Type 1 Diabetes MellitusNCT02910271
Clinical Features and Prevalence of Asymptomatic Peripheral Artery Disease in Patients With Type 1 Diabetes Mellitus
An observational study of Type 1 Diabetes Mellitus and Peripheral Artery Disease, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Type 1 Diabetes Mellitus, Peripheral Artery Disease
- How many people
- 299 participants
- Where
- 1 siteSpain
- Study dates
- May 2016to Mar 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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)].
Show all 9Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)
Madrid
About this study
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.
Read the 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:
- 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.
- Medical subject headings
- Diabetes Mellitus, Type 1, Peripheral Arterial Disease
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of PAD in asymptomatic patients with T1DM assessed by ankle-branchial index.
Measured: 2 years
Secondary outcomes (10)
Association between anthropometric parameters and asymptomatic peripheral artery disease in patients with type 1 diabetes mellitus.
Comparison of anthropometric parameters among patients with and without peripheral artery disease.
Anthropometric evaluation includes:
- Body mass index.
- Waist circumference.
- Body fat percentage with respect to total body weight assessed by bioelectrical impedance.
Measured: 2 years
Association between lipid profile and asymptomatic artery disease in patients with type 1 diabetes mellitus.
Comparison of lipids among patients with and without peripheral artery disease.
Lipid profile includes:
- Total cholesterol.
- LDL-cholesterol.
- HDL-cholesterol.
- Triglycerides.
- Total cholesterol / HDL-cholesterol.
- NonHDL cholesterol.
Measured: 2 years
Association between glycemic control and asymptomatic artery disease in patients with type 1 diabetes mellitus.
Comparison of glycosylated hemoglobin levels among patients with and without peripheral artery disease.
Measured: 2 years
Association between C-reactive protein and asymptomatic artery disease in patients with type 1 diabetes mellitus.
Comparison of circulating C-reactive protein among patients with and without peripheral artery disease.
Measured: 2 years
Association between homocysteine and asymptomatic artery disease in patients with type 1 diabetes mellitus.
Comparison of circulating homocysteine levels among patients with and without peripheral artery disease.
Measured: 2 years
Number and percentage of patients with pathological ankle-branchial index without screening criteria according to the current recommendations for subjects with type 1 diabetes mellitus.
Comparison of ankle-branchial index by doppler technique among patients with and without screening criteria according to the current recommendations for subjects with type 1 diabetes mellitus.
Measured: 2 years
Number and percentage of patients with type 1 diabetes mellitus, cardiovascular autonomic dysfunction and asymptomatic PAD.
Cardiovascular autonomic dysfunction will be assessed by orthostatism induced abnormal changes in systolic BP and diastolic BP.
Measured: 2 years
Number and percentage of patients with type 1 diabetes mellitus, cardiovascular autonomic dysfunction and asymptomatic PAD.
Cardiovascular autonomic dysfunction will be assessed by orthostatism induced abnormal changes in heart rate.
Measured: 2 years
Number and percentage of patients with type 1 diabetes mellitus, cardiovascular autonomic dysfunction and asymptomatic PAD.
Cardiovascular autonomic dysfunction will be assessed by RR interval variability response to expiration / inspiration, Valsalva maneuver and orthostatism.
Measured: 2 years
Prevalence of asymptomatic atherosclerotic carotid disease in patients with asymptomatic PAD.
Asymptomatic carotid atherosclerotic disease will be assessed by measuring the thickness of the intima by doppler technique.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2016 (estimated)
- Study startMay 2016
- Primary completionMar 2018
- Study completionMar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 299 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- María Lía Nattero Chávez, Principal investigator, Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02910271
- Sponsor's protocol ID
- PI464/15
- Status last verified
- Jul 2018
- First submitted
- 10 Aug 2016
- Last updated
- 2 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
de Ferranti SD, de Boer IH, Fonseca V, Fox CS, Golden SH, Lavie CJ, Magge SN, Marx N, McGuire DK, Orchard TJ, Zinman B, Eckel RH. Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association. Circulation. 2014 Sep 23;130(13):1110-30. doi: 10.1161/CIR.0000000000000034. Epub 2014 Aug 11. No abstract available.
PubMed 25114208American Diabetes Association. Peripheral arterial disease in people with diabetes. Diabetes Care. 2003 Dec;26(12):3333-41. doi: 10.2337/diacare.26.12.3333. No abstract available.
PubMed 14633825Murabito JM, D'Agostino RB, Silbershatz H, Wilson WF. Intermittent claudication. A risk profile from The Framingham Heart Study. Circulation. 1997 Jul 1;96(1):44-9. doi: 10.1161/01.cir.96.1.44.
