Regulation of oxidative stress by glycaemic control: evidence for an independent inhibitory effect of insulin therapy.
OBJECTIVE
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
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.
Monnier
L
L
Laboratory of Human Nutrition and Atherogenesis, University Institute of Clinical Research, 34093 Montpellier Cedex 5, France. louis.monnier@inserm.fr
Colette
C
C
Mas
E
E
Michel
F
F
Cristol
J P
JP
Boegner
C
C
Owens
D R
DR
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress
D015237:Dinoprost; D006442:Glycated Hemoglobin; D007328:Insulin; C517652:hemoglobin A1c protein, human; C075750:8-epi-prostaglandin F2alpha