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

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 μm 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 μm 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.