Muscle and Bone in Patients With Diabetes Mellitus and Neuropathy (SVT-DNP)

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

Study Overview

• Status: Recruiting
• Conditions: Diabetes Mellitus, Type 2; Sarcopenia; Diabetic Peripheral Neuropathy
• Intervention / Treatment: 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

• Study Type: Observational
• Enrollment (Estimated): 145

Contacts and Locations

• Study Contact: Name: Cato Van De Looverbosch; Phone Number: 0479922969; Email: cato.vandelooverbosch@ugent.be

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • Recruiting
    • Ghent University Hospital
    • Contact: Cato Van De Looverbosch; Phone Number: 0032479922969; Email: cato.vandelooverbosch@ugent.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

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

Description

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 %

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HC; healthy controls	Diagnostic test: Blood sampling; Fasting blood samples will be obtained.; Diagnostic test: Electromyoneurography (EMNG); 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.; Procedure: Muscle biopsy; Muscle biopsy of the m. gastrocnemius will be performed under local anesthesia using the modified Bergström technique.; Radiation: Quantitative peripheral computed tomography (qPCT); A qPCT scan of the calf will be performed.; Device: Mechanography; Single two leg jump, multiple one leg hopping, chair rise and sit to stand tests will be performed.; Diagnostic test: Electrocardiography (ECG); A 15-minute resting ECG will be performed.; Other: Questionnaires; 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).; Other: Anthropometry; 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.
T2DM DNP+; type 2 diabetes with diabetic neuropathy	Diagnostic test: Blood sampling; Fasting blood samples will be obtained.; Diagnostic test: Electromyoneurography (EMNG); 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.; Procedure: Muscle biopsy; Muscle biopsy of the m. gastrocnemius will be performed under local anesthesia using the modified Bergström technique.; Radiation: Quantitative peripheral computed tomography (qPCT); A qPCT scan of the calf will be performed.; Device: Mechanography; Single two leg jump, multiple one leg hopping, chair rise and sit to stand tests will be performed.; Diagnostic test: Electrocardiography (ECG); A 15-minute resting ECG will be performed.; Other: Questionnaires; 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).; Other: Anthropometry; 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.
T2DM DNP-; type 2 diabetes without diabetic neuropathy	Diagnostic test: Blood sampling; Fasting blood samples will be obtained.; Diagnostic test: Electromyoneurography (EMNG); 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.; Procedure: Muscle biopsy; Muscle biopsy of the m. gastrocnemius will be performed under local anesthesia using the modified Bergström technique.; Radiation: Quantitative peripheral computed tomography (qPCT); A qPCT scan of the calf will be performed.; Device: Mechanography; Single two leg jump, multiple one leg hopping, chair rise and sit to stand tests will be performed.; Diagnostic test: Electrocardiography (ECG); A 15-minute resting ECG will be performed.; Other: Questionnaires; 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).; Other: Anthropometry; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Nerve conduction velocity will be examined through EMNG examination to examine neuromotor function	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.	Capillarization will be examined through histological examination of the muscle specimen using Ulex europaeus I (UEA-I) staining.	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	Mitochondrial function will be examined through electron microscopy of the muscle specimen.	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.	Maximal force will be evaluated using mechanography through multiple one leg hopping.	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.	Maximal power will be evaluated using mechanography through the single two leg jump.	At enrollment
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.	Functional strength will be examined using mechanography through the chair rising test and heel rise test.	At enrollment
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.	Differences in the lifestyle factor physical activity will be examined through the International Physical Activity Questionnaire (IPAQ) - Long Form).	At enrollment
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.	Differences in the lifestyle factor food intake will be examined through a food frequency questionnaire.	At enrollment
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.	Differences in lifestyle factors smoking and ethyl consumption will be examined through non-official questionnaires.	At enrollment
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.	Differences in muscle density will be evaluated through pQCT of the calf.	At enrollment
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.	Differences in bone density will be evaluated through pQCT of the calf.	At enrollment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Heart rate variability will be examined through a 15-minute resting ECG.	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.	Differences in inflammation will be evaluated through blood analysis of IL-6.	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.	Differences in inflammation will be evaluated through blood analysis of TNFα.	At enrollment
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.	Differences in inflammation will be evaluated through blood analysis of CRP.	At enrollment
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.	Differences in inflammation will be evaluated through flow cytometry to assess mononuclear cell numbers.	At enrollment
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	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)	At enrollment
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	Citrate synthase activity will be examined using an activity assay (on the muscle sample).	At enrollment
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	SDHB expression will be examined through immunohistochemical staining for SDHB of the muscle specimen.	At enrollment
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.	Vascular endothelial growth factor concentrations will be examined through blood analysis.	At enrollment

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Collaborators: University Ghent
• Investigators: Principal Investigator: Bruno Lapauw, University Hospital, Ghent

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2023
• Primary Completion (Estimated): November 1, 2025
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: April 10, 2024
• First Submitted That Met QC Criteria: July 19, 2024
• First Posted (Actual): July 25, 2024

Study Record Updates

• Last Update Posted (Actual): July 25, 2024
• Last Update Submitted That Met QC Criteria: July 19, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Nervous System Diseases; Neurologic Manifestations; Endocrine System Diseases; Neuromuscular Diseases; Neuromuscular Manifestations; Pathological Conditions, Anatomical; Muscular Atrophy; Atrophy; Diabetes Mellitus; Diabetes Mellitus, Type 2; Peripheral Nervous System Diseases; Sarcopenia
• Other Study ID Numbers: ONZ-2023-0120; BOF.24Y.2023.0030.01 (Other Grant/Funding Number: Special Research Fund (Ghent University))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: After publication, anonymous individual participant data can be made available to other researchers upon request.
• IPD Sharing Time Frame: After publication
• IPD Sharing Access Criteria: Upon request to corresponding author
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

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