Fibrinolytic risk factor clustering and insulin resistance in healthy male relatives of men with intermittent claudication

Parry, D.J.; Grant, Peter J.; Scott, D.

doi:10.1002/bjs.5270

Cited by 4 publications

(7 citation statements)

References 43 publications

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“…In the univariate analyses we found that insulin resistance was negatively associated with sICAM‐1 and positively associated with IL‐6 and D‐dimer levels. The IL‐6 and D‐dimer findings, which were not sustained in the multivariate analyses, are consistent with observations in older adults (16) and indicate increased inflammation and coagulation with increasing insulin resistance. In a prior study of lean and obese middle‐aged adults sICAM‐1 was independently negatively associated with insulin sensitivity, indicating higher sICAM‐1 levels with increasing insulin resistance (17).…”

Section: Discussionsupporting

confidence: 85%

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Metabolic Predictors of Inflammation, Adhesion, and Coagulability in Healthy Younger‐aged Adults

Mills

Shapiro

Goldstein

et al. 2008

Obesity

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Elevated levels of inflammatory biomarkers are associated with the pathophysiology of cardiovascular diseases and are predictors of cardiovascular events. The objective of this study was to determine the unique contributions of metabolic factors as predictors of inflammation (C‐reactive protein (CRP) and interleukin‐6 (IL‐6)), adhesion (soluble intercellular adhesion molecule‐1 (sICAM‐1)), and coagulation (D‐dimer) in healthy younger‐aged adults. Participants were 83 women and 92 men (mean age 30.04 years, s.d. ± 4.8, range 22–39) of normal weight to moderate obese weight (mean BMI 24.4 kg/m2, s.d. ± 3.35, range 17–32). The primary data analytical approaches included Pearson correlation and multiple linear regression. Circulating levels of CRP, IL‐6, sICAM‐1, and D‐dimer were determined in plasma. Higher levels of CRP were independently associated with higher BMI, a greater waist‐to‐hip ratio, female gender, and higher triglycerides (P < 0.001). Higher IL‐6 levels were independently associated with a greater waist‐to‐hip ratio (P < 0.01). Higher levels of sICAM‐1 were independently associated with higher BMI, higher triglycerides, and lower insulin resistance (P < 0.001). Higher D‐dimer levels were independently associated with higher BMI and being female (P < 0.001). Having a higher BMI was most consistently associated with elevated biomarkers of inflammation, adhesion, and coagulation in this sample of healthy younger‐aged adults, although female gender, insulin resistance, and lipid levels were also related to the biomarkers. The findings provide insight into the adverse cardiovascular risk associated with elevated body weight in younger adults.

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Section: Discussionsupporting

confidence: 85%

“…In middle‐aged women, CRP is independently associated with fasting insulin levels (15). In older adults elevated D‐dimer levels accompany insulin resistance (16). In middle‐aged adults sICAM‐1 has been shown to be associated with insulin resistance (17), although other studies show no such association (18).…”

Section: Introductionmentioning

confidence: 99%

Metabolic Predictors of Inflammation, Adhesion, and Coagulability in Healthy Younger‐aged Adults

Mills

Shapiro

Goldstein

et al. 2008

Obesity

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“…The study population comprised 318 clinically healthy white males of European origin, characterised for the presence of the MetS and in whom stored plasma was available for analysis of NEP. Participant recruitment has been published previously (17;18). In brief, all subjects were free from clinical cardiovascular disease or previously diagnosed diabetes.…”

Section: Methodsmentioning

confidence: 99%

“…Analysis of fasting lipids, glucose, insulin and homeostasis model assessment (HOMA), tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) were carried out as previously described. (17;18)NEP was assayed according to an original protocol (19) modified in our laboratory using the fluorogenic substrate succinoyl-Ala-Ala-Phe-7-amido-4-methylcoumarin (200 μM) in a coupled assay with leucine aminopeptidase (50 μg/ml) in 50 mM Hepes/NaOH, 200 mM NaCl, 10 μM ZnCl 2 , 1% DMSO, pH 6.8 at room temperature in the dark. Fluorescence was measured using a Biotek Synergy HT plate reader (λ excitation = 380 nm and λ emission = 460 nm).…”

Section: Methodsmentioning

confidence: 99%

Neprilysin, obesity and the metabolic syndrome

et al. 2010

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ObjectiveNeprilysin (NEP), a zinc metallo-endopeptidase, has a role in blood pressure control and lipid metabolism. The present study tested the hypothesis that NEP is associated with insulin resistance and features of the metabolic syndrome (MetS) in a study of 318 healthy human subjects and in murine obesity and investigated NEP production by adipocytes in-vitro.Methods and ResultsIn 318 white European males, plasma NEP was elevated in the MetS and increased progressively with increasing MetS components. Plasma NEP activity correlated with insulin, homeostasis model assessment and body mass index in all subjects (p<0.01). Quantitative RT-PCR and Western blotting showed that in human pre-adipocytes NEP expression is upregulated 25-30 fold during differentiation into adipocytes. Microarray analysis of mRNA from differentiated human adipocytes confirmed high NEP expression comparable to adiponectin and plasminogen activator inhibitor-1. In a murine model of diet-induced insulin resistance, plasma NEP levels were significantly higher in high fat diet (HFD)-fed compared with normal chow diet (NCD)-fed animals (1642±529 and 820±487 pg/μl, respectively; p<0.01). Tissue NEP was increased in mesenteric fat in HFD compared with NCD-fed mice (p<0.05). NEP knock out mice did not display any changes in insulin resistance, glucose tolerance or body and epididymal fat pad weight compared to wild type mice.ConclusionsIn humans, NEP activity correlated with body mass index and measures of insulin resistance with increasing levels in subjects with multiple cardiovascular risk factors. NEP protein production in human adipocytes increased during cell differentiation and plasma and adipose tissue levels of NEP were increased in obese insulin resistant mice. Our results indicate that NEP associates with cardio-metabolic risk in the presence of insulin resistance and increases in obesity.

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“…Previous studies showed that IR was associated with atherosclerosis 14,15 and elevation of fibrinogen levels 16,17 as well as plasminogen activator inhibitor type 1 activity level. 16,[18][19][20] Other previous studies reported that an elevated fibrinogen level, 21,22 plasminogen activator inhibitor type 1 activity level, 23,24 and atherosclerosis [25][26][27] are associated with cerebral infarction. Therefore, we conclude that IR is associated with cerebral infarction.…”

Section: Discussionmentioning

confidence: 99%

Insulin Resistance and Risk of Cerebral Infarction in a Japanese General Population

Kaneda

Ishikawa

Sadakane

et al. 2013

Asia Pac J Public Health

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The aim of the study was to investigate the relation between insulin resistance and risk of cerebral infarction in a Japanese general population. The subjects were 2610 men and women without past history of stroke or myocardial infarction and who were under treatment for diabetes. Subjects were divided into quartiles by the homeostasis model assessment of insulin resistance (HOMA-IR), and Cox's proportional hazard model was used to calculate hazard ratios (HRs) for cerebral infarction. In men, the multivariate-adjusted HRs were 2.51 (95% confidence interval [CI] = 0.98-6.42) in quartile 1 (Q1), 1.43 (95% CI = 0.54-3.82) in Q2, and 2.13 (95% CI = 0.82-5.51) in Q4, using Q3 as the reference. In women, the multivariate-adjusted HRs were 2.12 (95% CI = 0.72-6.31) in Q1, 2.96 (95% CI = 1.06-8.26) in Q3, and 2.31 (95% CI = 0.80-6.69) in Q4, using Q2 as the reference. The association between risk of cerebral infarction and HOMA-IR was not dose dependent.

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Fibrinolytic risk factor clustering and insulin resistance in healthy male relatives of men with intermittent claudication

Abstract: Raised levels of PAI-1, tPA, D-dimer and estimated insulin resistance were present in the healthy male first-degree relatives of men with intermittent claudication. These data support the hypothesis of fibrinolytic risk factor clustering in this high-risk population.

Cited by 4 publications

References 43 publications

Metabolic Predictors of Inflammation, Adhesion, and Coagulability in Healthy Younger‐aged Adults

Metabolic Predictors of Inflammation, Adhesion, and Coagulability in Healthy Younger‐aged Adults

Neprilysin, obesity and the metabolic syndrome

Insulin Resistance and Risk of Cerebral Infarction in a Japanese General Population

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