Oxidative stress, inflammation, endothelial dysfunction and incidence of type 2 diabetes

Andrew O Odegaard, David R Jacobs Jr, Otto A Sanchez, David C Goff Jr, Alexander P Reiner, Myron D Gross, Andrew O Odegaard, David R Jacobs Jr, Otto A Sanchez, David C Goff Jr, Alexander P Reiner, Myron D Gross

Abstract

Background: Oxidative stress, inflammation and endothelial dysfunction are interrelated factors in the etiology of cardiovascular disease, but their linkage to type 2 diabetes is less clear. We examined the association of these biomarkers with incident type 2 diabetes (T2D).

Methods: Analysis of 2339 participants in the community-based coronary artery risk development in young adults (CARDIA) study. Participants (age 40.1 ± 3.6 years, 44 % Black, 58 % women) were free of diabetes, and were followed 10 years. Cox regression was used to estimate hazard ratios (HRs) for incident T2D adjusting for the other biomarkers under study, demographic and lifestyle measures, dietary biomarkers, BMI (kg/m(2)) and metabolic syndrome components.

Results: F2-isoprostanes and oxidized LDL (oxidative stress) were positively associated with incident T2D, but the associations were attenuated by adjustment for BMI. C-reactive protein was positively associated with T2D even with full adjustment: HR (95 % CI) = 2.21 (1.26-3.88) for quartile 4 (Q4) v. quartile 1 (Q1). The HR (95 % CI) for T2D for biomarkers of endothelial dysfunction ICAM-1 and E-selectin for Q4 v. Q1 were 1.64 (0.96-2.81) and 1.68 (1.04-2.71) respectively, with full adjustment. Including these two markers in a common risk score incorporating BMI and clinical measures improved the prediction probability of T2D: relative risk for the average person classified up compared to the average person classified down: 1.09, (1.06-1.13), P < 0.0001.

Conclusions: Biomarkers of inflammation and endothelial dysfunction were positively associated with incident T2D. ICAM-1 and E-selectin add to the prediction of T2D beyond a common risk score.

Keywords: Endothelial dysfunction; Incidence; Inflammation; Type 2 diabetes; Young adults; oxidative stress.

Figures

Fig. 1
Fig. 1
Results from the Improvement in Prediction Probability analysis adding E-selectin and ICAM-1 to a base risk score for T2D: The base risk score was ranked into quartiles (Q1–Q4). For each BP quartile, observed T2D incidence was plotted (middle bar in bold) as a reference point without reclassification. For each participant k, reclassification probability < 0 is labeled “Down”. Reclassification probability ≥0 is labeled “Up”. Participants reclassified “down” and “up” are plotted to the left and right of overall base risk within each BP quartile. The numbers on the X axis of the graph represent the N reclassified down or up and the overall N of the quartile (N “down” + N “up” = N “base”). The numbers (in italics) above each bar represent the estimated probability of incident T2D in participants reclassified down and up. When the probability of incident T2D for reclassification “up” is greater than the probability of incident T2D for reclassification “down”, there is improvement in prediction probability. A formal statistical test used Poisson regression of incident T2D dependent variable) on AP–BP, adjusting for BP. The Relative Risk for the midpoint of those reclassified “up” (75th percentile of AP–BP) vs the midpoint of reclassification “down” (75th percentile of AP–BP) was 1.09, 95 % Confidence interval (1.06–1.13), P < 0.0001

