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
This minireview briefly surveys the complexity of regulations governing the bone metabolism. The impact of clinical studies devoted to osteoporosis is briefly summarized and the emphasis is put on the significance of experimental mouse models based on an extensive use of genetically modified animals. Despite possible arising drawbacks, the studies in mice are of prime importance for expanding our knowledge on bone metabolism. With respect to human physiology and medicine, one should be always aware of possib le limitations as the experimental results may not be, or may be only to some extent, transposed to humans. If applicable to humans, results obtained in mice provide new clues for assessing un foreseen treatment strategies for patients. A recent publication representing in our opinion the important breakthrough in the field of bone metabolism in mice is commented in detail. It provides an evidence that skeleton is endocrine organ that affects energy metabolism and osteocalcin, a protein specifically synthesized and secreted by osteoblasts, is a hormone involved. If confirmed by other groups and applicable to humans, this study provides the awaited connection of long duration between bone disorders on one hand and obesity and diabetes on the other., O. Raška, K. Bernášková, I. Raška Jr., and Obsahuje seznam literatury
The aim of this study was to explore the changes in the adipokines leptin and adiponectin in obese patients with type 1 diabetes mellitus (T1DM) who underwent seven days of fasting and 21 days of low-calorie diet (LCD). The plasma leptin and adiponectin concentrations were measured in 14 obese patients with T1DM at baseline, immediately after 7 days of fasting, and after 21 days of LCD. 13 non-obese patients with T1DM were studied only after an overnight fasting. Bioimpedance technique was used for determination of body composition. Obese T1DM patients lost 6.0 kg (6.0; 6.8) (median, 25 %; 75 %) and decreased their fat tissue after fasting and LCD. Plasma leptin in obese T1DM was significantly higher than in non-obese T1DM patients: 9.10 (5.06; 25.89) vs. 1.71 (1.12; 7.08) μg ∙ l-1 and transiently decreased immediately after fasting: 3.45 μg ∙ l-1 (1.47; 7.00), (P<0.05). Adiponectin/leptin ratio in obese T1DM was significantly lower than in non-obese T1DM patients: 0.67 (0.57; 1.49) vs. 3.50 (2.46; 6.30) ∙ 103 and transiently increased immediately after fasting: 2.22 (1.26; 3.24) ∙ 103, (P<0.05). We conclude that obese patients with T1DM are characterized by hyperleptinemia that is reduced by prolonged fasting, but only slightly affected by low calorie diet., F. Musil, V. Blaha, A. Ticha, R. Hyspler, M. Haluzik, J. Lesna, A. Smahelova, L. Sobotka., and Obsahuje bibliografii
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
The gene for connexin 37 (Cx37) is considered to be one of the candidate genes for cardiovascul ar disease. We evaluated the association between Cx37 (1019C>T) gene polymorphism (Pro319Ser) and ankle brachial blood pressure index (ABI) in women with type 1 (n=178) and ty pe 2 (n=111) diabetes, and in women from general population (n=862). All women were genotyped for Cx37 polymorphism. In addition to traditional cardiovascular risk factors, ABI was analyzed. In women with type 1 diabetes, ABI significantly decreased from TT to CC carriers (p for trend= 0.008). A similar trend was seen in women with type 2 diabetes (p=0.050) and in women with waist circumference above 75 th percentile (94 cm; n=208) of the general population (p=0.049). The gene for Cx37 was associated with subclinical atherosclerosis in women with type 1 and 2 diabetes and in women with advanced central obesity. The presence of C allele indicated increased risk., J. Piťha, J. A. Hubáček, P. Piťhová., and Obsahuje bibliografii
Type 2 diabetes (T2D) as well as cardiovascular disease (CVD) represent major complications of obesity and associated metabolic disorders (metabolic sy ndrome). This review focuses on the effects of long-chain n-3 polyunsaturated fatty acids (omega-3) on insulin sensitivity and glucose homeostasis, which are improved by omega-3 in many animal models of metabolic syndrome, but remain frequently unaffected in humans. Here we focus on: (i) mechanistic aspects of omega-3 action, reflecting also our experiments in dietar y obese mice; and (ii) recent studies analysing omega-3’s effects in various categories of human subjects. Most animal experiments document beneficial effects of omega-3 on insulin sensitivity and glucose metabolism even under conditions of established obesity and insulin resistance. Besides positive results obtained in both cross- sectional and prospective cohort studies on healthy human populations, also some intervention studies in prediabetic subjects document amelioration of impaired glucose homeostasis by omega-3. However, the use of omega-3 to reduce a risk of new-onset diabetes in prediabetic subjects still remains to be further characterized. The results of a majority of clinical trials performed in T2D patients suggest that omega-3 have none or marginal effects on metabolic control, while effectively reducing hypertriglyceridemia in these pati ents. Despite most of the recent randomized clinical trials do not support the role of omega-3 in secondary prevention of CVD, this issue remains still controversial. Combined interventions using omega-3 and antidiabetic or hypolipidemic drugs should be further explored and considered for treatment of patients with T2D and other diseases., P. Flachs, M. Rossmeisl, J. Kopecky., 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
Cardiovascular diseases are the most common cause of mortality and morbidity in most populations. As the traditional modifiable risk factors (smoking, hypertension, dyslipidemia, diabetes mellitus, and obesity) were defined decades ago, we decided to analyze recent data in patients who survived acute coronary syndrome (ACS). The Czech part of the study included data from 999 males, and compared them with the post-MONICA study (1,259 males, representing general population). The Lithuanian study included 479 male patients and 456 age-matched controls. The Kazakhstan part included 232 patients and 413 controls. In two countries, the most robust ACS risk factor was smoking (OR 3.85 in the Czech study and 5.76 in the Lithuanian study), followed by diabetes (OR 2.26 and 2.07) and hypertension (moderate risk elevation with OR 1.43 and 1.49). These factors did not influence the ACS risk in Kazakhstan. BMI had no significant effect on ACS and plasma cholesterol was surprisingly significantly lower (P<0.001) in patients than in controls in all countries (4.80 ±1.11 vs. 5.76 ±1.06 mmol /l in Czechs; 5.32 ±1.32 vs. 5.71 ±1.08 mmol /l in Lithuanians; 4.88 ±1.05 vs. 5.38±1.13 mmol /l in Kazakhs/Russians). Results from our study indicate substantial heterogeneity regarding major CVD risk factors in different populations with the exception of plasma total cholesterol which was inversely associated with ACS risk in all involved groups. These data reflect ethnical and geographical differences as well as changing pattern of cardiovascular risk profiles., J. A. Hubacek, V. Stanek, M. Gebauerova, V. Adamkova, V. Lesauskaite, D. Zaliaduonyte-Peksiene, A. Tamosiunas, A. Supiyev, A. Kossumov, A. Zhumadilova, J. Pitha., and Obsahuje bibliografii