Insulin-Induced Decrease in Large Artery Stiffness Is Impaired in Uncomplicated Type 1 Diabetes Mellitus

Abstract

Abstract-Normal insulin action in vivo involves a decrease in stiffness of large arteries (a decrease in aortic pressure augmentation). We determined whether the ability of insulin to decrease arterial stiffness is altered in uncomplicated type 1 diabetes. Nine type 1 diabetic men (age 28Ϯ2 years, body mass index 24Ϯ1 kg/m 2 ) and 9 matched normal men were studied under normoglycemic hyperinsulinemic (sequential 2-hour insulin infusions of 1 [step 1] and 2 [step 2] mU ⅐ kg Ϫ1 ⅐ min Ϫ1) conditions. Central aortic pressure waveforms were synthesized from those recorded in periphery with applanation tonometry on the radial artery and a validated reverse transfer function to construct the central aortic pressure wave every 30 minutes. This allowed the determination of aortic augmentation (the pressure difference between the first and the second systolic peaks) and the augmentation index (augmentation divided by pulse pressure), as the measure of stiffness of large arteries. Whole-body glucose uptake was 44% (step 1) and 37% (step 2) lower (PϽ0.001) in the diabetic patients than in the normal subjects. At baseline, before the insulin infusion, augmentation averaged 0Ϯ1 and 2Ϯ1 mm Hg (NS) and the augmentation index was Ϫ1.5Ϯ4.5% and 4.0Ϯ3.7% (NS) in the normal and diabetic subjects, respectively. After 1 hour of hyperinsulinemia, the augmentation index had decreased significantly (PϽ0.01) to Ϫ9.5Ϯ4.8% in the normal subjects but remained at 4.4Ϯ4.2% in the diabetic patients. A significant decrease was not observed in the diabetic patients until 150 minutes (Ϫ1.2Ϯ4.1%, PϽ0.05 versus baseline). Whole-body glucose uptake was significantly inversely correlated with the change in the augmentation index during step 1 (rϭϪ0.61, PϽ0.01). Insulin resistance in type 1 diabetes involves a defect in the ability of insulin to decrease central aortic pressure. This defect could predispose these patients to premature stiffening of large arteries.

Acute hyperglycaemia rapidly increases arterial stiffness in young patients with type 1 diabetes

“…At least supraphysiological levels of insulin have been shown to decrease arterial stiffness [40], but it is very unlikely that the diminutive insulin secretion seen in healthy volunteers in this study would have had an effect on the results. In support of this assumption, no correlations between changes in insulin levels and changes in measures of arterial stiffness were found.…”

Relation between insulin and aortic stiffness: a population-based study

“…Another finding that at first glance appears to be in contrast with the findings in the present study comes from Yki-Jarvinen and coworkers, who in different groups of subjects have shown that infusion of insulin producing acute hyperinsulinaemia leads to a marked decrease in large arterial stiffness. 34,35 However, it should be pointed out that it could be difficult to compare the results from a dynamic research setting with acute changes in insulin levels with the results from a statistic research setting with fasting insulin levels as in the present study. Further at second glance, it appears that some sort of agreement exists between our results and the results from Yki-Jarvinen's group.…”

Obesity, Arterial Stiffness, and Cardiovascular Risk

“…In insulin-dependent patients with diabetes, arterial stiffness is predominantly and/or uniquely in-creased in femoral arteries. Finally, in normotensive individuals, insulin infusion reduces wave reflections in the thoracic aorta (32). Insulin resistance in type 2 diabetes reduces the ability of insulin to decrease central aortic pressure.…”