Background/Aims. The effect of benign obesity on subclinical cardiovascular disease is still questionable. The purpose of this study was to assess carotid intima media thickness (CIMT), as a marker of subclinical atherosclerosis, and to evaluate its relation to age, sex, and IGF-1 in metabolically healthy obese (MHO) subjects. Methods. A total of 75 MHO subjects and 80 age, and sex matched healthy nonobese control subjects were included in the study. Body mass index (BMI), waist circumference (WC), blood pressure, fasting plasma glucose, fasting insulin, HOMA-IR, lipid profile, insulin like growth factor-1 (IGF-1), and CIMT were assessed in all subjects. Results. MHO subjects had significantly higher CIMT and lower IGF-1 than healthy nonobese controls. Mean CIMT was significantly higher in MHO men age subgroup range from 30 to 50 years than in their age range matched (premenopausal) MHO women subgroup. In MHO subjects, CIMT was positively correlated with age, BMI, WC, SBP, HOMA-IR, TG, and LDL-C, and negatively correlated with IGF-1. Regression analysis revealed that middle age, male sex and IGF-1 remained independently associated with CIMT in MHO subjects. Conclusion. CIMT is elevated and IGF-1 is reduced in MHO subjects, and CIMT is independently associated with male gender, middle age, and IGF-1. Definition of healthy obesity may be broadened to include IMT measurement. 1. Introduction Metabolically healthy obese (MHO) term refers to obese individuals who are relatively insulin sensitive and normotensive and have favourable glucose and lipid profile inspite of high levels of obesity [1, 2]. Evidence suggests that MHO individuals as based on BMI criteria may account for as much as 20–30% of obese population [3, 4]. MHO subset of individuals is relatively protected from obesity related cardio-metabolic disturbances that increase cardiovascular disease (CVD) risk in metabolically abnormal obese [5]. However, data concerning the exact risk of CVD in MHO as compared to healthy normal weight individuals is limited, and most data are confined to women at narrow age range. Carotid artery intima media thickness (CIMT) is a non-invasive surrogate marker of subclinical atherosclerosis and an indicator of CVD risk [6, 7]. In addition, IMT is associated with age, male gender, obesity, and traditional risk factors [8–11]. Beside traditional CVD risk factors, obesity is associated with changes in insulin like growth factor-1 (IGF-1) [12, 13] which may be linked to atherosclerosis. Previous studies concerning the association between IGF-1 and atherosclerosis have
References
[1]
A. D. Karelis, M. Brochu, and R. Rabasa-Lhoret, “Can we identify metabolically healthy but obese individuals (MHO)?” Diabetes and Metabolism, vol. 30, no. 6, pp. 569–572, 2004.
[2]
M. Brochu, A. Tchernof, I. J. Dionne et al., “What are the physical characteristics associated with a normal metabolic profile despite a high level of obesity in postmenopausal women?” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 3, pp. 1020–1025, 2001.
[3]
R. P. Wildman, P. Muntner, K. Reynolds et al., “The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 1999-2004),” Archives of Internal Medicine, vol. 168, no. 15, pp. 1617–1624, 2008.
[4]
A. D. Karelis, D. H. St-Pierre, F. Conus, R. Rabasa-Lhoret, and E. T. Poehlman, “Metabolic and body composition factors in subgroups of obesity: what do we know?” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 6, pp. 2569–2575, 2004.
[5]
J. B. Meigs, P. W. F. Wilson, C. S. Fox et al., “Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease,” Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 8, pp. 2906–2912, 2006.
[6]
D. H. O’Learly and J. F. Polak, “Intima media thickness: a tool for atherosclerosis imaging and event prediction,” American Journal of Cardiology, vol. 90, no. 10, pp. 18–20, 2002.
[7]
M. W. Lorenz, H. S. Markus, M. L. Bots, M. Rosvall, and M. Sitzer, “Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis,” Circulation, vol. 115, no. 4, pp. 459–467, 2007.
[8]
C. Sinning, P. S. Wild, F. M. O. Echevarria et al., “Sex differences in early carotid atherosclerosis (from the community-based Gutenberg-Heart study),” American Journal of Cardiology, vol. 107, no. 12, pp. 1841–1847, 2011.
[9]
T.-Y. Tan, C.-H. Lu, T.-K. Lin, C.-W. Liou, Y.-C. Chuang, and U. Schminke, “Factors associated with gender difference in the intima-media thickness of the common carotid artery,” Clinical Radiology, vol. 64, no. 11, pp. 1097–1103, 2009.
[10]
J. Lo, S. E. Dolan, J. R. Kanter et al., “Effects of obesity, body compositionand adiponectin on carotid intima-media thickness in healthy women,” Journal of Clinical Endocrinology and Metabolism, vol. 9, no. 5, pp. 11677–11682, 2006.
