Abstract
Background: Nonalcoholic fatty liver disease (NAFLD), fatty infiltration of the liver in the absence of alcohol use, is a prevalent and serious complication of obesity. Obesity is a state of relative growth hormone (GH) deficiency, and GH has been identified as a candidate disease-modifying target in NAFLD because of its lipolytic and anti-inflammatory properties. However, it is not known whether individuals with NAFLD phenotyped by proton magnetic resonance spectroscopy (1H-MRS), the gold standard imaging modality for assessment of intrahepatic lipid (IHL) content, have lower peak stimulated GH levels as compared to those of similar age, sex and BMI without NAFLD.
Methods: We studied 99 generally healthy adults without diabetes or significant alcohol use, ages 19-67 y and BMI >25 kg/m2. All subjects underwent 1H-MRS for assessment of IHL content. Using a cutoff of >5.5%, 65 subjects had NAFLD and 34 did not (controls). GHRH-arginine stimulation testing was performed. GH was measured by immunoassay and IGF-1 by LC/MS/MS (Quest Diagnostics, CA, USA). Visceral and subcutaneous adipose tissue (VAT/SAT) were assessed by cross-sectional CT at L4. Results are reported as mean ±SD.
Results: There was no difference between NAFLD vs controls in mean age (48±12 vs 45±14 y, p=0.30), BMI (33±4 vs 33±7 kg/m2, p=0.96), sex (43% vs 44% female, p=0.90) or premenopausal status (50% vs 60%, p=0.50). Mean IHL was 21.8±13.3% (range 5.5-57.8%) and 2.9±1.1% (range 1.0-4.9%) in the NAFLD and control groups, respectively (p<0.0001). NAFLD subjects had higher ALT, total cholesterol, triglycerides, VLDL, LDL and lower HDL than controls. Fasting glucose was statistically but not clinically significantly higher in NAFLD vs controls (90±9 vs 86±7 mg/dL, p=0.03), and mean HbA1c did not differ significantly. There was a trend towards a higher mean VAT in the NAFLD vs controls (157±70 vs 131±67 g, p=0.07) but no difference in SAT. Mean peak stimulated GH was significantly lower in NAFLD vs controls (9.0±6.3 vs 15.4±11.2 ng/mL, p=0.003) which remained significant after controlled for age, BMI, sex and VAT. In a stepwise model including peak stimulated GH, VAT, age, BMI and sex, peak stimulated GH predicted 8% of the variability in IHL (p=0.004); no other variables were significant predictors of IHL. Mean IGF-1 (149±53 vs 151±49 ng/mL, p=0.80) and IGF-1 Z-score (-0.03±0.61 vs -0.03±0.68, p=0.90) were not significantly different between the groups.
Conclusion: Subjects with NAFLD have lower peak stimulated GH but similar IGF-1 levels compared to non-NAFLD controls of similar age, BMI and sex. Additionally, lower peak stimulated GH was predictive of higher IHL, independent of age, BMI, sex and VAT. This suggests that the relative GH deficiency of obesity may be an independent contributor to the development of NAFLD and that the GH axis and downstream signaling pathways may be a therapeutic target for this disease where few currently exist.
Is moderate alcohol use in nonalcoholic fatty liver disease good or bad? A critical review