Mapping body fat distribution: A key step towards the identification of the vulnerable patient?

Annals of Medicine

Volumn 44, Issue 8, 2012, Pages 758-772

  Arsenault, Benoit J ^a   Beaumont, Emilie Pelletier ^a,b   Després, Jean Pierre ^a,b   Larose, Eric ^a,b  

^a LAVAL UNIVERSITY   (Canada)

^b UNIVERSITÉ LAVAL   (Canada)

Author keywords

Atherosclerosis; Computed tomography; Ectopic fat accumulation; Glucose insulin homeostasis; Imaging; Inflammation; Insulin resistance; Magnetic resonance imaging; Type 2 diabetes; Visceral obesity

Indexed keywords

ADIPONECTIN; APOLIPOPROTEIN B; C REACTIVE PROTEIN; FATTY ACID; FIBRIC ACID DERIVATIVE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INSULIN; INTERLEUKIN 6; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; TRIACYLGLYCEROL; TUMOR NECROSIS FACTOR ALPHA;

ABDOMINAL FAT; ABDOMINAL OBESITY; ARTERIAL WALL THICKNESS; ATHEROGENESIS; ATHEROSCLEROTIC CARDIOVASCULAR DISEASE; BODY FAT DISTRIBUTION; CARDIOMETABOLIC RISK; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CAUSE OF DEATH; COMPUTER ASSISTED TOMOGRAPHY; DISEASE PREDISPOSITION; DYSLIPIDEMIA; EPICARDIAL ADIPOSE TISSUE; EPICARDIUM; GENETIC PREDISPOSITION; GLYCEMIC CONTROL; HEART INFARCTION; HUMAN; HYPERGLYCEMIA; HYPERINSULINEMIA; HYPERTENSION; INSULIN RELEASE; INSULIN RESISTANCE; INTRAABDOMINAL FAT; ISCHEMIC HEART DISEASE; LIFESTYLE MODIFICATION; LIPID LIVER LEVEL; LIPID STORAGE; METABOLIC SYNDROME X; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER; NUCLEAR MAGNETIC RESONANCE IMAGING; PANCREAS; PATHOPHYSIOLOGY; PERICARDIAL ADIPOSE TISSUE; PERICARDIUM; PHYSICAL ACTIVITY; PRIORITY JOURNAL; REVIEW; SUBCUTANEOUS FAT; WAIST CIRCUMFERENCE;

ADIPOSITY; CARDIOVASCULAR DISEASES; DIABETES MELLITUS, TYPE 2; HEART; HUMANS; INTRA-ABDOMINAL FAT; LIVER; RISK ASSESSMENT; SUBCUTANEOUS FAT;

EID: 84870805185     PISSN: 07853890     EISSN: 13652060     Source Type: Journal    
DOI: 10.3109/07853890.2011.605387     Document Type: Review

References (158)

1. McGee DL. Body mass index and mortality: a meta-analysis based on person-level data from twenty-six observational studies. Ann Epidemiol. 2005;15:87-97.
2. Balkau B, Deanfield JE, Despré s JP, Bassand JP, Fox KA, Smith SC Jr, et al. International Day for the Evaluation of Abdominal Obesity (IDEA): a study of waist circumference, cardiovascular disease, and diabetes mellitus in 168,000 primary care patients in 63 countries. Circulation. 2007; 116:1942-51.
3. Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004; 364:937-52.
4. Ohlson LO, Larsson B, Svardsudd K, Welin L, Eriksson H, Wilhelmsen L, et al. The influence of body fat distribution on the incidence of diabetes mellitus. 13.5 years of follow-up of the participants in the study of men born in 1913. Diabetes. 1985;34:1055-8.
5. Pischon T, Lahmann PH, Boeing H, Friedenreich C, Norat T, Tjonneland A, et al. Body size and risk of colon and rectal cancer in the European Prospective Investigation Into Cancer and Nutrition (EPIC). J Natl Cancer Inst. 2006;98:920-31.
6. Zhang C, Rexrode KM, van Dam RM, Li TY, Hu FB. Abdominal obesity and the risk of all-cause, cardiovascular, and cancer mortality: sixteen years of follow-up in US women. Circulation. 2008;117:1658-67.
7. Brown LK. A waist is a terrible thing to mind: central obesity, the metabolic syndrome, and sleep apnea hypopnea syndrome. Chest. 2002;122:774-8.
8. Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, et al. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2006;113:898-918.
