Obesity pp 83-108 | Cite as

Obesity-Related Diseases and Syndromes: Insulin Resistance, Type 2 Diabetes Mellitus, Non-alcoholic Fatty Liver Disease, Cardiovascular Disease, and Metabolic Syndrome



Fat accumulates within the body of a person who is overweight or obese until many small physiological changes accumulate to a tipping point where adipose tissue becomes “sick.” Adisopathy or “sick fat” leads to a host of other obesity-related diseases. In this chapter the development of adisopathy is discussed in detail with an emphasis on insulin resistance and the role of mitochondria, hormones, inflammatory markers and leptin. This chapter describes the mechanisms of disease for prediabetes and type 2 diabetes and explores the concept of metabolic syndrome. It also explains the pathophysiology of obesity as it relates to non-alcoholic fatty liver disease (NAFLD). The chapter ends with specific discussions about the relationships between obesity and other obesity-related diseases, including hypertension, dyslipidemia, atherosclerosis, coronary heart disease and stroke.


Obesity Genetic ResetTM Genetic ResettingTM Insulin resistance Metabolic syndrome Prediabetes Endothelial dysfunction Adipokines Diabetes Type 2 diabetes Non-alcoholic fatty liver disease Heart failure Stroke 


  1. 1.
    Kuk JL, Ardern CI. Are metabolically normal but obese individuals at lower risk for all-cause mortality? Diab Care. 2009;32(12):2297–9.CrossRefGoogle Scholar
  2. 2.
    Szendroedi J, Phielix E, Roden M. The role of mitochondria in insulin resistance and type 2 diabetes mellitus. Nat Rev Endocrinol. 2012;8:92–103.CrossRefGoogle Scholar
  3. 3.
    Messer JI, Jackman MR, Willis WT. Pyruvate and citric acid cycle carbon requirements in isolated skeletal muscle mitochondria. Am J Physiol Cell Physiol. 2004;286(3):C565–72.CrossRefPubMedGoogle Scholar
  4. 4.
    Hoppeler H, Fluck M. Plasticity of skeletal muscle mitochondria: structure and function. Med Sci Sports Exerc. 2003;35:95–104.CrossRefPubMedGoogle Scholar
  5. 5.
    Chomentowski P, Coen PM, Radikova A, Goodpaster BH, Toledo FG. Skeletal muscle mitochondria in insulin resistance: differences in intermyofibrillar versus subsarcolemmal subpopulations and relationship to metabolic flexibility. J Clin Endocrinol Metab. 2011;96:493–503.CrossRefGoogle Scholar
  6. 6.
    Abdul-Ghani MA, Matsuda M, Balas B, DeFronzo RA. Muscle and liver insulin resistance indexes derived from the oral glucose tolerance test. Diabetes Care. 2007;30:89–94.CrossRefPubMedGoogle Scholar
  7. 7.
    Reaven GM. Insulin resistance: the link between obesity and cardiovascular disease. Med Clin North Am. 2011;95(5):875–92.CrossRefPubMedGoogle Scholar
  8. 8.
    Yip J, Facchini FS, Reaven GM. Resistance to insulin-mediated glucose disposal as a predictor of cardiovascular disease. J Clin Endocrinol Metab. 1998;83:2773–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Reaven GM. All obese individuals are not created equal: insulin resistance is the major determinant of cardiovascular disease in overweight/obese individuals. Diabetes Vasc Dis Res. 2005;2:105–12.CrossRefGoogle Scholar
  10. 10.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9.CrossRefPubMedGoogle Scholar
  11. 11.
    Ascaso JF, Pardo S, Real JT, Lorente RI, Priego A, Carmena R. Diagnosing insulin resistance by simple quantitative methods in subjects with normal glucose metabolism. Diabetes Care. 2003;26:3320–5.CrossRefPubMedGoogle Scholar
  12. 12.
