Diverse Effect of Inflammatory Markers on Insulin Resistance and Insulin‐Resistance Syndrome in the Elderly

Abbatecola, Angela Marie; Ferrucci, Luigi; Grella, Rodolfo; Bandinelli, Stefania; Bonafè, Massimiliano; Barbieri, Michelangela; Corsi, A.; Lauretani, Fulvio; Franceschi, Claudio; Paolisso, Giuseppe

doi:10.1111/j.1532-5415.2004.52112.x

Cited by 105 publications

(75 citation statements)

References 30 publications

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“…In the long term, these levels are associated with fixed organ lesions associated with aging. 5,6,40,42 The reduced basal level of AGEs in F1 mice was attributable to low levels of AGEs in the Low-Fo dams. 36 This suggests that higher levels of oxidant AGEs in offspring of Reg-Fo dams may be attributable to placental transmission from mothers with high AGE levels.…”

Section: Discussionmentioning

confidence: 99%

Oral Glycotoxins Determine the Effects of Calorie Restriction on Oxidant Stress, Age-Related Diseases, and Lifespan

Cai

Zhu

et al. 2008

The American Journal of Pathology

168

185

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We previously showed that the content of advanced glycation end products (AGEs) in the diet correlates with serum AGE levels, oxidant stress (OS), organ dysfunction, and lifespan. We now show that the addition of a chemically defined AGE (methyl-glyoxal-BSA) to low-AGE mouse chow increased serum levels of AGEs and OS, demonstrating that dietary AGEs are oxidants that can induce systemic OS. OS predisposes to the development of cardiovascular and chronic kidney diseases; calorie restriction (CR) is the most studied means to decrease OS, increase longevity, and reduce OS-related organ damage in mammals. Because reduction of food intake also decreases oxidant AGE s intake , we asked whether the beneficial effects of CR in mammals are related to the restriction of oxidants or energy. Pair-fed mice were provided either a CR diet or a high-AGE CR diet in which AGEs were elevated by brief heat treatment (CR-high). Old CR-high mice developed high levels of 8-isoprostanes , AGEs , RAGE , and p66shc , coupled with low AGER1 and GSH/GSSG levels , insulin resistance , marked myocardial and renal fibrosis , and shortened lifespan. In contrast , old CR mice had low OS , p66shc , RAGE , and AGE levels , but high AGER1 levels , coupled with longer lifespan. Therefore , the beneficial effects of a CR diet may be partly related to reduced oxidant intake, a principal determinant of oxidant status in aging mice, rather than decreased energy intake.

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Section: Discussionmentioning

confidence: 99%

Oral Glycotoxins Determine the Effects of Calorie Restriction on Oxidant Stress, Age-Related Diseases, and Lifespan

Cai

Zhu

et al. 2008

The American Journal of Pathology

168

185

View full text Add to dashboard Cite

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“…It has also been shown that subcutaneous adipose tissue releases IL-6, but not TNF-a, in vivo (Mohamed-Ali et al, 1997), that circulating TNF-a levels are higher in abdominal obesity compared with peripheral obesity (Tsigos et al, 1999), and that obese adults without metabolic syndrome present with lower visceral and higher subcutaneous fat than obese adults with the metabolic syndrome (Koster et al, 2010). Higher IL-6 and TNF-a have also been associated with increased insulin resistance (Abbatecola et al, 2004), although this statement has been challenged (EscobarMorreale et al, 2003). As all MHO definitions included in this study had at least one marker of glucose metabolism (hyperglycaemia or insulin resistance defined by homeostasis model assessment status), it is possible that the lower levels of inflammatory biomarkers among MHO subjects could actually be due to a selection bias, that is, due to the criteria used to define MHO (absence of hyperglycaemia or insulin resistance).…”

