Prevalence and Correlations of Early Microvascular Complications in Young Type I Diabetic Patients: Role of Puberty

Abstract Introduction: Evolution of diabetes is associated with multiple disorders including metabolic, cellular and blood disturbances leading to various vascular complications (micro-and macro-angiopathies). Increased circulating levels of platelet-leukocyte aggregates (PLA) have been described in several thrombotic diseases. Material and Methods: In this study, we have evaluated the circulating PLA in diabetic patients and we have investigated whether they may be linked to the vascular complications currently occurring during diabetes evolution. Using flow cytometry assay, we have quantified PLA percentages in 65 diabetics (37 males/28 females, 57 ± 11 years old) including 20 patients with type I and 45 with type II diabetes, and 25 healthy subjects (15 males/10 females, 44 ± 9 years old). Labelling approach using specific monoclonal antibodies permitted us to identify platelet-polymorphonuclear aggregates (PPA) and platelet-monocyte aggregates (PMA). Results: We have observed a significant increase of PPA and PMA levels in diabetics (22 ± 12% and 45 ± 18%, respectively) compared to control subjects (7 ± 4% and 19 ± 10%, respectively). However, both PPA and PMA values were similar in the two types of diabetes and they were not correlated to the disease duration. Circulating PPA and PMA percentages were significantly enhanced in diabetics with vascular lesions (n=37; PPA: 24 ± 13%; PMA: 50 ± 18%) than in diabetics without vascular lesions (n=28; PPA: 18 ± 8%; PMA: 38 ± 15%). Patients with PPA > 18% and /or PMA > 38% had a more important vascular thrombotic damage (OR: 6; 95%; IC: 1.6; 23). The increased PMA circulating percentage seems to be more specific for micro-retinopathy occurrence (OR: 19, 95% IC: 2.3; 154). The rare patients with elevated PMA percentage and without vascular lesions have a shorter duration of diabetes (7 ± 5 years) than patients presenting retinopathy lesions (16 ± 11 years). Conclusion: Together our findings established a relationship between increased circulating PLA rate, particularly that of PMA, and the incidence of microvascular complications in diabetic patients. In addition, they reinforce the concept that pro-inflammatory cells are involved in diabetic retinopathy pathogenesis.

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Does Type II Diabetes Predispose to Retinal Vein Occlusion?

European Journal of Ophthalmology ◽

10.1177/112067219300300301 ◽

1993 ◽

Vol 3 (3) ◽

pp. 109-113 ◽

Cited By ~ 11

Author(s):

P.M. Dodson ◽

C.G. Clough ◽

S.M. Downes ◽

E.E. Kritzinger

Keyword(s):

Retinal Vein Occlusion ◽

Type I Diabetes ◽

Microvascular Complications ◽

Control Group ◽

Diabetic Patients ◽

Type I ◽

Type Ii ◽

Medical Conditions ◽

Vein Occlusion ◽

Diabetic Microvascular Complications

Retinal vein occlusion (RVO) not infrequently occurs in diabetic patients. Although the aetiology is unclear, it could relate to the other microvascular complications of diabetes. In the non-diabetic, both the central (CRVO) and branch (BRVO) forms are commonly associated with hypertension and hyperlipidaemia. We have therefore studied fifty type II diabetic patients with RVO compared to a carefully matched diabetic control group (n = 50) to elucidate underlying medical conditions and hence the aetiology of RVO in diabetic patients. The two groups were well matched. Diabetics with RVO showed a strikingly high prevalence of hypertension compared to the controls (72% versus 32%: p < 0.001) and a trend to increased hyperlipidaemia (54% versus 36%). Diabetic microvascular complications were more common in the control group (diabetic retinopathy and proteinuria). No significant differences were observed in mean HbA1 or weight, but current smoking habits and blood pressure levels were increased in the diabetics with RVO. 80% of diabetic patients with the BRVO form, were hypertensive. We conclude that the main underlying medical conditions for RVO in diabetics are hypertension and hyperlipidaemia, and these may be important in the aetiology as in the non-diabetic. RVO is more common in type II rather than type I diabetes, and does not associate with the presence of diabetic microvascular complications. Clinical assessment for hypertension and hyperlipidaemia is therefore important in diabetic patients with RVO, especially if recurrence of the condition and further visual loss is to be prevented.

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The Role of MicroRNAs in the Pathogenesis of Diabetic Nephropathy

International Journal of Endocrinology ◽

10.1155/2019/8719060 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Jian Tang ◽

Deyi Yao ◽

Haiying Yan ◽

Xing Chen ◽

Linjia Wang ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Molecular Mechanisms ◽

Microvascular Complications ◽

Diabetic Patients ◽

Hemodynamic Changes ◽

Clinical Value ◽

New Ideas ◽

Stage Renal Disease ◽

End Stage

Diabetic nephropathy (DN) is one of the most common microvascular complications in diabetic patients; it is also an important cause of renal dysfunction, renal fibrosis, and end-stage renal disease. Unfortunately, the pathogenesis of DN is complex and has not yet been fully elucidated; hence, the pathogenesis of DN to determine effective treatments of crucial importance is deeply explored. Early DN research focuses on hemodynamic changes and metabolic disorders, and recent studies have shown the regulatory role of microRNAs (miRNAs) in genes, which may be a new diagnostic marker and therapeutic target for diabetic nephropathy. In this review, we summarize the recent advances in the clinical value and molecular mechanisms of miRNAs in DN, providing new ideas for the diagnosis and treatment of DN.

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The Multi-Therapeutic Role of MSCs in Diabetic Nephropathy

Frontiers in Endocrinology ◽

10.3389/fendo.2021.671566 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yi Wang ◽

Su-Kang Shan ◽

Bei Guo ◽

Fuxingzi Li ◽

Ming-Hui Zheng ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Diabetic Kidney Disease ◽

Microvascular Complications ◽

Diabetic Patients ◽

Differentiation Potential ◽

Therapeutic Role ◽

Promising Strategy ◽

Stage Renal Disease ◽

End Stage

Diabetic nephropathy (DN) is one of the most common diabetes mellitus (DM) microvascular complications, which always ends with end-stage renal disease (ESRD). Up to now, as the treatment of DN in clinic is still complicated, ESRD has become the main cause of death in diabetic patients. Mesenchymal stem cells (MSCs), with multi-differentiation potential and paracrine function, have attracted considerable attention in cell therapy recently. Increasing studies concerning the mechanisms and therapeutic effect of MSCs in DN emerged. This review summarizes several mechanisms of MSCs, especially MSCs derived exosomes in DN therapy, including hyperglycemia regulation, anti-inflammatory, anti-fibrosis, pro-angiogenesis, and renal function protection. We also emphasize the limitation of MSCs application in the clinic and the enhanced therapeutic role of pre-treated MSCs in the DN therapy. This review provides balanced and impartial views for MSC therapy as a promising strategy in diabetic kidney disease amelioration.

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Challenges in Diabetic Micro-Complication Management: Focus on Diabetic Neuropathy

International Journal of Translational Medicine ◽

10.3390/ijtm1030013 ◽

2021 ◽

Vol 1 (3) ◽

pp. 175-186

Author(s):

Prawej Ansari ◽

J.M.A. Hannan ◽

Shofiul Azam ◽

Md. Jakaria

Keyword(s):

Diabetic Neuropathy ◽

Current Knowledge ◽

Microvascular Complications ◽

Clinical Manifestations ◽

Treatment Strategies ◽

Underlying Mechanism ◽

Sensory Function ◽

Diabetic Patients ◽

Type I ◽

Substantial Morbidity

The progression of diabetes leads to macro and microvascular complications, including diabetic neuropathy, which is the most prevalent microvascular complication with diabetes. Clinical manifestations of diabetic neuropathy begin with the loss of distal sensory function, pain, and substantial morbidity. It has been evident that ~50% of diabetic patients develop neuropathy at a certain stage in their lifetime. Interestingly, two major subtypes (type I and II) of diabetes do not share the same epidemiology and pathophysiology of diabetic neuropathy; thus, their management or treatment strategies may vary from each other. The past few decades of research suggest that many etiological features, diagnosis, and management complexities depend on the type of diabetes. However, the underlying mechanism of neuropathy in type I and type II diabetes remains unclear. This review provides the current knowledge on successful assessment, management, and pharmacological biomarkers to explore the treatment and surpass current challenges in diabetic neuropathy.

