Diabetes NewsJanuary 2012

Increased Risk of Hypertension After Gestational Diabetes Mellitus

Diabetes Care • July, 2011

Increasing evidence suggests the effect of gestational diabetes mellitus (GDM) extends beyond pregnancy for both mother and child. For instance, women with a history of GDM are at a substantially higher risk of type 2 diabetes; small-and-large vascular dysfunction; cardiovascular disease; metabolic syndrome and its components including hypertension. The current longitudinal study examines whether GDM is associated with an increased risk of hypertension later in life independent of other risk factors.

Research Design and Methods - The association between GDM and the subsequent risk of hypertension after index pregnancy was investigated among 25,305 women who reported at least one singleton pregnancy between 1991 and 2007 in the Nurses’ Health Study II.

The analysis was conducted among the 116,671 participants of the Nurses’ Health Study II, a longitudinal prospective cohort study established in 1989 and described in detail elsewhere. Questionnaires were distributed biennially to update lifestyle characteristics and health-related outcomes. The analysis included women if they reported at least one pregnancy lasting >6 months between 1991 and 2001 and were free of chronic disease. Participants were censored during follow up or if they reported a cardiovascular disease event. In all, 25,305 participants were included.

A physician diagnosis of GDM was ascertained by self-report on biannual questionnaires from 1989 through 2001, and has been previously validated. GDM is an established risk factor for type 2 diabetes, which is a well known correlate of hypertension. Participants were asked on each questionnaire if they received a physician’s diagnosis of high blood pressure (yes/no) and the date of the diagnosis, which was also previously validated.

Results - During sixteen years of follow up, GDM developed in 1,414 women (5.6%) and hypertension developed in 3,138. A multivariable Cox proportional hazards model showed women with a history of GDM had a 26% increased risk of developing hypertension compared with those without a history of GDM. The results were independent of pregnancy hypertension or subsequent type 2 diabetes.

Of the 23,305 participants included in the analysis, 1,414 (5.6%) were first exposed to GDM during their index or a subsequent pregnancy. Women with GDM were generally likely to be more obese, having a history of preeclampsia/toxemia, have a family history of diabetes/hypertension and were less likely to perform vigorous physical activity than women without GDM.

Documentation was made of 3,138 cases of hypertension during 317,892 person-years of follow up. The unadjusted incidence rate of hypertension was 1.76 cases per 100 person-years among women with GDM, and 0.95 cases per 100 person years among the unexposed. In the multivariable-adjusted model, the association was significant: exposure to GDM was associated with a 26% increased risk of hypertension. There was no evidence of effect modification by family history of hypertension, race or ethnicity.

Overall, type 2 diabetes developed in 244 participants (1%) after the index pregnancy and before hypertension or the end of follow up of whom 114 (47%) had been exposed to GDM before type 2 diabetes developed. Compared to participants without exposure to GDM or to type 2 diabetes the multivariable HR of incident hypertension was 2.55 among those who had both GDM and subsequent type 2 diabetes. This was similar to HR among women who had type 2 diabetes only. The association between GDM and incidence of hypertension remained significant among the participants who had GDM but did not subsequently develop type 2 diabetes. 

Conclusions - In a prospective cohort, researchers found that women exposed to GDM had an increased risk of hypertension in the years after pregnancy, even after adjusting for the major risk factors of hypertension. The precise underlying mechanisms for the observed association are unclear. During a normal pregnancy, insulin resistance in maternal tissues occurs to increase the glucose supply for the developing fetus. Previous research has demonstrated that women who developed GDM had an underlying susceptibility to glucose tolerance (i.e. β-cell dysfunction and chronic insulin resistance) such that they are more likely to develop GDM when facing metabolic challenges in pregnancy.  Defects in insulin sensitivity and secretion are both related to elevated hypertension risk. It is plausible that the association of GDM and subsequent hypertension reflects pre-existing common risk factors for GDM and hypertension. It is also biologically plausible that the results reflect a casual association between GDM and subsequent hypertension, such that lasting metabolic and vascular damage inflicted during pregnancy complicated by GDM increases the risk of hypertension will develop years later. However, prospective studies evaluating biologic risk factors before, during and after pregnancy are needed to further evaluate the casual association hypothesis.    

These results indicate that women with GDM are at significant increased risk of developing hypertension after their index pregnancy. A diagnosis of GDM may provide an opportunity to intervene with high-risk women years before hypertension would normally present. Further research is needed to understand the biologic mechanisms, as well as to measure the effect of GDM prevention or postpartum interventions on the long term risk of hypertension.

Reprinted with permission from the American Diabetes Association