Section: Discussionmentioning

confidence: 99%

The association between inflammatory biomarkers and metabolically healthy obesity depends of the definition used

et al. 2011

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Background/Objectives: To assess the distribution of interleukin (IL)-1b, IL-6, tumour necrosis factor (TNF)-a and C-reactive protein (CRP) according to the different definitions of metabolically healthy obesity (MHO). Subjects/Methods: A total of 881 obese (body mass index (BMI) X30 kg/m 2 ) subjects derived from the population-based CoLaus Study participated in this study. MHO was defined using six sets of criteria including different combinations of waist, blood pressure, total high-density lipoprotein cholesterol or low-density lipoprotein -cholesterol, triglycerides, fasting glucose, homeostasis model, high-sensitivity CRP, and personal history of cardiovascular, respiratory or metabolic diseases. IL-1b, IL-6 and TNF-a were assessed by multiplexed flow cytometric assay. CRP was assessed by immunoassay. Results: On bivariate analysis some, but not all, definitions of MHO led to significantly lower levels of IL-6, TNF-a and CRP compared with non-MH obese subjects. Most of these differences became nonsignificant after multivariate analysis. An posteriori analysis showed a statistical power between 9 and 79%, depending on the inflammatory biomarker and MHO definition considered. Further increasing sample size to overweight þ obese individuals (BMIX25 kg/m 2 , n ¼ 2917) showed metabolically healthy status to be significantly associated with lower levels of CRP, while no association was found for IL-1b. Significantly lower IL-6 and TNF-a levels were also found with some but not all MHO definitions, the differences in IL-6 becoming nonsignificant after adjusting for abdominal obesity or percent body fat. Conclusions: MHO individuals present with decreased levels of CRP and, depending on MHO definition, also with decreased levels in IL-6 and TNF-a. Conversely, no association with IL-1b levels was found.

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“…Linear regression was used to test for association of the three genotypes at each SNP with serum IL-1RA concentrations and other continuous traits. Serum concentrations of IFN-g, IL-10, TNF-a and IL-1b were low and below the desirable detectable limit, as described previously, 20 in 78, 63, 55 and 63% of individuals, respectively. Hence, we analyzed the association of these variables with independent genotypes and IL-1RA concentrations in ordered logistic regression models, after distributing the dependent variables in quantiles using STATAv9.…”

Section: Discussionmentioning

confidence: 99%

Common genetic variation in the gene encoding interleukin-1-receptor antagonist (IL-1RA) is associated with altered circulating IL-1RA levels

et al. 2007

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Interleukin-1-receptor antagonist (IL-1RA) modulates the biological activity of the proinflammatory cytokine interleukin-1 (IL-1) and could play an important role in the pathophysiology of inflammatory and metabolic traits. We genotyped seven single nucleotide polymorphisms (SNPs) that capture a large proportion of common genetic variation in the IL-1RN gene in 1256 participants from the Invecchiare in Chianti study. We identified five SNPs associated with circulating IL-1RA levels with varying degrees of significance (P-value range ¼ 0.016-4.9 Â 10 À5 ). We showed that this association is likely to be driven by one haplotype, most strongly tagged by rs4251961. This variant is only in weak linkage disequilibrium (r 2 ¼ 0.25) with a previously reported variable number of tandem repeats polymorphism (VNTR) in intron-2 although a second variant, rs579543, that tags the VNTR (r 2 ¼ 0.91), may also be independently associated with IL-1RA levels (P ¼ 0.03). We found suggestive evidence that the C allele at rs4251961 that lowers IL-1RA levels is associated with an increased IL-1b (P ¼ 0.03) level and may also be associated with interferon -g (P ¼ 0.03), a-2 macroglobulin (P ¼ 0.008) and adiponectin (P ¼ 0.007) serum levels. In conclusion, common variation across the IL-1RN gene is strongly associated with IL-1RA levels.

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Diverse Effect of Inflammatory Markers on Insulin Resistance and Insulin‐Resistance Syndrome in the Elderly

Abstract: Different inflammatory markers are associated with a diverse effect on IR and IRS in elderly nondiabetic subjects.

Cited by 105 publications

References 30 publications

Oral Glycotoxins Determine the Effects of Calorie Restriction on Oxidant Stress, Age-Related Diseases, and Lifespan

Oral Glycotoxins Determine the Effects of Calorie Restriction on Oxidant Stress, Age-Related Diseases, and Lifespan

The association between inflammatory biomarkers and metabolically healthy obesity depends of the definition used

Common genetic variation in the gene encoding interleukin-1-receptor antagonist (IL-1RA) is associated with altered circulating IL-1RA levels

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