Abstract
Background:
Insulin resistance and endothelial dysfunction share a reciprocal relationship that links the metabolic and cardiovascular sequelae of obesity. We characterized the brachial artery reactivity testing (BART) and carotid artery-intima media thickness (CIMT) in adolescents categorized as obese insulin resistant (OIR) and obese not insulin resistant (ONIR). Lipoprotein particle (p) analysis and inflammatory cytokines in OIR and ONIR groups were also analyzed.
Methods:
Obese adolescents (n=40; mean body mass index [BMI] 35.6) were categorized as ONIR and OIR based on their homeostatic model assessment of insulin resistance (HOMA-IR) calculation (≤or> than 3.4). Ultrasound measured conduit arterial function BART, microvascular function (post-ischemic hyperemia) and conduit artery structure CIMT.
Results:
BART did not differ according to IR status (mean±SD: 7.0±4.3% vs. 5.9±3.4% in ONIR and OIR, respectively, p=0.3, but post-ischemic hyperemia was significantly greater in the ONIR group (4.5±2.2 vs. 3.5±3, p=0.04). Atherogenic lipoprotein particles; large VLDL particles and small LDL particles were higher in the OIR compared to ONIR group.
Conclusions:
OIR adolescents demonstrate an inflamed atherogenic milieu compared to the ONIR adolescents. Microvascular function, but not conduit vessel structure or function, was impaired in association with IR.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: Supported in part by the NYU CTSA grant UL1 TR000038 from the National Center for Advancing Translational Sciences, National Institutes of Health. Office of Collaborative Science. Human Specimen Resource Center (HSRC): Director Dr Rachel Brody MD, PhD and Debra Morrison PhD. Irina Dektiarev: Ultrasound technologist; Department of Medicine. Eleanor De Candia and nursing at Clinical Translational Science Institute. Linda Rolnitsky MS, NYU-HHC Clinical Translational Science Institute (CTSI) Study Design, Biostatistics and Clinical Research Ethics Program.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Muniyappa R, Iantorno M, Quon MJ. An integrated view of insulin resistance and endothelial dysfunction. Endocrinol Metab Clin North Am 2008;37:685–711, ix–x.10.1016/j.ecl.2008.06.001Search in Google Scholar PubMed PubMed Central
2. Muniyappa R, Quon MJ. Insulin action and insulin resistance in vascular endothelium. Curr Opin Clin Nutr Metab Care 2007;10:523–30.10.1097/MCO.0b013e32819f8ecdSearch in Google Scholar PubMed
3. Kubota T, Kubota N, Kumagai H, Yamaguchi S, Kozono H, et al. Impaired insulin signaling in endothelial cells reduces insulin-induced glucose uptake by skeletal muscle. Cell Metab 2011;13:294–307.10.1016/j.cmet.2011.01.018Search in Google Scholar PubMed
4. Johansson GS, Arnqvist HJ. Insulin and IGF-I action on insulin receptors, IGF-I receptors, and hybrid insulin/IGF-I receptors in vascular smooth muscle cells. Am J Physiol Endocrinol Metab 2006;291:E1124–30.10.1152/ajpendo.00565.2005Search in Google Scholar PubMed
5. Villena JA, Roy S, Sarkadi-Nagy E, Kim KH, Sul HS. Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis. J Biol Chem 2004;279:47066–75.10.1074/jbc.M403855200Search in Google Scholar PubMed
6. Foley JE. Rationale and application of fatty acid oxidation inhibitors in treatment of diabetes mellitus. Diabetes Care 1992;15:773–84.10.2337/diacare.15.6.773Search in Google Scholar PubMed
7. Garvey WT, Kwon S, Zheng D, Shaughnessy S, Wallace P, et al. Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance. Diabetes 2003;52:453–62.10.2337/diabetes.52.2.453Search in Google Scholar PubMed
8. Aggoun Y, Farpour-Lambert N, Marchand L, Golay E, Maggio AB, et al. Impaired endothelial and smooth muscle functions and arterial stiffness appear before puberty in obese children and are associated with elevated ambulatory blood pressure. Eur Heart J 2008;29:792.10.1093/eurheartj/ehm633Search in Google Scholar PubMed
9. National high blood pressure education program working group on high blood pressure in children and adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 2004;114:555–74.10.1542/peds.114.S2.555Search in Google Scholar
10. Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 1976;58:259–63.10.1542/peds.58.2.259Search in Google Scholar
11. Long MT, Wang N, Larson MG, Mitchell GF, Palmisano J, et al. Nonalcoholic fatty liver disease and vascular function: cross-sectional analysis in the Framingham heart study. Arterioscler Thromb Vasc Biol 2015;35:1284–91.10.1161/ATVBAHA.114.305200Search in Google Scholar
12. Neovius M, Linne Y, Rossner S. BMI, waist-circumference and waist-hip-ratio as diagnostic tests for fatness in adolescents. Int J Obes 2005;29:163–9.10.1038/sj.ijo.0802867Search in Google Scholar
13. Organiztion WH. Waist circumference and waist–hip ratio. Report of a WHO expert consultation, Geneva, 8–11 December 2008. 2000Search in Google Scholar
14. Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM, et al. 2000 CDC Growth Charts for the United States: methods and development. Vital and health statisticsSeries 11, Data from the national health survey 2002;246:1–190.Search in Google Scholar
15. Harris RA, Nishiyama SK, Wray DW, Richardson RS. Ultrasound assessment of flow-mediated dilation. Hypertension 2010;55:1075–85.10.1161/HYPERTENSIONAHA.110.150821Search in Google Scholar
16. Stein JH, Korcarz CE, Hurst RT, Lonn E, Kendall CB, et al. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the American Society of Echocardiography Carotid Intima-Media Thickness Task Force. Endorsed by the Society for Vascular Medicine. J Am Soc Echocardiography 2008;21:93–111; quiz 189–190.10.1016/j.echo.2007.11.011Search in Google Scholar
17. Wendelhag I, Liang Q, Gustavsson T, Wikstrand J. A new automated computerized analyzing system simplifies readings and reduces the variability in ultrasound measurement of intima-media thickness. Stroke 1997;28:2195–200.10.1161/01.STR.28.11.2195Search in Google Scholar
18. Jelani QU, Norcliffe-Kaufmann L, Kaufmann H, Katz SD. Vascular endothelial function and blood pressure regulation in afferent autonomic failure. Am J Hypertens 2015;28:166–72.10.1093/ajh/hpu144Search in Google Scholar
19. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992;340:1111–5.10.1016/0140-6736(92)93147-FSearch in Google Scholar
20. Liang YL, Teede H, Kotsopoulos D, Shiel L, Cameron JD, et al. Non-invasive measurements of arterial structure and function: repeatability, interrelationships and trial sample size. Clin Sci (Lond) 1998;95:669–79.10.1042/cs0950669Search in Google Scholar PubMed
21. de Simone G, Roman MJ, Alderman MH, Galderisi M, de Divitiis O, et al. Is high pulse pressure a marker of preclinical cardiovascular disease? Hypertension 2005;45:575–9.10.1161/01.HYP.0000158268.95012.08Search in Google Scholar PubMed
22. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–9.10.1007/BF00280883Search in Google Scholar PubMed
23. Levy-Marchal C, Arslanian S, Cutfield W, Sinaiko A, Druet C, et al. Insulin resistance in children: consensus, perspective, and future directions. J Clin Endocrinol Metab 2010;95:5189–98.10.1210/jc.2010-1047Search in Google Scholar
