scholarly journals Sex hormone-binding globulin as a marker for hyperinsulinemia and/or insulin resistance in obese children

2000 ◽  
pp. 85-89 ◽  
Author(s):  
F Gascon ◽  
M Valle ◽  
R Martos ◽  
FJ Ruz ◽  
R Rios ◽  
...  

OBJECTIVE: A relationship between hyperinsulinemia and decreased serum sex hormone-binding globulin (SHBG) has been described in adults. We evaluated the usefulness of SHBG as an index of hyperinsulinemia and/or insulin resistance in obese children (aged 6-9 years) of both sexes and its possible influence on the androgenic status. DESIGN: We carried out a cross-sectional study of cases and controls. We studied 61 obese children (22 males, 39 females) with body mass index (BMI) superior to the 90(th) percentile and a control group of age- and sex-matched non-obese children. We measured serum glucose, insulin, TSH, free thyroxine, 17beta-estradiol, testosterone and SHBG. Also, we correlated these parameters with anthropometric measures. RESULTS: The obese group presented significantly elevated levels of insulin (P=0.001) and insulin/glucose ratio (P=0.0012) compared with the control group. SHBG (P=0.0001) and testosterone (P=0.0169) levels were significantly lower than those in the non-obese group. We did not find any difference in the free androgen index (FAI). Fasting insulin (r=-0.4512; P<0.001), BMI (r=-0.3185; P<0.05) and testosterone (r=-0.3705; P<0.01) were inversely correlated with SHBG concentration. According to multivariate analyses, insulin was the only independent predictor factor for serum SHBG concentration in the obese group (r partial=0.1280; P=0.0171). CONCLUSIONS: In summary, at this age there is a strong relationship between insulin and SHBG. The changes in SHBG levels of the obese group did not affect FAI and, therefore, they did not cause changes in the androgenic status. Our data support the role of insulin in the regulation of serum SHBG levels.

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Judith S Brand ◽  
Maroeska M Rovers ◽  
Yvonne T van der Schouw ◽  

Background: The role of testosterone in metabolic syndrome (MetS) etiology is receiving increasing attention, given the overlap of testosterone deficiency and MetS in ageing men. We conducted an individual participant data (IPD) meta-analysis to examine this association in a uniform way and to produce more precise estimates of risk overall and in certain subgroups. Methods: Individual participant data of 20 observational studies including 12,811 men (mean age: 58.6 ± 15.6 years) were pooled and cross-sectional as well as prospective associations between total testosterone (TT), sex hormone-binding globulin (SHBG), free testosterone (FT) and MetS were assessed. We calculated odds ratios (ORs) and hazard ratios (HRs) by study-specific quartiles of sex hormones using mixed effects models (with random effects at the study level) and tested for effect modification by age and body mass index (BMI). Results: Cross-sectional analyses revealed that men with low concentrations of TT, SHBG or FT were more likely to have MetS. ORs for the lowest versus highest quartile were 4.56 (95% CI 4.02-5.16) for TT, 5.26 (95% CI 4.49-6.17) for SHBG and 2.18 (95% CI 1.88-2.53) for FT. Associations were attenuated but remained significant after adjustment for BMI and insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)). Prospective analyses yielded similar results, but of smaller magnitude (HRs for the lowest versus highest quartile were 2.00 (95% CI 1.57-2.56) for TT, 2.71 (95% CI 1.99-3.70) for SHBG and 1.41 (95% CI 1.04-1.92) for FT). Stratified analyses revealed significant interactions by age and BMI, such that associations were strongest in young and nonobese men. Sex hormone concentrations decreased gradually with increasing number of MetS components and, for single components, were most strongly associated with abdominal obesity and hypertriglyceridemia. Conclusion: This meta-analysis of pooled individual data shows a robust, dose-response relationship of testosterone and SHBG concentrations with prevalent and incident MetS in men. The strong associations with abdominal obesity and hypertriglyceridemia provide insight into the underlying biological mechanisms.