    Qu H, Li Q, Rentfro AR, Fisher-Hoch SP, McCormick JB. The definition of insulin resistance using HOMA-IR for American of Mexican descent using machine learning. PLoS ONE. 2011;6(6):e21041.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Gayoso-Diz P, Otero-Gonzalez A, Rodriguez-Alvarez MX, Gude F, Garcia F, DeFrancisco A, Quintela AG. Insulin resistance (HOMA-IR) cut-off values and the metabolic syndrome in a general adult population: effect of gender and age: EPIRCE cross-sectional study. BMC Endocr Disord. 2013;13:47.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Rasmussen-Torvik LJ, Pankow JS, Jacobs DR, Steffen LM, Moran AM, Steinberger J, Sinaiko AR. Heritability and genetic correlations of insulin sensitivity measured by the euglycemic clamp. Diabet Med. 2007;24(11):1286–9.CrossRefPubMedGoogle Scholar
  15. 15.
    Staten MA, Stern MP, Miller WG, Steffes MW. Campbell SE for the insulin standardization workgroup. Diabetes Care. 2010;33(1):205–6.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Johnson JL, Duick DS, Chui MA, Aldasouqi SA. Identifying prediabetes using fasting insulin levels. Endocr Pract. 2010;16(1):47–52.CrossRefPubMedGoogle Scholar
  17. 17.
    Ter Horst KW, Gilijamse PW, Koopman KE, de Weijer BA, Brands M, Kootte RS, et al. Insulin resistance in obesity can be reliably identified from fasting plasma insulin. Int J Obes. 2015. doi: 10.1038/ijo.2015.125.Google Scholar
  18. 18.
    Haj Mouhamed D, Ezzaher A, Neffati F, Douki W, Gaha L, Najjar MF. Effect of cigarette smoking on insulin resistance risk. Ann Cardiol Angeiol (Paris). 2015. doi: 10.1016/j.ancard.2014.12.001.Google Scholar
  19. 19.
    Scherag A, Jarick I, Grothe J, Biebermann H, Scherag S, Volckmar AL, et al. Investigation of a genome wide association signal for obesity: synthetic association and haplotype analysis at the melanocortin 4 receptor gene locus. PLoS ONE. 2010;5(11):e13967.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316(5826):889–94.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Claussnitzer M, Dankel SN, Kyong-Han K, Quon G, Meulemena W, Haugen C, et al. FTO obesity variant circuitry and adipocyte browning in humans. N Engl J Med. 2015. doi: 10.1056/NEJMoa1502214.PubMedPubMedCentralGoogle Scholar
  22. 22.
    Li S, Zhao JH, Luan J, Langenberg C, Luben RN, Shaw KT, et al. Genetic predisposition to obesity leads to increased risk of type 2 diabetes. Diabetologia. 2011;54(4):776–82.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Choquet H, Meyre D. Genetics of obesity: what have we learned? Curr Genomics. 2011;12:169–79.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Ahmad T, Lee IM, Pare G, Chasman DI, Rose L, Ridker PM, Mora S. Lifestyle interaction with fat mass and obesity-associated (FTO) genotype and risk of obesity in apparently healthy U.S. women. Diabetes Care. 2011;34(3):675–80.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Li S, Zhao JH, Luan J, Ekelund U, Luben RN, Khaw KT, et al. Physical activity attenuates the genetic predisposition to obesity in 20,000 men and women from EPIC-Norfolk prospective population study. PLoS Med. 2010;7(8):e1000332.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Paneni F, Costantino S, Cosentino F. Role of oxidative stress in endothelial insulin resistance. World J Diabetes. 2015;6(2):326–32.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Yu T, Robotham JL, Yoon Y. Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology. Proc Natl Acad Sci USA. 2006;103:2653–8.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Chan DC. Fusion and fission: interlinked processes critical for mitochondrial health. Ann Rev Genet. 2012;46:265–87.CrossRefPubMedGoogle Scholar
  29. 29.
    Cheng Z, Almeida FA. Mitochondrial alternation in type 2 diabetes and obesity. Cell Cycle. 2014;13(6):890–7.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Toledo FG, Goodpaster BH. The role of weight loss and exercise in correcting skeletal muscle mitochondrial abnormalities in obesity, diabetes and aging. Mol Cell Endocrinol. 2013;379:30–4.CrossRefPubMedGoogle Scholar
  31. 31.
