Inflammation in the pathogenesis of microvascular complications in diabetes

Nguyen, Dung; Shaw, Lynn C.; Grant, Maria B.

doi:10.3389/fendo.2012.00170

Cited by 162 publications

(120 citation statements)

References 103 publications

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“…The prevalence of T2DM is increasing and is predicted to occur in approximately 5 % of the global population by 2025 [3]. The disorder is characterized by insulin resistance, hyperinsulinemia, b-cell dysfunction, and subsequent b-cell failure [4]; T2DM is associated with both microvascular (including retinopathy, nephropathy, and neuropathy) and macrovascular (cardiovascular diseases) complications [5][6][7]. The incidence of cardiovascular diseases is two to fourfold greater among people with T2DM [8].…”

Section: T2dmmentioning

confidence: 99%

Effect of cinnamon supplementation on glucose, lipids levels, glomerular filtration rate, and blood pressure of subjects with type 2 diabetes mellitus

Sengsuk

Sanguanwong²,

Tangvarasittichai

et al. 2015

Diabetol Int

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A randomized, double-blind, placebo-controlled trial was performed to investigate the effect of cinnamon supplementation on glucose, triglyceride (TG), and high density lipoprotein-cholesterol (HDL-C) levels, TG/HDL-C ratio, blood pressure (BP), and estimated glomerular filtration rate (eGFR) for ninety-nine type 2 diabetes mellitus (T2DM) patients. Forty nine (49) patients with T2DM were in the cinnamon group whereas 50 were in the placebo group. All participants received either a cinnamon or placebo capsule daily for the 60-day study period. At the end of the study, median glucose, TG, TG/HDL-C ratio, and BP were significantly decreased (p \ 0.005) whereas HDL-C and eGFR levels were significantly increased (p \ 0.005) in the cinnamon supplementation group. Interestingly, the study also revealed reduction of HbA1c levels after the 60-day study period. In the placebo group, glucose, TG levels tended to increase and HDL-C levels tended to decrease whereas systolic and diastolic BP, HbA1c, and BUN CT were significantly increased and eGFR was significantly reduced (p \ 0.005). Cinnamon supplementation reduced plasma glucose, HbA1c, triglyceride, TG/HDL-C ratio, and BP and increased HDL-C levels and eGFR in subjects with T2DM. Cinnamon supplementation may be beneficial for those with T2DM to prevent and control diabetic complications.

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Section: T2dmmentioning

confidence: 99%

Effect of cinnamon supplementation on glucose, lipids levels, glomerular filtration rate, and blood pressure of subjects with type 2 diabetes mellitus

Sengsuk

Sanguanwong²,

Tangvarasittichai

et al. 2015

Diabetol Int

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“…Development of pathologic ocular angiogenesis is linked with dysregulation of both lipid metabolism (2,3) and altered inflammation/macrophage function (4). Identification of key controlling mechanisms by which lipids and their metabolites modulate retinal tissue toward (or away from) a proinflammatory, proangiogenic state is critical for developing potential treatments.…”

mentioning

confidence: 99%

Nuclear receptor RORα regulates pathologic retinal angiogenesis by modulating SOCS3-dependent inflammation

Sun

Liu

SanGiovanni

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Pathologic ocular angiogenesis is a leading cause of blindness, influenced by both dysregulated lipid metabolism and inflammation. Retinoic-acid-receptor-related orphan receptor alpha (RORα) is a lipid-sensing nuclear receptor with diverse biologic function including regulation of lipid metabolism and inflammation; however, its role in pathologic retinal angiogenesis remains poorly understood. Using a mouse model of oxygen-induced proliferative retinopathy, we showed that RORα expression was significantly increased and genetic deficiency of RORα substantially suppressed pathologic retinal neovascularization. Loss of RORα led to decreased levels of proinflammatory cytokines and increased levels of antiinflammatory cytokines in retinopathy. RORα directly suppressed the gene transcription of suppressors of cytokine signaling 3 (SOCS3), a critical negative regulator of inflammation. Inhibition of SOCS3 abolished the antiinflammatory and vasoprotective effects of RORα deficiency in vitro and in vivo. Moreover, treatment with a RORα inverse agonist SR1001 effectively protected against pathologic neovascularization in both oxygen-induced retinopathy and another angiogenic model of very-low-density lipoprotein receptor (Vldlr)-deficient (Vldlr −/− ) mice with spontaneous subretinal neovascularization, whereas a RORα agonist worsened oxygen-induced retinopathy. Our data demonstrate that RORα is a novel regulator of pathologic retinal neovascularization, and RORα inhibition may represent a new way to treat ocular neovascularization.RORα | neovascularization | retinopathy | inflammation | SOCS3

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“…The tumor necrosis factor (TNF)-a pathway and chronic low-grade inflammation are closely involved in the pathogenesis of diabetesassociated complications (6). In this context, circulating TNF receptors were shown to be associated with diabetic nephropathy in patients with type 1 diabetes (7,8) and T2D (9).…”

mentioning

confidence: 99%

Association of Serum Concentration of TNFR1 With All-Cause Mortality in Patients With Type 2 Diabetes and Chronic Kidney Disease: Follow-up of the SURDIAGENE Cohort

et al. 2014

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OBJECTIVERenal dysfunction is a key risk factor for all-cause mortality in patients with type 2 diabetes (T2D). Circulating tumor necrosis factor receptor 1 (TNFR1) was recently suggested as a strong biomarker for end-stage renal failure in T2D. However, its relevance regarding all-cause death has yet to be conclusively established. We aimed to assess the prognostic value of serum TNFR1 concentration for all-cause death in T2D and diabetic kidney disease (DKD) from the SURDIAGENE (Survie, Diabete de type 2 et Genetique) study. RESEARCH DESIGN AND METHODSA total of 522 T2D patients with DKD (estimated glomerular filtration rate [eGFR] <60 and/or urinary albumin-to-creatinine ratio [uACR] >30 mg/mmol) were followed for a median duration of 48 months, and 196 deaths occurred. RESULTSIncidence rate (95% CI) for death increased as quartiles of TNFR1 concentration increased (first quartile: 4.7% patient-years [3.0-6.3%]; second quartile: 7.7% [5.4-10.0%]; third quartile: 9.3% [6.7-11.9%]; fourth quartile: 15.9% [12.2-19.5%]). In multivariate analysis taking age, diabetes duration, HbA1c, uACR, and eGFR into account, compared with the first quartile, patients from the fourth quartile had an adjusted hazard ratio for death of 2.98 (95% CI 1.70-5.23). The integrated discrimination improvement index was statistically significant when adding TNFR1 concentration to the UK Prospective Diabetes Study outcome equation (P = 0.031). CONCLUSIONSTNFR1 is a strong prognostic factor for all-cause mortality in T2D with renal dysfunction, and its clinical utility is suggested in addition to established risk factors for all-cause mortality.

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Inflammation in the pathogenesis of microvascular complications in diabetes

Cited by 162 publications

References 103 publications

Effect of cinnamon supplementation on glucose, lipids levels, glomerular filtration rate, and blood pressure of subjects with type 2 diabetes mellitus

Effect of cinnamon supplementation on glucose, lipids levels, glomerular filtration rate, and blood pressure of subjects with type 2 diabetes mellitus

Nuclear receptor RORα regulates pathologic retinal angiogenesis by modulating SOCS3-dependent inflammation

Association of Serum Concentration of TNFR1 With All-Cause Mortality in Patients With Type 2 Diabetes and Chronic Kidney Disease: Follow-up of the SURDIAGENE Cohort

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