Bone Properties Following Exercise Induced Changes in Insulin Sensitivity in People with Type 2 Diabetes

Not Applicable

Recruiting

• Conditions: Diabetes Mellitus, Type 2; Insulin Resistance; Bone Diseases, Metabolic; Osteoporosis, Osteopenia; Musculoskeletal Diseases; Metabolic Disease; Glucose Metabolism Disorders

• Registration Number: NCT06668090
• Lead Sponsor: Aarhus University Hospital

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-12-15
• Study First Submitted: 2024-10-30
• Study First Submitted QC: 2024-10-30
• Study First Posted: 2024-10-31
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-17
• Last Update Posted: 2025-03-19
• Primary Completion: 2025-07-01
• Study Completion: 2025-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Steady state plasma glucose during stage 1 of insulin suppression test (mmol/L)	100, 110 and 120 minutes after test-start. 12-week change. Comparison between pre-intervention and end-intervention steady state plasma glucose.	Subjects are administered a 25 μg octreotide bolus at time-point 0 minutes and subsequently infused with 0.27 μg octreotide / m2 • minute, 6 milliunits (mU) insulin / m2 • minute, and 50 mg glucose / m2 • min.
Steady state plasma glucose during stage 2 of insulin suppression test (mmol/L)	220, 230 and 240 minutes after test-start. 12-week change. Comparison between pre-intervention and end-intervention steady state plasma glucose	Subjects are administered a 25 μg octreotide bolus at time-point 0 minutes and subsequently infused with 0.27 μg octreotide / m2 • minute, 6 (mU) insulin / m2 • minute, and 50 mg glucose / m2 • minute. At time-point 120 minutes, infusion speeds are increased to to 32 mU insulin / m2 • minute and 267 mg glucose / m2 • minute.

Secondary Outcome Measures

Name	Time	Method
Circulating P1NP (µg/l)	12-week change. Comparison between pre-intervention and end-intervention	Measured during fasting and during stage 1 and 2 of the insulin suppression test
Circulating Sclerostin (µg/l)	12-week change. Comparison between pre-intervention and end-intervention	Measured during fasting and during stage 1 and 2 of the insulin suppression test
Ionized calcium (mmol/l)	12-week change. Comparison between pre-intervention and end-intervention	Fasting
Hemoglobin A1c (mmol/mol)	12-week change. Comparison between pre-intervention and end-intervention	During fasting.
Fasting Homeostatic Model Assessment for Insulin Resistance by C-peptide (arbitrary unit).	12-week change. Comparison between pre-intervention blood samples and end-intervention blood samples.
Circulating glucose (mmol/l)	12-week change. Comparison between pre-intervention and end-intervention	Fasting
Circulating insulin (pmol/l)	12-week change. Comparison between pre-intervention and end-intervention	Fasting
Alkaline phosphatase (total and bone type) (U/l)	12-week change. Comparison between pre-intervention and end-intervention	Fasting
Circulating CTX (µg/l)	12-week change. Comparison between pre-intervention and end-intervention	Measured during fasting and during stage 1 and 2 of the insulin suppression test They are measured during fasting and during stage 1 and 2 of the insulin suppression test
Circulating Osteocalcin (µg/l)	12-week change. Comparison between pre-intervention and end-intervention	Measured during fasting and during stage 1 and 2 of the insulin suppression test
Circulating Osteoglycin (µg/l)	12-week change. Comparison between pre-intervention and end-intervention	They are measured during fasting and during stage 1 and 2 of the insulin suppression test
Vitamin D (nmol/l)	12-week change. Comparison between pre-intervention and end-intervention	Fasting
Bone Mineral Density (t-score) in hip and spine	12-week change. Comparison between pre-intervention and end-intervention	Dual-energy X-ray absorptiometry (DXA).
Advanced glycation end-products (AGEs) in skin	12-week change. Comparison between pre-intervention and end-intervention	Measurement of skin autofluorescence in the forearm
Results from the HRpQCT scan including trabecular and cortical state	12-week change. Comparison between pre-intervention and end-intervention	Measured in the tibial and radial bone on the non-dominant side
Body composition assessed with whole-body Dual-energy X-ray absorptiometry (DXA)	12-week change. Comparison between pre-intervention and end-intervention	Measured during fasting
FIB-4 score	12-week change. Comparison between pre-intervention and end-intervention	Using age, ALAT, ASAT and thrombocytes
Alanine aminotransferase (unit(U)/l)	12-week change. Comparison between pre-intervention and end-intervention	Fasting
Triglycerides (mmol/l)	12-week change. Comparison between pre-intervention and end-intervention	Fasting
Blood pressure (mmHg)	12-week change. Comparison between pre-intervention and end-intervention	Average daytime and night-time ambulatory blood pressure. 24-hour ambulatory blood pressure measurement, measured every 20 minutes during daytime and every 30 minutes during nighttime.
Body composition assessed with bioelectric impedance analysis (BIA)	12-week change. Comparison between pre-intervention and end-intervention	Measured during fasting
Circulating adiponectin	12-week change. Comparison between pre-intervention and end-intervention	Fasting
Leptin (n/mL)	12-week change. Comparison between pre-intervention and end-intervention	Fasting
Alpha-hydroxybutyrate (μg/mL)	12-week change. Comparison between pre-intervention and end-intervention	Fasting
Monocyte chemoattractant protein-1 (pg/ml)	12-week change. Comparison between pre-intervention and end-intervention	Fasting
Interleukin 1 beta (pg/ml)	12-week change. Comparison between pre-intervention and end-intervention	Fasting
Interleukin 6 (pg/ml)	12-week change. Comparison between pre-intervention and end-intervention	Fasting
Estimated glomerular filtration rate (ml/min/1,73m2)	12-week change. Comparison between pre-intervention and end-intervention	Fasting
Circulating Parathyroid hormone (pmol/l)	12-week change. Comparison between pre-intervention and end-intervention	Measured during fasting and during stage 1 and 2 of the insulin suppression test
Aspartate aminotransferase (U)/l)	12-week change. Comparison between pre-intervention and end-intervention	Fasting
Thrombocytes (10^9/l)	12-week change. Comparison between pre-intervention and end-intervention	Fasting
Bioelectric impedance analysis (BIA)	12-week change. Comparison between pre-intervention and end-intervention	Following measurements will be evaluated: Phase angle, membrane capacitance, impedance, capacitive resistance, resistance.; Measured during fasting and stage 1 and 2 of insulin suppression test
Steady state glycerol and free fatty acids during stage 1 and 2 of insulin suppression test (mmol/L)	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.	Subjects are administered a 25 μg octreotide bolus at time-point 0 minutes and subsequently infused with 0.27 μg octreotide / m2 • minute, 6 (mU) insulin / m2 • minute, and 50 mg glucose / m2 • minute. At time-point 120 minutes, infusion speeds are increased to to 32 mU insulin / m2 • minute and 267 mg glucose / m2 • minute.
Total cholesterol (mmol/l),	12-week change. Comparison between pre-intervention and end-intervention	Fasting
Low density lipoprotein (LDL) (mmol/l)	12-week change. Comparison between pre-intervention and end-intervention	Fasting
High density lipoprotein (HDL) (mmol/l)	12-week change. Comparison between pre-intervention and end-intervention	Fastomg

Trial Locations

Locations (1)

Steno Diabetes Center Aarhus; 🇩🇰 Aarhus N, Denmark