Abstract
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. 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. 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. 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.
Highlights
Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease that ranges from isolated hepatic steatosis to its more severe form with hepatocyte ballooning, lobular inflammation and often fibrosis, known as non-alcoholic steatohepatitis (NASH)
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)
NAFLD is linked to lower total testosterone in patients with type 2 diabetes mellitus (T2DM), but likely given a common soil of insulin resistance/obesity and not from the severity of liver necroinflammation or fibrosis
Summary
Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease that ranges from isolated hepatic steatosis to its more severe form with hepatocyte ballooning, lobular inflammation and often fibrosis, known as non-alcoholic steatohepatitis (NASH). In the type 2 diabetes mellitus (T2DM) population, NAFLD affects 60–70% of patients [4, 5] with 50–70% of those patients demonstrating changes consistent with NASH [6, 7]. Studies have shown a strong association of T2DM and hypogonadotropic hypogonadism in males, with strong correlations of testosterone levels with obesity and insulin resistance in these studies as well [9, 10]. Increased inflammatory cytokines from adipose tissue and elevated leptin levels in association with central nervous system leptin resistance and insulin resistance may contribute to decreased testosterone production in obesity and T2DM [12, 13]. 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
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