Role of inflammation in diabetic complications

Navarro, Juan F.; Mora, Carmen

doi:10.1093/ndt/gfi155

Cited by 208 publications

(152 citation statements)

References 31 publications

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“…As a reported cause of insulin resistance (42) and diabetes complications (43), several small clinical trials have targeted TNF in diabetes (44)(45)(46)(47). The vast majority of these investigations primarily focused on blood glucose control and insulin sensitivity as clinical end points (44)(45)(46); a few of these trials indirectly assessed vasodilator responses via forearm perfusion (46,47).…”

Section: Discussionmentioning

confidence: 99%

Tumor Necrosis Factor/Sphingosine-1-Phosphate Signaling Augments Resistance Artery Myogenic Tone in Diabetes

et al. 2016

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Diabetes strongly associates with microvascular complications that ultimately promote multiorgan failure. Altered myogenic responsiveness compromises tissue perfusion, aggravates hypertension, and sets the stage for later permanent structural changes to the microcirculation. We demonstrate that skeletal muscle resistance arteries isolated from patients with diabetes have augmented myogenic tone, despite reasonable blood glucose control. To understand the mechanisms, we titrated a standard diabetes mouse model (high-fat diet plus streptozotocin [HFD/STZ]) to induce a mild increase in blood glucose levels. HFD/STZ treatment induced a progressive myogenic tone augmentation in mesenteric and olfactory cerebral arteries; neither HFD nor STZ alone had an effect on blood glucose or resistance artery myogenic tone. Using gene deletion models that eliminate tumor necrosis factor (TNF) or sphingosine kinase 1, we demonstrate that vascular smooth muscle cell TNF drives the elevation of myogenic tone via enhanced sphingosine-1-phosphate (S1P) signaling. Therapeutically antagonizing TNF (etanercept) or S1P (JTE013) signaling corrects this defect. Our investigation concludes that vascular smooth muscle cell TNF augments resistance artery myogenic vasoconstriction in a diabetes model that induces a small elevation of blood glucose. Our data demonstrate that microvascular reactivity is an early disease marker and advocate establishing therapies that strategically target the microcirculation.

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Section: Discussionmentioning

confidence: 99%

Tumor Necrosis Factor/Sphingosine-1-Phosphate Signaling Augments Resistance Artery Myogenic Tone in Diabetes

et al. 2016

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“…[7][8][9] It is a transmembrane homotrimeric protein generated by many cells, including fat, endothelial, and white blood cells. Subsequently, TNFa and its receptors are shed from the cell surface by a disintegrin and metalloproteinase 17.…”

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confidence: 99%

“…7 Experimental studies of the roles of the TNF pathway in the development of diabetic nephropathy and other kidney diseases were recently reviewed. [7][8][9][10] In addition to these laboratory studies, investigations in humans with T2D have associated the level of circulating markers of the TNF pathway with the risk of abnormal urinary albumin excretion, impaired renal function, and cardiovascular death. 5,[11][12][13] However, the authors of these studies did not seek to separate the effect of free TNFa from that of total TNFa or to investigate the independent effects of each of the TNFRs.…”

mentioning

confidence: 99%

Circulating TNF Receptors 1 and 2 Predict ESRD in Type 2 Diabetes

Niewczas

Gohda

Skupień

et al. 2012

Journal of the American Society of Nephrology

417

395

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Levels of proinflammatory cytokines associate with risk for developing type 2 diabetes but whether chronic inflammation contributes to the development of diabetic complications, such as ESRD, is unknown. In the 1990s, we recruited 410 patients with type 2 diabetes for studies of diabetic nephropathy and recorded their characteristics at enrollment. During 12 years of follow-up, 59 patients developed ESRD (17 per 1000 patient-years) and 84 patients died without ESRD (24 per 1000 patient-years). Plasma markers of systemic inflammation, endothelial dysfunction, and the TNF pathway were measured in the study entry samples. Of the examined markers, only TNF receptors 1 and 2 (TNFR1 and TNFR2) associated with risk for ESRD. These two markers were highly correlated, but ESRD associated more strongly with TNFR1. The cumulative incidence of ESRD for patients in the highest TNFR1 quartile was 54% after 12 years but only 3% for the other quartiles (P,0.001). In Cox proportional hazard analyses, TNFR1 predicted risk for ESRD even after adjustment for clinical covariates such as urinary albumin excretion. Plasma concentration of TNFR1 outperformed all tested clinical variables with regard to predicting ESRD. Concentrations of TNFRs moderately associated with death unrelated to ESRD. In conclusion, elevated concentrations of circulating TNFRs in patients with type 2 diabetes at baseline are very strong predictors of the subsequent progression to ESRD in subjects with and without proteinuria.

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“…5 Navarro JF proposed that activated innate immunity and inflammation are relevant factors in the pathogenesis of diabetes, with convincing data that type 2 diabetes includes an inflammatory component. 6 Woo et al, proved that elevated systemic neutrophil count is associated with the presence and severity of retinopathy as well as diabetes. This result indicates that systemic subclinical inflammation is related with retinopathy, and neutrophil-mediated inflammation may play an important role in the pathogenesis of retinopathy.…”

Section: Discussionmentioning

confidence: 99%

Study of relationship between WBC count and Diabetic complications

2017

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Background: There is plenty of evidence to support the fact that inflammation is a risk factor for atherosclerotic diseases and other lifestyle related diseases like diabetes and obesity. Elevated leukocyte count is associated with insulin resistance and is also associated with macro and micro vascular complications in diabetes. This study aimed to investigate the relation between peripheral total and differential WBC count in diabetes and its complications.Methods: This was a cross sectional observational study. It was carried out in the outpatient wing of Department of Medicine, M. G. M. Medical College and M.Y. Hospital. A total of 130 consecutive consenting diabetic patients (type 2) were selected. Those with any obvious stressful condition like acute illness were excluded. All the participants were screened for retinopathy, neuropathy, cerebrovascular disease and cardiovascular disease by history and clinical examination and had their height, weight, waist circumference, hip circumference and white blood cell counts notedResults: In the present study, most of the patients were middle aged patients (46 out of 130 were in age group 51-60 years) and were obese (60/130 had BMI of 26 to 30) with most of them having abdominal obesity (87% males i.e. 48/55 had waist hip ratio >0.90, 56% females i.e. 42/75 had waist hip ratio >0.85). It was found that, amongst 130 patients with type 2 diabetes 56% have WBC counts on the higher side of the normal range i.e. 7000-11000/cu mm. Polymorphs were also on higher side of the normal range in 47% of patients i.e. PMN= 61-70% and 26% had polymorphs above 70%. About 61% patients had monocyte count >6%. Out of the 130 patients, 35 had retinopathy, 57 had neuropathy and 9 had nephropathy as micro vascular complications while as macro vascular complications, 9 had a history of CVA, 14 had CAD and 4 had PVD. Also, maximum patients having micro and macro vascular complications had WBC counts in the range of 7000-11000.Conclusions: An elevated leukocyte count even within the normal range was associated with chronic complications in type 2 diabetes and can be used to predict development of micro and macro vascular complications in patients diagnosed with type 2 diabetes.

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Role of inflammation in diabetic complications

Cited by 208 publications

References 31 publications

Tumor Necrosis Factor/Sphingosine-1-Phosphate Signaling Augments Resistance Artery Myogenic Tone in Diabetes

Tumor Necrosis Factor/Sphingosine-1-Phosphate Signaling Augments Resistance Artery Myogenic Tone in Diabetes

Circulating TNF Receptors 1 and 2 Predict ESRD in Type 2 Diabetes

Study of relationship between WBC count and Diabetic complications

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