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Biomedical subjects

Marek Straczkowski

Publications and source records attributed to Marek Straczkowski.

15 recordsLinked to original sources
PubMed2006

Plasma levels of soluble tumor necrosis factor-alpha receptors are related to total and LDL-cholesterol in lean, but not in obese subjects.

BACKGROUND: Tumor necrosis factor-alpha (TNFalpha) is a mediator of insulin resistance. Plasma levels of soluble TNFalpha receptors (sTNFR1 and sTNFR2) probably reflect paracrine action of the cytokine. TNFalpha is also a regulator of lipid metabolism, however, data about impact of obesity on the relationships between TNFalpha and plasma lipids remain controversial. AIM: The purpose of the present study was to examine the associations of TNFalpha system with plasma lipids in lean and obese subjects with normal glucose metabolism. METHODS: We examined 63 subjects, 33 lean (BMI<25 kg x m(-2)) and 30 with marked overweight or obesity (BMI>27.8 kg x m(-2)). Anthropometric and biochemical parameters were measured. Oral glucose tolerance test and euglycemic hyperinsulinemic clamp were also performed. RESULTS: Obese subjects were markedly more insulin resistant and had higher levels of both TNFalpha receptors. Total (TC) and LDL-cholesterol (LDL-C), triglycerides (TG) and non-esterified fatty acids (NEFA) were also higher in the obese group. In obese subjects, both receptors were significantly related to TG and HDL-cholesterol (HDL-C), while sTNFR2 was also associated with NEFA. All those correlations disappeared after controlling for insulin sensitivity. In lean subjects, both receptors were related to TC, HDL-C and LDL-C. In that group, sTNFR1 predicted values of all those parameters independently of BMI, plasma glucose and insulin, and insulin sensitivity. CONCLUSION: We conclude that TNFalpha receptors are associated with plasma lipids in different way in lean and in obese subjects. TNFalpha system is probably important in determining cholesterol levels in lean subjects, while in obese this effect might be masked by other metabolic abnormalities.

Adult↗
PubMed2006

Plasma adiponectin concentration and tumor necrosis factor-alpha system activity in lean non-diabetic offspring of type 2 diabetic subjects.

OBJECTIVE: There is growing evidence that adiponectin function is related to the pathogenesis of insulin resistance. Insulin resistance might be present even in lean subjects with a strong family history of type 2 diabetes. The aim of the study was to look for adiponectin's role in the pathogenesis of insulin resistance in offspring of type 2 diabetic patients, and its relation to the activity of the tumor necrosis factor (TNF)-alpha system. RESEARCH DESIGN AND METHODS: The study was carried out in 23 lean offspring of type 2 diabetic subjects and in 23 controls matched for age, sex and body mass index. The oral glucose tolerance test for glucose and insulin estimations and hyperinsulinemic, euglycemic clamp studies were performed in all patients. The plasma concentration of adiponectin, TNF-alpha, soluble TNF receptors 1 and 2 (sTNFR1, sTNFR2), HbA1c, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein-cholesterol and triglycerides were estimated. RESULTS: The insulin sensitivity index, normalized for fat-free mass (M(ffm)) and adiponectin concentrations were markedly decreased in offspring of type 2 diabetic subjects compared with the control group (P = 0.0046 and P = 0.00058 respectively). TNF-alpha and sTNFR1 concentrations did not differ between the studied groups; however the concentration of sTNFR2 was markedly increased in the offspring of type 2 diabetic patients (P = 0.0002). Adiponectin concentration was positively correlated to the insulin sensitivity index (r = 0.34; P = 0.020) and to HDL-cholesterol (r = 0.29, P = 0.047) and was inversely related to sTNFR2 (r = -0.33, P = 0.027). CONCLUSIONS: The obtained results suggest that adiponectin could play a role in the pathogenesis of insulin resistance in lean offspring of type 2 diabetic subjects.

Adiponectin↗
PubMed2006

An alternative spliced variant of circulating soluble tumor necrosis factor-alpha receptor-2 is paradoxically associated with insulin action.

