Relationship of abdominal visceral and subcutaneous adipose tissue with lipoprotein particle number and size in type 2 diabetes

Susan Sam, Steven Haffner, Michael H Davidson, Ralph B D'Agostino Sr, Steven Feinstein, George Kondos, Alfonso Perez, Theodore Mazzone, Susan Sam, Steven Haffner, Michael H Davidson, Ralph B D'Agostino Sr, Steven Feinstein, George Kondos, Alfonso Perez, Theodore Mazzone

Abstract

Objective: Insulin resistance and type 2 diabetes are associated with an atherogenic lipoprotein profile. We examined the role of visceral and subcutaneous fat depots, independent of BMI, on the dyslipidemia associated with type 2 diabetes.

Research design and methods: A total of 382 subjects with type 2 diabetes underwent abdominal computed tomography to evaluate subcutaneous (SAT) and visceral adipose tissue (VAT) distribution and had anthropometric measurements to determine BMI and waist and hip circumference. Fasting blood was obtained for lipoprotein particle number and size using nuclear magnetic resonance spectroscopy. The relationship of lipoprotein particle number and size with BMI, SAT, and VAT was examined using multivariable regression models adjusted for age, sex, diabetes therapy, duration of diabetes, smoking, statin use, and A1C levels. The relation of VAT to lipoprotein particle number and size was further evaluated after the addition of BMI, BMI plus SAT, or BMI plus homeostatis is model assessment of insulin resistance (HOMA-IR) to the model.

Results: VAT was positively related to VLDL particle number (P < 0.0001), LDL particle number (P < 0.01), and VLDL size (P < 0.0001) and negatively related to LDL size (P < 0.0001) and HDL size (P < 0.0001). These relationships remained unchanged after addition of BMI and SAT to the model. After addition of HOMA-IR, VAT remained positively related to VLDL particle number (P < 0.0001) and size (P < 0.01) and negatively related to LDL and HDL particle size (P < 0.0001 for both comparisons). Neither BMI nor SAT was independently related to lipoprotein parameters.

Conclusions: In patients with type 2 diabetes, higher VAT independent of BMI was associated with higher VLDL and LDL particle number, larger VLDL particles, and smaller LDL and HDL particles. This lipoprotein pattern has been associated with increased risk for atherosclerosis and cardiovascular disease.

References

    1. Garvey WT, Kwon S, Zheng D, Shaughnessy S, Wallace P, Hutto A, Pugh K, Jenkins AJ, Klein RL, Liao Y: Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance. Diabetes 52: 453–462, 2003
    1. Goff DC Jr, D'Agostino RB Jr, Haffner SM, Otvos JD: Insulin resistance and adiposity influence lipoprotein size and subclass concentrations: results from the Insulin Resistance Atherosclerosis Study. Metabolism 54: 264–270, 2005
    1. Kuller L, Arnold A, Tracy R, Otvos J, Burke G, Psaty B, Siscovick D, Freedman DS, Kronmal R: Nuclear magnetic resonance spectroscopy of lipoproteins and risk of coronary heart disease in the cardiovascular health study. Arterioscler Thromb Vasc Biol 22: 1175–1180, 2002
    1. Mora S, Szklo M, Otvos JD, Greenland P, Psaty BM, Goff DC Jr, O'Leary DH, Saad MF, Tsai MY, Sharrett AR: LDL particle subclasses, LDL particle size, and carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 192: 211–217, 2007
    1. Mackey RH, Kuller LH, Sutton-Tyrrell K, Evans RW, Holubkov R, Matthews KA: Lipoprotein subclasses and coronary artery calcium in postmenopausal women from the healthy women study. Am J Cardiol 90: 71i–76i, 2002
    1. Liu ML, Ylitalo K, Nuotio I, Salonen R, Salonen JT, Taskinen MR: Association between carotid intima-media thickness and low-density lipoprotein size and susceptibility of low-density lipoprotein to oxidation in asymptomatic members of familial combined hyperlipidemia families. Stroke 33: 1255–1260, 2002
    1. Gardner CD, Fortmann SP, Krauss RM: Association of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women. JAMA 276: 875–881, 1996
    1. Stampfer MJ, Krauss RM, Ma J, Blanche PJ, Holl LG, Sacks FM, Hennekens CH: A prospective study of triglyceride level, low-density lipoprotein particle diameter, and risk of myocardial infarction. JAMA 276: 882–888, 1996
    1. Rajman I, Kendall MJ, Cramb R, Holder RL, Salih M, Gammage MD: Investigation of low density lipoprotein subfractions as a coronary risk factor in normotriglyceridaemic men. Atherosclerosis 125: 231–242, 1996
    1. Lamarche B, Tchernof A, Moorjani S, Cantin B, Dagenais GR, Lupien PJ, Despres JP: Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men: prospective results from the Quebec Cardiovascular Study. Circulation 95: 69–75, 1997
    1. Blake GJ, Otvos JD, Rifai N, Ridker PM: Low-density lipoprotein particle concentration and size as determined by nuclear magnetic resonance spectroscopy as predictors of cardiovascular disease in women. Circulation 106: 1930–1937, 2002
    1. Manson JE, Colditz GA, Stampfer MJ, Willett WC, Rosner B, Monson RR, Speizer FE, Hennekens CH: A prospective study of obesity and risk of coronary heart disease in women. N Engl J Med 322: 882–889, 1990
    1. Hubert HB, Feinleib M, McNamara PM, Castelli WP: Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation 67: 968–977, 1983
    1. Grundy SM: Obesity, metabolic syndrome, and cardiovascular disease. J Clin Endocrinol Metab 89: 2595–2600, 2004
    1. Wajchenberg BL: Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 21: 697–738, 2000
    1. Klein S: The case of visceral fat: argument for the defense. J Clin Invest 113: 1530–1532, 2004
    1. Garg A: Regional adiposity and insulin resistance. J Clin Endocrinol Metab 89: 4206–4210, 2004
    1. Arsenault BJ, Lachance D, Lemieux I, Almeras N, Tremblay A, Bouchard C, Perusse L, Despres JP: Visceral adipose tissue accumulation, cardiorespiratory fitness, and features of the metabolic syndrome. Arch Intern Med 167: 1518–1525, 2007
    1. Kelley DE, Thaete FL, Troost F, Huwe T, Goodpaster BH: Subdivisions of subcutaneous abdominal adipose tissue and insulin resistance. Am J Physiol Endocrinol Metab 278: E941–E948, 2000
    1. Wagenknecht LE, Langefeld CD, Scherzinger AL, Norris JM, Haffner SM, Saad MF, Bergman RN: Insulin sensitivity, insulin secretion, and abdominal fat: the Insulin Resistance Atherosclerosis Study (IRAS) Family Study. Diabetes 52: 2490–2496, 2003
    1. Nieves DJ, Cnop M, Retzlaff B, Walden CE, Brunzell JD, Knopp RH, Kahn SE: The atherogenic lipoprotein profile associated with obesity and insulin resistance is largely attributable to intra-abdominal fat. Diabetes 52: 172–179, 2003
    1. Nicklas BJ, Penninx BW, Ryan AS, Berman DM, Lynch NA, Dennis KE: Visceral adipose tissue cutoffs associated with metabolic risk factors for coronary heart disease in women. Diabetes Care 26: 1413–1420, 2003
    1. Hayashi T, Boyko EJ, Leonetti DL, McNeely MJ, Newell-Morris L, Kahn SE, Fujimoto WY: Visceral adiposity and the risk of impaired glucose tolerance: a prospective study among Japanese Americans. Diabetes Care 26: 650–655, 2003
    1. Goodpaster BH, Krishnaswami S, Resnick H, Kelley DE, Haggerty C, Harris TB, Schwartz AV, Kritchevsky S, Newman AB: Association between regional adipose tissue distribution and both type 2 diabetes and impaired glucose tolerance in elderly men and women. Diabetes Care 26: 372–379, 2003
    1. Carr DB, Utzschneider KM, Hull RL, Kodama K, Retzlaff BM, Brunzell JD, Shofer JB, Fish BE, Knopp RH, Kahn SE: Intra-abdominal fat is a major determinant of the National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome. Diabetes 53: 2087–2094, 2004
