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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertensive disorders of pregnancy, including gestational hypertension and preeclampsia, are leading causes of pregnancy-associated morbidity. Although insulin resistance and inflammation contribute to preeclampsia, prospective data regarding mechanisms of gestational hypertension are sparse. We conducted a prospective, nested case-control study to test the hypotheses that insulin resistance, marked by reduced sex hormone-binding globulin (SHBG) levels, and inflammation, marked by increased C-reactive protein levels, are similarly associated with gestational hypertension. We measured first-trimester C-reactive protein and SHBG levels in 51 women who subsequently developed gestational hypertension and 102 randomly selected normotensive pregnant controls. Compared with controls, first-trimester SHBG levels were significantly reduced among women who later developed gestational hypertension (176+/-73 versus 203+/-79 nmol/L; P=0.03), but there was no difference in C-reactive protein levels. There was statistically significant interaction among nulliparity, first-trimester SHBG levels, and risk of gestational hypertension, such that increasing SHBG levels were associated with significantly reduced risk of gestational hypertension among nulliparous women (odds ratio, 0.64 per 50-nmol/L increase; 95% confidence interval, 0.46, 0.90; P<0.01) but not among multiparous women. This association remained significant after adjusting for potential confounders (odds ratio, 0.55; 95% confidence interval, 0.31, 0.98; P=0.04). We conclude that insulin resistance, but not inflammation, is an independent risk factor for gestational hypertension among nulliparous women. Furthermore, important mechanistic differences exist in the pathogenesis of gestational hypertension comparing nulliparous and multiparous women.
Hypertension 2002 Dec
PMID:Insulin resistance but not inflammation is associated with gestational hypertension. 1246 74

Compensatory hyperinsulinemia stemming from peripheral insulin resistance is a well-recognized metabolic disturbance that is at the root cause of diseases and maladies of Syndrome X (hypertension, type 2 diabetes, dyslipidemia, coronary artery disease, obesity, abnormal glucose tolerance). Abnormalities of fibrinolysis and hyperuricemia also appear to be members of the cluster of illnesses comprising Syndrome X. Insulin is a well-established growth-promoting hormone, and recent evidence indicates that hyperinsulinemia causes a shift in a number of endocrine pathways that may favor unregulated tissue growth leading to additional illnesses. Specifically, hyperinsulinemia elevates serum concentrations of free insulin-like growth factor-1 (IGF-1) and androgens, while simultaneously reducing insulin-like growth factor-binding protein 3 (IGFBP-3) and sex hormone-binding globulin (SHBG). Since IGFBP-3 is a ligand for the nuclear retinoid X receptor alpha, insulin-mediated reductions in IGFBP-3 may also influence transcription of anti-proliferative genes normally activated by the body's endogenous retinoids. These endocrine shifts alter cellular proliferation and growth in a variety of tissues, the clinical course of which may promote acne, early menarche, certain epithelial cell carcinomas, increased stature, myopia, cutaneous papillomas (skin tags), acanthosis nigricans, polycystic ovary syndrome (PCOS) and male vertex balding. Consequently, these illnesses and conditions may, in part, have hyperinsulinemia at their root cause and therefore should be classified among the diseases of Syndrome X.
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PMID:Hyperinsulinemic diseases of civilization: more than just Syndrome X. 1452 33

Altered angiogenesis and insulin resistance, which are intimately related at a molecular level, characterize preeclampsia. To test if an epidemiological interaction exists between these two alterations, we performed a nested case-control study of 28 women who developed preeclampsia and 57 contemporaneous controls. Serum samples at 12 weeks of gestation were measured for sex hormone binding globulin (SHBG; low levels correlate with insulin resistance) and placental growth factor (PlGF; a proangiogenic molecule). Compared with controls, women who developed preeclampsia had lower serum levels of SHBG (208+/-116 versus 256+/-101 nmol/L, P=0.05) and PlGF (16+/-14 versus 67+/-150 pg/mL, P<0.001), and in multivariable analysis, women with serum levels of PlGF < or =20 pg/mL had an increased risk of developing preeclampsia (odds ratio [OR] 7.6, 95% CI 1.4 to 38.4). Stratified by levels of serum SHBG (< or =175 versus >175 mg/dL), women with low levels of SHBG and PlGF had a 25.5-fold increased risk of developing preeclampsia (P=0.10), compared with 1.8 (P=0.38) among women with high levels of SHBG and low levels of PlGF. Formal testing for interaction (PlGFxSHBG) was significant (P=0.02). In a model with 3 (n-1) interaction terms (high PlGF and high SHBG, reference), the risk for developing preeclampsia was as follows: low PlGF and low SHBG, OR 15.1, 95% CI 1.7 to 134.9; high PlGF and low SHBG, OR 4.1, 95% CI 0.45 to 38.2; low PlGF and high SHBG, OR 8.7, 95% CI 1.2 to 60.3. Altered angiogenesis and insulin resistance are additive insults that lead to preeclampsia.
Hypertension 2004 May
PMID:Insulin resistance and alterations in angiogenesis: additive insults that may lead to preeclampsia. 1502 32

