Sex difference determined the role of sex hormone-binding globulin in obese children during short-term weight reduction program

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Abstract

The relationship between hyperinsulinemia and decreased sex hormone-binding globulin (SHBG) levels has been observed in obese adults and children. Weight reduction not only increased insulin sensitivity but also elevated serum SHBG levels in obese adults and children. However, the correlation between the changes in insulin resistance indices and serum SHBG concentration during weight reduction program (WRP) is not fully understood, particularly in obese children. This study is to evaluate whether SHBG level is a potential biomarker that can be used to assess insulin resistance in obese children during a short-term WRP. Forty-eight obese Taiwanese children (11.7 ± 2.2 years; 25 boys and 23 girls) participating in 8-week WRP were studied. Anthropometric measurements, lipid profiles, insulin resistance indices, and serum SHBG concentration were recorded at baseline and at the end of the WRP. The results showed body weight (BW), body mass index (BMI), body fat percentage (BF%), body fat weight (BFW), and insulin resistance indices such as fasting insulin, fasting insulin to glucose ratio, homeostasis model assessment (HOMA) of insulin resistance, log (HOMA) all significantly decreased after the 8-week WRP. With respect to lipid profiles, only high-density lipoprotein cholesterol (HDL-C) levels increased in both sexes. At baseline, insulin resistance indices were inversely correlated with SHBG concentrations in girls, but not in boys. The difference in SHBG after WRP was 2.58 nmol/L (95% confidence interval [CI]: −3.51, 8.66) in boys and 0.58 nmol/L (95% CI: −5.23, 6.39) in girls. There was a trend toward increased serum SHBG levels in boys ( P = .39) and girls ( P = .84) after weight loss, but a significantly negative correlation between the change in SHBG and in each of the insulin resistance indices only in the girls after adjusting age and ΔBFW during WRP.

In conclusion, short-term WRP has the potential effects of decreased BW, BMI, BF%, and BFW, as well as increased serum HDL-C levels and insulin sensitivity in obese Taiwanese children. Although serum SHBG levels moderately increased in both sexes during short-term WRP, measuring the change in SHBG concentrations might be a potential biomarker to evaluate improvement in insulin resistance in girls only, and not in boys.

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Sex hormone-binding globulin and risk of type 2 diabetes in women and men.

Eric Ding, Yiqing Song, JoAnn Manson … (2009)

Circulating sex hormone-binding globulin levels are inversely associated with insulin resistance, but whether these levels can predict the risk of developing type 2 diabetes is uncertain. We performed a nested case-control study of postmenopausal women in the Women's Health Study who were not using hormone therapy (359 with newly diagnosed type 2 diabetes and 359 controls). Plasma levels of sex hormone-binding globulin were measured; two polymorphisms of the gene encoding sex hormone-binding globulin, SHBG, that were robustly associated with the protein levels were genotyped and applied in mendelian randomization analyses. We then conducted a replication study in an independent cohort of men from the Physicians' Health Study II (170 with newly diagnosed type 2 diabetes and 170 controls). Among women, higher plasma levels of sex hormone-binding globulin were prospectively associated with a lower risk of type 2 diabetes: multivariable odds ratios were 1.00 for the first (lowest) quartile of plasma levels, 0.16 (95% confidence interval [CI], 0.08 to 0.33) for the second quartile, 0.04 (95% CI, 0.01 to 0.12) for the third quartile, and 0.09 (95% CI, 0.03 to 0.21) for the fourth (highest) quartile (P<0.001 for trend). These prospective associations were replicated among men (odds ratio for the highest quartile of plasma levels vs. the lowest quartile, 0.10; 95% CI, 0.03 to 0.36; P<0.001 for trend). As compared with homozygotes of the respective wild-type allele, carriers of a variant allele of the SHBG single-nucleotide polymorphism (SNP) rs6259 had 10% higher sex hormone-binding globulin levels (P=0.005), and carriers of an rs6257 variant had 10% lower plasma levels (P=0.004); variants of both SNPs were also associated with a risk of type 2 diabetes in directions corresponding to their associated sex hormone-binding globulin levels. In mendelian randomization analyses, the predicted odds ratio of type 2 diabetes per standard-deviation increase in the plasma level of sex hormone-binding globulin was 0.28 (95% CI, 0.13 to 0.58) among women and 0.29 (95% CI, 0.15 to 0.58) among men, a finding that suggests that sex hormone-binding globulin may have a causal role in the risk of type 2 diabetes. Low circulating levels of sex hormone-binding globulin are a strong predictor of the risk of type 2 diabetes in women and men. The clinical usefulness of both SHBG genotypes and plasma levels in stratification and intervention for the risk of type 2 diabetes warrants further examination. 2009 Massachusetts Medical Society

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Overweight in childhood and adolescence.

