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Biomedical subjects

Naveed Sattar

Publications and source records attributed to Naveed Sattar.

At least 91 records · Page 5Linked to original sources
PubMed2003

Metabolic, inflammatory and haemostatic effects of a low-dose continuous combined HRT in women with type 2 diabetes: potentially safer with respect to vascular risk?

BACKGROUND: Conventional hormone replacement therapy (HRT) containing conjugated equine oestrogen (CEE) and medroxyprogesterone acetate (MPA) increases triglyceride, C-reactive protein (CRP) and coagulation Factor VII concentrations, potentially explaining their increased coronary heart disease (CHD) and stroke risk. OBJECTIVE: To assess the metabolic effects of a continuous combined HRT containing 1 mg oestradiol and 0.5 mg norethisterone or matching placebo. DESIGN: Double-blind, randomized placebo-controlled trial. PATIENTS: Fifty women with type 2 diabetes. MEASUREMENTS: Classical and novel risk factors for vascular disease. RESULTS: Triglyceride concentration was not altered (P = 0.31, change in active arm relative to placebo) and low-density lipoprotein (LDL) cholesterol concentration declined 13% (P = 0.018). IL-6 concentration (mean difference -1.42 pg/ml, 95% CI: -2-55 to -0-29 IU/dl, P = 0.015), Factor VII (-32 IU/dl, -43 to -21 IU/l, P < 0.001) and tissue plasminogen activator antigen (by 13%, P = 0.005) concentrations fell, but CRP was not significantly altered (P = 0.62). Fasting glucose (P = 0.026) also declined significantly, but there are no significant effects on HBA1c, Factor IX or APC resistance. CONCLUSIONS: HRT containing 1 mg oestradiol and 0.5 mg norethisterone may avoid the adverse metabolic effects potentially implicated in the elevated CHD and stroke risk induced by conventional higher dose HRT. This type of preparation may therefore be more suitable than conventional HRT for women at elevated CHD risk such as those with type 2 diabetes. Large randomized controlled trials of such low dose preparations, powered for cardiovascular end points, are now needed.

Autoantigens↗
PubMed2003

Maternal docosahexaenoic acid supplementation and fetal accretion.

Docosahexaenoic acid (DHA) (22 : 6n-3) is a polyunsaturated fatty acid that is an essential constituent of membranes, particularly of the nervous system. Infants acquire DHA from their mothers, either prenatally via the placenta or postnatally in milk. The present study aimed to test the hypothesis that maternal supplementation during the second and third trimesters of pregnancy enriches maternal and/or fetal DHA status. In a randomised, prospective, double-blind study 100 mothers received either fish-oil capsules containing 400 mg DHA/g (200 mg/d) (n 50), or placebo containing 810 mg oleic acid/g (400 mg/d) (n 50) from 15 weeks gestation until term. Venous blood samples were obtained from mothers at 15, 28 and 40 weeks, and from the umbilical cord at birth. Total fatty acids in plasma and erythrocytes were analysed by GC-MS. There were no significant differences between maternal groups in baseline DHA, as a proportion of total fatty acids (g/100 g total fatty acids) or concentration (nmol/ml), in plasma and erythrocytes. DHA concentrations in plasma at 28 weeks (P=0.02) and erythrocytes at both 28 weeks (P=0.03) and term (P=0.02) were 20 % higher in supplemented mothers than the placebo group. DHA accounted for a higher proportion of total fatty acids in erythrocytes of supplemented mothers at 28 weeks (P=0.003) and term (P=0.01). There were no significant differences between groups in DHA (g/100 g total fatty acids or nmol/l) in cord blood. Maternal DHA status was maximal in mid-trimester and declined to term, at a lower rate in supplemented compared with unsupplemented mothers. Maternal DHA supplementation significantly increases maternal DHA status and limits the last trimester decline in maternal status, aiding preferential transfer of DHA from mother to fetus.

Dietary Supplements↗
PubMed2003

The G-to-T point mutation in codon 34 of the factor XIII gene and the risk of pre-eclampsia.