9. Lemieux I, Drapeau V, Richard D, Bergeron J, Marceau P, Biron S, et al. Waist girth does not predict metabolic complications in severely obese men. Diabetes Care. 2006;29:1417-9.
10. Rasouli N, Molavi B, Elbein SC, Kern PA. Ectopic fat accumulation and metabolic syndrome. Diabetes Obes Metab. 2007;9:1-10.
11. Vague J. La diffé renciation sexuelle : facteur dé terminant des formes de l'obesit é . Presse Med. 1947;55:339-40.
12. Kvist H, Sjostrom L, Tylen U. Adipose tissue volume determinations in women by computed tomography: technical considerations. Int J Obes. 1986;10:53-67.
13. Krotkiewski M, Bjorntorp P, Sjostrom L, Smith U. Impact of obesity on metabolism in men and women. Importance of regional adipose tissue distribution. J Clin Invest. 1983;72:1150-62.
14. Katzmarzyk PT, Bray GA, Greenway FL, Johnson WD, Newton RL Jr, Ravussin E, et al. Racial differences in abdominal depot-specific adiposity in white and African American adults. Am J Clin Nutr. 2010;91:7-15.
15. Sniderman AD, Bhopal R, Prabhakaran D, Sarrafzadegan N, Tchernof A. Why might South Asians be so susceptible to central obesity and its atherogenic consequences? The adipose tissue overflow hypothesis. Int J Epidemiol. 2007;36:220-5.
16. Kadowaki T, Sekikawa A, Murata K, Maegawa H, Takamiya T, Okamura T, et al. Japanese men have larger areas of visceral adipose tissue than Caucasian men in the same levels of waist circumference in a population-based study. Int J Obes (Lond). 2006;30:1163-5.
17. Hoffman DJ, Wang Z, Gallagher D, Heymsfield SB. Comparison of visceral adipose tissue mass in adult African Americans and whites. Obes Res. 2005;13:66-74.
18. Rice T, P é russe L, Bouchard C, Rao DC. Familial clustering of abdominal visceral fat and total fat mass: the Qu é bec Family Study. Obes Res. 1996;4:253-61.
19. Romaguera D, Angquist L, Du H, Jakobsen MU, Forouhi NG, Halkjaer J, et al. Dietary determinants of changes in waist circumference adjusted for body mass index-a proxy measure of visceral adiposity. PLoS ONE. 2010;5:e11588.
20. Arner P. Human fat cell lipolysis: biochemistry, regulation and clinical role. Best Pract Res Clin Endocrinol Metab. 2005;19:471-82.
21. Jensen MD. Role of body fat distribution and the metabolic complications of obesity. J Clin Endocrinol Metab. 2008;93(11 Suppl 1):S57-63.
22. Stefan N, Machann J, Schick F, Claussen CD, Thamer C, Fritsche A, et al. New imaging techniques of fat, muscle and liver within the context of determining insulin sensitivity. Horm Res. 2005;64 Suppl 3:38-44.
23. Kuk JL, Katzmarzyk PT, Nichaman MZ, Church TS, Blair SN, Ross R. Visceral fat is an independent predictor of all-cause mortality in men. Obesity (Silver Spring). 2006;14:336-41.
24. Fujimoto WY, Bergstrom RW, Boyko EJ, Chen KW, Leonetti DL, Newell-Morris L, et al. Visceral adiposity and incident coronary heart disease in Japanese-American men. The 10-year follow-up results of the Seattle Japanese-American Community Diabetes Study. Diabetes Care. 1999;22:1808-12.
25. Boyko EJ, Fujimoto WY, Leonetti DL, Newell-Morris L. Visceral adiposity and risk of type 2 diabetes: a prospective study among Japanese Americans. Diabetes Care. 2000; 23:465-71.
26. Nicklas BJ, Penninx BW, Cesari M, Kritchevsky SB, Newman AB, Kanaya AM, et al. Association of visceral adipose tissue with incident myocardial infarction in older men and women: the Health, Aging and Body Composition Study. Am J Epidemiol. 2004;160:741-9.
27. Nicklas BJ, Cesari M, Penninx BW, Kritchevsky SB, Ding J, Newman A, et al. Abdominal obesity is an independent risk factor for chronic heart failure in older people. J Am Geriatr Soc. 2006;54:413-20.
28. Lear SA, Humphries KH, Kohli S, Frohlich JJ, Birmingham CL, Mancini GB. Visceral adipose tissue, a potential risk factor for carotid atherosclerosis: results of the Multicultural Community Health Assessment Trial (M-CHAT). Stroke. 2007;38:2422-9.
29. Kramer CK, von Muhlen D, Gross JL, Barrett-Connor E. A prospective study of abdominal obesity and coronary artery calcium progression in older adults. J Clin Endocrinol Metab. 2009;94:5039-44.
30. Carr MC, Brunzell JD. Abdominal obesity and dyslipidemia in the metabolic syndrome: importance of type 2 diabetes and familial combined hyperlipidemia in coronary artery disease risk. J Clin Endocrinol Metab. 2004;89: 2601-7.
31. Despr é s JP. Is visceral obesity the cause of the metabolic syndrome? Ann Med. 2006;38:52-63.
32. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet. 2005;365:1415-28.
33. Alberti KG, Zimmet P, Shaw J. The metabolic syndrome-a new worldwide definition. Lancet. 2005;366:1059-62.
34. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation. 2005;112:2735-52.
35. Galassi A, Reynolds K, He J. Metabolic syndrome and risk of cardiovascular disease: a meta-analysis. Am J Med. 2006;119:812-9.
36. Gami AS, Witt BJ, Howard DE, Erwin PJ, Gami LA, Somers VK, et al. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol. 2007;49:403-14.
37. Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2005;28:2289-304.
38. Carr DB, Utzschneider KM, Hull RL, Kodama K, Retzlaff BM, Brunzell JD, et al. Intra-abdominal fat is a major determinant of the National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome. Diabetes. 2004;53:2087-94.
39. Tong J, Boyko EJ, Utzschneider KM, McNeely MJ, Hayashi T, Carr DB, et al. Intra-abdominal fat accumulation predicts the development of the metabolic syndrome in non-diabetic Japanese-Americans. Diabetologia. 2007;50: 1156-60.
40. Arsenault BJ, Lachance D, Lemieux I, Almé ras N, Tremblay A, Bouchard C, et al. Visceral adipose tissue accumulation, cardiorespiratory fitness, and features of the metabolic syndrome. Arch Intern Med. 2007;167:1518-25.
41. Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007;116:39-48.
42. Smith SR, Lovejoy JC, Greenway F, Ryan D, deJonge L, de la Bretonne J, et al. Contributions of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity. Metabolism. 2001;50:425-35.
43. Pou KM, Massaro JM, Hoffmann U, Vasan RS, Maurovich-Horvat P, Larson MG, et al. Visceral and subcutaneous adipose tissue volumes are cross-sectionally related to markers of inflammation and oxidative stress: the Framingham Heart Study. Circulation. 2007;116:1234-41.
44. Cartier A, Lemieux I, Alm é ras N, Tremblay A, Bergeron J, Despr é s JP. Visceral obesity and plasma glucose-insulin homeostasis: contributions of interleukin-6 and tumor necrosis factor-alpha in men. J Clin Endocrinol Metab. 2008;93:1931-8.
45. Pich é ME, Lemieux S, Weisnagel SJ, Corneau L, Nadeau A, Bergeron J. Relation of high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and fibrinogen to abdominal adipose tissue, blood pressure, and cholesterol and triglyceride levels in healthy postmenopausal women. Am J Cardiol. 2005;96:92-7.
46. Porter SA, Massaro JM, Hoffmann U, Vasan RS, O'D onnel CJ, Fox CS. Abdominal subcutaneous adipose tissue: a protective fat depot? Diabetes Care. 2009;32:1068-75.
47. Preis SR, Massaro JM, Robins SJ, Hoffmann U, Vasan RS, Irlbeck T, et al. Abdominal subcutaneous and visceral adipose tissue and insulin resistance in the Framingham Heart Study. Obesity (Silver Spring). 2010;18:2191-8.
48. Canoy D, Boekholdt SM, Wareham N, Luben R, Welch A, Bingham S, et al. Body fat distribution and risk of coronary heart disease in men and women in the European Prospective Investigation Into Cancer and Nutrition in Norfolk cohort: a population-based prospective study. Circulation. 2007;116:2933-43.
49. Tchernof A. Visceral adipocytes and the metabolic syndrome. Nutr Rev. 2007;65(6 Pt 2):S24-9.
50. Yudkin JS, Kumari M, Humphries SE, Mohamed-Ali V. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis. 2000;148:209-14.
51. Hube F, Hauner H. The role of TNF-alpha in human adipose tissue: prevention of weight gain at the expense of insulin resistance? Horm Metab Res. 1999;31:626-31.