Author(s):  
Bahia Namavar Jahromi ◽  
Niloofar Borzou ◽  
Mohammad Ebrahim Parsanezhad ◽  
Zahra Anvar ◽  
Parvin Ghaemmaghami ◽  
...  

Background: Insulin resistance (IR) occurs in 50–70% of women with polycystic ovary syndrome (PCOS) and can be applied as a prediabetic feature in PCOS. Objective: In this study, indirect methods including fasting blood sugar (FBS), fasting insulin (FI), FBS/FI ratio, and quantitative insulin sensitivity check index (QUICKI) were compared with the homeostasis model assessment of insulin resistance (HOMA-IR) as a standard technique. The association of IR to sex hormone-binding globulin (SHBG) and several hormones was also analyzed. Materials and Methods: This cross-sectional study was performed on 74 PCOS women. Sensitivity and specificity of each IR method was calculated based on HOMA-IR. Hormonal profiles of the patients were compared between the groups with defined normal and abnormal values of IR. Results: Triglyceride levels had a positive association with FBS and HOMA-IR (p = 0.002 and p = 0.01, respectively) with a negative association to QUICKI and SHBG (p = 0.02 and p = 0.02, respectively). SHBG showed a significant negative association with FBS (p = 0.001). Dehydroepiandrosterone sulfate showed a positive association with FI (p = 0.002). Seven PCOS women showed abnormal SHBG levels (< 36 nmol/L) while expressed normal values of the rest of the studied variables. FI and QUICKI had the highest sensitivity while FBS/FI and QUICKI had the highest specificity when HOMA-IR was applied as a standard test. Conclusion: SHBG and triglyceride had a significant negative and positive association with IR, respectively. HOMA-IR followed by FI and QUICKI is the most sensitive test for the detection of IR. SHBG levels can be a helpful biomarker for the diagnosis of PCOS. Key words: Polycystic ovary syndrome, Insulin resistance, Sex hormone-binding globulin.


2010 ◽  
Vol 163 (6) ◽  
pp. 895-900 ◽  
Author(s):  
N H Birkebæk ◽  
A Lange ◽  
P Holland-Fischer ◽  
K Kristensen ◽  
S Rittig ◽  
...  

ObjectiveObesity in men is associated with reduced insulin sensitivity and hypoandrogenism, while obesity in women is associated with reduced insulin sensitivity and hyperandrogenism. In children, the effect of obesity and weight reduction on the hypothalamo-pituitary–gonadal axis is rarely investigated. The aim of the present study was to investigate the effect of weight reduction in obese Caucasian children on insulin sensitivity, sex hormone-binding globulin (SHBG), DHEAS and the hypothalamo-pituitary–gonadal axis.MethodsOne hundred and sixteen (65 females) obese children with a median age of 12.3 (7–15) years were examined before and after a 10-week stay at a weight loss camp. Examination included anthropometry and fasting blood samples measuring plasma glucose, serum insulin, SHBG, DHEAS, testosterone, 17β-oestradiol, FSH and LH.ResultsBody mass index (BMI) decreased (P<0.01), insulin sensitivity and SHBG increased (P<0.01), independent of gender and puberty. The changes in insulin sensitivity and the changes in SHBG correlated significantly (P<0.01) independent of gender, puberty and the changes in BMI. Testosterone increased in boys (P<0.01) and tended to decrease in girls (P=0.05, in girls after menarche (P=0.03)). FSH increased in boys and girls. LH increased in boys and was unchanged in girls.ConclusionsDuring weight loss, insulin sensitivity and SHBG increased significantly in obese children, and the changes in insulin sensitivity and the changes in SHBG correlated significantly independent of gender, puberty and the changes in BMI. There was sexual dimorphism in the changes of testosterone, with the changes in boys towards increased virilisation and the changes in girls towards less virilisation.


