Investigating Muscle Failure in Diabetic Myopathy

N/AActive Not RecruitingNCT05685927

University of Aarhus108 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

108

Conditions

Diabetes Mellitus Obesity Chronic Hyperglycaemia

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

Baseline: Evaluating the presence of sarcopenia in relation to the presence of hyperglycemia and/or obesity

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.

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

Baseline: Skeletal muscle Force-velocity assessment in relation to the presence of hyperglycemia and/or obesity

Assessed by isokinetic knee-extension and dorsal flexion on a Biodex Dynamometer at increasing angular-velocities

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

Baseline: Assessment of skeletal muscle fatigue in relation to the presence of hyperglycemia and/or obesity

Assessed by a fatiguing isotonic protocol for knee-extension and dorsal flexion on a Biodex Dynamometer including twitch-parameters of knee-extensors

Time frame: Fatigue in participants with diabetes and hyperglycemia (study 1) or obesity (study 2) as compared to healthy control participants at baseline

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 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 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

Assessed by phosphorus magnetic resonance spectroscopy (31P MRS) performed during an isotonic fatiguing exercise in a 3T MR-scanner

Time frame: 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

Assessed by phosphorus magnetic resonance spectroscopy (31P MRS) performed during an isotonic fatiguing exercise in a 3T MR-scanner

Time frame: 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

ENG is assessed in the Sural, Tibial and Peroneal nerve

Time frame: 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)

Time frame: Change from baseline to follow-up at an average of 6 months for study 1 and 12 months for study 3

Investigating Muscle Failure in Diabetic Myopathy

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes