Microcirculation in insulin resistance and diabetes: more than just a complication.

The microvascular bed is an anatomical entity which is governed by specific, highly regulated mechanisms which are closely adapted to the specific function of each vascular segment. Among those, small arteriolar vasomotion and capacity of small vessels to constrict in response to physical and humoral stimuli play a major role. Other processes of importance for the adequacy of nutritive perfusion are haemorheological properties of whole blood and red cells, adhesiveness of leukocytes and capillary permeability. This review provides some description of these phenomena, how they impact on organ function and how they appear in diabetes. Metformin, as a unique example among the drug arsenal, exerts various effects preferentially at the level of smallest vessels (arterioles, capillaries, venules). This review summarises our actual knowledge and includes several new data showing its high potential for reducing microvascular dysfunction. Most of these unique properties have also been demonstrated in non-diabetic animals or humans, suggesting they are intrinsic to the drug and not secondary to diabetic metabolic improvement. A particular focus is put on the relevance of metformin's capacity to stimulate slow wave arteriolar vasomotion and improve functional capillary density, whereby nutritive flow can be re-established. Finally, the implication of microcirculation in other aspects of insulin resistance and diabetes, such as macroangiopathy and metabolic control, is discussed and strengthens the concept of a broad involvement of microvascular dysfunction in these diseases as well as the potential interest of introducing adapted treatment early in the history of a patient's diabetes.