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    ED, diabetes, and CV risk: Update on treatment, risk reduction

    Diabetic men with erectile dysfunction often require aggressive ED therapy, should be assessed for CV risk

    Charles Walker, MDCharles Walker, MD Alfredo Suarez-Sarmiento, MDAlfredo Suarez-Sarmiento, MD Section Editor Steven A. Kaplan, MDSection Editor Steven A. Kaplan, MD

    Dr. Walker is assistant professor of urology and Dr. Suarez-Sarmiento is a research scientist in the department of urology, Yale University School of Medicine, New Haven CT. Dr. Kaplan is professor of urology at the Icahn School of Medicine at Mount Sinai and director of benign urologic diseases, Mount Sinai Health System, New York. Follow him on Twitter at @MaleHealthDoc.

    Of the commonly recognized causes of erectile dysfunction, diabetes is the second most common behind vascular causes (figure 1). The prevalence of erectile dysfunction in the general population is estimated to be 52% in men between age 40 and 70 years with a staggering 322 million men affected worldwide. According to 2012 U.S. census data, 15.5 million American men have diabetes, 50% of whom have sexual troubles caused by their disease. The prevalence of ED in diabetics is independently associated with duration of diabetes mellitus, occurs 10 to 15 years earlier than in men without diabetes, and is more severe and less responsive to oral treatment than in patients without the disease. 

    Related: Five key elements of a successful men’s health center

    The etiology of ED in diabetics is multifactorial and the determinants of pathogenesis include age, duration of diabetes, degree of glycemic control, presence of microvascular complications, and coexistence of cardiovascular disease. Normal penile erection requires an increase in neurologically mediated cavernosal arterial inflow, cavernosal smooth muscle relaxation, and restriction of venous outflow. Diabetes can cause irreversible damage to vascular endothelium, decreasing blood flow to the penis. Up to 60% to 70% of diabetic men have neuropathy, which impedes neurogenic activation of erections. Cavernosal smooth muscle fibrosis due to chronic inflammation is also common in diabetics and prevents normal smooth muscle relaxation. Inadequate inflow ultimately results in ineffective restriction to outflow.

    ED and diabetes: Pathophysiology

    Erectile dysfunction in diabetics is mediated by insulin resistance, which leads to endothelial dysfunction and atherosclerosis (figure 2). In epidemiologic studies, worse glycemic control correlates with higher rates of ED, and in animal studies insulin administration relieves diabetes-associated ED and improves surrogates for erectile function (J Urol 2003; 170:291-7). In men without diabetes, the addition of metformin to sildenafil citrate (Viagra) results in improved erectile function, suggesting that insulin regulation is involved in the pathogenesis of vasculogenic ED, even when overt diabetes mellitus is not present (J Androl 2012; 33:608-14).

    Diabetes, obesity, and the metabolic syndrome (MetS) are chronic inflammatory states that result in structural damage to the vascular endothelium of the penis and other vascular beds and impaired nitric oxide (NO) release in men with ED. NO causes cavernosal smooth muscle relaxation and inhibits platelet aggregation and adhesion. Reduced bioavailability of NO therefore results in vasoconstriction, platelet adhesion, and smooth muscle cell proliferation, which potentiates the atherosclerotic burden of the penile vasculature, further compromising cavernosal arterial inflow.

    Insulin resistance may also cause endothelial dysfunction through an NO-independent pathway mediated by endothelin-1. Insulin stimulates production of endothelin-1, a potent vasoconstrictor, and NO in vascular endothelium. In non-diabetic individuals, the vasodilatory effects of NO predominate; in insulin-resistant states, this does not occur, suggesting that in diabetes there is preservation of endothelin in the face of impaired NO production.

    Next: ED, DM, and metabolic syndrome

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