Leukocytic dysregulation in children with type 1 diabetes: relation to diabetic vascular complications

2022 ◽  
Author(s):  
Nouran Yousef Salah ◽  
Nesrine Radwan ◽  
Heba Mohamed Atif
Keyword(s):  
Type 1 Diabetes ◽  
Vascular Complications ◽  
Diabetic Vascular Complications

scholarly journals Plasma osteoprotegerin levels are associated with glycaemic status, systolic blood pressure, kidney function and cardiovascular morbidity in type 1 diabetic patients

2006 ◽  
Vol 154 (1) ◽  
pp. 75-81 ◽  
Author(s):  
Lars Melholt Rasmussen ◽  
Lise Tarnow ◽  
Troels Krarup Hansen ◽  
Hans-Henrik Parving ◽  
Allan Flyvbjerg
Keyword(s):  
Blood Pressure ◽  
Type 1 Diabetes ◽  
Systolic Blood Pressure ◽  
Kidney Function ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Diabetic Vascular Complications ◽  
Patients With Diabetes ◽  
Type 1 Diabetic Patients

Objective: The bone-related peptide osteoprotegerin (OPG) has recently been found in increased amounts in the vasculature in diabetes. It is produced by vascular smooth muscle and endothelial cells, and may be implicated in the development of vascular calcifications. OPG is present in the circulation, where increased amounts have been observed in patients with diabetes. In this study, we examined whether plasma OPG is associated with the glycaemic and vascular status of patients with type 1 diabetes. Methods: Two gender-, age- and duration-comparable groups of type 1 diabetic patients either with (n = 199) or without (n = 192) signs of diabetic nephropathy were studied. Plasma OPG was determined by an ELISA. Results: The plasma OPG concentration was significantly higher in patients with nephropathy than those without (3.11 (2.49–3.99) vs 2.57 (2.19–3.21) (median (interquartiles), ng/ml), P < 0.001). Plasma OPG correlated with haemoglobin A1c (HbA1c), systolic blood pressure and age in both groups and, in addition, with kidney function in the nephropathic group. These correlations remained significant in multivariate models. In addition, we found that plasma OPG concentrations were increased among patients with cardiovascular diseases (CVD), both in the normoalbuminuric and the nephropathic groups. The differences between nephropathic and normoalbuminuric, as well as subgroups with and without CVD, could largely be ascribed to changes in HbA1c, age, systolic blood pressure and creatinine. Conclusion: OPG is associated with glycaemic control and CVD in patients with type 1 diabetes, compatible with the hypothesis that OPG is associated with the development of diabetic vascular complications.

scholarly journals A review of risk factors associated with insulin omission for weight loss in type 1 diabetes

2021 ◽  
pp. 135910452110261
Author(s):  
Rebecca Hall ◽  
Leanna Keeble ◽  
Sandra-Ilona Sünram-Lea ◽  
Michelle To
Keyword(s):  
Risk Factors ◽  
Weight Loss ◽  
Type 1 Diabetes ◽  
Body Dissatisfaction ◽  
Vascular Complications ◽  
Anxiety And Depression ◽  
Weight Concerns ◽  
Complications And Mortality ◽  
Insulin Omission

Research suggests that as many as 60% of people with type 1 diabetes (T1D) admit to misusing insulin. Insulin omission (IO) for the purpose of weight loss, often referred to as diabulimia, is a behaviour becoming increasingly recognised, not least since prolonged engagement can lead to serious vascular complications and mortality. Several risk factors appear to be relevant to the development of IO, most notably gender, anxiety and depression and increased weight concerns and body dissatisfaction. Evidence suggests that women, especially young girls, are more likely to omit insulin as a method of weight loss compared to men. Mental health conditions such as anxiety and depression are increasingly prevalent in people with T1D compared to their peers, and appear to contribute to the risk of IO. Increased weight concerns and body dissatisfaction are further prominent risk factors, especially given increases in weight which often occur following diagnosis and the monitoring of weight by diabetes teams. This review presents evidence examining these risk factors which increase the likelihood of a person with T1D engaging in IO and highlights the complications associated with prolongment of the behaviour. Further research looking at the comorbidities of these risk factors, alongside other factors, would provide greater insight into understanding IO in people with T1D.

scholarly journals Sphingosine-1-phosphate inhibits high glucose-mediated ERK1/2 action in endothelium through induction of MAP kinase phosphatase-3