PubMed 9236415Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM Jr, White CJ, White J, White RA, Antman EM, Smith SC Jr, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B; American Association for Vascular Surgery; Society for Vascular Surgery; Society for Cardiovascular Angiography and Interventions; Society for Vascular Medicine and Biology; Society of Interventional Radiology; ACC/AHA Task Force on Practice Guidelines; American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; Vascular Disease Foundation. ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. J Am Coll Cardiol. 2006 Mar 21;47(6):1239-312. doi: 10.1016/j.jacc.2005.10.009. No abstract available.
PubMed 16545667Standards of Medical Care in Diabetes-2016: Summary of Revisions. Diabetes Care. 2016 Jan;39 Suppl 1:S4-5. doi: 10.2337/dc16-S003. No abstract available.
PubMed 26696680Leng GC, Fowkes FG. The Edinburgh Claudication Questionnaire: an improved version of the WHO/Rose Questionnaire for use in epidemiological surveys. J Clin Epidemiol. 1992 Oct;45(10):1101-9. doi: 10.1016/0895-4356(92)90150-l.
PubMed 1474406Parati G, Stergiou G, O'Brien E, Asmar R, Beilin L, Bilo G, Clement D, de la Sierra A, de Leeuw P, Dolan E, Fagard R, Graves J, Head GA, Imai Y, Kario K, Lurbe E, Mallion JM, Mancia G, Mengden T, Myers M, Ogedegbe G, Ohkubo T, Omboni S, Palatini P, Redon J, Ruilope LM, Shennan A, Staessen JA, vanMontfrans G, Verdecchia P, Waeber B, Wang J, Zanchetti A, Zhang Y; European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability. European Society of Hypertension practice guidelines for ambulatory blood pressure monitoring. J Hypertens. 2014 Jul;32(7):1359-66. doi: 10.1097/HJH.0000000000000221.
PubMed 24886823Nattero-Chavez L, Redondo Lopez S, Alonso Diaz S, Garnica Urena M, Fernandez-Duran E, Escobar-Morreale HF, Luque-Ramirez M. Association of Cardiovascular Autonomic Dysfunction With Peripheral Arterial Stiffness in Patients With Type 1 Diabetes. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2675-2684. doi: 10.1210/jc.2018-02729.
PubMed 30786000Nattero-Chavez L, Alonso Diaz S, Jimenez-Mendiguchia L, Garcia-Cano A, Fernandez-Duran E, Dorado Avendano B, Escobar-Morreale HF, Luque-Ramirez M. Sexual Dimorphism and Sex Steroids Influence Cardiovascular Autonomic Neuropathy in Patients With Type 1 Diabetes. Diabetes Care. 2019 Nov;42(11):e175-e178. doi: 10.2337/dc19-1375. Epub 2019 Sep 17. No abstract available.
PubMed 31530659Nattero-Chavez L, Bayona Cebada A, Fernandez-Duran E, Quintero Tobar A, Dorado Avendano B, Escobar-Morreale H, Luque-Ramirez M. "Arterial stiffness is not associated with changes in the circadian pattern of blood pressure in patients with type 1 diabetes mellitus and cardiovascular autonomic dysfunction". Diab Vasc Dis Res. 2023 May-Jun;20(3):14791641231173621. doi: 10.1177/14791641231173621.
PubMed 37184151Nattero-Chavez L, Luque-Ramirez M, Moncayo S, Alonso-Diaz S, Fernandez-Duran E, Redondo-Lopez S, Garcia-Urena M, Escobar-Morreale HF. Circulating soluble klotho is not associated with an elevated ankle-brachial index as a surrogate marker of early arterial calcification in patients with type 1 diabetes mellitus and no evidence of renal dysfunction. Diabetes Metab. 2019 Dec;45(6):589-592. doi: 10.1016/j.diabet.2018.01.009. Epub 2018 Jan 18. No abstract available.
PubMed 29398255Nattero-Chavez L, Redondo Lopez S, Alonso Diaz S, Garnica Urena M, Fernandez-Duran E, Escobar-Morreale HF, Luque-Ramirez M. The peripheral atherosclerotic profile in patients with type 1 diabetes warrants a thorough vascular assessment of asymptomatic patients. Diabetes Metab Res Rev. 2019 Feb;35(2):e3088. doi: 10.1002/dmrr.3088. Epub 2018 Nov 20.
