Effect of glycaemic control on the vascular nitric oxide system in patients with type 1 diabetes.

Objective: The mechanisms underlying the relationship between the vascular complications of diabetes and the glycaemic control are not well understood. We tested whether glycaemic control influences the functioning of the nitric oxide system in type 1 diabetic patients and the role for oxidative stress.

Methods: The changes in the forearm blood flow after the infusion in the brachial artery of NG-monomethyl-l-arginine, methacholine, methacholine plus superoxide dismutase, and nitroprusside were evaluated using strain gauge plethysmography in 14 healthy subjects and 24 patients with type 1 diabetes (12 with HbA(1c) < 7.5%; 12 with HbA(1c) > or = 7.5%). After adjusting insulin treatment, the vascular studies were repeated in the initially poorly controlled patients (HbA(1c) > or = 7.5%).

Results: Compared with healthy people, impaired vascular responses to NG-monomethyl-l-arginine (P = 0.0001), methacholine (P = 0.007) and nitroprusside (P = 0.0015) were found in the patients with type 1 diabetes and a poor glycaemic control (HbA(1c) >/= 7.5%), but not in subjects with good control (HbA(1c) < 7.5%). Superoxide dismutase improved the responses to methacholine only in those patients with poor control (P = 0.0037). After the adjustment of the insulin treatment in poorly-controlled patients, the responses improved and the effect of superoxide dismutase disappeared only in the patients that achieved good control (n = 9), but not in those who remained poorly-controlled (n = 3).

Conclusions: In patients with diabetes type 1, glycaemic control determines the functioning of the NO system by a reversible mechanism involving superoxide anions. This finding provides an explanation of the relationship between glycaemic control and vascular complications in diabetes.