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Type 2 diabetes may cause erectile dysfunction

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January 6, 2019

A genetic predisposition for type 2 diabetes may be associated with erectile dysfunction, suggesting that diabetes can be a cause of erectile issues, according to findings published in the American Journal of Human Genetics.

“Erectile dysfunction affects at least one in five men over 60, yet up until now little has been known about its cause,” Anna Murray, PhD, associate professor in human genetics at the University of Exeter Medical School in England, said in a press release. “Our paper echoes recent findings that the cause can be genetic, and it goes further. We found that a genetic predisposition to type 2 diabetes is linked to erectile dysfunction. That may mean that if people can reduce their risk of diabetes through healthier lifestyles, they may also avoid developing erectile dysfunction.”

In a genome-wide association study, researchers from the University of Exeter and the University of Oxford analyzed data from more than 220,000 men across three cohorts, 6,000 of whom experienced erectile dysfunction using data from the UK Biobank, the Estonian Genome Center of the University of Tartu cohort and hospital-recruited Partners HealthCare Biobank.

In linkage disequilibrium score regression, the researchers identified erectile dysfunction to share the greatest genetic correlation with type 2 diabetes, limb fat mass and whole-body fat mass. In Mendelian randomization analyses, they evaluated the potential causal role of nine predefined cardiometabolic traits on erectile dysfunction risk, including type 2 diabetes, insulin resistance, systolic blood pressure, LDL cholesterol, smoking, alcohol consumption, BMI, coronary heart disease and education level. In the analyses, researchers found that each 1-log higher genetic risk for type 2 diabetes increased the risk for erectile dysfunction, with an OR of 1.11 (95% CI, 1.05-1.17). They noted that insulin resistance likely represented a mediating pathway, with an OR of 1.36 for erectile dysfunction per 1-standard deviation genetically elevated insulin resistance (95% CI, 1.01-1.84). Researchers also found that higher systolic BP was associated with higher risk for erectile dysfunction, whereas LDL cholesterol, smoking or alcohol consumption were not linked to the condition.

Genetic risk for CHD showed weak effects on the risk for erectile dysfunction, suggesting that pathways leading to CHD may be implicated in erectile dysfunction, the researchers wrote.

“By aggregating data from three cohorts, including 6,175 [erectile dysfunction]-affected case subjects of European ancestry, we identified a locus associated with [erectile dysfunction], with several lines of evidence suggesting SIM1, highly expressed in the hypothalamus, to be the causal gene at this locus,” the researchers wrote. “Our findings provide human genetic evidence in support of the key role of the hypothalamus in regulating male sexual function.”

The researchers noted that few clinical trials of diabetes have reported erectile dysfunction as an outcome of improved glucose control, limiting the conclusions that can be drawn about whether treatment of diabetes is likely to have an impact on erectile dysfunction risk.

“Our finding is important as diabetes is preventable and indeed one can now achieve ‘remission’ from diabetes with weight loss, as illustrated in recent clinical trials,” Michael Holmes, MBBS, MSc, PhD, MRCP, associate professor in the department of population health at the University of Oxford, said in the release. “This goes beyond finding a genetic link to erectile dysfunction to a message that is of widespread relevance to the general public, especially considering the burgeoning prevalence of diabetes.” – by Regina Schaffer

Disclosures: The authors report no relevant financial disclosures.

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Perspective

The association between diabetes and erectile dysfunction is well-known, and a vast body of literature has demonstrated a threefold probability for men with diabetes having erectile dysfunction. Although erectile dysfunction is age-related, it can be present across the lifespan from adolescence, especially when there are risk factors such as diabetes, metabolic syndrome or cardiovascular diseases. Erectile dysfunction can affect up to 75% of men with diabetes, occurring at a younger age when compared with healthy men. Interestingly, erectile dysfunction has been proven to be a first sign of diabetes, diagnosed later in 12% to 30% of men.

Several identified factors contribute to the complex pathogenesis of diabetes-related erectile dysfunction, including diabetic neuropathy, vascular disease, hypogonadism, psychogenic components and drug side effects. 

Recently, Bovijn and colleagues provided evidence of a genetic causal link between type 2 diabetes and erectile dysfunction, identifying one locus at 6q16.3, located between MCHR2 and SIM1. Interestingly, it also represents a potential causal effect of systolic blood pressure.

These findings corroborate and start to explain previous studies that showed an association between erectile dysfunction and most of the classical CV risk factors, such as hypertension, hyperlipidemia, metabolic syndrome and depression. Although more and larger studies are necessary to further clarify the pathophysiology of what could prove to be an “erectile syndrome,” these data are enough to suggest a multidisciplinary approach to men experiencing erectile dysfunction and/or type 2 diabetes and/or CVD. Tailored management can positively impact quality of life.

Damiano Pizzol, MD, PhD

Operational Research Unit,
Doctors with Africa CUAMM,
Beira, Mozambique

Disclosure: Pizzol reports no relevant financial disclosures.