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Mitochondrial dysfunction is a potentially important player in the development of insulin resistance and type 2 diabetes mellitus (T2DM). We investigated the changes of mRNA expression of genes encoding main enzymatic complexes of mitochondrial respiratory chain in subcutaneous adipose tissue (SCAT) and peripheral monocytes (PM) of 11 subjects with simple obesity (OB), 16 obese patients with T2DM and 17 healthy lean subjects (C) before and after very low-calorie diet (VLCD) using quantitative real time PCR. At baseline in SCAT, both T2DM and OB group had decreased mRNA expression of all investigated mitochondrial genes with the exception of 2 complex I (NDUFA 12) and complex IV (COX 4/1) enzymes in OB subjects. In contrast, in PM only the expression of complex I enzymes NDUFA 12 and MT-ND5 was reduced in both T2DM and OB subjects along with decreased expression of citrate synthase (CS) in T2DM group. Additionally, T2DM subjects showed reduced activity of pyruvate dehydrogenase and complex IV in peripheral blood elements. VLCD further decreased mRNA expression of CS and complex I (NT-ND5) and II (SDHA) enzymes in SCAT and complex IV (COX4/1) and ATP synthase in PM of T2DM group, while increasing the activity of complex IV in their peripheral blood elements. We conclude that impaired mitochondrial biogenesis and decreased activity of respiratory chain enzymatic complexes was present in SCAT and PM of obese and diabetic patients. VLCD improved metabolic parameters and ameliorated mitochondrial oxidative function in peripheral blood elements of T2DM subjects but had only minor and inconsistent effect on mitochondrial gene mRNA expression in SCAT and PM.

Omentin is a novel adipokine with insulin-sensitizing effects expressed predominantly in visceral fat. We investigated serum omentin levels and its mRNA expression in subcutaneous adipose tissue (SCAT) of 11 women with type 2 diabetes mellitus (T2DM), 37 obese non-diabetic women (OB) and 26 healthy lean women (C) before and after various weight loss interventions: 2-week very-low-calorie diet (VLCD), 3-month regular exercise and laparoscopic sleeve gastrectomy (LSG). At baseline, both T2DM and OB groups had decreased serum omentin concentrations compared with C group while omentin mRNA expression in SCAT did not significantly differ among the groups. Neither VLCD nor exercise significantly affected serum omentin concentrations and its mRNA expression in SCAT of OB or T2DM group. LSG significantly increased serum omentin levels in OB group. In contrast, omentin mRNA expression in SCAT was significantly reduced after LSG. Baseline fasting serum omentin levels in a combined group of the studied subjects (C, OB, T2DM) negatively correlated with BMI, CRP, insulin, LDL-cholesterol, triglycerides and leptin and were positively related to HDL-cholesterol. Reduced circulating omentin levels could play a role in the etiopathogenesis of obesity and T2DM. The increase in circulating omentin levels and the decrease in omentin mRNA expression in SCAT of obese women after LSG might contribute to surgery-induced metabolic improvements and sustained reduction of body weight.

Appropriate differentiation capacity of adipose tissue significantly affects its ability to store lipids and to protect nonadipose tissues against lipid spillover and development of insulin resistance. Preadipocyte factor-1 (Pref-1) is an important negative regulator of preadipocyte differentiation. The aim of our study was to explore the changes in circulating Pref-1 concentrations in female subjects with obesity (OB) (n=19), females with obesity and type 2 diabetes mellitus (T2DM) (n=22), and sex- and age-matched healthy control subjects (C) (n=22), and to study its modulation by very low calorie diet (VLCD), acute hyperinsulinemia during isoglycemic-hyperinsulinemic clamp, and 3 months' treatment with PPAR-α agonist fenofibrate. At baseline, serum Pref-1 concentrations were significantly higher in patients with T2DM compared to control group, while only nonsignificant trend towards higher levels was observed in OB group. 3 weeks of VLCD decreased Pref-1 levels in both OB and T2DM group, whereas 3 months of fenofibrate treatment had no significant effect. Hyperinsulinemia during the clamp significantly suppressed Pref-1 levels in both C and T2DM subjects and this suppression was unaffected by fenofibrate treatment. In a combined population of all groups, circulating Pref-1 levels correlated positively with insulin, leptin and glucose levels and HOMA (homeostasis model assessment) index. We conclude that elevated Pref-1 concentrations in T2DM subjects may contribute to impaired adipose tissue differentiation capacity associated with insulin resistance in obese patients with T2DM. The decrease of Pref-1 levels after VLCD may be involved in the improvement of metabolic status and the amelioration of insulin resistance in T2DM patients.

Background Fatigue is a frequent symptom among patients with rheumatoid arthritis (RA) and contributes to decreased quality of life in these patients [1].There are various questionnaires to assess fatigue in rheumatic diseases among them the vitality scale from SF-36 [2]. Objectives To assess the effect of one year of biologic therapy on fatigue of RA patients and correlate it with other parameters of the disease like laboratory and clinical activity, function and the quality of life. Methods 1029 patients from the Czech Registry of patients with RA (ATTRA), who had been treated with first line biological therapy for a minimum of 1 year, were analyzed. Following parameters were assessed at the start of biological therapy and 12 months after: Fatigue was assessed using the ninth item from SF-36, question: “Did you feel tired during past 4 weeks?” Humoral activity according to ESR and CRP, clinical activity was assessed by No. of tender and swollen joints and by patient9s disease activity assessment (VAS100mm) and DAS28-CRP, function by HAQ and quality of life by EuroQOL and further items of SF-36 (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional and mental health). Improvement, disease activity, function and quality of life after 12 month of biological therapy was assessed by counts (percentages) and median (interquartile range) when describing categorical and continuous variables respectively. Significance of improvement after 12 months and significance of association between fatigue improvement and improvement in other parameters of disease was assessed using p-value of Wilcoxon Signed Ranks Test and Kruskal-Wallis H Test, respectively. Results 1.After 12 months there is a significant improvement of fatigue as well as parameters of activity, function and quality of life (p 2.As to the correlation of the change in fatigue with the change of parameters of activity, function and the quality of life, the differences between patients in whom the fatigue improved were stronger as compared with patients in whom fatigue worsened, or remained stable. 3.The improvement of fatigue correlates most strongly with those parameters assessed by pats.,DAS28-CRP,CRPand ESR, less significantly (but still significantly) with tender joint count-p=0,02 and surprisingly not with swollen joint count. Conclusions One year biological therapy of RA leads to significant improvement not only of clinical parameters of the disease, but also to significant improvement of fatigue. The improvement of fatigue strongly correlates with the improvement of clinical and humoral activity, function and quality of life. Absence of correlation with the No. of swollen joint is no clear and requires further clarification. References Suurmeijer TP, Walz M, MoumT, et al. Quality of life profiles in the first years of rheumatoid arthritis. Arthritis Rheum 2001;45:111-21. Ware JE Jr, Sherbourne CD. The MOS 36-item Short-Form Health Survey (SF-36). Conceptual framework and item selection. Med Care 19925;30:473-83 Acknowledgements Aknowledgment: Supported by the Research program of the Ministry of health of Czech Republic: IGA MZ CR: No. 000 000 23728 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3842