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

• 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)
  
  

• 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 ]
  

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.