Vascular Markers During OGTT in Diabetics and First-degree Relatives
Condition: Diabetes Mellitus
MeSH terms: Diabetes Mellitus
Study type: Observational [Patient Registry]

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).
    

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).
      
Biospecimen description: 
      Plasma in serum for fibrosis and inflammatory markers
    
Keywords: Arterial stiffness; Endothelial glycocalyx; Coronary flow reserve