Forearm Nitric Oxide Balance, Vascular Relaxation, and Glucose Metabolism in NIDDM Patients

Endothelium-dependent and -independent vascular responses were assessed in 10 NIDDM patients and 6 normal subjects with no evidence of atherosclerotic disease. Changes in forearm blood flow and arteriovenous (AV) serum nitrite/nitrate (NO₂⁻/NO₃^-) concentrations were measured in response to intra-arterial infusion of acetylcholine (ACh) (7.5, 15, 30 μg/min, endothelium-dependent response) and sodium nitroprusside (SNP) (0.3, 3, 10 μg/min, endothelium-independent response). Insulin sensitivity (determined by minimal model intravenous glucose tolerance test) was lower in NIDDM patients (0.82 ± 0.20 vs. 2.97 ± 0.29 10⁴ min · μU⁻¹ · ml⁻¹; P < 0.01). Baseline forearm blood flow (4.8 ± 0.3 vs. 4.4 ± 0.3 ml · 100 ml⁻¹ tissue · min⁻¹; NS), mean blood pressure (100 ± 4 vs. 92 ± 4 mmHg; NS), and vascular resistance (21 ± 1 vs. 21 ± 1 units; NS), as well as their increments during ACh and SNP, infusion were similar in both groups. No difference existed in baseline NO₂⁻/NO₃⁻ concentrations (4.09 ± 0.33 ]NIDDM patients] vs. 5.00 ± 0.48 μmol/1 ]control subjects]; NS), their forearm net balance (0.31 ± 0.08 ]NIDDM patients] vs. 0.26 ± 0.08 μmol/1 · 100 ml⁻¹ tissue · min⁻¹; NS), and baseline forearm glucose uptake. During ACh infusion, both NO₂⁻ and NO₃⁻ concentrations and net balance significantly increased in both groups, whereas glucose uptake increased only in control subjects. When data from NIDDM and control groups were pooled together, a correlation was found between the forearm AV NO₂⁻ and NO₃⁻ differences and blood flow (r = 0.494, P = 0.024). On the contrary, no correlation was evident between NO₂⁻ and NO₃⁻ concentrations or net balance and insulin sensitivity. In summary, 1) no difference existed in basal and ACh-stimulated NO generation and endothelium-dependent relaxation between uncomplicated NIDDM patients and control subjects; 2) in both NIDDM and control groups, forearm NO₂⁻ and NO₃⁻ net balance following ACh stimulation was related to changes in the forearm blood flow; and 3) ACh-induced increase in forearm blood flow was associated with an increase in glucose uptake only in control subjects but not in NIDDM patients. In conclusion, our results argue against a role of impaired NO generation and blood flow regulation in determining the insulin resistance of uncomplicated NIDDM patients; rather, it supports an independent insulin regulation of hemodynamic and metabolic effects.