A G-to-T point mutation in exon 2 of the FXIII A-subunit gene results in a leucine rather than valine at amino acid position 34 of the factor XIII molecule. The presence of leucine has been associated with a reduced risk of both arterial and venous thrombosis. We examined the prevalence of this point mutation in 102 cases of pre-eclampsia and 208 matched control subjects, as inherited and acquired risk factors for arterial and venous thrombosis are associated with an increased risk of pre-eclampsia. The GT genotype was observed in 38% of controls and 29.4% of cases and the TT genotype was observed in 6.7% of controls and 5.9% of cases. In subjects heterozygous for the T genotype (GT) the relative risk of pre-eclampsia was 0.7 [95% confidence interval (CI95 ) 0.4-1.1] when compared with the GG genotype. For subjects homozygous for the T allele the relative risk for pre-eclampsia was 0.8 (CI95 0.3-2.1) when compared with the GG genotype. The risk associated with the T allele in the heterozygous and homozygous forms compared with the GG genotype was 0.7 (CI95 0.4-1.1). We conclude that the presence of leucine at this site is not associated with a protection against pre-eclampsia to the magnitude of that reported in other thrombotic disease.

Adult↗
PubMed2003

Specific elevation in plasma tissue plasminogen activator antigen concentrations in South Asians relative to Europeans.

Elevated levels of haemostatic factors including tissue plasminogen activator (t-PA) antigen are associated with coronary heart disease in Europeans but data in South Asians are sparse. We performed a cross-sectional study of 111 healthy men and women aged 40-55 years (56 European and 55 Asian) frequency matched across a wide range of body mass index (17-34 kg/m2). All subjects had detailed adiposity and metabolic measurements, and five haemostatic factors were determined. South Asians had greater insulin resistance than Europeans (fasting insulin geometric mean, 7.1 versus 4.7 microU/ml, and 2-h insulin, 37.3 versus 14.1 microU/ml, respectively). There were no significant ethnic differences in the mean concentrations of fibrinogen, factor VII, von Willebrand factor, or fibrin D-dimer (P > 0.10). However, the t-PA antigen concentration was significantly elevated in South Asians compared with Europeans (mean, 10.6 versus 8.2 ng/ml, P = 0.001). t-PA correlated positively in both ethnic groups with features of the metabolic syndrome but the ethnic difference in t-PA persisted after adjustment for adiposity, metabolic and inflammatory variables (beta = 2.0, 95% confidence interval = 0.5-3.6, P = 0.012). We therefore hypothesize that elevated t-PA antigen may be a novel mechanism contributing to increased cardiovascular risk in South Asians.

Adult↗
PubMed2003

Low triglyceride, not low cholesterol concentration, independently predicts poor outcome following acute stroke.

BACKGROUND: Recent data have shown an unexpected association between poor outcome after acute stroke and lower serum cholesterol. Triglyceride concentration has been linked to coronary heart disease and stroke; however, there are currently no data on the relationship between triglyceride and stroke outcome. Such information may yield further mechanistic information on the relationship between lipids and stroke outcome. METHODS: We studied 1,310 nondiabetic patients presenting to our acute stroke unit with computed tomography-confirmed acute stroke. Fasting blood samples were drawn within 24 h of admission for glucose, lipids and a standard battery of biochemistry and hematological tests. Information on age, stroke type, admission blood pressure, smoking status, presence of atrial fibrillation, resolution time of symptoms and Oxfordshire Community Stroke Project clinical classification was collated. Stepwise proportional hazards regression was used to estimate the effect of the above variables on survival following stroke. RESULTS: Increased age (p < 0.0001), presence of atrial fibrillation (p = 0.009), hyperglycemia (p = 0.0005) and lower triglyceride level (p < 0.0001) independently predicted higher mortality; early resolution of symptoms (p = 0.005) independently predicted lower mortality. Although serum cholesterol level predicted outcome after adjusting for other prognostic factors, it did not remain significant when triglyceride level was entered into the model. The relative hazard per additional quartile of triglyceride was 0.84 (95% confidence interval 0.77-0.91). CONCLUSIONS: Low triglyceride concentration strongly predicts higher mortality following stroke, whereas serum cholesterol level is not an independent predictor. Outcome following stroke is thus related more strongly to triglyceride-rich than to cholesterol-rich lipoprotein concentrations. The mechanisms explaining this require further investigation.

Acute Disease↗
PubMed2003

Evidence for tissue selectivity of the synthetic androgen 7 alpha-methyl-19-nortestosterone in hypogonadal men.

