Investigating Muscle Failure in Diabetic Myopathy

Active, not recruiting

• Conditions: Weight Loss; Sarcopenia; Chronic Hyperglycaemia; Obesity; Diabetes Mellitus; Diabetic Myopathy
• Interventions: Drug: 6-months of medically assisted glycemic improvement; Procedure: Bariatric surgery

• Registration Number: NCT05685927
• Lead Sponsor: University of Aarhus

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-11-01
• Study First Submitted: 2023-01-03
• Study First Submitted QC: 2023-01-05
• Study First Posted: 2023-01-17
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-26
• Last Update Posted: 2025-03-03
• Primary Completion: 2025-09-30
• Study Completion: 2025-12-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 108

Inclusion Criteria

Study 1:

• Age: 18-60 years
• BMI: 18.5 - 39, minimum weight = 50kg
• Chronic hyperglycemia: HbA1c of ≥ 70 mmol/mol with a duration of ≥ 2 months prior to enrollment
• 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 - 30, 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 with expected motor deficits
• 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)

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Non-obese participants with dysregulated type 1 diabetes	6-months of medically assisted glycemic improvement	-
Non-obese participants with dysregulated type 2 diabetes	6-months of medically assisted glycemic improvement	-
Obese participants without type 2 diabetes	Bariatric surgery	-
Obese participants with type 2 diabetes	Bariatric surgery	-

Primary Outcome Measures

Name	Time	Method
Baseline: Evaluating the presence of sarcopenia in relation to the presence of hyperglycemia and/or obesity	The prevalence of sarcopenia in participants with diabetes and hyperglycemia (study 1) or obesity (study 2) as compared to healthy control participants at baseline	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.
Baseline: Skeletal muscle Force-velocity assessment in relation to the presence of hyperglycemia and/or obesity	The force-velocity relationship in participants with diabetes and hyperglycemia (study 1) or obesity (study 2) as compared to healthy control participants at baseline	Assessed by isokinetic knee-extension and dorsal flexion on a Biodex Dynamometer at increasing angular-velocities
Baseline: Assessment of skeletal muscle fatigue in relation to the presence of hyperglycemia and/or obesity	Fatigue in participants with diabetes and hyperglycemia (study 1) or obesity (study 2) as compared to healthy control participants at baseline	Assessed by a fatiguing isotonic protocol for knee-extension and dorsal flexion on a Biodex Dynamometer including twitch-parameters of knee-extensors
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
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
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 Outcome Measures

Name	Time	Method
31P MRS: Skeletal muscle bioenergetics and metabolic economy	Bioenergetics and metabolic economy in participants with diabetes and hyperglycemia (study 1) or obesity (study 2) as compared to healthy control participants at baseline	Assessed by phosphorus magnetic resonance spectroscopy (31P MRS) performed during an isotonic fatiguing exercise in a 3T MR-scanner
31P MRS: Changes of skeletal muscle bioenergetics and metabolic economy 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	Assessed by phosphorus magnetic resonance spectroscopy (31P MRS) performed during an isotonic fatiguing exercise in a 3T MR-scanner
ENG assessment of neuropathic changes	Change from baseline to follow-up at an average of 6 months for study 1 and 12 months for study 3	ENG is assessed in the Sural, Tibial and Peroneal nerve
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

Trial Locations

Locations (1)

Aarhus University Hospital, Denmark; 🇩🇰 Aarhus, Denmark