 The sample size calculation was based upon the changes in forearm blood flow in response to acetylcholine and sodium nitroprusside in normal and diabetic subjects during preliminary studies and from previously published studies by Caballero et al 10. The pooled standard deviation for changes from baseline to endpoint in forearm blood flow ml100gr per min in our laboratory is 1.20. In order to detect with 90 power a difference in forearm blood flow in response to these physiologic agents before and after 6 months of pioglitazone therapy, 40 completed patients are required. Assuming a dropout rate of approximately 20, 50 diabetic patients must be recruited to obtain 40 completers. Based on the laser Doppler skin blood flow measurements, we have an 80 chance of showing an improvement of 50 in skin blood in response to physiologic stimuli from 65 to 100 following pioglitazone therapy. Thus, we will have more than sufficient diabetic individuals to detect statistically significant changes in skin and muscle blood flow. 