52. Arnaud C, Burger F, Steffens S, Veillard NR, Nguyen TH, Trono D, et al. Statins reduce interleukin-6-induced C-reactive protein in human hepatocytes: new evidence for direct antiinflammatory effects of statins. Arterioscler Thromb Vasc Biol. 2005;25:1231-6.
53. Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD. Splanchnic lipolysis in human obesity. J Clin Invest. 2004;113:1582-8.
54. Frayn KN, Arner P, Yki-Jarvinen H. Fatty acid metabolism in adipose tissue, muscle and liver in health and disease. Essays Biochem. 2006;42:89-103.
55. Verrijken A, Francque S, Mertens I, Talloen M, Peiffer F, Van Gaal L. Visceral adipose tissue and inflammation correlate with elevated liver tests in a cohort of overweight and obese patients. Int J Obes (Lond). 2010;34:899-907.
56. Thamer C, Machann J, Haap M, Stefan N, Heller E, Schnodt B, et al. Intrahepatic lipids are predicted by visceral adipose tissue mass in healthy subjects. Diabetes Care. 2004;27:2726-9.
57. Eguchi Y, Eguchi T, Mizuta T, Ide Y, Yasutake T, Iwakiri R, et al. Visceral fat accumulation and insulin resistance are important factors in nonalcoholic fatty liver disease. J Gastroenterol. 2006;41:462-9.
58. Koda M, Kawakami M, Murawaki Y, Senda M. The impact of visceral fat in nonalcoholic fatty liver disease: cross-sectional and longitudinal studies. J Gastroenterol. 2007;42:897-903.
59. Wallace TM, Utzschneider KM, Tong J, Carr DB, Zraika S, Bankson DD, et al. Relationship of liver enzymes to insulin sensitivity and intra-abdominal fat. Diabetes Care. 2007;30:2673-8.
60. Park BJ, Kim YJ, Kim DH, Kim W, Jung YJ, Yoon JH, et al. Visceral adipose tissue area is an independent risk factor for hepatic steatosis. J Gastroenterol Hepatol. 2008;23:900-7.
61. Libby P. Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr. 2006;83:456S-60S.
62. Ross R, Glomset JA. The pathogenesis of atherosclerosis N Engl J Med. 1976;295:369-77.
63. Hotamisligil GS. Inflammation and metabolic disorders. Nature. 2006;444:860-7.
64. L afontan M, Girard J. Impact of visceral adipose tissue on liver metabolism. Part I: heterogeneity of adipose tissue and functional properties of visceral adipose tissue. Diabetes Metab. 2008;34(4 Pt 1):317-27.
65. Rocha VZ, Libby P. The multiple facets of the fat tissue. Thyroid. 2008;18:175-83.
66. Nishimura S, Manabe I, Nagasaki M, Seo K, Yamashita H, Hosoya Y, et al. In vivo imaging in mice reveals local cell dynamics and inflammation in obese adipose tissue. J Clin Invest. 2008;118:710-21.
67. Kintscher U, Hartge M, Hess K, Foryst-Ludwig A, Clemenz M, Wabitsch M, et al. T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arterioscler Thromb Vasc Biol. 2008;28:1304-10.
68. Rotter V, Nagaev I, Smith U. Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-alpha, overexpressed in human fat cells from insulin-resistant subjects. J Biol Chem. 2003; 278:45777-84.
69. Senn JJ, Klover PJ, Nowak IA, Mooney RA. Interleukin-6 induces cellular insulin resistance in hepatocytes. Diabetes. 2002;51:3391-9.
70. Cartier A, Lemieux I, Alm é ras N, Tremblay A, Bergeron J, Despr é s JP. Visceral obesity and plasma glucose-insulin homeostasis: contributions of interleukin-6 and tumor necrosis factor-alpha in men. J Clin Endocrinol Metab. 2008;93:1931-8.
71. Fontana L, Eagon JC, Trujillo ME, Scherer PE, Klein S. Visceral fat adipokine secretion is associated with systemic inflammation in obese humans. Diabetes. 2007;56:1010-3.
72. St-Pierre AC, Cantin B, Bergeron J, Pirro M, Dagenais GR, Despr é s JP, et al. Inflammatory markers and long-term risk of ischemic heart disease in men. A 13-year follow-up of the Quebec Cardiovascular Study. Atherosclerosis. 2005; 182:315-21.
73. Patterson CC, Smith AE, Yarnell JW, Rumley A, Ben-Shlomo Y, Lowe GD. The associations of interleukin-6 (IL-6) and downstream inflammatory markers with risk of cardiovascular disease: the Caerphilly Study. Atherosclerosis. 2010;209:551-7.