OBJECTIVE: Serum concentrations of soluble tumor necrosis factor-alpha (TNF-alpha) receptor 2 (sTNFR2) are associated with insulin resistance. In a recent study, we provided evidence for the existence of a biologically active form of sTNFR2 produced by alternative splicing (DS-TNFR2). We aimed to evaluate whether this circulating DS-TNFR2 is associated with insulin action in humans. DESIGN AND METHODS: Real time PCR (light cycler technology) evaluated DS-TNFR2 expression in monocytes. DS-TNFR2 was measured using a monoclonal antibody against an epitope present in TNFR2 (first 14 residues of the juxtamembrane region) but predicted to be absent in soluble proteolytic cleavage-produced TNFR2. Insulin sensitivity was measured using euglycemic hyperinsulinemic clamp (n = 76) and homeostatic model of assessment (HOMA) value in a replication study of 223 subjects. RESULTS: Real time PCR confirmed gene expression of DS-TNFR2 in monocytes from healthy subjects. A significant and positive association was found between serum DS-TNFR2 concentration and insulin sensitivity (P = 0.032, n = 76). This association was most significant in subjects with normal glucose tolerance (r = 0.44, P = 0.002). The subjects in whom DS-TNFR2 was detectable were more insulin sensitive than those with undetectable DS-TNFR2 (42.12+/-22.08 vs 31.71+/- 16.95 micromol x kg(-1) x min(-1), P = 0.039). DS-TNFR2 was inversely associated with body mass index, waist-to-hip ratio, systolic and diastolic blood pressure, fasting serum glucose, serum triglycerides and serum uric acid concentration and with the HOMA value (P = 0.03) in the replication study. Circulating DS-TNFR2 declined with increased number of components of the metabolic syndrome. CONCLUSION: Native sTNFR2 and DS-TNFR2 show opposite associations with insulin action. DS-TNFR2 might play a role as a counterpart of the proinflammatory environment associated with insulin resistance.

Adult↗
PubMed2004

Comparison of simple indices of insulin sensitivity using the euglycemic hyperinsulinemic clamp technique.

BACKGROUND: Insulin resistance is an important factor in the pathogenesis of type 2 diabetes mellitus and other diseases, collectively known as "metabolic syndrome". The gold standard in measuring insulin resistance is glucose clamp, but this method is difficult to apply in large studies. Therefore, indirect indices of insulin sensitivity are proposed. The aim of the present study was to compare these simple indices with data from clamp studies. MATERIAL/METHODS: We examined 51 obese subjects, 23 with impaired glucose tolerance (IGT), 28 with normal (obese-NGT), and 37 healthy lean controls. Insulin sensitivity was determined with the euglycemic hyperinsulinemic clamp technique. We estimated indices of insulin sensitivity: fasting plasma insulin (INS), logarithm INS (log [INS]), homeostasis model assessment (HOMA), logarithm HOMA (log [HOMA]) and quantitative insulin sensitivity check index (QUICKI). RESULTS: With clamp technique, we demonstrated a decrease in insulin sensitivity in both obese groups vs controls, and also in IGT compared to NGT subjects. The differences were significant when we used other indices of insulin sensitivity, except those for INS, log [INS] and HOMA between the two obese groups. Indirect indices correlated with insulin sensitivity derived from clamp in the whole population and in the subgroups of control and NGT-obese subjects. In the IGT group, only the correlations with log [INS], log [HOMA] and QUICKI were significant. CONCLUSIONS: Simple indices may give valuable information about insulin sensitivity in large studies. Indices based on log-transformed plasma glucose and insulin levels are recommended in subjects with IGT.

Adult↗
PubMed2004

Relationship between insulin sensitivity and sphingomyelin signaling pathway in human skeletal muscle.

