Association Between Inflammatory Markers and Progression to Kidney Dysfunction: Examining Different Assessment Windows in Patients With Type 1 Diabetes

Baker, Nathaniel L.; Hunt, Kelly J.; Stevens, Danielle; Járai, Gábor; Rosen, Glenn D.; Klein, Richard L.; Virella, Gabriel; Lopes‐Virella, Maria F.

doi:10.2337/dc17-0867

Cited by 22 publications

(15 citation statements)

References 30 publications

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“…Such a shift has been already reported by us previously in LDT1DM 18. Other features of such immunosenescence-like changes, such as an increased level of proinflammatory cytokines with the progression of the disease, have been also reported including our previous works 11 19. In this trial, we described additional changes, such as a reduction in the percentage of CD62L+CD45RA+CD31+ recent emigrants, shortening of T-cell telomeres and subtle expansions in several types of T-cell vβ TCR clones seen mainly in memory T-cell subsets.…”

Section: Discussionsupporting

confidence: 84%

Proinsulin-specific T regulatory cells may control immune responses in type 1 diabetes: implications for adoptive therapy

Gliwiński

Iwaszkiewicz-Grześ

Wołoszyn-Durkiewicz

et al. 2020

BMJ Open Diab Res Care

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ObjectiveHere we looked for possible mechanisms regulating the progression of type 1 diabetes mellitus (T1DM). In this disease, autoaggressive T cells (T conventional cells, Tconvs) not properly controlled by T regulatory cells (Tregs) destroy pancreatic islets.Research design and methodsWe compared the T-cell compartment of patients with newly diagnosed T1DM (NDT1DM) with long-duration T1DM (LDT1DM) ones. The third group consisted of patients with LDT1DM treated previously with polyclonal Tregs (LDT1DM with Tregs). We have also looked if the differences might be dependent on the antigen specificity of Tregs expanded for clinical use and autologous sentinel Tconvs.ResultsPatients with LDT1DM were characterized by T-cell immunosenescence-like changes and expansion of similar vβ/T-cell receptor (TCR) clones in Tconvs and Tregs. The treatment with Tregs was associated with some inhibition of these effects. Patients with LDT1DM possessed an increased percentage of various proinsulin-specific T cells but not GAD65-specific ones. The percentages of all antigen-specific subsets were higher in the expansion cultures than in the peripheral blood. The proliferation was more intense in proinsulin-specific Tconvs than in specific Tregs but the levels of some proinsulin-specific Tregs were exceptionally high at baseline and remained higher in the expanded clinical product than the levels of respective Tconvs in sentinel cultures.ConclusionsT1DM is associated with immunosenescence-like changes and reduced diversity of T-cell clones. Preferential expansion of the same TCR families in both Tconvs and Tregs suggests a common trigger/autoantigen responsible. Interestingly, the therapy with polyclonal Tregs was associated with some inhibition of these effects. Proinsulin-specific Tregs appeared to be dominant in the immune responses in patients with T1DM and probably associated with better control over respective autoimmune Tconvs.Trial registration numberEudraCT 2014-004319-35.

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Section: Discussionsupporting

confidence: 84%

Proinsulin-specific T regulatory cells may control immune responses in type 1 diabetes: implications for adoptive therapy

Gliwiński

Iwaszkiewicz-Grześ

Wołoszyn-Durkiewicz

et al. 2020

BMJ Open Diab Res Care

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“…Glowinska et al showed the relationship between increased sE-selectin concentrations and T1DM, whereas no correlation with T1DM was found for sP-selectin and sL-selectin levels [65]. Other research points towards the positive correlation between sE-selectin levels and retinopathy, nephropathy, and CVD [54,71,74,75]. However, the role of sE-selectin in prediction of cardiovascular complications in diabetes is not fully elucidated.…”

Section: Cell Adhesion Moleculesmentioning

confidence: 99%

The prognostic value of inflammatory and vascular endothelial dysfunction biomarkers in microvascular and macrovascular complications in type 1 diabetes

