Associations of reproductive hormones and glucose homeostasis with metabolic-associated fatty liver disease measured by transient elastography in a super-obese population

Abstract

BACKGROUND AND AIM: Low levels of sex hormone binding globulin (SHBG) have been associated with obesity and related metabolic diseases, including metabolic-associated fatty liver disease (MAFLD) and type 2 diabetes (T2D). However, as no studies have examined the relative significance of these relationships with MAFLD diagnosed by transient elastography or in a super-obese community-based population, we aimed to do so. METHODS: Patients were prospectively recruited into an observational cohort study as part of a public tertiary weight management service in western Sydney. Patients were referred by their primary care physician if they had a body mass index (BMI) > 35 kg/m2 with T2D, or a BMI > 40 kg/m2 with two obesity complications. Anthropometric measurements, metabolic and hormonal blood tests, body composition by dual-energy x-ray absorptiometry, and transient elastography data were collected at baseline. RESULTS: The cohort comprised 381 patients (mean age, 48.7 +/- 12 years; 67% female; mean BMI, 50.6 +/- 1.1 kg/m2). Overall, 85% of the cohort had steatosis when measured by controlled attenuation parameter (CAP) on transient elastography (FibroScan). This was significantly associated with low SHBG levels only in men, but with low homeostasis model assessment 2 (HOMA2)-derived insulin sensitivity only in women. Addition of T2D to steatosis did not significantly change the association of SHBG in either sex. In linear regression analysis, CAP was independently and significantly associated with higher BMI, higher glycated hemoglobin level, lower HOMA2 insulin sensitivity, and lower growth hormone (GH) levels in women, but there was no relationship with SHBG. In men, CAP was associated with lower SHBG levels, and there was no correlation with BMI, glycemic parameters, or GH levels. CONCLUSIONS: In our cohort, low SHBG levels did not correlate with glucose homeostasis either before or after controlling for MAFLD. The relationships of MAFLD with SHBG and glucose homeostasis were sex dimorphic. Further research is needed to confirm these findings.