Retinal Blood Flow and Microthrombi in Type 1 Diabetes
| Status: | Completed |
|---|---|
| Conditions: | Ocular, Diabetes |
| Therapuetic Areas: | Endocrinology, Ophthalmology |
| Healthy: | No |
| Age Range: | 18 - 45 |
| Updated: | 4/21/2016 |
| Start Date: | June 2003 |
| End Date: | March 2006 |
The project aims to find mechanisms for the abnormal retinal blood flow that in diabetic
patients often precedes any evidence of clinical retinopathy and may contribute to the
development of retinopathy.
Specifically, the projects tests the hypothesis that reduced retinal blood flow found in
young patients with type 1 diabetes reflects increased resistance in the small vessels of
the retina caused by the formation of small blood clots, called microthrombi; and that
antiplatelet agents normalize the reduced retinal blood flow.
patients often precedes any evidence of clinical retinopathy and may contribute to the
development of retinopathy.
Specifically, the projects tests the hypothesis that reduced retinal blood flow found in
young patients with type 1 diabetes reflects increased resistance in the small vessels of
the retina caused by the formation of small blood clots, called microthrombi; and that
antiplatelet agents normalize the reduced retinal blood flow.
The ultimate goal of this research is to contribute to the development of strategies to
prevent diabetic retinopathy. This project will test the hypothesis that antiplatelet agents
normalize the reduced blood flow observed early in the course of type 1 diabetes. If the
hypothesis is proven correct, the results will indicate that the formation of small blood
clots (microthrombi) occurs early in diabetic retinal vessels. In turn, because
microthrombosis could readily account for the occlusive microangiopathy that causes the
sight-threatening stages of diabetic retinopathy, the results will propose the desirability
of antiplatelet therapy for the prevention of diabetic retinopathy.
We have three specific aims:
1. To confirm that, under basal conditions, retinal blood flow measured with the laser
Doppler method in a group of type 1 diabetic patients with no or minimal retinopathy
differs from the flow measured in age- and sex-matched nondiabetic control subjects;
2. To determine whether the response of retinal blood flow to low-dose aspirin (81 mg/day)
administered for 2 months versus placebo, differs between type 1 diabetic patients with
no or minimal retinopathy and age- and sex-matched nondiabetic control subjects;
3. To determine whether in type 1 diabetic patients with no or minimal retinopathy the
response of retinal blood flow to low-dose aspirin differs from the response to
clopidogrel, a drug that interferes with platelet function downstream of the site of
aspirin action.
prevent diabetic retinopathy. This project will test the hypothesis that antiplatelet agents
normalize the reduced blood flow observed early in the course of type 1 diabetes. If the
hypothesis is proven correct, the results will indicate that the formation of small blood
clots (microthrombi) occurs early in diabetic retinal vessels. In turn, because
microthrombosis could readily account for the occlusive microangiopathy that causes the
sight-threatening stages of diabetic retinopathy, the results will propose the desirability
of antiplatelet therapy for the prevention of diabetic retinopathy.
We have three specific aims:
1. To confirm that, under basal conditions, retinal blood flow measured with the laser
Doppler method in a group of type 1 diabetic patients with no or minimal retinopathy
differs from the flow measured in age- and sex-matched nondiabetic control subjects;
2. To determine whether the response of retinal blood flow to low-dose aspirin (81 mg/day)
administered for 2 months versus placebo, differs between type 1 diabetic patients with
no or minimal retinopathy and age- and sex-matched nondiabetic control subjects;
3. To determine whether in type 1 diabetic patients with no or minimal retinopathy the
response of retinal blood flow to low-dose aspirin differs from the response to
clopidogrel, a drug that interferes with platelet function downstream of the site of
aspirin action.
Inclusion Criteria:
- Age 18-45 years,
- type 1 diabetes duration 1-15 years,
- absent or minimal retinopathy (EDTRS 20).
- Age- and gender-matched healthy controls
Exclusion Criteria:
- smoking,
- systemic diseases other than diabetes,
- retinal diseases other than diabetic retinopathy,
- pregnancy,
- bleeding disorders,
- aspirin allergy,
- use of anti-platelet agents,
- non-steroidal anti-inflammatory agents,
- angiotensin converting enzyme inhibitors,
- angiotensin receptor antagonists,
- Vitamin E in large doses.
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