    Shanik MH, Xu Y, Skrha J, Dankner R, Zick Y, Roth J. Insulin resistance and hyperinsulinemia. Diabetes Care. 2008;31(2):S262–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Sleigh A, Raymond-Barker P, Thackray K, Porter D, Hatunic M, Vottero A, Burren C, Mitchell C, McIntyre M, Brage S, et al. Mitochondrial dysfunction in patients with primary congenital insulin resistance. J Clin Invest. 2011;121:2457–61.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Zheng LD, Linarelli LE, Longhua L, Wall SS, Greenawald MH, Seidel RW, et al. Insulin resistance is associated with epigenetic and genetic regulation of mitochondrial DNA in obese humans. Clin Epigentics. 2015. doi: 10.1186/s13148-015-0093-1.Google Scholar
  34. 34.
    Sookoian S, Rosselli MS, Gemma C, Burgueno AL, Fernandez Gianotti T, Castano GO, Pirola CJ. Epigenetic regulation of insulin resistance in nonalcoholic fatty liver disease: impact of liver methylation of the peroxisome proliferator-activated receptor γ coactivator 1α promoter. Hepatology. 2010;52:1992–2000.CrossRefPubMedGoogle Scholar
  35. 35.
    Barres R, Yan J, Egan B, Treebak JT, Rasmussen M, Fritz T, Caidahl K, Krook A, O’Gorman DF, Zierath JR. Acute exercise remodels promoter methylation in human skeletal muscle. Cell Metab. 2012;15:405–11.CrossRefPubMedGoogle Scholar
  36. 36.
    Coelho M, Oliveira T, Fernandes R. Biochemistry of adipose tissue: an endocrine organ. Arch Med Sci. 2013;9:191–200.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Papaetis GS, Papakyriakou P, Panagiotou TN. Central obesity, type 2 diabetes and insulin: exploring a pathway full of thorns. Arch Med Sci. 2014;11(2):463–82.Google Scholar
  38. 38.
    Pedersen DJ, Guilherme A, Danai LV, Heyda L, Matevossian A, Cohen J, et al. A major role of insulin in promoting obesity-associated adipose tissue inflammation. Mol Metab. 2015;4:507–18.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Nathan DM, Davidson MB, DeFronzo RA, Heine RJ, Henry RR, Prately R, Zinman B. Impaired fasting glucose and impaired glucose tolerance. Diabetes Care. 2007;30(3):753–9.CrossRefPubMedGoogle Scholar
  40. 40.
    Zhang Y, Hu G, Zhang L, Mayo R, Chen L. A novel testing model for opportunistic screening of pre-diabetes and diabetes among U.S. adults. PLoS ONE. 2015. doi: 10.137/journal.pone.0120382.Google Scholar
  41. 41.
    Tabak AG, Herder C, Rathmann W, Brunner EJ, Kivimaki M. Lancet. 2012;379(9833):2279–90.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    DECODE Study Group. Age-and sex-specific prevalences of diabetes and impaired glucose regulation in 13 European cohorts. Diabetes Care. 2003;26(1):61–9.CrossRefGoogle Scholar
  43. 43.
    Bansal N. Prediabetes diagnosis and treatment: a review. World J Diabetes. 2015;6(2):296–303.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Haffner SM, Mykkanen L, Festa A, Burke JP, Stern MP. Insulin-resistant prediabetic subjects have more atherogenic risk factors than insulin–sensitive prediabetic subjects. Circulation. 2000;101:975–80.CrossRefPubMedGoogle Scholar
  45. 45.
    Bellamy L, Casas JP, Hingorani AD, et al. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet. 2009;373:1773–9.CrossRefPubMedGoogle Scholar
  46. 46.
    Ford ES, Williamson DF, Liu S. Weight change and diabetes incidence: findings from a national cohort of US adults. Am J Epidemiol. 1997;146:214–22.CrossRefPubMedGoogle Scholar
  47. 47.
    Meigs JB, Rutter MK, Sullivan LM, Fox CS, D’Agostino RB, Wilson BW. Impact of insulin resistance on risk of type 2 diabetes and cardiovascular disease in people with metabolic syndrome. Diabetes Care. 2007;30:1219–25.CrossRefPubMedGoogle Scholar
  48. 48.