24. van der Aa MP, Fazeli Farsani S, Knibbe CA, de Boer A, van der Vorst MM. Population-based studies on the epidemiology of insulin resistance in children. J Diabetes Res 2015;2015:362375.10.1155/2015/362375Search in Google Scholar
25. Brar PC, Mengwall L, Franklin BH, Fierman AH. Screening obese children and adolescents for prediabetes and/or type 2 diabetes in pediatric practices: a validation study. Clin Pediatr (Phila) 2014;53:771–6.10.1177/0009922814528571Search in Google Scholar
26. Tounian P, Aggoun Y, Dubern B, Varille V, Guy-Grand B, et al. Presence of increased stiffness of the common carotid artery and endothelial dysfunction in severely obese children: a prospective study. Lancet 2001;358:1400–4.10.1016/S0140-6736(01)06525-4Search in Google Scholar
27. Meyer A, Kundt G, Steiner M, Schuff-Werner P, Kienast W. Impaired flow-mediated vasodilation, carotid artery intima-media thickening, and elevated endothelial plasma markers in obese children: the impact of cardiovascular risk factors. Pediatrics 2006;117:1560.10.1542/peds.2005-2140Search in Google Scholar PubMed
28. Sass C, Herbeth B, Chapet O, Siest G, Visvikis S, et al. Intima-media thickness and diameter of carotid and femoral arteries in children, adolescents and adults from the Stanislas cohort: effect of age, sex, anthropometry and blood pressure. J Hypertens 1998;16:1593–602.10.1097/00004872-199816110-00005Search in Google Scholar PubMed
29. Newbern D, Gumus Balikcioglu P, Balikcioglu M, Bain J, Muehlbauer M, et al. Sex differences in biomarkers associated with insulin resistance in obese adolescents: metabolomic profiling and principal components analysis. J Clin Endocrinol Metab 2014;99:4730–9.10.1210/jc.2014-2080Search in Google Scholar PubMed PubMed Central
30. Miniello VL, Faienza MF, Scicchitano P, Cortese F, Gesualdo M, et al. Insulin resistance and endothelial function in children and adolescents. Int J Cardiol 2014;174:343–7.10.1016/j.ijcard.2014.04.115Search in Google Scholar PubMed
31. Magge SN, Stettler N, Koren D, Levitt Katz LE, Gallagher PR, et al. Adiponectin is associated with favorable lipoprotein profile, independent of BMI and insulin resistance, in adolescents. J Clin Endocrinol Metab 2011;96:1549–54.10.1210/jc.2010-2364Search in Google Scholar PubMed PubMed Central
32. Group TS. Lipid and inflammatory cardiovascular risk worsens over 3 years in youth with type 2 diabetes: the TODAY clinical trial. Diabetes Care 2013;36:1758–64.10.2337/dc12-2388Search in Google Scholar PubMed PubMed Central
33. Shah AS, Gao Z, Urbina EM, Kimball TR, Dolan LM. Prediabetes: the effects on arterial thickness and stiffness in obese youth. J Clin Endocrinol Metab 2014;99:1037–43.10.1210/jc.2013-3519Search in Google Scholar PubMed PubMed Central
34. Clerk LH, Vincent MA, Jahn LA, Liu Z, Lindner JR, et al. Obesity blunts insulin-mediated microvascular recruitment in human forearm muscle. Diabetes 2006;55:1436–42.10.2337/db05-1373Search in Google Scholar PubMed
35. Hayoz D, Weber R, Rutschmann B, Darioli R, Burnier M, et al. Postischemic blood flow response in hypercholesterolemic patients. Hypertension 1995;26:497–502.10.1161/01.HYP.26.3.497Search in Google Scholar PubMed
36. Montero D, Walther G, Perez-Martin A, Mercier CS, Gayrard S, et al. Effects of a lifestyle program on vascular reactivity in macro- and microcirculation in severely obese adolescents. J Clin Endocrinol Metab 2014;99:1019–26.10.1210/jc.2013-3394Search in Google Scholar PubMed
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