Comparación de los efectos de las estatinas sobre las concentraciones séricas de leptina y adiponectina

Ilustraciones

Autores:: Cárdenas Parra, Leidy Yurani

Tipo de recurso:: Masters Thesis

Fecha de publicación:: 2021

Institución:: Universidad de Caldas

Repositorio:: Repositorio Institucional U. Caldas

Idioma:: eng
spa

id	RUCALDAS2_5dc59009476ad9502addc113a1a9a28d
oai_identifier_str	oai:repositorio.ucaldas.edu.co:ucaldas/16626
network_acronym_str	RUCALDAS2
network_name_str	Repositorio Institucional U. Caldas
repository_id_str
dc.title.spa.fl_str_mv	Comparación de los efectos de las estatinas sobre las concentraciones séricas de leptina y adiponectina
title	Comparación de los efectos de las estatinas sobre las concentraciones séricas de leptina y adiponectina
spellingShingle	Comparación de los efectos de las estatinas sobre las concentraciones séricas de leptina y adiponectina Leptina Adiponectina Estatinas Lovastatina Atorvastatina Ciencias médicas Farmacología
title_short	Comparación de los efectos de las estatinas sobre las concentraciones séricas de leptina y adiponectina
title_full	Comparación de los efectos de las estatinas sobre las concentraciones séricas de leptina y adiponectina
title_fullStr	Comparación de los efectos de las estatinas sobre las concentraciones séricas de leptina y adiponectina
title_full_unstemmed	Comparación de los efectos de las estatinas sobre las concentraciones séricas de leptina y adiponectina
title_sort	Comparación de los efectos de las estatinas sobre las concentraciones séricas de leptina y adiponectina
dc.creator.fl_str_mv	Cárdenas Parra, Leidy Yurani
dc.contributor.advisor.none.fl_str_mv	Osorio, José Henry
dc.contributor.author.none.fl_str_mv	Cárdenas Parra, Leidy Yurani
dc.subject.proposal.spa.fl_str_mv	Leptina Adiponectina Estatinas Lovastatina Atorvastatina
topic	Leptina Adiponectina Estatinas Lovastatina Atorvastatina Ciencias médicas Farmacología
dc.subject.unesco.none.fl_str_mv	Ciencias médicas Farmacología
description	Ilustraciones
publishDate	2021
dc.date.accessioned.none.fl_str_mv	2021-05-20T21:48:05Z
dc.date.available.none.fl_str_mv	2021-05-20T21:48:05Z
dc.date.issued.none.fl_str_mv	2021-05-18
dc.type.spa.fl_str_mv	Trabajo de grado - Maestría
dc.type.coarversion.fl_str_mv	http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.coar.spa.fl_str_mv	http://purl.org/coar/resource_type/c_bdcc
dc.type.content.spa.fl_str_mv	Text
dc.type.driver.spa.fl_str_mv	info:eu-repo/semantics/masterThesis
format	http://purl.org/coar/resource_type/c_bdcc
dc.identifier.uri.none.fl_str_mv	https://repositorio.ucaldas.edu.co/handle/ucaldas/16626
dc.identifier.instname.spa.fl_str_mv	Universidad de Caldas
dc.identifier.reponame.spa.fl_str_mv	Repositorio institucional Universidad de Caldas
dc.identifier.repourl.spa.fl_str_mv	https://repositorio.ucaldas.edu.co
url	https://repositorio.ucaldas.edu.co/handle/ucaldas/16626 https://repositorio.ucaldas.edu.co
identifier_str_mv	Universidad de Caldas Repositorio institucional Universidad de Caldas
dc.language.iso.spa.fl_str_mv	eng spa
language	eng spa
dc.relation.references.spa.fl_str_mv	Rodríguez-Rodríguez E, Perea JM, López-Sobaler AM, Ortega RM. Obesidad, resistencia a la insulina y aumento de los niveles de adipoquinas: importancia de la dieta y el ejercicio físico. Nutr Hosp. 2009;24(4):415-21. Sanches JC, López DF, Pinzón OA, Sepúlveda JC. Adipocinas y síndrome metabólico: múltiples facetas de un proceso fisiopatológico complejo. Rev Colomb Cardiol. 2010;17(4):167-76. Elissondo N, Gómez Rosso L, Maidana P, Brites F. Adiponectina: una adipocitoquina con múltiples funciones protectoras. Acta Bioquímica Clínica Latinoam [Internet]. 2008 [citado 8 de mayo de 2019];42(1). Disponible en: http://www.redalyc.org/resumen.oa?id=53542104 Quenan YE, Osorio JH. Relación entre obesidad, adipocitoquinas y osteoatrosis: Una revisión. Univ Salud. 2017;19(3):410-8. Perelas A, Tsoulkani A, Perrea D. Effects of lipid-lowering drugs on adiponectin. Curr Vasc Pharmacol. 2010;8(6):836-48. Ghadge AA, Khaire AA, Kuvalekar AA. Adiponectin: A potential therapeutic target for metabolic syndrome. Cytokine Growth Factor Rev. 2018;39:151-8. González E, Díez JJ, Pérez Torres A, Bajo MA, Peso G del, Sánchez-Villanueva R, et al. Composición corporal y concentraciones de adipocitoquinas en hemodiálisis: la ganancia de grasa abdominal como factor de riesgo cardiovascular añadido. Nefrol Madr. 2017;37(2):138-48. Hiuge A, Tenenbaum A, Maeda N, Benderly M, Kumada M, Fisman EZ, et al. Effects of peroxisome proliferator-activated receptor ligands, bezafibrate and fenofibrate, on adiponectin level. Arterioscler Thromb Vasc Biol. 2007;27(3):635-41. Noguchi T, Kobayashi J, Yagi K, Nohara A, Yamaaki N, Sugihara M, et al. Comparison of effects of bezafibrate and fenofibrate on circulating proprotein convertase subtilisin/kexin type 9 and adipocytokine levels in dyslipidemic subjects with impaired glucose tolerance or type 2 diabetes mellitus: Results from a crossover study. Atherosclerosis. 1 de julio de 2011;217(1):165-70. Bulcão C, Giuffrida FMA, Ribeiro-Filho FF, Ferreira SRG. Are the beneficial cardiovascular effects of simvastatin and metformin also associated with a hormone-dependent mechanism improving insulin sensitivity? Braz J Med Biol Res. 2007;40(2):229-35. Sahebkar A. Head-to-head comparison of fibrates versus statins for elevation of circulating adiponectin concentrations: a systematic review and meta-analysis. Metabolism. 2013;62(12):1876-85. Pérez Agudelo JM. Estatinas. En: Tópicos Selectos en Farmacología. 1.a ed. Colombia: Copyright; 2021. p. 39 Mayorga MP. El adipocito como órgano endocrino. Implicaciones fisiopatológicas y terapéuticas. Rev Med. 2007;15(2):225-42. Marcano Y, Torcat J, Ayala L, Verdi B, Lairet C, Maldonado M, et al. Funciones Endocrinas del Tejido Adiposo. Revisión. Rev Venez Endocrinol Metab. 2006;4(1):15-21. Torres DG, González MFC, Morales RC, Rodríguez MB, Arteaga IR. Tejido adiposo como glándula endocrina. Implicaciones fisiopatológicas. Rev Finlay. 2011;1(2):131-151-151. Moreno MJ, Martínez JA. El tejido adiposo: órgano de almacenamiento y órgano secretor. An Sist Sanit Navar. 2009;25(0):29-39. Hausman GJ. Identification of adipose tissue primordia in perirenal tissues of pig fetuses: utility of phosphatase histochemistry. Acta Anat (Basel). 1987;128(3):236-42 Vázquez-Vela MEF, Torres N, Tovar AR. White adipose tissue as endocrine organ and its role in obesity. Arch Med Res. 2008;39(8):715- 28. Harris RBS. Direct and indirect effects of leptin on adipocyte metabolism. Biochim Biophys Acta. 2014;1842(3):414-23. Alhadeff AL, Conway SM, Ong ZY, Wald HS, Roitman MF, Grill HJ. Central leptin signaling transmits positive valence. Brain Res. 2019;1724:146441. Malacara JM. Mecanismos regulatorios de la ingestión de alimentos ¿al fin un tratamiento a la vista? Rev Endocrinol Nutr. 2004;12(4):188- 98. Meier U, Gressner AM. Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. Clin Chem. 2004;50(9):1511-25. Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology. 2004;145(5):2273-82. Masuzaki H, Ogawa Y, Isse N, Satoh N, Okazaki T, Shigemoto M, et al. Human obese gene expression. Adipocyte-specific expression and regional differences in the adipose tissue. Diabetes. 1995;44(7):855-8. Solberg R, Aas V, Thoresen GH, Kase ET, Drevon CA, Rustan AC, et al. Leptin expression in human primary skeletal muscle cells is reduced during differentiation. J Cell Biochem. 2005;96(1):89-96. De Matteis R, Puxeddu R, Riva A, Cinti S. Intralobular ducts of human major salivary glands contain leptin and its receptor. J Anat. 2002;201(5):363-70. Sobhani I, Bado A, Vissuzaine C, Buyse M, Kermorgant S, Laigneau J, et al. Leptin secretion and leptin receptor in the human stomach. Gut. 2000;47(2):178-83. Bjørbaek C, Kahn BB. Leptin signaling in the central nervous system and the periphery. Recent Prog Horm Res. 2004;59:305-31. Morales Villegas E. Síndrome X vs síndrome metabolico: Entendiendo sus coincidencias y sus diferencias hacia una «nueva cardiología». Arch Cardiol México. 2006;76:173-88. Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature. 2000;404(6778):661- 71. Münzberg H, Morrison CD. Structure, production and signaling of leptin. Metabolism. 2015;64(1):13-23 Barrios-Correa AA, Estrada JA, Contreras I. Leptin Signaling in the Control of Metabolism and Appetite: Lessons from Animal Models. J Mol Neurosci MN. 2018;66(3):390-402. Valle Mendiola A, Soto Cruz I. Vía JAK-STAT: Una Visión General. Vertientes Rev Espec En Cienc Salud [Internet]. 2013 [citado 8 de mayo de 2019];8(1-2). Disponible en: http://www.revistas.unam.mx/index.php/vertientes/article/view/32945 Martos-Moreno GÁ, Barrios V, Chowen JA, Argente J. Adipokines in childhood obesity. Vitam Horm. 2013;91:107-42. Kwon O, Kim KW, Kim M-S. Leptin signalling pathways in hypothalamic neurons. Cell Mol Life Sci CMLS. 2016;73(7):1457-77 Calvino C, Souza LL, Costa-e-Sousa RH, Almeida NAS, Trevenzoli IH, Pazos-Moura CC. Hypothyroidism reduces ObRb-STAT3 leptin signalling in the hypothalamus and pituitary of rats associated with resistance to leptin acute anorectic action. J Endocrinol. 2012;215(1):129-35. Minokoshi Y, Kim Y-B, Peroni OD, Fryer LGD, Müller C, Carling D, et al. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature. 2002;415(6869):339-43. Vettor R, Milan G, Rossato M, Federspil G. Review article: adipocytokines and insulin resistance. Aliment Pharmacol Ther. 2005;22 Suppl 2:3-10. Ronti T, Lupattelli G, Mannarino E. The endocrine function of adipose tissue: an update. Clin Endocrinol (Oxf). 2006;64(4):355-65. Gómez-Romero P, Alarcón-Sotelo A, Rodríguez-Weber F, Díaz-Greene E. La adiponectina como blanco terapéutico. Med Interna México. 2017;33(6):770-7. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001;86(5):1930-5. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest. 2006;116(7):1784-92. Wang Y, Lam KSL, Yau M, Xu A. Post-translational modifications of adiponectin: mechanisms and functional implications. Biochem J. 2008;409(3):623-33. Fang H, Judd RL. Adiponectin Regulation and Function. Compr Physiol. 2018;8(3):1031-63. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003;423(6941):762-9. Yamauchi T, Nio Y, Maki T, Kobayashi M, Takazawa T, Iwabu M, et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med. 2007;13(3):332-9. Achari AE, Jain SK. Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction. Int J Mol Sci. 2017;18(6). Martos-Moreno GA, Kopchick JJ, Argente J. Adipoquinas en el niño sano y con obesidad. An Pediatría. 