Published online before print June 23, 2008, doi: 10.1161/HYPERTENSIONAHA.108.113423
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(Hypertension. 2008;52:394.)
© 2008 American Heart Association, Inc.
Original Articles |
A Relationship Between Insulin Sensitivity and Vasodilation in Women With a History of Preeclamptic Pregnancy
From the Department of Obstetrics and Gynecology (K.H.L., R.J.K.), Helsinki University Central Hospital, Helsinki, Finland; Folkhälsan Research Center (K.H.L., M.R., P.-H.G.), Biomedicum, Helsinki, Finland; Department of Medicine (M.R., P.-H.G.), Division of Nephrology, Helsinki University Central Hospital, Helsinki, Finland; and the Department of Obstetrics and Gynecology (K.H.L.), Karolinska Institute, Stockholm, Sweden.
Correspondence to Risto J. Kaaja, Helsinki University Hospital, Department of Obstetrics and Gynecology, Haartmaninkatu 2, 00290 Helsinki, Finland. E-mail risto.kaaja{at}helsinki.fi
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Abstract |
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Women with a history of preeclampsia are characterized by vascular dysfunction and an increased risk of cardiovascular disease. In the present study we investigated whether insulin sensitivity is decreased in women with previous preeclampsia and whether it is associated with endothelium-dependent and/or -independent vasodilation and/or features of metabolic syndrome. Twenty-eight nonobese women with previous severe preeclampsia and 20 women with a previous normotensive pregnancy were studied 5 to 6 years after the index pregnancy. Vasodilation was measured by venous occlusion plethysmography after intra-arterial infusions of sodium nitroprusside and acetylcholine and insulin sensitivity by the intravenous glucose tolerance test using the minimal model technique. The women were tested for lipid profile, inflammatory status and endothelial activation. Insulin sensitivity did not differ between the groups (P=0.24). Insulin sensitivity correlated positively to endothelium-dependent vasodilation only in the patient group in both low (β=0.59; P=0.04) and high (β=0.53; P=0.04) concentrations of acetylcholine and in a high concentration of sodium nitroprusside (β=0.0007; P=0.006). In multivariate analysis, the waist/hip ratio (P=0.04) and serum triglycerides (P=0.04) had the most effect on insulin sensitivity in the patient group. Gestational weeks at the onset of preeclamptic hypertension (P=0.02) and proteinuria (P=0.02) associated positively with insulin sensitivity together with first-trimester body mass index (P=0.008) and maximum diastolic blood pressure during preeclampsia (P=0.005). The present study indicates a relation between insulin sensitivity with vascular dilatory function in women with previous preeclampsia. Furthermore, early onset preeclampsia correlates with impaired insulin sensitivity later in life.
Key Words: preeclampsia • insulin sensitivity • vasodilation • cardiovascular disease • plethysmography • postpartum
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Introduction |
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Normal pregnancy exposes women to profound changes in carbohydrate, protein and lipid metabolism.1 Hypertriglyceridemia and decreased insulin sensitivity characterize the third trimester of pregnancy,2–4 facilitating the maternal response to the energy demands of the fetus. These changes seem to be even more exaggerated in preeclampsia,4–8 but the mechanisms behind them are unclear,9 and findings have not always been consistent.10,11 Nevertheless, features of the metabolic syndrome have been shown to prevail for months to several years after a preeclamptic pregnancy.12–15 Because metabolic syndrome and insulin resistance are known risk factors of cardiovascular disease,16,17 persistence of metabolic abnormalities after preeclampsia could contribute to the increased risk of cardiovascular disease in these women.18–21 This process could also be related to endothelial dysfunction, a central feature in the pathophysiology of cardiovascular disease and shared by both insulin resistance22,23 and preeclampsia.24 We have shown previously impaired endothelium-dependent and endothelium-independent vasodilation in women with a history of preeclampsia.12 The aim of this study was to find out whether insulin sensitivity is impaired in this group of women with a history of preeclamptic pregnancy and whether this insulin sensitivity would be associated with vasodilation, metabolic status, or inflammatory markers that could act as mediators of the increased cardiovascular risk in these women.
