Paradoxical Associations of Diabetes and Obesity with Abdominal Aortic Aneurysm

Lu Wang, MD, PhD, Xi Zhang, PhD, Yiqing Song, MD, ScD


Abdominal aortic aneurysm (AAA), defined as a localized dilatation of abdominal aorta, is a significant cause of morbidity and mortality in aging populations. AAA is a life-threatening disease mainly because of the high fatality rates associated with aneurysm rupture. Early detection of AAAs will provide patients an opportunity to receive medical therapy and undergo elective repair before aneurysm rupture. Historically, AAA is considered a macrovascular atherosclerotic disease. Classic risk factors of atherosclerosis, such as advanced age, male gender, smoking, hyperlipidemia, and hypertension, have been associated with an increased risk of AAA formation and expansion. However, more recent laboratory and epidemiologic studies have challenged this conventional theory and indicate that the etiology of AAA is distinct from atherosclerosis per se. This review focused on the evidence on the seemingly paradoxical inverse and positive associations of diabetes and obesity, respectively, with AAA. AAA progresses more slowly in diabetics and diabetic patients are less likely to have a ruptured AAA at the time of repair, suggesting that diabetes or its medications may protect against the development and improve the prognosis of AAA. Meanwhile, obesity has been implicated in the pathogenesis of both diabetes and atherosclerosis, for which the key mechanisms include insulin resistance and release of adipokines. Data on the associations between measures of obesity and AAA are inconsistent. Insights into the relation between diabetes, obesity and AAA will help identify high-risk subpopulations for AAA screening and optimize prevention strategy for individual patients.  An improved knowledge of the mechanisms underlying the link between diabetes, obesity and AAA also has important therapeutic implications.

 [N A J Med Sci. 2017;10(2):83-87.   DOI:  10.7156/najms.2017.1002083]



abdominal aortic aneurysm (AAA), diabetes, obesity

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Svensjo S, Bjorck M, Gurtelschmid M, et al. Low prevalence of abdominal aortic aneurysm among 65-year-old Swedish men indicates a change in the epidemiology of the disease. Circulation. 2011;124: 1118-1123.

McCarthy RJ, Shaw E, Whyman MR, et al. Recommendations for screening intervals for small aortic aneurysms. Br J Surg. 2003;90:821-826.

Pfeifer M, Begerow B, Minne HW, et al. Effects of a short-term vitamin D(3) and calcium supplementation on blood pressure and parathyroid hormone levels in elderly women. J Clin Endocrinol Metab. 2001;86:1633-1637.

Simoni G, Pastorino C, Perrone R, et al. Screening for abdominal aortic aneurysms and associated risk factors in a general population. Eur J Vasc Endovasc Surg. 1995;10:207-210.

Newman AB, Arnold AM, Burke GL, et al. Cardiovascular disease and mortality in older adults with small abdominal aortic aneurysms detected by ultrasonography: the cardiovascular health study. Ann Intern Med. 2001;134:182-190.

Le MT, Jamrozik K, Davis TM, et al. Negative association between infra-renal aortic diameter and glycaemia: the Health in Men Study. Eur J Vasc Endovasc Surg. 2007;33:599-604.

Scott RA, Bridgewater SG, Ashton HA. Randomized clinical trial of screening for abdominal aortic aneurysm in women. Br J Surg. 2002;89:283-285.

Bown MJ, Cooper NJ, Sutton AJ, et al. The post-operative mortality of ruptured abdominal aortic aneurysm repair. Eur J Vasc Endovasc Surg. 2004;27:65-74.

Acosta S, Ogren M, Bengtsson H, et al. Increasing incidence of ruptured abdominal aortic aneurysm: a population-based study. J Vasc Surg. 2006;44:237-243.

Darling RC, Messina CR, Brewster DC, et al. Autopsy study of unoperated abdominal aortic aneurysms. The case for early resection. Circulation. 1977;56:II161-II164.

Ornish D. Comparison of diets for weight loss and heart disease risk reduction. JAMA. 2005;293:1589-1590.

Sakalihasan N, Limet R, Defawe OD. Abdominal aortic aneurysm. Lancet. 2005;365:1577-1589.

Schermerhorn M. A 66-year-old man with an abdominal aortic aneurysm: review of screening and treatment. JAMA. 2009;302:2015-2022.

Lederle FA, Wilson SE, Johnson GR, et al. Immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med. 2002;346:1437-1444.

Lawrence PF, Gazak C, Bhirangi L, et al. The epidemiology of surgically repaired aneurysms in the United States. J Vasc Surg. 1999;30:632-640.

EVAR trial participants. Endovascular aneurysm repair versus open repair in patients with abdominal aortic aneurysm (EVAR trial 1): randomised controlled trial. Lancet. 2005;365:2179-2186.

Nordon IM, Hinchliffe RJ, Holt PJ,et al. Review of current theories for abdominal aortic aneurysm pathogenesis. Vascular. 2009;17:253-263.

Ramiro E, Franch A, Castellote C, et al. Effect of Theobroma cacao flavonoids on immune activation of a lymphoid cell line. Br J Nutr. 2005;93:859-866.

Reed D, Reed C, Stemmermann G, et al. Are aortic aneurysms caused by atherosclerosis? Circulation. 1992;85:205-211.

Wong DR, Willett WC, Rimm EB. Smoking, hypertension, alcohol consumption, and risk of abdominal aortic aneurysm in men. Am J Epidemiol. 2007;165:838-845.

Lederle FA, Larson JC, Margolis KL, et al. Abdominal aortic aneurysm events in the women's health initiative: cohort study. BMJ. 2008;337:a1724.

Lederle FA, Johnson GR, Wilson SE, et al. Prevalence and associations of abdominal aortic aneurysm detected through screening. Aneurysm Detection and Management (ADAM) Veterans Affairs Cooperative Study Group. Ann Intern Med. 1997;126:441-449.

Smith FC, Grimshaw GM, Paterson IS, et al. Ultrasonographic screening for abdominal aortic aneurysm in an urban community. Br J Surg. 1993;80:1406-1409.

Pleumeekers HJ, Hoes AW, van der Does E, et al. Aneurysms of the abdominal aorta in older adults. The Rotterdam Study. Am J Epidemiol. 1995;142:1291-1299.

Lederle FA, Johnson GR, Wilson SE, et al. The aneurysm detection and management study screening program: validation cohort and final results. Aneurysm Detection and Management Veterans Affairs Cooperative Study Investigators. Arch Intern Med. 2000;160:1425-1430.

Kanagasabay R, Gajraj H, Pointon L, et al. Co-morbidity in patients with abdominal aortic aneurysm. J Med Screen. 1996;3:208-210.

Kent KC, Zwolak RM, Egorova NN, et al. Analysis of risk factors for abdominal aortic aneurysm in a cohort of more than 3 million individuals. J Vasc Surg. 2010;52:539-548.

Tornwall ME, Virtamo J, Haukka JK, et al. Life-style factors and risk for abdominal aortic aneurysm in a cohort of Finnish male smokers. Epidemiology. 2001;12:94-100.

Rodin MB, Daviglus ML, Wong GC, et al. Middle age cardiovascular risk factors and abdominal aortic aneurysm in older age. Hypertension. 2003;42:61-68.

Iribarren C, Darbinian JA, Go AS, et al. Traditional and novel risk factors for clinically diagnosed abdominal aortic aneurysm: the Kaiser multiphasic health checkup cohort study. Ann Epidemiol. 2007;17:669-678.

Baumgartner I, Hirsch AT, Abola MT, et al. Cardiovascular risk profile and outcome of patients with abdominal aortic aneurysm in out-patients with atherothrombosis: data from the Reduction of Atherothrombosis for Continued Health (REACH) Registry. J Vasc Surg. 2008;48:808-814.

Blanchard JF, Armenian HK, Friesen PP. Risk factors for abdominal aortic aneurysm: results of a case-control study. Am J Epidemiol. 2000;151:575-583.

Shteinberg D, Halak M, Shapiro S, et al. Abdominal aortic aneurysm and aortic occlusive disease: a comparison of risk factors and inflammatory response. Eur J Vasc Endovasc Surg. 2000;20:462-465.

Strachan DP. Predictors of death from aortic aneurysm among middle-aged men: the Whitehall study. Br J Surg. 1991;78:401-404.

Forsdahl SH, Singh K, Solberg S, et al. Risk factors for abdominal aortic aneurysms: a 7-year prospective study: the Tromso Study, 1994-2001. Circulation. 2009;119:2202-2208.

Giacovelli JK, Egorova N, Nowygrod R, et al. Insurance status predicts access to care and outcomes of vascular disease. J Vasc Surg. 2008;48:905-911.

Brady AR, Thompson SG, Fowkes FG, et al. Abdominal aortic aneurysm expansion: risk factors and time intervals for surveillance. Circulation. 2004;110:16-21.

Vega de Ceniga M, Gomez R, Estallo L, et al. Growth rate and associated factors in small abdominal aortic aneurysms. Eur J Vasc Endovasc Surg. 2006;31:231-236.

Golledge J, Karan M, Moran CS, et al. Reduced expansion rate of abdominal aortic aneurysms in patients with diabetes may be related to aberrant monocyte-matrix interactions. Eur Heart J. 2008;29:665-672.

Ferguson CD, Clancy P, Bourke B, et al. Association of statin prescription with small abdominal aortic aneurysm progression. Am Heart J. 159:307-313.

Thompson A, Cooper JA, Fabricius M, et al. An analysis of drug modulation of abdominal aortic aneurysm growth through 25 years of surveillance. J Vasc Surg. 52:55-61 e2.

Sweeting MJ, Thompson SG, Brown LC, et al. Meta-analysis of individual patient data to examine factors affecting growth and rupture of small abdominal aortic aneurysms. Br J Surg. 2012;99:655-665.

Rensing KL, Twickler TB. Abdominal aorta aneurysm: an exceptional expression of atherosclerotic disease in type II diabetes. Eur Heart J. 2008;29:581-582.

Dua MM, Miyama N, Azuma J, et al. Hyperglycemia modulates plasminogen activator inhibitor-1 expression and aortic diameter in experimental aortic aneurysm disease. Surgery. 2010;148:429-435.

Dunn EJ, Ariens RA, Grant PJ. The influence of type 2 diabetes on fibrin structure and function. Diabetologia. 2005;48:1198-1206.

Houard X, Rouzet F, Touat Z, et al. Topology of the fibrinolytic system within the mural thrombus of human abdominal aortic aneurysms. J Pathol. 2007;212:20-28.

Shimizu K, Mitchell RN, Libby P. Inflammation and cellular immune responses in abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol. 2006;26:987-994.

Norman PE, Davis TM, Le MT, et al. Matrix biology of abdominal aortic aneurysms in diabetes: mechanisms underlying the negative association. Connect Tissue Res. 2007;48:125-131.

Vorp DA. Biomechanics of abdominal aortic aneurysm. J Biomech. 2007;40:1887-1902.

Mauer SM. Structural-functional correlations of diabetic nephropathy. Kidney Int. 1994;45:612-622.

Astrand H, Ryden-Ahlgren A, Sundkvist G, et al. Reduced aortic wall stress in diabetes mellitus. Eur J Vasc Endovasc Surg. 2007;33:592-598.

Schouten O, van Laanen JH, Boersma E, et al. Statins are associated with a reduced infrarenal abdominal aortic aneurysm growth. Eur J Vasc Endovasc Surg. 2006;32:21-26.

Hackam DG, Thiruchelvam D, Redelmeier DA. Angiotensin-converting enzyme inhibitors and aortic rupture: a population-based case-control study. Lancet. 2006;368:659-665.

Li L, Mamputu JC, Wiernsperger N, et al. Signaling pathways involved in human vascular smooth muscle cell proliferation and matrix metalloproteinase-2 expression induced by leptin: inhibitory effect of metformin. Diabetes. 2005;54:2227-2234.