74. Tsigos C, Papanicolaou DA, Kyrou I, Defensor R, Mitsiadis CS, Chrousos GP. Dose-dependent effects of recombinant human interleukin-6 on glucose regulation. J Clin Endocrinol Metab. 1997;82:4167-70.
75. Cô t é M, Mauri è ge P, Bergeron J, Alm é ras N, Tremblay A, Lemieux I, et al. Adiponectinemia in visceral obesity: impact on glucose tolerance and plasma lipoprotein and lipid levels in men. J Clin Endocrinol Metab. 2005;90: 1434-9.
76. Okamoto Y, Kihara S, Funahashi T, Matsuzawa Y, Libby P. Adiponectin: a key adipocytokine in metabolic syndrome. Clin Sci (Lond). 2006;110:267-78.
77. 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;116:1784-92.
78. Matsuzawa Y, Funahashi T, Kihara S, Shimomura I. Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol. 2004;24:29-33.
79. Xu A, Wang Y, Keshaw H, Xu LY, Lam KS, Cooper GJ. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J Clin Invest. 2003;112:91-100.
80. van Herpen NA, Schrauwen-Hinderling VB. Lipid accumulation in non-adipose tissue and lipotoxicity. Physiol Behav. 2008;94:231-41.
81. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology. 2003;37:1202-19.
82. Lazo M, Clark JM. The epidemiology of nonalcoholic fatty liver disease: a global perspective. Semin Liver Dis. 2008; 28:339-50.
83. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40:1387-95.
84. Kotronen A, Juurinen L, Hakkarainen A, Westerbacka J, Corner A, Bergholm R, et al. Liver fat is increased in type 2 diabetic patients and underestimated by serum alanine aminotransferase compared with equally obese nondiabetic subjects. Diabetes Care. 2008;31:165-9.
85. Kelley DE, McKolanis TM, Hegazi RA, Kuller LH, Kalhan SC. Fatty liver in type 2 diabetes mellitus: relation to regional adiposity, fatty acids, and insulin resistance. Am J Physiol Endocrinol Metab. 2003;285:E906-16.
86. Nguyen-Duy TB, Nichaman MZ, Church TS, Blair SN, Ross R. Visceral fat and liver fat are independent predictors of metabolic risk factors in men. Am J Physiol Endocrinol Metab. 2003;284:E1065-71.
87. Kuk JL, Nichaman MZ, Church TS, Blair SN, Ross R. Liver fat is not a marker of metabolic risk in lean premenopausal women. Metabolism. 2004;53:1066-71.
88. Fracanzani AL, Valenti L, Bugianesi E, Vanni E, Grieco A, Miele L, et al. Risk of nonalcoholic steatohepatitis and fibrosis in patients with nonalcoholic fatty liver disease and low visceral adiposity. J Hepatol. 2011;54:1244-9.
89. Gastaldelli A, Cusi K, Pettiti M, Hardies J, Miyazaki Y, Berria R, et al. Relationship between hepatic/visceral fat and hepatic insulin resistance in nondiabetic and type 2 diabetic subjects. Gastroenterology. 2007;133:496-506.
90. Guerrero R, Vega GL, Grundy SM, Browning JD. Ethnic differences in hepatic steatosis: an insulin resistance paradox? Hepatology. 2009;49:791-801.
91. Amaro A, Fabbrini E, Kars M, Yue P, Schechtman K, Schonfeld G, et al. Dissociation between intrahepatic triglyceride content and insulin resistance in familial hypobetalipoproteinemia. Gastroenterology. 2010;139:149-53.
92. Smith HL, Willius FA. Adiposity of the heart. Arch Int Med. 1933;52:811-931.
93. McGavock JM, Victor RG, Unger RH, Szczepaniak LS. Adiposity of the heart, revisited. Ann Intern Med. 2006;144:517-24.
94. Rabkin SW. Epicardial fat: properties, function and relationship to obesity. Obes Rev. 2007;8:253-61.
95. Iacobellis G, Sharma AM. Epicardial adipose tissue as new cardio-metabolic risk marker and potential therapeutic target in the metabolic syndrome. Curr Pharm Des. 2007;13: 2180-4.
96. Roy PE. Lipid droplets in the heart interstitium: concentration and distribution. Recent Adv Stud Cardiac Struct Metab. 1975;10:17-27.
97. Shirani J, Berezowski K, Roberts WC. Quantitative measurement of normal and excessive (cor adiposum) subepicardial adipose tissue, its clinical significance, and its effect on electrocardiographic QRS voltage. Am J Cardiol. 1995;76:414-8.
