Serum irisin and its regulation by hyperinsulinemia in women with polycystic ovary syndrome.

Irisin is an adipokine/myokine which could be connected with insulin sensitivity. Polycystic ovary syndrome (PCOS) is characterized by oligo- or anovulation, polycystic ovary, hyperandrogenism and insulin resistance. The aim of the present study was to determine the relationship between serum irisin concentration and insulin sensitivity (Mffm) as well as the effect of insulin infusion on circulating irisin levels in PCOS women as compared with healthy controls. Seventy seven women were enrolled in the study - 57 with PCOS and 20 healthy controls matched for BMI and age. Hyperinsulinemic euglycemic clamps were performed in all of the study participants. The serum concentrations of irisin at baseline and after the clamp, as well as changes of serum irisin concentration in response to insulin supplied during the clamp (Δ irisin), were estimated. The mean serum concentrations of irisin at baseline and after hyperinsulinemia were higher in PCOS women in comparison to the control group (p=0.01; p=0.006, respectively). Insulin infusion resulted in a decrease of serum irisin concentration only in the PCOS group (p=0.007). In the control group, Δ irisin positively correlated with Mffm (r=0.56, p=0.009). In the entire group, multiple regression analysis showed that Δ irisin (ß=0.70, p=0.0002), FFAs 60' during the clamp study (ß=-0.22, p=0.01), SHBG (ß=0.54, p<0.0001) and the interaction between Δ irisin and PCOS (ß=-0.67, p=0.0004) were significantly associated with Mffm. The higher serum irisin concentrations at baseline and in response to insulin infusion might be secondary to insulin resistant conditions in PCOS women.

Serum anti-Müllerian hormone concentration in women with polycystic ovary syndrome and type 1 diabetes mellitus.

PURPOSE: A single prior study conducted in Chilean women has shown that women with type 1 diabetes mellitus (T1DM) and polycystic ovary syndrome (PCOS) have a normal serum anti-Müllerian hormone (AMH) concentrations despite polycystic ovarian morphology. As it is not clear why women with PCOS+T1DM would not have an elevated concentrations of AMH, we hypothesize that women with T1DM and PCOS have a similar hormonal profile and serum AMH levels as is observed in classic PCOS. METHODS: We studied 89 women: 37 with T1DM (16 with PCOS+T1DM, 21 with T1DM/no-PCOS), 36 with PCOS (PCOS) and 16 healthy women (control group) matched for age and body mass index (BMI). A clinical examination, determination of serum AMH and sex hormones, and an ultrasonographic evaluation of the ovaries were performed for all study participants. RESULTS: Serum AMH concentrations were significantly higher in women with PCOS+T1DM than in those with T1DM/no-PCOS (p<0.001) and was not different between both PCOS groups (PCOS vs PCOS+T1DM). Ovarian volume and ovarian follicle count did not differ between women with PCOS+T1DM and PCOS. The number of ovarian follicles was higher in patients with PCOS+T1DM and PCOS versus the control (p=0.007, p<0.001) and versus cases of T1DM/no-PCOS (p<0.001, p<0.001, respectively). Cross-sectionally, AMH concentrations correlated positively with luteinizing hormone (LH) (r=0.4; p<0.001), testosterone (r=0.2, p=0.02), ovarian volume (r=0.4, p<0.001) and follicle count (r=0.7, p<0.001). In both groups, PCOS+T1DM and PCOS, AMH was related to LH (r=0.5; p=0.036; r=0.3; p=0.031) and to ovarian follicle number (r=0.7; p<0.001; r=0.4; p=0.006). In multivariate logistic regression analysis, serum AMH was the only predictor of PCOS in T1DM women (OR=1.73; 95% CI 1.07-2.79, p=0.023). CONCLUSIONS: Women with T1DM and PCOS have a similar hormonal profile and serum AMH concentrations as observed in classic PCOS.

Relationships of serum soluble E-selectin concentration with insulin sensitivity and metabolic flexibility in lean and obese women.

