Understanding Muscular Deficits of Diabetic Myopathy
Overview
- Phase
- Not Applicable
- Intervention
- 6-months of medically assisted glycemic improvement
- Conditions
- Diabetes Mellitus
- Sponsor
- University of Aarhus
- Enrollment
- 108
- Locations
- 1
- Primary Endpoint
- Baseline: Evaluating the presence of sarcopenia in relation to the presence of hyperglycemia and/or obesity
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
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:
- Is chronic hyperglycemia in type 1 and 2 diabetes associated with functional and structural deficits of skeletal muscles unrelated to the presence of neuropathy?
- Is obesity associated with functional and structural impairments of skeletal muscles unrelated to the presence of type 2 diabetes ?
- 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
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)
Arms & Interventions
Non-obese participants with dysregulated type 1 diabetes
Intervention: 6-months of medically assisted glycemic improvement
Non-obese participants with dysregulated type 2 diabetes
Intervention: 6-months of medically assisted glycemic improvement
Obese participants with type 2 diabetes
Intervention: Bariatric surgery
Obese participants without type 2 diabetes
Intervention: Bariatric surgery
Outcomes
Primary Outcomes
Baseline: Evaluating the presence of sarcopenia in relation to the presence of hyperglycemia and/or obesity
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: Change from baseline to follow-up at an average of 6 months for study 1 and 12 months for study 3
Secondary Outcomes
- 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)
- 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)
- 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)
- 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)