Clinical trial NCT06668090: Bone Properties Following Exercise Induced Changes in Insulin Sensitivity in People with Type 2 Diabetes
Official title: Biochemical Bone Turnover Markers and Bone Mechanical Properties Following Exercise Induced Changes in Insulin Sensitivity in People with Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Insulin Resistance
Bone Diseases, Metabolic
Osteoporosis, Osteopenia
Musculoskeletal Diseases
Metabolic Disease
Glucose Metabolism Disorders
Keywords: Diabetes Mellitus, Type 2
Bone
Bioelectric impedance
Diabetic bone disease
Insulin supression test (IST)
Bone turnover
Lead sponsor: Aarhus University Hospital
Sponsor class: OTHER
Collaborators: name: The Novo Nordic Foundation
name: Aalborg University Hospital
First posted: 2024-10-31
Enrollment: 40
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Diabetes mellitus type 2 is associated with low bone turnover and increased risk of bone fractures.

Bone mineral density, however, is increased and cannot explain the increased fracture risk per se. The pathophysiology is not completely understood, but the decrease in bone turnover is believed to cause an accumulation of microcracks in bone tissue leading to bone fragility. The decrease in bone turnover may arise directly from insulin resistance or indirectly through formation of advanced glycation end-products.

The main aim objective is to investigate how increases in insulin sensitivity following 12 weeks of moderate intensity bike exercise affect biochemical bone turnover markers and biomechanical bone properties in individuals with diabetes mellitus type 2.


Eligibility criteria: Inclusion Criteria:

* Diabetes mellitus type 2
* Age ≥ 45 years
* Male or female sex
* Women must be postmenopausal

Exclusion Criteria:

* Recent substantial changes in diet (within 3 months)
* Recent substantial changes in activity level (within 3 months)
* Recent substantial weight changes (within 3 months)
* Current or previous treatment (within the last 2 years) with non-oral anti-diabetics or oral GLP-1 analogs
* HbA1c ≥ 90 mmol/mol
* HbA1c \< 48 mmol/mol without anti-diabetic medication
* Premature menopause (menopause before 40 years of age)
* Current pregnancy
* Treatment with one of the following medications:

  * Systemic glucocorticoids (within the last 2 years)
  * Antiresorptive or bone anabolic medication (ever)
  * Lithium (ever)
  * Anticonvulsive medication (current)
  * Menopausal replacement therapy (currently)
* Estimered glomerular filtrationsrate (eGFR) \< 60 mL/minutes
* High level of physical activity, assessed by the investigators to interfere with the study results
* Substantial cardiovascular, endocrine, renal, hepatic, rheumatological, gastrointestinal or other disorders assessed by the investigator
* Electronic implants
* Osteoporosis or other bone disease
* Resent bone fracture (within 6 months)
* Previous bone fracture in either both tibial bones or both radial bones
* Parathyroid or calcium metabolism disorder
* Vitamin D deficiency (\< 50 nmol/L)
* Other substantial medical disorder in unstable phase or active cancer within the last five years except spino- or basocellular carcinoma
* Lack of ability to complete the intervention
* Patients assessed uneligible by the investigator to participate in the study

Primary outcomes:
measure: Steady state plasma glucose during stage 1 of insulin suppression test (mmol/L)
timeFrame: 100, 110 and 120 minutes after test-start. 12-week change. Comparison between pre-intervention and end-intervention steady state plasma glucose.
measure: Steady state plasma glucose during stage 2 of insulin suppression test (mmol/L)
timeFrame: 220, 230 and 240 minutes after test-start. 12-week change. Comparison between pre-intervention and end-intervention steady state plasma glucose
Secondary outcomes:
measure: Hemoglobin A1c (mmol/mol)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Fasting Homeostatic Model Assessment for Insulin Resistance by C-peptide (arbitrary unit).
timeFrame: 12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
measure: Circulating glucose (mmol/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Circulating insulin (pmol/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Alkaline phosphatase (total and bone type) (U/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Circulating CTX (µg/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Circulating Osteocalcin (µg/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Circulating Osteoglycin (µg/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Circulating P1NP (µg/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Circulating Sclerostin (µg/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Ionized calcium (mmol/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Circulating Parathyroid hormone (pmol/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Vitamin D (nmol/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Bone Mineral Density (t-score) in hip and spine
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Advanced glycation end-products (AGEs) in skin
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Results from the HRpQCT scan including trabecular and cortical state
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Body composition assessed with whole-body Dual-energy X-ray absorptiometry (DXA)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: FIB-4 score
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Alanine aminotransferase (unit(U)/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Aspartate aminotransferase (U)/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Thrombocytes (10^9/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Bioelectric impedance analysis (BIA)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Steady state glycerol and free fatty acids during stage 1 and 2 of insulin suppression test (mmol/L)
timeFrame: 100, 110, 120, 220, 230 and 240 minutes after test-start. 12-week change. Comparison between pre-intervention and end-intervention steady state plasma glucose.
measure: Total cholesterol (mmol/l),
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Low density lipoprotein (LDL) (mmol/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: High density lipoprotein (HDL) (mmol/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Triglycerides (mmol/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Blood pressure (mmHg)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Body composition assessed with bioelectric impedance analysis (BIA)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Circulating adiponectin
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Leptin (n/mL)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Alpha-hydroxybutyrate (μg/mL)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Monocyte chemoattractant protein-1 (pg/ml)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Interleukin 1 beta (pg/ml)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Interleukin 6 (pg/ml)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Estimated glomerular filtration rate (ml/min/1,73m2)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
Other outcomes:
measure: Thyroid-stimulating hormone (international unit (IU)/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: High sensitivity C reactive protein (mg/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Thyroid stimulating hormone (pmol/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Creatinine (μmol/l)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Activity tracking
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Activity level - questionnaire
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Diet diary (3 days)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
measure: Urine albumin-to-creatinine ratio (mg/g)
timeFrame: 12-week change. Comparison between pre-intervention and end-intervention
Locations:
city: Aarhus N
country: Denmark
facility: Steno Diabetes Center Aarhus
Study officials:
References: