Mitochondrial DNA Copy Number and Leukocyte Telomere Length as Biomarkers in Type 2 Diabetic Patients
Type 2 diabetes mellitus, which is characterised by a combination of insulin resistance and insufficient insulin secretion is a major contributor to the burden of morbidity and mortality worldwide.
the mitochondrial genome contains multiple copies per cell. Because of its close proximity with higher levels of reactive oxidative species, mitochondrial DNA is prone to oxidative stress; which may lead to mitochondrial dysfunction, characterized by lowered oxidative capacity and reduction in energy production. Mitochondrial dysfunction is associated with aging process and can affect cellular functions and thereby results in a variety of human diseases such as cancer, neurodegenerative diseases, cardiovascular diseases, diabetes and metabolic syndrome .
Telomere length reflects the cumulative damage from those exposure factors and can be used as a potential indicator of biological aging. Shorter telomere length has been linked to the development of a variety of age-related diseases, such as cancer, cardiovascular disease and diabetes
Study Overview
Detailed Description
Type 2 diabetes mellitus, which is characterised by a combination of insulin resistance and insufficient insulin secretion is a major contributor to the burden of morbidity and mortality worldwide .The number of adults with type 2 diabetes mellitus is increasing worldwide and if the trend continues the number will rise to 693 million by 2045. Multiple risk factors have been associated with an increased risk of developing type 2 diabetes, including obesity, adverse lifestyle and genetic factors .
Mitochondria generate most of the cell's need for chemical energy in the form of ATP, and mitochondrial dysfunction has been implicated in various aspects of the development and complications of type 2 diabetes including insulin resistance, obesity and beta cell dysfunction. Mitochondrial DNA is a circular and double-stranded DNA molecule comprising 37 genes, of which 13 genes are involved in the electron transport chains and generation of ATP to provide energy for cells, while the remaining genes encode proteins involved in the assembly of amino acids into functional proteins . Unlike the nuclear genome, which normally has only two copies per cell, the mitochondrial genome contains multiple copies per cell. Because of its close proximity with higher levels of reactive oxidative species (ROS), mitochondrial DNA (mtDNA) is prone to oxidative stress; which may lead to mitochondrial dysfunction, characterized by lowered oxidative capacity and reduction in energy production. Mitochondrial dysfunction is associated with aging process and can affect cellular functions and thereby results in a variety of human diseases such as cancer, neurodegenerative diseases, cardiovascular diseases, diabetes and metabolic syndrome.On the other hand, improvement in mitochondrial function, even after critical illness, has been shown to be associated with better survival. Mitochondrial copy number (mtDNA-CN) is a surrogate marker of mitochondrial function . Higher mtDNA-CN is a biomarker of better mitochondrial function and vice versa. A lower mtDNA-CN has been observed in skeletal muscle and adipose tissue of individuals with obesity or type 2 diabetes .similarly, a lower mtDNA-CN in beta cells has also been associated with decreased beta cell function .
In recent years, the association between diabetes mellitus and accelerated biological aging, evaluated by the emerging biomarker (telomere length), has gained much attention.
Telomeres are DNA-protein complexes that cap the chromosomal DNA ends, which preserve genomic integrity and stability. Telomeres shorten during somatic cell division because DNA polymerase is unable to fully replicate the 3' end of DNA. This process can be reversed by an enzyme (telomerase) that is only active in certain replicating tissues, such as male germ cells and activated lymphocytes, stem cells and cancer cells . In normal human cells, telomerase levels are insufficient to maintain telomere length during cell division. When telomeres reach a critically short length, cell growth becomes limited and undergoes cellular senescence or apoptosis. Oxidative stress and chronic inflammation accelerate telomere attribution, resulting in replicative senescence and organ degeneration.Telomere length reflects the cumulative damage from those exposure factors and can be used as a potential indicator of biological aging. Shorter telomere length has been linked to the development of a variety of age-related diseases, such as cancer, cardiovascular disease and diabetes
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Contact
- Name: Hend Muhammed Naguib
- Phone Number: 01005287752
- Email: hendmnaguib@gmail.com
Study Locations
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Sohag, Egypt, 82515
- Recruiting
- Sohag Univversity
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Contact:
- Hend Muhammed Naguib, assistant lecturer
- Phone Number: 01005287752
- Email: hendmnaguib@gmail.com
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Contact:
- Marwa Shabaan Hashem, lecturer
- Phone Number: 01011047016
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- This study will include patients who have type 2 diabetes mellitus.
Exclusion Criteria:
• Patients who have any other chronic illness.
- Patients who have cancer.
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Cross-Sectional
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
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Group II
apparently healthy controls with no chronic illness of matched age and sex
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Genotyping by Real Time PCR
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Group I
patients with type 2 diabetes mellitus
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Genotyping by Real Time PCR
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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evaluate the potential of peripheral blood mtDNA-CN as biomarker in type 2 diabetic patients
Time Frame: within 3 days after collection of samples
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evaluate the potential of peripheral blood mtDNA-CN as biomarker in type 2 diabeticients pat patients by Real Time PCR
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within 3 days after collection of samples
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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evaluate the potential of leukocyte telomere length as biomarker in type 2 diabetic patients
Time Frame: within 3 days after collection of samples
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evaluate the potential of leukocyte telomere length as biomarker in type 2 diabetic patients
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within 3 days after collection of samples
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Hend Muhammed Naguib, Sohag University
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- Soh-Med-22-12-19
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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