Muscular Deficits of Diabetic Myopathy

Obesity Clinical Trial

Official title:

Understanding Muscular Deficits of Diabetic Myopathy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05685927
• Other study ID #: DM2021AS
• Status: Recruiting
• Start date: November 1, 2022
• Est. completion date: December 30, 2025

Study information

• Verified date: December 2023
• Source: University of Aarhus
• Contact: Anders Stouge, MD, PhD-student
• Phone: +4520973735
• Email: andestou[@]rm.dk
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this observational study is to assess if diabetes and obesity are independently related to functional and structural muscle deficits, and how muscular deficits relate to metabolic properties of diabetes and obesity. All studies will include clinical muscle strength and contractile examinations, functional tests, and MR imaging and spectroscopy techniques.

The main questions this project aims to answer are:

1. Is chronic hyperglycemia in type 1 and 2 diabetes associated with functional and structural deficits of skeletal muscles unrelated to the presence of neuropathy?

2. Is obesity associated with functional and structural impairments of skeletal muscles unrelated to the presence of type 2 diabetes ?

3. Does weight loss improve muscle metabolic flexibility and economy and modify skeletal muscle function and structure in obese subjects with and without type 2 diabetes?

The project will include three studies, intended to answer the hypotheses listed above:

Study 1: Evaluation of functional and structural muscular deficits of diabetic myopathy in relation to prolonged hyperglycemia prior to and 6 months following glycemic improvement in patients with type 1 and 2 diabetes

Study 2: Functional and structural muscular deficits in severely obese subjects with and without type 2 diabetes prior to assisted weight loss.

Study 3: Changes in functional and structural muscle properties following assisted weight loss in severely obese subjects with and without type 2 diabetes - a 1-year follow-up study.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 108
• Est. completion date: December 30, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

Study 1:

• Age: 18-60 years

• BMI: 18.5 - 27, minimum weight = 50kg

• Chronic hyperglycemia: HbA1c of = 70 mmol/mol with a duration of = 2 months

• Physical activity: Less than 3 x 60 min of structured physical activity per week

Study 2 & 3:

• Age: 25-60 years

• BMI: = 35

• Physical activity: Less than 3 x 60 min of structured physical activity per week

Healthy Control Participants:

• Age: 18-60 years

• BMI: 18.5 - 27, minimum weight = 50kg

• Physical activity: Less than 3 x 60 min of structured physical activity per week

Exclusion Criteria:

Study 1, 2, 3 and healthy controls:

• Diabetic neuropathy

• Uncontrolled cardiovascular or pulmonary disease, peripheral vascular disease, osteoarthropathy of the lower extremity, or any neurological og rheumatological disease which may affect muscle function, as well as any other disease that may effect ones ability to perform physical activity.

• Any Magnetic Resonance contraindications

• Any condition that by the principal investigator is expected to affect the participants ability to execute the study elements

Specifically for healthy control participants:

• The presence of diabetes or pre-diabetes (HbA1c =42 mmol/mol)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Hyperglycemia
• Muscular Diseases
• Obesity
• Sarcopenia
• Weight Loss

Intervention

Drug:
• 6-months of medically assisted glycemic improvement
Administrated by the clinic at Steno Diabetes Center, Aarhus, Denmark

Procedure:
• Bariatric surgery
Participants are examined prior to and 1 year following bariatric surgery in the Central Region, Denmark

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital, Denmark	Aarhus

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	EMG assessment of myopathic changes	Will be assessed in knee extensors and/or dorsal flexors on a subgroup of participants demonstrating significant fatigue during primary measures	Change from baseline to follow-up at an average of 6 months for study 1 and 12 months for study 3
Primary	Baseline: Evaluating the presence of sarcopenia in relation to the presence of hyperglycemia and/or obesity	The presence of sarcopenia is assessed based on recommended methods including measures of muscle strength (Biodex Dynamometer), muscle quantity and quality (MRI), and physical performance tests.	The prevalence of sarcopenia in participants with diabetes and hyperglycemia (study 1) or obesity (study 2) as compared to healthy control participants at baseline
Primary	Baseline: Skeletal muscle Force-velocity assessment in relation to the presence of hyperglycemia and/or obesity	Assessed by isokinetic knee-extension and dorsal flexion on a Biodex Dynamometer at increasing angular-velocities	The force-velocity relationship in participants with diabetes and hyperglycemia (study 1) or obesity (study 2) as compared to healthy control participants at baseline
Primary	Baseline: Assessment of skeletal muscle fatigue in relation to the presence of hyperglycemia and/or obesity	Assessed by a fatiguing isotonic protocol for knee-extension and dorsal flexion on a Biodex Dynamometer including twitch-parameters of knee-extensors	Fatigue in participants with diabetes and hyperglycemia (study 1) or obesity (study 2) as compared to healthy control participants at baseline
Primary	Changes in skeletal muscle force-velocity relationship with weight-loss or glycemic improvement		Change from baseline to follow-up at an average of 6 months for study 1 and 12 months for study 3
Primary	Changes in skeletal muscle fatigue in relation to weight-loss or glycemic improvement		Change from baseline to follow-up at an average of 6 months for study 1 and 12 months for study 3
Primary	Changes in parameters defining sarcopenia in relation to weight-loss or glycemic improvement		Change from baseline to follow-up at an average of 6 months for study 1 and 12 months for study 3
Secondary	31P MRS: Skeletal muscle bioenergetics and metabolic economy	Assessed by phosphorus magnetic resonance spectroscopy (31P MRS) performed during an isotonic fatiguing exercise in a 3T MR-scanner	Bioenergetics and metabolic economy in participants with diabetes and hyperglycemia (study 1) or obesity (study 2) as compared to healthy control participants at baseline
Secondary	31P MRS: Changes of skeletal muscle bioenergetics and metabolic economy in relation to weight-loss or glycemic improvement	Assessed by phosphorus magnetic resonance spectroscopy (31P MRS) performed during an isotonic fatiguing exercise in a 3T MR-scanner	Change from baseline to follow-up at an average of 6 months for study 1 and 12 months for study 3
Secondary	ENG assessment of neuropathic changes	ENG is assessed in the Sural, Tibial and Peroneal nerve	Change from baseline to follow-up at an average of 6 months for study 1 and 12 months for study 3
Secondary	Correlation analyses of primary measures with metabolic parameters including insulin resistance, HbA1c, metabolic economy, bioenergetics, and low-grade systemic inflammation (hs-CRP)		Change from baseline to follow-up at an average of 6 months for study 1 and 12 months for study 3