In vitro studies revealed that insulin resistance might be associated with the intracellular formation of ceramide, the second messenger in the sphingomyelin signaling pathway. The aim of the present study was to examine the content and composition of fatty acids in ceramide and sphingomyelin in human muscle and to evaluate their relationships with insulin sensitivity. The study was conducted on 27 male subjects with normal glucose tolerance. Euglycemic-hyperinsulinemic clamps and biopsies of vastus lateralis muscle were performed. In 10 subjects, additional biopsies were taken after a 4-h clamp and after a clamp with concurrent Intralipid/heparin infusion. We identified 13 ceramides and sphingomyelins according to fatty acid residues. Insulin sensitivity was related to total ceramide content (r = -0.49, P = 0.01) and to ceramide consisting of palmitic (r = -0.48, P = 0.011), palmitoleic (r = -0.45, P = 0.019), mirystic (r = -0.42, P = 0.028), and nervonic acid (r = -0.39, P = 0.047). Hyperinsulinemia did not affect estimated muscle parameters. Intralipid/heparin infusion resulted in a 24.73% decrease in insulin sensitivity (P = 0.007) and a 47.81% increase in ceramide content (P = 0.005). These changes were significantly related to each other (r = -0.64, P = 0.046). A relationship with the decrease in insulin sensitivity was also observed for ceramides consisting of palmitic (r = -0.68, P = 0.03) and linoleic (r = -0.66, P = 0.038) acid. Our data indicate that the sphingomyelin signaling pathway in muscle might be an important factor determining the development of insulin resistance in humans.

Adult↗
PubMed2003

Plasma interleukin 8 concentrations in obese subjects with impaired glucose tolerance.

BACKGROUND: Interleukin 8 (IL-8) is a cytokine with atherogenic properties. In vitro studies revealed that it is produced and secreted by human adipocytes. We recently reported that plasma IL-8 is increased in obese subjects with normal glucose tolerance (NGT). The aim of the present study was to measure plasma IL-8 concentrations in subjects with impaired glucose tolerance (IGT). METHODS: A total of 44 subjects with marked overweight or obesity (BMI > 27.8 kg/m2), 27 with NGT and 17 with IGT, were recruited for the present study. Plasma IL-8 levels were measured in fasting state, after an oral glucose tolerance test (OGTT) and after euglycemic hyperinsulinemic clamp. RESULTS: The studied groups did not differ in fasting IL-8 concentrations. Both OGTT and clamp resulted in a significant increase in plasma IL-8. The change in IL-8 after clamp was similar in both groups. In contrast, after OGTT plasma IL-8 levels (IL-8OGTT) were markedly higher in IGT individuals. In IGT, but not NGT group, IL-8OGTT was positively related to postload glucose and negatively to insulin sensitivity. CONCLUSION: Plasma IL-8 concentrations after glucose load are increased in obese IGT subjects in comparison to normoglycemic weight-matched individuals. Increase in plasma IL-8 might be both insulin-mediated (during clamp) and glucose-mediated (during OGTT).

Journal Article↗
PubMed2003

Soluble tumor necrosis factor-alpha receptors in young obese subjects with normal and impaired glucose tolerance.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is a possible link between obesity and impaired glucose tolerance (IGT) and type 2 diabetes. Data about TNF-alpha and soluble forms of its receptors (sTNFR1 and sTNFR2) in IGT are controversial. The aim of the present study was to assess plasma TNF-alpha, sTNFR1, and sTNFR2 levels and to evaluate the relationships with insulin resistance in obese subjects with IGT. RESEARCH DESIGN AND METHODS: A total of 104 subjects participated in the present study: 30 obese subjects with IGT (obese-IGT), 32 obese subjects with normal glucose tolerance (obese-NGT), and 42 lean healthy control subjects (control-NGT). Anthropometry and blood biochemical parameters were measured and euglycemic-hyperinsulinemic clamp was performed. RESULTS: Obese-IGT subjects were more insulin resistant in comparison with obese-NGT and control-NGT groups; obese-NGT subjects were more insulin resistant than control-NGT. Plasma sTNFR1 and sTNFR2 were markedly higher in both groups of obese subjects in comparison with control-NGT and in the obese-IGT versus obese-NGT group. Plasma sTNFR1 and sTNFR2 were inversely related to insulin sensitivity. Both relationships remained significant after adjustment for age, BMI, waist girth, percent body fat, plasma glucose, insulin, nonesterified fatty acids, cholesterol, and triglycerides. Correlation between sTNFR2 and insulin sensitivity was also present in all the groups analyzed separately, but the correlation between sTNFR1 and insulin sensitivity was present only in the obese-NGT group. CONCLUSIONS: Our data suggest that TNF-alpha receptors are increased in obese-IGT subjects and are related to insulin resistance. These findings indicate that the TNF-alpha system might contribute to the development of insulin resistance in glucose-intolerant subjects.

