High cumulative insulin exposure: a risk factor of atherosclerosis in type 1 diabetes?
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.
Muis
Marian J
MJ
Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, The Netherlands.
Bots
Michiel L
ML
Bilo
Henk J G
HJ
Hoogma
Roel P L M
RP
Hoekstra
Joost B L
JB
Grobbee
Diederick E
DE
Stolk
Ronald P
RP
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
D007004:Hypoglycemic Agents; D007328:Insulin