References

    1. Lahera V, Goicoechea M, de Vinuesa SG, Miana M, de las Heras N, Cachofeiro V, Luño J. Endothelial dysfunction, oxidative stress and inflammation in atherosclerosis: beneficial effects of statins. Curr Med Chem. 2007;14:243–248. doi: 10.2174/092986707779313381.
    1. Tabit CE, Chung WB, Hamburg NM, Vita JA. Endothelial dysfunction in diabetes mellitus: molecular mechanisms and clinical implications. Rev Endocr Metab Disord. 2010;11:61–74. doi: 10.1007/s11154-010-9134-4.
    1. Hess K, Marx N, Lehrke M. Cardiovascular disease and diabetes: the vulnerable patient. Eur Heart J Suppl. 2012;14:B4–B13. doi: 10.1093/eurheartj/sus002.
    1. Hu FB, Stampfer MJ. Is type 2 diabetes mellitus a vascular condition? Arterioscler Thromb Vasc Biol. 2003;23:1715–1716. doi: 10.1161/01.ATV.0000094360.38911.71.
    1. Ceriello A, Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol. 2004;24:816–823. doi: 10.1161/01.ATV.0000122852.22604.78.
    1. Shah S, Iqbal M, Karam J, Salifu M, McFarlane SI. Oxidative stress, glucose metabolism, and the prevention of type 2 diabetes: pathophysiological insights. Antioxid Redox Signal. 2007;9:911–929. doi: 10.1089/ars.2007.1629.
    1. Park K, Gross M, Lee DH, Holvoet P, Himes JH, Shikany JM, Jacobs DR., Jr Oxidative stress and insulin resistance: the coronary artery risk development in young adults study. Diabetes Care. 2009;32:1302–1307. doi: 10.2337/dc09-0259.
    1. Holvoet P, Lee DH, Steffes M, Gross M, Jacobs DR., Jr Association between circulating oxidized low-density lipoprotein and incidence of the metabolic syndrome. JAMA. 2008;299:2287–2293. doi: 10.1001/jama.299.19.2287.
    1. Il’yasova D, Spasojevic I, Base K, Zhang H, Wang F, Young SP, Millington DS, D’Agostino RB, Jr, Wagenknecht LE. Urinary F2-isoprostanes as a biomarker of reduced risk of type 2 diabetes. Diabetes Care. 2012;35:173–174. doi: 10.2337/dc11-1502.
    1. Meigs JB, Larson MG, Fox CS, Keaney JF, Jr, Vasan RS, Benjamin EJ. Association of oxidative stress, insulin resistance, and diabetes risk phenotypes: the Framingham Offspring Study. Diabetes Care. 2007;30:2929–2935.
    1. Wang X, Bao W, Liu J, Ouyang YY, Wang D, Rong S, Xiao X, Shan ZL, Zhang Y, Yao P, Liu LG. Inflammatory markers and risk of type 2 diabetes: a systematic review and meta-analysis. Diabetes Care. 2013;36:166–175. doi: 10.2337/dc12-0702.
    1. Brunner EJ, Kivimäki M, Witte DR, Lawlor DA, Davey Smith G, Cooper JA, Miller M, Lowe GD, Rumley A, Casas JP, Shah T, Humphries SE, Hingorani AD, Marmot MG, Timpson NJ, Kumari M. Inflammation, insulin resistance, and diabetes–Mendelian randomization using CRP haplotypes points upstream. PloS Med. 2008;5:e155. doi: 10.1371/journal.pmed.0050155.
    1. Park K, Steffes M, Lee DH, Himes JH, Jacobs DR., Jr Association of inflammation with worsening HOMA-insulin resistance. Diabetologia. 2009;52:2337–2344. doi: 10.1007/s00125-009-1486-5.
    1. Meigs JB, Hu FB, Rifai N, Manson JE. Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA. 2004;291:1978–1986. doi: 10.1001/jama.291.16.1978.
    1. Thorand B, Baumert J, Chambless L, Meisinger C, Kolb H, Döring A, Löwel H, Koenig W, MONICA/KORA Study Group Elevated markers of endothelial dysfunction predict type 2 diabetes mellitus in middle-aged men and women from the general population. Arterioscler Thromb Vasc Biol. 2006;26:398–405. doi: 10.1161/01.ATV.0000198392.05307.aa.
    1. Song Y, Manson JE, Tinker L, Rifai N, Cook NR, Hu FB, Hotamisligil GS, Ridker PM, Rodriguez BL, Margolis KL, Oberman A, Liu S. Circulating levels of endothelial adhesion molecules and risk of diabetes in an ethnically diverse cohort of women. Diabetes. 2007;56:1898–1904. doi: 10.2337/db07-0250.
    1. Stranges S, Rafalson LB, Dmochowski J, Rejman K, Tracy RP, Trevisan M, Donahue RP. Additional contribution of emerging risk factors to the prediction of the risk of type 2 diabetes: evidence from the Western New York Study. Obesity. 2008;16:1370–1376. doi: 10.1038/oby.2008.59.
    1. Hoogeveen RC, Ballantyne CM, Bang H, Heiss G, Duncan BB, Folsom AR, Pankow JS. Circulating oxidised low-density lipoprotein and intercellular adhesion molecule-1 and risk of type 2 diabetes mellitus: the Atherosclerosis Risk in Communities Study. Diabetologia. 2007;50:36–42. doi: 10.1007/s00125-006-0533-8.
