Comments on 'low serum sex hormone binding globulin is associated with nonalcoholic fatty liver disease in type 2 diabetic patients'.
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ABSTRACT:
SUBMITTER: Wang C
PROVIDER: S-EPMC4174595 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
| S-EPMC6225668 | biostudies-other
Project description:IntroductionCross-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.MethodsAmong 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.ResultsTotal 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.ConclusionsLower 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.
| S-EPMC6599461 | biostudies-literature
Project description:BackgroundNonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. Elevated sex hormone-binding globulin (SHBG) levels have been observed in the setting of HIV and may protect against some metabolic disorders. We aimed to investigate whether higher SHBG levels may protect against NAFLD in men with/without HIV.MethodsNAFLD was assessed using noncontrast computed tomography in 530 men in the Multicenter AIDS Cohort Study (MACS) who drank <3 alcoholic drinks/d and were uninfected with chronic hepatitis C or B (340HIV+, 190HIV-). Morning serum samples were tested for SHBG, total testosterone (TT), and adiponectin. Multivariable logistic regression was used to assess associations between HIV, SHBG, TT, adiponectin, and NAFLD.ResultsMedian SHBG was highest among HIV+/NAFLD- men and lowest among HIV-/NAFLD+ men. Adjusted for demographics, HIV, visceral adiposity, HOMA-IR, TT, and PNPLA3 genotype, higher SHBG was associated with lower odds of NAFLD (odds ratio [OR], 0.52 per doubling; 95% confidence interval [CI], 0.34-0.80). In separate multivariable models without SHBG, HIV (OR, 0.46; 95% CI, 0.26-0.79) and higher adiponectin (OR, 0.66 per doubling; 95% CI, 0.49-0.89) were associated with lower NAFLD odds, whereas TT was not significantly associated (OR, 0.74 per doubling; 95% CI, 0.53-1.04). Adjusting for SHBG attenuated the associations of HIV (OR, 0.61; 95% CI, 0.34-1.08) and adiponectin (OR, 0.74; 95% CI, 0.54-1.02) with NAFLD.ConclusionsSHBG levels were higher among HIV+ men, were independently associated with lower NAFLD, and could partially explain the associations of HIV and higher adiponectin with lower NAFLD in our cohort. These findings suggest that SHBG may protect against NAFLD, supporting further prospective and mechanistic studies.
| S-EPMC7047947 | biostudies-literature
Project description:Sex hormones have been linked with presence and severity of nonalcoholic fatty liver disease (NAFLD) in adults, but it is unknown if they affect severity of pediatric NAFLD. To examine associations of circulating SHBG, estrogens, and androgens with key histologic features of pediatric, biopsy-confirmed NAFLD. Baseline assessment of longitudinal cohorts and randomized clinical trials. Nonalcoholic Steatohepatitis Clinical Research Network. Children and adolescents ≤18 years with liver biopsy-confirmed NAFLD in the United States. We assayed SHBG, estrone, estradiol, dehydroepiandrosterone (DHEAS), androstenedione, and testosterone in relation to grade/stage of steatosis, portal inflammation, hepatic ballooning, fibrosis, and nonalcoholic steatohepatitis (NASH) severity using linear regression. Mean age of 573 children at the time of biopsy was 13.1 years (SD 2.8). Lower SHBG was inversely associated with steatosis severity in boys and girls (P = 0.001), and with portal inflammation in girls only (P for sex interaction <0.001). Higher testosterone was related to improved features of steatosis and fibrosis (P for sex interaction = 0.003 and 0.01, respectively) in boys, but detrimental in girls. In boys and girls, higher estrone, estradiol, and testosterone were associated with lower portal inflammation grade; higher estradiol was positively associated with hepatic ballooning severity; DHEAS was inversely associated with hepatic ballooning and NASH severity (all P < 0.05). Androstenedione was not associated with NAFLD features. Largely consistent with findings in adults, sex hormones are associated with distinct histologic features of NAFLD in children and adolescents. These hormone levels relate to differences with gender and pubertal change.
