Evidence for a role of tumor necrosis factor α in disturbances of triglyceride and glucose metabolism predisposing to coronary heart disease

Jovinge, Stefan; Hamsten, Anders; Tornvall, Per; Proudler, Anthony J.; Båvenholm, Peter; Ericsson, Carl‐Göran; Godsland, Ian F.; Fairé, Ulf dé; Nilsson, Jan

doi:10.1016/s0026-0495(98)90203-7

Cited by 160 publications

(102 citation statements)

References 27 publications

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“…Several studies have described subclinical inflammation by the association of MS, obesity, and diabetes with high circulating TNF-a levels (13,14). In this study, the serum concentration of TNF-a, an inflammatory cytokine implicated in IR, was analyzed in individuals diagnosed with or without MS. A significantly increased concentration of TNF-a was found in the MS group, similar to a previously reported study (15).…”

Section: Discussionmentioning

confidence: 99%

Establishment of a cut‐point value of serum TNF‐α levels in the metabolic syndrome

Gurrola-Díaz

Sánchez‐Enríquez

García-López

et al. 2009

Clinical Laboratory Analysis

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Cardiovascular diseases and type 2 diabetes are the major causes of mortality in Mexico. Metabolic syndrome (MS) is a cluster of factors that increase the risk to develop such diseases. Previous studies have shown that MS is associated with high tumor necrosis factor (TNF-a) levels. In fact, TNF-a has been proposed to be a useful marker for clinical diagnosis of inflammation at an early stage. Therefore, we analyzed TNF-a concentrations in Mexican individuals with or without MS and related these levels to the associated MS components. Clinical, anthropometric, and biochemical data were analyzed in 41 healthy and 39 MS individuals. Individuals were similarly grouped by age and gender.The serum TNF-a levels measured by a highly sensitive enzyme-linked immunosorbent assay (ELISA) kit were increased significantly in MS subjects compared with healthy individuals (Po0.001). The assay showed 78.1% sensitivity and 61.5% specificity with a cut-point level of 1.36 pg/mL. TNF-a levels higher than the cut-point value were correlated with insulin resistance indices. These findings support the hypothesis that serum TNF-a concentration could be a useful marker for early MS diagnosis. Nevertheless, we suggest the establishment of specific cut-point values in each studied population to evaluate potential clinical applications.

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Section: Discussionmentioning

confidence: 99%

Establishment of a cut‐point value of serum TNF‐α levels in the metabolic syndrome

Gurrola-Díaz

Sánchez‐Enríquez

García-López

et al. 2009

Clinical Laboratory Analysis

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“…5,6 TNF-a plasma concentrations increase in patients affected with premature coronary artery disease 7 and is involved in obesity and insulin resistance. 8,9 Its expression is regulated at the transcriptional level.…”

Section: Introductionmentioning

confidence: 99%

Biological variations, genetic polymorphisms and familial resemblance of TNF-α and IL-6 concentrations: STANISLAS cohort

et al. 2004

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Cytokines are involved in the development of several inflammatory diseases and atherosclerosis. Their variations in healthy individuals are not well defined. The aims of this study were: firstly, to identify factors affecting biological variation of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-a); secondly, to study their family resemblance; and thirdly, to evaluate the effect of two TNF-a (À308G/A and À238G/A) and two IL-6 polymorphisms (174G/C and À572G/C) on their corresponding circulating levels. A total of 171 healthy families selected from the STANISLAS cohort were studied. Age was negatively related to TNFa concentrations in offspring only (both sons and daughters). Additionally, IL-6 and TNF-a levels were differently influenced by gender, white blood cells, tobacco consumption, and HDL-cholesterol level. A weak significant familial resemblance for TNF-a concentration was observed in siblings only. There was no significant familial resemblance for IL-6 levels. The TNF-a À308A allele was associated with decreased TNFa concentrations in both offspring aged less than 18 and males without overweight (BMIo25 kg/m 2 ). Fathers carrying the IL-6 À174CC genotype had higher IL-6 levels than those with the IL-6 À174G allele. Parents with the IL-6 À572GG genotype had higher IL-6 concentrations than the C allele carriers. In this sample of healthy families, plasma levels of IL-6 and TNF-a were differently affected by biological parameters including age, gender and smoking, and the impact of their respective polymorphisms was influenced by gender, age and BMI.

