Determining the association between adipokine expression in multiple tissues and phenotypic features of non-alcoholic fatty liver disease in obesity.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is an obesity-associated disease, and in obesity adipokines are believed to be involved in the development of NAFLD. However, it is still not clear whether adipokines in the liver and/or adipose tissues can be related to the development of specific characteristics of NAFLD, such as steatosis and inflammation. We aimed to address this question by simultaneously examining the adipokine expression in three tissue types in obese individuals. METHODS: We enrolled 93 severely obese individuals with NAFLD, varying from simple steatosis to severe non-alcoholic steatohepatitis. Their expression of 48 adipokines in the liver, visceral and subcutaneous adipose tissue (SAT) was correlated to their phenotypic features of NAFLD. We further determined whether the correlations were tissue specific and/or independent of covariates, including age, sex, obesity, insulin resistance and type 2 diabetes (T2D). RESULTS: The expression of adipokines showed a liver- and adipose tissue-specific pattern. We identified that the expression of leptin, angiopoietin 2 (ANGPT2) and chemerin in visceral adipose tissue (VAT) was associated with different NAFLD features, including steatosis, ballooning, portal and lobular inflammation. In addition, the expression of tumor necrosis factor (TNF), plasminogen activator inhibitor type 1 (PAI-1), insulin-like growth factor 1 (somatomedin C) (IGF1) and chemokine (C-X-C motif) ligand 10 (CXCL10) in the liver tissue and the expression of interleukin 1 receptor antagonist (IL1RN) in both the liver and SAT were associated with NAFLD features. The correlations between ANGPT2 and CXCL10, and NAFLD features were dependent on insulin resistance and T2D, but for the other genes the correlation with at least one NAFLD feature remained significant after correcting for the covariates. CONCLUSIONS: Our results suggest that in obese individuals, VAT-derived leptin and chemerin, and hepatic expression of TNF, IGF1, IL1RN and PAI-1 are involved in the development of NAFLD features. Further, functional studies are warranted to establish a causal relationship.

Cognitive-educational treatment of fibromyalgia: a randomized clinical trial. I. Clinical effects.

OBJECTIVE: This randomized controlled clinical trial evaluates the effectiveness of outpatient group cognitive/educational treatment for patients with the fibromyalgia (FM) syndrome. We hypothesized that the combination of group education with cognitive treatment aimed at developing pain coping skills would be more effective than group education alone. METHODS: 131 patients with FM were randomly assigned to 3 conditions: an experimental condition, which was the combined cognitive/educational intervention (ECO); an attention control condition consisting of group education plus group discussion (EDI); and a waiting list control (WLC). For the treatment conditions ECO and EDI, assessments were made 2 weeks before treatment, at start of treatment, at post-treatment, and at 6 and 12 mo followup. WLC patients received only 3 assessments. RESULTS: There were no pretreatment differences between the groups, or between dropouts and patients who remained in the study. At post-treatment, and compared with the WLC, the ECO patients improved in knowledge about FM (p = 0.007) and pain coping (p < 0.001). EDI patients improved on pain coping (p = 0.005) and pain control (p = 0.002). EDI patients reported significantly less fear than ECO patients (p = 0.005). There were no other differential effects between ECO and EDI at post-treatment or 6 mo or 12 mo followup. Based on the reliability of change index for clinical significance, the relative short term success rates are 6.4 and 18.4% for ECO and EDI, respectively. CONCLUSION: The surplus value of a highly structured, 12 session group cognitive treatment added to group education cannot be supported by our study. In EDI, fear reduction might have enhanced pain coping and pain control, while poor compliance, the difficulty of homework assignments, and lack of individual support may have limited the effectiveness of ECO.

Cognitive-educational treatment of fibromyalgia: a randomized clinical trial. II. Economic evaluation.

OBJECTIVE: In this 3 year randomized clinical trial the cost effectiveness of a 6 week educational/cognitive intervention (ECO) is compared with an educational discussion intervention (EDI) and a waiting list condition (WLC). METHODS: A total of 131 patients with fibromyalgia were randomly allocated to the ECO, EDI, or WLC intervention. The ECO and EDI groups were followed for 12 months, whereas the WLC group was followed for 6 weeks. Direct health care and nonhealth care costs, and the indirect costs associated with lost production due to illness, were calculated. The effects were measured in terms of utilities, using rating scale and standard gamble methods. RESULTS: Treatment costs were estimated to be US $980 per patient for both ECO and EDI. The total direct health care costs of ECO treatment were US $1623 higher than those for EDI. This difference was significant. Indirect costs for the 2 groups were not significantly different. At 6 weeks there was a significant difference in rating scale utilities between the 3 groups, caused by a significantly greater improvement in the EDI group compared to the WLC group. However, no significant differences in either rating scale or standard gamble utilities were found between the ECO and EDI groups immediately after treatment, or at the 6 or 12 month followups. CONCLUSION: The economic evaluation showed that the addition of a cognitive component to the educational intervention led to significantly higher health care costs and no additional improvement in quality of life compared to the educational intervention alone. This conclusion is robust through a range of plausible values used in a sensitivity analysis.