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Methods |
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Pregnancy data on women treated for preeclampsia (International Classification of Diseases, Tenth Revision, diagnosis O14.1) at Helsinki University Central Hospital during the period 1996–1998 were collected. There were 120 women who fulfilled the criteria for preeclampsia (blood pressure of
140 mm Hg [systolic] or 90 mm Hg [diastolic] on 2 occasions after the 20th week of gestation and proteinuria 300 mg/24 hour or 1+ on dipstick). The medical charts were personally reviewed to confirm the accuracy of the diagnosis and associated medical problems. Women with concomitant disease, such as diabetes or a history of gestational diabetes, chronic hypertension, and kidney disease or coagulation disorders were excluded, and only women with registered 24-hour urine sampling were included. Suitable women (reachable, white, and living near Helsinki) were contacted from the remaining sample of 83. The patient group consisted of 30 women and the control group of 21 women selected at random from the records of normal, uncomplicated pregnancies during the same time period. All of the women were examined 5 to 6 years after the index pregnancy. Two women with hypertension, diagnosed after preeclamptic pregnancy, withheld their antihypertensive medication for 3 days before the study. The 2-day study measurements were performed after an overnight fast on both days. Demographic variables were recorded and blood pressure was measured by a trained midwife.12 Blood samples were collected for the analysis of glycosylated hemoglobin, sex hormone–binding globulin, uric acid, free testosterone, lipids (total cholesterol, high density lipoproteins, and triglycerides), lipoproteins (apolipoprotein A1, apolipoprotein B, and lipoprotein [a]), and proinflammatory mediators interleukin-6, sensitive C-reactive protein, and von Willebrand factor.17,25,26 Vasodilatory capacity was measured in vivo in the forearm by means of venous occlusion plethysmography (EC 4 Strain Gauge Plethysmograph, D.E. Hokanson, Inc) after the intra-arterial infusions of the endothelium-independent vasodilator sodium nitroprusside ([SNP] Nitropress, Abbott Laboratories) at concentrations of 3 and 10 µmol/L and endothelium-dependent vasodilator acetylcholine ([ACh] Miochol-E, Laboratories CIBA Vision Faure) at concentrations of 7.5 and 15 µmol/L, as described previously in detail.12 The following day, after controlling the blood pressure, insulin sensitivity was assessed by means of the insulin-enhanced intravenous glucose tolerance test (IVGTT) with minimal model analysis (MINMOD Millennium, Minmod, Inc).27 In our study, the IVGTT (12 samples) was performed with glucose injection (0.3 g/kg) and insulin injection (0.03 U/kg) IV at 0 and 20 minutes, respectively. Blood samples were collected at baseline and at 4, 6, 8, 10, 19, 22, 29, 37, 67, 90, and 180 minutes after administration of the glucose bolus for determination of glucose and insulin levels. During the IVGTT, the patients were resting supine and were asked not to move about in the room. The glucose and insulin values were then used to estimate the parameters of the minimal model computer analysis. Insulin sensitivity is expressed as the parameter sensitivity index, which is obtained from the disappearance curves of glucose and insulin. Blood glucose was measured by the hexokinase method (Glucoquant, Roche Diagnostics) and insulin by using AutoDelfia Insulin kit (Automatic Immunoassay System [B080-101], Perkin Elmer Life and Analytic Sciences, Inc). All of the used procedures adhered to the principles of the Declaration of Helsinki and were in accordance with institutional guidelines. The study protocol was approved by the ethics committee of Helsinki University Central Hospital. Every woman gave informed written consent to participate in the study. Three women (2 from the patient group and 1 from the control group) were excluded from the analysis because of technical problems during the IVGTT. This resulted in group sizes of 28 in the patient group and 20 in the control group that were used in the analyses.
Statistics
Normally distributed data are given as means±SDs and nonnormally distributed data as medians with interquartile ranges (25th to 75th percentiles). Student t test and the Mann–Whitney U test were used to assess the differences between the groups. For categorical data we applied Fisher’s exact probability test. To explore the variables associated with insulin sensitivity, univariate and multiple linear regression analyses were performed, and log-transformed insulin sensitivity index was used as the dependent variable. The association between vasodilation and insulin sensitivity was analyzed by means of Pearson’s correlation. Analyses were performed by using NCSS 2007 (Number Cruncher Statistical Systems). Values of P<0.05 were considered statistically significant.