The potent synthetic androgen 7 alpha-methyl-19-nortestosterone (MENT) is resistant to 5 alpha-reductase but is a substrate for aromatase. It may therefore offer selective sparing of the prostate gland while supporting other androgen-dependent tissues. MENT acetate implants were administered for 24 wk to 16 hypogonadal men, randomly allocated to 1 or 2 implants (groups I and II, respectively; releasing approximately 400 microg/d x implant). Hemoglobin concentration and hematocrit were maintained during MENT treatment. Prostate volume fell in group I and to a small, but statistically nonsignificant, degree in group II; the level of prostate-specific antigen fell significantly in both. Lumbar spine bone mineral density decreased in both groups. Sexual behavior and erectile function declined in group I, but were maintained in group II. Thus, overall, one MENT implant appeared to provide subphysiological androgen replacement. The 2-implant dose of MENT was able to maintain most androgen-dependent functions, except bone mass, and there was evidence to support selective sparing of the prostate gland. These results demonstrate for the first time in humans the selectivity of MENT in tissues dependent on 5 alpha-reductase. In addition, our data are consistent with the importance of adequate estrogenicity as part of the necessary spectrum of activity of an androgen for replacement therapy in men.

Adult↗
PubMed2003

Metformin or antiandrogen in the treatment of hirsutism in polycystic ovary syndrome.

Hirsutism is a common and distressing symptom frequently encountered in women with polycystic ovary syndrome (PCOS), who also show relative insulin resistance. The aim of this trial, in which hirsutism was the primary end point, was to compare the efficacy of the oral antihyperglycemic medication metformin with that of an established treatment, combined ethinyl estradiol and cyproterone acetate. Patients (n = 52) were randomized to receive either metformin (500 mg, three times daily) or Dianette (ethinyl estradiol, 35 micro g; cyproterone acetate, 2 mg) treatment for 12 months, with assessments before treatment, at 6 months, and at 12 months. Both objective and subjective methods of evaluating hirsutism were used, and in addition, patient perceptions were examined. The results show that metformin is potentially an effective treatment for moderate to severe hirsutism in women with PCOS. They also suggest that in some respects (Ferriman-Gallwey score and patient self-assessment), it is more efficacious than the standard treatment (Dianette). The objective evaluation of hair diameter reduction showed that both treatments were moderately effective at multiple anatomical sites. Dianette treatment was responsible for profound suppression of androgen activity, in contrast to metformin, which induced negligible change. However, metformin did reduce markers of insulin resistance. The data suggest that hirsutism may be effectively treated by reducing hyperinsulinemia.

Acne Vulgaris↗
PubMed2003

Enhancement of endothelial function by pregnancy: inadequate response in women with type 1 diabetes.

OBJECTIVE: Pregnant women with type 1 diabetes have a substantially increased risk of vascular complications. Our aim was to study vascular function and metabolic and inflammatory risk factors during the antenatal and postpartum periods in women with type 1 diabetes compared with healthy control subjects. RESEARCH DESIGN AND METHODS: A total of 15 women with diabetes and 30 control subjects were recruited in the third trimester of pregnancy. Of these women, 9 case subjects and 16 control subjects were reinvestigated in the postnatal period. Blood samples were collected and microvascular skin perfusion was assessed in vivo using laser Doppler imaging and iontophoretic administration of endothelial-dependent (acetylcholine [ACH]) and endothelial-independent (sodium nitroprusside [SNP]) vasodilators. RESULTS: Microvascular responses in both control subjects (ACH, P = 0.018; SNP, P = 0.01) and diabetic women (ACH, P = 0.029; SNP, P = 0.105) were better during pregnancy than in the postnatal period, although responses in women with diabetes were significantly inferior to those in control subjects during both periods (all P < 0.001, two-way ANOVA). This dysfunction existed despite similar lipoprotein profiles. The difference in vascular responsivity between case and control subjects was significantly attenuated by adjustment for differences in HbA(1c) but not C-reactive protein concentrations in the two groups. CONCLUSIONS: Pregnancy enhances microvascular function, but in women with diabetes, such improvements are insufficient to attain responses seen in healthy nonpregnant women. This suggests a persistent vascular defect in young women with type 1 diabetes that may contribute to adverse pregnancy outcome. Our data suggest a role for the chronic effects of hyperglycemia in the impaired vascular responsiveness in such women.

Acetylcholine↗
PubMed2003

Intercellular adhesion molecule-1 (ICAM-1) expression is upregulated by thrombin in human monocytes and THP-1 cells in vitro and in pregnant subjects in vivo.

