title: Insulin therapy has a complex relationship with measure of oxidative stress in type 2 diabetes: a case for further study.
abstract: 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.
authors.affiliation: Laboratory of Human Nutrition and Atherogenesis, University Institute of Clinical Research, Montpellier Cedex 5, France. louis.monnier@inserm.fr
authors.forename: Louis
authors.initials: L
authors.lastname: Monnier
authors.forename: Claude
authors.initials: C
authors.lastname: Colette
authors.forename: Françoise
authors.initials: F
authors.lastname: Michel
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Cristol
authors.forename: David R
authors.initials: DR
authors.lastname: Owens
mesh_terms: D000368:Aged; D015992:Body Mass Index; D031204:Caloric Restriction; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000178:diet therapy / Q000188:drug therapy / Q000378:metabolism; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D015203:Reproducibility of Results; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D015237:Dinoprost; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D045162:Thiazolidinediones; C517652:hemoglobin A1c protein, human; C075750:8-epi-prostaglandin F2alpha