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Adiponectin

D. Karasek, J. Gajdova, V. Kubickova, O. Krystynik, L. Cibickova, H. Vaverkova 3rd Department of Internal Medicine and Department of Clinical Biochemistry University Hospital Olomouc, Czech Republic.

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Adiponectin

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  1. D. Karasek, J. Gajdova, V. Kubickova, O. Krystynik, L. Cibickova, H. Vaverkova3rd Department of Internal Medicine and Department of Clinical Biochemistry University Hospital Olomouc, Czech Republic Selected adipokines in patients with type 2 diabetes: relationship to markers of endothelial dysfunction and arterial stiffness

  2. Adiponectin • one of the most abundant peptide hormones derived from adipose tissue • plays a major role in glucose and lipid metabolism and prevents development of cardiovascular changes due to its anti-oxidative, anti-inflammatory, endothelium-protective and anti-apoptotic effects • hypoadiponectinemia is associated with obesity, diabetes, hypertension, mixed dyslipidemia, metabolic syndrome, non-alcoholic steatosis, coronary artery disease, etc. Xu A, Vanhoutte PM. Am J Physiol Heart Circ Physiol. 2012 Fisman EZ, Tenenbaum A. Cardiovascular Diabetology 2014

  3. Adipocyte Fatty Acid Binding Protein • is formed mainly in adipocytes and macrophages, partially in lymphocytes, its main function is the binding of free fatty acids • increases lipolysis and insulin resistance, reduces contractility of cardiomyocytes, promotes chronic inflammation and formation of vulnerable atherosclerotic plaques • its increased levels were found in obesity, metabolic syndrome, T2DM, NASH, CAD, ischemic stroke • is a biomarker (maybe even the main mediator) of obesity related cardiovascular diseases Xu A, Vanhoutte PM. Am J Physiol Heart Circ Physiol. 2012 Pasterkamp G. Arterioscler Thromb Vasc Biol. 2012

  4. Fibroblast Growth Factor 21 • is produced by liver, pancreas, muscles and adipocytes • participates in the regulation of metabolism of sugars (increases insulin sensitivity, gluconeogenesis, glucose uptake) and fat (increases oxidation of fatty acids, ketogenesis, HDL-C levels, decreases TG and LDL-C) • stimulates thermogenesis and reduces weight (its analogs were tested as anti-obesity drugs) • its elevation is found in obesity, metabolic syndrome, non-alcoholic steatosis and coronary artery disease. (maybe due to its resistance or as a compensatory mechanism) Woo YC, et al. Clin Endocrinol (Oxf). 2013, Li H, et al. Front Med. 2013, Kim KH, Lee MS. Diabetes Metab J. 2014 , Jin L et al. Diabetes Metab J. 2016

  5. C1q/TNF-related protein 9 HC • is the closest adiponectin paralog (↓glycemia, ↓IR, anti-steatotic effect → ↓TG accumulation) • is predominantly expressed in adipose tissue • besides its metabolic roles that overlap with those of adiponectin, has attracted a lot of attention due to its beneficial cardiovascular effects detected in animal models: • significant endothelium-dependent vasorelaxation • suppression of neointimal hyperplasia and vascular smooth muscle cells proliferation • attenuation adverse cardiac remodeling In human: • its low levels correlated with visceral obesity,adverse metabolic profile and presence of metabolic syndrome • its circulated levels and local production protect against CAD XX • its high levels correlated with obesity and decreased after bariatric surgery and weight loss • its increased levels correlated with C-IMT in T2DM CAD Wong GW et al. FASEB J. 2009, Jung CH et al. J Clin Endocrinol Metab. 2014, Hwang YC et al. Int J Obes (Lond). 2014, Wang J et al. Biomed Res Int. 2015, Li J et al. Biochem Biophys Res Commun. 2015, Wolf RM et al. J Clin Endocrinol Metab. 2016, Asada M et al. J Diabetes Res. 2016