Wołoszyn-Durkiewicz¹,

Myśliwiec²

2019

pedm

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Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterised by a destruction of pancreatic β cells, which leads to absolute insulin deficiency. Persistently high glycaemia causes vascular damage throughout the body. Microvascular complications comprise the following: nephropathy, retinopathy, and neuropathy. Macrovascular complications include coronary heart disease (CHD), which may result in myocardial infarction, cerebrovascular disease (leading to strokes), and peripheral vascular disease. The pathogenesis of vascular complications is multifactorial and is probably the combination of direct glucose-mediated endothelial damage, oxidative stress, production of sorbitol, and advanced glycation end-products. Precise understanding of these mechanisms could help clinicians to identify diabetic complications earlier and subsequently implement indispensable therapy on time. It is vital to determine biomarkers of microvascular and macrovascular complications in children affected with T1DM. Advanced glycation end-products and their receptors, adhesive molecules, pro-and anti-inflammatory cytokines, enzymes such as N-acetyl-β-D-glucosaminidase, and growth factors are the subject of ongoing studies. Numerous biomarkers of diabetic microangiopathy are already known and may constitute therapeutic targets in the future. Unfortunately, despite substantial progress in the understanding of the processes by which microvascular and macrovascular complications develop, much effort still needs to be devoted to the matter, and further investigations are required.

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“…Nevertheless, few reports have explored the relationship between serum Fib levels and glucose metabolism in patients with newonset stable CAD. Moreover, Fib was also implicated in the presence of macrovascular complications and microvascular disorders in DM, [14,16,17] while there has been no study to investigate the impact of Fib levels on cardiovascular risk in individuals with impaired glucose regulation.…”

Section: Introductionmentioning

confidence: 99%

Fibrinogen is associated with glucose metabolism and cardiovascular outcomes in patients with coronary artery disease

Liu

Shi

et al. 2020

Cardiovasc Diabetol

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Background: The present cohort study aims to examine the relationship between fibrinogen (Fib) levels and glucose metabolism [fasting blood glucose (FBG) and hemoglobin A1c (HbA1c)] and investigate the impact of high Fib on cardiovascular outcomes in patients with stable CAD and pre-diabetes mellitus (pre-DM) or diabetes mellitus (DM). Methods:This study included 5237 patients from March 2011 to December 2015. Patients were distributed into three groups according to Fib levels (low Fib, median Fib, high Fib) and further categorized by glucose metabolism status [normal glucose regulation (NGR), Pre-DM, DM]. All patients were followed up for the occurrences of major adverse cardiovascular events (MACEs), including cardiovascular mortality, nonfatal MI, stroke, and unplanned coronary revascularization.Results: Linear regression analyses showed that FBG and HbA1c levels were positively associated with Fib in overall CAD participants, either with or without DM (all P < 0.001). During an average of 18,820 patient-years of follow-up, 476 MACEs occurred. High Fib was independently associated with MACEs after adjusting for confounding factors [Hazard Ratio (HR): 1.57, 95% confidence interval (CI) 1.26-1.97, P < 0.001]. Furthermore, DM but not pre-DM was a significant predictor of MACEs (P < 0.001 and P > 0.05, respectively). When patients were stratified by both glucose metabolism status and Fib levels, high Fib was associated with a higher risk of MACEs in pre-DM (HR 1.66, 95% CI 1.02-2.71, P < 0.05). Medium and high Fib levels were associated with an even higher risk of MACEs in DM (HR 1.86, 95% CI 1.14-3.05 and HR 2.28, 95% CI 1.42-3.66, all P < 0.05). After adding the combination of Fib and glucose status to the Cox model, the C-statistic was increased by 0.015 (0.001-0.026). Conclusions:The present study suggested that Fib levels were associated with FBG and HbA1c in stable CAD patients. Moreover, elevated Fib was independently associated with MACEs in CAD patients, especially among those with pre-DM and DM, suggesting that Fib may provide incremental value in the cardiovascular risk stratification of pre-DM and DM patients.

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Association Between Inflammatory Markers and Progression to Kidney Dysfunction: Examining Different Assessment Windows in Patients With Type 1 Diabetes

Abstract: Plasma markers of inflammation, endothelial dysfunction, and clotting/fibrinolysis are associated with progression to kidney dysfunction in type 1 diabetes during both short-term and long-term follow-up.

Cited by 22 publications

References 30 publications

Proinsulin-specific T regulatory cells may control immune responses in type 1 diabetes: implications for adoptive therapy

Proinsulin-specific T regulatory cells may control immune responses in type 1 diabetes: implications for adoptive therapy

The prognostic value of inflammatory and vascular endothelial dysfunction biomarkers in microvascular and macrovascular complications in type 1 diabetes

Fibrinogen is associated with glucose metabolism and cardiovascular outcomes in patients with coronary artery disease

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