2014 ◽  
Vol 99 (12) ◽  
pp. E2780-E2788 ◽  
Author(s):  
Stephen J. Winters ◽  
Jyothi Gogineni ◽  
Marjan Karegar ◽  
Charles Scoggins ◽  
Chris A. Wunderlich ◽  
...  

Context: The plasma level of sex hormone binding globulin (SHBG), a glycoprotein produced by hepatocytes, is subject to genetic, hormonal, metabolic, and nutritional regulation, and is a marker for the development of the metabolic syndrome and diabetes. Objective: Because the mechanism for these associations is unclear, and no studies of SHBG gene expression in humans have been published, SHBG mRNA was measured in human liver samples and related to anthropometric data. Setting: Inpatients at a private, nonprofit, university-associated hospital were studied. Participants: Subjects were fifty five adult men and women undergoing hepatic resection as treatment for cancer. Main Outcome Measures: Main outcome measures were SHBG mRNA and serum SHBG levels. Results: SHBG mRNA was a strong predictor of serum SHBG with higher levels of the mRNA and protein in women than in men. The relationship between SHBG mRNA and circulating SHBG differed in males and females consistent with a sex difference in post-transcriptional regulation. A strong positive correlation was found between the level of the mRNA for the transcription factor HNF4α and SHBG mRNA. Insulin resistance (IR), assessed by homeostatis model assessment, was related inversely to SHBG mRNA and to HNF4α mRNA as well as to circulating SHBG levels. These mRNAs, as well as serum SHBG, were higher when the hepatic triglyceride concentration was low, and decreased with increasing body mass index but were unrelated to age. Conclusions: Fat accumulation in liver and IR are important determinants of SHBG gene expression and thereby circulating SHBG levels that are perhaps mediated through effects on the transcription factor HNF4α. These findings provide a potential mechanism to explain why low SHBG predicts the development of type 2 diabetes.


2013 ◽  
Vol 78 (3) ◽  
pp. 321-329 ◽  
Author(s):  
Ian R. Wallace ◽  
Michelle C. McKinley ◽  
Patrick M. Bell ◽  
Steven J. Hunter

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Carla Basualto-Alarcón ◽  
Paola Llanos ◽  
Gerardo García-Rivas ◽  
Mayarling Francisca Troncoso ◽  
Daniel Lagos ◽  
...  

In men, 70% of circulating testosterone binds with high affinity to plasma sex hormone binding globulin (SHBG), which determines its bioavailability in their target cells. In recent years, a growing body of evidence has shown that circulating SHBG not only is a passive carrier for steroid hormones but also actively regulates testosterone signaling through putative plasma membrane receptors and by local expression of androgen-binding proteins apparently to reach local elevated testosterone concentrations in specific androgen target tissues. Circulating SHBG levels are influenced by metabolic and hormonal factors, and they are reduced in obesity and insulin resistance, suggesting that SHBG may have a broader clinical utility in assessing the risk for cardiovascular diseases. Importantly, plasma SHBG levels are strongly correlated with testosterone concentrations, and in men, low testosterone levels are associated with an adverse cardiometabolic profile. Although obesity and insulin resistance are associated with an increased incidence of cardiovascular disease, whether they lead to abnormal expression of circulating SHBG or its interaction with androgen signaling remains to be elucidated. SHBG is produced mainly in the liver, but it can also be expressed in several tissues including the brain, fat tissue, and myocardium. Expression of SHBG is controlled by peroxisome proliferator-activated receptor γ (PPARγ) and AMP-activated protein kinase (AMPK). AMPK/PPAR interaction is critical to regulate hepatocyte nuclear factor-4 (HNF4), a prerequisite for SHBG upregulation. In cardiomyocytes, testosterone activates AMPK and PPARs. Therefore, the description of local expression of cardiac SHBG and its circulating levels may shed new light to explain physiological and adverse cardiometabolic roles of androgens in different tissues. According to emerging clinical evidence, here, we will discuss the potential mechanisms with cardioprotective effects and SHBG levels to be used as an early metabolic and cardiovascular biomarker in men.


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