The markers of endothelial dysfunction, including soluble E-selectin (sE-selectin), are related to insulin resistance, which is associated with metabolic inflexibility, i.e., impaired stimulation of carbohydrate oxidation and impaired inhibition of lipid oxidation by insulin. Endothelial dysfunction may also be important in the metabolic syndrome. The aim of our study was to analyze the association of sE-selectin with insulin sensitivity and metabolic flexibility in lean and obese women. We examined 22 lean women (BMI < 25 kg m(-2)) and 26 overweight or obese women (BMI > 25 kg m(-2)) with normal glucose tolerance. A hyperinsulinemic euglycemic clamp and indirect calorimetry were performed. An increase in the respiratory exchange ratio in response to insulin was used as a measure of metabolic flexibility. Obese women had lower insulin sensitivity (P < 0.01), higher plasma sE-selectin (P = 0.007), and higher the metabolic syndrome total Z-score (MS Z-score) (P < 0.0001). Insulin sensitivity was negatively correlated with sE-selectin level (r = -0.24, P = 0.04). sE-selectin was associated with the rate of carbohydrate oxidation at the baseline state (r = 0.31, P = 0.007) and was negatively correlated with metabolic flexibility (r = -0.34, P = 0.003). MS Z-score correlated positively with sE-selectin level and negatively with metabolic flexibility and insulin sensitivity (r = 0.49, P < 0.0001, r = -0.29, P = 0.04, r = -0.51, P < 0.0001, respectively). In multiple regression analysis we observed that the relationship between metabolic flexibility and sE-selectin (ß = -0.36; P = 0.004) was independent of the other evaluated factors. Our data suggest that endothelial dysfunction as assessed by plasma sE-selectin is associated with metabolic flexibility, inversely and independently of the other estimated factors.

Normal metabolic flexibility despite insulin resistance women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder, where insulin resistance might be involved in the development of endocrine and metabolic abnormalities. Insulin resistance (IR) is connected with disturbances in switching between lipid and carbohydrate oxidation in response to insulin, called "metabolic inflexibility". The aim of the present study was to estimate the whole-body insulin sensitivity, lipid and carbohydrate oxidation, metabolic flexibility in lean and obese PCOS women. The study group consisted of 92 women with PCOS, 40 lean (BMI<25 kg/m²) and 52 overweight or obesity (BMI>25 kg/m²), and 30 healthy normally menstruating women (14 lean and 16 overweight/obese) with normal glucose tolerance. Hyperinsulinemic euglycemic clamp and indirect calorimetry were performed. An increase in respiratory exchange ratio in response to insulin was used as a measure of metabolic flexibility. Both the presence of PCOS (P<0.001) and obesity (P=0.005) were independently characterized by lower insulin sensitivity. PCOS (P=0.002) and obesity (P=0.001) independently predisposed to the lower non-oxidative glucose metabolism. Obese women had lower glucose oxidation (P=0.005) and higher lipid oxidation (P<0.001) in insulin-stimulated conditions in comparison to lean subject whereas PCOS had no effect on these parameters (P=0.29 and P=0.43; respectively). Metabolic flexibility was impaired in the obese (P=0.001) but it was not influenced by the presence of PCOS (P=0.78). Our data indicate that PCOS women have normal metabolic flexibility, which could suggest a distinct pathophysiological mechanism for insulin resistance in this group.

The effect of insulin infusion on the metabolites in cerebral tissues assessed with proton magnetic resonance spectroscopy in young healthy subjects with high and low insulin sensitivity.

OBJECTIVE: Insulin may play important roles in brain metabolism. Proton magnetic resonance spectroscopy ((1)H-MRS) of the central nervous system gives information on neuronal viability, cellular energy, and membrane status. To elucidate the specific role of insulin action in the brain, we estimated neurometabolites with (1)H-MRS and assessed their regulation by insulin infusion and their relationship with insulin sensitivity. RESEARCH DESIGN AND METHODS: We studied 16 healthy young men. (1)H-MRS was performed at baseline and after 240 min of euglycemic-hyperinsulinemic clamp. Voxels were positioned in the left frontal lobe, left temporal lobe, and left thalamus. The ratios of N-acetylaspartate (NAA), choline-containing compounds (Cho), myo-inositol, and glutamate/glutamine/γ-aminobutyric acid complex (Glx) to creatine (Cr) and nonsuppressed water signal were determined. The participants were divided into subgroups of high (high IS) and low (low IS) insulin sensitivity. RESULTS: Baseline neurometabolic substrates were not different between the groups. Insulin infusion resulted in an increase in frontal NAA/Cr and NAA/H2O and frontal and temporal Glx/Cr and Glx/H2O and a decrease in frontal Cho/Cr and temporal Cho/H2O and myo-inositol/H2O (all P < 0.05, except temporal Glx/H2O, P = 0.054, NS) in the high-IS, but not in the low-IS, group. Insulin sensitivity correlated positively with frontal NAA/Cr and NAA/H2O and temporal Glx/H2O and negatively with temporal myo-inositol/Cr and myo-inositol/H2O assessed during the second (1)H-MRS (all P < 0.05). CONCLUSIONS: Insulin might influence cerebral metabolites, and this action is impaired in subjects with low whole-body insulin sensitivity. Thus, our results provide a potential link between insulin resistance and altered metabolism of the central nervous system.