2013;78(3):189.e1-189.e15 Chinetti-Gbaguidi G, Fruchart J-C, Staels B. Role of the PPAR family of nuclear receptors in the regulation of metabolic and cardiovascular homeostasis: new approaches to therapy. Curr Opin Pharmacol. 2005;5(2):177-83. Yu Y-H, Ginsberg HN. Adipocyte signaling and lipid homeostasis: sequelae of insulin-resistant adipose tissue. Circ Res. 2005;96(10):1042-52. Vaiopoulos AG, Marinou K, Christodoulides C, Koutsilieris M. The role of adiponectin in human vascular physiology. Int J Cardiol. 2012;155(2):188-93. Ntaios G, Gatselis NK, Makaritsis K, Dalekos GN. Adipokines as mediators of endothelial function and atherosclerosis. Atherosclerosis. 2013;227(2):216-21. Barrera M del P, Pinilla AE, Cortés É, Mora G, Rodríguez MN. Metabolic syndrome: an interdisciplinary outlook. Rev Colomb Cardiol. 2008;15(3):111-26. Waite KJ, Floyd ZE, Arbour-Reily P, Stephens JM. Interferon-gamma-induced regulation of peroxisome proliferator-activated receptor gamma and STATs in adipocytes. J Biol Chem. 2001;276(10):7062-8. Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, et al. Role of leptin in the neuroendocrine response to fasting. Nature. 1996;382(6588):250-2 Légrádi G, Emerson CH, Ahima RS, Flier JS, Lechan RM. Leptin prevents fasting-induced suppression of prothyrotropin-releasing hormone messenger ribonucleic acid in neurons of the hypothalamic paraventricular nucleus. Endocrinology. 1997;138(6):2569-76. Yu WH, Kimura M, Walczewska A, Karanth S, McCann SM. Role of leptin in hypothalamic-pituitary function. Proc Natl Acad Sci U S A. 1997;94(3):1023-8. Emilsson V, Liu YL, Cawthorne MA, Morton NM, Davenport M. Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion. Diabetes. 1997;46(2):313-6. Fehmann HC, Berghöfer P, Brandhorst D, Brandhorst H, Hering B, Bretzel RG, et al. Leptin inhibition of insulin secretion from isolated human islets. Acta Diabetol. 1997;34(4):249-52 Pallett AL, Morton NM, Cawthorne MA, Emilsson V. Leptin inhibits insulin secretion and reduces insulin mRNA levels in rat isolated pancreatic islets. Biochem Biophys Res Commun. 1997;238(1):267-70. Tanizawa Y, Okuya S, Ishihara H, Asano T, Yada T, Oka Y. Direct stimulation of basal insulin secretion by physiological concentrations of leptin in pancreatic beta cells. Endocrinology. 1997;138(10):4513-6. Kawaji N, Yoshida A, Motoyashiki T, Morita T, Ueki H. Anti-leptin receptor antibody mimics the stimulation of lipolysis induced by leptin in isolated mouse fat pads. J Lipid Res. 2001;42(10):1671-7. Nigro E, Scudiero O, Monaco ML, Palmieri A, Mazzarella G, Costagliola C, et al. New Insight into Adiponectin Role in Obesity and ObesityRelated Diseases. BioMed Res Int. 7 de julio de 2014;2014:e658913. Zhang Y, Chua S. Leptin Function and Regulation. Compr Physiol. 2017;8(1):351-69. D’souza AM, Neumann UH, Glavas MM, Kieffer TJ. The glucoregulatory actions of leptin. Mol Metab. 2017;6(9):1052-65. Park H-K, Ahima RS. Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism. Metabolism. 2015;64(1):24-34 El-Zein O, Kreydiyyeh SI. Leptin inhibits glucose intestinal absorption via PKC, p38MAPK, PI3K and MEK/ERK. PloS One. 2013;8(12):e83360. Shibata R, Sato K, Pimentel DR, Takemura Y, Kihara S, Ohashi K, et al. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nat Med. 2005;11(10):1096-103. Oshima K, Nampei A, Matsuda M, Iwaki M, Fukuhara A, Hashimoto J, et al. Adiponectin increases bone mass by suppressing osteoclast and activating osteoblast. Biochem Biophys Res Commun. 2005;331(2):520-6. Jung UJ, Choi M-S. Obesity and Its Metabolic Complications: The Role of Adipokines and the Relationship between Obesity, Inflammation, Insulin Resistance, Dyslipidemia and Nonalcoholic Fatty Liver Disease. Int J Mol Sci. 2014;15(4):6184-223. Hui X, Lam KSL, Vanhoutte PM, Xu A. Adiponectin and cardiovascular health: an update. Br J Pharmacol. 2012;165(3):574-90. Ruan H, Dong LQ. Adiponectin signaling and function in insulin target tissues. J Mol Cell Biol. 2016;8(2):101-9. Takagi T, Matsuda M, Abe M, Kobayashi H, Fukuhara A, Komuro R, et al. Effect of pravastatin on the development of diabetes and adiponectin production. Atherosclerosis. 2008;196(1):114-21. Yin X, Tu L, Yang H. Effect of simvastatin on IL-6 and adiponectin secretion and mRNA expression in 3T3-L1 adipocytes. J Huazhong Univ Sci Technol Med Sci Hua Zhong Ke Ji Xue Xue Bao Yi Xue Ying Wen Ban Huazhong Keji Daxue Xuebao Yixue Yingdewen Ban. 2007;27(3):248-51. Chen Y, Ohmori K, Mizukawa M, Yoshida J, Zeng Y, Zhang L, et al. Differential impact of atorvastatin vs pravastatin on progressive insulin resistance and left ventricular diastolic dysfunction in a rat model of type II diabetes. Circ J Off J Jpn Circ Soc. 2007;71(1):144-52. Mäuser W, Perwitz N, Meier B, Fasshauer M, Klein J. Direct adipotropic actions of atorvastatin: differentiation state-dependent induction of apoptosis, modulation of endocrine function, and inhibition of glucose uptake. Eur J Pharmacol. 2007;564(1-3):37-46. Otto C, Otto B, Frost RJA, Vogeser M, Pfeiffer AFH, Spranger J, et al. Short-term therapy with atorvastatin or fenofibrate does not affect plasma ghrelin, resistin or adiponectin levels in type 2 diabetic patients with mixed hyperlipoproteinaemia. Acta Diabetol. 2007;44(2):65- 8. Sonmez A, Dogru T, Tasci I, Yilmaz MI, Pinar M, Naharci I, et al. The effect of fluvastatin on plasma adiponectin levels in dyslipidaemia. Clin Endocrinol (Oxf). 2006;64(5):567-72. Nakano S, Inada Y, Masuzaki H, Tanaka T, Yasue S, Ishii T, et al. Bezafibrate regulates the expression and enzyme activity of 11betahydroxysteroid dehydrogenase type 1 in murine adipose tissue and 3T3-L1 adipocytes. Am J Physiol Endocrinol Metab. 2007;292(4):E1213-1222. Chan K-C, Chou H-H, Huang C-N, Chou M-C. Atorvastatin administration after percutaneous coronary intervention in patients with coronary artery disease and normal lipid profiles: impact on plasma adiponectin level. Clin Cardiol. 2008;31(6):253-8. Ando H, Sugimoto K-I, Yanagihara H, Tsuruoka S, Saito T, Takamura T, et al. Effects of atorvastatin and pravastatin on glucose tolerance, adipokine levels and inflammatory markers in hypercholesterolaemic patients. Clin Exp Pharmacol Physiol. 2008;35(9):1012-7. Nakamura T, Kodama Y, Takano H, Umetani K, Fujioka D, Saito Y, et al. Increase in circulating levels of adiponectin after treatment with statin and fibrate in patients with coronary artery disease and hyperlipidemia. Atherosclerosis. 2007;193(2):449-51. Miyagishima K, Hiramitsu S, Kato S, Kato Y, Kitagawa F, Teradaira R, et al. Efficacy of atorvastatin therapy in ischaemic heart disease - effects on oxidized low-density lipoprotein and adiponectin. J Int Med Res. 2007;35(4):534-9. Blanco-Colio LM, Martín-Ventura JL, Gómez-Guerrero C, Masramon X, de Teresa E, Farsang C, et al. Adiponectin plasma levels are increased by atorvastatin treatment in subjects at high cardiovascular risk. Eur J Pharmacol. 2008;586(1-3):259-65. Koh KK, Quon MJ, Han SH, Ahn JY, Jin DK, Kim HS, et al. Vascular and metabolic effects of combined therapy with ramipril and simvastatin in patients with type 2 diabetes. Hypertens Dallas Tex 1979. 2005;45(6):1088-93 Devaraj S, Siegel D, Jialal I. Simvastatin (40 mg/day), adiponectin levels, and insulin sensitivity in subjects with the metabolic syndrome. Am J Cardiol. 2007;100(9):1397-9. Sakamoto K, Sakamoto T, Ogawa H, Kumamoto Joint Research on Hypercholesterolemia Investigators. The effect of 6 months of treatment with pravastatin on serum adiponection concentrations in Japanese patients with coronary artery disease and hypercholesterolemia: a pilot study. Clin Ther. 2006;28(7):1012-21. Sugiyama S, Fukushima H, Kugiyama K, Maruyoshi H, Kojima S, Funahashi T, et al. Pravastatin improved glucose metabolism associated with increasing plasma adiponectin in patients with impaired glucose tolerance and coronary artery disease. Atherosclerosis. 2007;194(2):e43-51. Inami N, Nomura S, Shouzu A, Omoto S, Kimura Y, Takahashi N, et al. Effects of pitavastatin on adiponectin in patients with hyperlipidemia. Pathophysiol Haemost Thromb. 2007;36(1):1-8. Nomura S, Shouzu A, Omoto S, Inami N, Tanaka A, Nanba M, et al. Correlation between adiponectin and reduction of cell adhesion molecules after pitavastatin treatment in hyperlipidemic patients with type 2 diabetes mellitus. Thromb Res. 2008;122(1):39-45. Qu H-Y, Xiao Y-W, Jiang G-H, Wang Z-Y, Zhang Y, Zhang M. Effect of atorvastatin versus rosuvastatin on levels of serum lipids, inflammatory markers and adiponectin in patients with hypercholesterolemia. Pharm Res. 2009;26(4):958-64. Tasci I, Erdem G, Ozgur G, Tapan S, Dogru T, Genc H, et al. LDL-cholesterol lowering increases plasma apelin in isolated hypercholesterolemia. Atherosclerosis. 2009;204(1):222-8. Sahebkar A, Giua R, Pedone C. Impact of Statin Therapy on Plasma Leptin Concentrations: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials: Impact of statin therapy on leptin plasma concentration: a meta-analysis. Br J Clin Pharmacol. 2016;82. Sun Y-M, Li J, Luan Y, Wang L-F. Effect of statin therapy on leptin levels in patients with coronary heart disease. Peptides. 2010;31(6):1205-7. Singh P, Zhang Y, Sharma P, Covassin N, Soucek F, Friedman PA, et al. Statins decrease leptin expression in human white adipocytes. Physiol Rep [Internet]. 2018 [citado 30 de noviembre de 2020];6(2). Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789723/ Werida R, Khairat I, Khedr NF. Effect of atorvastatin versus rosuvastatin on inflammatory biomarkers and LV function in type 2 diabetic patients with dyslipidemia. Biomed Pharmacother Biomedecine Pharmacother. 2021;135:111179. Gholamin S, Razavi S-M, Taghavi-Garmestani S-M, Ghorbanihaghjo A, Rashtchizadeh N, Safa J, et al. Lovastatin for reduction of leptin in nondialysis patients with type 2 diabetic nephropathy. Iran J Kidney Dis. 2014;8(3):201-6. Takahashi Y, Satoh M, Tabuchi T, Nakamura M. Prospective, randomized, single-blind comparison of effects of 6 months’ treatment with atorvastatin versus pravastatin on leptin and angiogenic factors in patients with coronary artery disease. Heart Vessels. 2012;27(4):337- 43 Velarde GP, Choudhary N, Bravo-Jaimes K, Smotherman C, Sherazi S, Kraemer DF. Effect of atorvastatin on lipogenic, inflammatory and thrombogenic markers in women with the metabolic syndrome. Nutr Metab Cardiovasc Dis. 2021;31(2):634-40. Szotowska M, Czerwienska B, Adamczak M, Chudek J, Wiecek A. Effect of Low-Dose Atorvastatin on Plasma Concentrations of Adipokines in Patients with Metabolic Syndrome. Kidney Blood Press Res. 2012;35(4):226-32. Lestavel S, Fruchart JC. Lipoprotein receptors. Cell Mol Biol Noisy--Gd Fr. 1994;40(4):461-81. Schoonjans K, Peinado-Onsurbe J, Fruchart JC, Tailleux A, Fiévet C, Auwerx J. 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors reduce serum triglyceride levels through modulation of apolipoprotein C-III and lipoprotein lipase. FEBS Lett. 1999;452(3):160-4. Estévez F, Samuel A. Tendencias actuales del uso de las estatinas en dislipidemias y otros efectos extralipídicos. Rev Cuba Angiol Cir Vasc. 2017;18(2):178-91. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J. 2020;41(1):111-88. Chegwin-Angarita C, Nieto-Ramírez IJ, Atehortúa L, A LJS. Las estatinas: Actividad biológica y producción biotecnológica. Rev Colomb Biotecnol. 2012;14(2):157-78 Narula J, Nakano M, Virmani R, Kolodgie FD, Petersen R, Newcomb R, et al. Histopathologic characteristics of atherosclerotic coronary disease and implications of the findings for the invasive and noninvasive detection of vulnerable plaques. J Am Coll Cardiol. 2013;61(10):1041-51. Pitt B, Loscalzo J, Monyak J, Miller E, Raichlen J. Comparison of lipid-modifying efficacy of rosuvastatin versus atorvastatin in patients with acute coronary syndrome (from the LUNAR study). Am J Cardiol. 2012;109(9):1239-46. Puri R, Nissen SE, Ballantyne CM, Barter PJ, Chapman MJ, Erbel R, et al. Factors underlying regression of coronary atheroma with potent statin therapy. Eur Heart J. 2013;34(24):1818-25. Mennickent C S, Bravo D M, Calvo M C, Avello L M. Efectos pleiotrópicos de las estatinas. Rev Médica Chile. 2008;136(6):775-82. Cordero A, Bertomeu-Martínez V, Mazón P, Fácila L, Cosín J, Bertomeu-González V, et al. Patients with cardiac disease: Changes observed through last decade in out-patient clinics. World J Cardiol. 2013;5(8):288-94. Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular Benefits and Diabetes Risks of Statin Therapy in Primary Prevention. Lancet. 2012;380(9841):565-71. Amarenco P, Bogousslavsky J, Callahan A, Goldstein LB, Hennerici M, Rudolph AE, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355(6):549-59. Oesterle A, Laufs U, Liao JK. Pleiotropic Effects of Statins on the Cardiovascular System. Circ Res. 2017;120(1):229-43. Pascual Fuster V. Tratamiento farmacológico de la dislipemia en pacientes de alto y muy alto riesgo cardiovascular. Rev Esp Sanid Penit. 2016;18(3):95-108. Ramos PM. Del concepto de estatinas de alta potencia a los efectos extralipídicos de las estatinas. Rev Esp Cardiol. 2015;15:22-7. Grundy Scott M., Stone Neil J., Bailey Alison L., Beam Craig, Birtcher Kim K., Blumenthal Roger S., et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(25):e1082-143. Kim JW, Yun KH, Kim EK, Kim YC, Joe D-Y, Ko JS, et al. Effect of High Dose Rosuvastatin Loading before Primary Percutaneous Coronary Intervention on Infarct Size in Patients with ST-Segment Elevation Myocardial Infarction. Korean Circ J. 2014;44(2):76-81. Vindas CA. Fármacos hipolipemiantes. Revista médica de Costarica y Centroamérica. 2013;607:529-37. Björnsson ES. Hepatotoxicity of statins and other lipid-lowering agents. Liver Int. 2017;37(2):173-8. Liu A, Wu Q, Guo J, Ares I, Rodríguez J-L, Martínez-Larrañaga M-R, et al. Statins: Adverse reactions, oxidative stress and metabolic interactions. Pharmacol Ther. 2019;195:54-84. González Jiménez E, Álvarez Ferre J. Estatinas: Características y Efectos sobre el Control Lipídico en el Niño y Adolescente Obeso. Rev Clínica Med Fam. 2011;4(1):69-75. Sirtori CR. The pharmacology of statins. Pharmacol Res. 2014;88:3-11. Florez J, Freijanes J. Fármacos hipolipoproteinemiantes. En: Florez J, Armijo JA, editores Farmacología Humana. Quinta. Barcelona: ELSEVIER MASSON; 2008. p. 1080-3. García-Sabina A, Gulín-Dávila J, Sempere-Serrano P, González-Juanatey C, Martínez-Pacheco R. Consideraciones específicas en la prescripción e intercambio terapéutico de estatinas. Farm Hosp. 2012;36(2):97-108. Abd TT, Jacobson TA. Statin-induced myopathy: a review and update. Expert Opin Drug Saf. 2011;10(3):373-87. Bellosta S, Corsini A. Statin drug interactions and related adverse reactions. Expert Opin Drug Saf. 2012;11(6):933-46. ACT Lovastatin. Lovastatin 20 mg and 40 mg tablets USP. Lipid Metabolism Regulator [Internet]. Actavis Pharma Company; 2017. Disponible en: https://pdf.hres.ca/dpd_pm/00042711.PDF Ministerio de Salud de Colombia. Resolución 8430 de 1993 - Colombia [Internet]. www.redjurista.com. [citado 6 de abril de 2021]. Disponible en: https://www.redjurista.com/Documents/resolucion_8430_de_1993.aspx IBM SPSS Software [Internet]. 2021 [citado 6 de abril de 2021]. Disponible en: https://www.ibm.com/co-es/analytics/spss-statisticssoftware Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998;395(6704):763-70. Morales Clavijo M, Carvajal Garcés CF. Obesidad y resistencia a la leptina. Gac Médica Boliv. 2010;33(1):63-8. Zhang F, Basinski MB, Beals JM, Briggs SL, Churgay LM, Clawson DK, et al. Crystal structure of the obese protein leptin-E100. Nature. 1997;387(6629):206-9. Auwerx J, Staels B. Leptin. Lancet Lond Engl. 1998;351(9104):737-42 Arch JR, Stock MJ, Trayhurn P. Leptin resistance in obese humans: does it exist and what does it mean? Int J Obes Relat Metab Disord J Int Assoc Study Obes. 1998;22(12):1159-63. Ostlund RE, Yang JW, Klein S, Gingerich R. Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. J Clin Endocrinol Metab. 1996;81(11):3909-13. Considine RV. Weight regulation, leptin and growth hormone. Horm Res. 1997;48 Suppl 5:116-21. Havel PJ, Kasim-Karakas S, Mueller W, Johnson PR, Gingerich RL, Stern JS. Relationship of plasma leptin to plasma insulin and adiposity in normal weight and overweight women: effects of dietary fat content and sustained weight loss. J Clin Endocrinol Metab. 1996;81(12):4406-13. Ho S, Tai E-S, Eng P, Ramli A, Tan C, Fok A. A study in the relationships between leptin, insulin, and body fat in Asian subjects. Int J Obes Relat Metab Disord J Int Assoc Study Obes. 1999;23:246-52 Koh KK, Quon MJ, Han SH, Lee Y, Park JB, Kim SJ, et al. Additive beneficial effects of atorvastatin combined with amlodipine in patients with mild-to-moderate hypertension. Int J Cardiol. 2011;146(3):319-25. Buldak L, Dulawa-Buldak A, Labuzek K, Okopien B. Effects of 90-day hypolipidemic treatment on insulin resistance, adipokines and proinflammatory cytokines in patients with mixed hyperlipidemia and impaired fasting glucose. Int J Clin Pharmacol Ther. 2012;50(11):805- 13. Carnevale R, Pignatelli P, Di Santo S, Bartimoccia S, Sanguigni V, Napoleone L, et al. Atorvastatin inhibits oxidative stress via adiponectinmediated NADPH oxidase down-regulation in hypercholesterolemic patients. Atherosclerosis. 2010;213(1):225-34. Kim J-H, Lee M-R, Shin J-A, Lee S-S, Lee J-M, You S-J, et al. Effects of pravastatin on serum adiponectin levels in female patients with type 2 diabetes mellitus. Atherosclerosis. 2013;227(2):355-9. Al-Azzam SI, Alkhateeb AM, Alzoubi KH, Alzayadeen RN, Ababneh MA, Khabour OF. Atorvastatin treatment modulates the interaction between leptin and adiponectin, and the clinical parameters in patients with type II diabetes. Exp Ther Med. 2013;6(6):1565-9. Anagnostis P, Selalmatzidou D, Polyzos SA, Panagiotou A, Slavakis A, Panagiotidou A, et al. Comparative effects of rosuvastatin and atorvastatin on glucose metabolism and adipokine levels in non-diabetic patients with dyslipidaemia: a prospective randomised open-label study. Int J Clin Pract. 2011;65(6):679-83. Viso M, Porrello B, Rauseo D, Reverón D, Rivas B, Galdona E, et al. Adiponectina y su relación con obesidad, insulinorresistencia y síndrome metabólico en adultos de la cohorte cdc de canarias en Venezuela. Rev Venez Endocrinol Metab. 2013;11(2):76-86. Krysiak R, Żmuda W, Marek B, Okopień B. Age may determine the effect of hypolipidemic agents on plasma adipokine levels in patients with elevated low-density lipoprotein cholesterol levels. Endokrynol Pol. 2016;67(3):271-6. Greenhill C. Obesity-induced hypermethylation of adiponectin gene. Nat Rev Endocrinol. 2015;11(9):504-504. Khan UI, Wang D, Sowers MR, Mancuso P, Everson-Rose SA, Scherer PE, et al. Race-ethnic differences in adipokine levels: the Study of Women’s Health Across the Nation (SWAN). Metabolism. 2012;61(9):1261-9. Elissondo N, Rosso L, Maidana P, Brites F. Adiponectin: An adipocytokine with multiple protective functions. Acta Bioquim Clin Latinoam. 2008;42:17-33 Stepien M, Stepien A, Banach M, Wlazel RN, Paradowski M, Rizzo M, et al. New obesity indices and adipokines in normotensive patients and patients with hypertension: comparative pilot analysis. Angiology. 2014;65(4):333-42. Song JC, White CM. Pharmacologic, pharmacokinetic, and therapeutic differences among angiotensin II receptor antagonists. Pharmacotherapy. 2000;20(2):130-9. Sica DA, Gehr TWB, Ghosh S. Clinical pharmacokinetics of losartan. Clin Pharmacokinet. 2005;44(8):797-814. Zhou S-F, Zhou Z-W, Yang L-P, Cai J-P. Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Wang Y-H, Jones DR, Hall SD. Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos Biol Fate Chem. 2005;33(5):664-71. Research C for DE and. Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. FDA [Internet]. 2020 [citado 30 de noviembre de 2020]; Disponible en: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-druginteractions-table-substrates-inhibitors-and-inducers Martínez C, Albet C, Agúndez JA, Herrero E, Carrillo JA, Márquez M, et al. Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists. Clin Pharmacol Ther. 1999;65(4):369-76. Turpeinen M, Uusitalo J, Jouko U, Jalonen J, Jorma J, Pelkonen O, et al. Multiple P450 substrates in a single run: rapid and comprehensive in vitro interaction assay. Eur J Pharm Sci Off J Eur Fed Pharm Sci. 2005;24(1):123-32. Facciolà G, Avenoso A, Scordo MG, Madia AG, Ventimiglia A, Perucca E, et al. Small effects of valproic acid on the plasma concentrations of clozapine and its major metabolites in patients with schizophrenic or affective disorders. Ther Drug Monit. 1999;21(3):341-5. Martín de Argila de Prados C. Seguridad de los inhibidores de la bomba de protones (IBP). Rev Esp Enfermedades Dig. 2011;103(2):98- 98. Stout SM, Cimino NM. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev. 2014;46(1):86-95. Hirota T, Ieiri I. Drug-drug interactions that interfere with statin metabolism. Expert Opin Drug Metab Toxicol. 