Genetic Physiopathology and Evolution of Type 2 Diabetes
Condition: Pre-Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Prediabetic State
Study type: Observational

Summary: 
      There are few longitudinal studies in the Caucasian population and even less in the Italian
      population in subjects with impaired glucose regulation to allow:

        1. An estimate of the rate of conversion to type 2 diabetes;

        2. To identify subjects at risk; and

        3. To assess the physiopathologic mechanisms responsible for the conversion.

      In order to set up a longitudinal study capable of defining the above parameters it is
      mandatory that the physiological, biochemical, and, genetic markers specific for IGR are
      identified. The goals of the present research proposal are:

        1. To clarify the physiological mechanisms responsible for IGR;

        2. To identify the biochemical and beta-cell auto-immune parameters present in IGR;

        3. Identify genetic markers.

      The subjects who will be identified will add up to other 900 individuals who will be
      recruited as part of a follow-up program sponsored by the Italian Society of Diabetes,
      specifically designed to assess conversion rate to diabetes.
    

Detailed description: 
      The main goal of the present research program is to recruit about 600 new subjects with IGR
      to be added to the 900 subjects which are collected as part of the GENFIEV project which has
      been designed as a 6-yr follow-up study to ascertain the rate of conversion to type 2
      diabetes in the Italian population. In particular the goal of the present research program
      will be to determine in a sample of the Italian population at greater risk for type 2
      diabetes than the general population:

        -  the pathophysiologic mechanisms responsible for the disorders of impaired glucose
           regulation (IGR). In particular we will evaluate insulin action and insulin secretion as
           a function of the degree of glucose tolerance by analyzing these parameters in normal
           subjects as well as in IFG/NGT, NFG/IGT, and IFG/IGT individuals;

        -  the biochemical markers associated with the disorders of impaired glucose regulation
           (IGR). In particular we will evaluate several biochemical parameters (lipid profile,
           coagulative profile, microlbuminuria, free-fatty acids, PAI-1, fibrinogen, creatinine,
           uric acid, HbA1c);

        -  the cardiovascular risk profile associated with the disorders of impaired glucose
           regulation (IGR). In particular, the relevant biochemical parameters will be integrated
           with measurements of arterial blood pressure as well as ECG recording;

        -  the genetic markers associated with the disorders of impaired glucose regulation (IGR).
           In particular subjects will be screened for HHEX, IGF2,BP2 CDKAL1,TCF2L7, CDKN2A/B,WFS1;

        -  the impact of environmental factors on the disorders of impaired glucose regulation
           (IGR).

      Finally, we will endeavour to assess the cellular pathways that may be affected by metabolic
      alterations typically occurring in concomitance with the disorders of impaired glucose
      regulation (IGR).
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Subjects will be recruited from outpatients diabetic units located in different areas of
        Italy.
      
Biospecimen description: 
      Serum and plasma sample, DNA
    
Keywords: prevention of diabetes; susceptibility genes; type 2 diabetes; insulin resistance; beta-cell funtion