98. Djaberi R, Schuijf JD, van Werkhoven JM, Nucifora G, Jukema JW, Bax JJ. Relation of epicardial adipose tissue to coronary atherosclerosis. Am J Cardiol. 2008;102:1602-7.
99. Gorter PM, de Vos AM, van der Graaf Y, Stella PR, Doevendans PA, Meijs MF, et al. Relation of epicardial and pericoronary fat to coronary atherosclerosis and coronary artery calcium in patients undergoing coronary angiography. Am J Cardiol. 2008;102:380-5.
100. Ahn SG, Lim HS, Joe DY, Kang SJ, Choi BJ, Choi SY, et al. Relationship of epicardial adipose tissue by echocardiography to coronary artery disease. Heart. 2008; 94:e7.
101. Greif M, Becker A, von Ziegler F, Lebherz C, Lehrke M, Broedl UC, et al. Pericardial adipose tissue determined by dual source CT is a risk factor for coronary atherosclerosis. Arterioscler Thromb Vasc Biol. 2009;29:781-6.
102. Divers J, Wagenknecht LE, Bowden DW, Carr JJ, Hightower RC, Register TC, et al. Ethnic differences in the relationship between pericardial adipose tissue and coronary artery calcified plaque: African-American-diabetes heart study. J Clin Endocrinol Metab. 2010;95:5382-9.
103. Rosito GA, Massaro JM, Hoffmann U, Ruberg FL, Mahabadi AA, Vasan RS, et al. Pericardial fat, visceral abdominal fat, cardiovascular disease risk factors, and vascular calcification in a community-based sample: the Framingham Heart Study. Circulation. 2008;117:605-13.
104. Mahabadi AA, Massaro JM, Rosito GA, Levy D, Murabito JM, Wolf PA, et al. Association of pericardial fat, intrathoracic fat, and visceral abdominal fat with cardiovascular disease burden: the Framingham Heart Study. Eur Heart J. 2009;30:850-6.
105. Fox CS, Gona P, Hoffmann U, Porter SA, Salton CJ, Massaro JM, et al. Pericardial fat, intrathoracic fat, and measures of left ventricular structure and function: the Framingham Heart Study. Circulation. 2009;119:1586-91.
106. McGavock JM, Lingvay I, Zib I, Tillery T, Salas N, Unger R, et al. Cardiac steatosis in diabetes mellitus: a 1H-magnetic resonance spectroscopy study. Circulation. 2007;116: 1170-5.
107. Zhou YT, Grayburn P, Karim A, Shimabukuro M, Higa M, Baetens D, et al. Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci USA. 2000;97:1784-9.
108. Paradise NF, Pilati CF, Payne WR, Finkelstein JA. Left ventricular function of the isolated, genetically obese rat' s heart. Am J Physiol. 1985;248(4 Pt 2):H438-44.
109. Kankaanpaa M, Lehto HR, Parkka JP, Komu M, Viljanen A, Ferrannini E, et al. Myocardial triglyceride content and epicardial fat mass in human obesity: relationship to left ventricular function and serum free fatty acid levels. J Clin Endocrinol Metab. 2006;91:4689-95.
110. Kim MK, Tomita T, Kim MJ, Sasai H, Maeda S, Tanaka K. Aerobic exercise training reduces epicardial fat in obese men. J Appl Physiol. 2009;106:5-11.
111. Sacks HS. Weight loss in obesity reduces epicardial fat thickness; so what? J Appl Physiol. 2009;106:1-2.
112. Sironi AM, Gastaldelli A, Mari A, Ciociaro D, Positano V, Buzzigoli E, et al. Visceral fat in hypertension: influence on insulin resistance and beta-cell function. Hypertension. 2004;44:127-33.
113. Mazurek T, Zhang L, Zalewski A, Mannion JD, Diehl JT, Arafat H, et al. Human epicardial adipose tissue is a source of inflammatory mediators. Circulation. 2003;108:2460-6.
114. Eiras S, Teijeira-Fernandez E, Shamagian LG, Fernandez AL, Vazquez-Boquete A, Gonzalez-Juanatey JR. Extension of coronary artery disease is associated with increased IL-6 and decreased adiponectin gene expression in epicardial adipose tissue. Cytokine. 2008;43:174-80.
