New IR Biomarkers (Myokines) in Colombian People
Condition: Insulin Resistance; Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus, Type 2; Insulin Resistance
Study type: Observational

Summary: 
      Around the world, the prevalence of type 2 diabetes mellitus (T2DM) has been increasing since
      the last two decades, with approximately 347 million patients with diabetes by 2013 according
      to the World Health Organization (WHO). This pronounced increase is due to an increase in the
      prevalence of obesity, reduction in physical activity levels, accelerated urbanization and
      aging of the population. In Colombia, T2DM ranks fifth in the main morbidity and mortality
      causes, including only deaths caused directly and without adding the strong influence that
      T2DM has on cardiovascular disease mortality.

      Insufficient tissue response to normal insulin concentrations, called insulin resistance, is
      one of the central pathophysiological mechanisms in the development of T2DM. However, there
      is currently no simple, practical, safe and reproducible method that allows the diagnosis or
      identification of insulin resistance, nor the follow-up to its evolution. At the moment, the
      gold standard for assessing the degree of insulin sensitivity or resistance is the
      "hyperinsulinemic-euglycemic clamp", a laborious technique, of high cost and high technical
      difficulty, requiring specialized personnel and hospitalization. Non-invasive methods based
      on mathematical regressions, such as the Homeostatic Model Assessment (HOMA-IR), are
      imperfect and widely variable, and have not been validated in the Latin American population,
      less Still Colombian.

      Therefore, the development of new, easily obtainable quantitative tools for the diagnosis of
      insulin resistance is required. This requires not only the identification of new and better
      biomarkers, but also the determination of their diagnostic performance and operational
      characteristics.

      This project will investigate 3 molecular targets (myokines), novel and easy to measure, with
      high probability of being good biomarkers of insulin resistance. The research will include
      validation of its association with insulin resistance measured by the reference method, as
      well as its measurement in apparently healthy individuals. Finally, operator-receiver
      characteristics of each test will be analyzed, in order to propose a cutoff point for the
      diagnosis of insulin resistance.
    

Detailed description: 
      The objectives of the project are: 1) To identify, within a group of 3 potential new
      biomarkers of insulin resistance, those that are significantly associated with the presence
      of this phenomenon in our population, 2) Establish, analyze and apply reference values for
      each one of these three biomarkers in Colombian population. 3) To evaluate the sensitivity,
      specificity, statistical C (operational performance), predictive values and likelihood ratios
      of each of the biomarkers studied for the diagnosis of insulin resistance versus a standard
      gold technique and 4) Different biomarkers evaluated, in order to select the best one (s) for
      clinical use, as well as to propose a cutoff point for detection of insulin resistance for
      each of them.

      Methodology: A cross-sectional, diagnostic test evaluation study will be conducted, including
      apparently healthy Adults of both sexes, with ages between 35 and 65 years, coming from
      Bogotá, without any significant comorbidity.

      As initial evaluation will be carried out measurement of height, weight, percentage of body
      fat, blood pressure, diet questionnaire, physical activity and sociocultural characteristics.
      For patients with prediabetes and T2DM, the time elapsed since the diagnosis will be
      obtained, as well as information about pharmacological or non-pharmacological treatment that
      they are receiving.

      For the serological evaluation, a sample of venous blood should be taken in the fasted state,
      with the aim of measuring the following markers: Fibroblast Growth Factor 21 (FGF21) ,
      Myonectin, and Myostatin. In addition to routine tests such as fasting glycemia, glycosylated
      hemoglobin, fasting insulinemia, lipid profile (total cholesterol, HDL cholesterol,
      triglycerides, LDL-C) and C-reactive protein. Additionally, all subjects will participate in
      an oral glucose tolerance test (OGTT).

      In addition to the gold standard of measurement of insulin resistance
      (hyperinsulinemic-euglycemic clamp), six of the tools currently available for the search of
      insulin resistance, all derived from calculations from the measurements of The HOMA beta-cell
      function (HOMA beta-cell%), insulin sensitivity index (ISI), index 1 / fasting insulin,
      corrected insulin response, insulin / glucose ratio and insulinemia Of fasting.

      For each biomarker, an operator / receiver characteristics curve (ROC curve) will be
      calculated, calculating diagnostic performance and cutoff points with the best combination of
      sensitivity and specificity. A first approximation will be made to baseline values for these
      tests, based on the distribution of the tests in healthy, and one or more insulin resistance
      biomarkers with their recommended cutoff points will be proposed.
    

Intervention name(s): No apply
Intervention type(s): Other
Observational model: Ecologic or Community
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Adults of both sexes, aged between 35 and 65 years, without any significant comorbidity
      
Keywords: biomarker; insulin resistance; myokine; clamp