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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although an association between the metabolic syndrome and hyperandrogenism has been suggested in women with polycystic ovarian syndrome, few studies have investigated this relationship in postmenopausal women. We measured estradiol, testosterone, and sex hormone-binding globulin (SHBG) and calculated the free androgen index (FAI) in 212 postmenopausal women not using hormone therapy in the Women's Health Study. A modified definition of the metabolic syndrome (3 or more of the following: abdominal obesity, hypertriglyceridemia, low high-density lipoprotein, elevated blood pressure, and abnormal glucose metabolism) from the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults was used. Women with the metabolic syndrome had higher mean levels of estradiol, testosterone, and FAI values and lower SHBG levels. Higher FAI and lower SHBG were associated with all components of the metabolic syndrome. After adjustment for BMI and other factors, women in the highest tertile of FAI had an odds ratio of 12.6 (95% confidence interval, 3.8-41.6) for the metabolic syndrome, whereas those in the lowest SHBG tertile had an odds ratio of 7.3 (95% confidence interval, 2.7-19.8). When stratified by body mass index, the associations with high FAI and low SHBG remained significant even in women with body mass index less than 26.7 kg/m2. An androgenic hormone profile is associated with both the individual components of the metabolic syndrome and clustering of metabolic abnormalities in postmenopausal women.
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PMID:Low sex hormone-binding globulin is associated with the metabolic syndrome in postmenopausal women. 1704 49

Using non-cholesterol sterols investigation several authors postulated a hypothesis that in the metabolic syndrome cholesterol endogenous synthesis is increased and its absorption decreased. Our study is the first attempt to evaluate the direct relation of cholesterol metabolism to the principal pathogenetic phenomenon of the metabolic syndrome--namely to insulin resistance. We have measured insulin sensitivity by two methods--Quicki (Quantitative Sensitivity Check Index) and intravenous insulin tolerance test (Kitt) and 3 indirect markers--fasting insulin level, fasting C-peptide level and SHBG (sex hormone binding globulin). The investigation was performed in three groups of subjects with a different prevalence of insulin resistance: 72 non-diabetics with ischemic heart disease, 117 young blood donors and 63 type 2 diabetics on diet therapy only. Analyzing altogether 60 relationships--between four sterols (lathosterol, squalene, sitosterol and campesterol) and five markers of insulin resistance in three groups of subjects--we have found only six significant relations between cholesterol synthesis and absorption and insulin resistance in all groups of patients. Our results indicate that there exists a significant relationship between insulin sensitivity and indices of either increased cholesterol synthesis or decreased cholesterol absorption. Insulin resistance explains only a part of both abnormalities mentioned above.
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PMID:Relation of cholesterol metabolism and non-cholesterol sterols to insulin resistance. 1708

Association of low sex hormone-binding globulin (SHBG) level with the risk of the metabolic syndrome (MetS) in men has previously been reported. A proline to alanine substitution in codon 12 of the peroxisome proliferator activated receptor gamma 2 (PPARgamma2) gene has been shown to be related to high insulin sensitivity. The relationship of SHBG levels with the Pro12Ala polymorphism of PPARgamma2 in men has not been previously studied. Therefore, we investigated the effect of the Pro12Ala polymorphism of PPARgamma2 on SHBG levels in 202 young Finnish men. The range of SHBG was from 3.30 to 73 nmol/L (geometric mean = 17.90; 95%CI = 16.62-19.25 nmol/L). Baseline SHBG levels tended to be lower in men who developed the MetS (n = 11) compared to men who did not develop the MetS (n = 169) (22.85 vs 17.26 nmol/L) on a high-caloric diet during their 6 mo military service. SHBG levels tended to be higher among the subjects with the Ala12Ala genotype compared to subjects with the Pro12Pro or Pro12Ala genotypes of the PPARgamma gene (27.7 vs 21.7 and 22.7 nmol/L). Among the carriers of the Pro12Pro genotype, those who developed the MetS (n = 8) had significantly lower levels of SHBG compared to men who did not develop the MetS (n = 93) (13.23 vs 24.22 nmol/L, p = 0.027). Among the subjects who developed the MetS those with the Pro12Pro genotype (n = 3) had significantly lower levels of SHBG compared to subjects with X12Ala (n = 8) (13.23 vs 28 nmol/L, p = 0.025). We conclude that the 12Ala allele of PPARgamma2 may influence SHBG levels in young Finnish men.
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PMID:The Pro12Ala polymorphism of the PPAR gamma 2 gene influences sex hormone-binding globulin level and its relationship to the development of the metabolic syndrome in young Finnish men. 1732 77

