New IR Biomarkers (Myokines) in Colombian People

Identification and Validation of Myonectin, Myostatin and FGF-21 as Insulin Resistance Biomarkers in Colombian People

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Insulin Resistance
• Intervention / Treatment: Other: No apply

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.

• Study Type: Observational
• Enrollment (Actual): 81

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adults of both sexes, aged between 35 and 65 years, without any significant comorbidity

Description

Inclusion Criteria:

• Age between 35-65 years
• Diligence of informed consent
• Absence of acute illness
• Body mass index less or greater than 25 kg/m2, and presence or absence of a previous diagnosis of diabetes according to the criteria previously stated.

Exclusion Criteria:

• Current therapy with insulin
• Type 1 diabetes
• Oral or injectable anticoagulation
• Previous diagnosis of insulinoma, insulinomatosis, glucagonoma, or other neoplastic disorders of the endocrine pancreas.
• Pregnant women
• BMI <18.5 kg / m2

Study Plan

How is the study designed?

Design Details

• Observational Models: Ecologic or Community
• Time Perspectives: Cross-Sectional

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incremental area under the insulin curve (iAUCins)	Area under the insulin curve in a 5-point oral glucose tolerance test, calculated with the trapezoid method, a reliable indicator of whole-body insulin resistance. Expressed in mg*(dL^-1)*(h^-1)	Once in every participant (Cross-sectional). Participants assessed over 6-months
Whole-body glucose disposal	Glucose disposal when steady state is reached in a hyperinsulinemic-euglycemic clamp, the gold-standard measure of whole-body insulin sensitivity. Expressed in mg*(Kg^-1)*(min^-1)	Once in every participant (Cross-sectional). Participants assessed over 6-months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HOMA-IR (Homeostasis Model Assessment - Insulin Resistance)	Product of the fasting glycemia in mmol/L and fasting insulinemia in microunits/mL, a surrogate measure of insulin resistance, especially in the fasting state.	Once in every participant (Cross-sectional). Participants assessed over 6-months

Collaborators and Investigators

• Sponsor: University of Los Andes, Columbia
• Collaborators: The Administrative Department of Science, Technology and Innovation, Colciencias; Universidad Militar Nueva Granada
• Investigators: Principal Investigator: Carlos O Mendivil, MD PhD, University of Los Andes

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2014
• Primary Completion (Actual): October 30, 2016
• Study Completion (Actual): December 16, 2016

Study Registration Dates

• First Submitted: August 4, 2017
• First Submitted That Met QC Criteria: August 8, 2017
• First Posted (Actual): August 9, 2017

Study Record Updates

• Last Update Posted (Actual): August 9, 2017
• Last Update Submitted That Met QC Criteria: August 8, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: biomarker; insulin resistance; clamp; myokine
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperinsulinism; Diabetes Mellitus, Type 2; Insulin Resistance
• Other Study ID Numbers: 120465745008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No