Skin and Retina Microvascular Endothelial Function in Healthy, Insulin Resistant and Type 2 Diabetic Subjects
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Observational

Summary: 
      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.
    

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.
    

Observational model: Case-Control
Time perspective: Prospective
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
      
Keywords: Retinal endothelia dysfunction; Type 2 diabetes mellitus; Insulin-resistance; micro-lightguide spectrophotometry; laserdopplerfluxmetry