    1. Friedman GD, Cutter GR, Donahue RP, Hughes GH, Hulley SB, Jacobs DR, Jr, Liu K, Savage PJ. CARDIA: study design, recruitment, and some characteristics of the examined subjects. J Clin Epidemiol. 1988;41:1105–1116. doi: 10.1016/0895-4356(88)90080-7.
    1. Bild DE, Jacobs DR, Liu K, Williams OD, Hilner JE, Perkins LL, Marcovina SM, Hulley SB. Seven-year trends in plasma low-density-lipoprotein cholesterol in young adults: the CARDIA Study. Ann Epidemiol. 1996;6:235–245. doi: 10.1016/1047-2797(96)00005-1.
    1. Smith DE, Lewis CE, Caveny JL, Perkins LL, Burke GL, Bild DE. Longitudinal changes in adiposity associated with pregnancy. The CARDIA Study. Coronary Artery Risk Development in Young Adults Study. JAMA. 1994;271:1747–1751. doi: 10.1001/jama.1994.03510460039030.
    1. Jacobs DRJ, Hahn LP, Haskell WL, Pirie P, Sidney S. Validity and reliability of a short physical activity history: CARDIA and the Minnesota Heart Health Program. J Cardiopulm Rehabil. 1989;9:448–459. doi: 10.1097/00008483-198911000-00003.
    1. Gross M, Steffes M, Jacobs DR, Jr, Yu X, Lewis L, Lewis CE, Loria CM. Plasma F2-isoprostanes and coronary artery calcification: the CARDIA Study. Clin Chem. 2005;51:125–131. doi: 10.1373/clinchem.2004.037630.
    1. Hozawa A, Jacobs DR, Jr, Steffes MW, Gross MD, Steffen LM, Lee DH. Associations of serum carotenoid concentrations with the development of diabetes and with insulin concentration: interaction with smoking: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Am J Epidemiol. 2006;163:929–937. doi: 10.1093/aje/kwj136.
    1. Gross MD, Bielinski SJ, Suarez-Lopez JR, Reiner AP, Bailey K, Thyagarajan B, Carr JJ, Duprez DA, Jacobs DR., Jr Circulating soluble intercellular adhesion molecule 1 and subclinical atherosclerosis: the Coronary Artery Risk Development in Young Adults Study. Clin Chem. 2012;58:411–420. doi: 10.1373/clinchem.2011.168559.
    1. Bibbins-Domingo K, Pletcher MJ, Lin F, Vittinghoff E, Gardin JM, Arynchyn A, Lewis CE, Williams OD, Hulley SB. Racial differences in incident heart failure among young adults. N Engl J Med. 2009;360:1179–1190. doi: 10.1056/NEJMoa0807265.
    1. Hozawa A, Jacobs DR, Jr, Steffes MW, Gross MD, Steffen LM, Lee D. Relationships of circulating carotenoid concentrations with several markers of inflammation, oxidative stress, and endothelial dysfunction: the Coronary Artery Risk Development in Young Adults (CARDIA)/Young Adult Longitudinal Trends in Antioxidants (YALTA) study. Clin Chem. 2007;53:447–455. doi: 10.1373/clinchem.2006.074930.
    1. Andersen LF, Jacobs DR, Jr, Gross MD, Schreiner PJ, Dale Williams O, Lee DH. Longitudinal associations between body mass index and serum carotenoids: the CARDIA study. Br J Nutr. 2006;95:358–365. doi: 10.1079/BJN20051638.
    1. Hozawa A, Jacobs DR, Jr, Steffes MW, Gross MD, Steffen LM, Lee DH. Circulating carotenoid concentrations and incident hypertension: the Coronary Artery Risk Development in Young Adults (CARDIA) study. J Hypertens. 2009;27:237–242. doi: 10.1097/HJH.0b013e32832258c9.
    1. Hollman PC, Cassidy A, Comte B, Heinonen M, Richelle M, Richling E, Serafini M, Scalbert A, Sies H, Vidry S. The biological relevance of direct antioxidant effects of polyphenols for cardiovascular health in humans is not established. J Nutr. 2011;141:989S–1009S. doi: 10.3945/jn.110.131490.
    1. Kelly AS, Steinberger J, Jacobs DR, Hong CP, Moran A, Sinaiko AR. Predicting cardiovascular risk in young adulthood from the metabolic syndrome, its component risk factors, and a cluster score in childhood. Int J Pediatr Obes. 2011;6:e283–e289. doi: 10.3109/17477166.2010.528765.
    1. Hope SA, Meredith IT. Cellular adhesion molecules and cardiovascular disease. Part I. Their expression and role in atherogenesis. Intern Med J. 2003;33:380–386. doi: 10.1046/j.1444-0903.2003.00378.x.
    1. Meigs JBSP, Sullivan LM, McAteer JB, Fox CS, Dupuis J, Manning AK, Florez JC, Wilson PW, D’Agostino RB, Sr, Cupples LA. Genotype score in addition to common risk factors for prediction of type 2 diabetes. N Engl J Med. 2008;359:2208–2219. doi: 10.1056/NEJMoa0804742.