2009 ◽  
Vol 296 (2) ◽  
pp. C339-C345 ◽  
Author(s):  
Angela M. Whetzel ◽  
David T. Bolick ◽  
Catherine C. Hedrick
Keyword(s):  
Endothelial Cells ◽  
Type 1 Diabetes ◽  
Vascular Complications ◽  
Nod Mice ◽  
Endothelial Activation ◽  
Adhesion Assay ◽  
Monocyte Adhesion ◽  
Map Kinase Phosphatase ◽  
Sphingosine 1 Phosphate

Endothelial activation is a key early event in vascular complications of Type 1 diabetes. The nonobese diabetic (NOD) mouse is a well-characterized model of Type 1 diabetes. We previously reported that Type 1 diabetic NOD mice have increased endothelial activation, with increased production of monocyte chemoattractant protein (MCP)-1 and IL-6, and a 30% increase of surface VCAM-1 expression leading to a fourfold increase in monocyte adhesion to the endothelium. Sphingosine-1-phosphate (S1P) prevents monocyte:endothelial interactions in these diabetic NOD mice. Incubation of diabetic NOD endothelial cells (EC) with S1P (100 nmol/l) reduced ERK1/2 phosphorylation by 90%, with no significant changes in total ERK1/2 protein. In the current study, we investigated the mechanism of S1P action on ERK1/2 to reduce activation of diabetic endothelium. S1P caused a significant threefold increase in mitogen-activated kinase phosphatase-3 (MKP-3) expression in EC. MKP-3 selectively regulates ERK1/2 activity through dephosphorylation. Incubation of diabetic NOD EC with S1P and the S1P1-selective agonist SEW2871 significantly increased expression of MKP-3 and reduced ERK1/2 phosphorylation, while incubation with the S1P1/S1P3 antagonist VPC23019 decreased the expression of MKP-3, both results supporting a role for S1P1 in MKP-3 regulation. To mimic the S1P-mediated induction of MKP-3 diabetic NOD EC, we overexpressed MKP-3 in human aortic endothelial cells (HAEC) cultured in elevated glucose (25 mmol/l). Overexpression of MKP-3 in glucose-cultured HAEC decreased ERK1/2 phosphorylation and resulted in decreased monocyte:endothelial interactions in a static monocyte adhesion assay. Finally, we used small interfering RNA to MKP-3 and observed increased monocyte adhesion. Moreover, S1P was unable to inhibit monocyte adhesion in the absence of MKP-3. Thus, one mechanism for the anti-inflammatory action of S1P in diabetic EC is inhibition of ERK1/2 phosphorylation through induction of MKP-3 expression via the S1P-S1P1 receptor axis.

Abstract 344: Endothelin-1 Overexpression Exaggerates Diabetes-induced Endothelial Dysfunction

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Noureddine IDRIS KHODJA ◽  
Muhammad Oneeb Rehman Mian ◽  
Tlili Barhoumi ◽  
Sofiane Ouerd ◽  
Jordan Gornitsky ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Endothelial Dysfunction ◽  
Vascular Complications ◽  
Fold Increase ◽  
Wild Type ◽  
No Donor ◽  
Meclofenamic Acid ◽  
Fibronectin Expression ◽  
Endothelium Dependent Relaxation