Serum visfatin is differentially regulated by insulin and free Fatty acids in healthy men.

CONTEXT: Serum visfatin is elevated in insulin-resistant states, ie, obesity, type 2 diabetes mellitus, and polycystic ovary syndrome, thus linking visfatin with the pathogenesis of insulin resistance. OBJECTIVE: Our objective was to evaluate the effect of hyperinsulinemia and the acute elevation of free fatty acids (FFAs) on serum visfatin in humans. DESIGN, SETTING AND SUBJECTS: We estimated serum visfatin during hyperinsulinemia and the insulin-resistant conditions caused by an acute elevation of FFAs in 19 healthy male volunteers (mean age, 25 ± 7 years; body mass index, 26 ± 4 kg/m(2)) at a university hospital. INTERVENTIONS: Intervention included a 6-hour euglycemic-hyperinsulinemic clamp without and with Intralipid/heparin infusion. MAIN OUTCOME MEASURES: Measurements were made of serum visfatin at baseline and at 2 and 6 hours during both clamp studies. RESULTS: Hyperinsulinemia resulted in a significant decrease in serum visfatin concentration (P = .043). Concomitant Intralipid/heparin infusion, which caused a reduction of insulin sensitivity by 40% (P < .0001), resulted in a marked increase in serum visfatin (P < .0001), which was already observed after 2 hours of FFAs increase (P < .0001). Serum visfatin during the clamp study after 2 and 6 hours of Intralipid/heparin infusion was significantly higher than respective values during the clamp study without the elevation of FFAs (both P < .0001). The increase in serum visfatin during Intralipid/heparin infusion was positively related to body weight (r = 0.54, P = .016) and γ-glutamyltransferase activity (r = 0.56, P = .011). CONCLUSIONS: Serum visfatin is differentially regulated by insulin and FFAs. One might hypothesize that the induction of insulin resistance by FFAs suppresses insulin inhibition of visfatin secretion, resulting in a serum visfatin increase in insulin-resistant conditions.

Circulating interleukin 6 and soluble forms of its receptors in relation to resting energy expenditure in women with anorexia nervosa.

CONTEXT: Anorexia nervosa (AN) is an eating disorder, resulting in sustained low weight and marked decrease in fat mass. Interleukin 6 (IL-6) may play a role in appetite, energy expenditure and body weight control. IL-6 acts through binding with membrane receptor (IL-6R) and activates glycoprotein 130 (gp130) signalling. Both IL-6R and gp130 are present in the blood in the soluble forms (sIL-6R and sgp130 respectively). sIL-6R sensitizes cells towards IL-6, whereas sgp130 inhibits gp130 signalling. OBJECTIVE: To estimate circulating IL-6/sIL-6R/sgp130 system and its relationships with body weight and resting energy expenditure (REE) in AN women. PATIENTS: We examined 19 women with AN and 27 healthy normal-weight female controls. MEASUREMENTS: Indirect calorimetry and the measurement of serum IL-6, sIL-6R and sgp130 concentrations were performed in all the subjects. RESULTS: REE was decreased in AN women (P < 0·001). Serum IL-6 was higher in AN women in comparison with control group (P = 0·005). Serum sIL-6R was lower (P = 0·009) and serum sgp130 was higher (P = 0·004) in AN women in comparison with controls. IL-6 and sIL-6R were related to REE in the entire study population (r = -0·54, P < 0·001 and r = 0·48, P = 0·001 respectively) and in AN group (r = -0·54, P = 0·024 and r = 0·60, P = 0·011 respectively). CONCLUSIONS: Increased IL-6 in AN seems to be compensated by the changes in sIL-6R and sgp130, which are directed towards inhibition of IL-6 action. The balance between these factors might play a role in the regulation of energy expenditure in AN.

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/m(2)). 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/m(2)) 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.

Hyperinsulinemia acutely increases serum macrophage inhibitory cytokine-1 concentration in anorexia nervosa and obesity.

