Clinical Features and Prevalence of Asymptomatic Peripheral Artery Disease in Patients With Type 1 Diabetes Mellitus
Condition: Type 1 Diabetes Mellitus; Peripheral Artery Disease
MeSH terms: Peripheral Arterial Disease; Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Observational

Summary: 
      AIMS: Determining the clinical features and prevalence of peripheral artery disease (PAD) in
      asymptomatics patients with type 1 diabetes mellitus (T1DM) and checking the validity of the
      current recommendations regarding for PAD screening in T1DM.

      METHODOLOGY: An observational and cross-sectional prevalence study. The whole group of
      patients (sample size calculated: 299 patients) will make the Edinburgh Questionnaire for
      detecting classic symptoms of intermittent claudication, and after verifying the absence of
      symptoms and exclusion criteria, they will be included in the study. All patients will
      undergo assessment of clinical parameters related to T1DM and classic cardiovascular risk
      factors, as well as, an analytical assessment of the lipid profile, HbA1c level,
      proinflammatory profile and oxidative stress status. They will also undergo a comprehensive
      anthropometric assessment including office blood pressure (BP) monitoring and ambulatory
      24-hours BP monitoring in patients with an indication as routine clinical practice,
      assessment of cardioautonomic function, and lastly an ankle-brachial index (ABI) by Doppler
      ultrasound, in the context of routine clinical practice in patients with clinical indication,
      or as an extraordinary procedure for participating in the study in patients who do not meet
      criteria for screening according to current recommendations.
    

Detailed description: 
      INTRODUCTION:

      PAD is a condition characterized by atherosclerotic occlusive disease of the lower
      extremities. While PAD is a major risk factor for lower-extremity amputation, it is also
      accompanied by a high likelihood for symptomatic cardiovascular and cerebrovascular disease.

      PAD is often more subtle in its presentation in patients with diabetes than in those without
      diabetes. In contrast to the focal and proximal atherosclerotic lesions of PAD found
      typically in other high-risk patients, in diabetic patients the lesions are more likely to be
      more diffuse and distal. Importantly, PAD in individuals with diabetes is usually accompanied
      by peripheral neuropathy with impaired sensory feedback, thus a classic history of
      claudication may be less common. Data from Framingham Heart Study revealed that 20% of PAD
      symptomatic patients had diabetes mellitus, but probably, this data greatly underestimates
      PAD prevalence. As well, it has been reported that of those with PAD, over one-half of
      patients are asymptomatic or have atypical symptoms, about one-third have claudication, and
      the rest have more severe disease. Also, patients with diabetes who have been identified with
      PAD are more prone to sudden ischemia secondary to arterial thrombosis or to have a pivotal
      event leading to neuroischemic ulceration or infection that rapidly results in an acute
      presentation with critical limb ischemia and risk of amputation.

      However, is important to note, that most clinical data about PAD and diabetes, are becoming
      from population studies and randomized clinical trials, made up exclusively with type 2
      patients, or more frequently, after analyzing all patients with diabetes diagnosis, without
      distinction between T1 to T2 subtypes. Thus, although much is known regarding PAD in the
      general population, the assessment and management of PAD in those with diabetes is less
      clear, especially in patients with T1DM diagnosis.

      In 2003, a Consensus Development Conference was held regarding PAD in diabetes. After a
      series of lectures by experts in the field of endocrinology, cardiology, vascular surgery,
      orthopedic surgery, podiatry, and nursing, a vascular medicine panel was asked to answer
      questions about the epidemiology and impact of PAD in people with diabetes, diagnosis and
      treatment of PAD, but always generalizing the management of T1 and T2 diabetes, under the
      unique same term of "diabetes".

      PAD diagnosing in patients with diabetes is of clinical importance for two reasons:

      i) to identify patients at high risk of subsequent cardiovascular and cerebrovascular disease
      ii) to diagnose and treat PAD, which may be associated with functional disability and limb
      loss.

      Preventive measures in a patient with subclinical disease will make possible to avoid acute
      and chronic complications. Therefore, the knowledge about the true prevalence of PAD in T1DM
      is relevant for setting the screening indication in this patients, given that this is
      frequently asymptomatic and it might be clinically different at presentation compared to type
      2 diabetes patients.

      AIMS:

      The main objective of this works is determine the clinical features and prevalence of PAD in
      asymptomatics patients with T1DM and check the validity of the current recommendations
      regarding for PAD screening in T1DM.

      METHODOLOGY:

      Observational and cross-sectional prevalence study will be conducted. A consecutive
      population of type 1 patients from our clinics (sample size calculated: 299 patients) will be
      screened by the Edinburgh Questionnaire (Leng & Fowkes 1992) for detecting classic symptoms
      of intermittent claudication, and after verifying the absence of symptoms and exclusion
      criteria, they will be included in the study.

        -  All patients will undergo assessment of clinical parameters related to T1DM (years of
           the initial diagnosis, insulin treatment, metabolic control, microvascular chronic
           complications), cardiovascular risk factors (hypertension, dyslipidemia, chronic
           smoking), prior cardiovascular disease (coronary and cerebrovascular disease), as well
           as, an analytical assessment including a lipid profile, HbA1c level, proinflammatory
           markers (C-reactive protein, homocysteine) and oxidative stress status.

        -  They will undergo a comprehensive anthropometric evaluation: weight, height, body mass
           index [BMI (kg / m2)], abdominal and hip circumference, and body fat percentage to total
           body weight by bioelectrical impedance.

        -  Office BP and ambulatory 24-hours BP monitoring in patients with an indication as
           routine clinical practice (Mancia G. et al 2013).

        -  Assessment of cardiovascular autonomic dysfunction: orthostatism systolic and diastolic
           BP, orthostatism heart rate, heart rate variability to expiration / inspiration,
           Valsalva and orthostatic.

        -  Diabetic foot exploration (including bilateral peripheral pulses, Neuropathy Symptoms
           Score questionnaire, monofilament exploration, and calibrated tuning fork).

        -  The ABI will be performed by Doppler ultrasound (HADECO® Minidop 8 Mhz), in the context
           of routine clinical practice in patients with clinical indication, or an extraordinary
           procedure for participating in the study in patients who do not meet criteria for
           screening according to current recommendations.

      The ABI will be measured in both posterior tibial and pedia arteries. Interpretation of ABI
      wil be as follows: Average: 0.90 to 1.20; mild arterial obstruction: 0.70 to 0.89; moderate
      arterial obstruction: 0.40 to 0.69; severe arterial obstruction < 0.40; poorly compressible
      arteries > 1.20.

      In patients with ABI > 1.20 or < 0.9, the examination will be completed as recommended
      guidelines about asymptomatic PAD diagnosis by assessing the graphic recording blood flow and
      assessment index finger-arm.
    

Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        Patients with prior diagnosis of T1DM ≥ 18 years old, consecutively selected from T1DM and
        Insulin Pump clinics of a tertiary Hospital in Madrid.