Early microvascular complications of prediabetes in mice with impaired glucose tolerance and dyslipidemia.
Microvascular complications are an important cause of morbidity in diabetic patients and can be detected in a significant number of patients at the time of diabetes diagnosis. However, little is known about the alterations in the microvasculature previous to the clinical manifestation of diabetes mellitus type 2. To obtain more insights into the early microvascular deterioration resulting from prediabetes, morphological and functional microvascular parameters were monitored using intravital fluorescence microscopy through a dorsal skin-fold chamber preparation in the uncoupling promotor-driven diphtheria toxin A chain (UCP1/DTA) mice. At the age of 12 weeks, the UCP1/DTA-mice were characterized by impaired glucose tolerance with concurrent unchanged fasting glucose, as well as dyslipidemia, hyperinsulinemia, hypertension and obesity. Prediabetic mice displayed combined hypertriglyceridemia and hypercholesterinemia. Associated with these prediabetic metabolic alterations, we demonstrate that microvascular density showed a dramatic decrease due to a reduction in perfused small vessels. A reduction in vascular density combined with unaltered blood flow in single vessels resulted in impaired tissue perfusion. Endothelial dysfunction with subsequently increased microvascular permeability and leukocyte-endothelium interactions were found. Our results of profound microvascular alterations at stages of normal fasting glucose underline the importance of early screening for prediabetes and associated microvascular complications.
Schaefer
Christian
C
Spine Center, University Medical Center Hamburg-Eppendorf, Martinistr 52, 20246 Hamburg, Germany. c.schaefer@uke.uni-hamburg.de
Biermann
Tanja
T
Schroeder
Malte
M
Fuhrhop
Ina
I
Niemeier
Andreas
A
Rüther
Wolfgang
W
Algenstaedt
Petra
P
Hansen-Algenstaedt
Nils
N
D000818:Animals; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000378:metabolism; D002199:Capillary Permeability; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D018149:Glucose Intolerance / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D055806:Microvessels / Q000503:physiopathology*; D011236:Prediabetic State / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology
D001786:Blood Glucose