Marek Strączkowski

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

CONTEXTnRetinol-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.nnnOBJECTIVEnThe 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.nnnDESIGN AND PARTICIPANTSnThe 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.nnnRESULTSnThere 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.nnnCONCLUSIONSnOur data indicate that serum RBP4 is related to decreased insulin sensitivity, mostly through its association with nonoxidative glucose metabolism.

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 5.0xa0months) 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 (Pxa0=xa00.011). The comparison of lipids profiles revealed that only LDL-cholesterol concentration was higher (Pxa0=xa00.011) in the group with subclinical hypothyroidism. After therapy, we observed an improvement of insulin sensitivity (Pxa0=xa00.012) and a decrease of plasma glucose (Pxa0=xa00.019) and soluble intercellular adhesion molecule-1 (Pxa0=xa00.01), 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.

Homocysteine concentrations and vascular complications in patients with type 2 diabetes

OBJECTIVEnHyperhomocysteinemia is a well known risk factor for the diseases of the cardiovascular system, which seem to be the main cause of increased mortality in patients with type 2 diabetes. The aim of the study was to evaluate the levels of homocysteine in patients with type 2 diabetes in respect to the regimen of diabetes treatment as well as the presence of diabetic complications.nnnMETHODSnThe investigation was carried out in the group of 64 patients with type 2 diabetes and in 18 healthy subjects from the control group. Clinical examination and measurements of homocysteine, folic acid, vitamin B12, glycosylated hemoglobin concentration and evaluation of parameters of the lipid metabolism, microalbuminuria and creatinine were done in both groups.nnnRESULTSnHomocysteine concentration was significantly higher in the group of patients with diabetes in comparison to the control group (p = 0.0007). Diabetic patients had significantly lower concentrations of folic acid (p = 0.028) and HDL cholesterol (p = 0.025) together with higher levels of systolic blood pressure (p = 0.007). In the group of patients with diabetes no differences in homocysteine levels were found in respect to diabetes treatment. Diabetic patients with coronary artery disease had significantly higher homocysteine concentration in comparison to the group with diabetes without history of coronary artery disease (p = 0.0097). Homocysteine levels correlated significantly with incidence of ischaemic heart disease (r = 0.44, p = 0.001) and microalbuminuria (r = 0.26, p = 0.019). Negative correlation was noticed in HDL concentrations (r = -0.30, p = 0.013) and the levels of folic acid (r = -0.30, p = 0.008).nnnCONCLUSIONnOur results suggest that hyperhomocysteinemia in diabetic patients may contribute to the development of chronic complications. The influence of diabetes treatment on Hcy levels requires further observations.

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.

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

OBJECTIVEnInsulin 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.nnnDESIGN AND METHODSnWe 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).nnnRESULTSnWe 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.nnnCONCLUSIONSnSerum 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.

The effect of a single bout of exhaustive exercise on muscle carbohydrate and lipid metabolism in a rat model of type 2 diabetes mellitus

Abstract The aim of the present study was to estimate whether a single bout of exhaustive exercise influences the glycogen and triglyceride (TG) content in red and white gastrocnemius muscle and in the liver of rats with experimental type 2 diabetes. Experiments were carried out on male Wistar rats fed from 8 to 11 weeks of age with isocaloric standard or high-fat diet (HFD) with a previous injection of low-dose of streptozotocin (STZ) or vehicle at 2 days of age (I, control group: II, HFD; III, STZ; IV, STZ+HFD). Group IV (STZ+HFD) represents a model of type 2 diabetes. Basal liver glycogen was markedly lower in all the studied groups compared to controls. Glycogen concentration after exercise fell significantly in the examined tissues in all groups in comparison to basal conditions. A significant TG accumulation in examined tissues was observed in all the studied groups in comparison to controls. Exercise decreased tissue TG content in all the groups, but it remained significantly higher in the experimental groups vs. control. We conclude that in this model of type 2 diabetes, a single bout of exercise reveals defective utilization of tissue carbohydrates and lipids.