    1. Vega GL, Adams-Huet B, Peshock R, Willett D, Shah B, Grundy SM: Influence of body fat content and distribution on variation in metabolic risk. J Clin Endocrinol Metab 91: 4459–4466, 2006
    1. Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, Vasan RS, Murabito JM, Meigs JB, Cupples LA, DÆAgostino RB Sr, OÆDonnell CJ: Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation 116: 39–48, 2007
    1. Abate N, Garg A, Peshock RM, Stray-Gundersen J, Adams-Huet B, Grundy SM: Relationship of generalized and regional adiposity to insulin sensitivity in men with NIDDM. Diabetes 45: 1684–1693, 1996
    1. Abate N, Garg A, Peshock RM, Stray-Gundersen J, Grundy SM: Relationships of generalized and regional adiposity to insulin sensitivity in men. J Clin Invest 96: 88–98, 1995
    1. Azuma K, Heilbronn LK, Albu JB, Smith SR, Ravussin E, Kelley DE: Adipose tissue distribution in relation to insulin resistance in type 2 diabetes mellitus. Am J Physiol Endocrinol Metab 293: E435–E442, 2007
    1. Mazzone T, Meyer PM, Feinstein SB, Davidson MH, Kondos GT, Dægostino RB Sr, Perez A, Provost JC, Haffner SM: Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. JAMA 296: 2572–2581, 2006
    1. Mazzone T, Meyer PM, Kondos GT, Davidson MH, Feinstein SB, Dægostino RB Sr, Perez A, Haffner SM: Relationship of traditional and nontraditional cardiovascular risk factors to coronary artery calcium in type 2 diabetes. Diabetes 56: 849–855, 2007
    1. DeNino WF, Tchernof A, Dionne IJ, Toth MJ, Ades PA, Sites CK, Poehlman ET: Contribution of abdominal adiposity to age-related differences in insulin sensitivity and plasma lipids in healthy nonobese women. Diabetes Care 24: 925–932, 2001
    1. Borkan GA, Gerzof SG, Robbins AH, Hults DE, Silbert CK, Silbert JE: Assessment of abdominal fat content by computed tomography. Am J Clin Nutr 36: 172–177, 1982
    1. Kosmiski LA, Kuritzkes DR, Lichtenstein KA, Glueck DH, Gourley PJ, Stamm ER, Scherzinger AL, Eckel RH: Fat distribution and metabolic changes are strongly correlated and energy expenditure is increased in the HIV lipodystrophy syndrome. AIDS 15: 1993–2000, 2001
    1. Bjorntorp P: “Portal” adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. Arteriosclerosis 10: 493–496, 1990
    1. Goodpaster BH, Thaete FL, Simoneau JA, Kelley DE: Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat. Diabetes 46: 1579–1585, 1997
    1. Thomas EL, Saeed N, Hajnal JV, Brynes A, Goldstone AP, Frost G, Bell JD: Magnetic resonance imaging of total body fat. J Appl Physiol 85: 1778–1785, 1998
    1. Basu A, Basu R, Shah P, Vella A, Rizza RA, Jensen MD: Systemic and regional free fatty acid metabolism in type 2 diabetes. Am J Physiol Endocrinol Metab 280: E1000–E1006, 2001
    1. Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD: Splanchnic lipolysis in human obesity. J Clin Invest 113: 1582–1588, 2004
    1. Goodpaster BH, Krishnaswami S, Harris TB, Katsiaras A, Kritchevsky SB, Simonsick EM, Nevitt M, Holvoet P, Newman AB: Obesity, regional body fat distribution, and the metabolic syndrome in older men and women. Arch Intern Med 165: 777–783, 2005
    1. Klein S, Fontana L, Young VL, Coggan AR, Kilo C, Patterson BW, Mohammed BS: Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N Engl J Med 350: 2549–2557, 2004
    1. Miyazaki Y, Glass L, Triplitt C, Wajcberg E, Mandarino LJ, DeFronzo RA: Abdominal fat distribution and peripheral and hepatic insulin resistance in type 2 diabetes mellitus. Am J Physiol Endocrinol Metab 283: E1135–E1143, 2002
    1. Festa A, Williams K, D'Agostino R Jr, Wagenknecht LE, Haffner SM: The natural course of (cell function in nondiabetic and diabetic individuals: the Insulin Resistance Atherosclerosis Study. Diabetes 55: 1114–1120, 2006
    1. Shoelson SE, Lee J, Goldfine AB: Inflammation and insulin resistance. J Clin Invest 116: 1793–1801, 2006
    1. Neels JG, Olefsky JM: Inflamed fat: what starts the fire? J Clin Invest 116: 33–35, 2006
    1. Varma V, Yao-Borengasser A, Rasouli N, Bodles AM, Phanavanh B, Lee MJ, Starks T, Kern LM, Spencer HJ III, McGehee RE Jr, Fried SK, Kern PA: Human visfatin expression: relationship to insulin sensitivity, intramyocellular lipids, and inflammation. J Clin Endocrinol Metab 92: 666–672, 2007
    1. Mertens I, Lemieux I, Verrijken A, Despres JP, Van Gaal LF: PAI-1 activity, but not fibrinogen or von Willebrand factor, is inversely related to LDL particle size in type 2 diabetes. Diabetes Metab Res Rev 24: 141–147, 2008
    1. 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 285: E906–E916, 2003
    1. Snijder MB, Zimmet PZ, Visser M, Dekker JM, Seidell JC, Shaw JE: Independent and opposite associations of waist and hip circumferences with diabetes, hypertension and dyslipidemia: the AusDiab Study. Int J Obes Relat Metab Disord 28: 402–409, 2004
    1. Kelley DE: Skeletal muscle triglycerides: an aspect of regional adiposity and insulin resistance. Ann N Y Acad Sci 967: 135–145, 2002
    1. Canoy D, Boekholdt SM, Wareham N, Luben R, Welch A, Bingham S, Buchan I, Day N, Khaw KT: 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 116: 2933–2943, 2007
    1. Costa J, Borges M, David C, Vaz Carneiro A: Efficacy of lipid lowering drug treatment for diabetic and non-diabetic patients: meta-analysis of randomised controlled trials. BMJ 332: 1115–1124, 2006

Source: PubMed

3
Abonnieren