ABNORMAL RHEOLOGIC EFFECTS OF GLYCERYL TRINITRATE IN PATIENTS WITH NON-INSULIN-DEPENDENT DIABETES-MELLITUS AND REVERSAL BY ANTIOXIDANTS

Objective: io evaluate 1) the hemorrheologic and hemodynamic effects o f glyceryl trinitrate in patients with non-insulin-dependent diabetes mellitus and 2) the influence of antioxidants on these effects. Design : Case-control study. Setting: University hospital clinic. Patients: 4 0 patients with diabetes and no evidence of cardiovascular complicatio ns and 40 controls matched for demographic variables and body habitus. Interventions: Sublingual glyceryl trinitrate (0.3 mg) and transderma l glyceryl trinitrate patches (10 mg/d). Vitamin E, 300 mg/d orally fo r 7 days, and glutathione, 600 mg intravenously or intramuscularly, we re given to test the effects of antioxidant supplementation. Measureme nts: Systolic, diastolic, and mean arterial pressure and heart rate; l eft ventricular ejection fraction; platelet aggregation, blood viscosi ty, and blood filterability in vitro and ex vivo. Results: Compared wi th controls, patients with diabetes had increased platelet aggregation to adenosine diphosphate (P < 0.005), increased blood viscosity (P < 0.001), and decreased blood filterability (P = 0.041) at baseline; blo od pressure, heart rate, and ejection fraction were similar in the two groups. In controls, both sublingual glyceryl trinitrate and transder mal glyceryl trinitrate patches significantly reduced platelet aggrega tion (-38%; 95% CI, -49% to -27%) and blood viscosity (-8%; CI, -11% t o -5%) and increased blood filterability (10%; CI, 7.0% to 13.1%). Sli ght but significant decreases in blood pressure and ejection fraction and an increase in heart rate were also seen in controls after adminis tration of glyceryl trinitrate (both preparations). In patients with d iabetes, glyceryl trinitrate paradoxically increased platelet aggregat ion (24%; CI, 15% to 33%) and blood viscosity (6%; CI, 2.9% to 8.8%) a nd decreased blood filterability (-7%; CI, -9.5% to -4.4%); hemodynami c values did not change significantly. In both groups, theologic respo nses to glyceryl trinitrate (end concentration, 100 and 200 ng/mL) in vitro were similar to those seen in ex vivo studies. Vitamin E and glu tathione normalized theologic responses to glyceryl trinitrate in pati ents with diabetes. Conclusions: Organic nitrates have beneficial effe cts on blood theology in controls but not in patients with diabetes, i n whom a paradoxical deterioration is seen. Antioxidant supplementatio n can normalize primary tolerance to the theologic effects of nitrates in diabetes.