[11]
M. A. Espeland, R. Tang, J. G. Terry, D. H. Davis, M. Mercuri, and J. R. Crouse III, “Associations of risk factors with segment-specific intimal-medial thickness of the extracranial carotid artery,” Stroke, vol. 30, no. 5, pp. 1047–1055, 1999.
[12]
C. S. Lam, M. H. Chen, S. M. Lacey et al., “Circulating insulin-like growth factor-1 and its binding protein-3: metabolic and genetic correlates in the community,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 30, pp. 1479–1484, 2010.
[13]
J. M. Faupel-Badger, D. Berrigan, R. Ballard-Barbash, and N. Potischman, “Anthropometric correlates of insulin-like growth factor 1 (IGF-1) and IGF binding protein-3 (IGFBP-3) levels by race/ethnicity and gender,” Annals of Epidemiology, vol. 19, no. 12, pp. 841–849, 2009.
[14]
S. Kawashi, N. Takeda, A. Sasaki et al., “Circulating insulin-like growth factor binding protein-3 is associated with early carotid atherosclerosis.,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, pp. 617–621, 2005.
[15]
E. Spilcke-Liss, N. Friedrich, M. D？rr et al., “Serum insulin-like growth factor I and its binding protein 3 in their relation to intima-media thickness: results of the Study of Health in Pomerania (SHIP),” Clinical Endocrinology, vol. 75, no. 1, pp. 70–75, 2011.
[16]
M. A. Marini, E. Succurro, S. Frontoni et al., “Metabolically healthy but obese women have an intermediate cardiovascular risk profile between healthy nonobese women and obese insulin-resistant women,” Diabetes Care, vol. 30, no. 8, pp. 2145–2147, 2007.
[17]
M. Hietaniemi, S. M. P？ykk？, O. Ukkola, M. P？iv？nsalo, and Y. A. Kes？niemi, “IGF-I concentrations are positively associated with carotid artery atherosclerosis in women,” Annals of Medicine, vol. 37, no. 5, pp. 373–382, 2005.
[18]
U. I. Khan, D. Wang, R. C. Thurston et al., “Burden of subclinical cardiovascular disease in “metabolically benign” and “at-risk” overweight and obese women: the Study of Women's Health Across the Nation (SWAN),” Atherosclerosis, vol. 217, no. 1, pp. 179–186, 2011.
[19]
S. M. Grundy, J. I. Cleeman, S. R. Daniels et al., “Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement,” Circulation, vol. 112, no. 17, pp. 2735–2752, 2005.
[20]
A. D. Karelis and R. Rabasa-Lhoret, “Inclusion of C-reactive protein in the identification of Metabolically Healthy but Obese (MHO) individuals,” Diabetes and Metabolism, vol. 34, no. 2, pp. 183–184, 2008.
[21]
D. R. Matthews, J. P. Hosker, and A. S. Rudenski, “Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man,” Diabetologia, vol. 28, no. 7, pp. 412–419, 1985.
[22]
W. T. Friedewald, R. I. Levy, and D. S. Fredrickson, “Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge,” Clinical Chemistry, vol. 18, no. 6, pp. 499–502, 1972.
[23]
J. ？rnl？v, E. Ingelsson, J. Sundstr？m, and L. Lind, “Impact of body mass index and the metabolic syndrome on the risk of cardiovascular disease and death in middle-aged men,” Circulation, vol. 121, no. 2, pp. 230–236, 2010.
[24]
J. Park, S. H. Kim, G. Y. Cho et al., “Obesity phenotype and cardiovascular changes,” Journal of Hypertension, vol. 29, no. 9, pp. 1765–1772, 2011.
[25]
E. M. Urbina, T. R. Kimball, C. E. McCoy, P. R. Khoury, S. R. Daniels, and L. M. Dolan, “Youth with obesity and obesity-related type 2 diabetes mellitus demonstrate abnormalities in carotid structure and function,” Circulation, vol. 119, no. 22, pp. 2913–2919, 2009.
[26]
M. Kozakova, C. Palombo, M. Paterni et al., “Body composition and common carotid artery remodeling in a healthy population,” Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 9, pp. 3325–3332, 2008.
[27]
A. Simon, J. Levenson, J. Bouthier, and B. Maarek, “Haemodynamic basis of early modifications of the large arteries in borderline hypertension,” Journal of Hypertension, vol. 5, no. 2, pp. 179–184, 1987.
