Study Investigating the Levels and Effects of Low-grade Inflammation in Diabetic Retinopathy of Type 1 Diabetes

Study Overview
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Brief Summary
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There is much evidence that localized low grade inflammatory processes may contribute to the microvascular complications of type 1 and type 2 diabetes mellitus including sight-threatening diabetic retinopathy. Some biomarkers for inflammation have been found to be elevated in diabetes patients and correlations between those biomarkers and the severity of diabetic complications have been found in the last years. The relation between this low grade inflammation and the microvascular changes observed in diabetic retinopathy is, however, not well characterized. In the present study patients with different stages of non-proliferative diabetic retinopathy will be included. Several markers of inflammation will be measured from blood samples. These markers will be related to vascular factors including flicker-induced vasodilatation as a marker of endothelial dysfunction and perifoveal leukocyte velocity and density as measured with the blue field entoptic phenomenon. In addition, the ophthalmologic status of the patients will be assessed according to the Modified Airlie House classification. A multiple regression model will be employed to study the association between the different methods.

Official Title
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A Cross-sectional Study Investigating the Levels and Effects of Low-grade Inflammation in Diabetic Retinopathy of Type 1 Diabetes

Conditions
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Inflammation, Diabetic Retinopathy

Intervention / Treatment
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* Procedure: Blood sampling
* Procedure: Noninvasive measurement of systemic hemodynamics
* Procedure: Visual acuity assessment
* Device: Blue field entoptic technique (Blue field stimulator, BFS-2050)
* Procedure: Ophthalmic examination and fundus photography
* Device: Retinal Vessel Analyzer (DVA)
* Device: High resolution optical coherence tomography (OCT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with type 1 diabetes mellitus with duration of > 1 year Men and women, age ≥ 18, nonsmokers Body mass index between 16 and 30 kg/m² Normal findings in the medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant or diabetes-related Mild, moderate or severe non-proliferative diabetic retinopathy Exclusion Criteria: Abuse of drugs or alcoholic beverages Participation in a clinical trial in the 3 weeks preceding the study Treatment with anti-inflammatory drugs in the 3 weeks before the study day Symptoms of a clinically relevant illness in the 3 weeks before the study day Blood donation or equivalent blood loss in the 3 weeks before the study day Other ocular pathologies than non-proliferative diabetic retinopathy Ametropia > 6 dpt History or family history of epilepsy Pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: Blood sampling|Determination of cytokine plasma levels (ELISA)|
|Procedure: Noninvasive measurement of systemic hemodynamics|performed once|
|Procedure: Visual acuity assessment|ETDRS charts|
|Device: Blue field entoptic technique (Blue field stimulator, BFS-2050)|performed once|
|Procedure: Ophthalmic examination and fundus photography|7 + 1 standard fields|
|Device: Retinal Vessel Analyzer (DVA)|Assessment of retinal vessel reactivity to stimulation with flickering light|
|Device: High resolution optical coherence tomography (OCT)|performed once|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma biomarkers for inflammation (CRP, TNF-α, IL-6, vWF, e-Selektin) |  | 1 day | 
| Perifoveal white cell blood flow (Blue field entoptic technique) |  | 1 day | 
| Retinal vessel reactivity to flicker stimulation (Retinal Vessel Analyzer) |  | 1 day | 
| Arteriolar to venous ratio |  | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Capillary blood glucose |  | 1 day | 
| Stage of diabetic retinopathy |  | 1 day | 
| Visual acuity |  | 1 day | 
| Intraocular pressure |  | 1 day | 
| Systolic/diastolic arterial blood pressure, pulse rate |  | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes mellitus, type 1, Inflammation, Cytokines, Vascular reactivity