Nonalcoholic Fatty Liver Disease Is Associated with Low Circulating Levels of Insulin-Like Growth Factor-I

Arturi, Franco; Succurro, Elena; Procopio, Cristina; Pedace, Elisabetta; Mannino, Gaia Chiara; Lugarà, Marina; Procopio, Teresa; Andreozzi, Francesco; Sciacqua, Angela; Hribal, Marta Letizia; Perticone, Francesco; Sesti, Giorgio

doi:10.1210/jc.2011-1227

Cited by 94 publications

(82 citation statements)

References 20 publications

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“…Conversely, a smaller study of 55 patients with NAFLD found no association between grade of fibrosis and GH concentrations. Perhaps unsurprisingly, as IGF1 is predominantly produced by the liver, there was a negative correlation between IGF1 and fibrosis stage (58) and low levels of circulating IGF1 in patients with NAFLD has been replicated in other studies (59). Using dynamic tests, peak levels of GH and IGF1 are reduced in patients with NAFLD (60), and in patients with pituitary disease, GH deficiency appears to be associated with increased hepatic lipid content (61).…”

Section: Oestrogensmentioning

confidence: 78%

Mechanisms in endocrinology: Non-alcoholic fatty liver disease in common endocrine disorders

Hazlehurst

Tomlinson

2013

European Journal of Endocrinology

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Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease spanning from simple benign steatosis to steatohepatitis with fibrosis and scarring that can eventually lead to cirrhosis. Its prevalence is rising rapidly and is developing into the leading indication for liver transplantation worldwide. Abnormalities in endocrine axes have been associated with NALFD, including hypogonadism, hypothyroidism, GH deficiency and hypercortisolaemia. In some instances, correction of the endocrine defects has been shown to have a beneficial impact. While in patients with type 2 diabetes the association with NAFLD is well established and recognised, there is a more limited appreciation of the condition among common endocrine diseases presenting with hormonal excess or deficiency. In this review, we examine the published data that have suggested a mechanistic link between endocrine abnormalities and NAFLD and summarise the clinical data endorsing these observations.

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Section: Oestrogensmentioning

confidence: 78%

Mechanisms in endocrinology: Non-alcoholic fatty liver disease in common endocrine disorders

Hazlehurst

Tomlinson

2013

European Journal of Endocrinology

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“…In addition, a meta-analysis of 42 observational studies demonstrated that elevated circulating IGF1 levels were significantly associated with prostate cancer risk (odds ratio, 1.21; 95% CI, 1.07-1.36) (Rowlands et al 2009). The liver is the main site of circulating IGF1 in humans (Jones & Clemmons 1995), and an increasing body of evidence has suggested that NAFLD is associated with low circulating levels of IGF1 (Arturi et al 2011, Fusco et al 2012. Thus, low circulating levels of IGF1 in NAFLD could explain to some extent why NAFLD is negatively associated with prostate cancer BCR after radical prostatectomy.…”

Section: Discussionmentioning

confidence: 99%

Nonalcoholic fatty liver disease is a negative risk factor for prostate cancer recurrence

Choi¹,

Lee²,

Yoon³

et al. 2014

Endocrine-Related Cancer

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Nonalcoholic fatty liver disease (NAFLD) is closely related to the metabolic syndrome, which is associated with an increased risk of various malignancies. In this study, we investigated the association between NAFLD and prostate cancer biochemical recurrence (BCR) after radical prostatectomy. Consecutive prostate cancer patients who underwent radical prostatectomy were enrolled from two hospitals in Korea and randomly assigned to the training (nZ147) or validation set (nZ146). The presence of NAFLD, BMI, preoperative prostate-specific antigen, and histological findings including Gleason score (GSc) were analyzed in regard to their association with BCR. NAFLD was diagnosed based on ultrasonography or unenhanced computed tomography images. BCR-free survival rates were calculated using the KaplanMeier method. In the training set, 32 (21.8%) patients developed BCR during a median follow-up period of 51 (inter-quartile range, 35-65) months. In the multivariate analysis, the presence of NAFLD (hazard ratio (HR), 0.36; 95% CI, 0.14-0.97; PZ0.04) was an independent negative predictive factor of BCR after adjustment for pathological GSc. Applied to the validation set, the presence of NAFLD maintained its prognostic value for longer time-to-BCR (HR, 0.17; 95% CI, 0.06-0.49; PZ0.001). In the subgroup analysis of patients with NAFLD, NAFLD fibrosis score was a single independent negative predictor for BCR (HR, 0.54; 95% CI, 0.30-0.98; PZ0.04). Our study demonstrated that NAFLD may play a protective role against BCR after radical prostatectomy for prostate cancer. Further study is warranted to elucidate the mechanism of protective effect in patients with NAFLD.

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“…In humans, NAFLD is associated with low circulating levels of IGF-I [65,66]. IL-6 and IGF-I are inde- …”

Section: Discussionmentioning

confidence: 99%

Essential roles of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in the liver [Review]

Takahashi

2012

Endocr J

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Abstract. Growth hormone (GH) and insulin-like growth factor-I (IGF-I) play essential roles in growth in childhood, and continue to have important metabolic actions in adults. Adult growth hormone deficiency (AGHD) is characterized by increased visceral adiposity, abnormal lipid profiles, premature atherosclerosis, decreased quality of life, and increased mortality. Recently, case reports and several clinical studies suggest that GHD state in adults is associated with an increased prevalence of nonalcoholic fatty liver disease (NAFLD) and progression to nonalcoholic steatohepatitis (NASH) or liver cirrhosis. As a mechanistic insight, growing evidence has revealed that GH as well as IGF-I play essential roles in the liver. Further investigation is necessary to clarify the precise mechanisms by which GH and IGF-I exert their effects in the liver; however, it should be noted that NAFLD/NASH has emerged as an important comorbidity in AGHD.

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Nonalcoholic Fatty Liver Disease Is Associated with Low Circulating Levels of Insulin-Like Growth Factor-I

Abstract: These data show that IGF-I levels are reduced in subjects with NAFLD and suggest that hepatic insulin resistance may affect IGF-I levels by modulating GH-stimulated synthesis of hepatic IGF-I.

Cited by 94 publications

References 20 publications

Mechanisms in endocrinology: Non-alcoholic fatty liver disease in common endocrine disorders

Mechanisms in endocrinology: Non-alcoholic fatty liver disease in common endocrine disorders

Nonalcoholic fatty liver disease is a negative risk factor for prostate cancer recurrence

Essential roles of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in the liver [Review]

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