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Vascular Markers During OGTT in Diabetics and First-degree Relatives

Completed
Conditions
Diabetes Mellitus
Registration Number
NCT02244736
Lead Sponsor
University of Athens
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).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
100
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Differences of endothelial function at baseline and during OGTT among the 3 groups.Baseline, 30 min, 60 min, 90 min, and 120 min during OGTT.

Differences of coronary flow reserve and endothelial glycocalyx thickness at baseline and during OGTT among the 3 groups.

Differences of vascular function at baseline and during OGTT among the 3 groups.Baseline, 30 min, 60 min, 90 min, and 120 min during OGTT.

Differences of pulse wave velocity, augmentation index and central aortic blood pressure at baseline and during OGTT among the 3 groups.

Secondary Outcome Measures
NameTimeMethod
Insulin resistance and endothelial functionBaseline, 30 min, 60 min, 90 min,120 min of OGTT

Association of insulin resistance with changes of coronary flow reserve and endothelial glycocalyx during OGTT

Insulin resistance and arterial stiffnessBaseline, 30 min, 60 min, 90 min, and 120 min during OGTT.

Association of insulin resistance with changes of pulse wave velocity, augmentation index and central aortic blood pressure during OGTT

Trial Locations

Locations (1)

''Attikon'' University General Hospital

🇬🇷

Athens, Attiki, Greece

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