Agnieszka Nikolajuk

High resistin and interleukin-6 levels are associated with gestational diabetes mellitus.

Resistin is a cysteine-rich adipokine originally described as a molecular link between obesity and insulin resistance in rodents. In this study, we hypothesised that serum resistin concentrations are elevated in patients with gestational diabetes mellitus (GDM) when compared with pregnant women with normal glucose tolerance (NGT) and related to proinflammatory interleukin-6 (IL-6) and other factors conferring insulin resistance. Serum resistin and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA) in 81 women with GDM, 82 women with NGT between 24 and 31 weeks of gestation and 25 healthy non-pregnant women. Resistin concentrations were significantly higher in the GDM (21.9 [17.55–25.40] ng/ml) than in the NGT group (19.03 [15.92–23.91] ng/ml, p = 0.047), as well as in the non-pregnant women (14.8 [13.7–16.6] ng/ml, p < 0.0001). Serum IL-6 levels were elevated in the GDM (1.0 [0.7–1.5] pg/ml) as compared with the NGT group (0.8 [0.5–1.1] pg/ml, p = 0.006) and the non-pregnant controls (0.7 [0.5–1.1] pg/ml, p = 0.04). Multiple regression analysis revealed that in the pregnant women circulating resistin was related to serum IL-6 (β = 0.33, p = 0.0004) but not to insulin or the index of insulin resistance. It is concluded that the finding of high resistin and IL-6 levels in women with gestational diabetes might confirm a role of low-grade inflammation in the pathogenesis of GDM.

Insulin resistance, serum adiponectin, and proinflammatory markers in young subjects with the metabolic syndrome

Insulin resistance is the underlying metabolic abnormality in the metabolic syndrome. The low-grade chronic inflammation may be associated with metabolic risk factors and atherogenesis. The aim of our study was to establish the link between the metabolic syndrome, as defined by the National Cholesterol Education Program (NCEP) criteria, and insulin sensitivity, serum adiponectin, and parameters of chronic inflammation in young subjects. The group of 223 subjects (mean age, 25.86 +/- 5.49 years; body mass index, 28.04 +/- 6.91 kg/m2) was studied. Oral glucose tolerance test, euglycemic hyperinsulinemic clamp, and estimation of serum adiponectin and proinflammatory factors were performed. The NCEP-defined metabolic syndrome was present in 49 subjects (21.97%). The higher the number of NCEP criteria fulfilled was, the bigger were the decrease in insulin sensitivity (P < .0001) and adiponectin (P < .0001) and the increase in fasting and postload insulin (both Ps < .0001), C-reactive protein (P < .0001), interleukin 18 (P < .0001), interleukin 6 (P < .0001), and soluble tumor necrosis factor-alpha receptors sTNFR1 (P < .0001) and sTNFR2 (P < .0001) observed. Multiple regression analysis revealed that adiponectin and inflammatory factors predicted NCEP score independent of insulin sensitivity (all adjusted beta values between .16 and .32, all Ps < .01). Young subjects with metabolic syndrome demonstrate an increased inflammatory response and lower adiponectin concentration.

Plasma apelin levels and apelin/APJ mRNA expression in patients with gestational diabetes mellitus

AIMS AND METHODS Apelin is a novel adipokine identified as an endogenous ligand of the G protein-coupled receptor APJ. In this study we compared plasma apelin concentrations in 101 patients with gestational diabetes (GDM) and 101 women with normal glucose tolerance (NGT) between 24 and 32 weeks of gestation (Group 1), as well as in 20 women with GDM and 16 subjects with NGT at term (Group 2). Apelin and APJ mRNA expression in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placental tissue were also measured in Group 2, using quantitative real-time PCR. RESULTS There were no significant differences in plasma apelin levels between the women with GDM and NGT (Group 1: 1555.6 [1281.2-1804.2]pg/ml vs 1656.5 [1430.2-1852.1]pg/ml, Group 2: 1607.9 [1453.4-1768.7]pg/ml vs 1493.8 [1316.8-1956.7]pg/ml) nor in apelin and APJ mRNA expression in SAT, VAT and placental tissue. Apelin mRNA expression was approximately 10 fold higher in placental than in adipose tissue (p<0.0001). Apelin and APJ mRNA expression correlated significantly in SAT (R=0.45, p=0.03), VAT (R=0.69, p=0.003) and placental tissue (R=0.37, p=0.03). CONCLUSIONS No associations between circulating apelin or apelin/APJ mRNA expression and GDM or the indices of insulin resistance were noted in our study.

Ceramide metabolism is affected by obesity and diabetes in human adipose tissue.