115. Teijeira-Fernandez E, Eiras S, Grigorian-Shamagian L, Fernandez A, Adrio B, Gonzalez-Juanatey JR. Epicardial adipose tissue expression of adiponectin is lower in patients with hypertension. J Hum Hypertens. 2008;22:856-63.
116. Sacks HS, Fain JN, Cheema P, Bahouth SW, Garrett E, Wolf RY, et al. Inflammatory genes in epicardial fat contiguous with coronary atherosclerosis in the metabolic syndrome and type 2 diabetes: changes associated with pioglitazone. Diabetes Care.2011;34:730-3.
117. Jacob S, Machann J, Rett K, Brechtel K, Volk A, Renn W, et al. Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects. Diabetes. 1999;48:1113-9.
118. Thamer C, Machann J, Bachmann O, Haap M, Dahl D, Wietek B, et al. Intramyocellular lipids: anthropometric determinants and relationships with maximal aerobic capacity and insulin sensitivity. J Clin Endocrinol Metab. 2003;88:1785-91.
119. Yim JE, Heshka S, Albu J, Heymsfield S, Kuznia P, Harris T, et al. Intermuscular adipose tissue rivals visceral adipose tissue in independent associations with cardiovascular risk. Int J Obes (Lond). 2007;31:1400-5.
120. Goodpaster BH, Krishnaswami S, Resnick H, Kelley DE, Haggerty C, Harris TB, et al. Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women. Diabetes Care. 2003;26:372-9.
121. G oodpaster BH, Krishnaswami S, Harris TB, Katsiaras A, Kritchevsky SB, Simonsick EM, et al. Obesity, regional body fat distribution, and the metabolic syndrome in older men and women. Arch Intern Med. 2005;165:777-83.
122. Delmonico MJ, Harris TB, Visser M, Park SW, Conroy MB, Velasquez-Mieyer P, et al. Longitudinal study of muscle strength, quality, and adipose tissue infiltration. Am J Clin Nutr. 2009;90:1579-85.
123. Kotronen A, Seppala-Lindroos A, Bergholm R, Yki-Jarvinen H. Tissue specificity of insulin resistance in humans: fat in the liver rather than muscle is associated with features of the metabolic syndrome. Diabetologia. 2008;51:130-8.
124. Bajaj M, Baig R, Suraamornkul S, Hardies LJ, Coletta DK, Cline GW, et al. Effects of pioglitazone on intramyocellular fat metabolism in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab.2010;95:1916-23.
125. Bollheimer LC, Skelly RH, Chester MW, McGarry JD, Rhodes CJ. Chronic exposure to free fatty acid reduces pancreatic beta cell insulin content by increasing basal insulin secretion that is not compensated for by a corresponding increase in proinsulin biosynthesis translation. J Clin Invest. 1998;101:1094-101.
126. Unger RH, Zhou YT. Lipotoxicity of beta-cells in obesity and in other causes of fatty acid spillover. Diabetes. 2001;50 Suppl 1:S118-21.
127. Lee Y, Hirose H, Ohneda M, Johnson JH, McGarry JD, Unger RH. Beta-cell lipotoxicity in the pathogenesis of non-insulin-dependent diabetes mellitus of obese rats: impairment in adipocyte-beta-cell relationships. Proc Natl Acad Sci USA. 1994 8;91:10878-82.
128. van der Zijl NJ, Goossens GH, Moors CC, van Raalte DH, Muskiet MH, Pouwels PJ, et al. Ectopic fat storage in the pancreas, liver, and abdominal fat depots: impact on betacell function in individuals with impaired glucose metabolism. J Clin Endocrinol Metab. 2011;96:459-67.
129. Heni M, Machann J, Staiger H, Schwenzer NF, Peter A, Schick F, et al. Pancreatic fat is negatively associated with insulin secretion in individuals with impaired fasting glucose and/or impaired glucose tolerance: a nuclear magnetic resonance study. Diabetes Metab Res Rev. 2010;26:200-5.
130. Brunham LR, Kruit JK, Pape TD, Timmins JM, Reuwer AQ, Vasanji Z, et al. Beta-cell ABCA1 influences insulin secretion, glucose homeostasis and response to thiazolidinedione treatment. Nat Med. 2007;13:340-7.
131. Vergeer M, Brunham LR, Koetsveld J, Kruit JK, Verchere CB, Kastelein JJ, et al. Carriers of loss-of-function mutations in ABCA1 display pancreatic beta-cell dysfunction. Diabetes Care. 2010;33:869-74.
132. van Raalte DH, van der Zijl NJ, Diamant M. Pancreatic steatosis in humans: cause or marker of lipotoxicity? Curr Opin Clin Nutr Metab Care. 2010;13:478-85.