William Dietz (2004)

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Prevalence of Pre-Diabetes and Its Association With Clustering of Cardiometabolic Risk Factors and Hyperinsulinemia Among U.S. Adolescents

Chaoyang Li, Earl S. Ford, Guixiang Zhao … (2009)

OBJECTIVE—Impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) are considered to constitute “pre-diabetes.” We estimated the prevalence of IFG, IGT, and pre-diabetes among U.S. adolescents using data from a nationally representative sample. RESEARCH DESIGN AND METHODS—We analyzed data from participants aged 12–19 years in the National Health and Nutrition Examination Survey 2005–2006. We used fasting plasma glucose and 2-h glucose during an oral glucose tolerance test to assess the prevalence of IFG, IGT, and pre-diabetes and used the log-binomial model to estimate the prevalence ratios (PRs) and 95% CIs. RESULTS—The unadjusted prevalences of IFG, IGT, and pre-diabetes were 13.1, 3.4, and 16.1%, respectively. Boys had a 2.4-fold higher prevalence of pre-diabetes than girls (95% CI 1.3–4.3). Non-Hispanic blacks had a lower rate than non-Hispanic whites (PR 0.6, 95% CI 0.4–0.9). Adolescents aged 16–19 years had a lower rate than those aged 12–15 years (0.6, 0.4–0.9). Overweight adolescents had a 2.6-fold higher rate than those with normal weight (1.3–5.1). Adolescents with two or more cardiometabolic risk factors had a 2.7-fold higher rate than those with none (1.5–4.8). Adolescents with hyperinsulinemia had a fourfold higher prevalence (2.2–7.4) than those without. Neither overweight nor number of cardiometabolic risk factors was significantly associated with pre-diabetes after adjustment for hyperinsulinemia. CONCLUSIONS—Pre-diabetes was highly prevalent among adolescents. Hyperinsulinemia was independently associated with pre-diabetes and may account for the association of overweight and clustering of cardiometabolic risk factors with pre-diabetes.

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Author and article information

Journal

Journal ID (nlm-ta): Medicine (Baltimore)

Journal ID (iso-abbrev): Medicine (Baltimore)

Journal ID (publisher-id): MEDI

Title: Medicine

Publisher: Wolters Kluwer Health

ISSN (Print): 0025-7974

ISSN (Electronic): 1536-5964

Publication date Collection: May 2017

Publication date (Electronic): 12 May 2017

Volume: 96

Issue: 19

Electronic Location Identifier: e6834

Affiliations

[a ]Department of Pediatrics, Tri-Service General Hospital

[b ]Graduate Institute of Medical Sciences

[c ]Department of Family and Community Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.

Author notes

[∗ ]Correspondence: Der-Ming Chu, Department of Pediatrics, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Cheng-Kung Road, Neihu, 114 Taipei, Taiwan (e-mail: derming@ 123456ndmctsgh.edu.tw ).

Article

Publisher ID: MD-D-16-05350 Accession ID: 06834

DOI: 10.1097/MD.0000000000006834

PMC ID: 5428600

PubMed ID: 28489766

SO-VID: 6e57d25d-c1c4-4a8b-aabb-a95d20b65aaa

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This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

History

Date received : 23 August 2016

Date revision received : 10 April 2017

Date accepted : 14 April 2017

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Keywords: insulin resistance,obese children,sex hormone-binding globulin,weight reduction program

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Keywords: insulin resistance, obese children, sex hormone-binding globulin, weight reduction program

Sex difference determined the role of sex hormone-binding globulin in obese children during short-term weight reduction program

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Sex and gender-sensitive medicine

Most cited references 32

Sex hormone-binding globulin and risk of type 2 diabetes in women and men.

Overweight in childhood and adolescence.

Prevalence of Pre-Diabetes and Its Association With Clustering of Cardiometabolic Risk Factors and Hyperinsulinemia Among U.S. Adolescents

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