Muscle and Bone in Patients with Diabetes Mellitus and Neuropathy

NCT06519942 | Recruiting DMC

• 2 other identifiers: ONZ-2023-0120BOF.24Y.2023.0030.01
• Study Type: observational
• Target: 145
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Diabetes Mellitus, Type 2; Diabetic Peripheral Neuropathy; Sarcopenia

Outcome Measures

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.

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

  At enrollment

Secondary Outcomes (11)

• 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

  At enrollment

• 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.

  At enrollment

• 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

  At enrollment

• 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.

  At enrollment

• 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.

  At enrollment

Other Outcomes (9)

• 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.

  At enrollment

• 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.

  At enrollment

• 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.

  At enrollment

Study Arms (3)

T2DM DNP+

type 2 diabetes with diabetic neuropathy

Diagnostic Test: Blood sampling; Diagnostic Test: Electromyoneurography (EMNG); Procedure: Muscle biopsy; Radiation: Quantitative peripheral computed tomography (qPCT); Device: Mechanography; Diagnostic Test: Electrocardiography (ECG); Other: Questionnaires; Other: Anthropometry

T2DM DNP-

type 2 diabetes without diabetic neuropathy

Diagnostic Test: Blood sampling; Diagnostic Test: Electromyoneurography (EMNG); Procedure: Muscle biopsy; Radiation: Quantitative peripheral computed tomography (qPCT); Device: Mechanography; Diagnostic Test: Electrocardiography (ECG); Other: Questionnaires; Other: Anthropometry

HC

healthy controls

Diagnostic Test: Blood sampling; Diagnostic Test: Electromyoneurography (EMNG); Procedure: Muscle biopsy; Radiation: Quantitative peripheral computed tomography (qPCT); Device: Mechanography; Diagnostic Test: Electrocardiography (ECG); Other: Questionnaires; Other: Anthropometry

Interventions

Blood sampling DIAGNOSTIC_TEST

Fasting blood samples will be obtained.

HC; T2DM DNP+; T2DM DNP-

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.

HC; T2DM DNP+; T2DM DNP-

Muscle biopsy PROCEDURE

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

HC; T2DM DNP+; T2DM DNP-

Quantitative peripheral computed tomography (qPCT) RADIATION

A qPCT scan of the calf will be performed.

HC; T2DM DNP+; T2DM DNP-

Mechanography DEVICE

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

HC; T2DM DNP+; T2DM DNP-

Electrocardiography (ECG) DIAGNOSTIC_TEST

A 15-minute resting ECG will be performed.

HC; T2DM DNP+; T2DM DNP-

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).

HC; T2DM DNP+; T2DM DNP-

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.

HC; T2DM DNP+; T2DM DNP-

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Participants will be recruited through the Ghent University Hospital, diabetes educators and podologists.

You may qualify if:

• 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

You may not qualify if:

• 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 %

Sponsors & Collaborators

• University Hospital, Ghent: lead
• University Ghent: collaborator

Study Sites (1)

Ghent University Hospital

Ghent, 9000, Belgium

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

blood sample, muscle biopsy sample

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Sarcopenia

Interventions

Blood Specimen Collection; Electrocardiography; Surveys and Questionnaires; Anthropometry

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Electrodiagnosis; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Physical Examination; Biometry; Epidemiologic Measurements

Study Officials

• Bruno Lapauw

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Cato Van De Looverbosch

CONTACT

0479922969; cato.vandelooverbosch@ugent.be

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2024
• First Posted: July 25, 2024
• Study Start: December 12, 2023
• Primary Completion: November 1, 2025
• Study Completion: November 1, 2025
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: After publication
• Access Criteria: Upon request to corresponding author

Locations

BE (1)