Insulin-induced decreases in aortic wave reflection and central systolic pressure are impaired in type 2 diabetes.
OBJECTIVE
To determine whether large arteries are resistant to insulin.


METHODS
Insulin normally acutely decreases central systolic pressure by decreasing wave reflection in vivo. This effect occurs before any changes in peripheral vascular resistance or heart rate under normoglycemic conditions. We determined whether the ability of insulin to decrease central aortic pressure is altered in uncomplicated type 2 diabetes. The study subjects consisted of 16 type 2 diabetic patients (age 54 +/- 2 years, BMI 29 +/- 1 kg/m(2)) and 19 matched nondiabetic individuals (51 +/- 2 years, 29 +/- 1 kg/m(2)) studied under normoglycemic-hyperinsulinemic conditions. Central aortic pressure waveforms were synthesized from those recorded in the periphery using applanation tonometry and a validated reverse transfer function to construct the central aortic pressure waveform every 30 min. This method allowed determination of aortic augmentation (the pressure difference between the first and second central systolic pressure waves) and the augmentation index (augmentation divided by pulse pressure).


RESULTS
Whole-body insulin sensitivity was 31% lower (P < 0.05) in the type 2 diabetic patients than in the normal subjects. Basally, before the insulin infusion, augmentation averaged 8.9 +/- 1.3 and 11.1 +/- 1.2 mmHg (NS) and the augmentation index averaged 23.1 +/- 2.1 and 27.5 +/- 2.1% (NS) in the normal subjects and diabetic patients, respectively. After 30 min of hyperinsulinemia, augmentation decreased significantly to 6.1 +/- 1.1 mmHg (P < 0.001) in the normal subjects but remained unchanged at 9.1 +/- 1.1 mmHg (NS) in type 2 diabetic patients. At 30 min, the augmentation index had decreased significantly (30 +/- 7% decrease) to 17.9 +/- 2.6% in the normal subjects but remained at 24.4 +/- 2.4% in the diabetic patients (13 +/- 4% decrease, P < 0.05 for change vs. normal subjects). Central systolic pressure decreased significantly by 30 min in the normal subjects but only after 120 min in the type 2 diabetic patients. There were no significant changes in heart rate, pulse pressure, or forearm blood flow during the first 120 min of the insulin infusion.


CONCLUSIONS
Insulin resistance in type 2 diabetes involves a delay in the ability of insulin to decrease central aortic pressure. This defect could predispose these patients to develop systolic hypertension.
Tamminen
Marjo
M
Department of Medicine, Division of Diabetes, University of Helsinki, Finland.
Westerbacka
Jukka
J
Vehkavaara
Satu
S
Yki-Järvinen
Hannele
H
D001011:Aorta / Q000187:drug effects / Q000503:physiopathology*; D001783:Blood Flow Velocity / Q000187:drug effects*; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D003971:Diastole / Q000187:drug effects; D005260:Female; D005542:Forearm / Q000098:blood supply; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011674:Pulse; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D013599:Systole / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects
D007328:Insulin; D008055:Lipids; D003404:Creatinine