PubMed 30338903Nattero-Chávez L, Alonso Díaz S, Montanez L, Fernández E, Redondo López S, Garnica Ureña M, Bayona A, Esxobar-Morreale HF, Luque-Ramírez M. 567-P: Influence of Sex on Cardioautonomic Neuropathy in Patients with Type 1 Diabetes. Diabetes 2019 Jun; 68(Supplement 1): -. https://doi.org/10.2337/db19-567-P
Nattero-Chavez L, Martinez-Garcia MA, Fernandez-Duran E, Redondo Lopez S, Dorado Avendano B, Escobar-Morreale HF, Luque-Ramirez M. Fasting serum copeptin and asymptomatic peripheral artery disease: No association in patients with type 1 diabetes mellitus. Diabetes Metab. 2021 May;47(3):101207. doi: 10.1016/j.diabet.2020.10.005. Epub 2020 Nov 4.
PubMed 33160031Nattero-Chavez L, Martinez-Garcia MA, Redondo Lopez S, Fernandez-Duran E, Dorado Avendano B, Escobar-Morreale HF, Luque-Ramirez M. High serum copeptin may be a marker of an increased carotid intima-media thickness in asymptomatic patients with type 1 diabetes. J Diabetes Complications. 2022 Jan;36(1):108085. doi: 10.1016/j.jdiacomp.2021.108085. Epub 2021 Nov 11.
PubMed 34823978
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical Features and Prevalence of Asymptomatic Peripheral Artery Disease in Patients With Type 1 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT02910271
- Acronym / sponsor ID
- PI464/15
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 299 participants (actual)
- Lead sponsor
- Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y CajalUniversity, hospital or other
- Study start
- May 2016 (actual)
- Primary completion
- Mar 2018 (actual)
- Study completion
- Mar 2018 (actual)
- First posted
- 22 Sep 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (9 listed)
- Previous diagnosis of T1DM before 30 years of age.
- 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)].
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Prevalence of PAD in asymptomatic patients with T1DM assessed by ankle-branchial index.
Time frame: 2 years
10 secondary outcomes
Association between anthropometric parameters and asymptomatic peripheral artery disease in patients with type 1 diabetes mellitus.
Time frame: 2 years
Association between lipid profile and asymptomatic artery disease in patients with type 1 diabetes mellitus.
Time frame: 2 years
Association between glycemic control and asymptomatic artery disease in patients with type 1 diabetes mellitus.
Time frame: 2 years
Association between C-reactive protein and asymptomatic artery disease in patients with type 1 diabetes mellitus.
Time frame: 2 years
Association between homocysteine and asymptomatic artery disease in patients with type 1 diabetes mellitus.
Time frame: 2 years
Number and percentage of patients with pathological ankle-branchial index without screening criteria according to the current recommendations for subjects with type 1 diabetes mellitus.
Time frame: 2 years
Number and percentage of patients with type 1 diabetes mellitus, cardiovascular autonomic dysfunction and asymptomatic PAD.
Time frame: 2 years
Number and percentage of patients with type 1 diabetes mellitus, cardiovascular autonomic dysfunction and asymptomatic PAD.
Time frame: 2 years
Number and percentage of patients with type 1 diabetes mellitus, cardiovascular autonomic dysfunction and asymptomatic PAD.
Time frame: 2 years
Prevalence of asymptomatic atherosclerotic carotid disease in patients with asymptomatic PAD.
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2024.
- Background: PubMed 25114208de Ferranti SD, de Boer IH, Fonseca V, Fox CS, Golden SH, Lavie CJ, Magge SN, Marx N, McGuire DK, Orchard TJ, Zinman B, Eckel RH. Type 1 diabetes mellitus and cardiovascular disease: a scientific statement from the American Heart Association and American Diabetes Association. Circulation. 2014 Sep 23;130(13):1110-30. doi: 10.1161/CIR.0000000000000034. Epub 2014 Aug 11. No abstract available.
- Background: PubMed 14633825American Diabetes Association. Peripheral arterial disease in people with diabetes. Diabetes Care. 2003 Dec;26(12):3333-41. doi: 10.2337/diacare.26.12.3333. No abstract available.
- Background: PubMed 9236415Murabito JM, D'Agostino RB, Silbershatz H, Wilson WF. Intermittent claudication. A risk profile from The Framingham Heart Study. Circulation. 1997 Jul 1;96(1):44-9. doi: 10.1161/01.cir.96.1.44.
- Background: PubMed 16545667Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WR, Olin JW, Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM Jr, White CJ, White J, White RA, Antman EM, Smith SC Jr, Adams CD, Anderson JL, Faxon DP, Fuster V, Gibbons RJ, Halperin JL, Hiratzka LF, Hunt SA, Jacobs AK, Nishimura R, Ornato JP, Page RL, Riegel B; American Association for Vascular Surgery; Society for Vascular Surgery; Society for Cardiovascular Angiography and Interventions; Society for Vascular Medicine and Biology; Society of Interventional Radiology; ACC/AHA Task Force on Practice Guidelines; American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; Vascular Disease Foundation. ACC/AHA 2005 guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): executive summary a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, Society of Interventional Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Peripheral Arterial Disease) endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation; National Heart, Lung, and Blood Institute; Society for Vascular Nursing; TransAtlantic Inter-Society Consensus; and Vascular Disease Foundation. J Am Coll Cardiol. 2006 Mar 21;47(6):1239-312. doi: 10.1016/j.jacc.2005.10.009. No abstract available.
