Author + information
- Received December 15, 1995
- Revision received April 26, 1996
- Accepted May 3, 1996
- Published online September 1, 1996.
- Peter Clarkson, BSc, M.R.C.P.∥,a,†,‡,1,
- David S. Celermajer, PhD, F.R.A.C.P.∗,1,
- Ann E. Donald1,∥,a,†,‡,
- Mike Sampson, M.D., M.R.C.P.†,1,
- Keld E. Sorensen, M.D.∥,a,†,‡,1,
- Mark Adams, M.B., F.R.A.C.P.∗,1,
- Dennis K. Yue, PhD, F.R.A.C.P.‡,1,
- D. John Betteridge, M.D., PhD, F.R.C.P.†,1 and
- John E. Deanfield, M.B., MChir, F.R.C.P.∥,a,†,‡∗,1
- ↵∗Address for correspondence: Dr. John E. Deanfield, The Cardiovascular Unit, Great Ormond Street Hospital for Children, NHS Trust Great Ormead Street, London WCIN 3IH, England, United Kingdom.
Objectives. This study sought to examine whether endothelial function is impaired in the large vessels of asymptomatic young adults with insulin-dependent diabetes and whether endothelial dysfunction is related to duration or control of diabetes, small-vessel disease or other vascular risk factors.
Background. Endothelial dysfunction is an early event in atherosclerosis, and large-vessel atherosclerotic disease is the major cause of morbidity and mortality in diabetes.
Methods. We compared 80 young adults with insulin-dependent diabetes (15 to 40 years old; mean [±SD] diabetes duration 13 ± 8 years) with 80 matched nondiabetic control subjects. Using high resolution vascular ultrasound, we measured brachial artery responses to reactive hypermia (with increased flow causing endothelium-dependent dilation) and sublingual glyceryltrinitrate (causing endothelium-independent dilation).
Results. For-mediated dilation was significantly impaired in diabetic subjects (5.0 ± 3.7% vs. 9.3 ± 3.8% in control subjects, p < 0.001). The ratio of flow-mediated dilation to glyceryltrinitrate-induced dilation was significantly lower in the diabetic subjects (p < 0.02), indicating that impaired dilation to increased flow was out of proportion to the impairment of the glyceryltrinitrate response in these subjects (15.6 ± 5.6% vs. 19.7 ± 6.6% in control subjects, p < 0.001). On multivariate analysis, flow-mediated dilation was inversely related to both duration of diabetes (r = 0.26, p < 0.05) and low density lipoprotein (LDL) cholesterol levels (r = −0.38, p < 0.005).
Conclusions. Vascular reactivity is impaired in the systemic arteries of asymptomatic young adults with insulin-dependent diabetes and may represent early large-vessel disease. The degree of impairment is related to the duration of diabetes, and these patients appear particularly vulnerable to damage from LDL cholesterol, even at levels considered acceptable in nondiabetic subjects.
↵1 We thank Amanda J. Powe, Sue McCarthy (deceased), Jacqui Robinson, Mary-Ann Bonney and Teresa Bull for technical assistance with the study. We are also indebted to C. J. Mathias, MD, National Hospital for Neurology and Neurosurgery, for the tests of autonomic function.
☆ This work was supported by grants from the British Heart Foundation and the Coronary Artery Disease Research Association (CORDA). London: and the National Heart Foundation of Australia and the National Health and Medical Research Council of Australia, Canberra.
- Received December 15, 1995.
- Revision received April 26, 1996.
- Accepted May 3, 1996.