Dataset Information

Sex Hormone-Binding Globulin Levels in Young Men Are Associated With Nonalcoholic Fatty Liver Disease in Midlife.

ABSTRACT: INTRODUCTION:Cross-sectional data note lower levels of testosterone and sex hormone-binding globulin (SHBG) levels in men with nonalcoholic fatty liver disease (NAFLD). Whether sex hormone levels in young men are predictive of later risk of NAFLD is not known. METHODS:Among men in the prospective population-based multicenter Coronary Artery Risk Development in Young Adults study (mean age 50; n = 837), we assessed whether testosterone and SHBG levels measured at study year 10 (median age 35 years) were associated with prevalent NAFLD at study year 25. NAFLD was defined using noncontrast abdominal computed tomography (CT) scan after excluding other causes of hepatic steatosis. The association of testosterone and SHBG with prevalent NAFLD was assessed by logistic regression. RESULTS:Total testosterone levels in young men were inversely associated with subsequent prevalent NAFLD on unadjusted analysis (odds ratio [OR] 0.64, 95% confidence interval 0.53-0.7, P < 0.001), although no longer significant after adjustment for year 10 metabolic covariates as well as change in metabolic covariates from years 10 to 25 (OR 0.99, 95% confidence interval 0.76-1.27). In contrast, there was a significant inverse association of SHBG with prevalent NAFLD, independent of testosterone and metabolic covariates (OR 0.68, OR 0.51-0.92, P = 0.013). On formal mediation testing, visceral adiposity was found to explain ?41.0% (95% confidence interval 27%-73%) of the association of lower SHBG with prevalent NAFLD. CONCLUSIONS:Lower levels of SHBG in young men are associated with increase in prevalent NAFLD in middle age, independent of comprehensive metabolic risk factors. SHBG may provide a novel marker of NAFLD risk in young men.

SUBMITTER: Sarkar M

PROVIDER: S-EPMC6599461 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Sex Hormone-Binding Globulin Levels in Young Men Are Associated With Nonalcoholic Fatty Liver Disease in Midlife.

Sarkar Monika M VanWagner Lisa B LB Terry James G JG Carr J Jeffrey JJ Rinella Mary M Schreiner Pamela J PJ Lewis Cora E CE Terrault Norah N

The American journal of gastroenterology 20190501 5

<h4>Introduction</h4>Cross-sectional data note lower levels of testosterone and sex hormone-binding globulin (SHBG) levels in men with nonalcoholic fatty liver disease (NAFLD). Whether sex hormone levels in young men are predictive of later risk of NAFLD is not known.<h4>Methods</h4>Among men in the prospective population-based multicenter Coronary Artery Risk Development in Young Adults study (mean age 50; n = 837), we assessed whether testosterone and SHBG levels measured at study year 10 (med ...[more]

PMID: 30730350

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Project description:Background:Sex hormone-binding globulin (SHBG), a glycoprotein synthesized by hepatocytes, has been linked to insulin resistance and hepatic lipid metabolism and is suggested to be associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the association of SHBG with NAFLD in Chinese adults. Methods:We conducted a community-based, cross-sectional study in China involving 2912 participants aged 40-75 years old. All participants underwent detection for hepatic fat infiltration by ultrasound in addition to providing complete medical history and undergoing physical and blood biochemical examinations. The association of serum SHBG with the presence of NAFLD was reported by adjusted odds ratio after applying logistic regression models. To further explore the relationship between SHBG and NAFLD, mRNA expression of SHBG and hepatocyte nuclear factor 4-? (HNF4?), as well as intrahepatic triglycerides, were determined from the liver tissues of 32 subjects with different degrees of steatosis. Results:Serum SHBG levels in patients with NAFLD (median, 43.8 nmol/L; interquartile range, 33.4-56.8 nmol/L) were significantly lower than those in non-NAFLD subjects (median, 63.4 nmol/L; interquartile range, 47.6-83.1 nmol/L). Serum SHBG levels were inversely correlated with WHR, trunk fat percentage, glucose, HOMA-IR, TG, UA and DHEAS, and were positively correlated with HDL-C levels (all p?<? 0.001). Logistic regression analysis indicated that serum SHBG levels were negatively associated with the presence of NAFLD in all subjects, as well as the subgroups stratified by sex, BMI and HOMA-IR (all p?<? 0.05). In human liver tissues, SHBG and HNF4? mRNA expression decreased along with the elevated grade of hepatic steatosis. Both SHBG and HNF4? mRNA expression levels were negatively correlated with intrahepatic triglycerides. Conclusions:These results demonstrate that SHBG levels were negatively associated with the presence of NAFLD in middle-aged and elderly Chinese adults.

Project description:ImportancePhysical activity (PA) is recommended for preventing and treating nonalcoholic fatty liver disease (NAFLD). Yet, how long-term patterns of intensity-based physical activity, including moderate-intensity PA (MPA) and vigorous-intensity PA (VPA), might affect the prevalence of NAFLD in middle age remains unclear.ObjectiveTo identify distinct intensity-based PA trajectories from young to middle adulthood and examine the associations between PA trajectories and NAFLD prevalence in midlife.Design, setting, and participantsThis population-based cohort of 2833 participants used the Coronary Artery Risk Development in Young Adults study data. The setting included field clinics in Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California. Data analysis was completed in March 2023.ExposuresPA was self-reported at 8 examinations over 25 years (1985-1986 to 2010-2011) and separately scored for MPA and VPA.Main outcomes and measuresNAFLD was defined as liver attenuation values less than 51 Hounsfield units after exclusion of other causes of liver fat, measured using computed tomography in year 25 (2010-2011).ResultsAmong a total of 2833 participants included in the sample, 1379 (48.7%) self-identified as Black, 1454 (51.3%) as White, 1206 (42.6%) as male, and 1627 (57.4%) as female from baseline (1985-1986) (mean [SD] age, 25.0 [3.6] years) to year 25 (2010-2011) (mean [SD] age, 50.1 [3.6] years). Three MPA trajectories were identified: very low stable (1514 participants [53.4%]), low increasing (1096 [38.7%]), and moderate increasing (223 [7.9%]); and 3 VPA trajectories: low stable (1649 [58.2%]), moderate decreasing (1015 [35.8%]), and high decreasing (169 [6.0%]). After adjustment for covariates (sex, age, race, study center, education, smoking status, and alcohol consumption), participants in the moderate decreasing (risk ratio [RR], 0.74; 95% CI, 0.54-0.85) and the high decreasing (RR, 0.59; 95% CI, 0.44-0.80) VPA trajectories had a lower risk of NAFLD in middle age, relative to participants in the low stable VPA trajectory. Adjustments for baseline body mass index and waist circumference attenuated these estimates, but the results remained statistically significant. The adjusted RRs across the MPA trajectories were close to null and not statistically significant.Conclusions and relevanceThis cohort study of Black and White participants found a reduced risk of NAFLD in middle age for individuals with higher levels of VPA throughout young to middle adulthood compared with those with lower VPA levels. These results suggest the need for promoting sustainable and equitable prevention programs focused on VPA over the life course to aid in lowering NAFLD risk.

Dataset Information

Sex Hormone-Binding Globulin Levels in Young Men Are Associated With Nonalcoholic Fatty Liver Disease in Midlife.

Publications

Sex Hormone-Binding Globulin Levels in Young Men Are Associated With Nonalcoholic Fatty Liver Disease in Midlife.

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