Glycemic management is inversely related to skeletal muscle microvascular endothelial function in patients with type 2 diabetes

Microvascular endothelial dysfunction precipitates cardiovascular disease mortality in patients with type 2 diabetes mellitus (T2DM). However, the relationship between glycemic management and microvascular endothelial function of these patients remains ill defined. We investigated the association between skeletal muscle microvascular endothelial function with glycemic management (HbA1c) and responses to an oral glucose challenge (OGTT) in 30 patients with T2DM (59 +/- 9 years, 31.2 +/- 5.1 kg/m(2), HbA1c = 7.3 +/- 1.3%). On study day 1, microvascular endothelial function was quantified as the increase (Delta from rest) in forearm vascular conductance (FVC, ml/min/100 mmHg) during intra-arterial acetylcholine infusion at 4.0 and 8.0 mu g/dl forearm volume/min (ACh4 and ACh8, respectively). [Glucose] and [insulin] were measured in a fasted state as well as following a 75 g OGTT on a second day with an additional fasting blood sample collected to measure HbA1c. FVC increased (Delta) 221 +/- 118 and 251 +/- 144 ml/min/100 mm Hg during ACh4 and ACh8 trials, respectively (p < 0.05 between doses). [Glucose] and [insulin] increased at the 1-h time point, relative to fasting levels, and remained elevated 2 h post-consumption (p < 0.05 for both variables and time points). [Glucose] nor [insulin], fasting or during the OGTT, were associated with Delta FVC during ACh4 or ACh8, respectively (p = 0.11-0.86), although HbA1c was inversely related (r = -0.47 and -0.46, respectively, p < 0.01 for both). Patients whose HbA1c met the ADA's therapeutic target of <= 7.0% had greater Delta FVC to ACh4 (272 +/- 147 vs. 182 +/- 74 ml/100 mm Hg/min) and ACh8 (324 +/- 171 vs. 196 +/- 90 ml/100 mm Hg/min, p < 0.05 for both trials) compared to those with >7.0%, respectively. Our data show glycemic management is related to acetylcholine-mediated vasodilation (e.g., microvascular endothelial function) in skeletal muscle of patients with T2DM.