title: Continuous subcutaneous insulin infusion in patients with type 2 diabetes: a cohort study to establish the relationship between glucose control and plasma oxidized low density lipoprotein.
abstract: BACKGROUND
  Oxidative stress is a detrimental feature of diabetes implicated in the progression of the disease and its complications. The relationship between insulin therapy and oxidative stress is complex. This study tested the hypothesis that improved glucose control, rather than insulin dose, is central to reduced oxidative stress in patients with type 2 diabetes following continuous subcutaneous insulin infusion (CSII).
  
  
  METHODS
  In this 16-week, multicenter study, 54 CSII-naïve patients with type 2 diabetes (age 57 ± 10 years, HbA1c 69 ± 15 mmol/mol [8.5 ± 1.4%], diabetes duration 13 ± 6 years) treated with either oral antidiabetic agents (OAD) alone (n = 17), basal insulin ± OAD (n = 17), or multiple daily injections (MDI) ± OAD (n = 20) were the evaluable group. Diabetes medications except metformin were discontinued, and 16 weeks of CSII was initiated. Insulin dose was titrated to achieve optimal glycemic control. A plasma marker of oxidative stress relevant to cardiovascular disease (oxidized low density lipoprotein [ox-LDL]) was assessed at baseline and week 16.
  
  
  RESULTS
  CSII improved glycemic control (HbA1c -13 ± 2 mmol/mol [-1.2 ± 0.2%]; fasting glucose -36.6 ± 8.4 mg/dL; mean glucose excursion -23.2 ± 6.5 mg/dL, mean ± SE; all P < .001) and reduced ox-LDL (-10.5%; P < .05). The antioxidant effect was cohort-independent (P > .05), but was significantly more pronounced in patients on statins (P = .019). The effect of CSII was more closely correlated to improvements in glucose excursion (P = .013) than to insulin dose (P > .05) or reduction in HbA1c (P > .05).
  
  
  CONCLUSIONS
  CSII induces depression of plasma ox-LDL associated with change in glucose control, rather than with change in insulin dose. The effect is augmented in patients receiving statins.
authors: Free Radical Research Facility, Department of Diabetes & Cardiovascular Science, University of the Highlands & Islands, Inverness, UK ian.megson@uhi.ac.uk.
authors: Ian L
authors: IL
authors: Megson
authors: Free Radical Research Facility, Department of Diabetes & Cardiovascular Science, University of the Highlands & Islands, Inverness, UK.
authors: Andrew T
authors: AT
authors: Treweeke
authors: Free Radical Research Facility, Department of Diabetes & Cardiovascular Science, University of the Highlands & Islands, Inverness, UK.
authors: Andrew
authors: A
authors: Shaw
authors: Free Radical Research Facility, Department of Diabetes & Cardiovascular Science, University of the Highlands & Islands, Inverness, UK.
authors: Sandra M
authors: SM
authors: MacRury
authors: LifeScan Scotland Ltd, Inverness, UK.
authors: Steven
authors: S
authors: Setford
authors: National Research Institute, Los Angeles, CA, USA.
authors: Juan P
authors: JP
authors: Frias
authors: Bergen County Pediatric Endocrinology, Hackensack, NJ, USA.
authors: Henry
authors: H
authors: Anhalt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use*; D007332:Insulin Infusion Systems; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D012307:Risk Factors; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein
keywords: glucose control; insulin pump therapy; oxidative stress; type 2 diabetes
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