Monocytes play a pivotal role in both the inflammatory and coagulation responses, which may be mediated through a variety of adhesion molecules on the cell surface, including intercellular adhesion molecule-1 (ICAM-1). Monocytes also possess thrombin receptors. In the current study, we have demonstrated that thrombin can upregulate ICAM-1 mRNA and induce ICAM-1 expression on the monocyte in vitro and that, in vivo, higher monocyte ICAM-1 expression is observed in pregnancy (which is characterised by a physiological increase in thrombin generation). In pregnant subjects, a positive correlation between monocyte ICAM-1 expression and a number of markers of vascular/thrombotic disease (including blood group, acquired activated protein C resistance and non-fasting plasma triglyceride levels) was observed. We also observed a significant relationship between monocyte ICAM-1 expression and soluble plasma ICAM-1 levels, which would be consistent with a contribution of monocytic ICAM-1 to the levels of free ICAM-1 observed in plasma during pregnancy. Consistent with a role in fibrinogen binding, our preliminary in vivo results suggest that monocyte ICAM-1 expression may be a useful marker of the thrombotic/inflammatory response, although further work is required to assess the relationship of monocyte ICAM-1 expression in thrombotic disorders.

Adult↗
PubMed2003

Microvascular dysfunction: a link between pre-eclampsia and maternal coronary heart disease.

Epidemiological studies have recently demonstrated a relationship between pre-eclampsia and coronary heart disease. Insulin resistance has been implicated as a common factor. We have demonstrated, for the first time, using laser Doppler imaging in vivo, impaired microvascular function in women 15-25 years following a pregnancy complicated by pre-eclampsia. Thus, microvascular dysfunction, which is associated with insulin resistance, may be a predisposing vascular mechanism for both coronary heart disease and pre-eclampsia. Pregnancies complicated by pre-eclampsia may identify women at risk of vascular disease in later life and may provide the opportunity for lifestyle and risk factor modification to alter maternal vascular disease risk.

Adult↗
PubMed2002

Analysis of obesity and hyperinsulinemia in the development of metabolic syndrome: San Antonio Heart Study.

OBJECTIVE: To use standardized cut-offs of body mass index (BMI), waist circumference, waist-to-hip ratio, and fasting insulin levels to predict the development of metabolic disorders and metabolic syndrome. RESEARCH METHODS AND PROCEDURES: We performed an 8-year follow-up study of 628 non-Hispanic whites and 1340 Mexican Americans, ages 25 to 64 years, from the second cohort of the San Antonio Heart Study. We defined metabolic disorders as dyslipidemia (triglycerides > or =2.26 mM or high-density lipoprotein <0.91 mM in men and <1.17 mM in women), hypertension (blood pressure > or =140 or >=90 mm Hg, or receiving antihypertensive medications), and type 2 diabetes (fasting glucose > or =7.0 mM, 2-hour test glucose > or =11.1 mM, or receiving anti-diabetic medications). People with at least two metabolic disorders were defined as having metabolic syndrome. RESULTS: High waist-to-hip ratio and fasting insulin levels were significant predictors of developing metabolic syndrome. High anthropometric indices remained significant predictors of metabolic syndrome after adjusting for fasting insulin. Waist circumference, BMI, and insulin had similar areas under the receiver operating characteristic curves (0.74 to 0.76). Further multivariate analyses combining these indices showed minimal increase in prediction. Of subjects who had a combination of high BMI (> or =30 kg/m(2)) and high waist circumference (above "Action Level 2"), 32% developed metabolic syndrome, compared with 10% of subjects with both low BMI and low waist circumference. DISCUSSION: These findings support the National Institutes of Health recommendations for reducing the risk of metabolic syndrome. Adjustment for baseline fasting insulin levels had only a small effect on the ability of anthropometric indices to predict the metabolic syndrome.

Adult↗
PubMed2002

The relationship between reduced vitamin antioxidant concentrations and the systemic inflammatory response in patients with common solid tumours.