Objective: Vascular disease associated with endothelial dysfunction is a major cause of morbidity in patients with type-1 diabetes. Endothelin (ET)-1 plays a role in diabetes-induced vascular complications, since ET-1 type A receptor blockade reduces diabetes-induced vascular injury. However, whether ET-1 contributes to diabetes-induced endothelial dysfunction remains unproven. We hypothesized that vascular ET-1 overexpression will exaggerate diabetes-induced endothelial dysfunction. Methods: Diabetes was induced by streptozotocin treatment (STZ, 55 mg/kg/day, ip) for 5 days in 6-week-old male wild-type (WT) mice and in mice overexpressing ET-1 restricted to the endothelium (eET-1). Mice were studied 14 weeks later. Blood was collected to determine glucose. Mesenteric artery reactivity and remodeling were evaluated using pressurized myography and aortic fibronectin expression by immnunofluorescence. Results: STZ-induced diabetes was confirmed by a 3-fold increase in glycemia in WT and eET-1 ( P <0.001). Diabetes impaired endothelium-dependent relaxation (EDR) reponses to acetylcholine in WT (60.9±6.4% vs 83.9±3.4%, P <0.05) and eET-1 (48.6±5.1% vs 81.5±5.2%, P <0.001). EDR impairment was exaggerated in eET-1 compared to WT ( P <0.05). Meclofenamic acid, an inhibitor of cyclooxygenase, increased EDR in eET-1 compared to WT (78.4±9.4% vs 66.7±3.2%, P <0.01), which was not observed in diabetic mice. L-NAME, an inhibitor of nitric oxide (NO) synthase, completely blocked EDR in WT, eET-1 and diabetic WT, but not in diabetic eET-1 (4.1±1.6%, 6.4±5.7%, 2.2±4.6% and 26.6±4.6%, P <0.05). Apamin plus Tram34, inhibitors of endothelium-dependent hyperpolarization inhibited EDR in the four groups. Endothelium-independent relaxation to sodium nitroprusside, a NO donor, was similar in the four groups. Diabetes reduced media/lumen in WT (2.7±0.3 vs 3.6±0.3, P <0.05) and eET-1 (2.9±0.2 vs 3.8±0.3, P <0.05). Diabetes decreased aortic fibronectin expression in WT (94.0±11.0 vs. 151.9±21.8 RFU/μm 2 , P <0.05) and eET-1 (66.3±8.7 vs. 146.6±20.7 RFU/μm 2 , P <0.05). Conclusion: ET-1 contributes to alterations in several pathways mediating endothelium-dependent relaxation in type-1 diabetes, leading to exaggerated endothelial dysfunction.

scholarly journals Molecular disorders of erythrocyte and platelet membranes in vascular complications of type 1 diabetes mellitus

2006 ◽  
Vol 5 (4) ◽  
pp. 33-41
Author(s):  
Ye. B. Kravets ◽  
N. V. Ryazantseva ◽  
N. M. Yakovleva ◽  
V. N. Butusova ◽  
O. M. Choudakova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Vascular Complications ◽  
Platelet Membranes

scholarly journals Sexual Dysfunction in Young Women with Type 1 Diabetes

2020 ◽  
Vol 17 (12) ◽  
pp. 4468
Author(s):  
Edyta Cichocka ◽  
Michał Jagusiewicz ◽  
Janusz Gumprecht
Keyword(s):  
Type 1 Diabetes ◽  
Urinary Tract ◽  
Sexual Function ◽  
Urinary Tract Infections ◽  
Vascular Complications ◽  
Chronic Complications ◽  
Patients With Diabetes ◽  
The Mean ◽  
Tract Infections

Introduction: Sexual dysfunctions (SD) are chronic complications that can develop due to vascular complications or autonomic neuropathy. Additionally, such complications can be of hormonal, infectious or psychogenic etiology. Objectives: The aim of study was to assess the sexual function and acceptance of the chronic disease in young sexually active women with type 1 diabetes (T1DM). Materials and methods: A total of 169 female patients with T1DM completed two standardized questionnaires, the Female Sexual Function Index (FSFI) and the Acceptance of Illness Scale (AIS). Other medical data were collected from medical history. Results: The mean FSFI score was 27.96 ± 5.00, and the mean AIS score was 29.67 ± 8.28. The score < 26 points in FSFI was obtained by 28.7% of patients. Analysis of correlation between the FSFI and the AIS showed that the higher the score on the FSFI, the higher the score on the AIS. Patients who underwent regular physical activity (55%) had a significantly higher acceptance of the disease (p = 0.0026) and reported painful intercourse significantly less frequently (p = 0.01). The value of HbA1c in the study group was 7.31 ± 1.25%. Patients with poorer glycemic control (HbA1c > 8%) obtained significantly lower scores on the FSFI (p = 0.03), whereas no differences were found on the AIS. Diabetes-related complications were observed in 25.5% of patients. The presence of chronic complications did not affect the results of the FSFI or the AIS. Patients with diabetes and hypertension had poorer functioning in the sexual sphere and had significantly lower scores on the FSFI. Past or present history of depression was reported by 36% of patients and also negatively affected acceptance of diabetes (p = 0.0015). Patients who reported recurrent urinary tract infections (17%) achieved significantly lower scores on the FSFI (p = 0.03) and showed that sex-related pain was significantly more prevalent (p = 0.02). In the case of the statement related to the embarrassment of people around the patient due to diabetes, patients with lower scores complained of SD significantly more often (p = 0.0033). Past deliveries, the type of labor, the use of contraceptives or the number of sexual partners had no influence on the overall assessment in both scales. However, in terms of desire, women who had delivered obtained higher scores (p = 0.0021). Conclusion: SD in women with T1DM may result from diabetes-related complications, hormonal disorders or recurrent genital or urinary tract infections. However, they usually have a psychological basis due to the lack of acceptance of the problems related to the treatment of diabetes.

