Obesity-diabetes-endocrinopathy – the metabolic connection
DOI:
https://doi.org/10.15584/ejcem.2022.4.12Keywords:
diabetes, endocrinopathy, hypogonadism, insulin resistance, obesityAbstract
Introduction and aim. The article outlines the mechanisms of interrelationships between obesity, type 2 diabetes, and certain disorders of the endocrine system. The paper explains how insulin resistance develops, which is a key link between obesity and several related disorders, how hypercortisolemia leads to the development of obesity and glucose intolerance, why thyroid dysfunctions are bidirectionally associated with metabolic disturbances, in what way excessive body weight leads to the hypogonadism in men, or how menopause promotes the development of abdominal obesity, carbohydrate intolerance and, in some cases type 2 diabetes.
Material and methods. Scientific articles were reviewed by searching for information using the online database with scientific articles, including PubMed, Google Scholar and other available scientific databases.
Analysis of the literature. The huge prevalence of obesity, diabetes, and hormonal disorders (e.g., autoimmune thyroid disease, female and male hypogonadism) over the contemporary world together with the serious health consequences of these conditions makes up a specific triangle of metabolic connections, increasingly absorbing the human, organizational and financial resources of health systems.
Conclusion. Recognizing the relationship between the components of this triangle and understanding the risks arising from this phenomenon may allow to effectively reduce its impact on our health.
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References
Chait A, den Hartigh LJ. Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease. Front Cardiovasc Med. 2020;7:22. doi: 10.3389/fcvm.2020.00022
Bray GA. Medical consequences of obesity. J Clin Endocrinol Metab. 2004;89(6):2583-2589. doi: 10.1210/jc.2004-0535
Chu DT, Minh Nguyet NT, Dinh TC, et al. An update on physical health and economic consequences of overweight and obesity. Diabetes Metab Syndr. 2018;12(6):1095-1100. doi: 10.1016/j.dsx.2018.05.004
Csige I, Ujvárosy D, Szabó Z, et al. The Impact of Obesity on the Cardiovascular System. J Diabetes Res. 2018;2018:3407306. doi: 10.1155/2018/3407306
Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444(7122):1027-1031. doi: 10.1038/nature05414
Heidari-Beni M. Early Life Nutrition and Non-Communicable Disease. Adv Exp Med Biol. 2019;1121:33-40. doi: 10.1007/978-3-030-10616-4_4
Ford ES, Williamson DF, Liu S. Weight change and diabetes incidence: findings from a national cohort of US adults. Am J Epidemiol. 1997;146(3):214-222. doi: 10.1093/oxfordjournals.aje.a009256
Bhupathiraju SN, Hu FB. Epidemiology of Obesity and Diabetes and Their Cardiovascular Complications. Circ Res. 2016;118(11):1723-1735. doi: 10.1161/CIRCRESAHA.115.306825
Ellis BA, Poynten A, Lowy AJ, et al. Long-chain acyl-CoA esters as indicators of lipid metabolism and insulin sensitivity in rat and human muscle. Am J Physiol Endocrinol Metab. 2000;279:E554-E560. doi: 10.1152/ajpendo.2000.279.3.E554
Kojta I, Chacińska M, Błachnio-Zabielska A. Obesity, Bioactive Lipids, and Adipose Tissue Inflammation in Insulin Resistance. Nutrients. 2020;12(5):1305-1319. doi: 10.3390/nu12051305
Ye J. Mechanisms of insulin resistance in obesity. Front Med. 2013;7(1):14-24. doi: 10.1007/s11684-013-0262-6
Moonishaa TM, Nanda SK, Shamraj M, Sivaa R, Sivakumar P, Ravichandran K. Evaluation of leptin as a marker of insulin resistance in type 2 diabetes mellitus. Int J Appl Basic Med Res. 2017;7(3):176-180. doi: 10.4103/ijabmr.IJABMR_278_16
Tiwari-Heckler S, Gan-Schreier H, Stremmel W, Chamulirat W, Pathil A. Circulating phospholipid patterns in NAFLD patients associated with a combination of metabolic risk factors. Nutrients. 2018;10(5):649. doi: 10.3390/nu10050649
Lustig RH, Sen S, Soberman JE, Velasquez-Mieyer PA. Obesity, leptin resistance, and the effects of insulin reduction. Int J Obes Relat Metab Disord. 2004;28(10):1344-1348. doi: 10.1038/sj.ijo.0802753
Bungau S, Behl T, Tit DM, et al. Interactions between leptin and insulin resistance in patients with prediabetes, with and without NAFLD. Exp Ther Med. 2020;20(6):197. doi: 10.3892/etm.2020.9327
Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes. Nature. 2001;409(6818):307-312. doi: 10.1038/35053000
Catalán V, Gómez-Ambrosi J, Rodríguez A, et al. Increased adipose tissue expression of lipocalin-2 in obesity is related to inflammation and matrix metalloproteinase-2 and metalloproteinase-9 activities in humans. J Mol Med (Berl). 2009;87:803-813. doi: 10.1007/s00109-009-0486-8
Papanicolaou DA, Wilder RL, Manolagas SC, Chrousos GP. The pathophysiologic roles of interleukin-6 in human disease. Ann Intern Med. 1998;128:127-137. doi: 10.7326/0003-4819-128-2-199801150-00009
Kern PA, Ranganathan S, Li C, Wood L, Ranganathan G. Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol Endocrinol Metab. 2001;280:E745-E751. doi: 10.1152/ajpendo.2001.280.5.E745
Małecki MT. Obesity – insulin resistance – type 2 diabetes mellitus. Kadriol Pol. 2006;64,10(6):561-566.
International Diabetes Federation. IDF Diabetes Atlas, 9th ed. Brussels, Belgium: 2019. Available at: https://www.diabetesatlas.org. Accessed February 14, 2020.
Chowdhury TA, Shaho S, Moolla A. Complications of diabetes: progress, but significant challenges ahead. Ann Transl Med. 2014;2(12):120. doi: 10.3978/j.issn.2305-5839.2014.08.12
Ryan DH, Yockey SR. Weight Loss and Improvement in Comorbidity: Differences at 5%, 10%, 15%, and Over. Curr Obes Rep. 2017;6(2):187-194. doi: 10.1007/s13679-017-0262
Cummings DE, Rubino F. Metabolic surgery for the treatment of type 2 diabetes in obese individuals. Diabetologia. 2018;61(2):257-264. doi: 10.1007/s00125-017-4513-y
Mazziotti G, Gazzaruso C, Giustina A. Diabetes in Cushing syndrome: basic and clinical aspects. Trends Endocrinol Metab. 2011;22(12):499-506. doi:10.1016/j.tem.2011.09.001
Hansen KB, Vilsbøll T, Bagger JI, Holst JJ, Knop FK. Reduced glucose tolerance and insulin resistance induced by steroid treatment, relative physical inactivity, and high-calorie diet impairs the incretin effect in healthy subjects. J Clin Endocrinol Metab. 2010;95(7):3309-3317. doi: 10.1210/jc.2010-0119
Pivonello R, De Leo M, Vitale P, et al. Pathophysiology of diabetes mellitus in Cushing's syndrome. Neuroendocrinology. 2010;92(1):77-81. doi: 10.1159/000314319
Pasquali R, Casanueva F, Haluzik M, et al. European Society of Endocrinology Clinical Practice Guideline: Endocrine work-up in obesity. Eur J Endocrinol. 2020;182(1):G1-G32. doi: 10.1530/EJE-19-0893.
Clemmons DR. Metabolic actions of insulin-like growth factor-I in normal physiology and diabetes. Endocrinol Metab Clin North Am. 2012;41(2):425-443. doi: 10.1016/j.ecl.2012.04.017
Kim SH, Park MJ. Effects of growth hormone on glucose metabolism and insulin resistance in human. Ann Pediatr Endocrinol Metab. 2017;22(3):145-152. doi:10.6065/apem.2017.22.3.145
Korner J, Lo J, Freda PU, Wardlaw SL. Treatment with cabergoline is associated with weight loss in patients with hyperprolactinemia. Obes Res. 2003;11(2):311-312.
Knudsen N, Laurberg P, Rasmussen LB, et al. Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. J Clin Endocrinol Metab. 2005;90(7):4019-4024. doi:10.1210/jc.2004-2225
Xu R, Huang F, Zhang S, Lv Y, Liu Q. Thyroid function, body mass index, and metabolic risk markers in euthyroid adults: a cohort study. BMC Endocr Disord. 2019;19(1):58. doi: 10.1186/s12902-019-0383-2
Ajjan RA, Watson PF, Findlay C, et al. The sodium iodide symporter gene and its regulation by cytokines found in autoimmunity. J Endocrinol. 1998;158(3):351-358. doi: 10.1677/joe.0.1580351
Perros P, McCrimmon RJ, Shaw G, Frier BM. Frequency of thyroid dysfunction in diabetic patients: value of annual screening. Diabet Med. 1995;12(7):622-627. doi: 10.1111/j.1464-5491.1995.tb00553.x
Hage M, Zantout MS, Azar ST. Thyroid disorders and diabetes mellitus. J Thyroid Res. 2011;2011:439463. doi: 10.4061/2011/439463
Dimitriadis G, Baker B, Marsh H, et al. Effect of thyroid hormone excess on action, secretion, and metabolism of insulin in humans. Am J Physiol. 1985;248(5Pt1):E593-E601. doi: 10.1152/ajpendo.1985.248.5.E593
Miki N, Ono M, Hizuka N, Aoki T, Demura H. Thyroid hormone modulation of the hypothalamic growth hormone (GH)-releasing factor-pituitary GH axis in the rat. J Clin Invest. 1992;90(1):113-120. doi: 10.1172/JCI115823
Tosi F, Moghetti P, Castello R, Negri C, Bonora E, Muggeo M. Early changes in plasma glucagon and growth hormone response to oral glucose in experimental hyperthyroidism. Metabolism. 1996;45(8):1029-1033. doi: 10.1016/s0026-0495(96)90275-9
Okajima F, Ui M. Metabolism of glucose in hyper- and hypo-thyroid rats in vivo. Glucose-turnover values and futile-cycle activities obtained with 14C- and 3H-labelled glucose. Biochem J. 1979;182 (2):565-575. doi:10.1042/bj1820565
Maratou E, Hadjidakis DJ, Kollias A, et al. Studies of insulin resistance in patients with clinical and subclinical hypothyroidism. Eur J Endocrinol. 2009;160(5):785-790. doi: 10.1530/EJE-08-079
Decherf S, Seugnet I, Kouidhi S, Lopez-Juarez A, Clerget-Froidevaux MS, Demeneix BA. Thyroid hormone exerts negative feedback on hypothalamic type 4 melanocortin receptor expression. Proc Natl Acad Sci USA. 2010;107(9):4471-4476. doi: 10.1073/pnas.0905190107
Lanni A, Moreno M, Lombardi A, Goglia F. Thyroid hormone and uncoupling proteins. FEBS Lett. 2003;543(1-3):5-10. doi: 10.1016/s0014-5793(03)00320-x
Gursoy NT, Tuncel E. The relationship between the glycemic control and the hypothalamus-pituitary-thyroid axis in diabetic patients. Turkish J Endocrinol Metab. 1999;4:163-168.
Rezzonico J, Rezzonico M, Pusiol E, Pitoia F, Niepomniszcze H. Introducing the thyroid gland as another victim of the insulin resistance syndrome. Thyroid. 2008;18(4):461-464. doi: 10.1089/thy.2007.0223
Ross A, Bhasin S: Hypogonadism: its prevalence anddiagnosis. Urol Clin North Am. 2016;43:163-176.
Sánchez-Garrido MA, Ruiz-Pino F, Manfredi-Lozano M, et al. Obesity-induced hypogonadism in the male: premature reproductive neuroendocrine senescence and contribution of Kiss1-mediated mechanisms. Endocrinology. 2014;155(3):1067-1079. doi: 10.1210/en.2013-1584
Tena-Sempere M, Pinilla L, Gonzalez LC, Dieguez C, Casanueva FF, Aguilar E. Leptin inhibits testosterone secretion from adult rat testis in vitro. J Endocrinol. 1999;161(2):211-218. doi: 10.1677/joe.0.1610211
Maggio M, Basaria S, Ceda GP, et al. The relationship between testosterone and molecular markers of inflammation in older men. J Endocrinol Invest. 2005;28(11 Suppl Proceedings):116-119.
Veldhuis J, Yang R, Roelfsema F, Takahashi P. Proinflammatory Cytokine Infusion Attenuates LH's Feedforward on Testosterone Secretion: Modulation by Age. J Clin Endocrinol Metab. 2016; 101(2):539-549. doi: 10.1210/jc.2015-3611
Morelli A, Sarchielli E, Comeglio P, et al. Metabolic syndrome induces inflammation and impairs gonadotropin-releasing hormone neurons in the preoptic area of the hypothalamus in rabbits. Mol Cell Endocrinol. 2014;382(1):107-119. doi: 10.1016/j.mce.2013.09.017
Shi Z, Araujo AB, Martin S, O'Loughlin P, Wittert GA. Longitudinal changes in testosterone over five years in community-dwelling men. J Clin Endocrinol Metab. 2013;98(8):3289-3297. doi:10.1210/jc.2012-3842
Smith MR, Lee H, Nathan DM. Insulin sensitivity during combined androgen blockade for prostate cancer. J Clin Endocrinol Metab. 2006;91(4):1305-1308. doi:10.1210/jc.2005-2507
Yialamas MA, Dwyer AA, Hanley E, Lee H, Pitteloud N, Hayes FJ. Acute sex steroid withdrawal reduces insulin sensitivity in healthy men with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2007;92(11):4254-4259. doi: 10.1210/jc.2007-0454
Rastrelli G, Filippi S, Sforza A, Maggi M, Corona G. Metabolic Syndrome in Male Hypogonadism. Front Horm Res. 2018;49:131-155. doi: 10.1159/000485999
Navarro G, Allard C, Xu W, Mauvais-Jarvis F. The role of androgens in metabolism, obesity, and diabetes in males and females. Obesity (Silver Spring). 2015;23(4):713-719. doi: 10.1002/oby.21033
Singh R, Artaza JN, Taylor WE, Gonzalez-Cadavid NF, Bhasin S. Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology. 2003;144(11):5081-5088.
Pal M, Khan J, Kumar R, Surolia A, Gupta S. Testosterone supplementation improves insulin responsiveness in HFD fed male T2DM mice and potentiates insulin signaling in the skeletal muscle and C2C12 myocyte cell line. PLoS One. 2019;14(11):e0224162
Richard-Eaglin A. Male and Female Hypogonadism. Nurs Clin North Am. 2018;53(3):395-405. doi: 10.1016/j.cnur.2018.04.006
Ebrahimi M, Akbari Asbagh F. Pathogenesis and causes of premature ovarian failure: an update. Int J Fertil Steril. 2011;5(2):54-65.
Kozakowski J, Gietka-Czernel M, Leszczyńska D, Majos A. Obesity in menopause - our negligence or an unfortunate inevitability? Menopause Rev. 2017;16(2):61-65. doi: 10.5114/pm.2017.68594
Santos RS, Frank AP, Fátima LA, Palmer BF, Öz OK, Clegg DJ. Activation of estrogen receptor alpha induces beiging of adipocytes. Mol Metab. 2018; 18: 51-59. doi: 10.1016/j.molmet.2018.09.002
Leeners B, Geary N, Tobler PN, Asarian L. Ovarian hormones and obesity. Hum Reprod Update. 2017;23(3):300-321. doi: 10.1093/humupd/dmw045
Clegg DJ, Brown LM, Zigman JM, et al. Estradiol-dependent decrease in the orexigenic potency of ghrelin in female rats. Diabetes. 2007;56(4):1051-1058. doi: 10.2337/db06-0015
Ravussin Y, Leibel RL, Ferrante AW Jr. A missing link in body weight homeostasis: the catabolic signal of the overfed state. Cell Metab. 2014;20(4):565-572. doi: 10.1016/j.cmet.2014.09.002
Melanson EL, Gavin KM, Shea KL, et al. Regulation of energy expenditure by estradiol in premenopausal women. J Appl Physiol. 2015;119(9):975-981. doi: 10.1152/japplphysiol.00473.2015
Asarian L, Geary N. Sex differences in the physiology of eating. Am J Physiol Regul Integr Comp Physiol. 2013;305(11):R1215-R1267. doi: 10.1152/ajpregu.00446.2012
Lee Y, Hirose H, Zhou YT, Esser V, McGarry JD, Unger RH. Increased lipogenic capacity of the islets of obese rats: a role in the pathogenesis of NIDDM. Diabetes. 1997;46(3):408-413. doi: 10.2337/diab.46.3.408
Zhu M, Mizuno A, Kuwajima M, et al. Ovarian hormone-induced beta-cell hypertrophy contributes to the homeostatic control of beta-cell mass in OLETF female rat, a model of Type II diabetes. Diabetologia. 1998;41(7):799-805. doi: 10.1007/s001250050990
Dobbs R, Sawers C, Thompson F, et al. Overcoming Obesity: An Initial Economic Analysis. McKinsey Global Institute; Jakarta, Indonesia: 2014
CD Risk Factor Collaboration (NCD-RisC). Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet. 2016;387(10027):1513-1530. doi: 10.1016/S0140-6736(16)00618-8
Caterson ID, Alfadda AA, Auerbach P, et al. Gaps to bridge: Misalignment between perception, reality and actions in obesity. Diabetes Obes Metab 2019; 21 (8): 1914-24. doi: 10.1111/dom.13752
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