Vascular Markers During OGTT in Diabetics and First-degree Relatives

National and Kapodistrian University of Athens

Status: Completed

Conditions: Diabetes Mellitus

Study type: Observational

Funder types: Other

Identifiers

NCT02244736

K-DM-ATTIKON

Details and patient eligibility

About

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).

Full 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).

Enrollment: 100 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

100 participants in 3 patient groups

Controls

Description:

Subjects with no family history of diabetes mellitus and normal OGTT

Relatives

Description:

First-degree relatives of patients with diabetes mellitus and normal OGTT

Diabetics

Description:

Subjects with abnormal OGTT