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“…Deletion of TNF-␣ or its receptors in obese knockout mice resulted in improved insulin sensitivity (7), and the actual defect induced by TNF-␣ is likely to be at or near the insulin receptor itself (8). TNF-␣ stimulates hepatic secretion of VLDL triglyceride (9,10).…”

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confidence: 99%

A Prospective Study of Soluble Tumor Necrosis Factor-α Receptor II (sTNF-RII) and Risk of Coronary Heart Disease Among Women With Type 2 Diabetes

Shai

Schulze²,

Manson

et al. 2005

Diabetes Care

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OBJECTIVE -Tumor necrosis factor-␣ (TNF-␣), a cytokine secreted by adipose tissue and other cells, might play a role in insulin resistance. RESEARCH DESIGN AND METHODS -Of 32,826 women from the Nurses' HealthStudy who provided blood at baseline, we followed 929 women with type 2 diabetes. During 10 years of follow-up, we documented 124 incident cases of coronary heart disease (CHD).RESULTS -After adjustment for age, smoking, BMI, and other cardiovascular risk factors, the relative risks (RRs) comparing extreme quartiles of soluble TNF-␣ receptor II (sTNF-RII) were 2.48 (95% CI 1.08 -5.69; P ϭ 0.034) for myocardial infarction (MI) and 2.02 (1.17-3.48; P ϭ 0.003) for total CHD. The probability of developing CHD over 10 years was higher among diabetic subjects with substantially higher levels of both sTNF-RII (Ͼ75th percentile) and HbA 1c (Ͼ7%), compared with diabetic subjects with lower levels (25% vs. 7%, P Ͻ 0.0001). Diabetic subjects with only higher sTNF-RII or HbA 1c had similar (16 -17%) risk. In a multivariate model, diabetic subjects with higher levels of both sTNF-RII and HbA 1c had an RR of 3.66 (1.85-7.22) for MI and 3.03 (1.82-5.05) for total CHD, compared with those with lower levels of both biomarkers.CONCLUSIONS -Increased levels of sTNF-RII were strongly associated with risk of CHD among diabetic women, independent of hyperglycemia. Diabetes Care 28:1376 -1382, 2005T umor necrosis factor-␣ (TNF-␣) is a mediator of obesity-related insulin resistance (1). This multifunctional cytokine is produced primarily by several types of cells involved in the atherosclerotic process, including macrophages, endothelial cells, and smooth muscle cells (2), but is also derived from muscle cells (3) and adipose tissue (4). Its expression is increased by obesity (5) and decreased by weight reduction (6). Deletion of TNF-␣ or its receptors in obese knockout mice resulted in improved insulin sensitivity (7), and the actual defect induced by TNF-␣ is likely to be at or near the insulin receptor itself (8). TNF-␣ stimulates hepatic secretion of VLDL triglyceride (9,10).Given the strong links among obesity, inflammation (11), type 2 diabetes, and vascular condition (12,13) and the potential role of TNF-␣ in insulin resistance, lipid metabolism, and inflammation, we hypothesize that TNF-␣ is associated with the development of coronary heart disease (CHD) in patients with type 2 diabetes. To test this hypothesis, we examined prospectively the association between plasma levels of soluble TNF-␣ receptor II (sTNF-RII, as a measure of TNF-␣ in plasma) and risk of CHD among women with type 2 diabetes in the Nurses' Health Study (NHS). RESEARCH DESIGN AND METHODS -The NHS was initiated in 1976 with the enrollment of 121,700 U.S. nurses aged 30 -55 years. This prospective cohort study is followed through questionnaires related to lifestyle factors and health outcomes that are mailed biennially. Of 32,826 study participants who provided blood samples in 1989 -1990, 1,194 had a confirmed diagnosis of type 2 diabetes. The present stu...

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Evidence for a role of tumor necrosis factor α in disturbances of triglyceride and glucose metabolism predisposing to coronary heart disease

Cited by 160 publications

References 27 publications

Establishment of a cut‐point value of serum TNF‐α levels in the metabolic syndrome

Establishment of a cut‐point value of serum TNF‐α levels in the metabolic syndrome

Biological variations, genetic polymorphisms and familial resemblance of TNF-α and IL-6 concentrations: STANISLAS cohort

A Prospective Study of Soluble Tumor Necrosis Factor-α Receptor II (sTNF-RII) and Risk of Coronary Heart Disease Among Women With Type 2 Diabetes

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