Haffner SM, Greenberg AS, Weston WM, et al. Effect of rosiglitazone treatment on nontraditional markers of cardiovascular disease in patients with type 2 diabetes mellitus. Circulation. 2002;106:679-684.

Miyama N, Dua MM, Yeung JJ, et al. Hyperglycemia limits experimental aortic aneurysm progression. J Vasc Surg. 2010;52:975-983.

Flegal KM, Carroll MD, Kit BK, et al. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA. 2012;307:491-497.

Williams DE, Prevost AT, Whichelow MJ, et al. A cross-sectional study of dietary patterns with glucose intolerance and other features of the metabolic syndrome. Br J Nutr. 2000;83:257-266.

Golledge J, Clancy P, Jamrozik K, et al. Obesity, adipokines, and abdominal aortic aneurysm: Health in Men study. Circulation. 2007;116:2275-2279.

Cronin O, Walker PJ, Golledge J. The association of obesity with abdominal aortic aneurysm presence and growth. Atherosclerosis. 2012;226(2):321-327.

Allison MA, Kwan K, DiTomasso D, et al. The epidemiology of abdominal aortic diameter. J Vasc Surg. 2008;48:121-127.

Long A, Bui HT, Barbe C, et al. Prevalence of abdominal aortic aneurysm and large infrarenal aorta in patients with acute coronary syndrome and proven coronary stenosis: a prospective monocenter study. Ann Vasc Surg. 2010;24:602-608.

Stackelberg O, Bjorck M, Sadr-Azodi O, et al. Obesity and abdominal aortic aneurysm. Br J Surg. 2012; 100(3):360-366.

Lee AJ, Fowkes FG, Carson MN, et al. Smoking, atherosclerosis and risk of abdominal aortic aneurysm. Eur Heart J. 1997;18:671-676.

Police SB, Putnam K, Thatcher S, et al. Weight loss in obese C57BL/6 mice limits adventitial expansion of established angiotensin II-induced abdominal aortic aneurysms. Am J Physiol Heart Circ Physiol. 2010;298:H1932-1938.

Choke E, Cockerill G, Wilson WR, et al. A review of biological factors implicated in abdominal aortic aneurysm rupture. Eur J Vasc Endovasc Surg. 2005;30:227-244.

Ouchi N, Kihara S, Arita Y, et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation. 1999;100:2473-2476.

Shamsuzzaman AS, Winnicki M, Wolk R, et al. Independent association between plasma leptin and C-reactive protein in healthy humans. Circulation. 2004;109:2181-2185.

Pang SS, Le YY. Role of resistin in inflammation and inflammation-related diseases. Cell Mol Immunol. 2006;3:29-34.

Chatterjee TK, Stoll LL, Denning GM, et al. Proinflammatory phenotype of perivascular adipocytes: influence of high-fat feeding. Circ Res. 2009;104:541-549.

Eringa EC, Bakker W, Smulders YM, et al. Regulation of vascular function and insulin sensitivity by adipose tissue: focus on perivascular adipose tissue. Microcirculation. 2007;14:389-402.

Barandier C, Montani JP, Yang Z. Mature adipocytes and perivascular adipose tissue stimulate vascular smooth muscle cell proliferation: effects of aging and obesity. Am J Physiol Heart Circ Physiol. 2005;289: H1807-1813.

Henrichot E, Juge-Aubry CE, Pernin A, et al. Production of chemokines by perivascular adipose tissue: a role in the pathogenesis of atherosclerosis? Arterioscler Thromb Vasc Biol. 2005;25:2594-2599.

Police SB, Thatcher SE, Charnigo R, et al. Obesity promotes inflammation in periaortic adipose tissue and angiotensin II-induced abdominal aortic aneurysm formation. Arterioscler Thromb Vasc Biol. 2009;29:14 58-1464.

Wanhainen A, Bergqvist D, Boman K, et al. Risk factors associated with abdominal aortic aneurysm: a population-based study with historical and current data. J Vasc Surg. 2005;41:390-396.

Golledge J, Norman PE. Atherosclerosis and abdominal aortic aneurysm: cause, response, or common risk factors? Arterioscler Thromb Vasc Biol. 2010;30:1075-1077.


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