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Results |
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Demographic data during the index pregnancy and at the time of the study are shown in Table 1. Indices of carbohydrate, androgen, and lipid metabolism were similar between the groups; there was no difference between the groups in insulin sensitivity (sensitivity index; Table 2). The correlation of insulin sensitivity with vasodilation achieved by vasodilators ACh and SNP was tested in low and high concentrations in both groups. A positive correlation was seen at both concentrations of ACh and high concentrations of SNP, but only in the patient group (Figures 1 and 2
). Multiple regression analyses showed that this positive association was independent of body composition (waist/hip ratio [WHR]) and inflammation (sensitive C-reactive protein) and lipids (triglycerides) with the exception of a high concentration of ACh (data not shown). Univariate analysis was performed to explore the rest of the variables associated with insulin sensitivity in the patient group (Table 3) and in the control group (Table 4). Of the pregnancy variables in the patient group, insulin sensitivity was associated negatively with first-trimester body mass index (BMI) and maximum diastolic blood pressure during preeclampsia and positively with earlier onset of preeclamptic hypertension and proteinuria and birth weight of the child. Among the measurements at the study, insulin sensitivity was associated negatively with body weight, WHR, and blood pressure. Furthermore, the lipids (triglycerides, total cholesterol, and apolipoprotein B), sensitive C-reactive protein, serum testosterone, and sex hormone–binding globulin correlated with insulin sensitivity (Table 3). Three variables of the highest explanatory value (r2) in univariate analysis of the patient group were chosen for multivariate analysis: WHR, triglycerides, and diastolic blood pressure during the study. This multivariate model explained 60% of insulin sensitivity in the patient group (Table 5). In the control group, insulin sensitivity correlated only with present BMI (Table 4).
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The univariate and multivariate analyses were also performed in the whole material in the same manner as done above. The variables chosen to multivariate analysis were serum triglycerides (r2=0.31), WHR (r2=0.25), diastolic blood pressure (r2=0.24), sensitive C-reactive protein (r2=0.17), and vasodilation after SNP10 (r2=0.17). In the multivariate analysis of the whole group, impaired insulin sensitivity was associated only with diastolic blood pressure (β=–1.3; P=0.04), and the total explanatory strength of the model was 51% (data not shown).
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Discussion |
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We did not find any difference in insulin sensitivity in women with previous preeclampsia as compared with the control women. Insulin sensitivity correlated to vasodilation but only in the preeclamptic group. Of the clinically important and statistically most relevant variables, the present WHR and serum triglycerides had most effect on insulin sensitivity in previously preeclamptic women. Interestingly, severity and gestational weeks at the onset of preeclampsia (diastolic blood pressure and earlier onset of proteinuria and hypertension) were associated with later insulin sensitivity. We used an insulin-enhanced IVGTT with minimal model analysis to assess insulin sensitivity. The calculations for glucose together with secreted and exogenous insulin values provide an index (sensitivity index) that quantifies the capacity of insulin to promote glucose disposal. The results with the minimal model are well documented and correlate with those of the hyperinsulinemic euglycemic clamp procedure.28,29 Endothelial function was assessed as the change in flow in resistance vessels of the forearm resulting from vasodilation after intra-arterial infusions of vasodilatory substances. This method is regarded as the "gold standard" for assessment of endothelial function. However, it is time consuming, relatively invasive, and requires substantial cooperation from the patient.26,30 Signs of decreased insulin sensitivity in close proximity to preeclamptic pregnancy have been shown by means of the minimal model5 and various other methods,31–34 although there are opposing results.35 Some of these studies have shown increased body weight in previously preeclamptic women, and comparisons might have been influenced by overweight5,33 or differences in body composition between groups.34 Girouard et al36 showed recently how indices of insulin sensitivity seemed to be impaired in women with a previous hypertensive pregnancy, but the difference disappeared when controlling for BMI. Our results are in agreement with this notion; increasing body weight (BMI) was associated with insulin sensitivity in both groups; however, with normal and similar BMI, no difference in insulin sensitivity was observed between the groups. Nevertheless, it is interesting that insulin sensitivity was associated with central obesity (WHR) only in the patient group, although WHR was still within the normal limits and similar between the groups. These results suggest that increasing central obesity adds to the risk of insulin resistance in women with history of preeclampsia in particular. Moreover, the process might begin even before the normal limits of WHR are surpassed. This might contribute to the increased cardiovascular risk in these women.37–38 Decreased insulin