Chronic Hyperglycaemia, Diabetes Mellitus, Diabetic Myopathy, Obesity, Sarcopenia, Weight Loss
Conditions
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.
Interventions
DRUG6-months of medically assisted glycemic improvement
Administrated by the clinic at Steno Diabetes Center, Aarhus, Denmark
PROCEDUREBariatric surgery
Participants are examined prior to and 1 year following bariatric surgery in the Central Region, Denmark
Sponsors
University of Aarhus
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Denmark
Outcome results
None listed