    Ali MK, Bullard KM, Saaddine JB, Cowie CC, Imperatore G, Gregg EW. Achievement of goals in U.S. diabetes care, 1999–2010. N Engl J Med. 2013;368:1613–24.CrossRefPubMedGoogle Scholar
  49. 49.
    Pi-Sunyer FX. Weight loss in type 2 diabetic patients. Diabetes Care. 2005;28(6):1526–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Uranga-Ocio JA, Bastus-Diez S, Delkader-Palacios D, Garcia-Cristobal N, Leal-Garcia A, Abalo-Delgado R. Enteric neuropathy associated to diabetes mellitus. Rev Esp Enferm Dig. 2015;107(6):366–73.PubMedGoogle Scholar
  51. 51.
    Smith D, Williams C, Ferris C. Diagnosis and treatment of chronic gastroparesis and chronic intestinal pseudo-obstruction. Gastroenterol Clin N Am. 2003;32:619–58.CrossRefGoogle Scholar
  52. 52.
    Kopacova M. Small intestinal bacterial overgrowth syndrome. World J Gastroenterol. 2010;16:2978–90.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Chandrasekharan B, Srinivasan S. Diabetes and the enteric nervous system. Neurogastroenterol Motil. 2007;19:951–60.PubMedPubMedCentralGoogle Scholar
  54. 54.
    Lambadiari V, Triantafyllou K, Dimitriadis GD. Insulin action in muscle and adipose tissue in type 2 diabetes: the significance of blood flow. World J Diabetes. 2015;6(4):626–33.PubMedPubMedCentralGoogle Scholar
  55. 55.
    Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. 1988;37(12):1595–607.CrossRefPubMedGoogle Scholar
  56. 56.
    American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care. 2014;38(1):S8–16.Google Scholar
  57. 57.
    Parikh RM, Mohan V. Changing definitions of metabolic syndrome. Indian J Endocrinol Metab. 2012;16(1):7–12.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640–5.CrossRefPubMedGoogle Scholar
  59. 59.
    Thorpe AA, Schlaich MP. Relevance of sympathetic nervous system activation in obesity and metabolic syndrome. J Diabetes Res. 2015. doi: 10.1155/2015/241583.Google Scholar
  60. 60.
    Rinella ME. Nonalcoholic fatty liver disease a systematic review. JAMA. 2015;313(22):2263–73.CrossRefPubMedGoogle Scholar
  61. 61.
    Zhang XQ, Xu DF, Yu CH, Chen WX, Li YM. Role of endoplasmic reticulum stress in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol. 2014;20(7):1768–76.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Kirpich IA, Marsano LS, McClain CJ. Gut-liver axis, nutrition, and non alcoholic fatty liver disease. Clin Biochem. 2015. doi: 10.1016/j.clinbiochem.2015.06.023.PubMedGoogle Scholar
  63. 63.
    Buchholz EM, Rathmore SS, Reid KJ, Jones PG, Chan PS, Rich MW, et al. Body mass index and mortality in acute myocardial infarction patients. Am J Med. 2012;125:796–803.CrossRefGoogle Scholar
  64. 64.
    Mullen JT, Moorman DW, Davenport DL. The obesity paradox: body mass index and outcomes in patients undergoing nonbariatric general surgery. Ann Surg. 2009;250:166–72.CrossRefPubMedGoogle Scholar
  65. 65.
    Migaj J, Prokop E, Straburzynska-Migaj E, Lesiak M, Grajek S, Mitkowski P. Does influence of obesity on prognosis differ in men and women? A study of obesity paradox in patients with acute coronary syndrome. Kardiol Pol. 2015. doi: 10.5603/KP.a2015.0087.PubMedGoogle Scholar
  66. 66.
    Banack HR, Kaufman JS. Does selection bias explain the obesity paradox among individuals with cardiovascular disease? Ann Epidemiol. 2015. doi: 10.1016/j.annepidem.2015.02.008.PubMedGoogle Scholar
  67. 67.
