Insulin Resistance and Alterations in Angiogenesis

Thadhani, Ravi; Ecker, Jeffrey L.; Mutter, Walter P.; Wolf, Myles; Smirnakis, Karen; Sukhatme, Vikas P.; Levine, Richard J.; Karumanchi, S. Ananth

doi:10.1161/01.hyp.0000124460.67539.1d

Cited by 88 publications

(31 citation statements)

References 42 publications

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“…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.…”

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confidence: 99%

Insulin Resistance in Preeclampsia

Roberts

Gammill

2006

Hypertension

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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 ...

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confidence: 99%

Insulin Resistance in Preeclampsia

Roberts

Gammill

2006

Hypertension

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“…48,49 The mechanisms by which these metabolic derangements predispose to preeclampsia are still poorly understood. Maternal prepregnancy obesity is one of the strongest modifi able risk factors for the development of preeclampsia.…”

Section: Metabolic Factorsmentioning

confidence: 99%

“…50 It has also been postulated that the additive insults of insulin resistance and alteration in angiogenesis may lead to preeclampsia. 49 Further insight into the relationships between these metabolic derangements and preeclampsia may shed more light on the pathogenesis of preeclampsia. Interventions that may correct these metabolic derangements such as good glycemic control and prepregnancy weight reduction deserve further study for the prevention of preeclampsia.…”

Section: Metabolic Factorsmentioning

confidence: 99%

Prevention of Preeclampsia: Is it Still a Disappointment?

Eddib

Yeh

2009

Clinical medicine. Women's health

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Preeclampsia is a major cause of maternal mortality worldwide, with many preventive strategies tested. In this review we intend to provide a synthesis of available studies of these strategies that have been tested, including systematic reviews. We will not be performing systematic review of the studies here. Of these strategies tested only low dose acetyl salicylic acid (ASA) and calcium can be considered helpful for prevention at this time. A recent meta-analysis showed a benefi t of low dose ASA for both high (RR 0.75, 95% CI 0.66 to 0.85) and moderate risk groups (RR 0.86, 95% CI 0.79 to 0.95). Therefore, low dose ASA in high risk groups may be useful, with a possible smaller benefi t in moderate to low risk women. Another meta-analysis looking at calcium shows benefi t for both high and low risk groups with an overall reduction in the risk of preeclampsia (RR 0.48, 95% CI 0.33 to 0.69). As a result, prenatal supplementation of calcium may be benefi cial for the prevention of preeclampsia. However, vitamins C and E, zinc, fi sh oil, and magnesium supplementation have been discounted as potential preventive strategies. Nitric oxide, folic acid, and antithrombotics have not been well studied and there is insuffi cient data for reliable conclusions to be made. Areas of ongoing research that appear promising in the prevention of preeclampsia include modifi able metabolic factors, angiogenic proteins, angiotensin receptor antibodies, and syncytiotrophoblast microparticles. Strategies targeting these areas may provide opportunities for therapeutic interventions.

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“…The level of maternal PlGF increases significantly in pregnancies complicated by non-insulin dependent diabetes or by gestational diabetes [7]. Altered angiogenesis associated with low PlGF levels and insulin resistance were shown to constitute additive insults that lead to pre-eclampsia [8]. Furthermore, hyperglycemia, as occurs in diabetes, is an important regulator of PlGF expression via upregulation of VEGF [9].…”

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confidence: 99%

“…antiplatelet medications, platelet disorders, von Willebrand factor (VWF) deficiencies or defects (i.e. von Willebrand disease; VWD)] [4,7,8]. I liken the PFA-100Ò CT to the activated partial thromboplastin time (APTT), a coagulation screening test for secondary hemostasis, and itself variably sensitive to deficiencies and defects in various clotting factors and anticoagulant medication.…”

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confidence: 99%