133. Par é A, Dumont M, Lemieux I, Brochu M, Almé ras N, Lemieux S, et al. Is the relationship between adipose tissue and waist girth altered by weight loss in obese men? Obes Res. 2001;9:526-34.
134. Longo R, Ricci C, Masutti F, Vidimari R, Croce LS, Bercich L, et al. Fatty infiltration of the liver. Quantification by 1H localized magnetic resonance spectroscopy and comparison with computed tomography. Invest Radiol. 1993;28:297-302.
135. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998;339: 229-34.
136. Dagenais GR, St-Pierre A, Gilbert P, Lamarche B, Despré s JP, Bernard PM, et al. Comparison of prognosis for men with type 2 diabetes mellitus and men with cardiovascular disease. CMAJ. 2009;180:40-7.
137. Saydah S, Tao M, Imperatore G, Gregg E. GHb level and subsequent mortality among adults in the U.S. Diabetes Care. 2009;32:1440-6.
138. Nathan DM. Long-term complications of diabetes mellitus. N Engl J Med. 1993;328:1676-85.
139. Orasanu G, Plutzky J. The pathologic continuum of diabetic vascular disease. J Am Coll Cardiol. 2009;53(5 Suppl):S35-42.
140. Creager MA, Luscher TF, Cosentino F, Beckman JA. Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: Part I. Circulation. 2003;108:1527-32.
141. Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560-72.
142. Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545-59.
143. Duckworth W, Abraira C, Moritz T, Reda D, Emanuele N, Reaven PD, et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med. 2009;360:129-39.
144. Blackburn P, Lemieux I, Lamarche B, Bergeron J, Perron P, Tremblay G, et al. Type 2 diabetes without the atherogenic metabolic triad does not predict angiographically assessed coronary artery disease in women. Diabetes Care. 2008;31:170-2.
145. Turner RC, Millns H, Neil HA, Stratton IM, Manley SE, Matthews DR, et al. Risk factors for coronary artery disease in non-insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). BMJ. 1998;316:823-8.
146. Lehto S, Ronnemaa T, Haffner SM, Pyorala K, Kallio V, Laakso M. Dyslipidemia and hyperglycemia predict coronary heart disease events in middle-aged patients with NIDDM. Diabetes. 1997;46:1354-9.
147. Alexander CM, Landsman PB, Teutsch SM, Haffner SM. NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes. 2003;52:1210-4.
148. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393-403.
149. Orchard TJ, Temprosa M, Goldberg R, Haffner S, Ratner R, Marcovina S, et al. The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial. Ann Intern Med. 2005;142:611-9.
150. Wing RR. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Arch Intern Med. 2010;170: 1566-75.
151. Deedwania P, Barter P, Carmena R, Fruchart JC, Grundy SM, Haffner S, et al. Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome: analysis of the Treating to New Targets study. Lancet. 2006;368:919-28.
152. Ballantyne CM, Olsson AG, Cook TJ, Mercuri MF, Pedersen TR, Kjekshus J. Influence of low high-density lipoprotein cholesterol and elevated triglyceride on coronary heart disease events and response to simvastatin therapy in 4S. Circulation. 2001;104:3046-51.
153. Scott R, O'B rien R, Fulcher G, Pardy C, D' E mden M, Tse D, et al. Effects of fenofibrate treatment on cardiovascular disease risk in 9,795 individuals with type 2 diabetes and various components of the metabolic syndrome: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetes Care. 2009;32:493-8.
154. ACCORD Study Group; Ginsberg HN, Elam MB, Lovato LC, Crouse JR 3rd, Leiter LA, Linz P, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med.2010;362:1563-74.
155. Hunink MG, Goldman L, Tosteson AN, Mittleman MA, Goldman PA, Williams LW, et al. The recent decline in mortality from coronary heart disease, 1980-1990. The effect of secular trends in risk factors and treatment. JAMA. 1997;277:535-42.
156. Ford ES, Ajani UA, Croft JB, Critchley JA, Labarthe DR, Kottke TE, et al. Explaining the decrease in U.S. deaths from coronary disease, 1980-2000. N Engl J Med. 2007;356:2388-98.
157. Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world-a growing challenge. N Engl J Med. 2007;356:213-5.
158. Olshansky SJ, Passaro DJ, Hershow RC, Layden J, Carnes BA, Brody J, et al. A potential decline in life expectancy in the United States in the 21st century. N Engl J Med. 2005;352:1138-45.