| S-EPMC7494240 | biostudies-literature
Project description:This study aimed to explore the combined associations of 25(OH)-vitamin D and sex hormone binding globulin (SHBG) with nonalcoholic fatty liver disease (NAFLD) in men and postmenopausal women. Our data, which were based on the population, were collected from 16 sites in East China in 2014. There were 2700 men with a mean age of 53 years and 1461 women over 55 who were considered postmenopausal enrolled in the study. Levels of 25(OH)D and SHBG were measured using chemiluminescence assay. NAFLD was measured using liver ultrasound. Multivariable-adjusted logistic regression models examined associations of 25(OH)D and SHBG tertiles with odds of mild and moderate-severe NAFLD. Both the low 25(OH)D and low SHBG groups were significantly associated with higher odds of mild NAFLD (men: OR 1.37, 95% CI 1.05, 1.78 in low 25(OH)D group; OR 1.73, 95% CI 1.23, 2.45 in low SHBG group; women: OR 1.51, 95% CI 1.08, 2.12 in low 25(OH)D group; OR 2.16, 95% CI 1.48, 3.14 in low SHBG group) and moderate-severe NAFLD (men: OR 1.61, 95% CI 1.24, 2.10 in low 25(OH)D group; OR 3.42, 95% CI 2.41, 4.87 in low SHBG group; women: OR 1.66, 95% CI 1.14, 2.42 in low 25(OH)D group; OR 6.84, 95% CI 4.31, 10.84 in low SHBG group). However, the combined association of low 25(OH)D and low SHBG was much larger, especially in moderate-severe NAFLD (men: OR 6.57, 95% CI 3.87, 11.18; women: OR 8.16, 95% CI 3.98, 16.73). The associations were independent of age, total testosterone, abdominal obesity, diabetes, and lipid profile. The negative associations of 25(OH)D and SHBG levels with NAFLD are strongest when viewed in combination in men and postmenopausal women. Further studies should determine the cause-effect relationship and investigate the underlying mechanisms of this finding.
| S-EPMC5291588 | biostudies-literature
Project description:BackgroundThe association between low serum testosterone levels, visceral adipose tissue (VAT), and metabolic syndrome is now well known. However, the relationship between hepatic steatosis and serum testosterone levels has not been extensively studied. Our aim was to investigate the association of serum total testosterone levels with nonalcoholic fatty liver disease (NAFLD), adjusting for the influence of VAT and insulin resistance.MethodsThis study is a retrospective observational cross-sectional one of healthy Korean men and was conducted at the Seoul National University Hospital Healthcare System Gangnam Center. We used data obtained from 495 men who were at least 20 years of age and who had undergone blood testing, abdominal computed tomography, and ultrasonography. Multiple logistic regression analysis was used to explore the association of serum total testosterone levels with NAFLD.ResultsMen in the low serum testosterone quintile were at a higher risk for NAFLD than men in the highest serum testosterone quintile. After adjusting for age, smoking, diabetes, exercise, BMI, triglycerides, and high-density-lipoprotein cholesterol, subjects with serum testosterone levels in the lowest quintile had an odds ratio (OR) (95% confidence interval (CI)) of 5.12 (2.43-10.77) for NAFLD (p value, 0.0004). The inverse association between serum testosterone and NAFLD was attenuated by further adjustment for variables including VAT; however, it remained statistically significant (OR (95% CI): 4.52 (2.09-9.80) in the lowest quintile; p value=0.004).ConclusionsA low serum total testosterone level was independently associated with NAFLD. This report is the first one suggesting the association remains unchanged even after controlling for VAT and insulin resistance.
| S-EPMC3406998 | biostudies-literature
Project description:This multi-center, cross-sectional study investigated the association between serum testosterone (T) levels, serum sex hormone-binding globulin (SHBG) levels, and the risk of metabolic syndrome (MS) in 3332 adult Chinese men. The prevalence of MS was 34.7%, and men with MS had lower serum levels of total T (TT) and SHBG than those without MS (P < 0.001). There was no significant difference in serum free T (FT) levels between subjects with and without MS (P = 0.627). In logistic regression analysis, the association between MS and serum SHBG levels persisted after adjusting for age, body mass index (BMI), smoking and drinking status, and serum TT (odds ratio [OR] 0.962, 95% confidence interval [95% CI] 0.954-0.969, P< 0.01). However, the association between serum TT level and the risk of MS was weak after adjusting for age, BMI, SHBG level, and smoking and drinking status (OR 0.981, 95% CI 0.960-1.007). Our study reveals that both serum TT and SHBG levels, but not serum FT, are inversely associated with the prevalence of MS and that serum SHBG is an independent and dominant risk factor for MS.
