Cardiometabolic Consequences of Gestational Dysglycemia

Conclusions:

The following are 10 points to remember about cardiometabolic consequences of gestational dysglycemia:

1. The development of gestational diabetes and even milder forms of dysglycemia during pregnancy represents a maternal phenotype at increased subsequent risk of developing type 2 diabetes mellitus (DM), metabolic syndrome, and with time, overt cardiovascular disease (CVD). A careful and systematic dissection of the hormonal, metabolic, and vascular changes occurring in such women during pregnancy and over postpartum years provides a unique opportunity to identify conventional and novel conditions and biomarkers whose modification may attenuate adverse long-term outcomes, particularly cardiovascular risk.

2. The American Diabetes Association (ADA) now advises universal third trimester screening. Earlier ADA guidelines incorporated an assessment of gestational diabetes risk and recommended either a one-step approach, a diagnostic 75 g or 100 g oral glucose tolerance test alone, or a two-step process with a screening 50 g glucose challenge test at first presentation and if found positive, an oral glucose tolerance test. Women can be classified into four distinct groups by their responses: 1) normal glucose challenge test, normal glucose tolerance (normal glucose challenge test, normal oral glucose tolerance test); 2) abnormal glucose challenge test, normal glucose tolerance (elevated glucose challenge test, but normal oral glucose tolerance test); 3) gestational impaired glucose tolerance (1 elevated glucose value on oral glucose tolerance test); and 3) gestational diabetes (≥2 elevated glucose values on oral glucose tolerance test). It is now evident that these milder degrees of glucose intolerance also place the mother at increased postpartum CV risk.

3. Gestational diabetes is managed initially with diet and lifestyle modification, but if this fails, with insulin therapy. Postpartum, glycemic status should be reassessed by an oral glucose tolerance test at 6-12 weeks and then at regular intervals thereafter.

4. Women with gestational diabetes are at increased risk for CVD. In one study, questionnaires were used to evaluate CVD risk in women with a family history of DM, followed an average of 30 years after giving birth. Self-reported prevalence of CVD was significantly greater in those with gestational diabetes compared to those without gestational diabetes (adjusted odds ratio [OR], 1.85; 95% confidence interval [CI], 1.21-2.82; p = 0.005). This association remained significant, after adjustment for age, ethnicity, and menopausal status (OR, 1.66; 95% CI, 1.07-2.57; p = 0.02). In that particular study, the women with gestational diabetes who self-reported coronary artery disease were on average 7 years younger than those who did not (45.5 ± 2.2 vs. 52.5 ± 1.9 years; p = 0.02).

5. Both gestational diabetes and milder manifestations of gestational dysglycemia predispose to dysglycemia soon after delivery, and between 20-30% of women with gestational diabetes will develop type 2 diabetes within the first 5 years postpartum, in part due to persistent pancreatic β-cell dysfunction.

6. Postpartum metabolic syndrome in gestational diabetes has been well described. When one cohort of women (n = 487) who were classified 3 months postpartum on the basis of the 2005 International Federation of Diabetes Guidelines, the prevalence of the metabolic syndrome was 10% in normal glucose tolerance women, 17.6% in gestational impaired glucose tolerance women, and 20% in gestational diabetes women (p = 0.016). Gestational dysglycemia was the only independent predictor of postpartum metabolic syndrome. For gestational impaired glucose tolerance women, the OR was 2.16 (95% CI, 1.05-4.42) and for gestational diabetes women, the OR was 2.05 (95% CI, 1.07-3.94).

7. Gestational diabetes has also been observed to be an independent predictor of plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride concentrations at 3 months postpartum. A graded increase in total cholesterol (p = 0.0047), LDL cholesterol (p = 0.0002), and triglycerides (p = 0.0002) across the gestational dysglycemic classes was also observed.

8. An increased risk of postpartum hypertension in women with gestational dysglycemia also has been reported. In one study at 3 months postpartum, both women with gestational impaired glucose tolerance and women with gestational diabetes had significantly higher systolic blood pressures than controls. In another study, a cohort which included both obese and nonobese women with gestational diabetes had higher mean blood pressures at 1 year postpartum in the group of control women without gestational diabetes.

9. Endothelium-dependent dilatation, measured via flow-mediated dilatation, has also been observed to be abnormal in women with prior gestational diabetes. Four published cross-sectional studies to date, conducted at times ranging from intrapartum to 5 years postpartum, have evaluated the flow-mediated dilatation of women with gestational dysglycemia. In one study, women were studied at 3-7 months postpartum when normoglycemia was restored in subjects. Three groups were compared including obese women with previous gestational diabetes, nonobese women with previous gestational diabetes, and women who were nonobese and normoglycemic during pregnancy. Flow-mediated dilatation was significantly lower in the obese and nonobese gestational diabetes groups compared with normoglycemia women.

10. Subclinical inflammation, mediated in part through the paracrine action of adipocytes, appears present in both gestational diabetes and type 2 diabetes. Adiponectin expression is reduced in obesity, insulin resistance, and type 2 diabetes, and when measured early in pregnancy, low adiponectin concentrations are associated with an increased risk of developing gestational diabetes during pregnancy. A recent study comparing markers of inflammation in women with prior gestational diabetes found significantly higher C-reactive protein (CRP), interleukin-6, plasminogen activator-1, and lower adiponectin concentrations than in control subjects; however, after adjustment for confounders, only high CRP and low adiponectin were associated with gestational diabetes.

Perspective:

Clearly, identification of gestational diabetes as a risk factor for diabetes and cardiovascular disease will assist women and their providers to initiate cardiovascular prevention early.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Diet, Hypertension

Keywords: Life Style, Coronary Artery Disease, Diabetes Mellitus, Type 2, Postpartum Period, Blood Pressure, Insulin Resistance, Glucose Intolerance, Cholesterol, Insulin-Secreting Cells, Diabetes, Gestational, Adiponectin, Plasminogen, Cardiovascular Diseases, Obesity, Hypertension, Inflammation, Interleukin-6, Dilatation, Hypogonadism, Metabolic Syndrome X, C-Reactive Protein, Pregnancy Trimester, Third, Blood Glucose, Diet, Triglycerides


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