2015;11(9):1435-47. Qian Y, Gurley BJ, Markowitz JS. The Potential for Pharmacokinetic Interactions Between Cannabis Products and Conventional Medications. J Clin Psychopharmacol. 2019;39(5):462-71. Zvyaga T, Chang S-Y, Chen C, Yang Z, Vuppugalla R, Hurley J, et al. Evaluation of six proton pump inhibitors as inhibitors of various human cytochromes P450: focus on cytochrome P450 2C19. Drug Metab Dispos Biol Fate Chem. 2012;40(9):1698-711. Ikemura N, Yamaori S, Kobayashi C, Kamijo S, Murayama N, Yamazaki H, et al. Inhibitory effects of antihypertensive drugs on human cytochrome P450 2J2 activity: Potent inhibition by azelnidipine and manidipine. Chem Biol Interact. 2019;306:1-9. Krasulova K, Holas O, Anzenbacher P. Influence of Amlodipine Enantiomers on Human Microsomal Cytochromes P450: Stereoselective Time-Dependent Inhibition of CYP3A Enzyme Activity. Mol J Synth Chem Nat Prod Chem [Internet]. 2017 [citado 6 de abril de 2021];22(11). Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150391/ Wang Y-C, Hsieh T-C, Chou C-L, Wu J-L, Fang T-C. Risks of Adverse Events Following Coprescription of Statins and Calcium Channel Blockers: A Nationwide Population-Based Study. Medicine (Baltimore). 2016;95(2):e2487. Tolou-Ghamari Z. Antiepileptic drugs (AEDs) polypharmacy could lead to buried pharmacokinetic interactions due to CYP450. Drug Metab Lett. 2012;6(3):207-12. Quesada A, Agustín J. Actualización en farmacoterapia: la farmacología de las estatinas. Primera parte. Rev Costarric Cardiol. 2002;4(2):61-61. Huetos Ruiz J. Diferentes estatinas, distintas interacciones. Farm Prof. 2005;19(10):61-3. Gazzerro P, Proto MC, Gangemi G, Malfitano AM, Ciaglia E, Pisanti S, et al. Pharmacological actions of statins: a critical appraisal in the management of cancer. Pharmacol Rev. 2012;64(1):102-46. Hirota T, Fujita Y, Ieiri I. An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins. Expert Opin Drug Metab Toxicol. 2020;16(9):809-22. Takara K, Kakumoto M, Tanigawara Y, Funakoshi J, Sakaeda T, Okumura K. Interaction of digoxin with antihypertensive drugs via MDR1. Life Sci. 2002;70(13):1491-500. Pauli-Magnus C, Rekersbrink S, Klotz U, Fromm MF. Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein. Naunyn Schmiedebergs Arch Pharmacol. 2001;364(6):551-7. Li W, Zeng S, Yu L-S, Zhou Q. Pharmacokinetic drug interaction profile of omeprazole with adverse consequences and clinical risk management. Ther Clin Risk Manag. 2013;9:259-71. Shah Y, Iqbal Z, Ahmad L, Khuda F, Khan A, Khan A, et al. Effect of Omeprazole on the Pharmacokinetics of Rosuvastatin in Healthy Male Volunteers. Am J Ther. 2016;23(6):e1514-23. Armada A, Martins C, Spengler G, Molnar J, Amaral L, Rodrigues AS, et al. Fluorimetric Methods for Analysis of Permeability, Drug Transport Kinetics, and Inhibition of the ABCB1 Membrane Transporter. Methods Mol Biol Clifton NJ. 2016;1395:87-103. Wang L, Sun Y. Efflux mechanism and pathway of verapamil pumping by human P-glycoprotein. Arch Biochem Biophys. 2020;696:108675. Gallo P, De Vincentis A, Pedone C, Nobili A, Tettamanti M, Gentilucci UV, et al. Drug-drug interactions involving CYP3A4 and pglycoprotein in hospitalized elderly patients. Eur J Intern Med. 2019;65:51-7. Li W, Zeng S, Yu L-S, Zhou Q. Pharmacokinetic drug interaction profile of omeprazole with adverse consequences and clinical risk management. Ther Clin Risk Manag. 2013;9:259-71. Leopoldo M, Nardulli P, Contino M, Leonetti F, Luurtsema G, Colabufo NA. An updated patent review on P-glycoprotein inhibitors (2011- 2018). Expert Opin Ther Pat. 2019;29(6):455-61. Adamczak M, Wiecek A, Funahashi T, Chudek J, Kokot F, Matsuzawa Y. Decreased plasma adiponectin concentration in patients with essential hypertension. Am J Hypertens. 2003;16(1):72-5. Miyazaki T, Shimada K, Mokuno H, Daida H. Adipocyte derived plasma protein, adiponectin, is associated with smoking status in patients with coronary artery disease. Heart. 2003;89(6):663 Pischon T, Girman CJ, Rifai N, Hotamisligil GS, Rimm EB. Association between dietary factors and plasma adiponectin concentrations in men. Am J Clin Nutr. 2005;81(4):780-6. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999;257(1):79-83. Yatagai T, Nagasaka S, Taniguchi A, Fukushima M, Nakamura T, Kuroe A, et al. Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 diabetes mellitus. Metabolism. 2003;52(10):1274-8. Yamamoto Y, Hirose H, Saito I, Nishikai K, Saruta T. Adiponectin, an Adipocyte-Derived Protein, Predicts Future Insulin Resistance: TwoYear Follow-Up Study in Japanese Population. J Clin Endocrinol Metab. 2004;89(1):87-90. Lindsay RS, Funahashi T, Hanson RL, Matsuzawa Y, Tanaka S, Tataranni PA, et al. Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet Lond Engl. 2002;360(9326):57-8. Rosado EL, Monteiro JB, Chaia V, Lago MF do. Efecto de la leptina en el tratamiento de la obesidad e influencia de la dieta en la secreción y acción de la hormona. Nutr Hosp. 2006;21(6):686-93. Miyatake N, Takahashi K, Wada J, Nishikawa H, Morishita A, Suzuki H, et al. Changes in serum leptin concentrations in overweight Japanese men after exercise. Diabetes Obes Metab. 2004;6:332-7. Waki H, Yamauchi T, Kamon J, Ito Y, Uchida S, Kita S, et al. Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J Biol Chem. 2003;278(41):40352-63. Vasseur F, Helbecque N, Dina C, Lobbens S, Delannoy V, Gaget S, et al. Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians. Hum Mol Genet. 2002;11(21):2607-14. Kondo H, Shimomura I, Matsukawa Y, Kumada M, Takahashi M, Matsuda M, et al. Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome. Diabetes. 2002;51(7):2325-8. Stumvoll M, Tschritter O, Fritsche A, Staiger H, Renn W, Weisser M, et al. Association of the T-G Polymorphism in Adiponectin (Exon 2) With Obesity and Insulin Sensitivity: Interaction With Family History of Type 2 Diabetes. Diabetes. 2002;51(1):37-41. Guan Z-W, Wu K-R, Li R, Yin Y, Li X-L, Zhang S-F, et al. Pharmacogenetics of statins treatment: Efficacy and safety. J Clin Pharm Ther. 2019;44(6):858-67. Fan LH, He Y, Xu W, Tian HY, Zhou Y, Liang Q, et al. Adiponectin may be a biomarker of early atherosclerosis of smokers and decreased by nicotine through KATP channel in adipocytes. Nutr Burbank Los Angel Cty Calif. 2015;31(7-8):955-8. Guimarães ES, Cerda A, Dorea EL, Bernik MMS, Gusukuma MC, Pinto GA, et al. Effects of short-term add-on ezetimibe to statin treatment on expression of adipokines and inflammatory markers in diabetic and dyslipidemic patients. Cardiovasc Ther. 2017;35(6). Tassaneeyakul W, Vannaprasaht S, Yamazoe Y. Formation of omeprazole sulphone but not 5-hydroxyomeprazole is inhibited by grapefruit juice. Br J Clin Pharmacol. 2000;49(2):139-44.
dc.rights.coar.fl_str_mv	http://purl.org/coar/access_right/c_abf2
dc.rights.accessrights.spa.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
rights_invalid_str_mv	http://purl.org/coar/access_right/c_abf2
dc.format.mimetype.spa.fl_str_mv	application/pdf
dc.publisher.faculty.spa.fl_str_mv	Facultad de Ciencias para la Salud
dc.publisher.place.spa.fl_str_mv	Manizales
dc.publisher.program.spa.fl_str_mv	Maestría en Ciencias Biomédicas
institution	Universidad de Caldas
bitstream.url.fl_str_mv	https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/1/LeidyYurani_CardenasParra_2021.pdf https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/3/Autorizaci%c3%b3n%20repositorio.pdf https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/4/Acta%20sustentaci%c3%b3n%20firma%20jurado%201.pdf https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/5/Acta%20sustentaci%c3%b3n%20firma%20jurado%202.PDF https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/6/PDF_%20documentos%20adicionales.pdf https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/7/license.txt https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/8/LeidyYurani_CardenasParra_2021.pdf.txt https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/10/Autorizaci%c3%b3n%20repositorio.pdf.txt https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/12/Acta%20sustentaci%c3%b3n%20firma%20jurado%201.pdf.txt https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/14/Acta%20sustentaci%c3%b3n%20firma%20jurado%202.PDF.txt https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/16/PDF_%20documentos%20adicionales.pdf.txt https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/9/LeidyYurani_CardenasParra_2021.pdf.jpg https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/11/Autorizaci%c3%b3n%20repositorio.pdf.jpg https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/13/Acta%20sustentaci%c3%b3n%20firma%20jurado%201.pdf.jpg https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/15/Acta%20sustentaci%c3%b3n%20firma%20jurado%202.PDF.jpg https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/17/PDF_%20documentos%20adicionales.pdf.jpg
bitstream.checksum.fl_str_mv	277bb74d59fff6287740d7e6acdefb14 0e8e1e8686ae21d6779595982fa87f30 80f8f390de1492c37a3b5ae6c24a7bcf ad804ddf9d35bac69b9278552ee44da4 e5e3f88999f4fe2f7982e1b5c801172c 2f9959eaf5b71fae44bbf9ec84150c7a 88852e9e0f12563246dee6258c96b712 26e0810bb88f78f5cc05c7c45e4bceca 93a9a207f3e803339f684d4824fc6d12 93a9a207f3e803339f684d4824fc6d12 1d086e7c0a3422c2fef839b02efe4360 c0567faca030b9ce7625fe61e4c12fae b599bc2f8b8fc540ccbd2e52d70f2c81 351f0bd185025cb93844db0223383285 a38599cbd6b9341e56b1c32f7f9ec316 d9b0588adabcc51c2c28e1a081cefc0e
bitstream.checksumAlgorithm.fl_str_mv	MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5 MD5
repository.name.fl_str_mv	Repositorio Digital de la Universidad de Caldas
repository.mail.fl_str_mv	bdigital@metabiblioteca.com
_version_	1800536710123094016
spelling	Osorio, José Henry43b46d33b293a5dc46681ff0a7e157a4Cárdenas Parra, Leidy Yurani8dd6a19771e025ca1c7b2428266226842021-05-20T21:48:05Z2021-05-20T21:48:05Z2021-05-18https://repositorio.ucaldas.edu.co/handle/ucaldas/16626Universidad de CaldasRepositorio institucional Universidad de Caldashttps://repositorio.ucaldas.edu.coIlustracionesspa: Los estudios que relacionan estatinas con adipocitoquinas, han reportado controversias; por lo que, es necesario contribuir a dilucidar la relación entre estas, el objetivo fue comparar las concentraciones séricas de leptina y adiponectina, según el régimen de estatina. Estudio observacional, transversal, de nivel relacional. Muestra 76 participantes, de los cuales se obtuvieron datos de los medicamentos consumidos y se cuantificó leptina y adiponectina mediante ELISA sándwich. El análisis relacional se realizó mediante U-Mann-Whitney y H-Kruskal-Wallis. La mediana de las concentraciones de leptina, fue mayor en quienes consumían atorvastatina que en quienes consumían lovastatina; por el contrario, la mediana de adiponectina, fue menor en quienes consumían atorvastatina, y significativamente inferiores en quienes recibían 40 mg/ día de atorvastatina (p=0,047). Las concentraciones séricas de leptina fueron homogéneas e independientes del régimen de estatina; por el contrario las de adiponectina, fueron menores en quienes consumían 40 mg/ día de atorvastatina. Las particularidades farmacocinéticas de lovastatina y atorvastatina; así como, las interacciones con otros grupos farmacológicos, son extensas y pueden modificar sus efectos, incluso los extralipídicos; de otro modo, muchas covariables como el sexo, la edad y el índice de masa corporal, influyen en la actividad secretora del tejido graso.eng: Studies linking statins with adipocytokines have reported controversies; Therefore, it is necessary to contribute to elucidating the relationship between these, the objective was to compare the serum concentrations of leptin and adiponectin, according to the statin regimen. Observational, cross-sectional, relational-level study. Sample 76 participants, from which data were obtained on the drugs consumed and leptin and adiponectin were quantified by sandwich ELISA. The relational analysis was performed using U-Mann-Whitney and H-Kruskal-Wallis. Median leptin concentrations were higher in those who consumed atorvastatin than in those who consumed lovastatin; on the contrary, the median adiponectin was lower in those who consumed atorvastatin, and significantly lower in those who received atorvastatin 40 mg / day (p = 0.047). Serum leptin concentrations were homogeneous and independent of the statin regimen; on the contrary, those of adiponectin were lower in those who consumed 40 mg / day of atorvastatin. The pharmacokinetic characteristics of lovastatin and atorvastatin; as well as, the interactions with other pharmacological groups are extensive and can modify their effects, even the extralipidic ones; otherwise, many covariates, such as sex, age, and body mass index, influence the secretory activity of fat tissue.RESUMEN / INTRODUCCIÓN / REVISIÓN BIBLIOGRÁFICA / OBJETIVOS / MATERIALES Y MÉTODOS / RESULTADOS / DISCUSIÓN / CONCLUSIONES / RECOMENDACIONES / BIBLIOGRAFÍAMaestríaMagister en Ciencias Biomédicasapplication/pdfengspaComparación de los efectos de las estatinas sobre las concentraciones séricas de leptina y adiponectinaTrabajo de grado - Maestríahttp://purl.org/coar/resource_type/c_bdccTextinfo:eu-repo/semantics/masterThesishttp://purl.org/coar/version/c_970fb48d4fbd8a85Facultad de Ciencias para la SaludManizalesMaestría en Ciencias BiomédicasRodríguez-Rodríguez E, Perea JM, López-Sobaler AM, Ortega RM. Obesidad, resistencia a la insulina y aumento de los niveles de adipoquinas: importancia de la dieta y el ejercicio físico. Nutr Hosp. 2009;24(4):415-21.Sanches JC, López DF, Pinzón OA, Sepúlveda JC. Adipocinas y síndrome metabólico: múltiples facetas de un proceso fisiopatológico complejo. Rev Colomb Cardiol. 2010;17(4):167-76.Elissondo N, Gómez Rosso L, Maidana P, Brites F. Adiponectina: una adipocitoquina con múltiples funciones protectoras. Acta Bioquímica Clínica Latinoam [Internet]. 2008 [citado 8 de mayo de 2019];42(1). Disponible en: http://www.redalyc.org/resumen.oa?id=53542104Quenan YE, Osorio JH. Relación entre obesidad, adipocitoquinas y osteoatrosis: Una revisión. Univ Salud. 2017;19(3):410-8.Perelas A, Tsoulkani A, Perrea D. Effects of lipid-lowering drugs on adiponectin. Curr Vasc Pharmacol. 2010;8(6):836-48.Ghadge AA, Khaire AA, Kuvalekar AA. Adiponectin: A potential therapeutic target for metabolic syndrome. Cytokine Growth Factor Rev. 2018;39:151-8.González E, Díez JJ, Pérez Torres A, Bajo MA, Peso G del, Sánchez-Villanueva R, et al. Composición corporal y concentraciones de adipocitoquinas en hemodiálisis: la ganancia de grasa abdominal como factor de riesgo cardiovascular añadido. Nefrol Madr. 2017;37(2):138-48.Hiuge A, Tenenbaum A, Maeda N, Benderly M, Kumada M, Fisman EZ, et al. Effects of peroxisome proliferator-activated receptor ligands, bezafibrate and fenofibrate, on adiponectin level. Arterioscler Thromb Vasc Biol. 2007;27(3):635-41.Noguchi T, Kobayashi J, Yagi K, Nohara A, Yamaaki N, Sugihara M, et al. Comparison of effects of bezafibrate and fenofibrate on circulating proprotein convertase subtilisin/kexin type 9 and adipocytokine levels in dyslipidemic subjects with impaired glucose tolerance or type 2 diabetes mellitus: Results from a crossover study. Atherosclerosis. 1 de julio de 2011;217(1):165-70.Bulcão C, Giuffrida FMA, Ribeiro-Filho FF, Ferreira SRG. Are the beneficial cardiovascular effects of simvastatin and metformin also associated with a hormone-dependent mechanism improving insulin sensitivity? Braz J Med Biol Res. 2007;40(2):229-35.Sahebkar A. Head-to-head comparison of fibrates versus statins for elevation of circulating adiponectin concentrations: a systematic review and meta-analysis. Metabolism. 2013;62(12):1876-85.Pérez Agudelo JM. Estatinas. En: Tópicos Selectos en Farmacología. 1.a ed. Colombia: Copyright; 2021. p. 39Mayorga MP. El adipocito como órgano endocrino. Implicaciones fisiopatológicas y terapéuticas. Rev Med. 2007;15(2):225-42.Marcano Y, Torcat J, Ayala L, Verdi B, Lairet C, Maldonado M, et al. Funciones Endocrinas del Tejido Adiposo. Revisión. Rev Venez Endocrinol Metab. 2006;4(1):15-21.Torres DG, González MFC, Morales RC, Rodríguez MB, Arteaga IR. Tejido adiposo como glándula endocrina. Implicaciones fisiopatológicas. Rev Finlay. 2011;1(2):131-151-151.Moreno MJ, Martínez JA. El tejido adiposo: órgano de almacenamiento y órgano secretor. An Sist Sanit Navar. 2009;25(0):29-39.Hausman GJ. Identification of adipose tissue primordia in perirenal tissues of pig fetuses: utility of phosphatase histochemistry. Acta Anat (Basel). 1987;128(3):236-42Vázquez-Vela MEF, Torres N, Tovar AR. White adipose tissue as endocrine organ and its role in obesity. Arch Med Res. 2008;39(8):715- 28.Harris RBS. Direct and indirect effects of leptin on adipocyte metabolism. Biochim Biophys Acta. 2014;1842(3):414-23.Alhadeff AL, Conway SM, Ong ZY, Wald HS, Roitman MF, Grill HJ. Central leptin signaling transmits positive valence. Brain Res. 2019;1724:146441.Malacara JM. Mecanismos regulatorios de la ingestión de alimentos ¿al fin un tratamiento a la vista? Rev Endocrinol Nutr. 2004;12(4):188- 98.Meier U, Gressner AM. Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. Clin Chem. 2004;50(9):1511-25.Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology. 2004;145(5):2273-82.Masuzaki H, Ogawa Y, Isse N, Satoh N, Okazaki T, Shigemoto M, et al. Human obese gene expression. Adipocyte-specific expression and regional differences in the adipose tissue. Diabetes. 1995;44(7):855-8.Solberg R, Aas V, Thoresen GH, Kase ET, Drevon CA, Rustan AC, et al. Leptin expression in human primary skeletal muscle cells is reduced during differentiation. J Cell Biochem. 2005;96(1):89-96.De Matteis R, Puxeddu R, Riva A, Cinti S. Intralobular ducts of human major salivary glands contain leptin and its receptor. J Anat. 2002;201(5):363-70.Sobhani I, Bado A, Vissuzaine C, Buyse M, Kermorgant S, Laigneau J, et al. Leptin secretion and leptin receptor in the human stomach. Gut. 2000;47(2):178-83.Bjørbaek C, Kahn BB. Leptin signaling in the central nervous system and the periphery. Recent Prog Horm Res. 2004;59:305-31.Morales Villegas E. Síndrome X vs síndrome metabolico: Entendiendo sus coincidencias y sus diferencias hacia una «nueva cardiología». Arch Cardiol México. 2006;76:173-88.Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature. 2000;404(6778):661- 71.Münzberg H, Morrison CD. Structure, production and signaling of leptin. Metabolism. 2015;64(1):13-23Barrios-Correa AA, Estrada JA, Contreras I. Leptin Signaling in the Control of Metabolism and Appetite: Lessons from Animal Models. J Mol Neurosci MN. 2018;66(3):390-402.Valle Mendiola A, Soto Cruz I. Vía JAK-STAT: Una Visión General. Vertientes Rev Espec En Cienc Salud [Internet]. 2013 [citado 8 de mayo de 2019];8(1-2). Disponible en: http://www.revistas.unam.mx/index.php/vertientes/article/view/32945Martos-Moreno GÁ, Barrios V, Chowen JA, Argente J. Adipokines in childhood obesity. Vitam Horm. 2013;91:107-42.Kwon O, Kim KW, Kim M-S. Leptin signalling pathways in hypothalamic neurons. Cell Mol Life Sci CMLS. 2016;73(7):1457-77Calvino C, Souza LL, Costa-e-Sousa RH, Almeida NAS, Trevenzoli IH, Pazos-Moura CC. Hypothyroidism reduces ObRb-STAT3 leptin signalling in the hypothalamus and pituitary of rats associated with resistance to leptin acute anorectic action. J Endocrinol. 2012;215(1):129-35.Minokoshi Y, Kim Y-B, Peroni OD, Fryer LGD, Müller C, Carling D, et al. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature. 2002;415(6869):339-43.Vettor R, Milan G, Rossato M, Federspil G. Review article: adipocytokines and insulin resistance. Aliment Pharmacol Ther. 2005;22 Suppl 2:3-10.Ronti T, Lupattelli G, Mannarino E. The endocrine function of adipose tissue: an update. Clin Endocrinol (Oxf). 2006;64(4):355-65.Gómez-Romero P, Alarcón-Sotelo A, Rodríguez-Weber F, Díaz-Greene E. La adiponectina como blanco terapéutico. Med Interna México. 2017;33(6):770-7.Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001;86(5):1930-5.Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest. 2006;116(7):1784-92.Wang Y, Lam KSL, Yau M, Xu A. Post-translational modifications of adiponectin: mechanisms and functional implications. Biochem J. 2008;409(3):623-33.Fang H, Judd RL. Adiponectin Regulation and Function. Compr Physiol. 2018;8(3):1031-63.Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003;423(6941):762-9.Yamauchi T, Nio Y, Maki T, Kobayashi M, Takazawa T, Iwabu M, et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med. 2007;13(3):332-9.Achari AE, Jain SK. Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction. Int J Mol Sci. 2017;18(6).Martos-Moreno GA, Kopchick JJ, Argente J. Adipoquinas en el niño sano y con obesidad. An Pediatría. 2013;78(3):189.e1-189.e15Chinetti-Gbaguidi G, Fruchart J-C, Staels B. Role of the PPAR family of nuclear receptors in the regulation of metabolic and cardiovascular homeostasis: new approaches to therapy. Curr Opin Pharmacol. 2005;5(2):177-83.Yu Y-H, Ginsberg HN. Adipocyte signaling and lipid homeostasis: sequelae of insulin-resistant adipose tissue. Circ Res. 2005;96(10):1042-52.Vaiopoulos AG, Marinou K, Christodoulides C, Koutsilieris M. The role of adiponectin in human vascular physiology. Int J Cardiol. 