Serum preadipocyte factor-1 concentrations in females with obesity and type 2 diabetes mellitus: the influence of very low calorie diet, acute hyperinsulinemia, and fenofibrate treatment.

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.

[The influence of 6-months treatment with exenatide on type 2 diabetes mellitus compensation, anthropometric and biochemical parameters]. / Vliv 6mesícního podávání exenatidu na kompenzaci diabetes mellitus 2. typu, antropometrické a biochemické parametry.

OBJECTIVES: Exenatide, a synthetic GLP-1 analogue, is a new antidiabetic agent from the group ofincretine mimetics coming into the daily clinical practice. In our study we evaluated the effect of 6-months treatment with exenatide on diabetes compensation, anthropometric and biochemical parameters in the patients with poorly controlled type 2 diabetes mellitus and obesity. METHOD: We included 18 patients with poorly controlled diabetes (mean HbA1c 8.5 +/- 0.3%) treated with diet and peroral antidiabetic agents (4 patients were treated with insulin in the past). Exenatide was administered via subcutaneous injection twice daily for 6 months. Patients were examined after 1 month, when the dose ofexenatide was increased from 5 microg twice daily to 10 microg twice daily and after 3 and 6 months. We evaluated the diabetes compensation, biochemical parameters, body weight changes and side effects ofexenatide. RESULTS: 6-months exenatide treatment significant decreased body weight (baseline vs 6 month treatment 107.3 +/- 4.4 kg vs 103.7 +/- 4.6 kg, p = 0.02), BMI (36.7 +/- 1.2 kg/m2 vs 35.3 +/- 1.3 kg/m2, p = 0.01) a HbA1c (8.5 +/- 0.3% vs 7.4 +/- 0.4%, p = 0.04) and increased HDL-cholesterol (0.92 +/- 0.1 mmol/l vs 0.98 +/- 0.1 mmol/l, p = 0.02). Fasting glycemia tended to decline at the end of the study, but the difference did not reach the statistical significance. The area under the curve of glycemia levels after the standardized breakfast in the subgroup of 8 patients after the 6-months exenatide treatment was significantly lower when compared to baseline values (2,908 +/- 148 vs 2,093 +/- 194, p = 0.03). Concentrations of total and LDL-cholesterol and triglycerides did not change significantly. The most frequent side effects of exenatide treatments were transient anorexia and nausea (38.5%), dyspepsia and functional gastrointestinal discomfort (38.5%) and various neuropsychical symptoms (nervosity and insomnia - 30.8%). Most of the side effects disappeared during the treatment, none of these side effects was a reason for discontinuation of a treatment. 3 minor hypoglycemic episodes occured in patients simultaneously treated with derivates of sulfonylurea, but no serious hypoglycemia occured during the entire study. CONCLUSION: Exenatide treatment in obese patients with poor diabetes control was accompanied by statistically significant decrease of body weight, improvement of diabetes control and increase in HDL-cholesterol.

Serum concentrations of adipocyte fatty acid binding protein in patients with anorexia nervosa.

Serum adipocyte fatty acid-binding protein (FABP) concentrations are linked to human obesity and other features of metabolic syndrome. Whether FABP associates with metabolic alterations in chronic malnutrition is unknown. In the present study, we measured fasting serum levels of FABP, leptin, soluble leptin receptor, adiponectin, resistin, C-reactive protein (CRP), insulin, glucose, cholesterol and triglycerides in 19 patients with a restrictive type of anorexia nervosa (AN) and in 16 healthy age-matched control women (C). Body mass index, serum leptin, and CRP concentrations were significantly lower, while serum adiponectin and soluble leptin receptor levels were significantly higher in AN relative to C group. Serum insulin, glucose, cholesterol and triglyceride levels did not differ between the groups studied. Serum FABP levels were unchanged in patients with AN and were not related to any of parameters studied. We conclude that, in contrast to patients with obesity where FAPB is a prominent marker of metabolic alterations, chronic malnutrition in AN does not significantly affect its serum levels.

[The influence of very-low-calorie diet on soluble adhesion molecules and their gene expression in adipose tissue of obese women]. / Vliv nízkokalorické diety na sérové koncentrace a expresi cytoadhezivních molekul v tukové tkáni u obézních zen.

