Clinical trial NCT02244736: Vascular Markers During OGTT in Diabetics and First-degree Relatives
Official title: Changes of the Endothelial Glycocalyx, the Elastic Properties of the Arteries and the Coronary Flow Reserve (CFR) During Oral Glucose Tolerance Test in Patients With New Onset Diabetes Mellitus and First-degree Relatives
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: 2014-09-19
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: 90 subjects, 30 first degree relatives of diabetics withnormal OGTT (relatives), 30 withnormal OGTT and no family history of diabetes (normals), and 30 with abnormal OGTT (diabetics).

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 association between damage of endothelial glycocalyx, impaired arterial elastic properties, and CFR in diabetics and first degree relatives has not been explored. The purpose of this study is to explore the association between damage of endothelial glycocalyx, impaired arterial elastic properties, and CFR in diabetics and first-degree relatives before and after during oral glucose tolerance test (OGTT).

Detailed description: The investigators plan to examine 90 subjects without known diabetes a standard 75-gr oral glucose tolerance test (OGTT) will be performed. \[30 first degree relatives of diabetics with normal OGTT (relatives), 30 with normal OGTT and no family history of diabetes (normals), and 30 with abnormal OGTT (diabetics) matched for age and sex\].

Plasma glucose and serum insulin levels will be measured in venous blood collected at 0, 30, 60, 90 and 120min after glucose loading. At the same time intervals, the investigators will measure:

1. the carotid to femoral pulse wave velocity (PWVc) using the Complior apparatus
2. the aortic pulse wave velocity (PWVa), central systolic blood pressure (cSBP) and augmentation index (AI) using an oscillometric method (Arteriograph,TensioMed) as markers of arterial stiffness and wave reflections
3. the coronary flow reserve (CFR) at baseline and after adenosine infusion (140 μg × kg-1 × min-1) for 3 minutes to assess coronary vasomotor function
4. the perfusion 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 glycocalyx thickness.

In addition, the investigators will measure free fatty acids, triglycerides, glycerol, C reactive protein (CRP), transforming growth factor-b (TGF-b), Lipoprotein-Associated Phospholipase A2, (LP-LPA2), tumor necrosis factor (TNF-a), interleukin 6 (IL6) and interleukin 10 (IL10) propeptide of type I procollagen, (PIP), propeptide of procollagen type III (PIIINP), matrix metallopeptidases 9 and 2 (MMP 9 and 2), macrophage-colony stimulating factor ( MCSF).

The investigators will measure insulin resistance a) after fasting, using homeostatic model assessment (HOMA) and hepatic insulin sensitivity (HIS) b) during oral glucose tolerance test (OGTT) using Matsuda index and insulin sensitivity index (ISI). The investigators will categorize patients in those with normal (\<140 mg/dl at 120 min) and those with abnormal OGTT (\>200mg/dl at 120min).

Eligibility criteria: Inclusion Criteria:

* subjects without known diabetes
* first degree relatives of diabetics

Exclusion Criteria:

* coronary or valvular heart disease
* congestive heart failure
* peripheral vascular disease
* liver or kidney failure
* history of alcohol or drug abuse

Primary outcomes:
measure: Differences of vascular function at baseline and during OGTT among the 3 groups.
timeFrame: Baseline, 30 min, 60 min, 90 min, and 120 min during OGTT.
measure: Differences of endothelial function at baseline and during OGTT among the 3 groups.
timeFrame: Baseline, 30 min, 60 min, 90 min, and 120 min during OGTT.
Secondary outcomes:
measure: Insulin resistance and arterial stiffness
timeFrame: Baseline, 30 min, 60 min, 90 min, and 120 min during OGTT.
measure: Insulin resistance and endothelial function
timeFrame: Baseline, 30 min, 60 min, 90 min,120 min of OGTT
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 Cardiology Department, University of Athens, Greece
name: Charalambos Koukoulis, 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: Maria Varoudi, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 2nd Cardiology Department, University of Athens, Greece
name: Vlasios Tritakis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: 2nd Cardiology Department, University of Athens, Greece
name: Helen Triantafyllidi, 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:
citation: Ikonomidis I, Lambadiari V, Pavlidis G, Koukoulis C, Kousathana F, Varoudi M, Spanoudi F, Maratou E, Parissis J, Triantafyllidi H, Paraskevaidis I, Dimitriadis G, Lekakis J. Insulin resistance and acute glucose changes determine arterial elastic properties and coronary flow reserve in dysglycaemic and first-degree relatives of diabetic patients. Atherosclerosis. 2015 Aug;241(2):455-62. doi: 10.1016/j.atherosclerosis.2015.06.006. Epub 2015 Jun 9.