Relationship of Soluble RAGE and RAGE Ligands HMGB1 and EN-RAGE to Endothelial Dysfunction in Type 1 and Type 2 Diabetes Mellitus

2012 ◽  
Vol 120 (05) ◽  
pp. 277-281 ◽  
Author(s):  
J. Škrha Jr ◽  
M. Kalousová ◽  
J. Švarcová ◽  
A. Muravská ◽  
J. Kvasnička ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Advanced Glycation Endproducts ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
Glycation Endproducts ◽  
Diabetic Vascular Complications ◽  
Soluble Rage

AbstractReceptor for advanced glycation endproducts (RAGE) plays the essential role in the pathogenesis of diabetic vascular complications. The aim of the study was to compare concentration of soluble RAGE and its ligands (EN-RAGE and HMGB1) with different biochemical parameters in Type 1 (T1DM) and Type 2 (T2DM) diabetes mellitus.Total number of 154 persons (45 T1DM, 68 T2DM, 41 controls) was examined and concentrations of sRAGE, EN-RAGE and HMGB1 were measured and compared to diabetes control, albuminuria, cell adhesion molecules and metalloproteinases (MMPs).Mean serum sRAGE concentration was higher in T1DM as compared to controls (1137±532 ng/l vs. 824±309 ng/l, p<0.01). Similarly, EN-RAGE was significantly higher in both diabetic groups (p<0.001) and HMGB1 concentrations were elevated in T2DM patients (p<0.01). Significant relationship was found between MMP9 and HMGB1 and EN-RAGE in diabetic patients. Inverse relationship was observed between MMP2 and MMP9 in both types of diabetic patients (r= − 0.602, p<0.002 and r= − 0.771, p<0.001). Significant positive correlation was found between sRAGE and ICAM-1, VCAM-1 or vWF (p<0.01 to p<0.001).We conclude that serum sRAGE and RAGE ligands concentrations reflect endothelial dysfunction developing in diabetes.

scholarly journals Interplay between Type 1 Diabetes Mellitus and Celiac Disease: Implications in Treatment

2018 ◽  
Vol 36 (6) ◽  
pp. 399-408 ◽  
Author(s):  
Navchetan Kaur ◽  
Sanjay K. Bhadada ◽  
Ranjana W. Minz ◽  
Devi Dayal ◽  
Rakesh Kochhar
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Celiac Disease ◽  
Type 1 Diabetes Mellitus ◽  
Prevalence Rate ◽  
Vascular Complications ◽  
Complex Situation ◽  
Disease Etiology ◽  
Organ Specific

Background: A complex interplay between genetic and environmental factors contributes to disease etiology of most of the autoimmune disorders. Type 1 diabetes mellitus (T1DM) and celiac disease (CD) are polygenic autoimmune diseases that have high propensity to coexist due to shared etiological factors like genetics and clinico-pathological overlaps. Summary: The mean prevalence rate for coexistence of these diseases is 8%, and this value is a gross underestimation as reported from biopsy-proven symptomatic cases. The prevalence rate will rise when studies will excavate bottom layers of the “celiac iceberg” to detect potential and silent celiac cases. The concomitant presence of both these disorders is a complex situation immunologically as well as clinically. There is an accentuated breakdown of tolerance and proinflammatory cytokine storm that leads to the progression of organ-specific autoimmunity to systemic. No immunomodulating drugs are advocated as exogenous insulin supplementation and gluten exclusion are recommended for T1DM and CD respectively. Nevertheless, these pose certain challenges to both the clinicians and the patients, as gluten free diet (GFD) has been described to have an impact on glycemic control, bone health, and vascular complications. Also intermittent gluten intake by these patients due to non-compliance with GFD also stimulates the autoreactive immune cells that result in an augmented immune response. Key Messages: Large public health studies are needed to estimate the prevalence of all forms of CD in T1DM patients. Strict global guidelines need to be formulated for the disease management and prognosis, and there is also a need for an extensive research on each front to thoroughly understand the co-occurrence of these diseases.

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