Insulin Resistance in Preeclampsia

Abstract

I n this issue of Hypertension, Parretti and her associates have tested the relationship of insulin resistance to preeclampsia. 1 They make 2 exciting observations. First, insulin resistance is more common in women who are destined to develop preeclampsia months before clinically evident disease. Second, simple assessments of insulin resistance based on a single determination of fasting insulin and glucose can predict preeclampsia at least as well as the current gold standard for prediction of preeclampsia, uterine artery Doppler velocimetry.Increased insulin resistance is well established to be associated with preeclampsia. 2 Its relevance as either a risk for preeclampsia or as causally important to its pathophysiology can be questioned. Most studies have not taken into account obesity, which is associated both with increased insulin resistance and with preeclampsia. There is no guarantee that insulin resistance is the mechanism by which obesity increases the risk of preeclampsia. Other relevant pathophysiological consequences of obesity include elevated inflammatory activity, 3 altered adipokines, 4 and higher concentrations of circulating asymmetrical dimethylarginine 5 (an endogenous inhibitor of NO synthase). In addition, several prior studies have identified insulin resistance only in women with manifest preeclampsia, questioning a cause and effect relationship. Parretti and colleagues avoid both pitfalls. Tests were done in early pregnancy before clinically evident preeclampsia and were limited to lean (body mass index Յ25) women. Thus, the study supports a direct association of insulin resistance and preeclampsia. Whether the insulin resistance is a component of the pathophysiology or whether it is a preexisting risk factor cannot be answered by the study. The latter would seem more likely based on the fact that insulin resistance is higher in women who have previously had preeclampsia 6 and that increased cholesterol, another component of the metabolic syndrome, can be demonstrated to be increased before a preeclamptic pregnancy. 7 How might insulin resistance increase the risk of preeclampsia? There is an extensive literature on insulin resistance and hypertension, and there are several suggestions to explain this relationship. Elevated insulin increases sympathetic tone and muscle blood flow and also in chronic settings (unlikely relevant to preeclampsia) increases vascular smooth muscle growth. 8 The effect of insulin resistance on blood pressure has been suggested by the finding that drugs that reduce insulin resistance (eg, thiazolidinediones) also lower blood pressure. 9 However, these drugs are also peroxisome proliferator activator receptor-␥ agonists and may have other effects, including inhibition of Ca 2ϩ channels, that reduce blood pressure.Insulin resistance is only one of the components of the metabolic syndrome that is present in preeclamptic women. Whether other components are the important factors is an open question. Altered lipids, especially increased free fatty acids 3 and perhaps ...

Gestational diabetes and pre-eclampsia: common antecedents?

“…The same consistency has not been reported for gestational diabetes (17). Reanalysis of this association with both outcomes is relevant, since smoking may be linked to pathophysiologic processes for both disorders (5,18,19).…”

“…Pre-eclampsia has been frequently reported as a complication of gestational diabetes (4) but the relationship between these two conditions is not well understood. Several studies suggest underlying common pathophysiology, including insulin resistance, chronic inflammation and endothelial dysfunction (5)(6)(7)(8)(9). Common risk factors, such as elevated body mass index and advanced age have been noted for each of the two conditions (10.11).…”

Recent Progress Toward the Understanding of the Pathophysiology of Hypertension During Preeclampsia

“…Although numerous factors including genetic, immunologic, behavioral, and environmental influences have been implicated in the pathogenesis of preeclampsia, the main focus of this Hypertension Highlight is to review recent studies that link endothelial dysfunction and hypertension in preeclampsia. [1][2][3][4][5][6][7][8][9][10][11] The pathophysiologic processes that underlie preeclampsia has been proposed to occur in 2 stages: stage 1, reduced placental perfusion, and stage 2, the maternal clinical syndrome. 1,4 Placental ischemia/hypoxia is believed to result in the release of a variety of placental factors that have profound effects on blood flow and arterial pressure regulation.…”

“…1,4,10,11 These factors include a host of molecules such as the soluble VEGF receptor-1 (sFlt-1), the angiotensin II type-1 receptor autoantibody (AT1-AA), and cytokines such as tumor necrosis factor (TNF)-␣ which in turn generate widespread dysfunction of the maternal vascular endothelium. [1][2][3][4][5][6][7][8][9][10][11] This dysfunction manifests as enhanced formation of factors such as endothelin, reactive oxygen species (ROS), thromboxane, 20-HETE, and augmented vascular sensitivity to angiotensin II. [1][2][3][4][5][6][7][8][9][10][11] In addition, preeclampsia is also associated with decreased formation of vasodilators such as nitric oxide (NO) and prostacyclin.…”

“…[1][2][3][4][5][6][7][8][9][10][11] In addition, preeclampsia is also associated with decreased formation of vasodilators such as nitric oxide (NO) and prostacyclin. [1][2][3][4][5][6][7][8][9][10][11] These alterations in vascular function not only lead to hypertension but multi-organ dysfunction, especially in women with early onset preeclampsia. 1,4,[11][12][13][14][15][16][17][18][19][20] Preterm preeclampsia remains a leading cause of maternal death and perinatal morbidity.…”