Testosterone deficiency in Type 2 diabetes

Don’t Leave it too late

Testosterone deficiency is especially common in this group of patients with about 40% of them suffering from the condition although sadly in the UK most of these patients are undiagnosed and therefore untreated.

A lot of patients just attribute their symptoms of poor health to their diabetes and also sadly testosterone measurements are rarely done by their doctors or lowish levels acted upon.

This is particularly sad as in other patients these patients quality of life is severely affected but also now there ae several large research studies that have been reported upon showing how dangerous it is for a diabetic to have this condition not treated.  The results from the largest study done in the world in diabetics which has been going on in the Midlands in the UK – THE BLAST STUDY alarmingly has shown that 20% of the patients in the study with low testosterone that was not treated have died within 5 years of the start of the study, whereas in the patients that were treated with testosterone the death rate was only 3.7%.

There is accumulating evidence for an association between low testosterone in men and the prevalence of type 2 diabetes (T2DM), with much of this suggesting that low testosterone predicts insulin resistance, metabolic syndrome* and T2DM development. 

Low SHBG* SHBG appears to predict metabolic syndrome/T2DM with some studies suggesting this association to be independent of serum testosterone. In fact; there is evidence that both low SHBG and low testosterone can predict the incidence of metabolic syndrome and T2DM independently of each other.  

*metabolic syndrome – a patient having at least 3 of the following 5 key risk factors – too much abdominal fat, i.e. increased waist line, high blood pressure, high triglycerides, low HDL cholesterol, high fasting blood glucose.  

*SHBG – a protein; it attaches to sex hormones in your blood.  

The T4DM study carried out in recent years in Australia found a 40% reduction in men progressing to type 2 diabetes when testosterone treatment was combined with lifestyle change versus lifestyle alone. The study also found that intensive lifestyle intervention over 2 years, despite moderate weight loss did not improve symptoms or free testosterone levels. These findings cast doubt on the reliance of lifestyle advice alone as our only strategy for dealing with an increasing prevalence of type 2 diabetes through out the world. 

Several studies have shown improvement to diabetic control in diabetic patients on testosterone treatment. 

Yassin et al – 2019  

Grotty et al – 2018 

Clinical awareness: 

Testosterone deficiency in men is common but is under recognised and therefore under diagnosed in men with type 2 diabetes. The American Diabetes Association in their standards of care, since 2018, have included testosterone deficiency as a common comorbidity in men with type 2 diabetes. The presence of a higher prevalence of low testosterone is also recognised in the UK on the website of Diabetes. So, the question is why in the UK are so few diabetics getting their testosterone level measured let along treated!”  

The association of symptomatic testosterone deficiency is included in many national and international guidelines on the management of this condition and yet it is a condition that is not considered by many clinicians, not only in medicine in general but also those in specialities such as diabetes, endocrinology and urology. Many specialists do not treat testosterone deficiency unless it has a classical cause but not so-called functional hypogonadism due to obesity for example. Testosterone deficiency is a cause of fatigue and tiredness but is not usually considered in the differential diagnosis of these symptoms. It is even not thought of and measure when a standard baseline for causes of fatigue and tiredness do not reveal an etiology.  Many men may not volunteer symptoms  of sexual problems due to embarrassment but will report a symptom which they are comfortable with on first meeting with a health professional. So, for the future recognition and appropriate management of testosterone deficiency it must be considered by health professionals who are usually in first contact with patients. These are the primary care physicians in general practice and their nursing staff.  

Erectile dysfunction is recognised and accepted as having a high prevalence in diabetes (>70%) and is caused by atherosclerosis (hardening of the arteries) and/or testosterone deficiency in the majority of patients. Erectile dysfunction may be the first presentation of cardiovascular disease (heart disease). There is a strong correlation of erectile dysfunction with “silent” coronary artery disease in diabetes. Even though this is well known, health professionals do not always ask the question at the diabetes annual review. Measurement of testosterone is mandatory in a man with erectile dysfunction.  The future development of enhanced recognition and diagnosis of testosterone deficiency (hypogonadism) in diabetes is primarily dependent on increasing the awareness of the condition which has to include a knowledge of the benefits to patients not only in disease outcome but also in the improvement of quality of life. The clinical awareness, including patient benefit does need to be conveyed to doctors and nurses by education, local and national guidelines. As with women’s health in primary care where a practice doctor is assigned to this interest area, there should equally be a doctor for men’s health.  Importantly, specialists in an area from either endocrinology, diabetes, sexual health and urology should take a lead role for developing a support network for general practitioners. This should include a referral system for patient assessment and review of patients if required, local guidelines, national guidelines and the involvement of medical societies and government.  

Evidence that PDE5 inhibitors (drugs such as Viagra, Sildenafil, Tadalafil) might reduce diabetes related morbidity and mortality.  

PDE5 inhibitors were developed as daily therapy to treat cardiovascular disease (angina) and improvements in erectile dysfunction were an incidental finding during clinical trials. Sildenafil and Tadalafil are licensed to treat pulmonary hypertension through their beneficial effects on endothelial dysfunction.  

Several cardiology reviews have highlighted the beneficial cardiovascular effects that would potentially reduce cardiovascular events e.g., heart attacks in high-risk populations such as men with type 2 diabetes. Currently Tadalafil 5mg is the only PDE5 inhibitor suitably licensed for daily use.  

Anderson et al. who followed a UK primary care population of 5956 UK men with type 2 diabetes over 6.9 years. A 31% reduction in all cause mortality and 26% reduction in heart attacks were reported in men taking PDE5 inhibitors.  

Andersson et al. reported data from a Swedish database of 43,415 men after first myocardial infarction (heart attack) for 5 years and found significant reduction in all cause and cardiovascular mortality and 30% reduction in new diagnosis of heart failure in men prescribed PDE5 inhibitors. The benefits were greater in men on more frequent dosing of PDE5 inhibitors i.e. best benefit was seen with daily dosing Tadalafil 5mg. These benefits were not seen with other treatments for erectile dysfunction.  

Scrantum et al. carried out a complex health care review and concluded that diagnosis, successful treatment of erectile dysfunction may promote improved adherence and management of other diseases. It may improve treatment outcome, decrease health care costs, and possibly prevent or improve deterioration in medical conditions commonly associated with erectile dysfunction i.e., heart disease and diabetes.  

Prevention of diabetic peripheral neuropathy (DPN)  

DPN occurs in approximately 30% of men with type 2 diabetes. Currently the main stay of prevention is through tight glycaemic control. There are numerous case reports of improvement in neuropathic pain and paraesthesia with PDE5 inhibitors.  

Depression in diabetes 

Depression is twice as common in men with type 2 diabetes with a prevalence of 25%. Several studies have shown an improvement in depression when men are treated effectively for their erectile dysfunction.   

This latest information was taken from “Testosterone in cardiometabolic and other diseases” Geoffrey I. Hackett & Michael Kirby. Publisher www.minervamedica.it  

The Leger Clinic