Central adiposity plays an important role in the insulin resistance of the polycystic ovary syndrome (PCOS) through the dysregulated production of various adipokines. Polycystic ovary syndrome has also been described as a low-grade inflammation state characterized by elevated levels of C-reactive protein (CRP). Furthermore, CRP is a strong independent predictor of the metabolic syndrome and cardiovascular disease. Recently, the adiponectin-to-leptin (A/L) ratio has been proposed as a potential atherogenic index in obese type 2 diabetic patients. The aim of this study was to evaluate the potential role of the A/L ratio in the metabolic and proinflammatory phenotype of PCOS. We studied 74 Greek women with PCOS (38 normal-weight and 36 overweight-obese women). The A/L ratio was negatively correlated with BMI (r = -0.79 P < .001), homeostasis model assessment (r = -0.642, P < .001), triglycerides (r = -0.67, P < .001), and total cholesterol (r = -0.38, P < .01), and positively correlated with high-density lipoprotein cholesterol (r = 0.38, P < .01) and sex hormone-binding globulin (r = 0.39, P = .001). After controlling for BMI, the A/L ratio was independently associated with insulin resistance indexes and triglycerides. Furthermore, the A/L ratio was negatively correlated with CRP (r = -0.746, P < .0001). Multiple regression analysis revealed that BMI and the A/L ratio were the only independent significant determinants of CRP (beta = .436, P = .003 and beta = -.398, P = .007, respectively). Studying normal-weight and overweight-obese women separately, we found an independent association between the A/L ratio and CRP in both groups (beta = -.460, P = .009 in normal-weight women and beta = -.570, P = .001 in overweight-obese women). In conclusion, the A/L ratio may serve as a biomarker of both insulin resistance and low-grade inflammation, providing the link between these cardiovascular risk factors in women with PCOS.
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PMID:The adiponectin-to-leptin ratio in women with polycystic ovary syndrome: relation to insulin resistance and proinflammatory markers. 1751 8

While obesity has a high prevalence in developed countries, the routine abnormalities seen from the clinical biochemistry laboratory that may be caused by obesity related pathology do not seem to be as common. Insulin resistance, which is often associated with obesity, is difficult to assess as formal procedures are too complex for clinical practice. Furthermore the interpretation of insulin levels is hampered by their in vivo variability, assay differences and the lack of reference intervals from an unaffected reference population. Interpretation of fasting glucose levels between 5.5 and 6.0mmol/L are also being debated however, it is useful to understand the age related changes in this parameter, which may also be due to increasing obesity in the reference population. The association of obesity and dyslipidaemia in the metabolic syndrome should focus on elevated triglycerides (>1.5mmol/L), which is associated with low HDLC and correlates with atherogenic small dense LDL. High triglycerides are also predictive of fatty liver and the common abnormality of an elevated ALT may not be appreciated if laboratories allow their reference intervals to increase as the population gets more obese with aging. SHBG levels fall with insulin resistance/hyperinsulinaemia and this needs to be taken into account when testosterone is measured. However, low SHBG is showing huge potential as a disease and prognostic marker in obesity. These commonly available tests provide useful insights for the obese patient and their utility may improve with future research into the growing problem of obesity.
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PMID:The clinical biochemistry of obesity-more than skin deep. 1761 Nov 53

There is growing evidence that obesity in women lead to a more severe form of hyperandrogenism and other endocrine abnormalities which may have some health implications later in life. Obese females are at higher risk for metabolic syndrome due to severe hyperandrogenemia. Calculated values for free testosterone are equivalent to those obtained by equilibrium dialysis, which is one of the reference measurement procedures (RMP) for estimation of free testosterone and may be capable of replacing values estimated using RMP's. For adult women correlations of body mass index (BMI) with calculated free (cFT) and bioavailable testosterone (cBT) are still rare, while these data are reported for peripubertal and adolescent girls. In this study we aimed to investigate the association between BMI and different androgen parameters (including calculated free and bioavailable testosterone, free androgen index, and sex hormone-binding globulin [SHBG]) in adult women with Hirsutism and with PCOS. In hirsute women with BMI > or = 25 kg/m2 measured total testosterone (TT) was significantly higher, SHBG was significantly lower and the calculated androgen parameter (FAI, cFT and cBT) were significantly higher compared to women with BMI < 25 kg/m2. In PCOS women with BMI > or = 25 kg/m2 TT was significantly higher, SHBG was significantly lower and the calculated androgen parameter (FAI, cFT and cBT) were also significantly higher compared to women with BMI < 25 kg/m2. In both the Hirsutism and PCOS-group there was a positive correlation between BMI and TT, cFT, and cBT, while BMI was negatively correlated with SHBG. In summary, in adult women with Hirsutism and PCOS obesity is associated with increased levels of TT and decreased levels of SHBG resulting in significant elevated calculated free and bioavailable testosterone levels. Obesity might lead to a more severe form of hyperandrogenism with elevated calculated free and bioavailable testosterone in the study population.
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PMID:Influence of body mass index on measured and calculated androgen parameters in adult women with Hirsutism and PCOS. 1770 84

