Clinical trial NCT05685927: Investigating Muscle Failure in Diabetic Myopathy
Official title: Understanding Muscular Deficits of Diabetic Myopathy
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Diabetes Mellitus
Obesity
Chronic Hyperglycaemia
Weight Loss
Diabetic Myopathy
Sarcopenia
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2023-01-17
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population consist of participants with type 1 diabetes (study 1) and participants with obesity and/or type 2 diabetes (study 1 and 2). Participants will be included at the Dept. of Endocrinology and Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark. Healthy control participants will be recruited by advertising in local media and at dedicated participant recruitment homepages.

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Baseline: Evaluating the presence of sarcopenia in relation to the presence of hyperglycemia and/or obesity
timeFrame: The prevalence of sarcopenia in participants with diabetes and hyperglycemia (study 1) or obesity (study 2) as compared to healthy control participants at baseline
measure: Baseline: Skeletal muscle Force-velocity assessment in relation to the presence of hyperglycemia and/or obesity
timeFrame: The force-velocity relationship in participants with diabetes and hyperglycemia (study 1) or obesity (study 2) as compared to healthy control participants at baseline
measure: Baseline: Assessment of skeletal muscle fatigue in relation to the presence of hyperglycemia and/or obesity
timeFrame: Fatigue in participants with diabetes and hyperglycemia (study 1) or obesity (study 2) as compared to healthy control participants at baseline
measure: Changes in skeletal muscle force-velocity relationship with weight-loss or glycemic improvement
timeFrame: Change from baseline to follow-up at an average of 6 months for study 1 and 12 months for study 3
measure: Changes in skeletal muscle fatigue in relation to weight-loss or glycemic improvement
timeFrame: Change from baseline to follow-up at an average of 6 months for study 1 and 12 months for study 3
measure: Changes in parameters defining sarcopenia in relation to weight-loss or glycemic improvement
timeFrame: Change from baseline to follow-up at an average of 6 months for study 1 and 12 months for study 3
Secondary outcomes:
measure: 31P MRS: Skeletal muscle bioenergetics and metabolic economy
timeFrame: Bioenergetics and metabolic economy in participants with diabetes and hyperglycemia (study 1) or obesity (study 2) as compared to healthy control participants at baseline
measure: 31P MRS: Changes of skeletal muscle bioenergetics and metabolic economy in relation to weight-loss or glycemic improvement
timeFrame: Change from baseline to follow-up at an average of 6 months for study 1 and 12 months for study 3
measure: ENG assessment of neuropathic changes
timeFrame: Change from baseline to follow-up at an average of 6 months for study 1 and 12 months for study 3
measure: Correlation analyses of primary measures with metabolic parameters including insulin resistance, HbA1c, metabolic economy, bioenergetics, and low-grade systemic inflammation (hs-CRP)
timeFrame: Change from baseline to follow-up at an average of 6 months for study 1 and 12 months for study 3
Other outcomes:
measure: EMG assessment of myopathic changes
timeFrame: Change from baseline to follow-up at an average of 6 months for study 1 and 12 months for study 3
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University Hospital, Denmark
Study officials:
affiliation: Aarhus University, Aarhus University Hospital, Denmark
name: Anders Stouge, MD, PhD-student
role: PRINCIPAL_INVESTIGATOR
References: