Obesity, hyperglycemia and endothelial function in inner city Bronx adolescents: a cross-sectional study

Chhavi Agarwal, Hillel W Cohen, Radhika H Muzumdar, Rubina A Heptulla, Venkat S Renukuntla, Jill Crandall, Chhavi Agarwal, Hillel W Cohen, Radhika H Muzumdar, Rubina A Heptulla, Venkat S Renukuntla, Jill Crandall

Abstract

Background: Along with the rise in obesity, cardiovascular disease (CVD) has become the major cause of death in developed countries. Although overt coronary heart disease rarely manifests during childhood, atherosclerosis can begin by the second decade of life. Therefore, identifying reliable risk markers of early vascular disease in childhood could be important. Alteration in endothelial function (EF) is an early preclinical marker of the atherosclerotic process and can be assessed non-invasively using reactive hyperemia peripheral arterial tonometry (RH-PAT). The purpose of this study was to investigate if obesity in children is associated with lower EF as measured with RH-PAT, and if obese children with impaired glucose regulation have further impairment in RH-PAT measured EF compared to obese children with normal glucose tolerance.

Methods: Cardiovascular risk factors, adipocytokines and EF using RH-PAT were evaluated in lean (n = 14) and obese (n = 37) adolescents (age 12-18 years). Based on an oral glucose tolerance test, the obese group was subdivided into: obese with normal (NGT, n = 22) and obese with impaired glucose regulation (IGR, n = 15).

Results: RH-PAT score was lower in obese subjects compared to lean controls (1.70 ± 0.02 vs. 1.98 ± 0.09, P = 0.02), indicating worse EF. This difference remained significant when adjusted for age, sex and ethnicity (P = 0.02). We observed a pattern of worsening EF with increasing metabolic burden, with RH-PAT scores of 1.98 ± 0.09,1.73 ± 0.08 and 1.65 ± 0.12 in the lean, obese-NGT and obese-IGR groups, respectively, ptrend = 0.03. Obese subjects were more insulin resistant [higher HOMA] (p = 0.03), and had higher levels of leptin (p = 0.004), hsCRP (p = 0.0004), and TNF-α (p = 0.03) compared to lean subjects. Adjusting for insulin resistance and adipocytokines substantially attenuated the obesity association with RH-PAT, suggesting that insulin resistance and inflammation may mediate the association of EF with obesity.

Conclusions: Risk factors for adult cardiovascular disease, including impaired EF, insulin resistance and inflammation, are evident in obese adolescents. Whether early detection of these cardiovascular risk factors will be useful for informing interventions to prevent disease progression needs further study.

Trial registration: Clinical Trials Identifier: NCT01879033.

Figures

Figure 1
Figure 1
RH-PAT score (unadjusted) in lean, obese NGT & obese IGR subjects.