CONTEXT: Macrophage inhibitory cytokine-1 (MIC-1) plays a role in the regulation of cellular responses to stress signals and inflammation. MIC-1 has also been implicated in mediation of tumour-induced anorexia and weight loss. Increased serum concentrations of MIC-1 were found in patients with anorexia nervosa (AN), obesity and type 2 diabetes. OBJECTIVE: To estimate serum MIC-1 concentration in women with AN and obese women, its regulation by hyperinsulinemia and relationship with insulin sensitivity. PATIENTS: We examined 20 women with AN, 28 healthy normal-weight female controls and 28 obese women. MEASUREMENTS: Serum MIC-1 concentration was measured in the fasting state and after 2-h euglycemic hyperinsulinemic clamp. RESULTS: At baseline, serum MIC-1 was higher in AN in comparison with other groups (normal-weight, P = 0·018; obese, P = 0·01). Hyperinsulinemia resulted in a significant increase in serum MIC-1 concentration in the entire study population (P < 0·001) and in AN (P < 0·001), normal-weight (P = 0·002) and obese (P < 0·001) groups analysed separately. Postclamp serum MIC-1 was still higher in AN women in comparison with other groups (normal-weight, P = 0·012; obese, P = 0·023). When normal-weight and obese women were analysed together, with the exclusion of AN group, an inverse correlation between insulin sensitivity and the change in serum MIC-1 during the clamp was observed (r = -0·27, P = 0·042). CONCLUSIONS: Hyperinsulinemia resulted in a significant increase in serum MIC-1 in different states of adiposity. Increased serum MIC-1 in AN women might be an additional factor responsible for weight loss in this group.

Decreased serum brain-derived neurotrophic factor concentration in young nonobese subjects with low insulin sensitivity.

OBJECTIVE: Insulin resistance and type 2 diabetes are associated with an increased risk of neurodegenerative diseases. Decreased brain-derived neurotrophic factor (BDNF) levels might play a role in the pathogenesis of neuropsychiatric disorders. The aim of our study was to estimate serum BDNF concentration in nonobese women divided into subgroups according to their insulin sensitivity. DESIGN AND METHODS: We studied 46 young, healthy, nonobese women. Insulin sensitivity was estimated with the euglycemic-hyperinsulinemic clamp technique. Then, participants were divided into subgroups of high (mean, 12.79±2.01mg/kg fat-free mass/min) and low insulin sensitivity (mean, 7.33±1.66mg/kg fat-free mass/min). RESULTS: We observed decreased serum BDNF concentration in women with low insulin sensitivity in comparison to high insulin sensitivity group (3306.11±603.10 vs 4141.91±755.37pg/mL, p=0.001). Serum BDNF was positively related to insulin sensitivity (r=0.43, p=0.003). This correlation remained significant after adjustment for other estimated parameters. CONCLUSIONS: Serum BDNF is decreased in young nonobese women with low insulin sensitivity. Early detection and prevention of insulin resistance might be useful in the prevention of neurodegenerative disorders.

Insulin sensitivity, plasma adiponectin and sICAM-1 concentrations in patients with subclinical hypothyroidism: response to levothyroxine therapy.

Subclinical hypothyroidism is associated with an increased risk of atherosclerosis. The aim of this study was to investigate the concentration of plasma soluble intercellular adhesion molecule-1 and adiponectin in relation to insulin sensitivity in patients with subclinical hypothyroidism and to estimate if L-thyroxine treatment had an influence on these parameters. 13 women with subclinical hypothyroidism and 14 euthyroid controls were included in the study. A physical examination was conducted, hyperinsulinemic euglycemic clamp and plasma soluble intercellular adhesion molecule-1, adiponectin and lipids profiles were measured at baseline in both groups and in the group with subclinical hypothyroidism the above procedures were performed after L-thyroxine therapy (mean time of treatment 5.0 months) in stable euthyroid state. Insulin sensitivity and adiponectin were not different at baseline in the two studied groups. Plasma soluble intercellular adhesion molecule-1 concentration was significantly higher in the patients with subclinical hypothyroidism (P = 0.011). The comparison of lipids profiles revealed that only LDL-cholesterol concentration was higher (P = 0.011) in the group with subclinical hypothyroidism. After therapy, we observed an improvement of insulin sensitivity (P = 0.012) and a decrease of plasma glucose (P = 0.019) and soluble intercellular adhesion molecule-1 (P = 0.01), whereas adiponectin concentration remained unchanged. We concluded that L-thyroxine treatment in patients with subclinical hypothyroidism might exert a beneficial effect by reducing cardiovascular risk factors.

Serum soluble glycoprotein 130 concentration is inversely related to insulin sensitivity in women with polycystic ovary syndrome.