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

Serum sex hormone-binding globulin (SHBG) is related to cardiometabolic disorders; but whether or not this relationship is purely secondary to hyperinsulinemia and/or obesity, which down-regulates SHBG, is unknown. The aim of the study was to investigate the association of SHBG and total testosterone with atherogenic dyslipidemias, metabolic syndrome (MS), and diabetes among predominantly elderly Turkish adults. After appropriate exclusions, 777 randomly selected male and female subjects with available measurements of both variables were eligible and were analyzed cross-sectionally, with diabetic subjects analyzed separately. Free testosterone was calculated. Metabolic syndrome was identified by the modified criteria of the Adult Treatment Panel III. Metabolic syndrome was identified in half the sample, which had a median age of 58 years. The odds of low SHBG concentrations (<45 nmol/L in men, <55 nmol/L in women) for the likelihood of 2 types of dyslipidemias, MS, and diabetes were examined by regression analyses in standard models including age, smoking status, presence of abdominal obesity, and insulin resistance (homeostasis model assessment of insulin resistance). In both sexes, low SHBG was associated independently with high triglyceride/low high-density lipoprotein dyslipidemia and with MS, at significant 2.2- to 4.5-fold odds ratios, independent of waist circumference or homeostasis model assessment of insulin resistance index. Low SHBG among women was additionally associated with the likelihood of hypertriglyceridemia with elevated apolipoprotein B and-at borderline significance-with that of diabetes, again when adjusted for the same confounders. In an elderly population with prevalent MS, low SHBG levels significantly associate with high triglyceride/low high-density lipoprotein dyslipidemia, MS, and, in women alone, diabetes and a dyslipidemia marking small dense low-density lipoprotein particles, all independent of abdominal obesity and insulin resistance. Low SHBG may be an important independent factor for cardiometabolic risk, particularly in women.
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PMID:Serum sex hormone-binding globulin, a determinant of cardiometabolic disorders independent of abdominal obesity and insulin resistance in elderly men and women. 1788 45

An important sex difference in body fat distribution is generally observed. Men are usually characterized by the android type of obesity, with accumulation of fat in the abdominal region, whereas women often display the gynoid type of obesity, with a greater proportion of their body fat in the gluteal-femoral region. Accordingly, the amount of fat located inside the abdominal cavity (intra-abdominal or visceral adipose tissue) is twice as high in men compared to women. This sex difference has been shown to explain a major portion of the differing metabolic profiles and cardiovascular disease risk in men and women. Association studies have shown that circulating androgens are negatively associated with intra-abdominal fat accumulation in men, which explains an important portion of the link between low androgens and features of the metabolic syndrome. In women, the low circulating sex hormone-binding globulin (SHBG) levels found in abdominal obesity may indirectly indicate that elevated free androgens are related to increased visceral fat accumulation. However, data on non SHBG-bound and total androgens are not unanimous and difficult to interpret for total androgens. These studies focusing on plasma levels of sex hormones indirectly suggest that androgens may alter adipose tissue mass in a depot-specific manner. This could occur through site-specific modulation of preadipocyte proliferation and/or differentiation as well as lipid synthesis and/or lipolysis in mature adipocytes. Recent results on the effects of androgens in cultured adipocytes and adipose tissue have been inconsistent, but may indicate decreased adipogenesis and increased lipolysis upon androgen treatment. Finally, adipose tissue has been shown to express several steroidogenic and steroid-inactivating enzymes. Their mere presence in fat indirectly supports the notion of a highly complex enzymatic system modulating steroid action on a local basis. Recent data obtained in both men and women suggest that enzymes from the aldoketoreductase 1C family are very active and may be important modulators of androgen action in adipose tissue.
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PMID:Androgens and body fat distribution. 1794 84

The liver produces plasma sex hormone-binding globulin (SHBG), which transports sex steroids and regulates their access to tissues. In overweight children and adults, low plasma SHBG levels are a biomarker of the metabolic syndrome and its associated pathologies. Here, we showed in transgenic mice and HepG2 hepatoblastoma cells that monosaccharides (glucose and fructose) reduce human SHBG production by hepatocytes. This occurred via a downregulation of hepatocyte nuclear factor-4alpha (HNF-4alpha) and replacement of HNF-4alpha by the chicken OVA upstream promoter-transcription factor 1 at a cis-element within the human SHBG promoter, coincident with repression of its transcriptional activity. The dose-dependent reduction of HNF-4alpha levels in HepG2 cells after treatment with glucose or fructose occurred in concert with parallel increases in cellular palmitate levels and could be mimicked by treatment with palmitoyl-CoA. Moreover, inhibition of lipogenesis prevented monosaccharide-induced downregulation of HNF-4alpha and reduced SHBG expression in HepG2 cells. Thus, monosaccharide-induced lipogenesis reduced hepatic HNF-4alpha levels, which in turn attenuated SHBG expression. This provides a biological explanation for why SHBG is a sensitive biomarker of the metabolic syndrome and the metabolic disturbances associated with increased fructose consumption.
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PMID:Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone-binding globulin gene. 1799 61


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