High sex hormone-binding globulin concentration is a risk factor for high fibrosis-4 index in middle-aged Japanese men

Fujihara, Yuya; Hamanoue, Nobuya; Yano, Hiromi; Tanabe, Makito; Akehi, Yuko; Nomiyama, Takashi; Yanase, Toshihiko

doi:10.1507/endocrj.ej18-0505

Cited by 15 publications

(14 citation statements)

References 39 publications

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“…This implies that FIB-4 index may represent a predictor for the risk of developing DM in non-diabetic Japanese people. This finding is not consistent with those of previously published studies, in which NAFLD was shown to increase insulin resistance, with a compensatory increase in insulin secretion 21,22 , which is eventually followed by the development of glucose intolerance or DM when this compensatory mechanism fails [5][6][7] , while relationships of FIB-4 index with HOMA-β but not with HOMA-R were recently reported in a population-based cross-sectional study of Japanese 23 . Although we have no precise explanation for this inconsistency, differences in study samples may be responsible.…”

Section: Discussioncontrasting

confidence: 99%

FIB-4 index is a marker for a subsequent decrease in insulin secretion in a non-diabetic Japanese population

Fujita

Daimon

Mizushiri

et al. 2020

Sci Rep

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Non-alcoholic fatty liver disease (NAFLD) is associated with a high risk of type 2 diabetes (DM), therefore, early diagnosis of NAFLD is important to prevent incident DM. FIB-4 index, a biomarker, often used to evaluate severity of NAFLD, may be useful to evaluate risk for incident DM in ordinary clinical setting. Here, we determined the association of FIB-4 index with changes in indices representing glucose metabolism with aging in a non-diabetic population. From among the participants of the population-based Iwaki study of Japanese people conducted during 2014–2017, 1,268 non-diabetic individuals with complete data sets (age: 51.4 ± 15.9 years; men/women: 485/773) were enrolled in a cross-sectional study. In addition, of the participants, 439 who attended consecutive appointments between 2014 and 2017 were enrolled in a longitudinal study that aimed to evaluate the changes in insulin secretion and resistance with aging (age: 53.1 ± 13.7 years; men/women: 178/261). The cross-sectional study showed significant correlations of FIB-4 index with homeostasis model of assessment (HOMA) indices, even after adjustment for multiple factors (HOMA-β: β = − 0.254, p < 0.001; HOMA-R: β = − 0.247, p < 0.001). The longitudinal study showed a significant association between FIB-4 index and the change in HOMA-β (p < 0.001) but not HOMA-R (p = 0.639) during the 3-year study period. Use of the optimal cut-off value of the FIB-4 index for the prediction of decreased insulin secretion (HOMA-β < 30), determined using receiver operating characteristic analysis (1.592), showed that individuals at risk had a hazard ratio of 2.22 (confidence interval 1.17−4.06) for decreased insulin secretion, after adjustment for confounders. FIB-4 index may represent a useful predictor of a subsequent decrease in insulin secretion, at least in a non-diabetic Japanese population.

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Section: Discussioncontrasting

confidence: 99%

FIB-4 index is a marker for a subsequent decrease in insulin secretion in a non-diabetic Japanese population

Fujita

Daimon

Mizushiri

et al. 2020

Sci Rep

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“…Furthermore, this group had also higher prevalence of detectable plasmatic HCVRNA. Importantly, liver fibrosis positively correlated with SHBG and TT levels as previously described [15][16][17][18][19][20][21]. As summarized in Fig.…”

Section: Discussionsupporting

confidence: 77%

“…In the general population T is reduced in up to 90% of men with cirrhosis [12] and in male patients with HCV-related chronic liver diseases [14]. In addition, the relationship between sex hormones and SHBG levels and Non Alcoholic Steato Hepatitis (NASH), Non Alcoholic Fatty Liver Disease (NAFLD) and liver fibrosis has been reported in some studies [15][16][17][18][19][20][21], although with non-conclusive data.…”

