Diabetes mellitus and abdominal aortic aneurysms: A review of the mechanisms underlying the negative relationship

Dattani, Nikesh; Sayers, Robert D.; Bown, Matthew J.

doi:10.1177/1479164118780799

Cited by 39 publications

(27 citation statements)

References 72 publications

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“…Regarding DM in our study, it seemed to have a protective effect for IA formation (6.8% in IA vs. 12.5% in controls; p = 0.001). Dattani et al [51] reported a negative association between AAA and DM. In addition, medications to treat DM can inhibit AAA formation and growth [51].…”

Section: Discussionmentioning

confidence: 99%

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Genomic Variations in Susceptibility to Intracranial Aneurysm in the Korean Population

Hong

Kim

Cho

et al. 2019

JCM

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Genome-wide association studies found genetic variations with modulatory effects for intracranial aneurysm (IA) formations in European and Japanese populations. We aimed to identify the susceptibility of single nucleotide polymorphisms (SNPs) to IA in a Korean population consisting of 250 patients, and 294 controls using the Asian-specific Axiom Precision Medicine Research Array. Twenty-nine SNPs reached a genome-wide significance threshold (5 × 10−8). The rs371331393 SNP, with a stop-gain function of ARHGAP32 (11q24.3), showed the most significant association with the risk of IA (OR = 43.57, 95% CI: 21.84–86.95; p = 9.3 × 10−27). Eight out of 29 SNPs—GBA (rs75822236), TCF24 (rs112859779), OLFML2A (rs79134766), ARHGAP32 (rs371331393), CD163L1 (rs138525217), CUL4A (rs74115822), LOC102724084 (rs75861150), and LRRC3 (rs116969723)—demonstrated sufficient statistical power greater than or equal to 0.8. Two previously reported SNPs, rs700651 (BOLL, 2q33.1) and rs6841581 (EDNRA, 4q31.22), were validated in our GWAS (Genome-wide association study). In a subsequent analysis, three SNPs showed a significant difference in expressions: the rs6741819 (RNF144A, 2p25.1) was down-regulated in the adrenal gland tissue (p = 1.5 × 10−6), the rs1052270 (TMOD1. 9q22.33) was up-regulated in the testis tissue (p = 8.6 × 10−10), and rs6841581 (EDNRA, 4q31.22) was up-regulated in both the esophagus (p = 5.2 × 10−12) and skin tissues (1.2 × 10−6). Our GWAS showed novel candidate genes with Korean-specific variations in IA formations. Large population based studies are thus warranted.

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Section: Discussionmentioning

confidence: 99%

“…Dattani et al [51] reported a negative association between AAA and DM. In addition, medications to treat DM can inhibit AAA formation and growth [51]. Therefore, further studies regarding DM and medications on IA formation and growth are needed.…”

Section: Discussionmentioning

confidence: 99%

Genomic Variations in Susceptibility to Intracranial Aneurysm in the Korean Population

Hong

Kim

Cho

et al. 2019

JCM

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“…Furthermore, increased levels of total cholesterol and apolipoprotein B, both markers easily quantified and major constituents of lipid metabolism, have been associated with increased growth rates of AAA [ 18 ]. On the other hand, given the potentially protective nature of diabetes mellitus in AAA, glycated hemoglobin (HbA1c) has been studied as a possible biomarker of inverse association with AAA expansion [ 52 , 53 , 54 , 55 ]. A lower growth rate was observed in patients with higher HbA1c levels; 1.8 mm/year decrease of rate in HbA1c 44–77 compared to 28–39 mmol/mol [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Circulating Biomarkers for the Prediction of Abdominal Aortic Aneurysm Growth

Nana

Dakis

Brodis

et al. 2021

JCM

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Background: Abdominal aortic aneurysm represents a distinct group of vascular lesions, in terms of surveillance and treatment. Screening and follow-up of patients via duplex ultrasound has been well established and proposed by current guidelines. However, serum circulating biomarkers could earn a position in individualized patient surveillance, especially in cases of aggressive AAA growth rates. A systematic review was conducted to assess the correlation of AAA expansion rates with serum circulating biomarkers. Methods: A data search of English medical literature was conducted, using PubMed, EMBASE, and CENTRAL, until 7 March 2021, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement (PRISMA) guidelines. Studies reporting on humans, on abdominal aortic aneurysm growth rates and on serum circulating biomarkers were included. No statistical analysis was conducted. Results: A total of 25 studies with 4753 patients were included. Studies were divided in two broad categories: Those reporting on clinically applicable (8 studies) and those reporting on experimental (17 studies) biomarkers. Twenty-three out of 25 studies used duplex ultrasound (DUS) for following patients. Amongst clinically applicable biomarkers, D-dimers, LDL-C, HDL-C, TC, ApoB, and HbA1c were found to bear the most significant association with AAA growth rates. In terms of the experimental biomarkers, PIIINP, osteopontin, tPA, osteopontin, haptoglobin polymorphisms, insulin-like growth factor I, thioredoxin, neutrophil extracellular traps (NETs), and genetic factors, as polymorphisms and microRNAs were positively correlated with increased AAA expansion rates. Conclusion: In the presence of future robust data, specific serum biomarkers could potentially form the basis of an individualized surveillance strategy of patients presenting with increased AAA growth rates.

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“…23,24 Hyperglycemia might influence angiogenesis, remodeling, extracellular matrix volume and glycation, advanced glycation end-products, inflammatory markers, oxidative stress, composition of the thrombus commonly present in an AAA, and transforming growth factor b signaling. [23][24][25] Furthermore, hemodynamic features of the aorta might differ between diabetic and nondiabetic patients, and computational fluid dynamic methods are currently evaluated to help understand such mechanisms. 26 Our methodology does not allow us to speculate about these mechanisms, however, as we have not assessed biomarkers.…”

Section: Discussionmentioning

confidence: 99%

Nationwide comparison of long-term survival and cardiovascular morbidity after acute aortic aneurysm repair in patients with and without type 2 diabetes

Taimour

Franzén

Zarrouk

et al. 2020

Journal of Vascular Surgery

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Objective: Epidemiologic data indicate decreased risk for development, growth, and rupture of abdominal aortic aneurysm (AAA) among patients with type 2 diabetes mellitus (DM). We therefore evaluated mortality and cardiovascular morbidity after acute repair of AAA in diabetic and nondiabetic patients. Methods: In this nationwide observational cohort study of patients registered in the Swedish Vascular Registry and the Swedish National Diabetes Register, we compared mortality and morbidity after acute open (n ¼ 1357 [61%]) or endovascular (n ¼ 860 [39%]) repair of ruptured (n ¼ 1469 [66%]) or otherwise symptomatic (n ¼ 748 [34%]) AAAs in 363 patients with and 1854 patients without DM with propensity score-adjusted analysis.Results: Follow-up was 3.91 years for patients with DM and 3.18 years for those without. In propensity-adjusted analysis, diabetic patients showed lower total mortality (relative risk [RR], 0.75; 95% confidence interval [CI], 0.59-0.95; P ¼ .016) and cardiovascular mortality (RR, 0.17; 95% CI, 0.06-0.50; P ¼ .01) than those without DM, whereas there were no differences in rates of major adverse cardiovascular events (RR, 1.10; 95% CI, 0.87-1.42; P ¼ .42), acute myocardial infarction (RR, 1.36; 95% CI, 0.70-2.63; P ¼ .37), or stroke (RR, 1.31; 95% CI, 0.84-2.03; P ¼ .23). Conclusions:Patients with type 2 DM had lower rates of both total and cardiovascular mortality after acute AAA repair than those without DM, whereas rates of cardiovascular events, acute myocardial infarction, and stroke did not differ between groups. This might be explained by putative protective effects of DM on the aortic wall. (J Vasc Surg 2020;71:30-8.)

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Diabetes mellitus and abdominal aortic aneurysms: A review of the mechanisms underlying the negative relationship

Abstract: The negative association between diabetes and abdominal aortic aneurysm is robust. Future studies should attempt to target the pathways identified in this review to develop novel therapeutic agents aimed at slowing or even halting aneurysm progression.

Cited by 39 publications

References 72 publications

Genomic Variations in Susceptibility to Intracranial Aneurysm in the Korean Population

Genomic Variations in Susceptibility to Intracranial Aneurysm in the Korean Population

Circulating Biomarkers for the Prediction of Abdominal Aortic Aneurysm Growth

Nationwide comparison of long-term survival and cardiovascular morbidity after acute aortic aneurysm repair in patients with and without type 2 diabetes

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