BACKGROUND: Adhesion molecules (AM) are proteins expressed on the endothelial surface that play an important role in development of endothelial dysfunction. Higher concentrations of AM were found in patients with atherosclerosis, obesity or type 2 diabetes mellitus. The aim of our study was to measure serum concentrations and gene expression of ICAM-1 (intercellular adhesion molecule 1), VCAM-1 (vascular adhesion molecule 1) and E-selectin in subcutaneous adipose tissue samples obtained by needle biopsy from obese women and healthy controls and to evaluate the effect of 3-weeks very-low-calorie diet (VLCD) on these parameters. METHODS AND RESULTS: 20 obese women (BMI 46.2 +/- 9.7 kg/m2) and 13 lean control women (BMI 23.8 +/- 2.3 kg/m2) were included into the study. Gene expression of AM in subcutaneous adipose tissue was measured using RT-PCR, serum AM levels were measured by multiplex immunoanalysis. At the baseline, serum E-selectin concentrations were higher in obese women compared to controls (24.4 +/- 2.3 vs. 15 +/- 1,5 ng/ml, p < 0,05). 3 weeks of VLCD significantly decreased BMI and serum E-selectin levels. Baseline mRNA expression of E-selectin, ICAM-1 and VCAM-1 in subcutaneous adipose tissue was lower in obese relative to lean women (p < 0.05). Weight reduction increased ICAM-1 and VCAM-1 gene expression (p < 0.05). CONCLUSIONS: Our results suggest that the subcutaneous adipose tissue is not the major source of the studied soluble adhesion molecules in obese women and that the regulation of AM local gene expression in subcutaneous adipose tissue probably differs from its circulating levels.

Increased angiotensinogen production in epicardial adipose tissue during cardiac surgery: possible role in a postoperative insulin resistance.

Critical illness induces among other events production of proinflammatory cytokines that in turn interfere with insulin signaling cascade and induce insulin resistance on a postreceptor level. Recently, local renin-angiotensin system of adipose tissue has been suggested as a possible contributor to the development of insulin resistance in patients with obesity. The aim of our study was to determine local changes of the renin-angiotensin system of subcutaneous and epicardial adipose tissue during a major cardiac surgery, which may serve as a model of an acute stress potentially affecting endocrine function of adipose tissue. Ten patients undergoing elective cardiac surgery were included into the study. Blood samples and samples of subcutaneous and epicardial adipose tissue were collected at the beginning and at the end of the surgery. Blood glucose, serum insulin and adiponectin levels were measured and mRNA for angiotensinogen, angiotensin-converting enzyme and angiotensin II type 1 receptor were determined in adipose tissue samples using RT PCR. Cardiac surgery significantly increased both insulin and blood glucose levels suggesting the development of insulin resistance, while serum adiponectin levels did not change. Expression of angiotensinogen mRNA significantly increased in epicardial adipose tissue at the end of surgery relative to baseline but remained unchanged in subcutaneous adipose tissue. Fat expression of angiotensin-converting enzyme and type 1 receptor for angiotensin II were not affected by surgery. Our study suggests that increased angiotensinogen production in epicardial adipose tissue may contribute to the development of postoperative insulin resistance.

[Pilot study to evaluate blood glucose control by a model predictive control algorithm with variable sampling rate vs. routine glucose management protocol in peri- and postoperative period in cardiac surgery patients]. / Pilotní studie pro srovnání pocítacového algoritmu s variabilním intervalem merení glykémie a standardního protokolu pro intenzivní inzulínovou terapii v peri- a pooperacním období u kardiochirurgických pacientu.

BACKGROUND: Increased blood glucose levels are frequently observed in critically ill patients. Recent studies have shown that the normalization of glycemia by intensive insulin therapy decreases mortality, length of the hospitalization and number of complications. METHODS AND RESULTS: The aim of this pilot study was to compare blood glucose control by an automated model predictive control algorithm with variable sampling rate (eMPC) with routine glucose management protocol (RP) in peri- and postoperative period in cardiac surgery patients. 20 patients were included into this study (14 men and 6 women, mean age 68 +/- 10 let, BMI 28.3 +/- 5.0 kg/m2). 10 patients were randomized for treatment using eMPC algorithm and 10 patients for routine protocol. All patients underwent elective cardiac surgery and were treated with continuous insulin infusion to maintain glycemia in target range 4.4-6.1 mmol/l. The study duration was 24 hours. Mean blood glucose was significantly lower in eMPC vs. RP group (5.80 +/- 0.45 vs. 7.23 +/- 0.84 mmol/l, p < 0.05). Percentage of time in target range was significantly higher in eMPC vs. RP group (67.6 +/- 8.7% vs. 27.6 +/- 15.8%, p < 0.05). Percentage of time above the target range was higher in RP vs. eMPC group. Average insulin infusion rate was higher in eMPC vs. RP group (4.18 +/- 1.19 vs. 3.24 +/- 1.43 IU/hour, p < 0.05). Average sampling interval was significantly shorter in eMPC vs. RP group (1.51 +/- 0.24 vs. 2.03 +/- 0.16 hour, p < 0.05). No severe hypoglycaemia in either group occurred during the study. CONCLUSIONS: The results of our pilot study suggest that eMPC algorithm is more effective in maintaining euglycemia in peri- and post-operative period in patients after cardiac surgery and comparably safe as compared to RP.

[Adiponectin and atherosclerosis]. / Adiponektin a ateroskleróza.