The menopausal status is associated with an increased risk of metabolic and cardiovascular diseases. Since the post-menopausal modifications have not been clearly investigated in obese women, we evaluated the influences of menopausal status on anthropometric, hormonal and biochemical characteristics in selected groups of normal-weight and obese women. We studied 92 female outpatients: 24 normal-weight pre-menopausal (Pre-NW) [body mass index (BMI) 23.6 +/- 0.48, age 44.8 +/- 0.68], 24 normal-weight post-menopausal (Post-NW) (BMI 23.7 +/- 0.44, age 55.5 +/- 0.69), 24 obese pre-menopausal (pre-OB) (BMI 32.3 +/- 0.45, age 44.6 +/- 0.75), 20 obese post-menopausal women (Post-OB) (BMI 32.9 +/- 0.57, age 55.2 +/- 0.82). All the subjects were non smokers and free from hypertension, diabetes or impaired glucose tolerance (IGT). Anthropometric parameters, body composition, 17 beta-estradiol, LH, FSH, androstenedione, SHBG, testosterone and leptin were determined. Free androgen index (FAI) and insulin resistance index (HOMA) were calculated. In comparison with Pre-OB, Post-OB had higher values of waist circumferences (p < 0.02), while Post-NW showed no difference. Total and LDL-cholesterol were high in Post-NW women, whereas in the obese subjects they were already elevated in the premenopausal period. SHBG levels declined and FAI increased in Post-OB in comparison with Pre-OB. SHBG levels showed an inverse correlation with BMI, waist and waist-to-hip ratio (WHR), while FAI positively correlated with waist values. Serum leptin levels were higher in Post-OB than in Pre-OB, whereas they were similar in normal-weight women. The rise of leptin levels may be related to the greater abdominal fat deposition. In addition, menopausal status of uncomplicated obese women is associated with a greater abdominal fat deposition and with higher values of free androgen index, which may be considered as factors of cardiovascular risk.
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PMID:Anthropometric, hormonal and biochemical differences in lean and obese women before and after menopause. 1550 88

Symptoms of andropause syndrome such as: erectile dysfunction, somatovegetative and psychic symptoms have been examined in groups of smoking and non-smoking patients between 45 and 75 years of age Tests of testosterone, prolactin and SHBG levels have been carried out. Earlier andropause, a lower level of testosterone as well as more common arterial hypertension have been found in the group of smoking patients.
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PMID:[Symptoms of andropausal syndrome in smoking and non-smoking males]. 1579 43

Studies in our laboratory and elsewhere have demonstrated numerous abnormalities of steroid and polypeptide hormone secretion in obesity: hyperestrogenemia and hypogonadotropic hypogonadism in obese men; diminished SHBG levels in both sexes; elevated free testosterone and free estradiol in obese women; PCOS-like gonadotropin and sex-hormone abnormalities in obese women; elevated serum insulin in both sexes; blunted stimulability of prolactin, growth hormone, and vasopressin in both sexes; and elevated basal levels and blunted stimulability and suppressibility of beta-endorphin in both sexes. All of these abnormalities have been clearly shown to be partly or completely reversible with weight loss, with the exception of the endorphin abnormalities. In that area, four out of the five studies reported show no reversibility with weight loss. Reversibility of nearly all the hormonal abnormalities of obesity (i.e., all but the hyperendorphinemia) by weight loss suggests that none of them is causative of obesity. Nevertheless, some of the reversible abnormalities may secondarily amplify the morbidity associated with obesity: the hyperinsulinemia may be related to the increased risk of hypertension, hyperlipidemia, coronary disease, and Type II diabetes; the elevated levels of free estradiol in obese women may be related to their increased risk of breast and endometrial cancer. The role of hyperendorphinemia in obesity clearly requires further investigation, since it is the only observed hormonal abnormality that appears to be non-reversible by weight loss, and also since there seems to be increased sensitivity to beta-endorphin in obesity. The possibility that endorphin abnormalities may be causal in obesity cannot be ruled out.
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PMID:A perspective on the hormonal abnormalities of obesity: are they cause or effect? 1635 9

Malnutrition is a major problem in developing countries, and obesity and eating disorders are increasingly common in developing as well as developed countries. The reproductive axis is closely linked to nutritional status, especially undernutrition in the female, and inhibitory pathways involving detectors in the hind brain suppress ovulation in subjects with weight loss. Recovery may occur after minimal reacquisition of weight because energy balance is more important than body fat mass. Anorexia nervosa and bulimia nervosa affect up to 5% of women of reproductive age causing amenorrhoea, infertility and, in those who do conceive, an increased likelihood of miscarriage. Obesity can affect reproduction through fat cell metabolism, steroids and secretion of proteins such as leptin and adiponectin and through changes induced at the level of important homeostatic factors such as pancreatic secretion of insulin, androgen synthesis by the ovary and sex hormone-binding globulin (SHBG) production by the liver. WHO estimates that 9 to 25% of women in developed countries are severely obese, and obese mothers are much more likely to have obese children, especially if they have gestational diabetes. Obesity-associated anovulation may lead to infertility and to a higher risk of miscarriage. Management of anovulation with obesity involves diet and exercise as well as standard approaches to ovulation induction. Many obese women conceive without assistance, but pregnancies in obese women have increased rates of pregnancy-associated hypertension, gestational diabetes, large babies, Cesarean section and perinatal mortality and morbidity. Among contraceptors, the fear of weight gain affects uptake and continuation of hormonal contraceptives, although existing trials indicate that any such effects are small. For all methods of hormonal contraception, weight above 70 kg is associated with increased failure rates.
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PMID:Nutrition and reproduction in women. 1644 60

