CD163 is a marker of macrophages with anti-inflammatory properties and its soluble form (sCD163) is considered a prognostic predictor of several diseases including type 2 diabetes mellitus (T2DM). We explored sCD163 levels at baseline and after very low-calorie diet (VLCD) or bariatric surgery in 32 patients with obesity (20 undergoing VLCD and 12 bariatric surgery), 32 obese patients with T2DM (22 undergoing VLCD and 10 bariatric surgery), and 19 control subjects. We also assessed the changes of CD163 positive cells of monocyte-macrophage lineage in peripheral blood and subcutaneous adipose tissue (SAT) in subset of patients. Plasma sCD163 levels were increased in obese and T2DM subjects relative to control subjects (467.2±40.2 and 513.8±37.0 vs. 334.4±24.8 ng/ml, p=0.001) and decreased after both interventions. Obesity decreased percentage of CD163+CD14+ monocytes in peripheral blood compared to controls (78.9±1.48 vs. 86.2±1.31 %, p=0.003) and bariatric surgery decreased CD163+CD14+HLA-DR+ macrophages in SAT (19.4±2.32 vs. 11.3±0.90 %, p=0.004). Our data suggest that increased basal sCD163 levels are related to obesity and its metabolic complications. On the contrary, sCD163 or CD163 positive cell changes do not precisely reflect metabolic improvements after weight loss., A. Cinkajzlová, Z. Lacinová, J. Kloučková, P. Kaválková, P. Trachta, M. Kosák, J. Krátký, M. Kasalický, K. Doležalová, M. Mráz, M. Haluzík., and Obsahuje bibliografii
PPAR-α agonists improve insulin sensitivity in rodent models of obesity/insulin resistance, but their effects on insulin sensitivity in humans are less clear. We measured insulin sensitivity by hyperinsulinemic-isoglycemic clamp in 10 obese females with type 2 diabetes before and after three months of treatment with PPAR-α agonist fenofibrate and studied the possible role of the changes in endocrine function of adipose tissue in the metabolic effects of fenofibrate. At baseline, body mass index, serum glucose, triglycerides, glycated hemoglobin and atherogenic index were significantly elevated in obese women with type 2 diabetes, while serum HDL cholesterol and adiponectin concentrations were significantly lower than in the control group (n=10). No differences were found in serum resistin levels between obese and control group. Fenofibrate treatment decreased serum triglyceride concentrations, while both blood glucose and glycated hemoglobin increased after three months of fenofibrate administration. Serum adiponectin or resistin concentrations were not significantly affected by fenofibrate treatment. All parameters of insulin sensitivity as measured by hyperinsulinemic-isoglycemic clamp were significantly lower in an obese diabetic group compared to the control group before treatment and were not affected by fenofibrate administration. We conclude that administration of PPAR-α agonist fenofibrate for three months did not significantly affect insulin sensitivity or resistin and adiponectin concentrations in obese subjects with type 2 diabetes mellitus. The lack of insulin-sensitizing effects of fenofibrate in humans relative to rodents could be due to a generally lower PPAR-α expression in human liver and muscle., K. Anderlová, R. Doležalová, J. Housová, L. Bošanská, D. Haluzíková, J. Křemen, J. Škrha, M. Haluzík., and Obsahuje bibliografii a bibiografické odkazy
Recent studies have demonstrated that adipocyte fatty acid binding proteins (FABP) may play a role in the etiopathogenesis of insulin resistance. The aim of our study was to assess serum FABP levels in obese patients with type 2 diabetes mellitus (T2DM) before and after 3 months of treatment with PPAR-α agonist fenofibrate (F) and to explore the relationship of FABP to biochemical parameters and measures of insulin sensitivity assessed by hyperinsulinemic-isoglycemic clamp. We measured biochemical parameters by standard laboratory methods, insulin sensitivity by hyperinsulinemic-isoglycemic clamp and serum concentrations of FABP by commercial ELISA kit in 11 obese females with T2DM before and after three months of treatment with PPAR-α agonist fenofibrate and in 10 lean healthy control women (C). Serum FABP levels were 2.5-fold higher in T2DM group relative to C and were not affected by fenofibrate treatment (C: 20.6±2.1 μg/l, T2DM before F: 55.6±5.7 μg/l, T2DM after F: 54.2±5.4 μg/l, p<0.0001 for C vs. T2DM before F). Hyperinsulinemia during the clamp significantly suppressed FABP levels in both C and T2DM group. FABP levels positively correlated with BMI, triglyceride levels, blood glucose, glycated hemoglobin, atherogenic index and insulin levels. An inverse relationship was found between FABP and HDL levels, metabolic clearance rate of glucose, M/I and MCRglc/I sensitivity indexes. We conclude that FABP levels are closely related to BMI, parameters of insulin sensitivity, HDL levels and measures of diabetes compensation. This combination makes FABP a valuable marker of metabolic disturbances in patients with type 2 diabetes mellitus., M. M. Haluzík ... [et al.]., and Obsahuje seznam literatury
The aim of our study was to measure serum concentrations of fibroblast growth factor 19 (FGF-19) in patients with obesity (OB), obesity and type 2 diabetes mellitus (T2DM) and healthy subjects (C) at baseline and after selected interventions. We measured serum FGF-19 levels and other biochemical and hormonal parameters in 29 OB and 19 T2DM females and 30 sex- and age-matched control subjects. The interventions were acute hyperinsulinemia during isoglycemic-hyperinsulinemic clamp (n=11 for T2DM and 10 for C), very-low calorie diet (VLCD, n=12 for OB) and 3 months treatment with PPAR- α agonist fenofibrate (n=11 for T2DM). Baseline serum FGF-19 levels were significantly lower in OB relative to C group (132.1±12.7 vs. 202.2±16.7 pg/ml, p<0.05), while no significant difference was observed between T2DM and OB or control group. Acute hyperinsulinemia tended to decrease FGF-19 levels in both healthy and T2DM subjects. Three weeks of VLCD in OB group had no significant effect on FGF-19, whereas three months of fenofibrate treatment markedly reduced FGF-19 levels in T2DM patients (194.58±26.2 vs. 107.47±25.0 pg/ml, p<0.05). We conclude that FGF-19 levels in our study were at least partially dependent upon nutritional status, but were not related to parameters of glucose metabolism or insulin sensitivity., M. Mráz ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Recent studies focused on epicardial fat, formerly relatively neglected component of the heart, have elucidated some of its key roles. It possesses several properties that can distinguish it from other adipose tissue depots. Its unique anatomical location in the heart predisposes the epicardial fat to be an important player in the physiological and biochemical regulation o f cardiac homeostasis. Obesity is associated with an increase in epicardial fat mass. Excess of cardiac fat can contribute to greater left ventricular mass and work, diastolic dysfunction and attenuated septal wall thickening. Imbalance in adipokines levels secreted in autocrine or paracrine fashion by epicardial fat can contribute to the activation of the key atherogenic pathways in the setting of metabolic syndrome. Epicardial fat has also been identified as an important source of pro-inflammatory mediato rs worsening endothelial dysfunction, eventually leading to coronary artery disease. Increased production of pro-inflammatory factors by epicardial fat can also contribute to systemic insulin resistance in patients undergoing cardiac surgery. Here we revie w the most important roles of epicardial fat with respect to heart disease in the context of other underlying pathologies such as obesity and type 2 diabetes mellitus., Z. Matloch, T. Kotulák, M. Haluzík., and Obsahuje bibliografii