Clinical Features and Prevalence of Asymptomatic Peripheral Artery Disease in Patients With Type 1 Diabetes Mellitus
Clinical Features and Prevalence of Asymptomatic Peripheral Artery Disease in Patients With Type 1 Diabetes Mellitus
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.
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.
Inclusion Criteria:

 -  Previous diagnosis of T1DM before 30 years of age.

 DM diagnostic criteria:

 -  DM cardinal symptoms (polyuria, polydipsia, unexplained weight loss) with plasma
 glucose ≥ 200 mg / dl, or diagnosis as diabetic ketoacidosis (DKA).

 -  fasting plasma glucose (≥ 8 h) ≥ 126 mg / dl.

 -  plasma glucose at 2 h in testing oral glucose tolerance test (75 g glucose) ≥ 200 mg /
 dl.

 -  glycosylated hemoglobin (HbA1c) ≥ 6.5% [as certified by the National method
 Glycohemoglobin Standardized Program (NGSP) and standardized according to the Diabetes
 Control and Complication Trial trial (DCCT)].

 The criteria b, c and d require confirmation, except in cases of hyperglycemia with acute
 decompensation (criteria a).

 -  Positive determination of a autoantibody serum markers of immune destruction against
 antigens cytoplasm of the islet cells (ICA), anti-insulin (AAI), and / or anti protein
 glutamate decarboxylase (GADA) at initial diagnosis time or during the course of the
 disease.

 Acceptance of participation in the study and sign the informed consent.

 Exclusion Criteria:

 -  Prior diagnosis of PAD, diabetic foot, leg amputation or symptoms in line with PAD
 according to the Edinburgh questionnaire for intermittent claudication.

 -  Diagnosis of type 2 diabetes, gestational diabetes, latent autoimmune diabetes in
 adults (LADA) or maturity-onset diabetes of youth (MODY) diabetes.

 -  Current pregnancy, institutionalized or terminal illness subjects.

 -  Refusal to participate in the study or to sign the informed consent.