[28]
T. A. Lakka, H.-M. Lakka, R. Salonen, G. A. Kaplan, and J. T. Salonen, “Abdominal obesity is associated with accelerated progression of carotid atherosclerosis in men,” Atherosclerosis, vol. 154, no. 2, pp. 497–504, 2001.
[29]
J. I. Recio-Rodriguez, M. A. Gomez-Marcos, M. C. Patino-Alonso, C. Agudo-Conde, E. Rodriguez-Sanchez, and L. Garcia-Ortiz, “Abdominal obesity vs general obesity for identifying arterial stiffness, subclinical atherosclerosis and wave reflection in healthy, diabetics and hypertensive,” BMC Cardiovascular Disorders, vol. 12, article 3, 2012.
[30]
M. de Michele, S. Panico, A. Iannuzzi et al., “Association of obesity and central fat distribution with carotid artery wall thickening in middle-aged women,” Stroke, vol. 33, no. 12, pp. 2923–2928, 2002.
[31]
J. J. Cao, A. M. Arnold, T. A. Manolio et al., “Association of carotid artery intima-media thickness, plaques, and C-reactive protein with future cardiovascular disease and all-cause mortality: the Cardiovascular Health study,” Circulation, vol. 116, no. 1, pp. 32–38, 2007.
[32]
L. G. Spagnoli, A. Mauriello, A. Orlandi, G. Sangiorgi, and E. Bonanno, “Age-related changes affecting atherosclerotic risk. Potential for pharmacological intervention,” Drugs and Aging, vol. 8, no. 4, pp. 275–298, 1996.
[33]
A. Tosetto, P. Prati, C. Baracchini, R. Manara, and F. Rodeghiero, “Age-adjusted reference limits for carotid intima-media thickness as better indicator of vascular risk: population-based estimates from the VITA project,” Journal of Thrombosis and Haemostasis, vol. 3, no. 6, pp. 1224–1230, 2005.
[34]
A. Juul, T. Scheike, M. Davidsen, J. Gyllenborg, and T. J？rgensen, “Low serum insulin-like growth factor I is associated with increased risk of ischemic heart disease: a population-based case-control study,” Circulation, vol. 106, no. 8, pp. 939–944, 2002.
[35]
E. E. Calle and R. Kaaks, “Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms,” Nature Reviews Cancer, vol. 4, no. 8, pp. 579–591, 2004.
[36]
D. V. Soares, L. D. Spina, R. R. de Lima Oliveira Brasil et al., “Carotid artery intima-media thickness and lipid profile in adults with growth hormone deficiency after long-term growth hormone replacement,” Metabolism, vol. 54, no. 3, pp. 321–329, 2005.
[37]
A. Colao, P. Marzullo, and G. Lombardi, “Effect of a six-month treatment with lanreotide on cardiovascular risk factors and arterial intima-media thickness in patients with acromegaly,” European Journal of Endocrinology, vol. 146, no. 3, pp. 303–309, 2002.
[38]
H. J. Arnqvist, “The role of IGF-system in vascular insulin resistance,” Hormone and Metabolic Research, vol. 40, no. 9, pp. 588–592, 2008.
[39]
Y. Higashi, S. Sukhanov, A. Anwar, S.-Y. Shai, and P. Delafontaine, “IGF-1, oxidative stress and atheroprotection,” Trends in Endocrinology and Metabolism, vol. 21, no. 4, pp. 245–254, 2010.
[40]
S. Sukhanov, Y. Higashi, S.-Y. Shai et al., “IGF-1 reduces inflammatory responses, suppresses oxidative stress, and decreases atherosclerosis progression in ApoE-deficient mice,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 12, pp. 2684–2690, 2007.
[41]
F. Perticone, A. Sciacqua, M. Perticone et al., “Low-plasma insulin-like growth factor-I levels are associated with impaired endothelium-dependent vasodilatation in a cohort of untreated, hypertensive caucasian subjects,” Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 7, pp. 2806–2810, 2008.
[42]
M. F. Walsh, M. Barazi, G. Pete, R. Muniyappa, J. C. Dunbar, and J. R. Sowers, “Insulin-like growth factor I diminishes in vivo and in vitro vascular contractility: role of vascular nitric oxide,” Endocrinology, vol. 137, no. 5, pp. 1798–1803, 1996.
[43]
F. Lanfranco, L. Gianotti, R. Giordano, M. Pellegrino, M. Maccario, and E. Arvat, “Ageing, growth hormone and physical performance,” Journal of Endocrinological Investigation, vol. 26, no. 9, pp. 861–872, 2003.
[44]
M. H. Rasmussen, A. Juul, and J. Hilsted, “Effect of weight loss on free insulin-like growth factor-I in obese women with hyposomatotropism,” Obesity, vol. 15, no. 4, pp. 879–886, 2007.
