The tide has turned in our understanding of both the effects of maternal hyperglycemia and the effectiveness of current treatment approaches. Consequently, we are facing an impending sea change in the way in which gestational diabetes is diagnosed and managed.
Recent research has detailed the risks posed to a fetus exposed to hyperglycemia during pregnancy – even at levels that in the past have been considered mild and, thus, largely inconsequential. We also now have evidence that we can offer therapies for gestational diabetes mellitus (GDM) with confidence that we can use them to change the outcome for the fetus, the newborn, the child, and possibly the adult.
This impending change comes after decades of diagnosing gestational diabetes based largely on relatively arbitrary thresholds. Dr. John B. O'sullivan and statistician Claire Mahan developed the diagnostic criteria more than 40 years ago based on certain statistical phenomena associated with the development of adult-onset diabetes after pregnancy. Before then, during the 1940s, 1950s, and 1960s, 1%-2% of all pregnant women were diagnosed with GDM.
In recent years, many of us have had the experience as clinicians of delivering larger, more obese babies whose mothers had been found to have “normal” blood glucose levels. Many of us also have delivered babies with significant adiposity, sometimes perilously low blood glucose, shoulder dystocia, nerve injuries, and other complications that typically occur as a consequence of fetal overgrowth.
We often attribute these complications to a diagnostic method we have known for some time wasn't perfect, but until recently, we did not have the clinical research findings to guide us in our efforts to fine-tune the diagnosis of GDM and turn the tide.
Insights on Fetal Risk
The landmark Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, led by Dr. Boyd E. Metzger, was an attempt to clarify what level of maternal glucose intolerance is associated with an excess risk of an adverse pregnancy outcome.
The HAPO study, which involved 15 centers in nine countries, examined the outcomes of more than 25,000 pregnancies. In designing the HAPO study, Dr. Metzger and his colleagues did something that had never formally been done before: They administered a 75-g oral glucose tolerance test (OGTT) to the mothers between 24 and 32 weeks' gestation (as close to 28 weeks as possible), and defined GDM as an abnormal 2-hour 75-g OGTT result. They then followed the births of women identified as having GDM, and compared them with the births of mothers who did not have gestational diabetes as defined by traditional measures.
Outside the United States, the 75-g, one-step OGTT has been the standard for GDM diagnosis for some time. In the United States, many of us still use an awkward two-step system in which women initially are given a 50-g oral challenge. Only if they register an excessive value on the 50-g challenge do they come back for a definitive 3-hour, 100-g OGTT.
Quite a few outcomes were measured in the HAPO study, but the major outcomes were birth weight greater than the 90th percentile, the level of cord-blood serum-C-peptide (an index of fetal beta-cell function and fetal hyperinsulinemia) above the 90th percentile, and percent body fat greater than the 90th percentile.
The glucose results of the majority of women remained blinded (data were not blinded if the 2-hour plasma glucose level was greater than 200 mg/dL, or diagnostic of diabetes, or if the fasting plasma glucose level exceeded 105 mg/dL or the random plasma glucose level was 160 mg/dL). After birth and the assessment of fetal outcomes, these outcomes were arrayed against earlier results of the mothers' 2-hour 75-g glucose challenge tests and the fasting blood glucose levels, both of which were measured at the same time during pregnancy. (Fasting plasma glucose levels varied from as little as 75 mg/dL all the way up to the predefined threshold of 100 mg/dL.)
Considering percent of body fat greater than the 90th percentile, one would expect no more than 10% of babies without diagnosed GDM in the mothers to have hyperinsulinemia and large amounts of body fat.
Dr. Metzger found otherwise: 17% of babies whose mothers had a fasting blood glucose of 90 mg/dL, for instance – a level most clinicians have viewed as normal – had large levels of body fat, and many of these babies also had hyperinsulinemia. Overall, there was no “golden” level of maternal glucose that predicted a fat baby. However, neonatal adiposity increased progressively as fasting blood glucose levels rose above 80 mg/dL.
In the case of 1-hour 75-g OGTT results, fatness increased progressively at levels greater than 105 mg/dL, and with 2-hour results, fatness rose progressively at levels over 90 mg/dL (Diabetes 2009;58:453–9).