  6. Allograft Inflammatory Factor–1 • is not produced by adipocytes, but by macrophages, which belong to numerous cells presented in fat tissue • promotes macrophages, VSMCs and endothelial cells activation, proliferation and migration • correlates with clinical (BMI, waist) and biochemical (FPG, TG, HDL-C, HbA1c, uric acid) metabolic parameters and maybe associated with atherogenesis Tian Y et al. Am J Physiol Cell Physiol. 2009, Fukui M et al. Metabolism. 2012, Zhao YY et al. Cell Immunol. 2013, Wang J et al. Cell Physiol Biochem. 2013, Fukui M et al. Diabetes Res Clin Pract. 2012

  7. Aim of study, subjects • To compare adipokines levels in patients with diabetes and in healthy individuals • To determine their relationship to indicators of early vascular damage Subjects 54 patients with type 2 diabetes (32 men, 22 women) and 21 healthy controls (8 men, 13 women) Anti-diabetic medication (%)Co-morbidities (%)

  8. Methods Cross-sectional study: • adiponectin, A-FABP, FGF-21, CTRP-9, AIF-1 • anthropological parameters (BMI, waist, SBP, DBP), smoking, diabetes duration • lipids: CH, TG, HDL-C, LDL-C, apoB • parameters of insulin resistanceand diabetes compensation: insulin, C-peptide, FBG, HOMA, HbA1C • parameters of inflammation and CKD: hs-CRP, IL-6, ACR, eGF • markers of endothelial dysfunction: vWF, PAI-1, t-PA • markers of arterial stiffness (SfymgoCor): augmentation index (AIx=AP/ PP*100) a pulse wave velocity (PWV)

  9. Markers of vascular damage ANOVA (after adjustment for age, sex and BMI),* p<0.05, ** p<0.01 *** p<0.001

  10. Adiponectin (μg/ml) ANOVA (after adjustment for age, sex and BMI) Statistically significant correlations (Pearson´s correlation coefficient, p<0.05): Negative: age (r=-0.25), BMI (r=-0.31), waist (r=-0.59), smoking (r=-0.24), TG (r=-0.39), HbA1C (r=-0.47), C-peptide (r=-0.24) vWF (r=-0.29), PAI-1 (r=-0.35) Positive: HDL-C (r=0.68) p<0.05 p<0.001 p<0.001

  11. A-FABP (ng/ml) ANOVA (after adjustment for age, sex and BMI) Statistically significant correlations (Pearson´s correlation coefficient, p<0.05): Positive: age (r=0.43), BMI (r=0.56), waist (r=0.82), SBP (r=-0.29), pulse (r=0.29), HbA1C (r=0.41), C-peptide (r=0.28), FBG (r=0.24), insulin (r=0.29) vWF (r=0.61), PAI-1 (r=0.47), AIx (r=0.39) Negative: HDL-C (r=-0.38) p<0.01 p<0.001 p<0.01

  12. FGF-21 (pg/ml) ANOVA (after adjustment for age, sex and BMI) Statistically significant correlations (Pearson´s correlation coefficient, p<0.05): Positive: hs-CRP (r=0.23), HbA1C (r=0.24), non-HDL-C (r=0.24), ACR (r=0.28) PAI-1 (r=0.27) Negative: HDL-C (r=-0.38) n.s. n.s. n.s.

  13. CTRP-9 (pg/ml) ANOVA (after adjustment for age, sex and BMI) Statistically significant correlations (Pearson´s correlation coefficient, p<0.05): Negative: C-peptide (r=-0.26) n.s. n.s. n.s.

  14. AIF-1 (pg/ml) ANOVA (after adjustment for age, sex and BMI) Statistically significant correlations (Pearson´s correlation coefficient, p<0.05): Positive: non-HDL-C (r=0.27) Negative: HDL-C (r=-0.35) n.s. n.s. n.s.

  15. Conclusion • Patients with type 2 diabetes have significantly higher levels of A-FABP and lower levels of adiponectin. • The levels of these adipokines correlate with indicators of vascular damage and could thus directly contribute to cardiovascular risk individuals with diabetes. • A-FABP could participate in direct endothelium damage. • The increase of FGF-21 could be a secondary result as an effort to increase low adiponectin (maybe also CTRP-9) levels and to protect vessels against the vascular injury. A-FABP fat tissue endothelium ↑ FGF-21 adiponectin, (CTRP-9 ?) liver

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