mahan for interpretation of an oral glucose tolerance test (OGTT) during pregnancy focused on the level of risk for the development of diabetes in the mother. With modifications, these criteria remain in use in the United States in 2016. There is a longstanding controversy about the value of detecting and treating gestational diabetes. Two issues are the focus of concern. The first is whether the adverse outcomes that occur in pregnancies complicated by gestational diabetes are independently linked to maternal hyperglycemia or to confounding factors, such as obesity and/or higher maternal age. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study addressed this question. The HAPO Study demonstrated an independent association between maternal glucose from 75 g OGTTs performed at 24–32 (mean 27.8) weeks of gestation and the four independent primary study outcomes of birth weight above the 90th percentile, cord blood C-peptide above the 90th percentile, neonatal hypoglycemia, and primary cesarean delivery. Odds ratios were calculated for risk of outcomes associated with a one standard deviation increase in glucose at each of the three time points (fasting, 1-hour, and 2-hour) of the OGTT. The odds ratios, all of which were statistically significant, were in the range of 1.38–1.46 for birth weight above the 90th percentile, 1.37–1.55 for cord blood C-peptide above the 90th percentile, 1.08–1.11 for primary cesarean delivery, and 1.08–1.13 for neonatal hypoglycemia. There were no obvious thresholds at which risks increased. The second issue, whether diagnosing and treating mild gestational diabetes reduces adverse outcomes, was the focus of two large randomized clinical trials. Both trials showed significant improvement in some perinatal outcomes when gestational diabetes was diagnosed and treated compared to when caregivers were blinded to the diagnosis and gestational diabetes was not treated. For example, rates of macrosomia (birth weight ≥4,000 g) were reduced from 21% and 14% in the untreated groups to 10% and 6%, respectively, in the treated groups of the two studies. Rates of the combined outcome of preeclampsia and gestational hypertension decreased from 18% and 14% in untreated to 12% and 9%, respectively, in treated groups in the two studies. The prevalence of gestational diabetes has increased substantially from the 1980s onward in parallel with increases in the frequency of obesity and overweight, type 2 diabetes, impaired glucose tolerance, and impaired fasting glucose in the general population. For example, in pregnant women receiving prenatal care in the Northern California Kaiser Permanente Clinics, the overall frequencies of gestational diabetes were 4.7% in 1991 and 7.2% in 2000. The rate increased progressively with some year-to-year variation related to differences in age and racial/ethnic mix of the cohort. Based primarily on associations between glucose values and perinatal outcomes in the HAPO Study, the International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommended new glucose threshold values for the diagnosis of gestational diabetes (fasting, 1-hr, and 2-hr plasma glucose concentrations of 92, 180, and 153 mg/dL, respectively, with one or more values meeting or exceeding the threshold being diagnostic of gestational diabetes). Use of the IADPSG diagnostic thresholds leads to an additional increase in the prevalence of gestational diabetes. For this reason, some have recommended that more randomized treatment trials should be conducted to specifically assess the benefit of treating gestational diabetes cases that meet the IADPSG diagnostic thresholds but not older criteria for gestational diabetes. Thus, in the future as in the past, controversy about gestational diabetes is likely to remain part of diabetes in the United States.