References

    1. Childhood obesity facts. [ ]
    1. Liu J, Wade TJ, Tan H. Cardiovascular risk factors and anthropometric measurements of adolescent body composition: a cross-sectional analysis of the third national health and nutrition examination survey. Int J Obesity. 2007;31:59–64. doi: 10.1038/sj.ijo.0803347.
    1. Olshansky SJ, Passaro DJ, Hershow RC, Layden J, Carnes BA, Brody J, Hayflick L, Butler RN, Allison DB, Ludwig DS. A potential decline in life expectancy in the United States in the 21st century. N Engl J Med. 2005;352:1138–1145. doi: 10.1056/NEJMsr043743.
    1. Gidding SS, Bao W, Srinivasan SR, Berenson GS. Effects of secular trends in obesity on coronary risk factors in children: the Bogalusa heart study. J Pediatr. 1995;127:868–874. doi: 10.1016/S0022-3476(95)70020-X.
    1. Davis PH, Dawson JD, Riley WA, Lauer RM. Carotid intimal-medial thickness is related to cardiovascular risk factors measured from childhood through middle age: the Muscatine study. Circulation. 2001;104:2815–2819. doi: 10.1161/hc4601.099486.
    1. Li S, Chen W, Srinivasan SR, Bond MG, Tang R, Urbina EM, Berenson GS. Childhood cardiovascular risk factors and carotid vascular changes in adulthood: the Bogalusa heart study. JAMA: J Am Med Assoc. 2003;290:2271–2276. doi: 10.1001/jama.290.17.2271.
    1. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362:801–809. doi: 10.1038/362801a0.
    1. Hamburg NM, Keyes MJ, Larson MG, Vasan RS, Schnabel R, Pryde MM, Mitchell GF, Sheffy J, Vita JA, Benjamin EJ. Cross-sectional relations of digital vascular function to cardiovascular risk factors in the Framingham heart study. Circulation. 2008;117:2467–2474. doi: 10.1161/CIRCULATIONAHA.107.748574.
    1. Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007;115:1285–1295.
    1. Rubinshtein R, Kuvin JT, Soffler M, Lennon RJ, Lavi S, Nelson RE, Pumper GM, Lerman LO, Lerman A. Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events. Eur Heart J. 2010;31:1142–1148. doi: 10.1093/eurheartj/ehq010.
    1. Nohria A, Gerhard-Herman M, Creager MA, Hurley S, Mitra D, Ganz P. Role of nitric oxide in the regulation of digital pulse volume amplitude in humans. J Appl Physiol. 2006;101:545–548. doi: 10.1152/japplphysiol.01285.2005.
    1. Yudkin JS. Adipose tissue, insulin action and vascular disease: inflammatory signals. Int J Obesity and related metabolic disorders: J Int Assoc Stud Obesity. 2003;27(Suppl 3):S25–S28.
    1. Safar ME, Czernichow S, Blacher J. Obesity, arterial stiffness, and cardiovascular risk. J Am Soc Nephrol: JASN. 2006;17:S109–S111. doi: 10.1681/ASN.2005121321.
    1. Hamburg NM, Palmisano J, Larson MG, Sullivan LM, Lehman BT, Vasan RS, Levy D, Mitchell GF, Vita JA, Benjamin EJ. Relation of brachial and digital measures of vascular function in the community: the Framingham heart study. Hypertension. 2011;57:390–396. doi: 10.1161/HYPERTENSIONAHA.110.160812.
    1. Tounian P, Aggoun Y, Dubern B, Varille V, Guy-Grand B, Sidi D, Girardet JP, Bonnet D. Presence of increased stiffness of the common carotid artery and endothelial dysfunction in severely obese children: a prospective study. Lancet. 2001;358:1400–1404. doi: 10.1016/S0140-6736(01)06525-4.
    1. Zhu W, Huang X, He J, Li M, Neubauer H. Arterial intima-media thickening and endothelial dysfunction in obese Chinese children. Eur J Pediatr. 2005;164:337–344. doi: 10.1007/s00431-005-1642-y.
    1. Watts K, Beye P, Siafarikas A, O'Driscoll G, Jones TW, Davis EA, Green DJ. Effects of exercise training on vascular function in obese children. J Pediatr. 2004;144:620–625. doi: 10.1016/j.jpeds.2004.02.027.
    1. Patry-Parisien J, Shields M, Bryan S. Comparison of waist circumference using the world health organization and national institutes of health protocols. Health reports/Statistics Canada, Canadian Centre for Health Information = Rapports sur la sante/Statistique Canada, Centre canadien d'information sur la sante. 2012;23:53–60.
    1. Turner M, Burns SM, Knight L, Ward K, Garo A, Morris T, Hooper E, Conaway M. Weight management practices among heart and vascular health care providers in an ambulatory setting. Medsurg Nurs. 2012;21:222–232.
    1. Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves JW, Hill MN, Jones DH, Kurtz T, Sheps SG, Roccella EJ. et al.Recommendations for blood pressure measurement in humans: an AHA scientific statement from the council on high blood pressure research professional and public education subcommittee. J Clin Hypertens. 2005;7:102–109. doi: 10.1111/j.1524-6175.2005.04377.x.