Ceramide is involved in development of insulin resistance. However, there are no data on ceramide metabolism in human adipose tissue. The aim of our study was to examine sphingolipid metabolism in fat tissue from obese nondiabetic (n = 11), obese diabetic (n = 11), and lean nondiabetic (n = 8) subjects. The content of ceramide (Cer), dihydroceramide (dhCer), sphingosine (SPH), sphinganine (SPA), sphingosine‐1‐phosphate (S1P; pmol/mg of protein), the expression (mRNA) and activity of key enzymes responsible for Cer metabolism: serine palmitoyltransferase (SPT), neutral and acidic sphingomyelinase (nSMase and aSMase, respectively), and neutral and acidic ceramidase (nCDase and aCDase, respectively) were examined in human adipose tissue. The contents of SPA and Cer were significantly lower whereas the content of dhCer was higher in both obese groups than the respective values in the lean subjects. The expression of examined enzymes was elevated in both obese groups. The SPT and CDases activity increased whereas aSMase activity deceased in both obese groups. We have found correlation between adipose tissue Cer content and plasma adiponectin concentration (r = 0.69, P < 0.001) and negative correlation between total Cer content and HOMA‐IR index (homeostasis model of insulin resistance) (r = −0.67, P < 0.001). We have found that both obesity and diabetes affected pathways of sphingolipid metabolism in the adipose tissue. J. Cell. Physiol. 227: 550–557, 2012.

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

BackgroundInterleukin 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).MethodsA 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.ResultsThe 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.ConclusionPlasma 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).

Serum Retinol Binding Protein 4 Is Related to Insulin Resistance and Nonoxidative Glucose Metabolism in Lean and Obese Women with Normal Glucose Tolerance

CONTEXT Retinol-binding protein (RBP) 4 is secreted by adipose tissue and is postulated to be a determinant of insulin sensitivity. The mechanisms of RBP4 insulin desensitizing action remain unclear. OBJECTIVE The aim of the present study was to estimate the relationships between serum RBP4 concentration with insulin sensitivity and oxidative and nonoxidative glucose metabolism in lean and obese women. DESIGN AND PARTICIPANTS The study group consisted of 67 women with normal glucose tolerance, 27 lean and 40 overweight or obese. Insulin sensitivity was estimated with the euglycemic hyperinsulinemic clamp. Glucose and lipid oxidation was measured with indirect calorimetry in the basal state and during the last 30 min of the clamp. Nonoxidative glucose metabolism was calculated in insulin-stimulated conditions by subtracting glucose oxidation from total glucose metabolism. RESULTS There was no difference in serum RBP4 concentration between lean and obese women. Serum RBP4 was inversely related to insulin sensitivity and nonoxidative glucose metabolism in the entire group (r = -0.36, P =0.003 in both cases) and within the subgroups of lean (r = -0.41, P =0.034 and r = -0.41, P =0.031) and obese women (r = -0.41, P =0.009 and r = -0.40, P =0.01, respectively). These relationships were independent of potential confounding factors. RBP4 levels were not associated with oxidative metabolism of glucose or lipid. CONCLUSIONS Our data indicate that serum RBP4 is related to decreased insulin sensitivity, mostly through its association with nonoxidative glucose metabolism.

Circulating Brain-Derived Neurotrophic Factor Concentration Is Downregulated by Intralipid/Heparin Infusion or High-Fat Meal in Young Healthy Male Subjects

OBJECTIVE Insulin resistance and type 2 diabetes are associated with an increased risk of neurodegenerative diseases. Brain-derived neurotrophic factor (BDNF) regulates neuronal differentiation and synaptic plasticity, and its decreased levels are supposed to play a role in the pathogenesis of Alzheimer’s disease and other disorders. The aim of the current study was to estimate the effects of hyperinsulinemia and serum free fatty acids (FFA) elevation on circulating BDNF concentration in humans. RESEARCH DESIGN AND METHODS We studied 18 healthy male subjects (mean age 25.6 ± 3.0 years; mean BMI 26.6 ± 4.8 kg/m2). Serum and plasma BDNF concentration was measured in the baseline state and in the 120 and 360 min of euglycemic hyperinsulinemic clamp with or without intralipid/heparin infusion. Furthermore, plasma BDNF was measured in 20 male subjects (mean age 22.7 ± 2.3 years; mean BMI 24.9 ± 1.5 kg/m2) 360 min after a high-fat meal. RESULTS Insulin sensitivity was reduced by ∼40% after 6 h of intralipid/heparin infusion (P < 0.001). During both clamps, serum and plasma BDNF followed the same pattern. Hyperinsulinemia had no effect on circulating BDNF. Raising FFA had no effect on circulating BDNF in 120 min; however, it resulted in a significant decrease by 43% in serum and by 35% in plasma BDNF after 360 min (P = 0.005 and 0.006, respectively). High-fat meal also resulted in a decrease by 27.8% in plasma BDNF (P = 0.04). CONCLUSIONS Our data show that raising FFA decreases circulating BDNF. This might indicate a potential link between FFA-induced insulin resistance and neurodegenerative disorders.

