scholarly journals Thrombopoietin Contributes to Enhanced Platelet Activation in Patients with Type 1 Diabetes Mellitus

2021 ◽  
Vol 22 (13) ◽  
pp. 7032
Author(s):  
Ornella Bosco ◽  
Barbara Vizio ◽  
Gabriella Gruden ◽  
Martina Schiavello ◽  
Bartolomeo Lorenzati ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Platelet Activation ◽  
Healthy Subjects ◽  
Diabetic Patients ◽  
Potential Contribution ◽  
Atherosclerotic Cardiovascular Disease

Atherosclerotic cardiovascular disease is the major cause of morbidity and mortality in patients with type 1 diabetes mellitus (T1DM). Enhanced platelet reactivity is considered a main determinant of the increased atherothrombotic risk of diabetic patients. Thrombopoietin (THPO), a humoral growth factor able to stimulate megakaryocyte proliferation and differentiation, also modulates the response of mature platelets by enhancing both activation and binding to leukocytes in response to different agonists. Increased THPO levels have been reported in different clinical conditions characterized by a generalized pro-thrombotic state, from acute coronary syndromes to sepsis/septic shock, and associated with elevated indices of platelet activation. To investigate the potential contribution of elevated THPO levels in platelet activation in T1DM patients, we studied 28 T1DM patients and 28 healthy subjects. We measured plasma levels of THPO, as well as platelet-leukocyte binding, P-selectin, and THPO receptor (THPOR) platelet expression. The priming activity of plasma from diabetic patients or healthy subjects on platelet–leukocyte binding and the role of THPO on this effect was also studied in vitro. T1DM patients had higher circulating THPO levels and increased platelet–monocyte and platelet–granulocyte binding, as well as platelet P-selectin expression, compared to healthy subjects, whereas platelet expression of THPOR did not differ between the two groups. THPO concentrations correlated with platelet–leukocyte binding, as well as with fasting glucose and Hb1Ac. In vitro, plasma from diabetic patients, but not from healthy subjects, primed platelet–leukocyte binding and platelet P-selectin expression. Blocking THPO biological activity using a specific inhibitor prevented the priming effect induced by plasma from diabetic patients. In conclusion, augmented THPO may enhance platelet activation in patients with T1DM, potentially participating in increasing atherosclerotic risk.

scholarly journals Association of the CCR5 gene with type 1 diabetes mellitus

2013 ◽  
Vol 59 (2) ◽  
pp. 3-6
Author(s):  
O I Kopylova ◽  
T L Kuraeva ◽  
E Iu Lavrikova ◽  
E V Titovich ◽  
A G Nikitin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Healthy Subjects ◽  
Significant Rise ◽  
Diabetic Patients ◽  
Ccr5 Gene ◽  
Base Pair Deletion ◽  
Time Amplification

Aim of the study. To elucidate the association between the polymorphous marker A/del132 of the CCR5 gene with type 1 diabetes mellitus. Materials and methods. The study included 177 patients with type 1 diabetes mellitus (DM1) and 408 healthy subjects (ethnic Russians). CR5 alleles and genotypes were identified with the use of the real-time amplification technique. Results. It was shown that the CCR5 allele without 32 base pair deletion (allele A) predominated in both diabetic patients and diabetes-free subjects. The difference between their occurrence in the two groups was insignificant. At the same time, we documented a significant rise in the frequency of del132/del132 genotype in the diabetic patients compared with the healthy subjects (p=0.008). It is concluded that carriers of the CCR5-del32/del32 genotype in the Russian population of Moscow are at high risk of developing type 1 diabetes mellitus.

scholarly journals Association of the polymorphous marker G6230A of the CTLA4 gene with type 1 diabetes mellitus in the patients of Russian descent

2012 ◽  
Vol 58 (4) ◽  
pp. 14-17
Author(s):  
O I Kopylova ◽  
T L Kuraeva ◽  
E Iu Lavrikova ◽  
E V Titovich ◽  
A G Nikitin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Healthy Subjects ◽  
Molecular Mechanisms ◽  
Control Group ◽  
Diabetic Patients ◽  
Potential Candidate ◽  
Ctla4 Gene

