Changes in the Retinal and Carotid Microcirculation After Restoring Normoglycemia in Patients With Type 2 Diabetes

• Conditions: Arteriosclerosis; Diabetic Retinopathy; Carotid Atherosclerosis; Type 2 Diabetes Mellitus; Microangiopathy

• Registration Number: NCT03594591
• Lead Sponsor: Hospital Clinic of Barcelona

Brief Summary

This is a prospective and observational study in patients with type two diabetes. The study hypothesis is that chronic hyperglycemia causes an increase in the microcirculation on the carotid artery wall and retina, evaluated by angio-OCT. Furthermore, the reestablishment of normoglycemia would decrease this microcirculation, which could trigger hypoxic and ischemic changes, accelerating preclinical atherosclerosis. The study goal is to describe the microangiopathy in both territories in patients with type two diabetes and chronic hyperglycemia, and to evaluate changes after the reestablishment of normoglycemia.

Detailed Description

This is a prospective and observational study in patients with type two diabetes. The study hypothesis is that chronic hyperglycemia causes an increase in the microcirculation on the carotid artery wall (evaluating vasa vasorum by contrast-assessed carotid ultrasound) and retina (evaluated by angio-OCT). Furthermore, the reestablishment of normoglycemia would decrease this microcirculation, which could trigger hypoxic and ischemic changes, accelerating preclinical atherosclerosis. The primary outcome is to describe the microangiopathy in both territories in 20 patients with type two diabetes and chronic hyperglycemia (basal), and to evaluate the changes after the reestablishment of normoglycemia (at 1, 3 and 6 months). Additionally, clinical, laboratory, diet and biomarkers will be evaluated.

Study Timeline

• Study Start: 2018-01-02
• Study First Submitted: 2018-05-10
• Status Verified: 2018-07
• Study First Submitted QC: 2018-07-13
• Study First Posted: 2018-07-20
• Last Update Submitted: 2018-07-20
• Last Update Posted: 2018-07-24
• Primary Completion: 2020-01-01
• Study Completion: 2020-01-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Patients with type two diabetes with chronic hyperglycemia (HbA1c >9%) in who a swift and maintained improvement in glycemic control is expected, as a consequence of the antidiabetic treatment decided by usual care owing to the clinical situation.

   This treatment will include, in many cases, albeit not always, insulin (basal, basal-plus, mixes, or multiple doses). The usual clinical scenario will be failure to non-insulin antidiabetic drugs or to combined treatment (basal insulin and non-insulin drugs). Patients with new diagnose of type two diabetes who start treatment (insulin and non-insulin drugs) in which a long-evolution diabetes is suspected will also be candidates.

2. Caucasian and age between 35 and 75 years.

3. Informed consent by the patient or legal tutor.

Exclusion Criteria

1. Previous history of carotid territory interventionism (stent o endarterectomy).
2. Presence of carotid plaques in the first centimetre of the posterior wall of the common carotid artery.
3. Ophtalmologic: Proliferative diabetic retinopathy and/or diabetic macular oedema, retinal photocoagulation, intravitreous therapy and/or vitreo-retinal surgery, myopia of >6 diopters, history of non-diabetic vascular retinopathy.
4. Stage 4 chronic kidney disease (estimated glomerular filtration <30 ml/min/1,73m2), organ transplant, HIV chronic infection, active tuberculosis, active malaria, chronic b or C hepatitis, cirrhosis or intestinal inflammatory disease.
5. Current pregnancy or breastfeeding, o gestational desire in the following two years.
6. History of alcohol or drug dependence (except for caffeine and nicotine) in the former 5 years, active depression or psychiatric disease, dementia, presence of another chronic or debilitating disease with short life-expectancy, institutionalization or severe disability.
7. Presence of contraindications for the use of ecographic contrast.
8. Current Participation in another study protocol.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Changes in retinal microcirculation (perifoveal vessel density)	0, 1, 3 and 6 months	Changes in perifoveal vessel density, OCTA images will be processed to obtain vascular density measurements in this area (mm-1)
Changes in arterial wall microcirculation (vasa-vasorum density)	0, 3 and 6 months	Changes vasa-vasorum (VV) density, VV signal as the ratio of the contrast agent signal of the VV and that of the lumen of the artery

Secondary Outcome Measures

Name	Time	Method
Changes in retinal microcirculation (Total Avascular Area )	0, 1, 3 and 6 months	OCTA images will be processed to obtain total avascular area measurements (mm2)
Changes in retinal microcirculation (Parafoveal vessel density )	0, 1, 3 and 6 months	OCTA images will be processed to obtain vascular density measurements in this area (mm-1)
Changes in retinal microcirculation (Foveal Avascular Area)	0, 1, 3 and 6 months	OCTA images will be processed to obtain foveal avascular zone area measurements (mm2)

Trial Locations

Locations (1)

Hospital Clínic de Barcelona; 🇪🇸 Barcelona, Spain