Muscular Deficits of Diabetic Myopathy
Study Details
Study Description
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:
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Is chronic hyperglycemia in type 1 and 2 diabetes associated with functional and structural deficits of skeletal muscles unrelated to the presence of neuropathy?
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Is obesity associated with functional and structural impairments of skeletal muscles unrelated to the presence of type 2 diabetes ?
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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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Non-obese participants with dysregulated type 1 diabetes
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Drug: 6-months of medically assisted glycemic improvement
Administrated by the clinic at Steno Diabetes Center, Aarhus, Denmark
|
| Non-obese participants with dysregulated type 2 diabetes
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Drug: 6-months of medically assisted glycemic improvement
Administrated by the clinic at Steno Diabetes Center, Aarhus, Denmark
|
| Obese participants with type 2 diabetes
|
Procedure: Bariatric surgery
Participants are examined prior to and 1 year following bariatric surgery in the Central Region, Denmark
|
| Obese participants without type 2 diabetes
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Procedure: Bariatric surgery
Participants are examined prior to and 1 year following bariatric surgery in the Central Region, Denmark
|
| Healthy control participants
|
Outcome Measures
Primary Outcome Measures
- 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 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 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 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
- 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]
Other Outcome Measures
- EMG assessment of myopathic changes [Change from baseline to follow-up at an average of 6 months for study 1 and 12 months for study 3]
Will be assessed in knee extensors and/or dorsal flexors on a subgroup of participants demonstrating significant fatigue during primary measures
Eligibility Criteria
Criteria
Inclusion Criteria:
Study 1:
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Age: 18-60 years
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BMI: 18.5 - 27, minimum weight = 50kg
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Chronic hyperglycemia: HbA1c of ≥ 70 mmol/mol with a duration of ≥ 2 months
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Physical activity: Less than 3 x 60 min of structured physical activity per week
Study 2 & 3:
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Age: 25-60 years
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BMI: ≥ 35
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Physical activity: Less than 3 x 60 min of structured physical activity per week
Healthy Control Participants:
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Age: 18-60 years
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BMI: 18.5 - 27, minimum weight = 50kg
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Physical activity: Less than 3 x 60 min of structured physical activity per week
Exclusion Criteria:
Study 1, 2, 3 and healthy controls:
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Diabetic neuropathy
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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.
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Any Magnetic Resonance contraindications
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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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Aarhus University Hospital, Denmark | Aarhus | Denmark | 8000 |
Sponsors and Collaborators
- University of Aarhus
Investigators
- Principal Investigator: Anders Stouge, MD, PhD-student, Aarhus University, Aarhus University Hospital, Denmark
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DM2021AS