The role of endothelial dysfunction in the pathophysiology of erectile dysfunction in diabetes and in determining response to treatment.
BACKGROUND
Erectile dysfunction (ED) in diabetes is related to autonomic neuropathy and endothelial dysfunction. We studied the relative importance of these factors in diabetic and non-diabetic men with ED and determined if they predict responses to treatment with sildenafil.


METHODS
Thirty-three men, aged 35-65 years, with ED (20 diabetic, 13 non-diabetic), 15 of whom were sildenafil responders and 18 non-responders, were compared with 30 age and risk-matched control subjects (15 diabetic, 15 non-diabetic). Subjects with ED completed the International Index of Erectile Function (IIEF) questionnaire. Endothelial function was assessed by changes in brachio-radial and femoro-tibial arterial pulse-wave velocity (pulse-wave velocity) during reactive hyperaemia, expressed as percentage endothelium-dependent dilatation. Autonomic function was assessed by heart rate variation during expiration and inspiration (E/I ratio) and during the valsalva manoeuvre.


RESULTS
The respective changes in pulse-wave velocity, in the arm and leg [mean (sd)] were 0.71 (6.5)% and 3.5 (6.4)% in the impotent diabetic men, 0.7 (7.6)% and 2.4 (5.9)% in the non-diabetic impotent men, -0.68 (5.7)% and -1.31 (7.2)% in the non-impotent diabetic men and 7.7 (3.7)% and 7.6 (3.4)% in the control subjects. There was a significant interaction between ED and diabetic status such that there was significantly impaired vascular response in the diabetic group (both with and without ED) and in the non-diabetic group with ED compared with the non-diabetic control group (P = 0.01 and P = 0.001 for brachio-radial and femoro-tibial measures, respectively). The E/I ratios of the diabetic men were significantly lower than those of the control subjects [1.17 (0.14) vs. 1.33 (0.16), P < 0.02), but there were no differences in the measures of autonomic neuropathy between the groups with ED and those with normal erectile function. Amongst diabetic men, the initial IIEF scores (maximum score 30, low score indicates more severe ED) were significantly higher in sildenafil-responders than non-responders [16.3 (8.4), vs. 6.8 (7 1), P < 0.02]. The rate of sildenafil response was not significantly affected by the measures of endothelial or autonomic function.


CONCLUSIONS
ED in both diabetic and non-diabetic men is characterized by marked endothelial dysfunction in comparison with non-diabetic control subjects. Response to sildenafil is not predicted by either endothelial function or autonomic function, but in diabetic men appears to be related to the initial degree of erectile dysfunction.
Pegge
N C
NC
Cardiac Centre, Department of Urology, Morriston Hospital, Swansea, UK.
Twomey
A M
AM
Vaughton
K
K
Gravenor
M B
MB
Ramsey
M W
MW
Price
D E
DE
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010410:Penile Erection / Q000187:drug effects; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use*; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate