Gender, clamped hyperglycemia and arterial stiffness in patients with uncomplicated type 1 diabetes mellitus

Abstract

Background: Diabetes mellitus (DM) reduces female gender-mediated protection against the development of renal disease possibly through effects on hyperglycemia. Women with DM also exhibit increased arterial stiffness, which may promote renal disease progression. The mechanisms responsible for increased arterial stiffness in women and the possible role of acute changes in ambient glycemia remain unknown.

Methods: Blood pressure, augmentation index (AIx), pulse wave velocity (PWV) and circulating mediators of the renin angiotensin system and nitric oxide (cGMP) were measured in men (n = 22) and women (n = 19) with uncomplicated type 1 DM under clamped euglycemic and hyperglycemic conditions.

Results: At baseline, men exhibited higher levels of angiotensin II (p = 0.030) and lower cGMP levels (p = 0.004), higher systolic blood pressure (124 ± 2 versus 109 ± 2 mmHg, p < 0.0001) and pulse pressure (42 ± 2 versus 58 ± 2 beats per minute, p < 0.0001). For arterial stiffness, radial (−8.0 ± 2.6% versus +5.4 ± 3.7%, p < 0.0001) and carotid AIx (−4.7 ± 2.9 versus +12.5 ± 3.0, p < 0.0001) were lower in men versus women. In contrast, carotid-femoral PWV was similar in men and women (5.20 ± 0.30 versus 5.13 ± 0.17, respectively, p = 0.853). In response to clamped hyperglycemia, systolic blood pressure increased in women (109 ± 2 to 112 ± 2 mmHg, p = 0.005) but not men. Serum aldosterone increased and cGMP declined in women but not in men. Clamped hyperglycemia did not influence arterial stiffness in either group and radial and carotid AIx remained higher in women.

Conclusions: Arterial stiffness is higher in women with type 1 DM. This effect is not dependent on the effects of clamped hyperglycemia or neurohormonal activation.

• Arterial stiffness
• gender
• hyperglycemia
• nitric oxide
• renin angiotensin system
• type 1 diabetes

Acknowledgements

D.Z.I.C. researched data, wrote the manuscript; A.M. edited and revised the manuscript.

The authors would also like to thank Dr Paul Yip and Jenny Cheung-Hum for their invaluable assistance with biochemical assays included in this work. The authors are grateful to the study participants whose time and effort are critical to the success of this research program.