BACKGROUND AND AIMS: The majority of patients with advanced cancer have reduced circulating concentrations of the vitamin antioxidants including retinol, alpha-tocopherol and carotenoids. However, the basis of this reduction is not known. Vitamin antioxidant concentrations have been reported to be correlated with a systemic inflammatory response (as evidenced by C-reactive protein) in normal subjects and in patients with lung cancer. In order to determine whether this relationship was independent of tumour type patients other common solid tumours were studied. METHODS: Fasting circulating concentrations of vitamin antioxidants and C-reactive protein were measured in normal subjects (n=30) and patients with breast (n=15), prostate (n=15) and colorectal cancer (n=11). RESULTS: Concentrations of C-reactive protein were higher (P<0.0001) and vitamin antioxidants lower (P<0.0001) in the cancer patients. In normal subjects and cancer patients, C-reactive protein concentrations were inversely correlated with circulating concentrations of retinol (r(2)=0.162), alpha-tocopherol (r(2)=0.297), lutein (r(2)=0.256), lycopene (r(2)=-0.171), alpha-(r(2)=0.140) and beta-carotene (r(2)=0.254): (all P<0.001). CONCLUSIONS: Concentrations of retinol, alpha -tocopherol and carotenoids are inversely associated with the magnitude of the systemic inflammatory response. These relationships appear to be independent of the presence and type of cancer.

Adult↗
PubMed2002

Supraphysiological concentrations of estradiol in menopausal women given repeated implant therapy do not adversely affect lipid profiles.

BACKGROUND: The effects of oral estrogen therapy (ERT) on lipids and metabolic parameters are well known, in contrast to the effects of subcutaneously administered estrogen, particularly high concentrations of estrogen. We examined metabolic parameters in cohorts of women with and without subcutaneous estrogen therapy with concomitant supra-normal concentrations of estradiol (SE). METHODS: Lipids and lipoprotein concentrations, low density lipid (LDL) subfractions, and activity of hepatic lipase (HL) were assessed in 30 menopausal women with SE and 19 control subjects not using ERT, matched for body mass index and age. RESULTS: Waist-hip ratio (WHR) and fasting insulin (FI) concentrations were lower in the SE group compared with the women not on ERT (P < 0.05). The concentrations of triglyceride and high density lipid (HDL) cholesterol were similar (P > 0.1), whereas total cholesterol (P < 0.05), LDL cholesterol (P < 0.05), and HL activity (P < 0.01) were lower in the SE group. Concentrations of the large, buoyant LDL I subfraction were significantly lower in the SE group (P < 0.05), but there was no difference in LDL III concentrations. CONCLUSIONS: Women with SE have similar triglyceride and HDL cholesterol levels but lower LDL cholesterol concentrations compared with post-menopausal women not taking ERT. The observations that the SE group showed reduced fasting insulin and WHR suggest that supra-normal circulating concentrations of estradiol, delivered subcutaneously, may beneficially influence insulin metabolism.

Body Constitution↗
PubMed2002

Factors critical to iontophoretic assessment of vascular reactivity: implications for clinical studies of endothelial dysfunction.

Skin microvascular responses to iontophoresis of acetylcholine, an endothelium-dependent vasodilator, and sodium nitroprusside, an endothelium-independent vasodilator, were measured using a laser Doppler imager whose software controlled iontophoretic current delivery in an integrated fashion. A novel feature involved monitoring voltage across the iontophoresis chambers during current application (total charge: 8 mC). Both drugs elicited vasodilatation but with differing magnitudes and time courses, whereas current delivery with only vehicle (0.5% NaCl) present was ineffective. During drug delivery a three-to fourfold difference in calculated skin resistance was observed between subjects, with higher resistance being associated with lower dilator responses to both drugs. There was a significant (p < 0.0001) linear inverse correlation between perfusion.time and resistance.time integrals for both acetylcholine ( r = -0.86) and sodium nitroprusside ( r = -0.96). This was corrected in individual subjects by multiplying individual perfusion values by the resistance.time integral, which reduced response variability. Cyclooxygenase inhibition by aspirin apparently attenuated acetylcholine and sodium nitroprusside vasodilator responses but after correcting for skin resistance there was no longer any difference. Monitoring voltage across the iontophoretic circuit is critical, as effective drug delivery in individual subjects is influenced by the circuit resistance that can be corrected for. These findings have implications for clinical studies that use the iontophoresis technique for assessing vascular function.

Acetylcholine↗
PubMed2002

Circulating concentrations of "free" leptin in relation to fat mass and appetite in gastrointestinal cancer patients.

