Regulation of oxidative stress by glycaemic control: evidence for an independent inhibitory effect of insulin therapy

Diabetologia. 2010 Mar;53(3):562-71. doi: 10.1007/s00125-009-1574-6. Epub 2009 Nov 5.


Aims/hypothesis: We examined whether type of diabetes and/or insulin treatment can modulate the impact of sustained hyperglycaemia and glycaemic variability as activators of oxidative stress.

Methods: This was an observational study in 139 patients with diabetes, 48 with type 1, 60 with type 2 treated by oral hypoglycaemic agents (OHAs) alone and 31 with type 2 treated with insulin plus OHAs. In addition, two groups of ten patients with type 2 diabetes were investigated either before and after introducing insulin treatment (add-on insulin group) or before and after add-on OHA therapy to metformin (add-on OHA group). Oxidative stress was estimated from 24 h urinary excretion rates of 8-isoprostaglandin F2alpha (8-iso-PGF2alpha). HbA(1c) was assessed and mean amplitude of glycaemic excursions (MAGE) was estimated by continuous monitoring.

Results: The 24 h excretion rate of 8-iso-PGF2alpha (median [range] picomoles per millimole of creatinine) was much higher (p < 0.0001) in type 2 diabetes patients treated with OHAs alone (112 [26-329]) than in the type 1 diabetes group (65 [29-193]) and the type 2 diabetes group treated with insulin (69 [30-198]). It was associated with HbA(1c) (F = 12.9, p = 0.0008) and MAGE (F = 7.7, p = 0.008) in non-insulin-treated, but not in insulin-treated patients. A significant reduction in 24 h excretion rate of 8-iso-PGF2alpha from 126 (47-248) to 62 (35-111] pmol/mmol of creatinine was observed in the add-on insulin group (p = 0.005) but not in the add-on OHA group.

Conclusions/interpretation: In type 1 and type 2 diabetes, insulin exerts an inhibitory effect on oxidative stress, a metabolic disorder that is significantly activated by sustained hyperglycaemia and glucose variability in non-insulin-treated type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 2 / drug therapy
  • Dinoprost / analogs & derivatives
  • Dinoprost / metabolism
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hyperglycemia / metabolism*
  • Insulin / metabolism*
  • Male
  • Middle Aged
  • Oxidative Stress*


  • Glycated Hemoglobin A
  • Insulin
  • hemoglobin A1c protein, human
  • 8-epi-prostaglandin F2alpha
  • Dinoprost