Evaluation of biochemical and clinical markers of endothelial dysfunction and their correlation with urinary albumin excretion in patients with type 1 diabetes mellitus

Polat, Şefika Burçak; Uğurlu, Nagihan; Aslan, Nabi; Çuhacı, Neslihan; Ersoy, Reyhan; Çakır, Bekir

doi:10.1590/2359-3997000000116

Cited by 21 publications

(17 citation statements)

References 35 publications

(32 reference statements)

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“…The inflammatory factors, including TNF-α and IL-6, are related to IR in T2DM 37 . In addition, several biological markers related to diabetic risk, such as sICAM-1 and sVCAM-1, are proposed as biomarkers of endothelial dysfunction 38 . Vascular inflammation and increased levels of sICAM-1 and sVCAM-1 were associated with IR 39 .…”

Section: Discussionmentioning

confidence: 99%

Exercise Reduces Insulin Resistance in Type 2 Diabetes Mellitus via Mediating the lncRNA MALAT1/MicroRNA-382-3p/Resistin Axis

Liu

Fan

Xie

et al. 2019

Molecular Therapy - Nucleic Acids

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Insulin resistance (IR) is the primary pathological mechanism underlying type 2 diabetes mellitus (T2DM). Here, the study aimed to ascertain whether and how exercise mediates IR in T2DM. An in vivo mouse model of high-fat diet-induced IR and an in vitro high-glucose-induced IR model were constructed. High long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression was detected in T2MD and was positively correlated with HOMA-IR and resistin levels. Then, short hairpin RNA targeting MALAT1 (sh-MALAT1) or pcDNA-MALAT1 was delivered into human umbilical vein endothelial cells (HUVECs) to knock down or upregulate its expression, respectively. Silencing of MALAT1 resulted in reduced levels of resistin, Ang II, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), endothelin-1 (ET-1), and p-insulin receptor substrate-1 (p-IRS)/ISR-1, and decreased cell migration, as well as enhanced glucose uptake and levels of nitric oxide (NO) and p-Akt/Akt. In the IR mouse model, exercise was observed to downregulate MALAT1 to reduce resistin, whereby exercise reduced homeostatic model assessment-insulin resistance (HOMA-IR). Besides, exercise also elevated microRNA-382-3p (miR-382-3p) expression in the serum of IR mice. Dual-luciferase reporter and RNA binding protein immunoprecipitation (RIP) assays identified that MALAT1 could bind to miR-382-3p to upregulate resistin. Collectively, the key observations of the study provide evidence that inhibition of MALAT1 elevates miR-382-3p to repress resistin, which consequently underlies the mechanism of exercise protecting against IR, highlighting a direction for T2DM therapy development.

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Section: Discussionmentioning

confidence: 99%

Exercise Reduces Insulin Resistance in Type 2 Diabetes Mellitus via Mediating the lncRNA MALAT1/MicroRNA-382-3p/Resistin Axis

Liu

Fan

Xie

et al. 2019

Molecular Therapy - Nucleic Acids

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“…One explanation is that, although local organ-specific reduction of VCAM1 occurs, such as in the kidney, liver and lung (Irwin, et al 2015), systemic VCAM1 expression is not reduced. This is possible because very little is known about the regulation of VCAM1 or the regulation of catabolism of soluble cell adhesion molecules in vivo (Ballantyne and Entman 2002), and sVCAM1 levels are positively associated with the degree of urinary albumin excretion(Polat, et al 2016). The lack of decrease in sVCAM1 is also consistent with continued activity of free haem despite Hp, as discussed further below.…”

Section: Discussionmentioning

confidence: 99%

Sustained treatment of sickle cell mice with haptoglobin increases HO‐1 and H‐ferritin expression and decreases iron deposition in the kidney without improvement in kidney function

et al. 2016

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There is growing evidence that extracellular haemoglobin and haem mediate inflammatory and oxidative damage in sickle cell disease. Haptoglobin (Hp), the scavenger for free haemoglobin, is depleted in most patients with sickle cell disease due to chronic haemolysis. Although single infusions of Hp can ameliorate vaso-occlusion in mouse models of sickle cell disease, prior studies have not examined the therapeutic benefits of more chronic Hp dosing on sickle cell disease manifestations. In the present study, we explored the effect of Hp treatment over a three-month period in sickle mice at two dosing regimens: the first at a moderate dose of 200 mg/kg thrice weekly and the second at a higher dose of 400 mg /kg thrice weekly. We found that only the higher dosing regimen resulted in increased haem-oxygenase-1 and heavy chain ferritin (H-ferritin) expression and decreased iron deposition in the kidney. Despite the decreased kidney iron deposition following Hp treatment, there was no significant improvement in kidney function. However, there was a nearly significant trend towards decreased liver infarction.

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“…Microalbuminuria is associated with an increased risk of fatal and non-fatal cardiovascular disease and all-cause mortality [26]. Abnormality of vascular endothelium has been implicated as constituting a link between microalbuminuria and atherosclerotic cardiovascular disease in type 2 diabetes mellitus [27].…”

Section: Discussionmentioning

confidence: 99%

“…Microalbuminuria reflects systemic and renal transvascular albumin leakage which is perhaps due to the low vessel wall content of the heparan sulfate component of systemic endothelial glycocalyx, a protein rich surface layer on the endothelium [27,33]. This generalized increased vascular permeability also causes leakiness of collagen, cholesterol and advanced glycated end products (AGEs) that have been reported in the myocardium of diabetics and is thought to contribute to geometry remodeling seen in diabetic patients [9].…”

Section: Discussionmentioning

confidence: 99%

Association of Microalbuminuria with Abnormal Left Ventricular Geometry Patterns in Nigerian Normotensive Type 2 Diabetic Patients

Shogade¹

2019

EJPM

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To compare left ventricular (LV) geometry patterns among normotensive type 2 diabetics (NT2DM) with normoalbuminuria, NT2DM with microalbuminuria and healthy controls. A cross-sectional study conducted at the medical outpatient department of a Teaching Hospital from January 2013 to March 2014. Sixty-three normoalbuminuric NT2DM, 71 microalbuminuric NT2DM and fifty-nine healthy controls were recruited. Microalbuminuria was tested for using Micral test strips (Roche, Germany). Trans-thoracic echocardiography was carried out on all subjects. Relative wall thickness (RWT), left ventricular mass index (LVMI) and LV geometry patterns were compared among the three groups. The three groups were age and sex-matched and appropriate statistical tests were used for comparisons with p<0.05. The proportions of abnormal LV geometry (33.3% vs 71.4% vs 84.5%), LVMI and RWT showed a significant stepwise increase from healthy controls through normoalbuminuric NT2DM and to microalbuminuric NT2DM (all p<0.01). Concentric remodeling (CR) was the commonest pattern among the three groups. Left ventricular mass index and RWT correlated significantly with duration of DM and body mass index (all p< 0.01). Microalbuminuria showed a strong direct association with abnormal LV geometry (OR 3.27, 95% CI 1.63-6.57, p<0.01) while duration of DM was found to be an independent predictor of LV geometry remodeling (OR 1.23, 95% CI 1.02-1.49, p = 0.03) among normotensive diabetics. Although CR was the commonest pattern across the three patient groups, those with microalbuminuria had the highest proportion and risk of LV remodeling. Early screening and prompt treatment of microalbuminuria in NT2DM is hereby recommended.

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Evaluation of biochemical and clinical markers of endothelial dysfunction and their correlation with urinary albumin excretion in patients with type 1 diabetes mellitus

Cited by 21 publications

References 35 publications

Exercise Reduces Insulin Resistance in Type 2 Diabetes Mellitus via Mediating the lncRNA MALAT1/MicroRNA-382-3p/Resistin Axis

Exercise Reduces Insulin Resistance in Type 2 Diabetes Mellitus via Mediating the lncRNA MALAT1/MicroRNA-382-3p/Resistin Axis

Sustained treatment of sickle cell mice with haptoglobin increases HO‐1 and H‐ferritin expression and decreases iron deposition in the kidney without improvement in kidney function

Association of Microalbuminuria with Abnormal Left Ventricular Geometry Patterns in Nigerian Normotensive Type 2 Diabetic Patients

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