Visfatin in gestational diabetes: Serum level and mRNA expression in fat and placental tissue

AIMS AND METHODS In this study we measured: (1) serum visfatin concentrations in pregnant women with normal glucose tolerance (NGT) and gestational diabetes mellitus (GDM) between 26 and 33 weeks of gestation, using two immunoassays: EIA and ELISA; (2) serum visfatin levels (ELISA) and its mRNA expression (quantitative real-time PCR) in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placental tissue from women with NGT and GDM at term. RESULTS Visfatin concentrations (measured by EIA and ELISA) did not differ in the women with GDM and NGT between 26 and 33 weeks of gestation but were significantly lower in GDM than in NGT subjects at term (2.7 [0.7-4.6] vs 5.2 [3.7-5.9]ng/ml, p=0.02). There was no difference in visfatin mRNA expression in fat and placental tissue between the two subgroups. Regression analysis revealed that visfatin mRNA expression was significantly related to interleukin-6 and tumour necrosis factor-alpha mRNA expression in SAT (beta=0.39, p=0.009 and beta=0.47, p=0.002) and placental tissue (beta=0.37, p=0.03 and beta=0.49, p=0.005). CONCLUSIONS Circulating visfatin was significantly lower in the GDM than in the NGT subjects at term, although no differences in its mRNA expression in fat and placental tissues were observed.

Increased suppression of serum ghrelin concentration by hyperinsulinemia in women with anorexia nervosa

CONTEXT Ghrelin is a peptide secreted mainly by the stomach, which has the ability to stimulate appetite and food intake. Serum ghrelin concentration decreases rapidly after a meal, probably because of the concurrent increase in serum insulin. Anorexia nervosa (AN) is an eating disorder, which is characterized by high serum ghrelin concentration; however, the regulation of circulating ghrelin by insulin in this disorder remains unclear. OBJECTIVE To estimate serum ghrelin concentration in the fasting state and after hyperinsulinemia in women with AN. DESIGN AND PARTICIPANTS We examined 19 women with AN, 26 lean healthy women, and 25 women who were overweight or obese. Serum ghrelin concentration was measured in the fasting state and after euglycemic hyperinsulinemic clamp. RESULTS Insulin sensitivity was similar in AN and normal-weight women, and was markedly decreased in the obese subjects. In the fasting state, serum ghrelin was higher in AN group than in other groups (normal-weight, P=0.017; obese, P=0.0001) and in normal-weight women than in obese women (P=0.044). Hyperinsulinemia resulted in a marked decrease in serum ghrelin in AN (P<0.0001) and normal-weight women (P=0.002). The fall in serum ghrelin was higher in AN group than in other groups (normal-weight, P=0.0008; obese, P=0.0001), and was related to insulin sensitivity (r=0.24, P<0.05). In multiple regression analysis, only fasting serum ghrelin and the presence of AN were independent predictors of this fall. CONCLUSIONS Women with AN have an increased suppression of serum ghrelin by hyperinsulinemia. This phenomenon might lead to an increased and more rapid feeling of satiety in AN.

Circulating pro- and anti-inflammatory cytokines in Polish women with gestational diabetes.

In this study we measured serum concentrations of proinflammatory interleukin-6, interleukin-8, and interleukin-18 as well as anti-inflammatory interleukin-10 in 30 pregnant women with normal glucose tolerance, in 32 women with abnormal results of a 50-g glucose challenge test, and in 57 patients with gestational diabetes mellitus. Patients with gestational diabetes had significantly higher IL-6 (median 1.0 [0.7-1.5] vs. 0.7 [0.4-0.8] pg/ml, p=0.001), IL-8 (2.1 [1.1-4.2] pg/ml vs. 0.7 [0.4-0.9] pg/ml, p<0.0001), and IL-18 (249.3 [188.5-318.7] pg/ml vs. 186.7 [139.9-243.9] pg/ml, p=0.005) as well as lower IL-10 levels than healthy pregnant women (0.6 [0.5-1.5] pg/ml vs. 2.9 [1.8-3.2] pg/ml, p<0.0001). After adjusting for glucose, insulin, and BMI values, the differences in IL-8 and IL-18 became insignificant, whereas the differences in IL-6 and IL-10 levels remained highly significant (p<0.0001). The subjects with abnormal glucose challenge test results had higher IL-6 levels (0.9 [0.7-1.3] pg/ml, p=0.005) and similar levels of other cytokines as compared with the women with normal glucose tolerance. Our results suggest an impaired balance between circulating pro- and anti-inflammatory cytokines in patients with gestational diabetes; however, a significant contribution of maternal obesity to the increased levels of IL-8 and IL-18 should be underlined.