Intra-individual Variability and Circadian Rhythm of VEGF Levels and Interaction With Biomarkers

Study Overview
=================
Brief Summary
-----------------
The study evaluates the intra-individual variability of VEGF levels over a period of 6 months as well as the circadian variation of VEGF levels, both under standardized conditions in patients with type 2 diabetes without DME and matched subjects with normal glucose tolerance (NGT). Secondary objectives of the study are to evaluate the relationship of individual VEGF-levels to biomarkers of inflammation, HbA1c and major cardiovascular risk factors.

Official Title
-----------------
Intra-individual Variability and Circadian Rhythm of Systemic Vascular Endothelial Growth Factor (VEGF) Levels and Interaction With Biomarkers of Inflammation in Subjects With Normal Glucose Tolerance (NGT) and Patients With Type 2 Diabetes Without Diabetic Macular Edema (DME)

Conditions
-----------------
Diabetic Macular Edema

Intervention / Treatment
-----------------
* Other: Frequent blood and urine sampling and blood pressure measurement


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Written informed consent Age equal to or between 50 and 80 years Subjects with normal glucose tolerance confirmed by glucose tolerance test (control group) or patients with type 2 diabetes: diabetes duration 5-25 years; HbA1c equal to or between 6.5 and 9% (diabetes group) Ability to understand and follow study-related instructions Exclusion Criteria: DME hsCRP > 10 mg/dl Acute infections Acute or chronic inflammatory diseases Immune diseases Treatment with immune suppressive drugs Treatment with glucocorticoids Myocardial infarction and stroke within 1 year before inclusion Hemorrhage within the previous 5 years Surgeries within the previous 3 months Oncological diseases Women who are pregnant or breast-feeding

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Control group<br>Subjects with normal glucose tolerance | Other: Frequent blood and urine sampling and blood pressure measurement<br>* Blood and urine sampling for the determination of VEGF and biomarkers<br>|
| Diabetes group<br>Patients with type 2 diabetes | Other: Frequent blood and urine sampling and blood pressure measurement<br>* Blood and urine sampling for the determination of VEGF and biomarkers<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VEGF-A | Plasma levels determined in the morning under fasted conditions | Baseline, month 1, 2, 3, 4, 5 and 6 | 
| VEGF-B | Plasma levels determined in the morning under fasted conditions | Baseline, month 1, 2, 3, 4, 5 and 6 | 
| VEGF-C | Plasma levels determined in the morning under fasted conditions | Baseline, month 1, 2, 3, 4, 5 and 6 | 
| Placental growth factor | Plasma levels determined in the morning under fasted conditions | Baseline, month 1, 2, 3, 4, 5 and 6 | 
| VEGF-A | Plasma levels determined over the day | Hourly over 12 hours | 
| VEGF-B | Plasma levels determined over the day | Hourly over 12 hours | 
| VEGF-C | Plasma levels determined over the day | Hourly over 12 hours | 
| Placental growth factor | Plasma levels determined over the day | Hourly over 12 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycated hemoglobin (HbA1c) | Plasma levels determined in the morning under fasted conditions | Baseline, month 1, 2, 3, 4, 5 and 6 | 
| High-sensitivity C-reactive protein (hCRP) | Serum levels determined in the morning under fasted conditions | Baseline, month 1, 2, 3, 4, 5 and 6 | 
| Matrix metallopeptidase 9 (MMP-9) | Plasma levels determined in the morning under fasted conditions | Baseline, month 1, 2, 3, 4, 5 and 6 | 
| MMP-9 | Plasma levels determined over the day | Hourly over 12 hours | 
| Adiponectin | Serum levels determined in the morning under fasted condition | Baseline, month 1, 2, 3, 4, 5 and 6 | 
| Adiponectin | Serum levels determined over the day | Hourly over 12 hours | 
| Cystatin C | Serum levels determined in the morning under fasted condition | Baseline, month 1, 2, 3, 4, 5 and 6 | 
| Cystatin C | Serum levels determined over the day | Hourly over 12 hours | 
| Albumin | Urine levels determined in the morning under fasted condition | Baseline, month 1, 2, 3, 4, 5 and 6 | 
| Creatinine | Urine levels determined in the morning under fasted condition | Baseline, month 1, 2, 3, 4, 5 and 6 | 
| Creatinine | Serum levels determined in the morning under fasted condition | Baseline, month 1, 2, 3, 4, 5 and 6 | 
| Blood pressure |  | Baseline, month 1, 2, 3, 4, 5 and 6, once over 24 hours |