Recent studies have suggested that circulating concentrations of leptin might play a role in cancer cachexia. In the first part of the study, we compared circulating concentrations of free and total leptin, percent fat mass, and the inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6), together with appetite score, in age- and gender-matched healthy controls (n = 11) and advanced gastrointestinal cancer patients (n = 26). In the second part of the study, the same measurements were repeated before and after megestrol acetate treatment of weight-losing gastrointestinal cancer patients (n = 10). Body mass index and percent fat mass were significantly lower (P < 0.05) and IL-6 and CRP were significantly higher (P < 0.05) in cancer patients than in controls. There was no difference in the percentage of leptin bound in the circulation between controls and cancer patients. Circulating "free" leptin concentrations correlated with percent fat mass in controls (r = 0.745, P = 0.008) and cancer patients (r = 0.600, P = 0.001). In cancer patients, circulating leptin concentrations, either free or total, were not correlated with IL-6 or CRP concentrations. When adjusted for fat mass, the circulating concentrations of free and total leptin were significantly lower in the cancer patients (P < 0.01). Megestrol acetate treatment significantly increased circulating free and total leptin concentrations in the cancer patients (P < 0.05). There was a significant positive correlation between the change in circulating concentrations of free and total leptin and the change in percent fat mass (r = 0.685, P < 0.05 and r = 0.661, P < 0.05, respectively). The results of the present study indicate that the proportions of free and bound leptin in the circulation do not differ between normal subjects and patients with gastrointestinal cancer and in both groups are related to fat mass. Furthermore, the increase in circulating leptin concentrations after megestrol acetate treatment is not associated with any alteration in leptin binding.

Aged↗
PubMed2002

Maternal obesity is associated with dysregulation of metabolic, vascular, and inflammatory pathways.

Obesity is increasing in prevalence worldwide and in all age groups. In nonpregnant individuals, obesity is associated with dyslipidemia; hyperinsulinemia; vascular dysfunction; and, more recently, low-grade chronic inflammation. However, whether such effects are sustained during pregnancy has been sparsely investigated but is important to establish, given the association of maternal obesity with numerous adverse metabolic and vascular consequences. We consecutively recruited 47 healthy women in the third trimester of pregnancy and divided the participants into 2 groups, lean [n = 24; median body mass index (BMI), 22.1 kg/m(2)] and obese (n = 23; median BMI, 31.0 kg/m(2)) around the median first trimester BMI. The age, parity, and smoking history were comparable in both groups. A detailed panel of metabolic and inflammatory parameters was measured and an in vivo assessment of endothelial-dependent and -independent microvascular function made using laser doppler imaging. Although low-density lipoprotein cholesterol and glycosylated hemoglobin were similar, fasting triglyceride concentrations were higher [2.70 (interquartile range, 2.3-3.21) vs. 2.20 (IQ range, 2.0-2.6) mmol/liter, P = 0.02] and high-density lipoprotein concentrations were lower [1.55 (IQ range, 1.1-1.7) vs. 1.72 (IQ range, 1.4-2.0) mmol/liter, P = 0.02] in the obese group. Leptin [55.6 (range, 45-64.4) ng/ml vs. 23.8 (range, 13.2-35.2) ng/ml, P < 0.0001] and fasting insulin [14.5 (range, 11.4-27.3) vs. 6.5 (range, 4.6-9.7) mU/liter, P < 0.0001] levels were more than double. Similarly, levels of inflammatory parameters, IL-6 [3.15 (range, 2.4-3.5) vs. 2.1 (range, 1.73-2.85) pg/ml, P = 0.003], and sensitive C-reactive protein [4.45 (range, 2.9-6.6) vs. 2.25 (range, 0.92-3.65) mg/ml, P = 0.0015] were also substantially elevated. Both endothelial-dependent and -independent vasodilatory responses were significantly reduced in the obese group (P = 0.0003 and P = 0.02, respectively, ANOVA) and systolic blood pressure was higher (P = 0.01). Metabolic factors, C-reactive protein (r = 0.289, P = 0.049), and insulin (r = 0.339, P = 0.02) were related inversely to endothelial-dependent function. These comprehensive data demonstrate that, as in nonpregnant obese individuals, obesity in pregnancy is associated not only with marked hyperinsulinemia (without necessarily glucose dysregulation) and dyslipidemia but also impaired endothelial function, higher blood pressure, and inflammatory up-regulation. Such a spectrum of risk factors may contribute to maternal complications in obese women and, as a result, influence fetal programming of adult vascular disease. Clearly, these data provide further rationale to examine the potential benefits of preconceptual weight loss and antenatal exercise.

Adult↗