Therapeutic improvement of glucoregulation in newly diagnosed type 2 diabetes patients is associated with a reduction of IL-17 levels

Šumarac-Dumanović, Mirjana; Jeremić, Danka; Pantovic, Aleksandar; Janjetović, Kristina; Stamenkovic-Pejkovic, Danica; Cvijović, Goran; Stevanović, Darko; Micić, Dragan; Trajkovič, Vladimir

doi:10.1016/j.imbio.2013.03.002

Cited by 43 publications

(28 citation statements)

References 45 publications

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“…Roohi A et al [41] reported no association between serum IL17 levels and type 1 and 2 diabetes. Another study found that therapeutic improvement of glucoregulation in newly diagnosed type 2 DM patients is associated with a reduction of IL-17 levels [42]. Our study suggest a protective IL17 cytokine against the risk for type 2 DM (HR = 0.76), which is controversial and novel to the already known pro-inflammatory role of IL17 family cytokines.…”

Section: Discussionmentioning

confidence: 54%

Novel inflammatory markers for incident pre-diabetes and type 2 diabetes: the Rotterdam Study

et al. 2017

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The immune response involved in each phase of type 2 diabetes (T2D) development might be different. We aimed to identify novel inflammatory markers that predict progression from normoglycemia to pre-diabetes, incident T2D and insulin therapy. We used plasma levels of 26 inflammatory markers in 971 subjects from the Rotterdam Study. Among them 17 are novel and 9 previously studied. Cox regression models were built to perform survival analysis. Main Outcome Measures: During a follow-up of up to 14.7 years (between April 1, 1997, and Jan 1, 2012) 139 cases of pre-diabetes, 110 cases of T2D and 26 cases of insulin initiation were identified. In age and sex adjusted Cox models, IL13 (HR = 0.78), EN-RAGE (1.30), CFH (1.24), IL18 (1.22) and CRP (1.32) were associated with incident pre-diabetes. IL13 (0.62), IL17 (0.75), EN-RAGE (1.25), complement 3 (1.44), IL18 (1.35), TNFRII (1.27), IL1ra (1.24) and CRP (1.64) were associated with incident T2D. In multivariate models, IL13 (0.77), EN-RAGE (1.23) and CRP (1.26) remained associated with pre-diabetes. IL13 (0.67), IL17 (0.76) and CRP (1.32) remained associated with T2D. IL13 (0.55) was the only marker associated with initiation of insulin therapy in diabetics. Various inflammatory markers are associated with progression from normoglycemia to pre-diabetes (IL13, EN-RAGE, CRP), T2D (IL13, IL17, CRP) or insulin therapy start (IL13). Among them, EN-RAGE is a novel inflammatory marker for pre-diabetes, IL17 for incident T2D and IL13 for pre-diabetes, incident T2D and insulin therapy start.Electronic supplementary materialThe online version of this article (doi:10.1007/s10654-017-0236-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 54%

Novel inflammatory markers for incident pre-diabetes and type 2 diabetes: the Rotterdam Study

et al. 2017

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“…Relevance of the trialogue (IFNγ→ A. muciniphila →glucose metabolism) to human health is further supported by evidence of increased levels of IFNγ producing cells in diabetes4748 and decrease abundance of A. muciniphila 25323334 in obese and diabetic patients. Interestingly, A. muciniphila levels have been recently demonstrated to negatively correlate with several inflammation markers associated with metabolic disease in mice49.…”

Section: Discussionmentioning

confidence: 96%

Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism

et al. 2016

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Cross-talk between the gut microbiota and the host immune system regulates host metabolism, and its dysregulation can cause metabolic disease. Here, we show that the gut microbe Akkermansia muciniphila can mediate negative effects of IFNγ on glucose tolerance. In IFNγ-deficient mice, A. muciniphila is significantly increased and restoration of IFNγ levels reduces A. muciniphila abundance. We further show that IFNγ-knockout mice whose microbiota does not contain A. muciniphila do not show improvement in glucose tolerance and adding back A. muciniphila promoted enhanced glucose tolerance. We go on to identify Irgm1 as an IFNγ-regulated gene in the mouse ileum that controls gut A. muciniphila levels. A. muciniphila is also linked to IFNγ-regulated gene expression in the intestine and glucose parameters in humans, suggesting that this trialogue between IFNγ, A. muciniphila and glucose tolerance might be an evolutionally conserved mechanism regulating metabolic health in mice and humans.

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“…However, previous study has shown that serum level of IL-17 was elevated in type 2 diabetes mellitus patients with poor glucoregulation compared to those with good glucoregulation, and that reduction of HbA1c upon treatment was associated with a significant decrease in serum IL-17 level [39]. In addition, Xu et al [40] have demonstrated that the ratio of IL-17A + CD4 + T cells in peripheral blood mononuclear cells increased in rats with streptozotocin (STZ)-induced type 1 diabetes, and intravitreal injection of anti-IL 23Rp19 antibody, which blocks the IL-23-Th17-IL-17A pathway, improved the blood-retinal barrier function in STZ-treated rats.…”

Section: Discussionmentioning

confidence: 99%

Association between aqueous humor and vitreous fluid levels of Th17 cell-related cytokines in patients with proliferative diabetic retinopathy

et al. 2017

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Inflammation is known to be involved in the progression of diabetic retinopathy. We have recently reported that vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFα are higher than the respective serum levels in proliferative diabetic retinopathy (PDR) patients, and that vitreous levels of these cytokines are higher in PDR than in other non-inflammatory vitreoretinal diseases or uveitis associated with sarcoidosis. In the present study, we investigated inflammatory cytokines including Th17 cell-related cytokines in aqueous humor samples obtained from eyes with PDR, and analyzed the association between the aqueous humor and vitreous fluid levels of individual cytokines. The study group consisted of 31 consecutive type 2 diabetic patients with PDR who underwent cataract surgery and vitrectomy for vitreous hemorrhage and/or tractional retinal detachment. Undiluted aqueous humor was collected during cataract surgery, and then vitreous fluid was obtained using a 25G vitreous cutter inserted into the mid-vitreous cavity at the beginning of vitrectomy. IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, soluble CD40 ligand (sCD40L), and TNFα levels in the aqueous humor and vitreous fluid were measured using a beads-array system. Although IL-17A was detected in the aqueous humor of eyes with PDR and the level correlated with IL-17A level in the vitreous fluid, both percent detectable and level of IL-17A in the aqueous humor were significantly lower than those in the vitreous fluid. Vitreous IL-17A level was related significantly to IL-10, IL-22, and TNFα levels in aqueous humor as well as in vitreous fluid, On the other hand, aqueous IL-17A level was not related significantly to aqueous or vitreous levels of IL-10, IL-22 or TNFα level. The present study demonstrated that IL-17A level and detectable rate in the aqueous humor of patients with PDR are markedly lower than those in the vitreous fluid and aqueous IL-17A does not correlate with vitreous levels of other cytokines, and hence should not be used as a surrogate for IL-17A in the vitreous fluid.

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Therapeutic improvement of glucoregulation in newly diagnosed type 2 diabetes patients is associated with a reduction of IL-17 levels

Cited by 43 publications

References 45 publications

Novel inflammatory markers for incident pre-diabetes and type 2 diabetes: the Rotterdam Study

Novel inflammatory markers for incident pre-diabetes and type 2 diabetes: the Rotterdam Study

Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism

Association between aqueous humor and vitreous fluid levels of Th17 cell-related cytokines in patients with proliferative diabetic retinopathy

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