Insulin therapy has a complex relationship with measure of oxidative stress in type 2 diabetes: a case for further study

BACKGROUND: Because pharmacotherapies in type 2 diabetes exert complex effects, we examined the different anti-diabetic strategies, especially the influence of insulin doses, on the activation of oxidative stress, a key player in atherosclerosis, ageing and the risk of cancer. METHODS: This observational study included 122 persons with type 2 diabetes, 61 treated with oral hypoglycaemic agents alone (group I), 61 treated with a combination of oral hypoglycaemic agents and insulin at either a low dose (<0.40 unit/kg/day, group IIa, n = 30) or high dose (≥0.40 unit/kg/day, group IIb, n = 31) of insulin. Oxidative stress was estimated from 24-h urinary excretion rates of 8-iso-prostaglandin F2α. Haemoglobin A(1c) (%) was also measured to assess overall diabetic control. RESULTS: The 24-h excretion rates of 8-iso-prostaglandin F2α [median (range) pmol/mmol of creatinine] were much lower in group IIa [68 (32-220)] than in either group I [120 (26-329) p < 0.001] or group IIb [101 (30-289) p = 0.026]. Considering groups IIa and IIb as a whole, a significant and positive relationship (p = 0.021) was observed between insulin dose and 8-iso-prostaglandin F2α. Haemoglobin A(1c) was comparable in the three groups. CONCLUSIONS: The main benefit of insulin therapy is the restoration and maintenance of near normal glycaemia. However insulin at elevated doses can promote oxidative stress which is thought to be an important mediator of some of the deleterious effects of insulin. Our study shows that the link between insulin action and oxidative stress in type 2 diabetes is complex and warrants further study.