The role of testosterone on the development of hypertension is controversial, especially in women with polycystic ovary syndrome (PCOS) who have higher prevalence of obesity and insulin resistance than women without PCOS. Little is known about the association between serum testosterone level and blood pressure in young women with PCOS. In the 151 young Taiwanese women with PCOS enrolled in this cross-sectional study, we measured the body mass index, waist circumference, blood pressure, fasting glucose, fasting insulin, lipid profile, and hormone profiles. The free androgen index, total testosterone, and sex hormone-binding globulin, but not the level of dehydroepiandrosterone sulfate, significantly correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP). In multiple linear regression models adjusted for age, body mass index, and other anthropometric, metabolic, and hormonal variables, the level of serum free androgen index or total testosterone, but not the sex hormone-binding globulin, were independently related to SBP and DBP. The age- and body mass index-adjusted least-square mean of serum-free androgen index levels were significantly different between the highest quartile and other quartiles of the SBP and DBP levels. The high bioavailable testosterone levels (free androgen index: >or=19%) in women with PCOS increased the risk of elevated blood pressure (SBP >or=130 mm Hg and/or DBP >or=85 mm Hg) with an odds ratio of 3.817 (P=0.029; 95% CI: 1.14 to 12.74) after adjustment for age, anthropometric measures, and metabolic profiles. Our results suggest that the characteristic hyperandrogenemia in young women with PCOS was associated with an elevated SBP and DBP independent of age, insulin resistance, obesity, or dyslipidemia.
Hypertension 2007 Jun
PMID:Relationship between androgen levels and blood pressure in young women with polycystic ovary syndrome. 1757 51

Upper body obesity and the related metabolic disorder type 2 diabetes have been identified as risk factors for breast cancer, and associated with late-stage disease and a poor prognosis. Components of the metabolic syndrome, including visceral adiposity, insulin resistance, hyperglycemia and hyperinsulinemia, with or without clinically manifest diabetes mellitus, low serum high-density lipoprotein cholesterol and hypertension have all been related to increased breast cancer risk. The biochemical mechanisms include extraglandular oestrogen production, reduced sex hormone-binding globulin with consequent elevation of the bioactive plasma free oestradiol and increased insulin biosynthesis, all of which exert mitogenic effects on both untransformed and neoplastic breast epithelial cells. Obesity, type 2 diabetes and the metabolic syndrome also have in common an increased production of leptin and a decreased production of adiponectin by adipose tissue, with consequent elevations and reductions, respectively, in the circulating levels of these two adipokines. These changes in plasma leptin and adiponectin, acting through endocrine and paracrine mechanisms, have been associated in several studies with an increase in breast cancer risk and, perhaps, to more aggressive tumours; studies in vitro showed that leptin stimulates, and adiponectin inhibits, tumour cell proliferation and the microvessel angiogenesis which is essential for breast cancer development and progression.
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PMID:Adiposity, type 2 diabetes and the metabolic syndrome in breast cancer. 1771 97

In 1987 when Reaven introduced syndrome X (metabolic syndrome, or MS), we were studying skeletal muscle insulin resistance and found that when rodents were fed a high-fat, refined-sugar (HFS) diet, insulin resistance developed along with aspects of MS, including hyperinsulinemia, hypertension, hypertriglyceridemia, and obesity. MS was controlled in rodents by switching them to a low-fat, starch diet and was controlled in humans with a low-fat starch diet and daily exercise (Pritikin Program). Others reported inverse relations between serum insulin and sex hormone-binding globulin (SHBG). When subjects were placed on the Pritikin Program, insulin fell and SHBG rose and it was suggested that prostate cancer might also be an aspect of MS. A bioassay was developed with tumor cell lines grown in culture and stimulated with serum before and after a diet and exercise intervention. Diet and exercise altered serum factors that slowed the growth rate and induced apoptosis in androgen-dependent prostate cancer cells. Changes in serum with diet and exercise that might be important include reductions in insulin, estradiol, insulin-like growth factor-I (IGF-I), and free testosterone with increases in SHBG and IGF binding protein-1. Hyperinsulinemia stimulates liver production of IGF-I, plays a role in the promotion of prostate cancer, and thus is the cornerstone for both MS and prostate cancer. Adopting a low-fat starch diet with daily exercise controls MS and should reduce the risk of prostate cancer.
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PMID:Prostate cancer prevention by nutritional means to alleviate metabolic syndrome. 1826 84


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