Leukocyte Profiles Differ Between Type 1 and Type 2 Diabetes and Are Associated With Metabolic Phenotypes: Results From the German Diabetes Study (GDS)

Menart-Houtermans, Barbara; Rütter, R; Nowotny, Bettina; Rosenbauer, Joachim; Koliaki, Chrysi; Kahl, S.; Simon, Marie‐Christine; Szendroedi, Julia; Schloot, Nanette C.; Roden, Michael

doi:10.2337/dc14-0316

Cited by 70 publications

(55 citation statements)

References 40 publications

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“…The finding suggests that T2-MZP B cells are involved in metabolic regulation. These observations are consistent with a previous study showing that glycemia and lipidemia are associated with immune cells (35). …”

Section: Discussionsupporting

confidence: 94%

Altered Peripheral B-Lymphocyte Subsets in Type 1 Diabetes and Latent Autoimmune Diabetes in Adults

et al. 2015

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OBJECTIVEB lymphocytes play an important role in the immunopathogenesis of autoimmune diabetes. We hypothesized that the altered B-cell subset phenotype is associated with autoimmune diabetes.RESEARCH DESIGN AND METHODSPatients with type 1 diabetes (T1D) (n = 81), latent autoimmune diabetes in adults (LADA) (n = 82), or type 2 diabetes (T2D) (n = 95) and healthy control subjects (n = 218) with normal glucose tolerance (NGT) were recruited. We determined the percentage of circulating B-lymphocyte subsets, including CD19+CD23−CD21+ (marginal zone B [MZB]), CD19+CD23+CD21− (follicular B [FoB]), and CD19+CD5+CD1dhi (interleukin-10–producing regulatory B [B10]) cells by flow cytometry.RESULTSPatients with T1D or LADA had increased percentages of MZB cells and decreased percentages of FoB cells compared with healthy control subjects with NGT and patients with T2D. Moreover, patients with T1D showed the lowest frequency of B10 cells compared with patients with LADA or T2D, whereas healthy control subjects expressed the highest frequency of B10 cells. Of note, the frequency of MZB cells was negatively associated and the frequency of FoB cells was positively associated with fasting C-peptide (FCP). The frequency of B10 cells was positively correlated with FCP and negatively correlated with hemoglobin A1c.CONCLUSIONSThe data show that patients with T1D or LADA express an altered frequency of B-cell subsets, which is associated with islet function and glycemia. These findings suggest that B lymphocytes may be involved in loss of self-tolerance and β-cell destruction and could be used as a biomarker and potential target for immunological intervention.

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Section: Discussionsupporting

confidence: 94%

Altered Peripheral B-Lymphocyte Subsets in Type 1 Diabetes and Latent Autoimmune Diabetes in Adults

et al. 2015

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“…In diabetes subjects, monocyte counts are increased in T2D, but not T1D patients [21, 22]. It would be interesting to investigate whether subsets of monocytes are affected in T1D patients, especially because animal studies show that hyperglycemia specifically increases inflammatory Ly6-C hi monocytes, whereas non-inflammatory Ly6-C lo monocytes were largely unaffected [23].…”

Section: Hyperglycemia Associates With Monocyte Activation To Contribmentioning

confidence: 99%

Diabetes propels the risk for cardiovascular disease: sweet monocytes becoming aggressive?

Diepen

Thiem

Stienstra

et al. 2016

Cell. Mol. Life Sci.

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Diabetes strongly predisposes to cardiovascular disease (CVD), the leading cause of mortality in these patients, as well as in the entire population. Hyperglycemia is an important cardiovascular risk factor as shown by the observation that even transient periods of hyperglycemia, despite return to normoglycemia during follow-up, increase the risk for CVD, a phenomenon termed ‘hyperglycemic memory’. The molecular mechanisms underlying this phenomenon remain largely unknown. As inflammation plays an important role in the pathogenesis of atherosclerosis, we propose that long-term functional reprogramming of monocytes and macrophages, induced by hyperglycemia, plays an important role in the phenomenon of hyperglycemic memory leading to cardiovascular complications in patients with diabetes. In this review, we discuss recent insights showing that innate immune cells possess the capacity to reprogram their function through epigenetically mediated rewiring of gene transcription, a process termed ‘trained immunity’. The long-term reprogramming of monocytes can be induced by microbial as well as metabolic products, and involves a shift in cellular metabolism from oxidative phosphorylation to aerobic glycolysis. We hypothesize that hyperglycemia in diabetes patients induces long-term activation of monocytes and macrophages through similar mechanisms, thereby contributing to plaque development and subsequent macrovascular complications.