- Background: PubMed 26696680Standards of Medical Care in Diabetes-2016: Summary of Revisions. Diabetes Care. 2016 Jan;39 Suppl 1:S4-5. doi: 10.2337/dc16-S003. No abstract available.
- Background: PubMed 1474406Leng GC, Fowkes FG. The Edinburgh Claudication Questionnaire: an improved version of the WHO/Rose Questionnaire for use in epidemiological surveys. J Clin Epidemiol. 1992 Oct;45(10):1101-9. doi: 10.1016/0895-4356(92)90150-l.
- Background: PubMed 24886823Parati G, Stergiou G, O'Brien E, Asmar R, Beilin L, Bilo G, Clement D, de la Sierra A, de Leeuw P, Dolan E, Fagard R, Graves J, Head GA, Imai Y, Kario K, Lurbe E, Mallion JM, Mancia G, Mengden T, Myers M, Ogedegbe G, Ohkubo T, Omboni S, Palatini P, Redon J, Ruilope LM, Shennan A, Staessen JA, vanMontfrans G, Verdecchia P, Waeber B, Wang J, Zanchetti A, Zhang Y; European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability. European Society of Hypertension practice guidelines for ambulatory blood pressure monitoring. J Hypertens. 2014 Jul;32(7):1359-66. doi: 10.1097/HJH.0000000000000221.
- Background: PubMed 30786000Nattero-Chavez L, Redondo Lopez S, Alonso Diaz S, Garnica Urena M, Fernandez-Duran E, Escobar-Morreale HF, Luque-Ramirez M. Association of Cardiovascular Autonomic Dysfunction With Peripheral Arterial Stiffness in Patients With Type 1 Diabetes. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2675-2684. doi: 10.1210/jc.2018-02729.
- Background: PubMed 31530659Nattero-Chavez L, Alonso Diaz S, Jimenez-Mendiguchia L, Garcia-Cano A, Fernandez-Duran E, Dorado Avendano B, Escobar-Morreale HF, Luque-Ramirez M. Sexual Dimorphism and Sex Steroids Influence Cardiovascular Autonomic Neuropathy in Patients With Type 1 Diabetes. Diabetes Care. 2019 Nov;42(11):e175-e178. doi: 10.2337/dc19-1375. Epub 2019 Sep 17. No abstract available.
- Background: PubMed 37184151Nattero-Chavez L, Bayona Cebada A, Fernandez-Duran E, Quintero Tobar A, Dorado Avendano B, Escobar-Morreale H, Luque-Ramirez M. "Arterial stiffness is not associated with changes in the circadian pattern of blood pressure in patients with type 1 diabetes mellitus and cardiovascular autonomic dysfunction". Diab Vasc Dis Res. 2023 May-Jun;20(3):14791641231173621. doi: 10.1177/14791641231173621.
- Results publication: PubMed 29398255Nattero-Chavez L, Luque-Ramirez M, Moncayo S, Alonso-Diaz S, Fernandez-Duran E, Redondo-Lopez S, Garcia-Urena M, Escobar-Morreale HF. Circulating soluble klotho is not associated with an elevated ankle-brachial index as a surrogate marker of early arterial calcification in patients with type 1 diabetes mellitus and no evidence of renal dysfunction. Diabetes Metab. 2019 Dec;45(6):589-592. doi: 10.1016/j.diabet.2018.01.009. Epub 2018 Jan 18. No abstract available.
- Results publication: PubMed 30338903Nattero-Chavez L, Redondo Lopez S, Alonso Diaz S, Garnica Urena M, Fernandez-Duran E, Escobar-Morreale HF, Luque-Ramirez M. The peripheral atherosclerotic profile in patients with type 1 diabetes warrants a thorough vascular assessment of asymptomatic patients. Diabetes Metab Res Rev. 2019 Feb;35(2):e3088. doi: 10.1002/dmrr.3088. Epub 2018 Nov 20.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
María Lía Nattero Chávez principal investigator
Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Type 1 Diabetes Mellitus and Peripheral Artery Disease, run by Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevalence of PAD in asymptomatic patients with T1DM assessed by ankle-branchial index. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02910271, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2024.