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Atherosclerosis. 2005 Jul;181(1):185-92.

High cumulative insulin exposure: a risk factor of atherosclerosis in type 1 diabetes?

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Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, The Netherlands.



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.


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).


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.


These findings provide evidence that a high cumulative dose of regular insulin is a risk factor for atherosclerosis.

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