The risk of devolvement of type 1 diabetes mellitus (DM1) remains a challenging problem because neither etiology of the disease nor its prognosis and genetic predisposition to this condition are clearly understood. The development of any autoimmune process starts from the disturbance of subtle molecular mechanisms involved in the regulation of the immune system. Therefore, the genes controlling the function of its major components are at the same time the potential candidate genes encoding for the predisposition to DM1. Their association with the disease was studied by means of comparative analysis of the frequency distribution of alleles and genotypes of the polymorphous rs3087243 (G6230A) marker of the CTLA4 gene encoding for antigen-4 of cytotoxic T-lymphocytes. The present study included 257 patients presenting with type 1 diabetes mellitus and 526 healthy subjects. Genotypes were identified by the "real time" amplification technique. The AA genotype was found to occur less frequently in the diabetic patients than in the control group (11.3% and 22.1% respectively). In contrast, the frequency of the GG genotype was higher in the patients with DM1 than in the healthy subjects (44.7% and 37.5% respectively). It is concluded that the polymorphous rs3087243 marker of the CTLA4 gene is significantly associated with the predisposition to the development of type 1 diabetes mellitus in the patients of Russian descent.

scholarly journals Molecular-genetic, immunological bases and prophylaxis of diabetes mellitus in children

2011 ◽  
Vol 57 (1) ◽  
pp. 9-18
Author(s):  
E V Titovich
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Russian Population ◽  
Research Centre ◽  
Diabetic Patients ◽  
Genetic Studies

Since the autoimmune nature of type 1 diabetes mellitus came to become known some 40 years ago, continuous investigations have been carried out in an attempt to improve approaches to prognostication of this disease and develop new safe and efficacious methods for its prevention. For all that, many aspects of diabetes pathogenesis still remain far from clear. In most cases (roughly 85%), type 1 diabetes mellitus (DM1) develops sporadically in the absence of a relevant familial or hereditary history of this condition. Accordingly, the first-degree relatives account for only 15% of all DM1 patients. The risk of development of DM1 in the Russian population estimated by the researchers of the Children' Department, Endocrinological Research Centre, is relatively low (0.2%). It depends on many factors, such as the number of ill and healthy relatives, the chronological age of a given patient and the age of onset of clinical manifestations in his (her) relatives. Type 1 diabetes-predisposing and protective haplotypes were identified in the Russian population based on the results of molecular-genetic studies involving 599 children and adolescents with DM1. These and immunological data were used to distinguish between risk groups in the families of diabetic patients and the rationale was proposed for the dynamic follow-up of these subjects. It is concluded that estimation of the risk of type 1 diabetes mellitus based on the results of molecular-genetic studies and monitoring immunological markers constitutes the first step in the elaboration of preventive measures designed to prevent or delay the development of the disease.

scholarly journals Type 1 Diabetes Mellitus Donor Mesenchymal Stromal Cells Exhibit Comparable Potency to Healthy Controls In Vitro

2016 ◽  
Vol 5 (11) ◽  
pp. 1485-1495 ◽  
Author(s):  
Lindsay C. Davies ◽  
Jessica J. Alm ◽  
Nina Heldring ◽  
Guido Moll ◽  
Caroline Gavin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Healthy Controls

ALLERGIC DISEASES IN TYPE 1 DIABETIC PATIENTS: A BRIEF REVIEW

2015 ◽  
Vol 18 (2-3) ◽  
pp. 65-71
Author(s):  
Alina Gabriela Dutu ◽  
◽  
Silviu Albu ◽  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Autoimmune Disease ◽  
Type 1 Diabetes Mellitus ◽  
Allergic Diseases ◽  
Developed Countries ◽  
Diabetic Patients ◽  
Inverse Association ◽  
Stepping Stones

Type 1 diabetes mellitus is considered an autoimmune disease mediated by Th1 lymphocytes, while allergic diseases are characterized by Th2-mediated immune response. Their incidence is rising in developed countries and the interaction between autoimmune and atopic diseases has been a subject of interest for decades. There are many controversies about the association or mutual exclusion of these diseases, but classical paradigm based on the assumption that diseases mediated by Th1 and Th2 should be mutually exclusive, has been revised considering both the role of regulatory T cells Threg, and the environmental factors involved. The aim of this review is to investigate the association of allergic diseases (rhinitis, asthma, dermatitis) in patient diagnosed with type 1 diabetes mellitus. The studies that attempted to shed light on this topic had surprisingly varied results. These ranged from statistically significant proof of an inverse association between an autoimmune disease and one or several atopic ones to other implying positive associations. Although up to now studies on this subject present seemingly discordant results, each attempt raises new questions and sheds light on new factors involved in the interaction of these diseases. They present much needed stepping stones for future studies to learn from and adapt.