    1. Pencina MJ, D’Agostino RB, Sr, D’Agostino RB, Jr, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27:207–212. doi: 10.1002/sim.3106.
    1. Duprez DA, Jacobs DR, Jr, Lutsey PL, Bluemke DA, Brumback LC, Polak JF, Peralta CA, Greenland P, Kronmal RA. Association of small artery elasticity with incident cardiovascular disease in older adults: the multi-ethnic study of atherosclerosis. Am J Epidemiol. 2011;174:528–536. doi: 10.1093/aje/kwr120.
    1. Jacobs DRJ, Brumback LC. Reply—Re: “Association of small artery elasticity with incident cardiovascular disease in older adults: the Multi-ethnic Study of Atherosclerosis”. Am J Epidemiol. 2012;175:156–158. doi: 10.1093/aje/kwr486.
    1. Kerr KF, Wang Z, Janes H, McClelland RL, Psaty BM, Pepe MS. Net reclassification indices for evaluating risk prediction instruments: a critical review. Epidemiology. 2014;25:114–121. doi: 10.1097/EDE.0000000000000018.
    1. Dallmeier D, Larson MG, Wang N, Fontes JD, Benjamin EJ, Fox CS. Addition of inflammatory biomarkers did not improve diabetes prediction in the community: the framingham heart study. J Am Heart Assoc. 2012;1:e000869. doi: 10.1161/JAHA.112.000869.
    1. Halliwell B, Lee CY. Using isoprostanes as biomarkers of oxidative stress: some rarely considered issues. Antioxid Redox Signal. 2010;13:145–156. doi: 10.1089/ars.2009.2934.
    1. Halliwell B, Whiteman M. Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Br J Pharmacol. 2004;142:231–255. doi: 10.1038/sj.bjp.0705776.
    1. Meigs JB, O’donnell CJ, Tofler GH, Benjamin EJ, Fox CS, Lipinska I, Nathan DM, Sullivan LM, D’Agostino RB, Wilson PW. Hemostatic markers of endothelial dysfunction and risk of incident type 2 diabetes: the Framingham Offspring Study. Diabetes. 2006;55:530–537. doi: 10.2337/diabetes.55.02.06.db05-1041.
    1. Rossi R, Cioni E, Nuzzo A, Origliani G, Modena MG. Endothelial-dependent vasodilation and incidence of type 2 diabetes in a population of healthy postmenopausal women. Diabetes Care. 2005;28:702–707. doi: 10.2337/diacare.28.3.702.
    1. Duncan BB, Schmidt MI, Offenbacher S, Wu KK, Savage PJ, Heiss G. Factor VIII and other hemostasis variables are related to incident diabetes in adults. The Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care. 1999;22:767. doi: 10.2337/diacare.22.5.767.
    1. Wannamethee SG, Sattar N, Rumley A, Whincup PH, Lennon L, Lowe GD. Tissue plasminogen activator, von Willebrand factor, and risk of type 2 diabetes in older men. Diabetes Care. 2008;31:995–1000. doi: 10.2337/dc07-1569.
    1. Raynor LA, Pankow JS, Duncan BB, Schmidt MI, Hoogeveen RC, Pereira MA, Young JH, Ballantyne CM. Novel risk factors and the prediction of type 2 diabetes in the Atherosclerosis Risk in Communities (ARIC) study. Diabetes Care. 2013;36:70–76. doi: 10.2337/dc12-0609.
    1. Chao C, Song Y, Cook N, Tseng CH, Manson JE, Eaton C, Margolis KL, Rodriguez B, Phillips LS, Tinker LF, Liu S. The lack of utility of circulating biomarkers of inflammation and endothelial dysfunction for type 2 diabetes risk prediction among postmenopausal women: the Women’s Health Initiative Observational Study. Arch Intern Med. 2010;170:1557–1565. doi: 10.1001/archinternmed.2010.312.
    1. Mazière C, Morlière P, Santus R, Marcheux V, Louandre C, Conte MA, Mazière JC. Inhibition of insulin signaling by oxidized low density lipoprotein. Protective effect of the antioxidant Vitamin E. Atherosclerosis. 2004;175:23–30. doi: 10.1016/j.atherosclerosis.2004.02.006.
    1. Maddux BA, See W, Lawrence JC, Jr, Goldfine AL, Goldfine ID, Evans JL. Protection against oxidative stress-induced insulin resistance in rat L6 muscle cells by mircomolar concentrations of alpha-lipoic acid. Diabetes. 2001;50:404–410. doi: 10.2337/diabetes.50.2.404.
    1. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med. 1999;340:448–454. doi: 10.1056/NEJM199902113400607.
    1. Pinkney JH, Stehouwer CD, Coppack SW, Yudkin JS. Endothelial dysfunction: cause of the insulin resistance syndrome. Diabetes. 1997;46:s9–s13. doi: 10.2337/diab.46.2.S9.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する