P>Objective To investigate the possibility of reversing endothelial dysfunction and inflammation by glucose normalization, antioxidants and insulin per se, in different subgroups of Type 1 diabetic patients. Methods Three subgroups of Type 1 diabetic patients were studied: patients within 1 month of diagnosis (subgroup 1); patients with approximately 5 years' disease duration and with glycated haemoglobin (HbA(1c)) < 7.0% (subgroup 2) or > 7.0% since diagnosis (subgroup 3). Participants underwent four procedures: 2-h hyperglycaemic clamp followed by: (A) 12 h near-normalization of blood glucose, with the addition of vitamin C during the last 6 h; (B) 12-h vitamin C and near-normalization of blood glucose for the last 6 h; (C) both vitamin C and near-normalization of blood glucose for 12 h; (D) hyperglycaemic-hyperinsulinaemic clamp for 12 h, with the addition of vitamin C during the last 6 h. Results After 2 h of hyperglycaemia, markers of endothelial dysfunction, nitrotyrosine, 8-iso prostaglandin F2 alpha, soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, interleukin (IL)-6 and IL-18 were increased in all the subgroups. Levels were normalized, at all time points, by treatments A, B and C in the subgroups 1 and 2. In the third subgroup, levels were normalized only by the simultaneous normalization of blood glucose and vitamin C treatment. During treatment D, the levels were improved at 6 h in all the subgroups, but normalized at 12 h only after vitamin C in subgroups 1 and 2, but not in subgroup 3. Conclusions This study suggests that different subgroups of Type 1 diabetic patients react identically to acute hyperglycaemia and insulin, but differently to glucose normalization.