    1. American Diabetes A. Diagnosis and classification of diabetes mellitus. Diabetes care. 2010;33(Suppl 1):S62–S69.
    1. Katsuki A, Sumida Y, Gabazza EC, Murashima S, Furuta M, Araki-Sasaki R, Hori Y, Yano Y, Adachi Y. Homeostasis model assessment is a reliable indicator of insulin resistance during follow-up of patients with type 2 diabetes. Diabetes care. 2001;24:362–365. doi: 10.2337/diacare.24.2.362.
    1. Kuvin JT, Mammen A, Mooney P, Alsheikh-Ali AA, Karas RH. Assessment of peripheral vascular endothelial function in the ambulatory setting. Vasc Med. 2007;12:13–16. doi: 10.1177/1358863X06076227.
    1. Bonetti PO, Pumper GM, Higano ST, Holmes DR Jr, Kuvin JT, Lerman A. Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. J Am Coll Cardiol. 2004;44:2137–2141. doi: 10.1016/j.jacc.2004.08.062.
    1. Matsuzawa Y, Sugiyama S, Sugamura K, Nozaki T, Ohba K, Konishi M, Matsubara J, Sumida H, Kaikita K, Kojima S. et al.Digital assessment of endothelial function and ischemic heart disease in women. J Am Coll Cardiol. 2010;55:1688–1696. doi: 10.1016/j.jacc.2009.10.073.
    1. Mahmud FH, Hill DJ, Cuerden MS, Clarson CL. Impaired vascular function in obese adolescents with insulin resistance. J Pediatr. 2009;155:678–682. doi: 10.1016/j.jpeds.2009.04.060.
    1. Chiavaroli V, Giannini C, De Marco S, Chiarelli F, Mohn A. Unbalanced oxidant-antioxidant status and its effects in pediatric diseases. Redox Rep: Commun Free Radical Res. 2011;16:101–107. doi: 10.1179/174329211X13049558293551.
    1. Reinehr T, de Sousa G, Toschke AM, Andler W. Long-term follow-up of cardiovascular disease risk factors in children after an obesity intervention. Am J Clin Nutr. 2006;84:490–496.
    1. Iannuzzi A, Licenziati MR, Acampora C, Renis M, Agrusta M, Romano L, Valerio G, Panico S, Trevisan M. Carotid artery stiffness in obese children with the metabolic syndrome. Am J Cardiol. 2006;97:528–531. doi: 10.1016/j.amjcard.2005.08.072.
    1. Gunnell DJ, Frankel SJ, Nanchahal K, Peters TJ, Davey Smith G. Childhood obesity and adult cardiovascular mortality: a 57-y follow-up study based on the Boyd Orr cohort. Am J Clin Nutr. 1998;67:1111–1118.
    1. Must A, Jacques PF, Dallal GE, Bajema CJ, Dietz WH. Long-term morbidity and mortality of overweight adolescents. A follow-up of the Harvard growth study of 1922 to 1935. New Engl J Med. 1992;327:1350–1355. doi: 10.1056/NEJM199211053271904.
    1. King GL, Wakasaki H. Theoretical mechanisms by which hyperglycemia and insulin resistance could cause cardiovascular diseases in diabetes. Diabetes care. 1999;22(Suppl 3):C31–C37.
    1. Cusi K, Maezono K, Osman A, Pendergrass M, Patti ME, Pratipanawatr T, DeFronzo RA, Kahn CR, Mandarino LJ. Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle. J Clin Invest. 2000;105:311–320. doi: 10.1172/JCI7535.
    1. Lowe GD, Pepys MB. C-reactive protein and cardiovascular disease: weighing the evidence. Curr Atheroscler Rep. 2006;8:421–428. doi: 10.1007/s11883-006-0040-x.
    1. Maury E, Brichard SM. Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol. 2010;314:1–16. doi: 10.1016/j.mce.2009.07.031.
    1. Caballero AE, Bousquet-Santos K, Robles-Osorio L, Montagnani V, Soodini G, Porramatikul S, Hamdy O, Nobrega AC, Horton ES. Overweight Latino children and adolescents have marked endothelial dysfunction and subclinical vascular inflammation in association with excess body fat and insulin resistance. Diabetes care. 2008;31:576–582.
    1. Nathan DM, Meigs J, Singer DE. The epidemiology of cardiovascular disease in type 2 diabetes mellitus: how sweet it is … or is it? Lancet. 1997;350(Suppl 1):SI4–SI9.
    1. Kawano H, Motoyama T, Hirashima O, Hirai N, Miyao Y, Sakamoto T, Kugiyama K, Ogawa H, Yasue H. Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. J Am Coll Cardiol. 1999;34:146–154. doi: 10.1016/S0735-1097(99)00168-0.
    1. Wright E Jr, Scism-Bacon JL, Glass LC. Oxidative stress in type 2 diabetes: the role of fasting and postprandial glycaemia. Int J Clin Pract. 2006;60:308–314. doi: 10.1111/j.1368-5031.2006.00825.x.
    1. Montagnana M, Salvagno GL, Lippi G. Circadian variation within hemostasis: an underrecognized link between biology and disease? Semin Thromb Hemost. 2009;35:23–33. doi: 10.1055/s-0029-1214145.

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