Serum fibroblast growth factor 21 in human obesity: regulation by insulin infusion and relationship with glucose and lipid oxidation.

Objective:Fibroblast growth factor 21 (FGF21) reduces plasma glucose and triglycerides, and increases free fatty acid oxidation in animal models of diabetes. The aim of the present study was to assess the relationships of serum FGF21 with glucose oxidation (GOx) and lipid oxidation (LOx) in the baseline and insulin-stimulated conditions in lean and obese subjects.Design:Cross-sectional study.Subjects:Eighty-four subjects with normal glucose tolerance, 42 lean (body mass index (BMI) <25u2009kgu2009m−2) and 42 overweight or obese (BMI between 25 and 40u2009kgu2009m−2).Measurements:Euglycemic hyperinsulinemic clamp and indirect calorimetry in the baseline state and during last 30u2009min of the clamp. The change in respiratory quotient (ΔRQ) in response to insulin was used as a measure of metabolic flexibility. Serum FGF21 was determined in the baseline state and after the clamp.Results:Obese subjects had higher LOx in the baseline and insulin-stimulated conditions, lower insulin-stimulated GOx and ΔRQ (all P<0.05). Fasting serum FGF21 did not differ between the groups. Insulin infusion resulted in an increase in serum FGF21 in the obese (P=0.0001), but not in the lean group (P=0.76). Postclamp serum FGF21 was higher in the obese subjects (P=0.0007). In this group, postclamp FGF21 was related to LOx during the clamp (r=0.32, P=0.044), change in GOx and LOx in response to insulin (r=−0.44, P=0.005; r=0.47, P=0.002; respectively) and ΔRQ (r=−0.50, P=0.001).Conclusions:An increase in serum FGF21 in response to insulin in obese subjects might represent inappropriate response, possibly associated with metabolic inflexibility in obesity and insulin resistance.

The influence of insulin infusion on the metabolism of amyloid β peptides in plasma.

Accumulating body of evidence suggests pathophysiologic links between Alzheimers disease and diabetes mellitus (DM). For example, the two crucial peptides playing a role in both degenerative disorders, amyloid β (Aβ) and insulin, are metabolized by the same enzyme, insulin degrading enzyme. Euglycemic hyperinsulinemic clamp is a method of estimating insulin sensitivity, based on the assumption that during steady‐state hyperinsulinemic euglycemia, glucose infusion rate equals tissue glucose uptake, that is, the higher the glucose infusion rate, the higher the insulin sensitivity.

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 (1H-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 1H-MRS and assessed their regulation by insulin infusion and their relationship with insulin sensitivity. RESEARCH DESIGN AND METHODS We studied 16 healthy young men. 1H-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 1H-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.

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 (BMIxa0<xa025xa0kgxa0m−2) and 26 overweight or obese women (BMIxa0>xa025xa0kgxa0m−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 (Pxa0<xa00.01), higher plasma sE-selectin (Pxa0=xa00.007), and higher the metabolic syndrome total Z-score (MS Z-score) (Pxa0<xa00.0001). Insulin sensitivity was negatively correlated with sE-selectin level (rxa0=xa0−0.24, Pxa0=xa00.04). sE-selectin was associated with the rate of carbohydrate oxidation at the baseline state (rxa0=xa00.31, Pxa0=xa00.007) and was negatively correlated with metabolic flexibility (rxa0=xa0−0.34, Pxa0=xa00.003). MS Z-score correlated positively with sE-selectin level and negatively with metabolic flexibility and insulin sensitivity (rxa0=xa00.49, Pxa0<xa00.0001, rxa0=xa0−0.29, Pxa0=xa00.04, rxa0=xa0−0.51, Pxa0<xa00.0001, respectively). In multiple regression analysis we observed that the relationship between metabolic flexibility and sE-selectin (βxa0=xa0−0.36; Pxa0=xa00.004) 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.