Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-α or its receptors

Muller, Sylviane; Martin, Stéphan; Köenig, Wolfgang; Hanifi-Moghaddam, Pejman; Rathmann, Wolfgang; Haastert, Burkhard; Giani, Guido; Illig, Thomas; Thorand, Barbara; Kolb, Hubert

doi:10.1007/s00125-002-0829-2

Cited by 290 publications

(236 citation statements)

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“…Both methods gave similar results when identical samples were analysed [28]. Serum levels of IL-6 were determined by ELISA [5]. The intra-and interassay CV values of quality control test sera were as follows: MCP-1, <10 and 19.9%; IL-8, <10 and 10.9%; IP-10, <10 and 35.1%; CRP-IRMA, 4.0 and 12.0%; CRP nephelometric assay, 2.5 and 5.1%; IL-6, <10 and <10%.…”

Section: Methodsmentioning

confidence: 91%

“…The type 2 diabetes-related immune activation includes upregulation of multiple acute phase proteins, cytokines and soluble adhesion molecules [3][4][5][6][7]. However, studies addressing the association of several immune mediators with type 2 diabetes in the same population indicate that there is no general upregulation of systemic immune mediator expression, but rather a specific and differential activation [5,7]. Data on IL-10 suggest that elevated expression of this cytokine in peripheral blood might even be protective against type 2 diabetes [8].…”

Section: Introductionmentioning

confidence: 99%

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Chemokines as risk factors for type 2 diabetes: results from the MONICA/KORA Augsburg study, 1984–2002

et al. 2006

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Aims/hypothesis: The chemokines monocyte chemoattractant protein-1 (MCP-1), IL-8 and interferon-γ-inducible protein-10 (IP-10) are released by adipocytes and appear to be involved in atherosclerosis. We hypothesised that these chemokines may be risk factors for the development of type 2 diabetes. Subjects and methods: Using a case-cohort design based on data from the population-based Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Kooperative Gesundheitsforschung in der Region Augsburg/Cooperative Health Research in the Region of Augsburg (KORA Augsburg) study, chemokine levels at baseline were analysed in 526 individuals with and 1,695 individuals without incident type 2 diabetes. The mean follow-up time was 10.8 years. Results: MCP-1 was associated with type 2 diabetes, largely independently of classic risk factors, whereas various clinical and metabolic parameters as well as lifestyle factors were major confounders of the association of IL-8 and IP-10 with type 2 diabetes. Further adjustment for C-reactive protein (CRP) and IL-6 had no impact on the observed associations. The hazard ratio (HR) for subjects with systemic concentrations of all three chemokines (MCP-1, IL-8 and IP-10) above the respective median compared with those with all chemokines below or equal to the median was 1.79 (95% CI 1.18-2.72) and was comparable with the HR for elevated CRP and IL-6 together (adjusted for age, sex, survey, BMI, systolic blood pressure, total cholesterol:HDL cholesterol ratio, physical activity, alcohol intake, smoking and parental history of diabetes). Conclusions/interpretation: Elevated concentrations of MCP-1, IL-8 and IP-10 are associated with incident type 2 diabetes. Whereas the association of IL-8 and IP-10 with diabetes was attenuated by multivariable adjustment, high MCP-1 levels contributed to diabetes risk independently of previously described clinical, metabolic and immunological risk factors.

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Section: Methodsmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Chemokines as risk factors for type 2 diabetes: results from the MONICA/KORA Augsburg study, 1984–2002

et al. 2006

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“…28 Furthermore, the increase in CRP and other inflammatory markers, such as IL-6, was not fully explained by BMI in impaired glucose tolerance and type 2 diabetes. 29 The acute-phase protein SAA correlates positively with obesity 8 and is higher in people with type 2 diabetes mellitus and impaired glucose tolerance than in non-diabetic controls. 23,29 Male subjects with coronary heart disease (CHD) have markedly higher SAA levels than those without CHD 30 and SAA may, due to its interaction with HDL-cholesterol, be a factor in the accelerated atherosclerosis of diabetes.…”