| S-EPMC4814971 | biostudies-literature
Project description:AimTo examine the association between lifetime alcohol consumption and significant liver disease in type 2 diabetic patients with NAFLD.MethodsA cross-sectional study assessing 151 patients with NAFLD at risk of clinically significant liver disease. NAFLD fibrosis severity was classified by transient elastography; liver stiffness measurements ≥8.2 kPa defined significant fibrosis. Lifetime drinking history classified patients into nondrinkers, light drinkers (always ≤20 g/day), and moderate drinkers (any period with intake >20 g/day).ResultCompared with lifetime nondrinkers, light and moderate drinkers were more likely to be male (p = 0.008) and to be Caucasian (p = 0.007) and to have a history of cigarette smoking (p = 0.000), obstructive sleep apnea (p = 0.003), and self-reported depression (p = 0.003). Moderate drinkers required ≥3 hypoglycemic agents to maintain diabetic control (p = 0.041) and fibrate medication to lower blood triglyceride levels (p = 0.044). Compared to lifetime nondrinkers, light drinkers had 1.79 (95% CI: 0.67-4.82; p = 0.247) and moderate drinkers had 0.91 (95% CI: 0.27-3.10; p = 0.881) times the odds of having liver stiffness measurements ≥8.2 kPa (adjusted for age, gender, and body mass index).ConclusionsIn diabetic patients with NAFLD, light or moderate lifetime alcohol consumption was not significantly associated with liver fibrosis. The impact of lifetime alcohol intake on fibrosis progression and diabetic comorbidities, in particular obstructive sleep apnea and hypertriglyceridemia, requires further investigation.
| S-EPMC5687130 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD) is characterized by low HDL cholesterol, but the activity of the HDL-associated antioxidative enzyme paraoxonase-1 (PON-1) remains unclear. To determine the association of PON-1 with suspected NAFLD, we measured serum enzyme activity in 7,622 participants of the Prevention of Renal and Vascular End-Stage Disease cohort. A fatty liver index (FLI) ≥60, a proxy of NAFLD, was present in 2,083 participants (27.3%) and coincided with increased prevalence of T2D, metabolic syndrome (MetS), (central) obesity, elevated triglycerides, and low HDL cholesterol (all P < 0.001). In men and women combined, serum PON-1 activity did not vary according to elevated FLI (P = 0.98), whereas in men with elevated FLI PON-1 activity was increased (P = 0.016). In multivariable linear regression analyses (adjusted for age, sex, T2D, MetS, alcohol use, and smoking), PON-1 activity was unexpectedly associated with elevated FLI (β = 0.083; P < 0.001). In a sensitivity analysis (n = 5,126) that excluded subjects with positive cardiovascular history, impaired estimated glomerular filtration rate, elevated urinary albumin excretion, and drug use, PON-1 activity was also independently associated with elevated FLI (β = 0.045; P = 0.017). These results indicate that PON-1 is paradoxically maintained and may even be increased in NAFLD despite inverse associations with metabolic disorders and low HDL cholesterol.
| S-EPMC6314263 | biostudies-literature
Project description:Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder and is associated with various metabolic diseases, including type 2 diabetes mellitus. There are no approved drugs for NAFLD, and the only approved treatment option is weight reduction. As insulin resistance plays an important role in the development of NAFLD, many anti-diabetic drugs have been evaluated for the treatment of NAFLD. Improvement of liver enzymes has been demonstrated by many anti-diabetic drugs, but histological assessment still remains insufficient. Pioglitazone could become the first-line therapy for T2DM patients with NAFLD, based on evidence of histological improvement in patients with biopsy-proven nonalcoholic steatohepatitis (NASH). Liraglutide, another promising alternative, is not yet recommended in patients with NAFLD/NASH due to limited evidence. Therefore, well-designed randomized controlled trials should be performed in the near future to demonstrate if and how anti-diabetic drugs can play a role in the treatment of NAFLD.
| S-EPMC7641556 | biostudies-literature