Endothelial dilator function is impaired in people with type 2 diabetes mellitus (T2DM). Prior research indicates that this can be improved with intravenous administration of ascorbate or L-arginine, but whether these agents have this effect when administered by the clinically practical oral route is unknown. To investigate this question, 10 premenopausal women with T2DM and 10 healthy, premenopausal, non-diabetic women received, in random sequence, a 1-week administration of oral L-arginine (9 g daily) or vitamins E (1800 mg) and C (1000 mg) with an intervening 1-week washout period. Flow-mediated brachial artery dilation (FMD) was measured by ultrasonography and forearm blood flow was measured by plethysmography before and following blood pressure cuff-induced forearm ischemia before and after each week of results.

At baseline, the women with T2DM had lesser FMD responses (0.028 ± 0.006 cm vs 0.056 ± 0.008 cm, p, 0.05). Post-ischemic forearm hyperemia was reduced at baseline in T2DM compared with controls (16.4 ± 1.8 vs 26.0 ± 1.4 ml 100 ml^–1 min^–1, p <0.05). Administration of L-arginine caused a 50 ± 12% increase in FMD in T2DM (p < 0.05) and raised post-ischemic forearm blood flow by 29 ± 8% (p < 0.05). No significant changes were seen in controls. Administration of vitamins E and C in women with T2DM produced an increase in the brachial artery diameter response of 79 ± 15% (p < 0.05), but did not significantly increase the hyperemic blood flow response (p = NS). No significant changes in the responses of controls from pre to post vitamin administration were observed. We concluded that administration of two types of oral agents improved measures of endothelial function in people with T2DM.