Section: Discussionmentioning

confidence: 99%

“…29 The acute-phase protein SAA correlates positively with obesity 8 and is higher in people with type 2 diabetes mellitus and impaired glucose tolerance than in non-diabetic controls. 23,29 Male subjects with coronary heart disease (CHD) have markedly higher SAA levels than those without CHD 30 and SAA may, due to its interaction with HDL-cholesterol, be a factor in the accelerated atherosclerosis of diabetes. 23 The finding of SAA in atherosclerotic plaques supports a link between inflammation, lipoprotein metabolism and the development of atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

CRP reduction following gastric bypass surgery is most pronounced in insulin-sensitive subjects

et al. 2005

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OBJECTIVE: Obesity is frequently associated with insulin resistance, dyslipidemia, hypertension and an increased risk of cardiovascular disease, reflected in elevated markers of inflammation, in particular C-reactive protein (CRP). To what extent the insulin resistance or the obesity per se contributes to increased CRP levels is unclear. In morbidly obese patients, gastric bypass surgery causes marked changes in body weight and improves metabolism, thereby providing informative material for studies on the regulation of inflammatory markers. DESIGN: Prospective, surgical intervention study of inflammatory markers in morbidly obese subjects. SUBJECTS: In total, 66 obese subjects with mean age 39 y and mean body mass index (BMI) 45 kg/m 2 were studied prior to and 6 and 12 months following Roux-en-Y gastric bypass (RYGBP) surgery. MEASUREMENTS: Serum concentrations of high sensitivity CRP, serum amyloid A (SAA) and interleukin-6 (IL-6), as well as markers of glucose and lipid metabolism. RESULTS: Prior to surgery, CRP levels were elevated compared to the reference range of healthy, normal-weight subjects. CRP correlated with insulin sensitivity, as reflected by the homeostatic model assessment (HOMA) index, but not BMI, when corrected for age and gender. Surgery reduced BMI from 45 to 31 kg/m 2 and lowered CRP, SAA and IL-6 levels by 82, 57 and 50%, respectively, at 12 months. The reduction in CRP was inversely related to HOMA at baseline independently of the change in body weight (r ¼ À0.36, P ¼ 0.005). At 12 months, 140 and 40% reductions in CRP were seen in subjects with HOMA o 4 (insulin sensitive) and HOMA49 (insulin resistant) despite similar reductions in BMI. Reductions in SAA and IL-6 tended to parallel the changes in CRP, but were less informative. CONCLUSION: In morbidly obese subjects, gastric bypass surgery lowers energy intake, reduces inflammatory markers and improves insulin sensitivity. Despite a marked reduction in body weight, only a small effect on CRP levels was seen in insulinresistant patients, indicating that flexibility of circulating CRP levels is primarily dependent upon insulin sensitivity rather than energy supply.

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“…Such a modest increase may not be sufficient to be of pathological relevance, particularly when considering that the spread of serum concentrations between individuals is usually 10-to 100-fold [61]. A different situation emerges when paracrine effects of immune mediators are being considered.…”

Section: Excess Nutrients/obesitymentioning

confidence: 99%

The global diabetes epidemic as a consequence of lifestyle-induced low-grade inflammation

Kolb¹,

2009

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The recent major increase in the global incidence of type 2 diabetes suggests that most cases of this disease are caused by changes in environment and lifestyle. All major risk factors for type 2 diabetes (overnutrition, low dietary fibre, sedentary lifestyle, sleep deprivation and depression) have been found to induce local or systemic low-grade inflammation that is usually transient or milder in individuals not at risk for type 2 diabetes. By contrast, inflammatory responses to lifestyle factors are more pronounced and prolonged in individuals at risk of type 2 diabetes and appear to occur also in the pancreatic islets. Chronic low-grade inflammation will eventually lead to overt diabetes if counter-regulatory circuits to inflammation and metabolic stress are compromised because of a genetic and/or epigenetic predisposition. Hence, it is not the lifestyle change per se but a deficient counter-regulatory response in predisposed individuals which is crucial to disease pathogenesis. Novel approaches of intervention may target these deficient defence mechanisms.

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Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-α or its receptors

Cited by 290 publications

References 50 publications

Chemokines as risk factors for type 2 diabetes: results from the MONICA/KORA Augsburg study, 1984–2002

Chemokines as risk factors for type 2 diabetes: results from the MONICA/KORA Augsburg study, 1984–2002

CRP reduction following gastric bypass surgery is most pronounced in insulin-sensitive subjects

The global diabetes epidemic as a consequence of lifestyle-induced low-grade inflammation

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