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      Levels of Serum 25(OH)VD 3, HIF-1 α, VEGF, vWf, and IGF-1 and Their Correlation in Type 2 Diabetes Patients with Different Urine Albumin Creatinine Ratio

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      Journal of Diabetes Research
      Hindawi Publishing Corporation

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          Abstract

          Objective. To investigate changes in serum 25(OH)VD 3, HIF-1 α, VEGF, vWf, IGF-1, and their correlation in type 2 diabetes patients at different stages of diabetic kidney disease (DKD). Methods. 502 type 2 diabetes patients were divided into three groups: Normoalbuminuric group (201 patients), Microalbuminuric group (171 patients), and Macroalbuminuric group (130 patients). Serum 25-hydroxyvitamin D 3 [25(OH)VD 3] was measured by chemiluminescence. Serum hypoxia-inducible factor-1 α (HIF-1 α), vascular endothelial growth factor (VEGF), von Willebrand factor (vWf), and insulin-like growth factor-1 (IGF-1) were determined by enzyme-linked immunosorbent assay. We detected the aforementioned serum factors in all cases and 224 control subjects. Results. Serum HIF-1 α, VEGF, vWf, and IGF-1 in type 2 diabetes patients were significantly higher than those in the control group and increased with the increase of Ln(ACR), respectively ( P < 0.001). Serum 25(OH)VD 3 was significantly lower in type 2 diabetes patients and decreased with the increase of Ln(ACR) ( P < 0.001). Ln(ACR) was positively correlated with duration, HbA1c, Scr, BUN, TC, LDL, TG, UA, HIF-1 α, VEGF, IGF-1, vWf, and Fg and negatively correlated with 25(OH)VD 3 and eGFR. Conclusion. Serum HIF-1 α, VEGF, vWf, and IGF-1 may be involved in DKD process through inflammation, angiogenesis, and endothelial injury. Serum 25(OH)VD 3 may have protective effects on DKD partly by inhibiting inflammation, abnormal angiogenesis, and vascular endothelial dysfunction.

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          Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications.

          Recent developments indicate that pathophysiological mechanisms leading to beta-cell damage, insulin resistance, and the vascular complications of diabetes include an activation of the inflammation cascade, endothelial dysfunction, and procoagulant imbalance. Their circulating biomarkers may therefore provide opportunities for early diagnosis and targets for novel treatments. Circulating biomarkers of these pathways such as TNFalpha, IL-6, C-reactive protein (CRP) (inflammation), vascular cellular adhesion molecule-1, interstitial cellular adhesion molecule-1, E-selectin, von Willebrand factor (endothelial dysfunction), plasminogen activator inhibitor-1, fibrinogen, P-selectin (procoagulant state), and adiponectin (antiinflammation) may be associated with development of both type 1 and type 2 diabetes and some studies, particularly in type 2 diabetes, have demonstrated that certain biomarkers may have independent predictive value. Similarly studies have shown that these biomarkers may be associated with development of diabetic nephropathy and retinopathy, and again, particularly in type 2 diabetes, with cardiovascular events as well. Finally, the comorbidities of diabetes, namely obesity, insulin resistance, hyperglycemia, hypertension and dyslipidemia collectively aggravate these processes while antihyperglycemic interventions tend to ameliorate them. Increased CRP, IL-6, and TNFalpha, and especially interstitial cellular adhesion molecule-1, vascular cellular adhesion molecule-1, and E-selectin are associated with nephropathy, retinopathy, and cardiovascular disease in both type 1 and type 2 diabetes. Whereas further work is needed, it seems clear that these biomarkers are predictors of increasing morbidity in prediabetic and diabetic subjects and should be the focus of work testing their clinical utility to identify high-risk individuals as well as perhaps to target interventions.
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            Growth hormone, insulin-like growth factor-1, and the kidney: pathophysiological and clinical implications.

            Besides their growth-promoting properties, GH and IGF-1 regulate a broad spectrum of biological functions in several organs, including the kidney. This review focuses on the renal actions of GH and IGF-1, taking into account major advances in renal physiology and hormone biology made over the last 20 years, allowing us to move our understanding of GH/IGF-1 regulation of renal functions from a cellular to a molecular level. The main purpose of this review was to analyze how GH and IGF-1 regulate renal development, glomerular functions, and tubular handling of sodium, calcium, phosphate, and glucose. Whenever possible, the relative contributions, the nephronic topology, and the underlying molecular mechanisms of GH and IGF-1 actions were addressed. Beyond the physiological aspects of GH/IGF-1 action on the kidney, the review describes the impact of GH excess and deficiency on renal architecture and functions. It reports in particular new insights into the pathophysiological mechanism of body fluid retention and of changes in phospho-calcium metabolism in acromegaly as well as of the reciprocal changes in sodium, calcium, and phosphate homeostasis observed in GH deficiency. The second aim of this review was to analyze how the GH/IGF-1 axis contributes to major renal diseases such as diabetic nephropathy, renal failure, renal carcinoma, and polycystic renal disease. It summarizes the consequences of chronic renal failure and glucocorticoid therapy after renal transplantation on GH secretion and action and questions the interest of GH therapy in these conditions.
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              Neovascularization in diabetes and its complications. Unraveling the angiogenic paradox.

              Diabetes mellitus (DM) is a chronic metabolic disease characterized by the presence of hyperglycemia, which can lead to many complications over time. These complications, such as nephropathy, retinopathy, neuropathy, impaired wound healing and accelerated atherosclerosis, are implicated with a large number of cellular and subcellular changes on vessels. In agreement, evidence indicates that in retinopathy, nephropathy and atherosclerotic plaque, there is excessive angiogenesis, whereas in wound healing and myocardial perfusion, blood vessel growth is impaired. Despite the awareness of this angiogenic paradox, many questions remain unanswered. This review aims at highlighting the different microvascular and macrovascular complications that are often concurrent in diabetic patients. A revision of the recent findings published in the literature regarding the angiogenic paradox will be performed. Apparently, endothelial dysfunction, as well as molecules such as vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF) play a major role in diabetic vascular complications. Specific tissues with impaired angiogenesis exhibit microenvironment features, such as increased PAI-1/uPA ratio and decreased blood flow, whereas TGFbeta increases extracellular matrix deposition, preventing the vascularization process. In addition, the monocytes/macrophages are important in endothelium activation for arteriogenesis and its arteriogenic response is reduced, leading to impaired collateral artery growth. Moreover, molecular mechanisms involved will be addressed, including abnormalities in growth factor, cytokines and metabolic derangements. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                J Diabetes Res
                J Diabetes Res
                JDR
                Journal of Diabetes Research
                Hindawi Publishing Corporation
                2314-6745
                2314-6753
                2016
                16 March 2016
                : 2016
                : 1925424
                Affiliations
                Department of Endocrinology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, China
                Author notes

                Academic Editor: Giovanni Annuzzi

                Article
                10.1155/2016/1925424
                4812448
                27069929
                498d86c6-275b-4e79-85b2-2cc1e81c1c09
                Copyright © 2016 Ying Shao et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 October 2015
                : 25 January 2016
                : 14 February 2016
                Categories
                Research Article

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