title: High cumulative insulin exposure: a risk factor of atherosclerosis in type 1 diabetes?
abstract: BACKGROUND
  Since insulin therapy might have an atherogenic effect, we studied the relationship between cumulative insulin dose and atherosclerosis in type 1 diabetes. We have focused on patients with type 1 diabetes instead of type 2 diabetes to minimise the effect of insulin resistance as a potential confounder.
  
  
  METHODS
  An observational study was performed in 215 subjects with type 1 diabetes treated with multiple insulin injection therapy. Atherosclerosis was assessed by measurement of carotid intima-media thickness (CIMT).
  
  
  RESULTS
  The cumulative dose of regular insulin showed a positive and significant relation with CIMT: increase of 21 microm in CIMT per S.D. of insulin use (95% CI: 8-35 adjusted for gender and age), which remained unchanged after adjustment for duration of diabetes, HbA1c, BMI, pulse pressure, physical activity and carotid lumen diameter. A similar relation was found for intermediate-acting insulin: 15.5 microm per S.D. (2-29), which was no longer present after further adjustment.
  
  
  CONCLUSIONS
  These findings provide evidence that a high cumulative dose of regular insulin is a risk factor for atherosclerosis.
authors.affiliation: Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, The Netherlands.
authors.forename: Marian J
authors.initials: MJ
authors.lastname: Muis
authors.forename: Michiel L
authors.initials: ML
authors.lastname: Bots
authors.forename: Henk J G
authors.initials: HJ
authors.lastname: Bilo
authors.forename: Roel P L M
authors.initials: RP
authors.lastname: Hoogma
authors.forename: Joost B L
authors.initials: JB
authors.lastname: Hoekstra
authors.forename: Diederick E
authors.initials: DE
authors.lastname: Grobbee
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Stolk
mesh_terms: D000328:Adult; D001161:Arteriosclerosis / Q000139:chemically induced* / Q000000981:diagnostic imaging; D002339:Carotid Arteries / Q000000981:diagnostic imaging; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; 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; D008875:Middle Aged; D015999:Multivariate Analysis; D012307:Risk Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging; D017540:Tunica Media / Q000000981:diagnostic imaging; D014463:Ultrasonography
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin