Muscle and Bone in Patients With Diabetes Mellitus and Neuropathy
NCT Number: NCT06519942
Acronym: SVT-DNP
Status: RECRUITING
Study Type: OBSERVATIONAL
Conditions: Diabetes Mellitus, Type 2|Diabetic Peripheral Neuropathy|Sarcopenia
Interventions: 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
Sponsor: University Hospital, Ghent
Collaborators: University Ghent
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 145
Study Design: Observational Model: |Time Perspective: p
Start Date: 2023-12-12
Completion Date: 2025-11
Locations: Ghent University Hospital, Ghent, 9000, Belgium

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

Primary Outcome Measures: 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: 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: 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