The Value of Treatment
There is controversy in some circles about the value of treating women with gestational diabetes mellitus (GDM), a condition that occurs in about 5% of pregnancies. This article will describe evidence clearly demonstrating that treatment has been effective and that the current standard of regular screening and treatment aimed at normalizing maternal blood glucose levels should continue.
The concept of looking for a form of diabetes in pregnancy arose from the observation of high perinatal mortality in women who subsequently developed diabetes. Initial studies found a 4.3 fold increased perinatal mortality in untreated GDM compared with controls (ie., non-GDM). Since this finding there have been few prospective studies which have not included some form of therapy for all patients. Even with treatment, however, the majority of studies around the world have found an increased risk of adverse pregnancy outcomes with GDM.
Recent investigations have shown adverse perinatal outcomes with lowermaternal glucose values than would have been considered abnormal by the original Sullivan criteria. This led the Fourth International Workshop-Conference on Gestational Diabetes Mellitus to recommend lower values on the glucose tolerance test (Coustan-Carpenter) be used when diagnosing GDM. The association of GDM with adverse perinatal outcomes has been established beyond a reasonable doubt.Some people arguing for a trial examining no treatment in GDM, quote studies that show only minor complications. However, all diabetic patients in these trials received some treatment. Were the complications relatively minor because no treatment was needed or was it because the treatment given was moderately effective? This can best be answered by reviewing studies with minimal or no treatment, focusing on the most severe complications.
An important concept in all types of diabetes is that different levels of hyperglycemia (high blood sugar) are associated with different complications. Fasting glucose levels of 6.1 to 6.9 mmol are associated with an increased risk of macrovascular disease while values greater than 6.9 mmol carry an additional risk of microvascular complications including damage to the eyes (retinopathy), kidneys (renopathy), nerves (neuropathy) and blood vessels.
A direct relationship has been established between maternal blood glucose levels and perinatal mortality for all types of diabetes in pregnancy, including GDM. Patients with a mean glucose less than 5.6 mmol had a 3.8 percent perinatal mortality, compared to 16 percent when the mean blood glucose was 5.6 to 8.3 mmol and 24 percent for those greater than 8.3 mmol.
Studies focusing on GDM begin with those showing the relationship between an abnormal glucose tolerance test (GTT) and perinatal mortality in patients who were not treated. Perinatal mortality is generally 2 to 3.3 times greater in women with diabetes than in those without diabetes.
Several studies demonstrated that intensified treatment (ie., reduction) of blood glucose resulted in a marked reduction in mortality compared with previous pregnancies. Mortality was reduced from a range of 7.4 to 27.5 percent to 0 to 1.8 percent.In recent studies perinatal mortality remains at an increased level when tight glucose control was either not attempted or not achieved. A large maternity hospital in Kuwait treated GDM patients with insulin but found that the degree of patient monitoring and compliance was not as high as in many other centres.
The relative risk for total perinatal mortality was two (95% CI 1.2 to 3.7) and unexplained intrauterine deaths was 13.4 (95% CI 2.9 to 61.6) compared with controls. Another study used diet treatment for gestational diabetes if the preprandial (prior to a meal) glucose levels were 4 to 7 mmol and only started insulin when the values were greater than 7 mmol, which is much higher that currently recommended. The perinatal mortality in this study was 49.2/1000 compared to a background of 11.6/1000. While modern treatment approaches have resulted in normal perinatal mortality in recent studies, these studies demonstrate the danger of sub-optimal glucose control.
A number of studies show an increased risk of congenital malformations in GDM. Absolute risks range from 5.1 percent to 16 percent, all significantly higher than the corresponding control groups.
There is general agreement that there is an increased risk of macrosomia (abnormally large body) in GDM with its associated risks of birth trauma and operative delivery. The relative importance of hyperglycemia in the development of macrosomia in GDM has been challenged, with some believing that associated maternal age and obesity are major causative factors. A recent study clarifies this issue by finding that while maternal pregravid (before pregnancy) weight and weight gain during pregnancy were important determinants of birth weight in non-diabetics, these factors were not important if the mother had GDM.
There is growing evidence that inadequately treated GDM has lifelong adverse effects. The incidence of Type 2 diabetes is increasing at all ages and there is a great deal of interest in identifying those at high risk. High maternal glucose levels during pregnancy increase the risk of adolescent obesity and impaired glucose tolerance, an association that is independent of maternal weight and type of diabetes. There has also been interest in the finding that small birth weight, but not large birth weight, is associated with an increased risk of Type 2 diabetes. Further analysis shows that this is only true for women who do not have diabetes during their pregnancy. For infants of diabetic mothers the curve is U-shaped with both small and large birth weights carrying a significantly increased risk of early Type 2 diabetes.
Treatment of GDM has been shown to result in improved outcomes. A number of studies have now shown that perinatal outcome is directly related to maternal glucose levels and that the attainment of maternal normoglycemia will result in outcomes no different from uncomplicated pregnancies.
One large, prospective, population-based study compared conventional with intense treatment of GDM. The intense group had significantly better outcomes including less macrosomia, fewer caesarian sections, shoulder dystocias (difficult labour), metabolic complications, special care nursing admissions and shorter length of hospital stays. Outcomes in the intense group were no different from the control population without diabetes.
Finally, there is the issue of cost. Analysis has found that three dollars are saved for every dollar spent in the diagnosis and treatment of GDM.
In conclusion, untreated GDM has severe short and long term complications and intense glycemic control can reduce the risk compared to that of non-diabetic controls. The value of treatment of GDM has been proven beyond a reasonable doubt and should remain the current standard of care.
Dr. David Thompson is the acting head of the Division of Endocrinology at University of British Columbia. He is an expert in gestational diabetes and maintains a medical practice as well as a research program.
References
- Persson B., Hanson U.. Neonatal morbidities in gestational diabetes. Diabetes Care 1998; 21 (supplement 2) B1- B167.
- Langer O., Is normoglycemia the correct threshold to prevent complications in the pregnant diabetic patient? Diabetes Reviews 1996; 4:2- 10.
- Langer O., Rodriguez D., Xenakis E., Mc Farland M., Berkus M., Arredondo F.. Intensified versus conventional management of gestational diabetes. American Journal Obstetrics Gynecology 1994; 170:1036-1047.