sensitivity is related to impaired endothelial function.23 Most likely insulin sensitivity is the preceding feature23; however, opposing hypotheses have also been suggested.39 To our knowledge, there are no previous studies on insulin sensitivity and its relationship to vascular dilatory function during preeclampsia or after preeclamptic pregnancy. We have previously shown impaired endothelium independent and -dependent vascular dilatory capacity in women with a history of preeclampsia.12 In the present study, a significant positive association between vasodilation and insulin sensitivity was found only in the patient group. This correlation was shown in a low concentration of endothelium-independent vasodilation and both low and high concentrations of endothelium-dependent vasodilation. This positive association was independent of body composition and inflammation; however, the relation to triglycerides was not as clear. There is a well-known association between triglycerides and insulin sensitivity,17 which is apparent also in the present study, and in that light it can be regarded as comprehensible that association between vasodilation and insulin sensitivity could be affected by triglycerides. However, because this dependency on triglycerides with ACh15 was not seen in SNP10 or ACh7.5, these results remain to be confirmed. Altogether, the results suggest that there is another factor(s) having an effect on the association between vascular function and insulin sensitivity, not simply the components of metabolic syndrome. Other than the mechanisms by which insulin resistance could affect endothelial function,23 it has been hypothesized that signaling within vascular smooth muscle cells might be affected by insulin resistance.40 However, it needs to be recognized that, despite these differences in vascular dilatation in association with insulin sensitivity, the difference between the groups does not reach significance, which might be resulting from the limited size of the study material and needs to be supported in bigger materials. The observation that blood pressure was significantly higher in the patient group is similar to the findings in previous studies.19 It also had a significant association with insulin sensitivity, however, not reaching significance in multivariate analysis against WHR and serum triglycerides in the patient group. The importance of blood pressure is, however, seen in the multivariate analysis of the whole group where diastolic blood pressure is the only significant variable explaining insulin sensitivity. In previous studies, insulin resistance has been suggested to coexist or even be causally related to hypertension.41 Suggested mechanisms include impaired NO-mediated endothelial vasodilation, increased sodium retention resulting from insulin resistance, and enhanced sympathetic nervous system activity.41,42 We could not find significant association between endothelium-independent or endothelium-dependent vasodilation and blood pressure in multivariate analysis in our previous study with these women; however, we cannot rule out its impact on vasodilation because of the small study group.12 In the present study, insulin sensitivity correlated, as expected, with parameters of metabolic syndrome.43,44 Serum triglycerides had significant association with insulin sensitivity, together with WHR, in the multivariate analysis. However, we did not find evidence of more metabolic syndrome in our patient group, which could be explained by normal and similar BMI and WHR and a relatively small number of women studied. Preeclampsia is known to be more severe if it starts early in gestation,45 and such women have been suggested to be at an even greater risk for cardiovascular disease.18 In the present study, higher blood pressure during preeclampsia (diastolic) and earlier gestational weeks at the onset of preeclamptic hypertension and at the onset of proteinuria were associated with decreased insulin sensitivity in the patient group. However, the daily amount of proteinuria and the classical definition criterion for severity of preeclampsia did not correlate with later vasodilation46 and did not have any association with insulin sensitivity in the present study. Low birth weight of the child, shown to add in the risk for cardiovascular risk of the mother,18 was shown to be associated with insulin sensitivity. Thus, these study results suggest that insulin sensitivity plays a role in the increased risk for cardiovascular disease in women with a history of early onset preeclampsia. We acknowledge that the number of patients was limited. The study protocol was time consuming and relatively invasive; intra-arterial infusions of vasoactive substances require substantial cooperation and commitment of the studied person. However, this is the first study in which vascular function has been examined with plethysmography and intra-arterial infusions and results have been related to insulin sensitivity in women with previous preeclampsia.
Conclusion
After pregnancy affected by preeclampsia, the main risk factors for cardiovascular disease are still within normal limits, and the overall risk for cardiovascular disease is low. However, increasing central obesity and unfavorable lipid status in the form of increased triglycerides, together with severe, early onset preeclampsia, seem to be related to decreasing insulin sensitivity. In addition, there seems to be a close relation between insulin sensitivity and vascular dilatory function. These findings might have an impact on the increased risk of cardiovascular disease in this group of women.
Perspectives
Cardiovascular disease is the leading cause of death in women, and the incidence is not declining. In the past years, several studies have shown evidence that preeclampsia is a novel risk marker for cardiovascular disease, and it is thought to share pathogenetic mechanisms with cardiovascular disease instead of being a direct cause. Regarding shared risk factors, components of metabolic disease (increased visceral fat, blood pressure, and dyslipidemia) have been shown to be of special interest. In the present study we suggest that women with a history of severe preeclampsia respond to increased visceral fat with an enhanced insulin-resistant manner, which seems to be associated with impaired vasodilation. The earlier the onset of preeclampsia, the more insulin resistant these women are later. Gradually, in years after preeclampsia, increasing weight and visceral fat add to the risk for metabolic syndrome and cardiovascular disease. Primary prevention of cardiovascular disease in this group of women is a realistic perspective and should be undertaken, and reproductive history needs to be considered when dealing with cardiovascular medicine.
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Acknowledgments |
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We thank our research nurse Eija Kortelainen for her assistance in physical measurements and for laboratory work and Elisabeth Berg, BSc, for her help with statistical matters.
Sources of Funding
This work was financially supported by a special governmental grant for health sciences research (No. 2220), the Folkhälsan Research Foundation, Finska Läkaresällskapet, the Paulo Foundation, the Else and Wilhelm Stockmann Foundation, and the Foundation for Obstetrical and Gynecological Research (Karolinska Institute).
Disclosures
None.
Received March 17, 2008; first decision April 8, 2008; accepted May 19, 2008.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Herrera E. Metabolic adaptations in pregnancy and their implications for the availability of substrates to the fetus. Eur J Clin Nutr. 2000; 54: s47–s51.[Medline] [Order article via Infotrieve]
2. Berkowitz K. Insulin resistance and preeclampsia. Clin Perinatol. 1998; 25: 873–885.[Medline] [Order article via Infotrieve]
3. Ryan EA. Hormones and insulin resistance during pregnancy. Lancet. 2003; 29: 1777–1778.
4. Kaaja R. Insulin resistance syndrome in preeclampsia. Sem Reprod Endocrin. 1998; 16: 41–46.
5. Kaaja R, Laivuori H, Laakso M, Tikkanen MJ, Ylikorkala O. Evidence of a state of increased insulin resistance in preeclampsia. Metabolism. 1999; 48: 892–896.[CrossRef][Medline] [Order article via Infotrieve]
6. Solomon CG, Seely EW. Brief review: hypertension in pregnancy: a manifestation of the insulin resistance syndrome? Hypertension. 2001; 37: 232–239.
7. Thadhani R, Ecker JL, Mutter WP, Wolf M, Smirnakis KV, Sukhatme VP, Levine RJ, Karumanchi SA. Insulin resistance and alterations in angiogenesis: additive insults that may lead to preeclampsia. Hypertension. 2004; 43: 988–992.
8. Parretti E, Lapolla A, Dalfra M, Pacini G, Mari A, Cioni R, Marzari C, Scarselli G, Mello G. Preeclampsia in lean normotensive normotolerant pregnant women can be predicted by simple insulin sensitivity indexes. Hypertension. 2006; 47: 449–453.
9. Roberts JM, Gammill H. Insulin resistance in preeclampsia. Hypertension. 2006; 47: 341–342.
10. Caruso A, Ferrazzani S, De Carolis S, Lucchese A, Lanzone A, De Santis A, Paradisi G. Gestational hypertension but not pre-eclampsia is associated with insulin resistance syndrome characteristics. Hum Reprod. 1999; 14: 219–223.