Obesity combined with other components of the insulin resistance syndrome is an important risk factor for atherosclerosis and its complications. The exact mechanisms through which the above diseases are linked have not yet been fully elucidated. One of the possible links may be a disturbance of the endocrine function of the adipose tissue of obese persons which produces an increased amount of proinflammatory and proatherogenic hormones and a lower amount of factors protecting against such pathologies. Adiponectin is the only hormone produced by the adipose tissue with a proven antiinflammatory and antiatherosclerotic effect. This hormone is predominantly produced by adipocytes and its concentrations are decreased in patients with obesity, insulin resistance and atherosclerosis. The objective of the article is to summarize current experimental and clinical knowledge of the links between adiponectin and atherosclerosis and to discuss possible utilization of adiponectin as a marker for atherosclerosis, and the potential for its exploitation in the prevention and/or treatment of atherosclerosis.

[The treatment of hyperglycaemia in critically ill patients: comparison of standard protocol and computer algorithm]. / Lécba hyperglykemie u kriticky nemocných pacientu: srovnání standardního protokolu a pocítacového algoritmu.

INTRODUCTION: Hyperglycemia is commonly observed in patients hospitalized on intensive care units. It is has been demonstrated that normalization of blood glucose level using intensive insulin therapy significantly improves prognosis of these patients. The aim of our study was comparison of standard protocol of intensive insulin therapy used on cardiac surgery ICU in General University Hospital in Prague and computer algorithm MPC (Model Predictive Control). PATIENTS AND METHODS: 20 patients with glycaemia higher than 6.7 mmol/l at the time of admission to ICU were included into the study, 10 subjects were randomized for standard treatment, 10 for treatment with MPC algorithm. Glycaemia was measured hourly during 48 hours, insulin infusion was rate was adjusted hourly in MPC algorithm or in 1-2 hours in standard protocol group. RESULTS: Blood glucose levels were in the target range significantly longer in MPC relative to standard protocol group (26.3 +/- 2.1 hrs vs 20.3 +/- 2.5 hrs). Mean blood glucose was also lower using MPC algorithm (6.47 +/- 0.11 vs 6.72 +/- 0.23 mmol/l). On the contrary the target range was established faster using standard protocol (8.9 +/- 1.2 vs 10.3 +/- 0.9 hrs), duration of hyperglycaemia was the same in both groups (7.3 +/- 1.9 in standard protocol vs 7.3 +/- 1.3 hrs in MPC algorithm). Average 48-hours insulin dose was higher in MPC than standard protocol group (230.2 +/- 38.8 vs 199.1 +/- 27.8 IU/48 hrs). 2 hypoglycaemic episodes occured in 2 patients in standard protocol group. CONCLUSIONS: Our results show that the use of MPC algorithm result in more effective blood glucose control in critically ill patients than standard protocol.

[The influence of obesity on the gene expression of adiponectin and its receptor in subcutaneous adipose tissue]. / Vliv obezity na genovou expresi adiponektinu a jeho receptoru v subkutánní tukové tkáni.

UNLABELLED: The objective of the study was to measure the concentration of adiponectin in plasma, its mRNA expression and the expression of the adiponectin receptors AdipoR1 and AdipoR2 in subcutaneous adpipose tissue (ST) of women with various levels of fat in their organism. A further objective of the study was to determine to what extent the stated parameters correlate with obesity as defined by BMI (body mass index) and how it can be affected by a very low calorie diet (VLCD). PATIENT SAMPLE: The sample of 70 women was divided into groups by BMI: patients with class 3 obesity (BMI > 40 kg.m(-2), n = 25), patients with class 1 and 2 obesity (BMI 30-40 kg.m(-2), n = 15), overweight patients (BMI 25-30 kg.m(-2), n = 10) and a normal healthy control group (BMI 20-25 kg.m(-2), n = 20). In the case of 14 women with class 3 obesity, the parameters were measured before and after a three-week diet with an energy content of 2200 kJ (550 kcal)/day (VLCD). METHOD: Plasma concentrations of adiponectin were measured using an ELISA kit (LINCO Research, USA). Subcutaneous adipose tissue was taken using biopsy. RNA was isolated using a MagNA Pure Compact RNA Isolation Kit (Tissue) (Roche, SRN). The gene expression of adiponectin, AdipoR1 and AdipoR2 was determined using the real-time PCR (RT-PCR) method on a ABI Real-Time PCR 7500 instrument (Applied Biosystems, USA) with TaqMan Gene Expression Assays hydrolisation probes. beta-2-mikroglobulin (beta2M) was used as an endogenous control, to which the data was normalised. RESULTS: The circulatory concentration of adiponectin, its mRNA expression and the mRNA expression of AdipoR1 in ST correlate negatively with BMI (r = -0.524, p < 0.001; r = -0.460, p < 0 001; p = -0.354, p = 0.004). The expression of AdipoR2 in ST did not correlate with BMI. The VLCD reduced weight by 9% but did not affect the plasma concentration of adiponectin or the rate of its expression, or the expression of AdipoR1 and AdipoR2. CONCLUSION: Our results show that not only the circulatory concentration of adiponectin but also its mRNA expression and the expression of AdipoR1 in ST are significantly lower in obese women compared to a control group and may contribute to the development of metabolic complications in obesity.