Clinical trial NCT01898572: Carotid Atherosclerosis In Newly Diagnosed Type 2 Individuals
Official title: Carotid Intimae-media Thickness (CIMT) and Carotid Plaque (CP) Presence as Risk Markers of Cardiovascular Disease at the Time of Type 2 Diabetes Diagnosis
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Type II Diabetes Mellitus Without Mention of Complication
Keywords: Newly Diagnosed Type II Diabetes Mellitus
Carotid Intimae-media Thickness
Carotid Plaque
Cardiovascular Disease
Lead sponsor: Hospital Clinic of Barcelona
Sponsor class: OTHER
Collaborators: name: Consorci d'Atenció Primària de Salut de l'Eixample
First posted: 2013-07-12
Enrollment: 200
Sex: ALL
Minimum age (years): 40
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Primary care area: 3 Primary care centers in the city center of Barcelona (Spain)

Brief summary: It has been hypothesized, based on recent trials, that only early intervention can reduce cardiovascular morbidity and mortality in individuals with type 2 diabetes (T2DM). This finding may imply that atherosclerosis at diabetes diagnosed, is either negligible, or at early, or non-advanced, still modifiable disease stage. However, sparse information is available regarding atherosclerosis prevalence and its characteristics at diabetes presentation. Furthermore, although cardiovascular disease (CVD) prevention is the major goal of treatment in T2DM, risk assessment tools, mostly based on traditional CV risk factors, lack of adequate specificity to identify individuals at higher risk. Therefore, non-invasive tests, such as carotid ultrasound, have been recommended to better define CV risk in several groups of individuals, including those with intermediate risk or with T2DM.

This clinical study aims to improve the investigators knowledge on cardiovascular disease (CVD) in subjects with newly diagnosed T2DM (NEWDM). The investigators hypothesis is that carotid ultrasound (carotid intimae media thickness \[CIMT\] and carotid plaque \[CP\]) will show a worse subclinical/preclinical CVD stage in NEWDM compared with non-diabetic (CONTROL) individuals. Moreover, carotid ultrasound will also identify T2DM individuals at a higher risk in whom intervention should be more intensive.

Because individuals with T2DM have a higher prevalence of several CV risk factors, NEWDM will be matched with CONTROL individuals, not only for age and sex (the main determinants of atherosclerosis), but also for known, treated hypertension and dyslipidemia, and smoking habit.

The investigators will study NEWDM and CONTROL individuals without clinical CVD. This is a cross-sectional and longitudinal (18 months of follow-up) case-control study. The main study variables will be carotid ultrasound derived variables. The main aims of the study are: 1) to investigate CIMT and CP prevalence differences between NEWDM and CONTROL subjects; 2) to characterize the subset of NEWDM subjects with a higher CIMT (≥ mean+1SD o ≥ P75th) or CP presence; and 3) to early characterize individuals in whom subclinical CVD worsens (CIMT progression ≥ mean + 1SD o ≥ P75th) even after standard (according to clinical guidelines) diabetes treatment.

Detailed description: Hypothesis:

In a Mediterranean population, the investigators hypothesized that the CIMT and the presence of carotid plaque (CP):

1. Are higher in patients with newly diagnosed T2DM than in a control population before and after adjusting for cardiovascular risk factors,
2. Can identify subjects with T2DM with increased cardiovascular risk at the beginning of the disease, and,
3. Can identify subjects in whom subclinical cardiovascular disease progresses despite treatment of T2DM according to clinical practice.

Aims:

Primary objectives:

1. To investigate differences in CIMT and the presence of CP in subjects with NEWDM and a control population. Cross-sectional study.
2. To identify and characterize the subset of NEWDM subjects presenting an increased CIMT (greater than the mean + 1SD or ≥ P75th) or carotid plaque presence. Cross-sectional study
3. To early characterize individuals in whom subclinical CVD worsens (CIMT progression ≥ mean + 1SD o ≥ P75th) even after multifactorial treatment of diabetes according to guidelines. Longitudinal study design with repeated measures.

Secondary objectives:

1. To study the main determinants of CIMT and the CP presence in NEWDM subjects and a control population. In addition to the cardiovascular risk factors will be studied:

   1. association with Mediterranean diet biomarkers (serum and urine) and diet adherence (semiquantitative food frequency questionnaire)
   2. genetic determinants of CVD
2. To investigate the main determinants of progression of CIMT in subjects treated according to clinical practice guidelines
3. To investigate the association of baseline CIMT, its progression, and the presence of CP with clinical scores used to estimate cardiovascular risk. These scores are: REGICOR (Registre Gironí del Cor: the Gerona Heart Register), a calibrated Framingham Score for a Mediterranean population, low risk SCORE (Systematic Coronary Risk Evaluation), and the UKPDS (United Kingdom Prospective Diabetes Study) score (specific for T2DM).
4. To identify carotid plaque biomarkers by a metabolomic approach

Eligibility criteria: Inclusion Criteria:

* Adult men and women older than 40 years and less than 75 years.
* Newly Diagnosed T2DM (NEWDM). NEWDM is a subject without previous history of diabetes who has laboratory evidence consistent with diabetes (American Diabetes Association) within the last year.

Exclusion criteria:

* Previous cardiovascular events such as, but not limited to, myocardial infarction, acute coronary syndrome or chronic stroke, peripheral arterial disease, or revascularization surgery in any territory.
* Congestive heart failure (class III-IV).
* Cancer of any kind (except basal cell or for cervical carcinoma insitu) unless disease free is documented in the past five years.
* Anemia or known coagulopathy.
* Serum creatinine greater than 1.5 mg / dl or MDRD (Modification of Diet in Renal Disease) equation \<50.
* Any organ transplant (except cornea)
* Known HIV-positive, active tuberculosis, malaria, chronic viral hepatitis B or C, cirrhosis of any aetiology.
* Pregnant or gestational idea in the next 2-3 years to inclusion.
* History of alcohol dependence (or abusive consumption) or other drugs in the past five years.
* Psychiatric illness that would entail adherence problems.
* Participation in a clinical trial protocol or investigational drugs.
* Debilitating chronic illness or short life expectancy to prevent adherence or therapeutic intensification is not the goal of managing your diabetes.
* ECG signs of ischemic heart disease.
* Diabetes type 1 or anti-GAD antibody positive.

Control population will be excluded based on the same criteria.

Primary outcomes:
measure: Carotid Plaque presence(CP)
timeFrame: Baseline
measure: Carotid Intima Media Thickness (CIMT)
timeFrame: Baseline
Secondary outcomes:
measure: Changes in plaque height
timeFrame: Baseline to 18 months
measure: Changes in CIMT at different territories
timeFrame: Baseline to 18 months
measure: Changes in lifestyle
timeFrame: Baseline to 18 months
measure: CIMT
timeFrame: Baseline
Other outcomes:
measure: Changes in fat intake
timeFrame: Baseline to 18 months
measure: Diet intake
timeFrame: Baseline
Locations:
city: Barcelona
country: Spain
facility: Hospital Clinic of Barcelona
state: Cataluña
Study officials:
affiliation: Hospital Clinic Barcelona (Spain)
name: Emilio Ortega, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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