11. Bartha JL, Romero-Carmona R, Torrejon-Cardoso R, Comino-Delgado R. Insulin, insulin-like growth factor-1, and insulin resistance in women with pregnancy-induced hypertension. Am J Obstet Gynecol. 2002; 187: 735–740.[CrossRef][Medline] [Order article via Infotrieve]
12. Lampinen K, Rönnback M, Kaaja R, Groop PH. Impaired vascular dilatation in women with a history of preeclampsia. J Hypertens. 2006; 24: 751–756.[Medline] [Order article via Infotrieve]
13. Laivuori H, Tikkanen MJ, Ylikorkala O. Hyperinsulinemia 17 years after preeclamptic first pregnancy. J Crin Endocrinol Metab. 1996; 81: 2908–2911.[CrossRef]
14. Forest JC, Girouard J, Massé J, Moutquin JM, Kharfi A, Ness RB, Roberts JM, Giguère Y. Early occurrence of metabolic syndrome after hypertension in pregnancy. Obstet Gynecol. 2005; 105: 1373–1380.[Medline] [Order article via Infotrieve]
15. Hubel CA, Snaedal S, Ness RB, Weissfeld LA, Geirsson RT, Roberts JM, Arngrimsson R. Dyslipoproteinaemia in postmenopausal women with a history of eclampsia. Br J Obstet Gynaecol. 2000; 107: 776–784.
16. Laakso M, Sarlund H, Salonen R, Suhonen M, Pyörälä K, Salonen TJ, Karhapää P. Asymptomatic atherosclerosis and insulin resistance. Arterioscler Thromb. 1991; 11: 1068–1076.
17. Reaven GM. Insulin resistance, the insulin resistance syndrome, and cardiovascular disease. Panminerva Med. 2005; 47: 201–210.[Medline] [Order article via Infotrieve]
18. Irgens HU, Reiaeter L, Irgens LM, Lie RT. Long-term mortality of mothers and fathers after pre-eclampsia: a population-based cohort study. BMJ. 2001; 323: 1213–1216.
19. Wilson BJ, Watson MS, Prescott GJ, Sunderland S, Campbell DM, Hannaford P, Smith WC. Hypertensive diseases in pregnancy and risk of hypertension and stroke in later life: results from cohort study. BMJ. 2003; 326: 845–851.
20. Haukkamaa L, Salminen M, Laivuori H, Leinonen H, Hiilesmaa V, Kaaja R. Risk for subsequent coronary artery disease after preeclampsia. Am J Cardiol. 2004; 15: 805–808.
21. Sattar N. Do pregnancy complications and CVD share common antecedents? Atherosclerosis. 2004; 5 (suppl): 3–7.[Medline] [Order article via Infotrieve]
22. Tooke JE, Hanneman MM. Adverse endothelial function and the insulin resistance syndrome. J Intern Med. 2000; 247: 425–431.[CrossRef][Medline] [Order article via Infotrieve]
23. Wheatcroft SB, Williams IL, Shah AM, Kearney MT. Pathophysiological implications of insulin resistance on vascular endothelial function. Diabet Med. 2003; 20: 255–268.[CrossRef][Medline] [Order article via Infotrieve]
24. Chambers JC, Fusi L, Malik IS, Haskard DO, DeSwiet M, Kooner JS. Association of maternal endothelial dysfunction with preeclampsia. JAMA. 2001; 285: 1607–1612.
25. Yudkin JS, Kumari M, Humphries SE, Mohamed-Ali V. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis. 2000; 148: 209–214.[CrossRef][Medline] [Order article via Infotrieve]
26. Felmeden DC, Lip GYH. Endothelial function and its assessment. Expert Opin Investig Drugs. 2005; 14: 1319–1336.[CrossRef][Medline] [Order article via Infotrieve]
27. Boston RC, Stefanovski D, Moate PJ, Sumner AE, Watanabe RM, Bergman RN. MINMOD Millenium: a computer program to calculate glucose effectiveness and insulin sensitivity from the frequently sampled intravenous glucose tolerance test. Diabetes Technol Ther. 2003; 5: 1003–1015.[CrossRef][Medline] [Order article via Infotrieve]
28. Bergman RN, Prager R, Volund A, Olefsky JM. Equivalence of the insulin sensitivity index in man derived by the minimal model method and the euglycemic glucose clamp. J Clin Invest. 1987; 79: 790–800.[Medline] [Order article via Infotrieve]
