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Abstract Details
Severity of non-alcoholic steatohepatitis is not linked to testosterone concentration in patients with type 2 diabetes
PLoS One. 2021 Jun 2;16(6):e0251449. doi: 10.1371/journal.pone.0251449. eCollection 2021.
Kristin Alexandra Dayton1, Fernando Bril23, Diana Barb2, Jinping Lai4, Srilaxmi Kalavalapalli2, Kenneth Cusi23
Author information
1Department of Pediatrics, Division of Pediatric Endocrinology, University of Florida, Gainesville, Florida, United States of America.
2Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, Florida, United States of America.
3Malcom Randall Veterans Administration Medical Center, Gainesville, Florida, United States of America.
4Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida, United States of America.
Abstract
Background: Hypogonadism is reported to occur in non-alcoholic fatty liver disease (NAFLD), but earlier studies used low-sensitivity diagnostic techniques (CT, ultrasound), for NAFLD diagnosis. We hypothesized that if hypogonadism was due to NAFLD, and not solely attributable to underlying obesity/diabetes, it would be more severe in the presence of steatohepatitis (NASH). To examine the influence of liver disease on testosterone in males with type 2 diabetes mellitus (T2DM), we used gold-standard liver imaging with MR-spectroscopy (1H-MRS), and performed liver biopsies to grade/stage the NAFLD.
Methods: In this cross-sectional study, we measured in 175 males with T2DM total and free testosterone, markers of insulin resistance, and intrahepatic triglyceride content (IHTG) by 1H-MRS. Those with NAFLD on imaging underwent a liver biopsy.
Results: Total testosterone was higher in the group without NAFLD ("No-NAFLD"; n = 48) compared to isolated steatosis (IS; n = 62) or NASH (n = 65) (385 ± 116 vs. 339 ± 143 vs. 335 ± 127 ng/ml, ptrend 0.03). Testosterone was also lower in obese vs. non-obese subjects in both the No-NAFLD and IS groups (p = 0.06 and p = 0.11, respectively), but not in obese vs. non-obese patients with NASH (p = 0.81). IHTG was independently associated with total testosterone (ß = -4.8, p = 0.004). None of the liver histology characteristics were associated with lower testosterone.
Conclusions: NAFLD is linked to lower total testosterone in patients with T2DM, but likely given a common soil of insulin resistance/obesity and not from the severity of liver necroinflammation or fibrosis. Nevertheless, clinicians should consider screening patients with T2DM and NAFLD for hypogonadism.