Muscle and Bone in Patients With Diabetes Mellitus and Neuropathy

Recruiting

• Conditions: Diabetic Peripheral Neuropathy; Diabetes Mellitus, Type 2; 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

• Registration Number: NCT06519942
• Lead Sponsor: University Hospital, Ghent

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

Detailed Description

Not available

Study Timeline

• Study Start: 2023-12-12
• Study First Submitted: 2024-04-10
• Status Verified: 2024-07
• Study First Submitted QC: 2024-07-19
• Last Update Submitted: 2024-07-19
• Study First Posted: 2024-07-25
• Last Update Posted: 2024-07-25
• Primary Completion: 2025-11
• Study Completion: 2025-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 145

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
T2DM DNP+	Electromyoneurography (EMNG)	type 2 diabetes with diabetic neuropathy
T2DM DNP+	Quantitative peripheral computed tomography (qPCT)	type 2 diabetes with diabetic neuropathy
T2DM DNP+	Questionnaires	type 2 diabetes with diabetic neuropathy
HC	Blood sampling	healthy controls
T2DM DNP+	Blood sampling	type 2 diabetes with diabetic neuropathy
T2DM DNP+	Muscle biopsy	type 2 diabetes with diabetic neuropathy
T2DM DNP-	Muscle biopsy	type 2 diabetes without diabetic neuropathy
T2DM DNP-	Mechanography	type 2 diabetes without diabetic neuropathy
T2DM DNP-	Electrocardiography (ECG)	type 2 diabetes without diabetic neuropathy
HC	Anthropometry	healthy controls
T2DM DNP+	Mechanography	type 2 diabetes with diabetic neuropathy
T2DM DNP+	Electrocardiography (ECG)	type 2 diabetes with diabetic neuropathy
T2DM DNP-	Blood sampling	type 2 diabetes without diabetic neuropathy
T2DM DNP-	Anthropometry	type 2 diabetes without diabetic neuropathy
HC	Electrocardiography (ECG)	healthy controls
T2DM DNP+	Anthropometry	type 2 diabetes with diabetic neuropathy
T2DM DNP-	Electromyoneurography (EMNG)	type 2 diabetes without diabetic neuropathy
T2DM DNP-	Quantitative peripheral computed tomography (qPCT)	type 2 diabetes without diabetic neuropathy
T2DM DNP-	Questionnaires	type 2 diabetes without diabetic neuropathy
HC	Quantitative peripheral computed tomography (qPCT)	healthy controls
HC	Electromyoneurography (EMNG)	healthy controls
HC	Muscle biopsy	healthy controls
HC	Mechanography	healthy controls
HC	Questionnaires	healthy controls

Primary Outcome Measures

Name	Time	Method
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.	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 Outcome Measures

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

Trial Locations

Locations (1)

Ghent University Hospital; 🇧🇪 Ghent, Belgium