29. Saad MF, Anderson RL, Laws A, Watanabe RM, Kades WW, Chen YD, Sands RE, Pei D, Savage PJ, Bergman RN. A comparison between the minimal model and the glucose clamp in the assessment of insulin sensitivity across the spectrum of glucose tolerance. Insulin Resistance Atherosclerosis Study. Diabetes. 1994; 43: 1114–1121.[Abstract]
30. Higashi Y, Yoshizumi M. New methods to evaluate endothelial function: method for assessing endothelial function in humans using a strain-gauge plethysmography: Nitric oxide-dependent and -independent vasodilation. J Pharmacol Sci. 2003; 93: 399–404.[CrossRef][Medline] [Order article via Infotrieve]
31. Sowers JR, Standley PR, Jacober S, Niyoqi T, Simpson L. Postpartum abnormalities of carbohydrate and cellular calcium metabolism in pregnancy induced hypertension. Am J Hypertens. 1993; 6: 302–307.[Medline] [Order article via Infotrieve]
32. Fuh MMT, Yin CS, Pei D, Sheu WHH, Jeng CY, Ida Chen YD, Reaven GM. Resistance to insulin-mediated glucose uptake and hyperinsulinemia in women who had preeclampsia during pregnancy. Am J Hypertens. 1995; 8: 768–771.[CrossRef][Medline] [Order article via Infotrieve]
33. Nisell H, Erikssen C, Persson B, Carlström K. Is carbohydrate metabolism altered among women who have undergone a preeclamptic pregnancy? Gynecol Obstet Invest. 1999; 48: 241–246.[CrossRef][Medline] [Order article via Infotrieve]
34. Wolf M, Hubel CA, Lam C, Sampson M, Ecker JL, Ness RB, Rajakumar A, Daftary A, Shakir ASM, Seely E, Roberts JM, Sukhatme VP, Karumanchi SA, Thadhani R. Preeclampsia and future cardiovascular disease: potential role of altered angiogenesis and insulin resistance. J Clin Endocrinol Metab. 2004; 89: 6239–6243.
35. Jacober SJ, Morris DA, Sowers JR. Postpartum blood pressure and insulin sensitivity in African-Am women with recent preeclampsia. Am J Hypertens. 1994; 7: 933–936.[Medline] [Order article via Infotrieve]
36. Girouard J, Moutquin JM, Forest JC. Previous hypertensive disease of pregnancy is associated with alterations of markers of insulin resistance. Hypertension. 2007; 49: 1056–1062.
37. Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature. 2006; 444: 875–880.[CrossRef][Medline] [Order article via Infotrieve]
38. Ritchie SA, Connell JMC. The link between abdominal obesity, metabolic syndrome and cardiovascular disease. Nutr Metab Cardiovasc Dis. 2007; 17: 319–326.[CrossRef][Medline] [Order article via Infotrieve]
39. Pinkney JH, Stehouwer CD, Coppack SW, Yudkin JS. Endothelial dysfunction: cause of the insulin resistance syndrome. Diabetes. 1997; 46: s9–s13.[Medline] [Order article via Infotrieve]
40. Wang CC, Gurevich I, Draznin B. Insulin affects vascular smooth muscle cell phenotype and migration via distinct signaling pathways. Diabetes. 2003; 52: 2562–2569.
41. Sowers JR, Frohlich ED. Insulin and insulin resistance: impact on blood pressure and cardiovascular disease. Med Clin North Am. 2004; 88: 63–82.[CrossRef][Medline] [Order article via Infotrieve]
42. Schobel HP, Fischer T, Heuszer K, Geiger H, Schmieder RE. Preeclampsia – a state of sympathetic overactivity. N Engl J Med. 1996; 335: 1480–1485.
43. Grundy SM. Obesity, metabolic syndrome, and cardiovascular disease. J Clin Endocrinol Metab. 2004; 89: 2595–2600.
44. Alberti KG, Zimmet P, Shaw J. The metabolic syndrome – a new worldwide definition. Lancet. 2005; 366: 1059–1062.[CrossRef][Medline] [Order article via Infotrieve]
45. Anonymous. Report of the national high blood pressure education programme working group on high blood pressure in pregnancy. Am J Obstet Gynecol. 2000; 183: s1–s22.[CrossRef]
46. Lampinen K, Rönnback M, Kaaja R, Groop PH. Renal and vascular function in women with previous preeclampsia: a comparison of low- and high degree proteinuria. Kidney Int. 2006; 70: 1818–1822.[CrossRef][Medline] [Order article via Infotrieve]
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