Many studies employing a variety of physiological techniques have demonstrated impaired responses on the part of the superficial smaller blood vessels of diabetics who had no evidences of large vessel disease. In 1930, Starr1 performed "wheal tests" with histamine injected intracutaneously in the legs of stabilized diabetics. He found that in 50 diabetic patients without evidence of arteriosclerosis, 8 had markedly diminished and 17 had moderately diminished wheal formation (50% hyporeactive). In another group of 25 diabetic patients who had evidence of generalized arteriosclerosis but with excellent dorsalis pedis pulsations, 11 had markedly diminished and 9 had markedly decreased wheal responses (80% hyporeactors). Starr also noted that hyporeaction occurred but was reversible in patients with acidosis.
In a more recent study, 7 out of 16 diabetics without demonstrable vascular disease showed inadequate temperature elevation of the skin of the toes after the intravenous administration of tolazoline hydrochloride (Priscoline),2