Diabetes mellitus is a complex metabolic disorder or more precisely a group of disorders, which affect many organ systems and have a profound negative effect on the patient’s health and mortality. Treatment and management are consequently difficult and, in many cases, further complicated by often asymptomatic conditions such as peripheral artery disease (PAD).
The association between diabetes and a myriad of cardiovascular diseases (CVDs) is well established as is the additional deleterious effect diabetes has on the incidence, severity and mortality from CVDs – a leading cause of death [1, 2]. More specifically, diabetic patients (particularly those with type 2, although there is a growing number of those with type 1 diabetes) are more likely to be obese and many of them are hypertensive (prevalence between 10% and 30% for those with type 1 and up to 60% for type 2 diabetes), both of which are recognised risk factors for CVDs [2, 3, 4, 5].
Even more, diabetics are at risk of developing cardiovascular autonomic neuropathy (CAN) a serious complication that develops in approximately 25% of patients with type 1 and one in three patients with type 2 diabetes and is associated with increased mortality and greater risk of silent myocardial ischaemia and is even indicative of the possibility of development of stroke [6]. Diabetes is a major risk factor for the development of coronary artery disease (CAD), the leading cause of mortality worldwide [7].
Diabetics have higher mortality rates due to CAD than non-diabetics and higher rates of mortality, morbidity and re-infarction following a myocardial infarction (MI), with one-year mortality rates (from the time of diagnosis) in the ballpark of 50% [8, 9]. More worrying, diabetic patients have far higher rates of silent myocardial ischaemia, delaying proper and timely treatment of underlying CAD – the rates range from 10–20% for diabetics to just 1–4% for non-diabetics [10, 11].
One of the factors for increased incidence and higher prevalence of silent myocardial ischaemia (in diabetics) is diabetic neuropathy (affecting between 25% and 30% of diabetics) [12, 13]. However, the harmful effects of diabetes on the nervous system extend to other parts of the cardiovascular system and organ groups and may mask symptoms of other conditions, which are often only diagnosed through other means/methods. One such example is, of course, PAD.
Comorbidity between diabetes and PAD or LEAD (Lower-Extremity Artery Disease), as it is increasingly named due to the fact that it most commonly affects the lower extremities, is well known although there is a certain level of mystery regarding the exact prevalence of PAD amongst diabetics.
Prevalence of the most typical symptom of PAD, i.e. intermittent claudication, is well researched and estimated to be 3.5 times more prevalent in male and 8.6 times more prevalent in female diabetics than non-diabetics (in comparison with respective gender) [14]. Prevalence of symptomatic PAD in diabetic patients in general is estimated to be at least 20%, but that number is likely far too low as PAD is far more often asymptomatic [15]. It should be kept in mind that only 10% of all patients with PAD have typical symptoms, 40% are entirely symptomatic and the rest have symptoms that could be attributed to other medical conditions [16, 17].
But why aren’t there more cases of diagnosed PAD amongst diabetics in the light of overwhelming evidence on the link between the two diseases?
The answer is twofold with the first part being the aforementioned diabetic neuropathy and the difficulties in differentiating (in the absence of modern diagnostic methods) between pain and discomfort of vascular or neurological origin [18]. The second part is the underutilisation of Ankle-Brachial (pressure) Index (ABPI or ABI) assessment for PAD diagnosis [19]. The reasons for this are manifold and range from inexperience in using a Doppler probe to measure the ABI to difficulties accurately assessing ABI in those with calcified arteries (more prevalent in diabetics) [20]. Many of those rather trivial difficulties can be easily solved, starting with the use of an oscillometric-plethysmographic diagnostic device for easy and error-free assessment (handy tool for preventive screening) to substituting ABI for a Toe-Brachial Index (TBI) measurement [21, 22].
Timely diagnosis of PAD in diabetic patients is crucial for preventing a myriad of serious complications whose severity is exacerbated by the deleterious effect of diabetes on the atherosclerotic process. Many patients (about 50% of them although some studies propose even higher numbers that go to 76%) with critical limb ischaemia (CLI), an advanced form of PAD with high morbidity and mortality, also have diabetes and they have worse outcomes than those individuals with just CLI [23, 24, 25]. In connection with that, specifically the arterial (insufficiency) ulcers (ischaemic wounds) as one of the components of CLI, there are usually considerable difficulties differentiating between ulcers in diabetic patients as some may have more than one type of ulcer (arterial, venous and neuropathic diabetic) [26]. Other assessment methods (like TBI) may have to be used [27].
Management of PAD in diabetic patients is difficult and complex and (often) compounded by other comorbid conditions like CAD, hypertension and diabetic dyslipidaemia (altered levels of serum cholesterol and triglycerides) [28]. Still, much can be done by the patients her/himself by secondary risk reduction, i.e. lifestyle changes, including: weight reduction, smoking cessation, physical activity and a healthy diet [29].
Patients with diabetes mellitus are at an increased risk of PAD (LEAD) and therefore prime candidates for an ABI or TBI assessment if they have calcified arteries or any other condition that preclude the former diagnostic method. Timely diagnosis and holistic, concurrent management of both conditions is crucial for mitigating complications and decreasing the likelihood of adverse outcomes.