Profile of the Immune and Inflammatory Response in Individuals With Prediabetes and Type 2 Diabetes

Großmann, Vera; Schmitt, Volker H.; Zeller, Tanja; Panova‐Noeva, Marina; Schulz, Andreas; Laubert‐Reh, Dagmar; Juenger, Claus; Schnabel, Renate B.; Abt, Tobias G.J.; Laskowski, Rafael; Wiltink, Jörg; Schulz, Eberhard; Blankenberg, Stefan; Lackner, Karl J.; Münzel, Thomas; Wild, Philipp S.

doi:10.2337/dc14-3008

Cited by 215 publications

(192 citation statements)

References 39 publications

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“…In line with this, elevated circulating levels of pro-inflammatory cytokines characterize the early (or pre-clinical) stages of T2D and exhibit a graded increase with the disease progression (Duncan et al 2003, Grossmann et al 2015. Interestingly, recent studies also suggest links between inflammation and ER stress in T2D patients at the level of the immune system.…”

Section: Type 2 Diabetesmentioning

confidence: 61%

Endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation

Meyerovich

Ortis

Allagnat

et al. 2016

Journal of Molecular Endocrinology

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Insulin-secreting pancreatic β-cells are extremely dependent on their endoplasmic reticulum (ER) to cope with the oscillatory requirement of secreted insulin to maintain normoglycemia. Insulin translation and folding rely greatly on the unfolded protein response (UPR), an array of three main signaling pathways designed to maintain ER homeostasis and limit ER stress. However, prolonged or excessive UPR activation triggers alternative molecular pathways that can lead to β-cell dysfunction and apoptosis. An increasing number of studies suggest a role of these pro-apoptotic UPR pathways in the downfall of β-cells observed in diabetic patients. Particularly, the past few years highlighted a cross talk between the UPR and inflammation in the context of both type 1 (T1D) and type 2 diabetes (T2D). In this article, we describe the recent advances in research regarding the interplay between ER stress, the UPR, and inflammation in the context of β-cell apoptosis leading to diabetes.

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Section: Type 2 Diabetesmentioning

confidence: 61%

Endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation

Meyerovich

Ortis

Allagnat

et al. 2016

Journal of Molecular Endocrinology

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“…Regarding circulating C-reactive protein (CRP), for example, higher levels were observed in prediabetes (i.e., impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT)) compared with normal glucose tolerance (NGT), whereas only minor differences in CRP levels were observed between people with prediabetes and type 2 diabetes (3). In contrast, systemic levels of interleukin (IL)-6 or IL18 seemed to be similar in individuals with NGT and prediabetes, but higher in those with type 2 diabetes compared with those with prediabetes (3,4). Thus, different biomarkers of subclinical inflammation are related to early vs late stages of glycaemic deterioration, but little is known about the underlying pathophysiology (5).…”

Section: Introductionmentioning

confidence: 85%

Biomarkers of subclinical inflammation and increases in glycaemia, insulin resistance and beta-cell function in non-diabetic individuals: the Whitehall II study

Herder

Færch

Carstensen‐Kirberg

et al. 2016

European Journal of Endocrinology

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Objective: Higher systemic levels of pro-inflammatory biomarkers and low adiponectin are associated with increased risk of type 2 diabetes, but their associations with changes in glycaemic deterioration before onset of diabetes are poorly understood. We aimed to study whether inflammation-related biomarkers are associated with 5-year changes in glucose and insulin, HbA1c, insulin sensitivity and beta-cell function before the diagnosis of type 2 diabetes and whether these associations may be bidirectional. Design and methods: We used multiple repeat measures (17 891 person-examinations from 7683 non-diabetic participants) from the Whitehall II study to assess whether circulating high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6), IL1 receptor antagonist (IL1Ra) and adiponectin are associated with subsequent changes in glycaemia, insulin, insulin resistance and beta-cell function (based on oral glucose tolerance tests). We examined bidirectionality by testing if parameters of glucose metabolism at baseline are associated with changes in inflammation-related biomarkers. Results: Higher hsCRP and IL6 were associated with increases in fasting insulin, insulin resistance and, for IL6, with beta-cell function after adjustment for confounders. Higher adiponectin was associated with decreases in fasting glucose, HbA1c, fasting insulin, insulin resistance and beta-cell function. The reverse approach showed that 2-h glucose and insulin sensitivity were associated with changes in IL1Ra. Fasting insulin and insulin resistance showed inverse associations with changes in adiponectin. Conclusions: Subclinical inflammation is associated with development of increased glycaemia, insulin resistance and beta-cell function in non-diabetic individuals. These findings are consistent with the hypothesis that inflammationrelated processes may increase insulin resistance and lead to a compensatory upregulation of beta-cell function. European Journal of Endocrinology175:5 368 Clinical Study C Herder and others Inflammation and glucose metabolism

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“…Grossmann et al in 2015, noted that neopterin level was positively associated with the prevalence of the diabetes disease 13 . As well, neopterin considered as a marker of diabetic progression and complication 14 .…”

Section: Discussionmentioning

confidence: 99%

Untitled

2017

IJPSR

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Neopterin, pyrazino-pyrimidine compound, is a metabolite of guanosine triphosphate and is produced by the activated monocytes, macrophages and dendritic cells upon stimulation by interferon gamma produced by Tlymphocytes. Aim: This study purposed to analyze the serum level of neopterin and to evaluate its correlation with other markers of inflammation in patients with type 2 diabetes at various stages of diabetic nephropathy. Methods: The study done on 80 patients, aged (60 years ±5) with type 2 diabetes, and 60 healthy subjects, aged (50 years±8) recruited from outpatient clinic of nephrology department in Al yarmouk hospital. The serum levels of neopterin, high sensitive C-reactive protein (hs-CRP), interluekin-six (IL-6), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) were assayed by using enzyme-linked immunosorbent assays (ELISA) kits, and studied. Results: The level of serum neopterin was higher in diabetic patients than in control subjects. There were gradual increases of serum neopterin levels from stage two to stage three and four in diabetic patients. Serum neopterin level correlated positively with serum levels of hs-CRP, IL-6, and IFN-γ and correlated negatively with estimated glomerular filtration rate value. Conclusion: Serum neopterin level is elevated and correlated with the severity of diabetic nephropathy. It may use as a good biomarker for an accurate identification and prognosis of the diseases associated with the activation of cell-mediated immunity.

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Profile of the Immune and Inflammatory Response in Individuals With Prediabetes and Type 2 Diabetes

Cited by 215 publications

References 39 publications

Endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation

Endoplasmic reticulum stress and the unfolded protein response in pancreatic islet inflammation

Biomarkers of subclinical inflammation and increases in glycaemia, insulin resistance and beta-cell function in non-diabetic individuals: the Whitehall II study

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