Skin and Retina Microvascular Endothelial Function in Healthy, Insulin Resistant and Type 2 Diabetic Subjects

This study has been completed.
Sponsor:
Collaborators:
Institute for Clinical Research and Development (ikfe) GmbH
Johannes Gutenberg University Mainz
University of Erlangen-Nürnberg Medical School
Information provided by:
ELAB-Logistics
ClinicalTrials.gov Identifier:
NCT01241370
First received: November 10, 2010
Last updated: November 15, 2010
Last verified: November 2010
  Purpose

The purpose of this study is to investigate microvascular endothelial function in the retina of lean, obese, and type 2 diabetic subjects and to compare microvascular endothelial function in the retina with several other established markers of endothelial and microvascular function.


Condition
Diabetes Mellitus, Type 2

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Official Title: Skin and Retina Microvascular Endothelial Function in Healthy, Insulin Resistant and Type 2 Diabetic Subjects

Resource links provided by NLM:


Further study details as provided by ELAB-Logistics:

Primary Outcome Measures:
  • Comparison of retinal microvascular endothelial function in obese insulin sensitive, insulin-resistant and type 2 diabetic subjects with retinal microvascular endothelial function in lean healthy control subjects. [ Time Frame: 2-28 days ] [ Designated as safety issue: No ]
    Measurements were taken from the superficial retinal layer (300 µm) using a scanning laser doppler flowmetry at 720 nm (Heidelberg Retina Flowmeter, Heidelberg Engineering)


Secondary Outcome Measures:
  • Comparison of microvascular endothelial function in the skin in obese and type 2 diabetic subjects with microvascular endothelial function in lean healthy control subjects. [ Time Frame: 2-28 days ] [ Designated as safety issue: No ]
    A simultaneous micro-lightguide spectrophotometry and laserdoppler-fluxmetry were used to measure the microvascular skin blood flow and postcapillary tissue oxygenation in a depth of 2 mm at the lower forearm (oxygen to see (O2C), Lea Medizintechnik, Giessen, Germany).

  • Comparison of microvascular endothelial function in the retina with microvascular endothelial function in the skin in diabetic and in non-diabetic subjects. [ Time Frame: 2-28 days ] [ Designated as safety issue: No ]
  • Comparison of morphologic changes in retinal vessels (atrio-venous-ratio, diameter) in diabetic and in non-diabetic subjects. [ Time Frame: 2-28 days ] [ Designated as safety issue: No ]
  • Comparison of the Oral Glucose Tolerance Test (OGTT) in the different subject groups with skin and retinal endothelial function. [ Time Frame: 2-28 days ] [ Designated as safety issue: No ]

Enrollment: 78
Study Start Date: May 2009
Study Completion Date: April 2010
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Groups/Cohorts
Lean healthy subjects
Homeostasis Model Assessment score (HOMAs) ≤ 2, Body Mass Index (BMI) ≤ 28 kg/m2
Insulin-resistnat subjects
HOMAs > 2, BMI > 28 kg/m2
Type 2 diabetic patients

Detailed Description:

Insulin resistance is an early feature in obese patients lasting from hyperinsulinaemia with normal glycaemic control to impaired glucose tolerance and clinically manifest type 2 diabetes. Insulin resistance is closely associated to endothelial dysfunction and many other cardiovascular risk markers summarised under the definition of the metabolic syndrome. During the recent years, insulin resistance and the development of endothelial dysfunction were recognized as important pathogenetic drivers in the development of atherosclerosis and major predictors in the development of micro and macrovascular complications like retinopathy, nephropathy, myocardial infarction or stroke.

Several different technologies have been developed for the measurement of endothelial function in distinct vascular compartments like the flow mediated vasodilatation in the brachial artery, or numerous laser Doppler based technologies for the measurement of endothelial dependent microvascular blood flow responses in the skin. Even retinal vascular morphology could be easily visualized by direct fundoscopy, the investigation of retinal endothelial function had been a diagnostical challenge for decades. During the recent years, laser doppler scanning of the retina has become a widely used technology for the measurement of microvascular blood flow in the retina. Recently a new stimulation technology for the investigation of endothelial function in the retina has been developed and validated. Application of flickering light to the retina increases retinal blood flow by the stimulation of endothelial nitric oxide (NO) release, and laser Doppler scanning of the retina before and after the flicker light application could be used for the investigation of microvascular endothelial function in the eye. For assessing the stage of retinopathy a retinal image of 45° (papilla-centered) will be performed using a digital non-mydriatic fundus camera (Kowa Nonmyd 5). The image will be evaluated in respect to diabetic and hypertensive retinopathy in a standardized method. Also the equivalent arteriolar and venous diameter of the retinal vessels will be measured and the arterio-venous ratio will be calculated.

  Eligibility

Ages Eligible for Study:   30 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

It is planned to recruit up to 60 obese male and female subjects, stratified according to the following,

20 non-diabetic subjects with HOMAs ≤ 2, BMI < 28 kg/m² 20 non-diabetic subjects with HOMAs > 2, BMI ≥ 28 kg/m² 20 type 2 diabetic patients

Criteria

Inclusion Criteria:

  • Age: 30 to 70 years
  • Have given informed consent to participate in this study in accordance with local regulations
  • Are reliable and willing to make themselves available for the duration of the study and will abide by the study restrictions

Exclusion Criteria:

  • Smoking within the last 6 months
  • Pre-proliferative or proliferative diabetic retinopathy
  • Have a history of drug or alcohol abuse within the last 5 years
  • Pregnant or intend to become pregnant during the course of the study
  • Have a condition (including known drug abuse, alcohol abuse, or psychiatric disorder) which, in the opinion of the investigator, precludes the patient from following and completing the protocol
  • Epilepsy
  • Lack of compliance or another, similar reason, that, in the judge of the investigator, precludes satisfactory participation in the study.
  • Treatment with nitrates, angiotensin converting enzyme (ACE)-inhibitors, or angiotensin (AT) II blockers
  • Treatment with glitazones
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01241370

Locations
Germany
ikfe GmbH, clinic
Mainz, Germany, 55116
Sponsors and Collaborators
ELAB-Logistics
Institute for Clinical Research and Development (ikfe) GmbH
Johannes Gutenberg University Mainz
University of Erlangen-Nürnberg Medical School
Investigators
Principal Investigator: Thomas Forst, MD Ikfe GmbH
  More Information

No publications provided

Responsible Party: Prof. Dr. Thomas Forst / CEO ikfe GmbH, ikfe GmbH
ClinicalTrials.gov Identifier: NCT01241370     History of Changes
Other Study ID Numbers: IKFE-RET-001
Study First Received: November 10, 2010
Last Updated: November 15, 2010
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by ELAB-Logistics:
Retinal endothelia dysfunction
Type 2 diabetes mellitus
Insulin-resistance
micro-lightguide spectrophotometry
laserdopplerfluxmetry

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014