Clinical trial NCT03010956: Changes in Arterial Stiffness and Endothelial Glycocalyx in Patients With Poorly Controlled Diabetes Mellitus Type 1 or Type 2 After Optimization of Antidiabetic Medication.
Official title: Changes in Arterial Stiffness and Endothelial Glycocalyx in Patients With Poorly Controlled Diabetes Mellitus Type 1 or Type 2 After Optimization of Antidiabetic Medication.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetes Mellitus
Keywords: Arterial stiffness
Endothelial glycocalyx
Coronary flow reserve
Lead sponsor: University of Athens
Sponsor class: OTHER
First posted: 2017-01-05
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CROSSOVER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population will consist of 30 patients with uncontrolled type 1 diabetes and 30 patients with uncontrolled type 2 diabetes.

Brief summary: Arterial stiffness is associated with increased risk for cardiovascular disease. Moreover, the integrity of endothelial glycocalyx plays a vital role in vascular permeability, inflammation and elasticity. The purpose of this study is to investigate changes in arterial stiffness and endothelial glycocalyx thickness in patients with poorly controlled diabetes mellitus type 1 or type 2 after glycemic control by optimal medication.

Detailed description: The investigators will study two groups matched for age and sex: 30 patients with uncontrolled type 1 diabetes and 30 patients with uncontrolled type 2 diabetes. Individuals should not be treated with statins, beta-blockers, ACE inhibitors, sartans, hormonal preparations, drugs that interfere with the function of platelets and hemostasis. Furthermore, they should not have heart failure, nephropathy and retinopathy. 10 people will remain uncontrolled after the expiration of 3 months after the modification of antidiabetic medication used as a control group .

At 0, 3, 6 and 12 months the investigators will measure:

1. Carotid-femoral pulse wave velocity (PWV, m/sec) and augmentation index (AI%) by the method of arteriography (Arteriograph, TensioMed) and Complior (SP ALAM).
2. Perfused boundary region (PBR, micrometers) of the sublingual arterial microvessels (ranged from 5-25 micrometers) using Sideview Darkfield imaging (Microscan, Glycocheck). Increased PBR is considered an accurate non invasive index of reduced endothelial glucocalyx thickness.
3. Flow mediated dilatation (FMD) of the brachial artery.
4. Determination of following parameters in blood: glucose, insulin, free fatty acids, triglycerides, glycerol, C-reactive protein (CRP), transforming growth factor-b (TGF-b), Lipoprotein-Associated Phospholipase A2 (LP-LPA2), tumor necrosis factor-a (TNF-a), IL6 and IL10 (interleukins), propeptide of type I procollagen (PIP), propeptide of procollagen type III (PIIINP), matrix metallopeptidases 9 and 2 (MMP), macrophage-colony stimulating factor (MCSF), growth differentiation factor-15 (GDF-15), N-terminal pro b-type natriuretic peptide (NT-proBNP) and galectin-3.

Eligibility criteria: Inclusion Criteria:

* Patients with uncontrolled diabetes mellitus

Exclusion Criteria:

* valvular heart disease
* congestive heart failure
* peripheral vascular disease
* liver or kidney failure
* history of alcohol or drug abuse
* treatment with statins, beta- blockers, ACE inhibitors or sartans

Primary outcomes:
measure: Differences in pulse wave velocity at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication.
timeFrame: Baseline, 3 months, 6 months, and 12 months.
measure: Differences in augmentation index at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication.
timeFrame: Baseline, 3 months, 6 months, and 12 months.
measure: Differences in endothelial glycocalyx at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication.
timeFrame: Baseline, 3 months, 6 months, and 12 months.
measure: Differences in flow mediated dilation (FMD) at baseline and 3, 6 and 12 months after the modification of the antidiabetic medication.
timeFrame: Baseline, 3 months, 6 months, and 12 months.
Secondary outcomes:
measure: Endothelial glycocalyx and pulse wave velocity.
timeFrame: Baseline, 3 months, 6 months, and 12 months.
measure: Endothelial glycocalyx and coronary flow reserve.
timeFrame: Baseline, 3 months, 6 months, and 12 months.
Other outcomes:
Locations:
city: Athens
country: Greece
facility: ''Attikon'' University General Hospital
state: Attiki
Study officials:
affiliation: 2nd Cardiology Department, University of Athens, Greece
name: Ignatios Ikonomidis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 2nd Cardiology Department, University of Athens, Greece
name: George Pavlidis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 2nd Department of Internal Medicine, University of Athens, Greece
name: Vaia Lambadiari, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 2nd Department of Internal Medicine, University of Athens, Greece
name: Fotini Kousathana, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 2nd Cardiology Department, University of Athens, Greece
name: Constantinos Tymbas, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 2nd Department of Internal Medicine, University of Athens, Greece
name: George Dimitriadis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 2nd Cardiology Department, University of Athens, Greece
name: John Lekakis, MD
role: PRINCIPAL_INVESTIGATOR
References: