To date, insights into the mechanisms underlying impaired glucose regulation in GDM have not had an important impact on clinical management during pregnancy. The focus for antepartum care is on the use of standard antidiabetic treatments, mostly appropriate nutrition and exogenous insulin delivery but more recently administration of selected oral antidiabetic agents (63
), to normalize maternal pre- and postprandial glucose levels and minimize fetal overnutrition. Fetal ultrasound measurements have also been used to refine the identification of pregnancies in which the fetus demonstrates signs of excessive adiposity — pregnancies in which the need to aggressively lower maternal glucose is the greatest (66
After pregnancy, the main focus of clinical care should be on reducing the risk of diabetes and detecting and treating diabetes that does develop. Measurement of fasting glucose in the immediate postpartum period will identify women with persistent fasting hyperglycemia in the diabetic range. Other women should have an OGTT sometime during the first 2–6 months postpartum and, if not diabetic, annual testing for diabetes. Family planning is important to reduce the occurrence of unplanned pregnancies in the presence of poorly controlled diabetes (68
), a scenario that leads to serious birth defects in offspring (69
Classification of patients into 1 of the 3 major subtypes of GDM discussed in this review can aid in clinical management. Lean patients are less likely to be insulin resistant than overweight or obese patients, so autoimmune and monogenic forms of diabetes should be considered in such patients. Screening for evolving autoimmune diabetes by measuring antibodies to GAD may be warranted, particularly in women with no strong family history of diabetes who are from ethnic groups in which type 1 diabetes is relatively common. Although there are no established treatments to modify the progression to type 1 diabetes, careful monitoring of glucose levels is advised because patients can rapidly develop diabetes after pregnancy (30
). Genotyping for monogenic diabetes is still primarily a research tool, but clinical tests are being developed. Early-onset diabetes with a relevant family history (autosomal dominant inheritance for MODY; maternal inheritance for mitochondrial mutations) may provide a clue to the diagnosis. In addition, Ellard et al. (34
) have provided 4 clinical criteria that have relatively high specificity for identifying women with the glucokinase mutations that cause 1 form of MODY, MODY2: (a) persisting fasting hyperglycemia (105–145 mg/dl) after pregnancy; (b) a small (less than 82 mg/dl) increment in glucose above the fasting level during a 75-g, 2-hour OGTT; (c) insulin treatment during at least 1 pregnancy but subsequently controlled on diet; and (d) a first-degree relative with type 2 diabetes, GDM, or fasting serum or plasma glucose greater than 100 mg/dl. The constellation was infrequent in patients in the United Kingdom, but 80% of women who met all 4 criteria had glucokinase mutations. Identification of monogenic forms of diabetes is important for genetic counseling.
There is currently no clinical role for genetic testing for variants that have been associated with polygenic forms of type 2 diabetes (see “Insulin resistance, β cell dysfunction, and GDM,” above). The variants cannot be used reliably to discriminate between normal individuals and individuals affected with diabetes and, just as importantly, testing is not available to clinicians. On the other hand, recent advances in the understanding of mechanistic links between GDM and type 2 diabetes have been translated into clinical care aimed at reducing the risk of diabetes. At least 2 studies of diabetes prevention in high-risk individuals have included women with a history of GDM. In the US Diabetes Prevention Program (DPP) (70
), intensive lifestyle modification to promote weight loss and increase physical activity resulted in a 58% reduction in the risk of type 2 diabetes in adults with impaired glucose tolerance. GDM was one of the risk factors that led to inclusion in the study. Protection against diabetes was observed in all ethnic groups. Treatment with metformin in the same study also reduced the risk of diabetes, but to a lesser degree and primarily in the youngest and most overweight participants. To date, specific results from women with a history of GDM have not been published.
The Troglitazone in Prevention of Diabetes (TRIPOD) study was conducted exclusively on Hispanic women with recent GDM. Assignment to treatment with the insulin-sensitizing drug troglitazone was associated with a 55% reduction in the incidence of diabetes. Protection from diabetes was closely linked to initial reductions in endogenous insulin requirements and ultimately associated with stabilization of pancreatic β cell function (62
). Stabilization of β cell function was also observed when troglitazone treatment was started at the time of initial detection of diabetes by annual glucose tolerance testing (71
). The DPP and TRIPOD studies support clinical management that focuses on aggressive treatment of insulin resistance to reduce the risk of type 2 diabetes and, at least in Hispanic women, to preserve pancreatic β cell function.
Taken together, these 2 studies suggest that postpartum management of women with clinical characteristics suggesting a risk for type 2 diabetes should focus on treatment of insulin resistance and monitoring of glycemia both to assess success (as reflected by stabilization of glucose levels) and to detect diabetes if it develops.