Adult↗
PubMed2003

Insulin resistance in the first-degree relatives of persons with type 2 diabetes.

BACKGROUND: Type 2 diabetes is characterized by impaired insulin secretion and insulin resistance. Both genetic and environmental factors are thought to play a role in the pathogenesis of this disease. Obesity is associated with increased risk of type 2 diabetes, but some metabolic abnormalities may also be present in lean, predisposed subjects. The aim of the present study was to assess insulin sensitivity in lean normoglycemic offspring of parents with type 2 diabetes. MATERIAL/METHODS: We examined 17 lean offspring (BMI<25 kg x m-2) whose parents had type 2 diabetes, and 17 age, sex and BMI-matched subjects without family history of diabetes as controls. Anthropometric and biochemical measurements, oral glucose tolerance test (OGTT), and euglycemic hyperinsulinemic clamp were performed. RESULTS: The subjects did not differ in anthropometric measurements, and all had normal glucose tolerance according to WHO criteria. Offspring of type 2 diabetic parents were markedly more hyperinsulinemic (p<0.05) and insulin resistant (p<0.005). The ratio of the increase in insulin to the increase in glucose during the first 30 minutes of the OGTT, a crude index of first-phase insulin secretion, did not differ between groups. Insulin sensitivity was negatively related to fasting plasma insulin (r=-0.67, p<0.001) and non-esterified fatty acids (r=-0.43, p<0.02). CONCLUSIONS: Insulin resistance is present even in young lean subjects at high risk to develop type 2 diabetes. Our data suggest that insulin resistance may be a primary abnormality in the pathogenesis of this disease.

Adult↗
PubMed2003

[Insulin resistance in obese subjects with impaired glucose tolerance. Studies with hyperinsulinemic euglycemic clamp technique].

Insulin resistance is a key factor in the pathogenesis of impaired glucose tolerance (IGT) and type 2 diabetes and is also associated with greater risk for cardiovascular disease. Insulin resistance is more common in obese individuals and is considered to be the link between obesity and IGT and diabetes. The aim of the present study was to assess insulin resistance in obese subjects with IGT. We examined 57 subjects with marked overweight or obesity (BMI > > 27.8 kg x m-2), 27 with IGT and 30 with normal glucose tolerance (NGT), assessed by an oral glucose tolerance test, according to WHO criteria. Thirty lean (BMI < 25 kg x m-2) healthy subjects served as a control group. Anthropometric and biochemical parameters were measured. Insulin sensitivity was evaluated with hyperinsulinemic euglycemic clamp technique. Subjects with IGT had higher levels of glucose, insulin, non-esterified fatty acids and glycated hemoglobin than obese with NGT, all those parameters were also higher in both obese groups in comparison to controls. We showed significant differences in insulin sensitivity between the studied groups, an index of the whole-body glucose uptake was decreased in both obese groups in comparison to controls, and it was also lower in IGT than in obese NGT group. We observed marked negative correlations between insulin sensitivity and estimated anthropometric and biochemical parameters. Our study indicates that insulin resistance is an important factor determining a deterioration of glucose tolerance in subjects with overweight and obesity.

Adult↗
PubMed2003

[Assessment of insulin sensitivity during exercise training program in obese women. Comparison of simple indices with hyperinsulinemic euglycemic clamp technique].

