Diabetes mellitus TIPO 2: rol de la insulinorresistencia y la hiperinsulinemia en la etiopatogenia
Palabras clave:
Diabetes mellitus tipo 2, insulinorresistencia, hiperinsulinemia, hiperglicemia, etiopatogeniaResumen
La diabetes mellitus tipos 2 (DM2) es un trastorno endocrino-metabólico altamente prevalente a nivel mundial, por lo que representa un grave problema de salud pública. Si bien su etiología es multifactorial, la hiperinsulinemia y la insulinorresistencia (IR) figuran como un punto clave en la etiopatogenia de la enfermedad. Así pues, se ha descrito como ambos factores, en conjunto con altos niveles de glucosa plasmática, contribuyen directamente con el desarrollo de la DM2 y sus complicaciones. Los mecanismos fisiopatológicos que llevan a la IR son diversos, destacando entre ellos la inflamación crónica de bajo grado, las alteraciones en el perfil secretor de los adipocitos, los altos niveles de ácidos grasos libres, la glucotoxicidad, y la presencia de ciertas mutaciones genéticas. Ante tal problemática, la comunidad científica ha buscado estrategias preventivas no farmacológicas contra la IR. Evidencia clínica ha demostrado como las intervenciones nutricionales y la actividad física pueden mejorar el perfil inflamatorio, la sensibilidad a la insulina y el control de la glucosa plasmática en pacientes obesos, con IR o con DM2. Por lo tanto, es recomendable que la población en riesgo de padecer IR y DM2 mantengan un estilo de vida saludable que aminore las probabilidades de desarrollar dichas entidades clínicas. El objetivo del presente artículo de revisión es describir el rol de la IR y la hiperinsulinemia en la etiopatogenia de la DM2, así como exponer el abordaje preventivo no farmacológico contra la IR y la DM2.
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Al-Lawati JA. Diabetes Mellitus: A Local and Global Public Health Emergency!. Oman Med J. 2017;32(3):177-179. doi:10.5001/omj.2017.34.
World Health Organization. Diabetes [Internet]. [citado 7 de febrero de 2022]. Disponible en: https://www.who.int/news-room/fact-sheets/detail/diabetes.
El-Kebbi IM, Bidikian NH, Hneiny L, Nasrallah MP. Epidemiology of type 2 diabetes in the Middle East and North Africa: Challenges and call for action. World Journal of Diabetes [Internet]. 15 de septiembre de 2021 [citado 7 de febrero de 2022];12(9):1401-25. Disponible en: https://www.wjgnet.com/1948-9358/full/v12/i9/1401.htm.
Khan MAB, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of Type 2 Diabetes - Global Burden of Disease and Forecasted Trends. J Epidemiol Glob Health. 2020; 10(1):107-111. doi:10.2991/jegh.k.191028.001.
American Diabetes Association. The cost of diabetes | ada [Internet]. [citado 7 de febrero de 2022]. Disponible en: https://www.diabetes.org/resources/statistics/cost-diabetes.
Penckofer S, Ferrans CE, Velsor-Friedrich B, Savoy S. The psychological impact of living with diabetes: women’s day-to-day experiences. Diabetes Educ. 2007;33(4):680-690. doi:10.1177/0145721707304079.
Kotwas A, Karakiewicz B, Zabielska P, Wieder-Huszla S, Jurczak A. Epidemiological factors for type 2 diabetes mellitus: evidence from the Global Burden of Disease. Arch Public Health [Internet]. diciembre de 2021 [citado 7 de febrero de 2022];79(1):110. Disponible en: https://archpublichealth.biomedcentral.com/articles/10.1186/s13690-021-00632-1.
Silva EFF, Ferreira CMM, Pinho L. Risk factors and complications in type 2 diabetes outpatients. Rev Assoc Med Bras (1992). 2017 Jul;63(7):621-627. doi: 10.1590/1806-9282.63.07.621. PMID: 28977088.
Papatheodorou K, Banach M, Bekiari E, Rizzo M, Edmonds M. Complications of Diabetes 2017. J Diabetes Res. 2018;2018:3086167. Published 2018 Mar 11. doi:10.1155/2018/3086167.
Hajek T, McIntyre R, Alda M. Bipolar disorders, type 2 diabetes mellitus, and the brain. Curr Opin Psychiatry. 2016 Jan;29(1):1-6. doi: 10.1097/YCO.0000000000000215. PMID: 26575297.
Bellou V, Belbasis L, Tzoulaki I, Evangelou E. Risk factors for type 2 diabetes mellitus: An exposure-wide umbrella review of meta-analyses. PLoS One. 2018;13(3):e0194127. Published 2018 Mar 20. doi:10.1371/journal.pone.0194127.
Fletcher B, Gulanick M, Lamendola C. Risk factors for type 2 diabetes mellitus. J Cardiovasc Nurs. 2002 Jan;16(2):17-23. doi: 10.1097/00005082-200201000-00003. PMID: 11800065.
Thomas DD, Corkey BE, Istfan NW, Apovian CM. Hyperinsulinemia: An Early Indicator of Metabolic Dysfunction. J Endocr Soc. 2019;3(9):1727-1747. Published 2019 Jul 24. doi:10.1210/js.2019-00065.
Taylor R. Insulin resistance and type 2 diabetes. Diabetes. 2012 Apr;61(4):778-9. doi: 10.2337/db12-0073. PMID: 22442298; PMCID: PMC3314346.
Albosta M, Bakke J. Intermittent fasting: is there a role in the treatment of diabetes? A review of the literature and guide for primary care physicians. Clin Diabetes Endocrinol. 2021 Feb 3;7(1):3. doi: 10.1186/s40842-020-00116-1. PMID: 33531076; PMCID: PMC7856758.
Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, Ostolaza H, Martín C. Pathophysiology of Type 2 Diabetes Mellitus. Int J Mol Sci. 2020 Aug 30;21(17):6275. doi: 10.3390/ijms21176275. PMID: 32872570; PMCID: PMC7503727.
Petersen MC, Shulman GI. Mechanisms of Insulin Action and Insulin Resistance. Physiol Rev. 2018 Oct 1;98(4):2133-2223. doi: 10.1152/physrev.00063.2017. PMID: 30067154; PMCID: PMC6170977.
Wilcox G. Insulin and insulin resistance. Clin Biochem Rev. 2005;26(2):19-39.
Morita I, Tanimoto K, Akiyama N, Naya N, Fujieda K, Iwasaki T, Yukioka H. Chronic hyperinsulinemia contributes to insulin resistance under dietary restriction in association with altered lipid metabolism in Zucker diabetic fatty rats. Am J Physiol Endocrinol Metab. 2017 Apr 1;312(4):E264-E272. doi: 10.1152/ajpendo.00342.2016. Epub 2017 Jan 31. PMID: 28143857.
Shanik MH, Xu Y, Skrha J, Dankner R, Zick Y, Roth J. Insulin resistance and hyperinsulinemia: is hyperinsulinemia the cart or the horse? Diabetes Care. 2008 Feb;31 Suppl 2:S262-8. doi: 10.2337/dc08-s264. PMID: 18227495.
Barclay JL, Shostak A, Leliavski A, Tsang AH, Jöhren O, Müller-Fielitz H, Landgraf D, Naujokat N, van der Horst GT, Oster H. High-fat diet-induced hyperinsulinemia and tissue-specific insulin resistance in Cry-deficient mice. Am J Physiol Endocrinol Metab. 2013 May 15;304(10):E1053-63. doi: 10.1152/ajpendo.00512.2012. Epub 2013 Mar 26. PMID: 23531614.
Ghadieh HE, Russo L, Muturi HT, Ghanem SS, Manaserh IH, Noh HL, Suk S, Kim JK, Hill JW, Najjar SM. Hyperinsulinemia drives hepatic insulin resistance in male mice with liver-specific Ceacam1 deletion independently of lipolysis. Metabolism. 2019 Apr;93:33-43. doi: 10.1016/j.metabol.2019.01.008. Epub 2019 Jan 19. PMID: 30664851; PMCID: PMC6401268.
Lee Y, Fluckey JD, Chakraborty S, Muthuchamy M. Hyperglycemia- and hyperinsulinemia-induced insulin resistance causes alterations in cellular bioenergetics and activation of inflammatory signaling in lymphatic muscle. FASEB J. 2017 Jul;31(7):2744-2759. doi: 10.1096/fj.201600887R. Epub 2017 Mar 15. PMID: 28298335; PMCID: PMC5471512.
Turner MC, Martin NRW, Player DJ, Ferguson RA, Wheeler P, Green CJ, Akam EC, Lewis MP. Characterising hyperinsulinemia-induced insulin resistance in human skeletal muscle cells. J Mol Endocrinol. 2020 Apr;64(3):125-132. doi: 10.1530/JME-19-0169. PMID: 31990657.
Kahn, S., Hull, R. & Utzschneider, K. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444, 840–846 (2006). https://doi.org/10.1038/nature05482.
Assimacopoulos-Jeannet F, Brichard S, Rencurel F, Cusin I, Jeanrenaud B. In vivo effects of hyperinsulinemia on lipogenic enzymes and glucose transporter expression in rat liver and adipose tissues. Metabolism. 1995 Feb;44(2):228-33. doi: 10.1016/0026-0495(95)90270-8. PMID: 7869920.
Fryk E, Olausson J, Mossberg K, Strindberg L, Schmelz M, Brogren H, et al. Hyperinsulinemia and insulin resistance in the obese may develop as part of a homeostatic response to elevated free fatty acids: A mechanistic case-control and a population-based cohort study. EBioMedicine [Internet]. marzo de 2021 [citado 9 de febrero de 2022];65:103264. Disponible en: https://linkinghub.elsevier.com/retrieve/pii/S2352396421000578.
Bermúdez V, Durán P, Rojas E, Díaz MP, Rivas J, Nava M, Chacín M, Cabrera de Bravo M, Carrasquero R, Ponce CC, Górriz JL, D Marco L. The Sick Adipose Tissue: New Insights Into Defective Signaling and Crosstalk With the Myocardium. Front Endocrinol (Lausanne). 2021 Sep 15;12:735070. doi: 10.3389/fendo.2021.735070. PMID: 34603210; PMCID: PMC8479191.
Pitsavos C, Tampourlou M, Panagiotakos DB, et al. Association Between Low-Grade Systemic Inflammation and Type 2 Diabetes Mellitus Among Men and Women from the ATTICA Study. Rev Diabet Stud. 2007;4(2):98-104. doi:10.1900/RDS.2007.4.98.
Heilbronn LK, Campbell LV. Adipose tissue macrophages, low grade inflammation and insulin resistance in human obesity. Curr Pharm Des. 2008;14(12):1225-30. doi: 10.2174/138161208784246153. PMID: 18473870.
McNally AK, Anderson JM. Macrophage fusion and multinucleated giant cells of inflammation. Adv Exp Med Biol. 2011;713:97-111. doi: 10.1007/978-94-007-0763-4_7. PMID: 21432016.
Orr JS, Puglisi MJ, Ellacott KL, Lumeng CN, Wasserman DH, Hasty AH. Toll-like receptor 4 deficiency promotes the alternative activation of adipose tissue macrophages. Diabetes. 2012 Nov;61(11):2718-27. doi: 10.2337/db11-1595. Epub 2012 Jun 29. PMID: 22751700; PMCID: PMC3478520.
Nieto-Vazquez I, Fernández-Veledo S, Krämer DK, Vila-Bedmar R, Garcia-Guerra L, Lorenzo M. Insulin resistance associated to obesity: the link TNF-alpha. Arch Physiol Biochem. 2008 Jul;114(3):183-94. doi: 10.1080/13813450802181047. Erratum in: Arch Physiol Biochem. 2009 May;115(2):117. PMID: 18629684.
Rehman K, Akash MSH, Liaqat A, Kamal S, Qadir MI, Rasul A. Role of Interleukin-6 in Development of Insulin Resistance and Type 2 Diabetes Mellitus. Crit Rev Eukaryot Gene Expr. 2017;27(3):229-236. doi: 10.1615/CritRevEukaryotGeneExpr.2017019712. PMID: 29199608.
Jager J, Grémeaux T, Cormont M, Le Marchand-Brustel Y, Tanti JF. Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology. 2007 Jan;148(1):241-51. doi: 10.1210/en.2006-0692. Epub 2006 Oct 12. PMID: 17038556; PMCID: PMC1971114.
Makki K, Froguel P, Wolowczuk I. Adipose tissue in obesity-related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm. 2013;2013:139239. Published 2013 Dec 22. doi:10.1155/2013/139239.
Shetty S, Kumari S. Fatty acids and their role in type 2 diabetes (Review). Exp Ther Med [Internet]. 2 de mayo de 2021 [citado 8 de febrero de 2022];22(1):706. Disponible en: http://www.spandidos-publications.com/10.3892/etm.2021.10138.
Freeman AM, Pennings N. Insulin Resistance. [Updated 2021 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507839/.
Liu L, Mei M, Yang S, Li Q. Roles of chronic low-grade inflammation in the development of ectopic fat deposition. Mediators Inflamm. 2014;2014:418185. doi:10.1155/2014/418185.
Del Prato S. Role of glucotoxicity and lipotoxicity in the pathophysiology of Type 2 diabetes mellitus and emerging treatment strategies. Diabet Med. 2009 Dec;26(12):1185-92. doi: 10.1111/j.1464-5491.2009.02847.x. PMID: 20002468.
Robertson RP, Harmon J, Tran PO, Poitout V. Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes. 2004 Feb;53 Suppl 1:S119-24. doi: 10.2337/diabetes.53.2007.s119. PMID: 14749276.
Osegbe I, Okpara H, Azinge E. Relationship between serum leptin and insulin resistance among obese Nigerian women. Ann Afr Med. 2016;15(1):14-19. doi:10.4103/1596-3519.158524.
Katsiki N, Mikhailidis DP, Banach M. Leptin, cardiovascular diseases and type 2 diabetes mellitus. Acta Pharmacol Sin. 2018;39(7):1176-1188. doi:10.1038/aps.2018.40.
Paz-Filho G, Mastronardi C, Wong ML, Licinio J. Leptin therapy, insulin sensitivity, and glucose homeostasis. Indian J Endocrinol Metab. 2012;16(Suppl 3):S549-S555. doi:10.4103/2230-8210.105571.
Li S, Shin HJ, Ding EL, van Dam RM. Adiponectin levels and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA [Internet]. 8 de julio de 2009 [citado 8 de febrero de 2022];302(2):179. Disponible en: http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.2009.976.
Nigro E, Scudiero O, Monaco ML, et al. New insight into adiponectin role in obesity and obesity-related diseases. Biomed Res Int. 2014;2014:658913. doi:10.1155/2014/658913.
Wang Y, Meng RW, Kunutsor SK, et al. Plasma adiponectin levels and type 2 diabetes risk: a nested case-control study in a Chinese population and an updated meta-analysis. Sci Rep. 2018;8(1):406. Published 2018 Jan 10. doi:10.1038/s41598-017-18709-9.
Ruderman NB, Carling D, Prentki M, Cacicedo JM. AMPK, insulin resistance, and the metabolic syndrome. J Clin Invest. 2013;123(7):2764-2772. doi:10.1172/JCI67227.
Yadav A, Kataria MA, Saini V, Yadav A. Role of leptin and adiponectin in insulin resistance. Clin Chim Acta. 2013 Feb 18;417:80-4. doi: 10.1016/j.cca.2012.12.007. Epub 2012 Dec 22. PMID: 23266767.
Haluzík MM, Haluzík M. PPAR-alpha and insulin sensitivity. Physiol Res. 2006;55(2):115-22. Epub 2005 May 24. PMID: 15910175.
Mambiya M, Shang M, Wang Y, Li Q, Liu S, Yang L, et al. The play of genes and non-genetic factors on type 2 diabetes. Front Public Health [Internet]. 19 de noviembre de 2019 [citado 9 de febrero de 2022];7:349. Disponible en: https://www.frontiersin.org/article/10.3389/fpubh.2019.00349/full.
Mercado MM, McLenithan JC, Silver KD, Shuldiner AR. Genetics of insulin resistance. Curr Diab Rep. 2002 Feb;2(1):83-95. doi: 10.1007/s11892-002-0063-9. PMID: 12643127.
Sethi A, Foulds N, Ehtisham S, Ahmed SH, Houghton J, Colclough K, Didi M, Flanagan SE, Senniappan S. Heterozygous Insulin Receptor (INSR) Mutation Associated with Neonatal Hyperinsulinemic Hypoglycaemia and Familial Diabetes Mellitus: Case Series. J Clin Res Pediatr Endocrinol. 2020 Nov 25;12(4):420-426. doi: 10.4274/jcrpe.galenos.2019.2019.0106. Epub 2020 Jan 28. Erratum in: J Clin Res Pediatr Endocrinol. 2021 Jun 2;13(2):249. PMID: 31989990; PMCID: PMC7711633.
Melo BF, Sacramento JF, Ribeiro MJ, Prego CS, Correia MC, Coelho JC, Cunha-Guimaraes JP, Rodrigues T, Martins IB, Guarino MP, Seiça RM, Matafome P, Conde SV. Evaluating the Impact of Different Hypercaloric Diets on Weight Gain, Insulin Resistance, Glucose Intolerance, and its Comorbidities in Rats. Nutrients. 2019 May 28;11(6):1197. doi: 10.3390/nu11061197. PMID: 31141900; PMCID: PMC6627141.
Adeva-Andany MM, González-Lucán M, Fernández-Fernández C, Carneiro-Freire N, Seco-Filgueira M, Pedre-Piñeiro AM. Effect of diet composition on insulin sensitivity in humans. Clin Nutr ESPEN. 2019 Oct;33:29-38. doi: 10.1016/j.clnesp.2019.05.014. Epub 2019 Jun 6. PMID: 31451269.
Mirabelli M, Russo D, Brunetti A. The Role of Diet on Insulin Sensitivity. Nutrients. 2020;12(10):3042. Published 2020 Oct 4. doi:10.3390/nu12103042.
Jans A, Konings E, Goossens GH, Bouwman FG, Moors CC, Boekschoten MV, Afman LA, Müller M, Mariman EC, Blaak EE. PUFAs acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increase postprandial insulin sensitivity. Am J Clin Nutr. 2012 Apr;95(4):825-36. doi: 10.3945/ajcn.111.028787. Epub 2012 Feb 15. PMID: 22338035.
Wei Y, Meng Y, Li N, Wang Q, Chen L. The effects of low-ratio n-6/n-3 PUFA on biomarkers of inflammation: a systematic review and meta-analysis. Food Funct. 2021 Jan 7;12(1):30-40. doi: 10.1039/d0fo01976c. Epub 2020 Nov 24. PMID: 33232407.
Tzima N, Pitsavos C, Panagiotakos DB, Skoumas J, Zampelas A, Chrysohoou C, Stefanadis C. Mediterranean diet and insulin sensitivity, lipid profile and blood pressure levels, in overweight and obese people; the Attica study. Lipids Health Dis. 2007 Sep 19;6:22. doi: 10.1186/1476-511X-6-22. PMID: 17880675; PMCID: PMC2045655.
Kim K-H, Kim YH, Son JE, Lee JH, Kim S, Choe MS, et al. Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage. Cell Res. 2017;27(11):1309–26.
Trepanowski JF, Kroeger CM, Barnosky A, Klempel M, Bhutani S, Hoddy KK, et al. Effects of alternate-day fasting or daily calorie restriction on body composition, fat distribution, and circulating adipokines: Secondary analysis of a randomized controlled trial. Clin Nutr Edinb Scotl. 2018;37(6 Pt A):1871–8.
Khoo J, Dhamodaran S, Chen D-D, Yap S-Y, Chen RY-T, Tian RH-H. Exercise-Induced Weight Loss is More Effective than Dieting for Improving Adipokine Profile, Insulin Resistance, and Inflammation in Obese Men. Int J Sport Nutr Exerc Metab. 2015;25(6):566–75.
Abd El-Kader SM, Al-Jiffri OH, Neamatallah ZA, AlKhateeb AM, AlFawaz SS. Weight reduction ameliorates inflammatory cytokines, adipocytokines and endothelial dysfunction biomarkers among Saudi patients with type 2 diabetes. Afr Health Sci. 2020;20(3):1329–36.
Elloumi M, Ben Ounis O, Makni E, Van Praagh E, Tabka Z, Lac G. Effect of individualized weight-loss programmes on adiponectin, leptin and resistin levels in obese adolescent boys. Acta Paediatr Oslo Nor 1992. 2009;98(9):1487–93.
Dubé JJ, Allison KF, Rousson V, Goodpaster BH, Amati F. Exercise dose and insulin sensitivity: relevance for diabetes prevention. Med Sci Sports Exerc. 2012;44(5):793-799. doi:10.1249/MSS.0b013e31823f679f.
Sampath Kumar A, Maiya AG, Shastry BA, Vaishali K, Ravishankar N, Hazari A, Gundmi S, Jadhav R. Exercise and insulin resistance in type 2 diabetes mellitus: A systematic review and meta-analysis. Ann Phys Rehabil Med. 2019 Mar;62(2):98-103. doi: 10.1016/j.rehab.2018.11.001. Epub 2018 Dec 13. PMID: 30553010.
Whillier S. Exercise and Insulin Resistance. Adv Exp Med Biol. 2020;1228:137-150. doi: 10.1007/978-981-15-1792-1_9. PMID: 32342455.
Bird SR, Hawley JA. Update on the effects of physical activity on insulin sensitivity in humans. BMJ Open Sport Exerc Med. 2017;2(1):e000143. Published 2017 Mar 1. doi:10.1136/bmjsem-2016-000143+.
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