F2 isoprostane is already increased at the onset of type 1 diabetes mellitus: Effect of glycemic control

Abstract Much evidence has suggested that oxidative stress (OS) may play a role in the pathogenesis of diabetic complications. However, the relationship between hyperglycemia and OS is inconsistent in diabetic clinical studies. The aim of this study was to evaluate the effect of normalization of blood glucose levels on urinary 8-epi-prostaglandin F 2α (8-epi-PGF 2α ) excretion at the onset of type 1 diabetes. We studied 14 type 1 diabetic patients (50% males; mean age, 24.3 ± 4.9 years) and 14 control subjects matched by age and body mass index. A 24-hour urine collection was performed to determine 8-epi-PGF 2α as an integrated index of OS production at baseline, before starting insulin therapy, and 16 weeks later. Insulin treatment induced a significant reduction in glycosylated hemoglobin (HbA 1c ) (from 11.5% to 5.4% P = .0001), triglycerides (from 1.0 to 0.8 mmol/L, P = .002), and an increase in high-density lipoprotein (HDL)-cholesterol levels (from 1.1 to 1.5 nmol/L, P = .01) at week 16. This improvement in metabolic control was associated with a statistically significant reduction in 8-epi-PGF 2α values (from 92.0 ± 41.5 to 66.9 ± 28.9 pg/mg urinary reatinine excretion, P = .015), although compared with the control group, 8-epi-PGF 2α values remained higher in diabetic patients (66.9 ± 28.9 v 39.1 ± 13.8 pg/mg creatinine, P = .004). Enhanced OS is present in early clinical phases of type 1 diabetes, and the amelioration in metabolic control is associated with improvement in this pathogenic pathway.