Insulin resistance is a key element of metabolic syndrome, which includes disturbances of glucose tolerance, obesity, hypertension, coronary heart disease dyslipidemia and many other defects. An important problem in scientific research is precise measurement of insulin sensitivity. The method considered "the gold standard" is glucose clamp, however, it is difficult to apply this method in large studies. Therefore, simple indices of insulin resistance are proposed. It remains unclear whether those indices are able to reflect changes occurring during insulin-sensitizing intervention. The aim of the present study was to assess the use of indirect indices for the changes in insulin sensitivity during exercise training and to compare those indices with results derived from clamp. Fourteen obese normoglycemic women participated in 12-week exercise training program, which included exercise performed on a bicycle ergometer, 5 days a week for 30 minutes. Insulin sensitivity (M/FFM value) before and after training was measured with hyperinsulinemic euglycemic clamp technique. Simple indices of insulin resistance were also assessed: fasting plasma insulin (INS), logarithm INS (log [INS]), homeostasis model assessment (HOMA), logarithm HOMA (log [HOMA]) and quantitative insulin sensitivity check index (QUICKI). Before training, all those indices were markedly related to M/FFM. After training, an increase in M/FFM was observed. None of the examined indices markedly changed after training. There was no correlations between changes of evaluated indices and in M/FFM during training, and no relationships of those parameters after training. Our study indicates that simple indices are not able to reflect changes occurring during insulin-sensitizing intervention.

Adult↗
PubMed2002

Elevated soluble intercellular adhesion molecule-1 levels in obesity: relationship to insulin resistance and tumor necrosis factor-alpha system activity.

Intercellular adhesion molecule-1 (ICAM-1) is 1 of the possible factors linking obesity and diabetes with cardiovascular disease, however, the mechanism of the increase in ICAM-1 concentration in obesity remains unclear. Therefore, the aim of the present study was to assess plasma soluble ICAM-1 (sICAM-1) levels in obese subjects with normal glucose tolerance and to evaluate whether those levels may be related to insulin resistance and tumor necrosis factor-alpha (TNFalpha) system activity. The study was performed in 8 lean and 15 obese subjects. Anthropometric and biochemical parameters were measured, and insulin sensitivity was evaluated using the euglycemic hyperinsulinemic clamp technique (insulin infusion, 50 mU x kg(-1) x h(-1)). Obese subjects were markedly more hyperinsulinemic and insulin resistant and had higher plasma soluble TNF receptor 2 (sTNFR2) and sICAM-1 levels. sICAM-1 was related positively to body mass index (BMI), waist-to-hip ratio (WHR), percent of body fat, glycated hemoglobin (HbA(1c)), plasma insulin and triglycerides (TG), TNFalpha, and sTNFR2 and negatively to insulin sensitivity. Multiple regression analysis showed that only sTNFR2 and insulin sensitivity were independent predictors of sICAM-1 concentrations and were responsible for 66% of sICAM-1 variability. We conclude that an increase in plasma sICAM-1 concentration in obesity is related to TNFalpha system activation and insulin resistance.

Adult↗
PubMed2002

Circulating E-selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in men with coronary artery disease assessed by angiography and disturbances of carbohydrate metabolism.

It is hypothesized that adhesion molecules could be an early predictor of coronary artery disease. Therefore we investigated the relationship between the concentrations of soluble forms of adhesion molecules and disturbances of glucose metabolism in 78 men referred for coronary angiography but with no previous history of diabetes. The group consisted of 78 men (mean age, 47.6 +/- 7.0 years; mean body mass index [BMI], 28.4 +/- 3.24 with the symptoms of angina pectoris and positive exercise test. All subjects were given a standard oral glucose tolerance test (OGTT) with glucose and insulin estimations. Fasting plasma concentrations of the soluble (s) forms of E-selectin, intercellular adhesion cell molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and HbA(1c) were also measured. According to the OGTT, 10.2% of the patients (n = 8) fulfilled the criteria for type 2 diabetes mellitus and 44.9% (n = 35) for impaired glucose tolerance (IGT). The highest concentrations of sE-selectin were observed in patients with type 2 diabetes mellitus and were significantly higher in comparison to the group with normal glucose tolerance and IGT. The concentration of sVCAM-1 increased with the progression of disturbances of glucose metabolism and remained the highest in type 2 diabetic patients. sICAM-1 concentration was not significantly different. sE-selectin concentration correlated significantly with fasting glucose (r = 0.23, P =.041), postload glucose (r = 0.39, P =.001), and postload insulin (r = 0.28, P =.023). sVCAM-1 was significantly related to the postload glucose concentration (r = 0.30, P =.009). A significant correlation between sICAM-1 concentration and postload insulin was also observed (r = 0.27, P =.025). This would suggest that hyperglycemia increases sE-selectin and sVCAM-1 in plasma, which reflects excessive formation of atherosclerotic plaques in patients with disturbances of glucose metabolism.