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The ERM Complex: A New Player Involved in Diabetes-induced Vascular Leakage

Current Medicinal Chemistry ◽

10.2174/0929867325666181016162327 ◽

2020 ◽

Vol 27 (18) ◽

pp. 3012-3022 ◽

Cited By ~ 1

Author(s):

Olga Simó-Servat ◽

Cristina Hernández ◽

Rafael Simó

Keyword(s):

Vascular Dysfunction ◽

Microvascular Complications ◽

Focal Adhesions ◽

Vascular Leakage ◽

Diabetic Patients ◽

Erm Proteins ◽

Cytoskeleton Reorganization ◽

Tnf Α ◽

Diabetic Microvascular Complications

Background: Microvascular complications remain an important cause of morbidity in diabetic patients, and they are associated with a significant economic burden for healthcare systems. Vascular leakage is one of the earlier hallmarks in diabetic microvascular complications. Ezrin, Radixin and Moesin (ERM) proteins have recently been involved in vascular dysfunction under the effect of molecular mediators of diabetes complications. In this review, we will present the available evidence regarding the role of these proteins in vascular leakage and their putative implication in diabetic microvascular complications. Methods and Results: A comprehensive literature search of the electronic MEDLINE database was performed between November 2017 and January 2018. As a result, 36 articles have been reviewed and discussed. Discussion: ERM proteins are cytoskeleton-membrane linkers, and when activated in endothelial cells are able to induce cytoskeleton reorganization in stress fibers leading to the disassembly of focal adhesions and the formation of paracellular gaps which result in an increase of vascular permeability. The activation of these proteins is induced by mediators involved in diabetic complications such as PKC activation, TNF-α, AGEs and oxidative stress. In conclusion, ERMs play an essential role in endothelium homeostasis and can be envisaged as a new therapeutic molecular target for preventing or arresting diabetes-induced vascular leakage.

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The Role of Oxidative Stress in Diabetic Neuropathy: Generation of Free Radical Species in the Glycation Reaction and Gene Polymorphisms Encoding Antioxidant Enzymes to Genetic Susceptibility to Diabetic Neuropathy in Population of Type I Diabetic Patients

Cell Biochemistry and Biophysics ◽

10.1007/s12013-014-0365-y ◽

2014 ◽

Vol 71 (3) ◽

pp. 1425-1443 ◽

Cited By ~ 45

Author(s):

Mark A. Babizhayev ◽

Igor A. Strokov ◽

Valery V. Nosikov ◽

Ekaterina L. Savel’yeva ◽

Vladimir F. Sitnikov ◽

...

Keyword(s):

Oxidative Stress ◽

Antioxidant Enzymes ◽

Free Radical ◽

Diabetic Neuropathy ◽

Genetic Susceptibility ◽

Gene Polymorphisms ◽

Diabetic Patients ◽

Type I ◽

Radical Species

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Diabetes Mellitus and Cardiovascular Prevention: The Role and the Limitations of Currently Available Antiplatelet Drugs

International Journal of Vascular Medicine ◽

10.1155/2011/250518 ◽

2011 ◽

Vol 2011 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

A. Tufano ◽

E. Cimino ◽

M. N. D. Di Minno ◽

P. Ieranò ◽

E. Marrone ◽

...

Keyword(s):

Diabetes Mellitus ◽

Secondary Prevention ◽

Cardiovascular Events ◽

Microvascular Complications ◽

Cardiovascular Prevention ◽

Antiplatelet Drugs ◽

Diabetic Patients ◽

Primary And Secondary Prevention ◽

Vascular Events

Diabetes mellitus (DM) is associated with macrovascular and microvascular complications. Platelets have a “key role” in atherogenesis and its thrombotic complications in subjects with DM. Moreover, the concomitant presence of multiple “classical” cardiovascular risk factors in diabetic subjects contributes to enhanced atherothrombotic risk. Antiplatelet agents are effective in primary and secondary prevention of arterial thrombosis (cardiovascular events, ischaemic stroke, and peripheral arterial occlusive disease). The role of chronic administration of antiplatelet drugs in primary prevention of arterial vascular events is known to be less clear than in secondary prevention, and, also in diabetic patients, the decision to give primary prophylaxis should be taken on an individual-patient basis, after a careful evaluation of the balance between the expected benefits and the risk of major bleedings. Although, currently, treatment has proven useful in reducing vascular events, diabetic patients continue to have a higher risk of adverse cardiovascular events compared with those in nondiabetic patients. This paper reviews the role of currently available antiplatelet drugs in primary and secondary prevention of vascular events in diabetic patients and the limitations of these drugs, and it discusses the role of novel and more potent antiplatelets and of new agents currently under clinical development.

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