Section: Introductionmentioning

confidence: 99%

Hypogonadism and liver fibrosis in HIV-infected patients

Quirós-Roldán

Porcelli

Pezzaioli

et al. 2021

J Endocrinol Invest

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Purpose Hypogonadism is frequent in HIV-infected men and might impact on metabolic and sexual health. Low testosterone results from either primary testicular damage, secondary hypothalamic-pituitary dysfunction, or from liver-derived sex-hormone-binding-globulin (SHBG) elevation, with consequent reduction of free testosterone. The relationship between liver fibrosis and hypogonadism in HIV-infected men is unknown. Aim of our study was to determine the prevalence and type of hypogonadism in a cohort of HIV-infected men and its relationship with liver fibrosis. Methods We performed a cross-sectional retrospective study including 107 HIV-infected men (median age 54 years) with hypogonadal symptoms. Based on total testosterone (TT), calculated free testosterone, and luteinizing hormone, five categories were identified: eugonadism, primary, secondary, normogonadotropic and compensated hypogonadism. Estimates of liver fibrosis were performed by aspartate aminotransferase (AST)-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) scores. Results Hypogonadism was found in 32/107 patients (30.8%), with normogonadotropic (10/107, 9.3%) and compensated (17/107, 15.8%) being the most frequent forms. Patients with secondary/normogonadotropic hypogonadism had higher body mass index (BMI) (p < 0001). Patients with compensated hypogonadism had longer HIV infection duration (p = 0.031), higher APRI (p = 0.035) and FIB-4 scores (p = 0.008), and higher HCV co-infection. Univariate analysis showed a direct significant correlation between APRI and TT (p = 0.006) and SHBG (p = 0.002), and between FIB-4 and SHBG (p = 0.045). Multivariate analysis showed that SHBG was independently associated with both liver fibrosis scores. Conclusion Overt and compensated hypogonadism are frequently observed among HIV-infected men. Whereas obesity is related to secondary hypogonadism, high SHBG levels, related to liver fibrosis degree and HCV co-infection, are responsible for compensated forms.

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“… 88 Recent studies have demonstrated that testosterone is also closely associated with metabolic syndrome, type 2 diabetes, and NAFLD. 89 - 94 Production of testosterone gradually decreases with aging, and the prevalence of these diseases increases at an older age.…”

Section: Gender Differencementioning

confidence: 99%

Characteristic Features of Nonalcoholic Fatty Liver Disease in Japan with a Focus on the Roles of Age, Sex and Body Mass Index

Tobari

Hashimoto

2020

Gut and Liver

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This review provides an update on the characteristics of nonalcoholic fatty liver disease (NAFLD), with a focus on the effects of age, sex, and body mass index. Age is a risk factor for NAFLD progression; however, extremely old patients have unique features, namely, the associations between metabolic comorbidities and NAFLD are weaker and NAFLD is not a risk factor for mortality. The prevalence of NAFLD is higher in men than in premenopausal women, whereas the reverse is true after menopause. Thus, before menopause, estrogen may have protective effects against NAFLD. Our hospital data showed that over 25% of male patients with NAFLD and almost 40% of female patients with NAFLD, especially elderly patients, were nonobese. Although histological steatosis and activity were associated with body mass index, the prevalence of nonalcoholic steatohepatitis was not. The prevalence of advanced fibrosis showed a significant sex difference. Advanced fibrosis was significantly more frequent among severely obese men but the prevalence was lower among severely obese women. This difference could be because a substantial proportion of severely obese women were premenopausal; thus, estrogen may have much stronger effects on the development of fibrosis than on obesity. Further studies are required to develop tailored management strategies.

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High sex hormone-binding globulin concentration is a risk factor for high fibrosis-4 index in middle-aged Japanese men

Cited by 15 publications

References 39 publications

FIB-4 index is a marker for a subsequent decrease in insulin secretion in a non-diabetic Japanese population

FIB-4 index is a marker for a subsequent decrease in insulin secretion in a non-diabetic Japanese population

Hypogonadism and liver fibrosis in HIV-infected patients

Characteristic Features of Nonalcoholic Fatty Liver Disease in Japan with a Focus on the Roles of Age, Sex and Body Mass Index

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