Biomarkers↗
PubMed2002

Plasma interleukin-8 concentrations are increased in obese subjects and related to fat mass and tumor necrosis factor-alpha system.

Obesity is associated with the increased risk of cardiovascular disease; however, mechanisms responsible for such an increase are not fully understood. IL-8 is a cytokine that might have atherogenic properties. Recent in vitro studies revealed that IL-8 is produced and secreted by human adipocytes. The aim of the present study was to evaluate plasma IL-8 concentrations in obese subjects and the relationships between circulating IL-8 and anthropometric and biochemical parameters and TNF-alpha system. A total of 75 subjects with normal glucose tolerance, 35 lean and 40 obese, were recruited for this study. Plasma IL-8 levels were measured in fasting state, after an oral glucose tolerance test and after the euglycemic hyperinsulinemic clamp. A significant increase in plasma IL-8 was observed in the obese group. In simple regression analysis, performed for the initial evaluation of relationships, plasma IL-8 was related to body mass index, percentage of body fat, fat mass (FM), and soluble TNF-alpha receptor 2 (sTNFR2) in both groups and with waist-to-hip ratio and sTNFR1 in the obese. In multiple regression analysis, FM, waist-to-hip ratio, gender, sTNFR2, and low density lipoprotein cholesterol were responsible for 44% of IL-8 variability. During oral glucose tolerance testing, mean plasma IL-8 concentrations increased in both groups, whereas clamp resulted in a significant increase in plasma IL-8 only in the obese. We conclude that plasma IL-8 levels are increased in obese subjects, and are related to FM and TNF-alpha system. Increase in circulating IL-8 might be one of the factors linking obesity with greater cardiovascular risk.

Adipose Tissue↗
PubMed2002

Increased plasma-soluble tumor necrosis factor-alpha receptor 2 level in lean nondiabetic offspring of type 2 diabetic subjects.

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is one of the proposed mediators of insulin resistance, upregulated in human obesity. Insulin resistance, however, might precede the development of obesity, especially in subjects with a family history of type 2 diabetes. Therefore, the aim of the present study was to assess plasma levels of TNF-alpha and soluble forms of its receptors (soluble TNF-alpha receptors 1 [sTNFR1] and 2 [sTNFR2]) and to evaluate the relationship of the TNF-alpha system with insulin resistance in lean, nondiabetic offspring of type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We compared 20 lean offspring (BMI <25 kg/m(2), 8 men and 12 women) of type 2 diabetic patients with 20 lean subjects with no family history of diabetes, matched for age, sex, and BMI (control group). Anthropometry and blood biochemical parameters were measured, and insulin sensitivity was evaluated with the euglycemic-hyperinsulinemic clamp technique. RESULTS: Both men and women in the offspring group were markedly more insulin-resistant and had higher plasma levels of sTNFR2 (all P < 0.05). TNF-alpha, sTNFR1, and other examined parameters did not differ between the studied groups. Both TNF-alpha receptors were related to waist-to-hip ratio (WHR), fat-free mass (FFM), plasma total cholesterol, HDL cholesterol, LDL cholesterol, and nonesterified fatty acids (NEFAs). sTNFR2, but not sTNFR1, was also associated with insulin sensitivity (r = -0.49, P = 0.001). This relationship remained significant after adjustment for WHR, FFM, plasma insulin, and NEFA. CONCLUSIONS: TNF-alpha system might be involved in modulating insulin action before the onset of obesity in subjects at high risk for type 2 diabetes.

Adipose Tissue↗