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“…Fractalkine, also known as CX3CL1, is a chemokine with chemotactic activity for monocytes, T cells, and NK cells, all of which play important roles in the development of numerous inflammatory conditions including arthritis, atherosclerosis, insulin resistance and T2D [19–21]. However, it is not clear whether the plasma fractalkine levels are modulated in T2D, and if so, how do these changes relate with the inflammatory chemokines and cytokines in diabetic patients.…”

Section: Introductionmentioning

confidence: 99%

Increased circulatory levels of fractalkine (CX3CL1) are associated with inflammatory chemokines and cytokines in individuals with type-2 diabetes

Sindhu

Akhter

Arefanian

et al. 2017

J Diabetes Metab Disord

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BackgroundFractalkine (CX3CL1) is involved in the development of numerous inflammatory conditions including metabolic diseases. However, changes in the circulatory fractalkine levels in type-2 diabetes (T2D) and their relationship with inflammatory chemokines/cytokines remain unclear. The aim of the study was to determine the T2D-associated modulations in plasma fractalkine levels and investigate their relationship with circulatory chemokines/cytokines.MethodsA total of 47 plasma samples were collected from 23 T2D and 24 non-diabetic individuals selected over a wide range of body mass index (BMI). Clinical metabolic parameters were determined using standard commercial kits. Fractalkine and chemokines/cytokines were measured using Luminex X-MAP® technology. C-reactive protein (CRP) was measured by ELISA. The data were compared using unpaired t-test and the dependence between two variables was assessed by Pearson’s correlation coefficient (r).ResultsPlasma fractalkine levels were significantly higher (P = 0.005) in T2D patients (166 ± 14.22 pg/ml) as compared with non-diabetics (118 ± 8.90 pg/ml). In T2D patients, plasma fractalkine levels correlated positively (P ≤ 0.05) with inflammatory chemokines/cytokines including CCL3 (r = 0.52), CCL4 (r = 0.85), CCL11 (r = 0.51), CXCL1 (r = 0.67), G-CSF (r = 0.91), IFN-α2 (r = 0.97), IL-17A (r = 0.79), IL-1β (r = 0.97), IL-12P70 (r = 0.90), TNF-α (r = 0.58), and IL-6 (r = 0.60). In non-diabetic individuals, fractalkine levels correlated (P ≤ 0.05) with those of CCL4 (r = 0.49), IL-1β (r = 0.73), IL-12P70 (r = 0.41), and TNF-α (r = 0.50). Notably, plasma fractalkine levels in T2D patients associated with systemic inflammation (CRP) (r = 0.65, P = 0.02).ConclusionsThe altered plasma fractalkine levels associate differentially with inflammatory chemokines/cytokines in T2D patients which may have implications for T2D immunopathogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s40200-017-0297-3) contains supplementary material, which is available to authorized users.

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Leukocyte Profiles Differ Between Type 1 and Type 2 Diabetes and Are Associated With Metabolic Phenotypes: Results From the German Diabetes Study (GDS)

Cited by 70 publications

References 40 publications

Altered Peripheral B-Lymphocyte Subsets in Type 1 Diabetes and Latent Autoimmune Diabetes in Adults

Altered Peripheral B-Lymphocyte Subsets in Type 1 Diabetes and Latent Autoimmune Diabetes in Adults

Diabetes propels the risk for cardiovascular disease: sweet monocytes becoming aggressive?

Increased circulatory levels of fractalkine (CX3CL1) are associated with inflammatory chemokines and cytokines in individuals with type-2 diabetes

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