2012;155(2):188-93.Ntaios G, Gatselis NK, Makaritsis K, Dalekos GN. Adipokines as mediators of endothelial function and atherosclerosis. Atherosclerosis. 2013;227(2):216-21.Barrera M del P, Pinilla AE, Cortés É, Mora G, Rodríguez MN. Metabolic syndrome: an interdisciplinary outlook. Rev Colomb Cardiol. 2008;15(3):111-26.Waite KJ, Floyd ZE, Arbour-Reily P, Stephens JM. Interferon-gamma-induced regulation of peroxisome proliferator-activated receptor gamma and STATs in adipocytes. J Biol Chem. 2001;276(10):7062-8.Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, et al. Role of leptin in the neuroendocrine response to fasting. Nature. 1996;382(6588):250-2Légrádi G, Emerson CH, Ahima RS, Flier JS, Lechan RM. Leptin prevents fasting-induced suppression of prothyrotropin-releasing hormone messenger ribonucleic acid in neurons of the hypothalamic paraventricular nucleus. Endocrinology. 1997;138(6):2569-76.Yu WH, Kimura M, Walczewska A, Karanth S, McCann SM. Role of leptin in hypothalamic-pituitary function. Proc Natl Acad Sci U S A. 1997;94(3):1023-8.Emilsson V, Liu YL, Cawthorne MA, Morton NM, Davenport M. Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion. Diabetes. 1997;46(2):313-6.Fehmann HC, Berghöfer P, Brandhorst D, Brandhorst H, Hering B, Bretzel RG, et al. Leptin inhibition of insulin secretion from isolated human islets. Acta Diabetol. 1997;34(4):249-52Pallett AL, Morton NM, Cawthorne MA, Emilsson V. Leptin inhibits insulin secretion and reduces insulin mRNA levels in rat isolated pancreatic islets. Biochem Biophys Res Commun. 1997;238(1):267-70.Tanizawa Y, Okuya S, Ishihara H, Asano T, Yada T, Oka Y. Direct stimulation of basal insulin secretion by physiological concentrations of leptin in pancreatic beta cells. Endocrinology. 1997;138(10):4513-6.Kawaji N, Yoshida A, Motoyashiki T, Morita T, Ueki H. Anti-leptin receptor antibody mimics the stimulation of lipolysis induced by leptin in isolated mouse fat pads. J Lipid Res. 2001;42(10):1671-7.Nigro E, Scudiero O, Monaco ML, Palmieri A, Mazzarella G, Costagliola C, et al. New Insight into Adiponectin Role in Obesity and ObesityRelated Diseases. BioMed Res Int. 7 de julio de 2014;2014:e658913.Zhang Y, Chua S. Leptin Function and Regulation. Compr Physiol. 2017;8(1):351-69.D’souza AM, Neumann UH, Glavas MM, Kieffer TJ. The glucoregulatory actions of leptin. Mol Metab. 2017;6(9):1052-65.Park H-K, Ahima RS. Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism. Metabolism. 2015;64(1):24-34El-Zein O, Kreydiyyeh SI. Leptin inhibits glucose intestinal absorption via PKC, p38MAPK, PI3K and MEK/ERK. PloS One. 2013;8(12):e83360.Shibata R, Sato K, Pimentel DR, Takemura Y, Kihara S, Ohashi K, et al. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nat Med. 2005;11(10):1096-103.Oshima K, Nampei A, Matsuda M, Iwaki M, Fukuhara A, Hashimoto J, et al. Adiponectin increases bone mass by suppressing osteoclast and activating osteoblast. Biochem Biophys Res Commun. 2005;331(2):520-6.Jung UJ, Choi M-S. Obesity and Its Metabolic Complications: The Role of Adipokines and the Relationship between Obesity, Inflammation, Insulin Resistance, Dyslipidemia and Nonalcoholic Fatty Liver Disease. Int J Mol Sci. 2014;15(4):6184-223.Hui X, Lam KSL, Vanhoutte PM, Xu A. Adiponectin and cardiovascular health: an update. Br J Pharmacol. 2012;165(3):574-90.Ruan H, Dong LQ. Adiponectin signaling and function in insulin target tissues. J Mol Cell Biol. 2016;8(2):101-9.Takagi T, Matsuda M, Abe M, Kobayashi H, Fukuhara A, Komuro R, et al. Effect of pravastatin on the development of diabetes and adiponectin production. Atherosclerosis. 2008;196(1):114-21.Yin X, Tu L, Yang H. Effect of simvastatin on IL-6 and adiponectin secretion and mRNA expression in 3T3-L1 adipocytes. J Huazhong Univ Sci Technol Med Sci Hua Zhong Ke Ji Xue Xue Bao Yi Xue Ying Wen Ban Huazhong Keji Daxue Xuebao Yixue Yingdewen Ban. 2007;27(3):248-51.Chen Y, Ohmori K, Mizukawa M, Yoshida J, Zeng Y, Zhang L, et al. Differential impact of atorvastatin vs pravastatin on progressive insulin resistance and left ventricular diastolic dysfunction in a rat model of type II diabetes. Circ J Off J Jpn Circ Soc. 2007;71(1):144-52.Mäuser W, Perwitz N, Meier B, Fasshauer M, Klein J. Direct adipotropic actions of atorvastatin: differentiation state-dependent induction of apoptosis, modulation of endocrine function, and inhibition of glucose uptake. Eur J Pharmacol. 2007;564(1-3):37-46.Otto C, Otto B, Frost RJA, Vogeser M, Pfeiffer AFH, Spranger J, et al. Short-term therapy with atorvastatin or fenofibrate does not affect plasma ghrelin, resistin or adiponectin levels in type 2 diabetic patients with mixed hyperlipoproteinaemia. Acta Diabetol. 2007;44(2):65- 8.Sonmez A, Dogru T, Tasci I, Yilmaz MI, Pinar M, Naharci I, et al. The effect of fluvastatin on plasma adiponectin levels in dyslipidaemia. Clin Endocrinol (Oxf). 2006;64(5):567-72.Nakano S, Inada Y, Masuzaki H, Tanaka T, Yasue S, Ishii T, et al. Bezafibrate regulates the expression and enzyme activity of 11betahydroxysteroid dehydrogenase type 1 in murine adipose tissue and 3T3-L1 adipocytes. Am J Physiol Endocrinol Metab. 2007;292(4):E1213-1222.Chan K-C, Chou H-H, Huang C-N, Chou M-C. Atorvastatin administration after percutaneous coronary intervention in patients with coronary artery disease and normal lipid profiles: impact on plasma adiponectin level. Clin Cardiol. 2008;31(6):253-8.Ando H, Sugimoto K-I, Yanagihara H, Tsuruoka S, Saito T, Takamura T, et al. Effects of atorvastatin and pravastatin on glucose tolerance, adipokine levels and inflammatory markers in hypercholesterolaemic patients. Clin Exp Pharmacol Physiol. 2008;35(9):1012-7.Nakamura T, Kodama Y, Takano H, Umetani K, Fujioka D, Saito Y, et al. Increase in circulating levels of adiponectin after treatment with statin and fibrate in patients with coronary artery disease and hyperlipidemia. Atherosclerosis. 2007;193(2):449-51.Miyagishima K, Hiramitsu S, Kato S, Kato Y, Kitagawa F, Teradaira R, et al. Efficacy of atorvastatin therapy in ischaemic heart disease - effects on oxidized low-density lipoprotein and adiponectin. J Int Med Res. 2007;35(4):534-9.Blanco-Colio LM, Martín-Ventura JL, Gómez-Guerrero C, Masramon X, de Teresa E, Farsang C, et al. Adiponectin plasma levels are increased by atorvastatin treatment in subjects at high cardiovascular risk. Eur J Pharmacol. 2008;586(1-3):259-65.Koh KK, Quon MJ, Han SH, Ahn JY, Jin DK, Kim HS, et al. Vascular and metabolic effects of combined therapy with ramipril and simvastatin in patients with type 2 diabetes. Hypertens Dallas Tex 1979. 2005;45(6):1088-93Devaraj S, Siegel D, Jialal I. Simvastatin (40 mg/day), adiponectin levels, and insulin sensitivity in subjects with the metabolic syndrome. Am J Cardiol. 2007;100(9):1397-9.Sakamoto K, Sakamoto T, Ogawa H, Kumamoto Joint Research on Hypercholesterolemia Investigators. The effect of 6 months of treatment with pravastatin on serum adiponection concentrations in Japanese patients with coronary artery disease and hypercholesterolemia: a pilot study. Clin Ther. 2006;28(7):1012-21.Sugiyama S, Fukushima H, Kugiyama K, Maruyoshi H, Kojima S, Funahashi T, et al. Pravastatin improved glucose metabolism associated with increasing plasma adiponectin in patients with impaired glucose tolerance and coronary artery disease. Atherosclerosis. 2007;194(2):e43-51.Inami N, Nomura S, Shouzu A, Omoto S, Kimura Y, Takahashi N, et al. Effects of pitavastatin on adiponectin in patients with hyperlipidemia. Pathophysiol Haemost Thromb. 2007;36(1):1-8.Nomura S, Shouzu A, Omoto S, Inami N, Tanaka A, Nanba M, et al. Correlation between adiponectin and reduction of cell adhesion molecules after pitavastatin treatment in hyperlipidemic patients with type 2 diabetes mellitus. Thromb Res. 2008;122(1):39-45.Qu H-Y, Xiao Y-W, Jiang G-H, Wang Z-Y, Zhang Y, Zhang M. Effect of atorvastatin versus rosuvastatin on levels of serum lipids, inflammatory markers and adiponectin in patients with hypercholesterolemia. Pharm Res. 2009;26(4):958-64.Tasci I, Erdem G, Ozgur G, Tapan S, Dogru T, Genc H, et al. LDL-cholesterol lowering increases plasma apelin in isolated hypercholesterolemia. Atherosclerosis. 2009;204(1):222-8.Sahebkar A, Giua R, Pedone C. Impact of Statin Therapy on Plasma Leptin Concentrations: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials: Impact of statin therapy on leptin plasma concentration: a meta-analysis. Br J Clin Pharmacol. 2016;82.Sun Y-M, Li J, Luan Y, Wang L-F. Effect of statin therapy on leptin levels in patients with coronary heart disease. Peptides. 2010;31(6):1205-7.Singh P, Zhang Y, Sharma P, Covassin N, Soucek F, Friedman PA, et al. Statins decrease leptin expression in human white adipocytes. Physiol Rep [Internet]. 2018 [citado 30 de noviembre de 2020];6(2). Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5789723/Werida R, Khairat I, Khedr NF. Effect of atorvastatin versus rosuvastatin on inflammatory biomarkers and LV function in type 2 diabetic patients with dyslipidemia. Biomed Pharmacother Biomedecine Pharmacother. 2021;135:111179.Gholamin S, Razavi S-M, Taghavi-Garmestani S-M, Ghorbanihaghjo A, Rashtchizadeh N, Safa J, et al. Lovastatin for reduction of leptin in nondialysis patients with type 2 diabetic nephropathy. Iran J Kidney Dis. 2014;8(3):201-6.Takahashi Y, Satoh M, Tabuchi T, Nakamura M. Prospective, randomized, single-blind comparison of effects of 6 months’ treatment with atorvastatin versus pravastatin on leptin and angiogenic factors in patients with coronary artery disease. Heart Vessels. 2012;27(4):337- 43Velarde GP, Choudhary N, Bravo-Jaimes K, Smotherman C, Sherazi S, Kraemer DF. Effect of atorvastatin on lipogenic, inflammatory and thrombogenic markers in women with the metabolic syndrome. Nutr Metab Cardiovasc Dis. 2021;31(2):634-40.Szotowska M, Czerwienska B, Adamczak M, Chudek J, Wiecek A. Effect of Low-Dose Atorvastatin on Plasma Concentrations of Adipokines in Patients with Metabolic Syndrome. Kidney Blood Press Res. 2012;35(4):226-32.Lestavel S, Fruchart JC. Lipoprotein receptors. Cell Mol Biol Noisy--Gd Fr. 1994;40(4):461-81.Schoonjans K, Peinado-Onsurbe J, Fruchart JC, Tailleux A, Fiévet C, Auwerx J. 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors reduce serum triglyceride levels through modulation of apolipoprotein C-III and lipoprotein lipase. FEBS Lett. 1999;452(3):160-4.Estévez F, Samuel A. Tendencias actuales del uso de las estatinas en dislipidemias y otros efectos extralipídicos. Rev Cuba Angiol Cir Vasc. 2017;18(2):178-91.Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J. 2020;41(1):111-88.Chegwin-Angarita C, Nieto-Ramírez IJ, Atehortúa L, A LJS. Las estatinas: Actividad biológica y producción biotecnológica. Rev Colomb Biotecnol. 2012;14(2):157-78Narula J, Nakano M, Virmani R, Kolodgie FD, Petersen R, Newcomb R, et al. Histopathologic characteristics of atherosclerotic coronary disease and implications of the findings for the invasive and noninvasive detection of vulnerable plaques. J Am Coll Cardiol. 2013;61(10):1041-51.Pitt B, Loscalzo J, Monyak J, Miller E, Raichlen J. Comparison of lipid-modifying efficacy of rosuvastatin versus atorvastatin in patients with acute coronary syndrome (from the LUNAR study). Am J Cardiol. 2012;109(9):1239-46.Puri R, Nissen SE, Ballantyne CM, Barter PJ, Chapman MJ, Erbel R, et al. Factors underlying regression of coronary atheroma with potent statin therapy. Eur Heart J. 2013;34(24):1818-25.Mennickent C S, Bravo D M, Calvo M C, Avello L M. Efectos pleiotrópicos de las estatinas. Rev Médica Chile. 2008;136(6):775-82.Cordero A, Bertomeu-Martínez V, Mazón P, Fácila L, Cosín J, Bertomeu-González V, et al. Patients with cardiac disease: Changes observed through last decade in out-patient clinics. World J Cardiol. 2013;5(8):288-94.Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular Benefits and Diabetes Risks of Statin Therapy in Primary Prevention. Lancet. 2012;380(9841):565-71.Amarenco P, Bogousslavsky J, Callahan A, Goldstein LB, Hennerici M, Rudolph AE, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355(6):549-59.Oesterle A, Laufs U, Liao JK. Pleiotropic Effects of Statins on the Cardiovascular System. Circ Res. 2017;120(1):229-43.Pascual Fuster V. Tratamiento farmacológico de la dislipemia en pacientes de alto y muy alto riesgo cardiovascular. Rev Esp Sanid Penit. 2016;18(3):95-108.Ramos PM. Del concepto de estatinas de alta potencia a los efectos extralipídicos de las estatinas. Rev Esp Cardiol. 2015;15:22-7.Grundy Scott M., Stone Neil J., Bailey Alison L., Beam Craig, Birtcher Kim K., Blumenthal Roger S., et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139(25):e1082-143.Kim JW, Yun KH, Kim EK, Kim YC, Joe D-Y, Ko JS, et al. Effect of High Dose Rosuvastatin Loading before Primary Percutaneous Coronary Intervention on Infarct Size in Patients with ST-Segment Elevation Myocardial Infarction. Korean Circ J. 2014;44(2):76-81.Vindas CA. Fármacos hipolipemiantes. Revista médica de Costarica y Centroamérica. 2013;607:529-37.Björnsson ES. Hepatotoxicity of statins and other lipid-lowering agents. Liver Int. 2017;37(2):173-8.Liu A, Wu Q, Guo J, Ares I, Rodríguez J-L, Martínez-Larrañaga M-R, et al. Statins: Adverse reactions, oxidative stress and metabolic interactions. Pharmacol Ther. 2019;195:54-84.González Jiménez E, Álvarez Ferre J. Estatinas: Características y Efectos sobre el Control Lipídico en el Niño y Adolescente Obeso. Rev Clínica Med Fam. 2011;4(1):69-75.Sirtori CR. The pharmacology of statins. Pharmacol Res. 2014;88:3-11.Florez J, Freijanes J. Fármacos hipolipoproteinemiantes. En: Florez J, Armijo JA, editores Farmacología Humana. Quinta. Barcelona: ELSEVIER MASSON; 2008. p. 1080-3.García-Sabina A, Gulín-Dávila J, Sempere-Serrano P, González-Juanatey C, Martínez-Pacheco R. Consideraciones específicas en la prescripción e intercambio terapéutico de estatinas. Farm Hosp. 2012;36(2):97-108.Abd TT, Jacobson TA. Statin-induced myopathy: a review and update. Expert Opin Drug Saf. 2011;10(3):373-87.Bellosta S, Corsini A. Statin drug interactions and related adverse reactions. Expert Opin Drug Saf. 2012;11(6):933-46.ACT Lovastatin. Lovastatin 20 mg and 40 mg tablets USP. Lipid Metabolism Regulator [Internet]. Actavis Pharma Company; 2017. Disponible en: https://pdf.hres.ca/dpd_pm/00042711.PDFMinisterio de Salud de Colombia. Resolución 8430 de 1993 - Colombia [Internet]. www.redjurista.com. [citado 6 de abril de 2021]. Disponible en: https://www.redjurista.com/Documents/resolucion_8430_de_1993.aspxIBM SPSS Software [Internet]. 2021 [citado 6 de abril de 2021]. Disponible en: https://www.ibm.com/co-es/analytics/spss-statisticssoftwareFriedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature. 1998;395(6704):763-70.Morales Clavijo M, Carvajal Garcés CF. Obesidad y resistencia a la leptina. Gac Médica Boliv. 2010;33(1):63-8.Zhang F, Basinski MB, Beals JM, Briggs SL, Churgay LM, Clawson DK, et al. Crystal structure of the obese protein leptin-E100. Nature. 1997;387(6629):206-9.Auwerx J, Staels B. Leptin. Lancet Lond Engl. 1998;351(9104):737-42Arch JR, Stock MJ, Trayhurn P. Leptin resistance in obese humans: does it exist and what does it mean? Int J Obes Relat Metab Disord J Int Assoc Study Obes. 1998;22(12):1159-63.Ostlund RE, Yang JW, Klein S, Gingerich R. Relation between plasma leptin concentration and body fat, gender, diet, age, and metabolic covariates. J Clin Endocrinol Metab. 1996;81(11):3909-13.Considine RV. Weight regulation, leptin and growth hormone. Horm Res. 1997;48 Suppl 5:116-21.Havel PJ, Kasim-Karakas S, Mueller W, Johnson PR, Gingerich RL, Stern JS. Relationship of plasma leptin to plasma insulin and adiposity in normal weight and overweight women: effects of dietary fat content and sustained weight loss. J Clin Endocrinol Metab. 1996;81(12):4406-13.Ho S, Tai E-S, Eng P, Ramli A, Tan C, Fok A. A study in the relationships between leptin, insulin, and body fat in Asian subjects. Int J Obes Relat Metab Disord J Int Assoc Study Obes. 1999;23:246-52Koh KK, Quon MJ, Han SH, Lee Y, Park JB, Kim SJ, et al. Additive beneficial effects of atorvastatin combined with amlodipine in patients with mild-to-moderate hypertension. Int J Cardiol. 2011;146(3):319-25.Buldak L, Dulawa-Buldak A, Labuzek K, Okopien B. Effects of 90-day hypolipidemic treatment on insulin resistance, adipokines and proinflammatory cytokines in patients with mixed hyperlipidemia and impaired fasting glucose. Int J Clin Pharmacol Ther. 2012;50(11):805- 13.Carnevale R, Pignatelli P, Di Santo S, Bartimoccia S, Sanguigni V, Napoleone L, et al. Atorvastatin inhibits oxidative stress via adiponectinmediated NADPH oxidase down-regulation in hypercholesterolemic patients. Atherosclerosis. 2010;213(1):225-34.Kim J-H, Lee M-R, Shin J-A, Lee S-S, Lee J-M, You S-J, et al. Effects of pravastatin on serum adiponectin levels in female patients with type 2 diabetes mellitus. Atherosclerosis. 2013;227(2):355-9.Al-Azzam SI, Alkhateeb AM, Alzoubi KH, Alzayadeen RN, Ababneh MA, Khabour OF. Atorvastatin treatment modulates the interaction between leptin and adiponectin, and the clinical parameters in patients with type II diabetes. Exp Ther Med. 2013;6(6):1565-9.Anagnostis P, Selalmatzidou D, Polyzos SA, Panagiotou A, Slavakis A, Panagiotidou A, et al. Comparative effects of rosuvastatin and atorvastatin on glucose metabolism and adipokine levels in non-diabetic patients with dyslipidaemia: a prospective randomised open-label study. Int J Clin Pract. 2011;65(6):679-83.Viso M, Porrello B, Rauseo D, Reverón D, Rivas B, Galdona E, et al. Adiponectina y su relación con obesidad, insulinorresistencia y síndrome metabólico en adultos de la cohorte cdc de canarias en Venezuela. Rev Venez Endocrinol Metab. 2013;11(2):76-86.Krysiak R, Żmuda W, Marek B, Okopień B. Age may determine the effect of hypolipidemic agents on plasma adipokine levels in patients with elevated low-density lipoprotein cholesterol levels. Endokrynol Pol. 2016;67(3):271-6.Greenhill C. Obesity-induced hypermethylation of adiponectin gene. Nat Rev Endocrinol. 2015;11(9):504-504.Khan UI, Wang D, Sowers MR, Mancuso P, Everson-Rose SA, Scherer PE, et al. Race-ethnic differences in adipokine levels: the Study of Women’s Health Across the Nation (SWAN). Metabolism. 2012;61(9):1261-9.Elissondo N, Rosso L, Maidana P, Brites F. Adiponectin: An adipocytokine with multiple protective functions. Acta Bioquim Clin Latinoam. 2008;42:17-33Stepien M, Stepien A, Banach M, Wlazel RN, Paradowski M, Rizzo M, et al. New obesity indices and adipokines in normotensive patients and patients with hypertension: comparative pilot analysis. Angiology. 2014;65(4):333-42.Song JC, White CM. Pharmacologic, pharmacokinetic, and therapeutic differences among angiotensin II receptor antagonists. Pharmacotherapy. 2000;20(2):130-9.Sica DA, Gehr TWB, Ghosh S. Clinical pharmacokinetics of losartan. Clin Pharmacokinet. 2005;44(8):797-814.Zhou S-F, Zhou Z-W, Yang L-P, Cai J-P. Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.Wang Y-H, Jones DR, Hall SD. Differential mechanism-based inhibition of CYP3A4 and CYP3A5 by verapamil. Drug Metab Dispos Biol Fate Chem. 2005;33(5):664-71.Research C for DE and. Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. FDA [Internet]. 2020 [citado 30 de noviembre de 2020]; Disponible en: https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-druginteractions-table-substrates-inhibitors-and-inducersMartínez C, Albet C, Agúndez JA, Herrero E, Carrillo JA, Márquez M, et al. Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists. Clin Pharmacol Ther. 1999;65(4):369-76.Turpeinen M, Uusitalo J, Jouko U, Jalonen J, Jorma J, Pelkonen O, et al. Multiple P450 substrates in a single run: rapid and comprehensive in vitro interaction assay. Eur J Pharm Sci Off J Eur Fed Pharm Sci. 2005;24(1):123-32.Facciolà G, Avenoso A, Scordo MG, Madia AG, Ventimiglia A, Perucca E, et al. Small effects of valproic acid on the plasma concentrations of clozapine and its major metabolites in patients with schizophrenic or affective disorders. Ther Drug Monit. 1999;21(3):341-5.Martín de Argila de Prados C. Seguridad de los inhibidores de la bomba de protones (IBP). Rev Esp Enfermedades Dig. 2011;103(2):98- 98.Stout SM, Cimino NM. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev. 2014;46(1):86-95.Hirota T, Ieiri I. Drug-drug interactions that interfere with statin metabolism. Expert Opin Drug Metab Toxicol. 2015;11(9):1435-47.Qian Y, Gurley BJ, Markowitz JS. The Potential for Pharmacokinetic Interactions Between Cannabis Products and Conventional Medications. J Clin Psychopharmacol. 2019;39(5):462-71.Zvyaga T, Chang S-Y, Chen C, Yang Z, Vuppugalla R, Hurley J, et al. Evaluation of six proton pump inhibitors as inhibitors of various human cytochromes P450: focus on cytochrome P450 2C19. Drug Metab Dispos Biol Fate Chem. 2012;40(9):1698-711.Ikemura N, Yamaori S, Kobayashi C, Kamijo S, Murayama N, Yamazaki H, et al. Inhibitory effects of antihypertensive drugs on human cytochrome P450 2J2 activity: Potent inhibition by azelnidipine and manidipine. Chem Biol Interact. 