Insulin Resistance and Preeclampsia in Gestational Diabetes Mellitus

Abstract

OBJECTIVE -To compare the degree of insulin resistance in women with gestational diabetes mellitus (GDM) who do and do not develop preeclampsia.RESEARCH DESIGN AND METHODS -We conducted a prospective cohort study of initially normotensive women with GDM who underwent oral glucose tolerance tests (OGTTs), intravenous glucose tolerance tests (IVGTTs), and glucose clamp studies in the early third trimester (n ϭ 150) and 15 months postpartum (n ϭ 89). After delivery, the women were categorized as nonpreeclamptic or preeclamptic (systolic blood pressure [SBP] Ն140 mmHg, diastolic blood pressure [DBP] Ն90 mmHg, and at least Ͼ1ϩ proteinuria or Ͼ300 mg/24 h). Metabolic parameters between the groups were compared by 2 or Fisher's exact tests and ANOVA with P Ͻ 0.05 as significant.RESULTS -A total of 29 women (19%) developed preeclampsia, which was mild in 21 and severe in 8 women. At entry, there were no differences in age, weight indexes, and glycemic measures between the nonpreeclamptic and preeclamptic groups. Those with preeclampsia were significantly taller (61.5 Ϯ 2.4 vs. 60.1 Ϯ 2.3 in, P ϭ 0.003), were more often nulliparous (38 vs. 16%, P ϭ 0.01), and had higher entry SBP (112 Ϯ 10 vs. 103 Ϯ 6.9 mmHg, P Ͻ 0.0001) and DBP (64 Ϯ 9 vs. 59 Ϯ 5 mmHg, P ϭ 0.002). No significant differences between the groups were found in any measures of the OGTT glucose levels, insulin sensitivity index, glucose effectiveness, acute response to glucose, or disposition index, nor were there any differences found in the euglycemic clamp measures of basal or steady-state levels of glucose, insulin, free fatty acid, hepatic glucose output, peripheral glucose clearance, C-peptide, or glucagon. At 15 months postpartum, blood pressure levels remained significantly higher in the preeclamptic group (n ϭ 19) compared with the nonpreeclamptic group (n ϭ 70). No differences in any glycemic or insulin resistance measures were found.CONCLUSIONS -Women with GDM were uniformly insulin resistant. Those who developed preeclampsia, when compared with those who remained nonpreeclamptic, were not more insulin resistant in either the third trimester or 15 months postpartum. However, women who developed preeclampsia had blood pressure levels that were significantly higher, although still in the normal range, than those of women who remained nonpreeclamptic. Diabetes Care 28:1995-2000, 2005H ypertension, a common disorder complicating pregnancy (6 -9%), remains a leading cause of maternal mortality (ϳ15%) in the U.S. (1) and worldwide (2). Hypertensive disorders are increased two-to threefold in pregnancies complicated by diabetes, and insulin resistance has been proposed as an important etiologic factor (3). Women with pregestational and gestational diabetes mellitus (GDM) have been reported to have both increased risk of preeclampsia (10 -50 and 10 -30%, respectively) and insulin resistance when compared with women with normal glucose tolerance whose rate of preeclampsia is 5-7% (1-6). Several studies have reported an association between preeclampsia and i...

Association Between Insulin Resistance, Glucose Intolerance, and Hypertension in Pregnancy

“…Women with insulin-dependent diabetes antedating pregnancy are known to have an increased risk of hypertension in pregnancy, 27 but these women primarily have insulin deficiency rather than insulin resistance, and they often have renal dysfunction that might underlie blood pressure elevation. More recently, risk of hypertension in pregnancy has been reported by some, 18,[28][29][30][31] although not all 32,33 investigators to be increased among women with gestational diabetes, a disorder associated with underlying insulin resistance. 34 Some, 31,35 but not other, 18 studies have suggested a relation between less-striking degrees of glucose intolerance and subsequent hypertension in pregnancy.…”

Insulin resistance: The possible link between gestational diabetes mellitus and hypertensive disorders of pregnancy

“…Insulin resistance is also recognized as a key mechanism in type 1 diabetes mellitus [16,17]. Similarly, in pregnant patients, insulin resistance can escalate, especially when associated with other factors that lead to the development of PIH, GDM, or both [9].…”

“…Pregnant women with GDM have been shown in population studies to have increased risk of PIH compared with nondiabetic patients, and pregnant patients with hypertension (especially if obese) are at increased risk for developing GDM during the pregnancy [6,7]. It has been hypothesized that this association, at least in part, could be due to insulin resistance, which is a physiologic phenomenon and adaptation in normal pregnancy but that in the predisposed individual with other risk factors could lead to pathologic processes (ie, hyperinsulinemia), such as the development of PIH, GDM, or both [8][9][10]. Insulin resistance increases in severity during gestation [10] and becomes prominent in the late second and third trimesters [11,12].…”

Insulin Resistance Is Associated with Gestational Hypertension and Not with Preeclampsia: A Population-Based Screening Study

“…GH has been associated with hyperinsulinemia [2,9,10,11,12,13]. No similar associations were reported regarding the relationship between PE and IR either in normoglycemic pregnancies or in GDM [14,15,16,17,18,19]. PE is associated with a failure in the trophoblast invasion of the spiral arteries of the placenta, and it may lead to impaired uteroplacental perfusion and to the release of several vasoactive factors into maternal circulation that finally cause endothelial dysfunction, vasoconstriction and hypertension [20].…”