    Costanzo P, Cleland JGF, Pellicori P, Clark AL, Hepburn D, Kilpatirck ES, et al. The obesity paradox in type 2 diabetes mellitus: relationship of body mass index to prognosis: a cohort study. Ann Int Med. 2015;162(9):610–8.CrossRefPubMedGoogle Scholar
  68. 68.
    Jerant A, Bertakis KD, Franks P. Body mass index and health care utilization in diabetic and nondiabetic individuals. Med Care. 2015. doi: 10.1097/MLR.343.PubMedGoogle Scholar
  69. 69.
    Kortelainen MI, Porvari K. Extreme obesity and associated cardiovascular disease verified at autopsy: time trends over 3 decades. Am J Forensic Med Pathol. 2011;32:372–7.CrossRefPubMedGoogle Scholar
  70. 70.
    Fadini GP, Boscaro E, de Kreutzenberg S, Agostini C, Seeger F, Dimmeler S, et al. Time course and mechanisms of circulating progenitor cell reduction in the natural history of type 2 diabetes. Diabetes Care. 2010;33:1097–102.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Graziani F, Biasucci LM, Cialdella P, Lizzo G, Giubilato S, Della Bono R, et al. Thromboxane production in morbidly obese subjects. Am J Cardiol. 2011;107:1656–61.CrossRefPubMedGoogle Scholar
  72. 72.
    Feldman AM, Combes A, Wagner D, Kadakomi T, Kubota T, Li YY, McTierman C. J Am Coll Cardiol. 2000;35(3):537–44.CrossRefPubMedGoogle Scholar
  73. 73.
    Savage DB, Petersen KF, Shulman GI. Disordered lipid metabolism and the pathogenesis of insulin resistance. Physiol Rev. 2007;87:507–20.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Stone NJ, Robinson JG, Lichtenstien AH, Goff DC, Lloyd-Jones DM, Smith SC, et al. Treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk in adults: synopsis of the 2013 American College of Cardiology/American Heart Association cholesterol guideline. Ann Intern Med. 2014;160:339–43.CrossRefPubMedGoogle Scholar
  75. 75.
    Graham R, Mancher M, Wolman DM, Greenfield S, Steinberg E, editors. Institute of medicine. Clinical guidelines we can trust. Washington, DC: National Academies Press; 2011.Google Scholar
  76. 76.
    Xu W, Shubina M, Goldberg SI, Turchin A. Body mass index and all-cause mortality in patients with hypertension. Obesity. 2015. doi: 10.1002/oby.21129.Google Scholar
  77. 77.
    Hsu CY, McCulloch CE, Iribarren C, Darbinian J, Go AS. Body mass index and risk for end-stage renal disease. Ann Intern Med. 2006;144(1):21–8.CrossRefPubMedGoogle Scholar
  78. 78.
    Bueter M, Ahmed A, Ashrafian H, le Roux CW. Surg Obes Relat Dis. 2009;5(5):615–20.CrossRefPubMedGoogle Scholar
  79. 79.
    Tanida M, Yamamoto N, Shibamoto T, Rahmouni K. Involvement of hypothalamic AMP-activated protein kinase in leptin-induces sympathetic nerve activation. PLoS ONE. 2013;8(2):e56660.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Greenfield JR. Melanocortin signaling and the regulation of blood pressure in human obesity. J Neuroendocrinol. 2011;23(2):186–93.CrossRefPubMedGoogle Scholar
  81. 81.
    Carmichael CY, Wainford RD. Hypothalamic signaling mechanisms in hypertension. Curr Hypertens Rep. 2015;17:39–47.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Hall JE, do Carmo JM, da Silva AA, Wang Z, et al. Obesity-induces hypertension: interaction of neurohumoral and renal mechanisms. Circ Res. 2015;116(6):991–1006.CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Soleimani M. Insulin resistance and hypertension: new insights. Kidney Int. 2015;87:497–9.CrossRefPubMedGoogle Scholar
  84. 84.
    Romero-Corral A, Montori VM, Somers VK, Korinek J, Thomas RJ, Allison TG, et al. Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies. Lancet. 2006;368(9536):666–78.CrossRefPubMedGoogle Scholar
  85. 85.
    Schenkeveld L, Magro M, Oemrawsingh RM, Lenzen M, de Jaegere P, Jan van Geuns R, et al. The influence of optimal medical treatment on the “obesity paradox”, body mass index and long-term mortality in patients treated with percutaneous coronary interventions: a prospective cohort study. BMJ Open. 2012;2:e000535.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Luna-Luna M, Medina-Urrutia A, Vargas-Alarcon G, Coss-Rovirosa F, Vargas-Barron J, Perez-Mendez O. Adipose tissue in metabolic syndrome: onset and progression of atherosclerosis. Arch Med Res. 2015. doi: 10.1016/j.arcmed.2015.05.007.PubMedGoogle Scholar
  87. 87.
    Di Chiara T, Argano C, Scaglione A, Corrao S, Pinto A, Scaglione R. Circulating adiponectin: a cardiometabolic marker associated with global cardiovascular risk. Acta Cardiol. 2015;70(1):33–40.PubMedGoogle Scholar
  88. 88.
    Berg AH, Scherer PE. Adipose tissue, inflammation and cardiovascular disease. Circ Res. 2005;96:939–49.CrossRefPubMedGoogle Scholar
  89. 89.
    Wu X, Zhu B, Fu L, Wang H, Zhou B, Zou S, Shi J. Prevalence, incidence, and mortality of stroke in the Chinese island populations: a systematic review. PLoS ONE. 2013;8:e78629.CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Wu EQ, Birnbaum HG, Mareva M, Tuttle E, Castor AR, Jackman W, Ruskin J. Economic burden and co-morbidities of atrial fibrillation in a privately insured population. Curr Med Res Opin. 2005;21:1693–9.CrossRefPubMedGoogle Scholar
  91. 91.
    Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, Singer DE. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention: the AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) study. JAMA. 2001;285:2370–5.CrossRefPubMedGoogle Scholar
  92. 92.
    Friberg L, Rosenqvist M, Lip GY. Evaluation of risk stratification schemes for ischemic stroke and bleeding in 182,678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J. 2012;33:1500–10.CrossRefPubMedGoogle Scholar
  93. 93.
    Hajhosseiny R, Matthews GK, Lip GY. The metabolic syndrome, atrial fibrillation and stroke: tackling an emerging epidemic. Heart Rhythm. 2015. doi: 10.1016/j.hrthm.2015.06.038.PubMedGoogle Scholar
  94. 94.
    Liu J, Butler KR, Buxbaum SG, Sung JH, Campbell BW, Taylor HA. Leptinemia and its association with stroke and coronary heart disease in the Jackson Heart Study. Clin Endocrinol (Oxford). 2010;72:32–7.CrossRefGoogle Scholar
  95. 95.
    Wang TJ, Parise H, Levy D, D’Agostino RB, Wolf PA, Vasan RS, Benjamin EJ. JAMA. 2004;292(20):2471–7.CrossRefPubMedGoogle Scholar
  96. 96.
    Ashrafian H, Frenneaux MP, Opie LH. Metabolic mechanisms in heart failure. Circulation. 2015. doi: 10.1161/Circulationaha.1007.702795.Google Scholar
  97. 97.
    Hardy CM, Birse RT, Wolf MJ, Yu L, Bodmer R, Gibbs AG. Obesity-associated cardiac dysfunction in starvation-selectee drosophila melanogaster. Am J Physiol Regul Integr Comp Physiol. 2015. doi: 10.1152/ajpregu.00160.2015.Google Scholar
  98. 98.
    Khavandi K, Khavandi A, Asghar O, Greenstein A, Withers S, Heagerty AM, Malik R. Diabetic cardiomyopathy—a distinct disease? Best Pract Res Clin Endocrinol Metab. 2009;23(3):347–60.CrossRefPubMedGoogle Scholar
  99. 99.
    Waddingham MT, Edgley AJ, Tsuchimochi H, Kelly DJ, Shirai M, Pearson JT. Contractile apparatus dysfunction early in the pathophysiology of diabetic cardiomyopathy. World J Diabetes. 2015;6(7):943–60.CrossRefPubMedPubMedCentralGoogle Scholar

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© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Banner University Medical CenterUniversity of Arizona School of Medicine – PhoenixPhoenixUSA

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