2019;306:1-9.Krasulova K, Holas O, Anzenbacher P. Influence of Amlodipine Enantiomers on Human Microsomal Cytochromes P450: Stereoselective Time-Dependent Inhibition of CYP3A Enzyme Activity. Mol J Synth Chem Nat Prod Chem [Internet]. 2017 [citado 6 de abril de 2021];22(11). Disponible en: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150391/Wang Y-C, Hsieh T-C, Chou C-L, Wu J-L, Fang T-C. Risks of Adverse Events Following Coprescription of Statins and Calcium Channel Blockers: A Nationwide Population-Based Study. Medicine (Baltimore). 2016;95(2):e2487.Tolou-Ghamari Z. Antiepileptic drugs (AEDs) polypharmacy could lead to buried pharmacokinetic interactions due to CYP450. Drug Metab Lett. 2012;6(3):207-12.Quesada A, Agustín J. Actualización en farmacoterapia: la farmacología de las estatinas. Primera parte. Rev Costarric Cardiol. 2002;4(2):61-61.Huetos Ruiz J. Diferentes estatinas, distintas interacciones. Farm Prof. 2005;19(10):61-3.Gazzerro P, Proto MC, Gangemi G, Malfitano AM, Ciaglia E, Pisanti S, et al. Pharmacological actions of statins: a critical appraisal in the management of cancer. Pharmacol Rev. 2012;64(1):102-46.Hirota T, Fujita Y, Ieiri I. An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins. Expert Opin Drug Metab Toxicol. 2020;16(9):809-22.Takara K, Kakumoto M, Tanigawara Y, Funakoshi J, Sakaeda T, Okumura K. Interaction of digoxin with antihypertensive drugs via MDR1. Life Sci. 2002;70(13):1491-500.Pauli-Magnus C, Rekersbrink S, Klotz U, Fromm MF. Interaction of omeprazole, lansoprazole and pantoprazole with P-glycoprotein. Naunyn Schmiedebergs Arch Pharmacol. 2001;364(6):551-7.Li W, Zeng S, Yu L-S, Zhou Q. Pharmacokinetic drug interaction profile of omeprazole with adverse consequences and clinical risk management. Ther Clin Risk Manag. 2013;9:259-71.Shah Y, Iqbal Z, Ahmad L, Khuda F, Khan A, Khan A, et al. Effect of Omeprazole on the Pharmacokinetics of Rosuvastatin in Healthy Male Volunteers. Am J Ther. 2016;23(6):e1514-23.Armada A, Martins C, Spengler G, Molnar J, Amaral L, Rodrigues AS, et al. Fluorimetric Methods for Analysis of Permeability, Drug Transport Kinetics, and Inhibition of the ABCB1 Membrane Transporter. Methods Mol Biol Clifton NJ. 2016;1395:87-103.Wang L, Sun Y. Efflux mechanism and pathway of verapamil pumping by human P-glycoprotein. Arch Biochem Biophys. 2020;696:108675.Gallo P, De Vincentis A, Pedone C, Nobili A, Tettamanti M, Gentilucci UV, et al. Drug-drug interactions involving CYP3A4 and pglycoprotein in hospitalized elderly patients. Eur J Intern Med. 2019;65:51-7.Li W, Zeng S, Yu L-S, Zhou Q. Pharmacokinetic drug interaction profile of omeprazole with adverse consequences and clinical risk management. Ther Clin Risk Manag. 2013;9:259-71.Leopoldo M, Nardulli P, Contino M, Leonetti F, Luurtsema G, Colabufo NA. An updated patent review on P-glycoprotein inhibitors (2011- 2018). Expert Opin Ther Pat. 2019;29(6):455-61.Adamczak M, Wiecek A, Funahashi T, Chudek J, Kokot F, Matsuzawa Y. Decreased plasma adiponectin concentration in patients with essential hypertension. Am J Hypertens. 2003;16(1):72-5.Miyazaki T, Shimada K, Mokuno H, Daida H. Adipocyte derived plasma protein, adiponectin, is associated with smoking status in patients with coronary artery disease. Heart. 2003;89(6):663Pischon T, Girman CJ, Rifai N, Hotamisligil GS, Rimm EB. Association between dietary factors and plasma adiponectin concentrations in men. Am J Clin Nutr. 2005;81(4):780-6.Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999;257(1):79-83.Yatagai T, Nagasaka S, Taniguchi A, Fukushima M, Nakamura T, Kuroe A, et al. Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 diabetes mellitus. Metabolism. 2003;52(10):1274-8.Yamamoto Y, Hirose H, Saito I, Nishikai K, Saruta T. Adiponectin, an Adipocyte-Derived Protein, Predicts Future Insulin Resistance: TwoYear Follow-Up Study in Japanese Population. J Clin Endocrinol Metab. 2004;89(1):87-90.Lindsay RS, Funahashi T, Hanson RL, Matsuzawa Y, Tanaka S, Tataranni PA, et al. Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet Lond Engl. 2002;360(9326):57-8.Rosado EL, Monteiro JB, Chaia V, Lago MF do. Efecto de la leptina en el tratamiento de la obesidad e influencia de la dieta en la secreción y acción de la hormona. Nutr Hosp. 2006;21(6):686-93.Miyatake N, Takahashi K, Wada J, Nishikawa H, Morishita A, Suzuki H, et al. Changes in serum leptin concentrations in overweight Japanese men after exercise. Diabetes Obes Metab. 2004;6:332-7.Waki H, Yamauchi T, Kamon J, Ito Y, Uchida S, Kita S, et al. Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J Biol Chem. 2003;278(41):40352-63.Vasseur F, Helbecque N, Dina C, Lobbens S, Delannoy V, Gaget S, et al. Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians. Hum Mol Genet. 2002;11(21):2607-14.Kondo H, Shimomura I, Matsukawa Y, Kumada M, Takahashi M, Matsuda M, et al. Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome. Diabetes. 2002;51(7):2325-8.Stumvoll M, Tschritter O, Fritsche A, Staiger H, Renn W, Weisser M, et al. Association of the T-G Polymorphism in Adiponectin (Exon 2) With Obesity and Insulin Sensitivity: Interaction With Family History of Type 2 Diabetes. Diabetes. 2002;51(1):37-41.Guan Z-W, Wu K-R, Li R, Yin Y, Li X-L, Zhang S-F, et al. Pharmacogenetics of statins treatment: Efficacy and safety. J Clin Pharm Ther. 2019;44(6):858-67.Fan LH, He Y, Xu W, Tian HY, Zhou Y, Liang Q, et al. Adiponectin may be a biomarker of early atherosclerosis of smokers and decreased by nicotine through KATP channel in adipocytes. Nutr Burbank Los Angel Cty Calif. 2015;31(7-8):955-8.Guimarães ES, Cerda A, Dorea EL, Bernik MMS, Gusukuma MC, Pinto GA, et al. Effects of short-term add-on ezetimibe to statin treatment on expression of adipokines and inflammatory markers in diabetic and dyslipidemic patients. Cardiovasc Ther. 2017;35(6).Tassaneeyakul W, Vannaprasaht S, Yamazoe Y. Formation of omeprazole sulphone but not 5-hydroxyomeprazole is inhibited by grapefruit juice. Br J Clin Pharmacol. 2000;49(2):139-44.info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2LeptinaAdiponectinaEstatinasLovastatinaAtorvastatinaCiencias médicasFarmacologíaORIGINALLeidyYurani_CardenasParra_2021.pdfLeidyYurani_CardenasParra_2021.pdfLeidyYurani_CardenasParra_2021.pdfapplication/pdf1813169https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/1/LeidyYurani_CardenasParra_2021.pdf277bb74d59fff6287740d7e6acdefb14MD51Autorización repositorio.pdfAutorización repositorio.pdfCarta de autorizaciónapplication/pdf482793https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/3/Autorizaci%c3%b3n%20repositorio.pdf0e8e1e8686ae21d6779595982fa87f30MD53Acta sustentación firma jurado 1.pdfActa sustentación firma jurado 1.pdfActa de sustentaciónapplication/pdf131679https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/4/Acta%20sustentaci%c3%b3n%20firma%20jurado%201.pdf80f8f390de1492c37a3b5ae6c24a7bcfMD54Acta sustentación firma jurado 2.PDFActa sustentación firma jurado 2.PDFActa de sustentación2application/pdf68459https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/5/Acta%20sustentaci%c3%b3n%20firma%20jurado%202.PDFad804ddf9d35bac69b9278552ee44da4MD55PDF_ documentos adicionales.pdfPDF_ documentos adicionales.pdfAnexosapplication/pdf765399https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/6/PDF_%20documentos%20adicionales.pdfe5e3f88999f4fe2f7982e1b5c801172cMD56LICENSElicense.txtlicense.txttext/plain; charset=utf-814828https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/7/license.txt2f9959eaf5b71fae44bbf9ec84150c7aMD57TEXTLeidyYurani_CardenasParra_2021.pdf.txtLeidyYurani_CardenasParra_2021.pdf.txtExtracted texttext/plain124758https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/8/LeidyYurani_CardenasParra_2021.pdf.txt88852e9e0f12563246dee6258c96b712MD58Autorización repositorio.pdf.txtAutorización repositorio.pdf.txtExtracted texttext/plain5618https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/10/Autorizaci%c3%b3n%20repositorio.pdf.txt26e0810bb88f78f5cc05c7c45e4bcecaMD510Acta sustentación firma jurado 1.pdf.txtActa sustentación firma jurado 1.pdf.txtExtracted texttext/plain1259https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/12/Acta%20sustentaci%c3%b3n%20firma%20jurado%201.pdf.txt93a9a207f3e803339f684d4824fc6d12MD512Acta sustentación firma jurado 2.PDF.txtActa sustentación firma jurado 2.PDF.txtExtracted texttext/plain1259https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/14/Acta%20sustentaci%c3%b3n%20firma%20jurado%202.PDF.txt93a9a207f3e803339f684d4824fc6d12MD514PDF_ documentos adicionales.pdf.txtPDF_ documentos adicionales.pdf.txtExtracted texttext/plain6195https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/16/PDF_%20documentos%20adicionales.pdf.txt1d086e7c0a3422c2fef839b02efe4360MD516THUMBNAILLeidyYurani_CardenasParra_2021.pdf.jpgLeidyYurani_CardenasParra_2021.pdf.jpgGenerated Thumbnailimage/jpeg8696https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/9/LeidyYurani_CardenasParra_2021.pdf.jpgc0567faca030b9ce7625fe61e4c12faeMD59Autorización repositorio.pdf.jpgAutorización repositorio.pdf.jpgGenerated Thumbnailimage/jpeg11194https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/11/Autorizaci%c3%b3n%20repositorio.pdf.jpgb599bc2f8b8fc540ccbd2e52d70f2c81MD511Acta sustentación firma jurado 1.pdf.jpgActa sustentación firma jurado 1.pdf.jpgGenerated Thumbnailimage/jpeg11431https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/13/Acta%20sustentaci%c3%b3n%20firma%20jurado%201.pdf.jpg351f0bd185025cb93844db0223383285MD513Acta sustentación firma jurado 2.PDF.jpgActa sustentación firma jurado 2.PDF.jpgGenerated Thumbnailimage/jpeg11312https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/15/Acta%20sustentaci%c3%b3n%20firma%20jurado%202.PDF.jpga38599cbd6b9341e56b1c32f7f9ec316MD515PDF_ documentos adicionales.pdf.jpgPDF_ documentos adicionales.pdf.jpgGenerated Thumbnailimage/jpeg13353https://repositorio.ucaldas.edu.co/bitstream/ucaldas/16626/17/PDF_%20documentos%20adicionales.pdf.jpgd9b0588adabcc51c2c28e1a081cefc0eMD517ucaldas/16626oai:repositorio.ucaldas.edu.co:ucaldas/166262021-11-03 22:16:55.874Repositorio Digital de la Universidad de Caldasbdigital@metabiblioteca.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

Comparación de los efectos de las estatinas sobre las concentraciones séricas de leptina y adiponectina

Publicaciones similares