OBJECTIVE: Insulin resistance might play a role in the pathogenesis of polycystic ovarian syndrome (PCOS). The family of glycoprotein 130 (gp130) cytokines could influence insulin action. One of these cytokines is interleukin (IL)-6, which exerts a short-term insulin-sensitizing effect, whereas in a long-term period, it might induce insulin resistance. Some other gp130 activators are supposed to have beneficial metabolic effects. Gp130 is present in the circulation in the soluble form (sgp130), which inhibits intracellular gp130 signaling. The aim of the present study was to estimate the relation between sgp130 and insulin sensitivity in women with PCOS. RESEARCH DESIGN AND METHODS: We studied 78 women with PCOS (35 lean and 43 obese) and 34 healthy women (18 lean and 16 obese). The euglycemic-hyperinsulinemic clamp and the measurements of serum sgp130, IL-6, soluble IL-6 receptor (sIL-6R), and sex hormones were performed. RESULTS: Both obesity and PCOS were characterized by an increased sgp130 (P < 0.0001 and P = 0.0002, respectively). sIL-6R concentration was lower (P = 0.0036) in women with PCOS independently of obesity. Serum sgp130 was negatively correlated with insulin sensitivity when control and PCOS women were analyzed together (r = -0.36, P < 0.0001) and in the PCOS subjects separately (r = -0.34, P = 0.002). In multiple regression analysis, this correlation was significant after adjustment for BMI, waist, percent of body fat, postload glucose and insulin, triglycerides, and high-sensitive C-reactive protein. CONCLUSIONS: Serum sgp130 is inversely and independently associated with insulin sensitivity in women with PCOS. An increased serum sgp130 in obesity and PCOS suggests an inhibition of intracellular gp130 signaling in insulin-resistant conditions.

Insulin sensitivity, metabolic flexibility, and serum adiponectin concentration in women with anorexia nervosa.

Anorexia nervosa (AN) is an eating disorder resulting in sustained low weight and marked decrease in fat mass. The lack of adipose tissue observed in lipodystrophies is accompanied by insulin resistance. It remains unclear if the same phenomenon would be present in AN. The objective of the study was to estimate insulin sensitivity, oxidative and nonoxidative glucose metabolism in insulin-stimulated conditions, metabolic flexibility, and serum adiponectin concentration in women with AN. We examined 21 women with AN and 24 healthy normal-weight female controls. Euglycemic hyperinsulinemic clamp, indirect calorimetry, and the measurement of serum adiponectin concentration were performed in all the subjects. We did not observe differences in insulin sensitivity, oxidative and nonoxidative glucose metabolism in insulin-stimulated conditions, and metabolic flexibility between AN and control subjects. Serum adiponectin was higher in AN women in comparison with control group (P = .002). Women with AN have normal insulin sensitivity because of the preserved response of glucose oxidation, nonoxidative glucose metabolism in response to insulin, and normal metabolic flexibility. High adiponectin concentration and normal insulin sensitivity in anorectic women suggest that in AN the adipocytes are still capable of functioning at the level that is sufficient to prevent the metabolic consequences.

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.

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.

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.

Serum visfatin in relation to insulin resistance and markers of hyperandrogenism in lean and obese women with polycystic ovary syndrome.

BACKGROUND: Visfatin, a protein secreted by adipose tissue, is suggested to play a role in pathogenesis of insulin resistance. In polycystic ovary syndrome (PCOS), insulin resistance might be involved in the development of endocrine and metabolic abnormalities. The aim of the study was to asses the relation between serum visfatin concentration and insulin sensitivity and markers of hyperandrogenism in lean and obese PCOS patients. METHODS: The study group consisted of 70 women with PCOS (23 lean and 47 obese) and 45 healthy women (25 lean and 20 obese). Euglycemic hyperinsulinemic clamp and the measurements of serum visfatin, sex hormones were performed. RESULTS: The PCOS group had lower insulin sensitivity (P=0.00049) and higher serum visfatin (P=0.047) in comparison to the control group. The decrease in insulin sensitivity was present in both the lean (P=0.019) and obese (P=0.0077) PCOS subjects, whereas increase in serum visfatin was observed only in lean PCOS subjects (P=0.012). In the whole group, serum visfatin was negatively correlated with insulin sensitivity (r=-0.27, P=0.004). This relationship was also observed in the subgroup of lean (r=-0.30, P=0.038), but not obese women. Additionally, in lean women, visfatin was associated with serum testosterone (r=0.47, P=0.002) and free androgen index (r=0.48, P=0.002), independently of other potential confounding factors. CONCLUSIONS: Visfatin is associated with insulin resistance and markers of hyperandrogenism in lean PCOS patients.