Association between urinary N-acetyl-beta-glucosaminidase and its isoenzyme patterns and microangiopathy in type 1 diabetes mellitus

1991 ◽  
Vol 37 (10) ◽  
pp. 1696-1699 ◽  
Author(s):  
C D Agardh ◽  
E Agardh ◽  
A Isaksson ◽  
B Hultberg
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Metabolic Control ◽  
Isoenzyme Pattern ◽  
Diabetic Patients ◽  
Type 1 Diabetic Patients ◽  
Isoenzyme Patterns ◽  
Apparently Healthy

Abstract Urinary N-acetyl-beta-glucosaminidase (NAG) and its isoenzymes (NAG A and NAG B) in samples from 87 type 1 diabetic patients and 40 apparently healthy reference subjects were studied with enzyme immunoassays. The diabetic patients had higher concentrations of urinary NAG than did the control subjects (P less than 0.01), but the isoenzyme pattern did not differ. There was a positive correlation between metabolic control (Hb A1c concentrations) and total NAG (P less than 0.01), NAG A (P less than 0.01), and NAG B (P less than 0.001). The diabetic patients were divided into three groups, depending on the degree of retinopathy. Subjects with severe forms of retinopathy did not have increased concentrations of urinary NAG unless they had concomitant nephropathy. The isoenzyme pattern was similar irrespective of degree of retinopathy or nephropathy. The results indicate that concentrations of urinary NAG are positively correlated to the degree of nephropathy, whereas there is no such correlation to the degree of retinopathy.

scholarly journals High-glucose-induced miR-214-3p inhibits BMSCs osteogenic differentiation in type 1 diabetes mellitus

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Rongze Wang ◽  
Yuanxu Zhang ◽  
Fujun Jin ◽  
Gongchen Li ◽  
Yao Sun ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Osteogenic Differentiation ◽  
High Glucose ◽  
Bone Homeostasis ◽  
Marrow Mesenchymal Stem Cells

Abstract Type 1 diabetes mellitus (T1DM) is an autoimmune insulin-dependent disease associated with destructive bone homeostasis. Accumulating evidence has proven that miRNAs are widely involved in the regulation of bone homeostasis. However, whether miRNAs also regulate osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in T1DM mice is under exploration. In this study, miRNA microarray was utilized to screen the differentially expressed miRNAs, which uncovered that miR-214-3p potentially inhibited BMSCs osteogenic differentiation in T1DM mice. We found that high glucose suppressed BMSCs osteogenic differentiation with significant elevation of the miR-214-3p expression. Further study found that the osteogenic differentiation of BMSCs was inhibited by AgomiR-214-3p while enhanced by AntagomiR-214-3p in BMSCs supplemented with high glucose. Moreover, we found that miR-214-3p knockout T1DM mice were resistant to high-glucose-induced bone loss. These results provide a novel insight into an inhibitory role of high-glucose-induced miR-214-3p in BMSCs osteogenic differentiation both in vitro and in vivo. Molecular studies revealed that miR-214-3p inhibits BMSCs osteogenic differentiation by targeting the 3′-UTR of β-catenin, which was further corroborated in human bone specimens and BMSCs of T1DM patients. Taken together, our study discovered that miR-214-3p is a pivotal regulator of BMSCs osteogenic differentiation in T1DM mice. Our findings also suggest that miR-214-3p could be a potential target in the treatment of bone disorders in patients with T1DM.

scholarly journals MECHANISMS IN ENDOCRINOLOGY: Seizures and type 1 diabetes mellitus: current state of knowledge

2012 ◽  
Vol 167 (6) ◽  
pp. 749-758 ◽  
Author(s):  
Alberto Verrotti ◽  
Alessandra Scaparrotta ◽  
Cristina Olivieri ◽  
Francesco Chiarelli
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Neurological Diseases ◽  
Underlying Mechanism ◽  
Acid Decarboxylase ◽  
Diabetic Patients ◽  
Current State ◽  
Metabolic Conditions

In this review, we will try to analyze the possible coexistence between epilepsy or seizures and type 1 diabetes mellitus (T1DM), in order to establish if there is more than a casual association, and to investigate possible mechanisms underlying this link. Anti-glutamic acid decarboxylase antibodies (GAD-Abs) have been associated with T1DM and a great number of neurological diseases such as epilepsy. Epilepsy can be a feature of a large variety of autoimmune or inflammatory disorders. GAD-Abs can have a role at the basis of the possible link between epilepsy and T1DM, although their real pathogenetic mechanism in neurological diseases is still unknown. Metabolic conditions such as hypoglycemia and hyperglycemia, common problems in diabetic patients, may be also implicated, even if their underlying mechanism is minimally understood.

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