Factors predisposing to pre-eclampsia in women with gestational diabetes

Background Lipid abnormalities occur before the onset of pre-eclampsia but their role in its pathogenesis is unclear. We tested the hypothesis that lipid abnormalities precede and contribute to the development of pre-eclampsia using women with gestational diabetes (GDM) as a focus population. Methods One hundred and eighty-four women with a diagnosis of GDM were studied. Anthropometry, blood pressure, fasting lipids, glucose homeostasis, markers of inflammation and endothelial damage were measured and family history of disease was assessed to determine those measures at diagnosis of GDM that best predicted the development of pre-eclampsia. Results Twelve percent of women with GDM developed pre-eclampsia. At diagnosis of GDM, total cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides were not different in women who subsequently developed pre-eclampsia (GDM-PE). GDM-PE had elevated body mass index, blood pressure, fasting glucose, insulin, uric acid, and C-reactive protein (CRP), which have all been linked with the ‘metabolic syndrome'. They had a greater degree of microalbuminuria and more frequently reported a family history of hypertension and maternal gestational diabetes. In logistic regression, the significant independent predictors for developing pre-eclampsia were fasting glucose, CRP, a family history of hypertension and the proband's mother having gestational diabetes. Conclusion The results suggest that, in GDM, increased severity of insulin resistance and related features of the ‘metabolic syndrome', rather than lipid abnormalities, are precursors to the development of pre-eclampsia and hence are likely to be implicated in the pathophysiology of this disorder. Moreover, these women are likely to be at particularly high risk of long-term cardiovascular disease and Type 2 diabetes.

[1]  C. Lamendola,et al.  Differentiation Between Obesity and Insulin Resistance in the Association With C-Reactive Protein , 2002, Circulation.

[2]  H. Parving,et al.  Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: progressive, interrelated, and independently associated with risk of death. , 2002, Diabetes.

[3]  I. Conget,et al.  Uric acid concentration in subjects at risk of type 2 diabetes mellitus: relationship to components of the metabolic syndrome. , 2002, Metabolism: clinical and experimental.

[4]  A. Hingorani,et al.  Levels of C‐reactive protein in pregnant women who subsequently develop pre‐eclampsia , 2002, BJOG : an international journal of obstetrics and gynaecology.

[5]  F. Lauszus,et al.  Ambulatory blood pressure as predictor of preeclampsia in diabetic pregnancies with respect to urinary albumin excretion rate and glycemic regulation , 2001, Acta obstetricia et gynecologica Scandinavica.

[6]  R. T. Lie,et al.  Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study. , 2001, BMJ : British Medical Journal.

[7]  M. Wolf,et al.  Obesity and preeclampsia: the potential role of inflammation. , 2001 .

[8]  S. Djurovic,et al.  Dyslipidemia in early second trimester is mainly a feature of women with early onset pre‐eclampsia , 2001, BJOG : an international journal of obstetrics and gynaecology.

[9]  J. Pell,et al.  Pregnancy complications and maternal risk of ischaemic heart disease: a retrospective cohort study of 129 290 births , 2001, The Lancet.

[10]  B. Balkau,et al.  Is Microalbuminuria an Integrated Risk Marker for Cardiovascular Disease and Insulin Resistance in Both Men and Women? , 2001, Journal of cardiovascular risk.

[11]  K. Borch-Johnsen,et al.  Elevated Urinary Albumin Excretion Is Associated With Impaired Arterial Dilatory Capacity in Clinically Healthy Subjects , 2001, Circulation.

[12]  J. Baeten,et al.  Pregnancy complications and outcomes among overweight and obese nulliparous women. , 2001, American journal of public health.

[13]  J. Higgins,et al.  The detection, investigation and management of hypertension in pregnancy: executive summary , 2000, The Australian & New Zealand journal of obstetrics & gynaecology.

[14]  J. Ritchie,et al.  Does a predisposition to the metabolic syndrome sensitize women to develop pre-eclampsia? , 1999, Journal of hypertension.

[15]  A. Hofman,et al.  Associations of C-reactive protein with measures of obesity, insulin resistance, and subclinical atherosclerosis in healthy, middle-aged women. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[16]  R. Dersimonian,et al.  Prostacyclin and thromboxane changes predating clinical onset of preeclampsia: a multicenter prospective study. , 1999, JAMA.

[17]  N. Schneiderman,et al.  History of gestational diabetes, insulin resistance and coronary risk. , 1999, Journal of diabetes and its complications.

[18]  H. Laivuori,et al.  Evidence of a state of increased insulin resistance in preeclampsia. , 1999, Metabolism: clinical and experimental.

[19]  S. Coppack,et al.  C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[20]  P. Damm Gestational diabetes mellitus and subsequent development of overt diabetes mellitus. , 1998, Danish medical bulletin.

[21]  M. Koga,et al.  Relationship between circulating vascular cell adhesion molecule‐1 and microvascular complications in Type 2 diabetes mellitus , 1998, Diabetic medicine : a journal of the British Diabetic Association.

[22]  J. Oats,et al.  Gestational diabetes mellitus ‐ management guidelines: The Australasian Diabetes in Pregnancy Society , 1998, The Medical journal of Australia.

[23]  J. Murai,et al.  Maternal and fetal modulators of lipid metabolism correlate with the development of preeclampsia. , 1997, Metabolism: clinical and experimental.

[24]  L. Poston,et al.  Association of gestational diabetes with abnormal maternal vascular endothelial function , 1997, British journal of obstetrics and gynaecology.

[25]  M. Hod,et al.  Microalbuminuria as an early marker of severity in hypertensive pregnant women. , 1996, Journal of human hypertension.

[26]  R. Sokol,et al.  Insulin resistance and increased body mass index in women developing hypertension in pregnancy , 1996 .

[27]  K. S. Khan,et al.  Plasma glucose and pre‐eclampsia , 1996, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[28]  D. Grobbee,et al.  Serum lipids in early pregnancy and risk of pre‐eclampsia , 1996, British journal of obstetrics and gynaecology.

[29]  A. Coats,et al.  Second trimester ambulatory blood pressure in nulliparous pregnancy: A useful screening test for preeclampsia? , 1994, British journal of obstetrics and gynaecology.

[30]  J. Ritchie,et al.  Plasma and urinary endothelin 1, prostacyclin metabolites and platelet consumption in pre-eclampsia and essential hypertensive pregnancy. , 1994, Blood pressure.

[31]  L. Poston,et al.  Abnormal endothelial cell function of resistance arteries from women with preeclampsia. , 1993, American journal of obstetrics and gynecology.

[32]  S. Sidney,et al.  A multivariate analysis of risk factors for preeclampsia , 1992, JAMA.

[33]  R N Bergman,et al.  Insulin sensitivity and B‐cell responsiveness to glucose during late pregnancy in lean and moderately obese women with normal glucose tolerance or mild gestational diabetes , 1991, American journal of obstetrics and gynecology.

[34]  David Pee,et al.  Return to a Note on Screening Regression Equations , 1989 .

[35]  J. Moutquin,et al.  A prospective study of blood pressure in pregnancy: prediction of preeclampsia. , 1985, American journal of obstetrics and gynecology.

[36]  P. Nestel,et al.  The hyperlipidemia of pregnancy in normal and complicated pregnancies. , 1979, American journal of obstetrics and gynecology.

[37]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.

[38]  E. Bonora,et al.  Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. , 2000, Diabetes care.

[39]  R. Bendel,et al.  Elevated lipoprotein lipids and gestational hormones in women with diet-treated gestational diabetes mellitus compared to healthy pregnant controls. , 1998, Journal of diabetes and its complications.