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NCT Number: NCT06519942

Muscle and Bone in Patients with Diabetes Mellitus and Neuropathy

The goal of this observational study is to evaluate muscle fiber type composition in people with type 2 diabetes mellitus (T2DM) with a common complication of T2DM: diabetic peripheral neuropathy (DNP), specifically diabetic sensorimotor polyneuropathy. Researchers will also look into factors related to DNP: inflammation, the use of energy in the cell, nerve function and the tiny blood vessels in the muscle.

The main question it aims to answer is: Are there differences in muscle fiber type composition between persons with T2DM with and without DNP, in comparison to sex and age-matched healthy peers?

Participants will partake in the following tests:

* electromyoneurography (EMNG): evaluation of nerve function, damage and repair; for diagnosis of DNP or other diseases of the nerves * blood analysis: researchers will measure insulin, blood sugar, lipid profile, inflammation * muscle biopsy in the calf (m. gastrocnemius): a doctor will take a small sample of muscle to evaluate the muscle shape and structure * mechanography: patients will perform functional tests (e.g. standing up from a chair), researchers will evaluate maximal power and maximal force of the muscles by jumping tests * questionnaires: on food intake, physical activity, smoking history, alcohol use, medical history * measurement of height, weight, and the comparison of the hip and waist circumference * peripheral Quantitative Computed Tomography (pQCT): scan of the calf for muscle density and bone density * electrocardiography (ECG): evaluation of electrical signals of the heart

Researchers will compare (1) patients with T2DM with DNP, (2) patients with T2DM without DNP, and (3) healthy persons to see if there are differences in muscle fiber type composition

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Key information

Conditions

Diabetes Mellitus, Type 2 Atrophy Diabetes Mellitus Diabetic Peripheral Neuropathy Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Muscular Atrophy Nervous System Diseases Neurologic Manifestations Neuromuscular Manifestations Nutritional and Metabolic Diseases Pathological Conditions, Anatomical Pathological Conditions, Signs and Symptoms Sarcopenia Signs and Symptoms

Age range

40 year–70 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Ghent University Hospital

Ghent, 9000, Belgium

Location status: Recruiting

Location contact

Cato Van De Looverbosch

CONTACT

[email protected]

0032479922969

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

All participants:

  • Between 40-70 years of age
  • BMI between 18,5 - 35 kg/m2

Persons with T2DM:

  • More than 10-year clinical diagnosis of T2DM

Exclusion criteria

All participants:

  • Possible other causes of nerve impairment (vitamin B12 deficiency, excessive alcohol consumption, chemotherapy)
  • Immobilisation (1) > 3 months in past history or (2) > 4 weeks in past 6 months
  • Chronic conditions affecting the vital organs (New York Heart Association (NYHA) 3/4, Global Initiative for Obstructive Lung Disease (GOLD) 3/4, cystic fibrosis)
  • Hypogonadism
  • Inflammatory joint or intestinal diseases
  • Chronic muscle diseases
  • Active malignancy
  • Malnutrition disease, eating disorder or bariatric surgery
  • Medication use (anticoagulants, glucocorticoids, anti-androgen or anti-estrogen treatment) persons with T2DM:
  • Insufficient control of diabetes (HbA1c >9%)

Healthy controls:

  • Fasting glucose > 100 mg/dl
  • HbA1c > 5.7 %

Treatment and study plan

Blood sampling

Diagnostic Test

Fasting blood samples will be obtained.

Electromyoneurography (EMNG)

Diagnostic Test

Nerve conduction of sensory and motor nerves of the upper and lower limb will be performed, including F- and H-waves. Needle EMNG of the m. tibialis anterior, m. gastrocnemius (medial head), m. tensor fascia lata and m. gluteus maximus) will be performed.

Muscle biopsy

Procedure

Muscle biopsy of the m. gastrocnemius will be performed under local anesthesia using the modified Bergström technique.

Quantitative peripheral computed tomography (qPCT)

Radiation

A qPCT scan of the calf will be performed.

Mechanography

Device

Single two leg jump, multiple one leg hopping, chair rise and sit to stand tests will be performed.

Electrocardiography (ECG)

Diagnostic Test

A 15-minute resting ECG will be performed.

questionnaires

Other

Questionnaires will be performed to collect information on medical background (drug use, comorbidities, symptoms of peripheral neuropathy, ...) and lifestyle factors (ethyl consumption, food intake, physical activity, smoking).

Anthropometry

Other

Length and hip:waist ratio will be measured. Furthermore, body weight and composition will be determined by bio-impedance measurement. Systolic and diastolic blood pressure (mean of 3 times) will be evaluated.

Primary outcomes

  1. Differences in muscle fiber type composition in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls.

    Time frame: At enrollment

    Differences in muscle fiber type distribution, percentage and cross-sectional area will be evaluated through myosin heavy chain (MHC) immunostaining of the muscle specimen.

Secondary outcomes

  1. Differences in nerve conduction velocity in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls

    Time frame: At enrollment

    Nerve conduction velocity will be examined through EMNG examination to examine neuromotor function

  2. Differences in capillarization in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls.

    Time frame: At enrollment

    Capillarization will be examined through histological examination of the muscle specimen using Ulex europaeus I (UEA-I) staining.

  3. Differences in electron microscopic properties assessing mitochondrial function in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls

    Time frame: At enrollment

    Mitochondrial function will be examined through electron microscopy of the muscle specimen.

  4. Differences in maximal force in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls.

    Time frame: At enrollment

    Maximal force will be evaluated using mechanography through multiple one leg hopping.

  5. Differences in maximal power in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls.

    Time frame: At enrollment

    Maximal power will be evaluated using mechanography through the single two leg jump.

  6. Differences in functional muscle strength in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls.

    Time frame: At enrollment

    Functional strength will be examined using mechanography through the chair rising test and heel rise test.

  7. Differences in physical activity levels in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls.

    Time frame: At enrollment

    Differences in the lifestyle factor physical activity will be examined through the International Physical Activity Questionnaire (IPAQ) - Long Form).

  8. Differences in food intake in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls.

    Time frame: At enrollment

    Differences in the lifestyle factor food intake will be examined through a food frequency questionnaire.

  9. Differences in lifestyle factors in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls.

    Time frame: At enrollment

    Differences in lifestyle factors smoking and ethyl consumption will be examined through non-official questionnaires.

  10. Differences in muscle density in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls.

    Time frame: At enrollment

    Differences in muscle density will be evaluated through pQCT of the calf.

  11. Differences in bone density in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls.

    Time frame: At enrollment

    Differences in bone density will be evaluated through pQCT of the calf.

Other outcomes

  1. Differences in heart rate variability in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls.

    Time frame: At enrollment

    Heart rate variability will be examined through a 15-minute resting ECG.

  2. Differences in interleukin 6 (IL-6) concentration in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls.

    Time frame: At enrollment

    Differences in inflammation will be evaluated through blood analysis of IL-6.

  3. Differences in tumor necrosis factor alpha (TNFα) concentration in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls.

    Time frame: At enrollment

    Differences in inflammation will be evaluated through blood analysis of TNFα.

  4. Differences in C-reactive protein (CRP) concentration in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls.

    Time frame: At enrollment

    Differences in inflammation will be evaluated through blood analysis of CRP.

  5. Differences in mononuclear cell numbers in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls.

    Time frame: At enrollment

    Differences in inflammation will be evaluated through flow cytometry to assess mononuclear cell numbers.

  6. Differences in protein concentrations for AMPK and PGC-1α in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls

    Time frame: At enrollment

    Differences in protein concentrations for 5' adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) will be examined using western blotting (on the muscle sample)

  7. Differences in citrate synthase activity in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls

    Time frame: At enrollment

    Citrate synthase activity will be examined using an activity assay (on the muscle sample).

  8. Differences in succinate dehydrogenase B (SDHB) expression in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls

    Time frame: At enrollment

    SDHB expression will be examined through immunohistochemical staining for SDHB of the muscle specimen.

  9. Differences in vascular endothelial growth factor (VEGF) concentrations in persons with type 2 diabetes with diabetic peripheral neuropathy compared to persons with type 2 diabetes without diabetic neuropathy and healthy controls.

    Time frame: At enrollment

    Vascular endothelial growth factor concentrations will be examined through blood analysis.

Study contacts

Contact information is provided by the study sponsor or research team.

Cato Van De Looverbosch

CONTACT

[email protected]

0479922969

Sponsors and collaborators

Lead sponsor

University Hospital, Ghent

Other

Collaborators

  • University Ghent

Registry information

Acronym: SVT-DNP

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Jul 25, 2024
Registry last updated
Sep 19, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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