Hypoadiponectinemia Predicts the Severity of Hepatic Fibrosis and Pancreatic Beta-Cell Dysfunction in Nondiabetic Nonobese Patients with Nonalcoholic Steatohepatitis

Abstract

OBJECTIVES:The relationships between the adipokines tumor necrosis factor (TNF)-α and adiponectin and the parameters of glucose homeostasis and severity of liver disease were assessed in nonobese nondiabetic subjects with nonalcoholic steatohepatitis (NASH). METHODS:A frequently sampled intravenous glucose tolerance test, serum cytokine measurement, and 7-day alimentary record were performed in 20 biopsy-proven NASH patients and 45 age-, sex-, and BMI-matched controls (30 insulin sensitive and 15 insulin resistant). RESULTS:Patients with NASH had impaired pancreatic β-cell function compared with both insulin-sensitive (adaptation index, AI: 97.7 ± 17.7 vs 307.4 ± 24.1 min -2 mmol -1 L; p = 0.00001) and insulin-resistant (adaptation index, AI: 97.7 ± 17.7 vs 201.4 ± 41.1 min -2 mmol -1 L; p = 0.001) controls. Serum adiponectin levels were also significantly lower in the NASH group than in the two control groups and correlated with adaptation index and with the severity of hepatic steatosis, necroinflammation, and fibrosis. When NASH patients were grouped according to the severity of histological liver damage, adiponectin was the only variable discriminating patients with higher necroinflammatory grade and fibrosis score from those with milder lesions.CONCLUSIONS: β-cell secretory impairment is present in nonobese patients with NASH before glucose intolerance appears and may contribute to their increased risk for developing diabetes. Hypoadiponectinemia is a feature of NASH and may have a pathogenetic role in β-cell dysfunction and in hepatic necroinflammation and fibrosis, independently of insulin resistance, visceral fat accumulation, TNF-α axis activity, and dietary habits. Our findings provide further rationale for therapeutic approaches aimed at increasing adiponectin levels together with restoring β-cell function and insulin sensitivity.(Am J Gastroenterol 2005;100:2438-2446)

Nonalcoholic fatty liver disease: a challenge for pediatricians

“…27,46,[79][80][81] Research results has shown HOMA-IR has notably higher levels in NASH in comparison with simple steatosis, especially in obese children. 32,36,44,[82][83][84][85] In addition, the degree of liver involvement as diagnosed by ultrasonography and level of insulin secretion (oral glucose tolerance test) and IR (HOMA-IR) have shown compatible results. 22,30 There are also some studies based on comparison between different techniques of insulin sensitivity measurement, cutoff point 26,79 and accompanying biochemical test such as a lipid profile.…”

“…Reactive oxygen species: cytochrome P-450, 111 myeloperoxidase, nitric oxide synthase, lipid peroxidation products such as oxidized LDL, thiobarbituric acid-reacting substances 112 2. Inflammatory: TNFa, 113 adiponectine, 57,58,114,115 CRP, 48,83 visfatin, resistin, interleukin-6 and retinol binding protein-4 75,82 3. Apopetosis: cytokine-18 51,52 and fibrosis: hyaluronic acid 114 Table 2 represents the research results about the role of this group in predicting NASH.…”

Low adiponectin concentration during pregnancy predicts postpartum insulin resistance, beta cell dysfunction and fasting glycaemia

“…Specifically, adiponectin receptors are expressed on beta cells [28,29], although in vitro studies have reported conflicting findings with respect to the ability of adiponectin to stimulate insulin secretion [29,30]. In humans, low circulating adiponectin concentration has been associated with beta cell dysfunction in some [21,[31][32][33][34], but not all [29,35], studies, possibly because of differences in: (1) the methods used to evaluate beta cell function; (2) the populations under study; and (3) their sample sizes. Of note, the only two previous studies examining this question during pregnancy have indeed linked hypoadiponectinaemia and beta cell dysfunction in women with and without GDM [21,31].…”

High serum adiponectin correlates with advanced liver disease in patients with chronic hepatitis B virus infection

“…Because adiponectin appears to induce insulin sensitivity and modulate inflammatory responses, its level in both healthy subjects and patients with different stages of liver diseases, particularly in those with nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C virus (HCV) infection, has been partly unraveled . Consistently, serum adiponectin levels tend to be lower in patients with elevated serum alanine aminotransferase (ALT) values and those with fibrosis [23,26,27]. Paradoxically, serum adiponectin level seemed higher in patients with impaired liver function such as those with advanced fibrosis or cirrhosis, possibly because of decreased hepatic extraction of adiponectin [28][29][30].…”