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

Biochemical Bone Turnover Markers and Bone Mechanical Properties Following Exercise Induced Changes in Insulin Sensitivity in People With Type 2 Diabetes

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.

Study Overview

• Status: Completed
• Conditions: Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Musculoskeletal Diseases; Insulin Resistance; Bone Diseases, Metabolic; Metabolic Disease; Osteoporosis, Osteopenia
• Intervention / Treatment: Behavioral: Moderate intensity bike exercise

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus N, Denmark, 8200
    • Steno Diabetes Center Aarhus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Exercise; Moderate intensity bike exercise thrice weekly for 12 week added to the usual activity level. Each participant receive an individual exercise program based on their maximum heart rate. Exercise is not supervised, but compliance is monitored. It will either be performed at home or at gyms. No changes in diet.	Behavioral: Moderate intensity bike exercise; Participants will do moderate intensity bike exercise for up to one hour thrice weekly for 12 weeks.
No Intervention: Control/no intervention; 12 weeks with usual activity level. No changes in diet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Steady state plasma glucose during stage 1 of insulin suppression test (mmol/L)	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.	100, 110 and 120 minutes after test-start. 12-week change. Comparison between pre-intervention and end-intervention steady state plasma glucose.
Steady state plasma glucose during stage 2 of insulin suppression test (mmol/L)	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.	220, 230 and 240 minutes after test-start. 12-week change. Comparison between pre-intervention and end-intervention steady state plasma glucose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hemoglobin A1c (mmol/mol)	During fasting.	12-week change. Comparison between pre-intervention and end-intervention
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)	Fasting	12-week change. Comparison between pre-intervention and end-intervention
Circulating insulin (pmol/l)	Fasting	12-week change. Comparison between pre-intervention and end-intervention
Alkaline phosphatase (total and bone type) (U/l)	Fasting	12-week change. Comparison between pre-intervention and end-intervention
Circulating CTX (µg/l)	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	12-week change. Comparison between pre-intervention and end-intervention
Circulating Osteocalcin (µg/l)	Measured during fasting and during stage 1 and 2 of the insulin suppression test	12-week change. Comparison between pre-intervention and end-intervention
Circulating Osteoglycin (µg/l)	They are measured during fasting and during stage 1 and 2 of the insulin suppression test	12-week change. Comparison between pre-intervention and end-intervention
Circulating P1NP (µg/l)	Measured during fasting and during stage 1 and 2 of the insulin suppression test	12-week change. Comparison between pre-intervention and end-intervention
Circulating Sclerostin (µg/l)	Measured during fasting and during stage 1 and 2 of the insulin suppression test	12-week change. Comparison between pre-intervention and end-intervention
Ionized calcium (mmol/l)	Fasting	12-week change. Comparison between pre-intervention and end-intervention
Circulating Parathyroid hormone (pmol/l)	Measured during fasting and during stage 1 and 2 of the insulin suppression test	12-week change. Comparison between pre-intervention and end-intervention
Vitamin D (nmol/l)	Fasting	12-week change. Comparison between pre-intervention and end-intervention
Bone Mineral Density (t-score) in hip and spine	Dual-energy X-ray absorptiometry (DXA).	12-week change. Comparison between pre-intervention and end-intervention
Advanced glycation end-products (AGEs) in skin	Measurement of skin autofluorescence in the forearm	12-week change. Comparison between pre-intervention and end-intervention
Results from the HRpQCT scan including trabecular and cortical state	Measured in the tibial and radial bone on the non-dominant side	12-week change. Comparison between pre-intervention and end-intervention
Body composition assessed with whole-body Dual-energy X-ray absorptiometry (DXA)	Measured during fasting	12-week change. Comparison between pre-intervention and end-intervention
FIB-4 score	Using age, ALAT, ASAT and thrombocytes	12-week change. Comparison between pre-intervention and end-intervention
Alanine aminotransferase (unit(U)/l)	Fasting	12-week change. Comparison between pre-intervention and end-intervention
Aspartate aminotransferase (U)/l)	Fasting	12-week change. Comparison between pre-intervention and end-intervention
Thrombocytes (10^9/l)	Fasting	12-week change. Comparison between pre-intervention and end-intervention
Bioelectric impedance analysis (BIA)	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	12-week change. Comparison between pre-intervention and end-intervention
Steady state glycerol and free fatty acids during stage 1 and 2 of insulin suppression test (mmol/L)	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.	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.
Total cholesterol (mmol/l),	Fasting	12-week change. Comparison between pre-intervention and end-intervention
Low density lipoprotein (LDL) (mmol/l)	Fasting	12-week change. Comparison between pre-intervention and end-intervention
High density lipoprotein (HDL) (mmol/l)	Fastomg	12-week change. Comparison between pre-intervention and end-intervention
Triglycerides (mmol/l)	Fasting	12-week change. Comparison between pre-intervention and end-intervention
Blood pressure (mmHg)	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.	12-week change. Comparison between pre-intervention and end-intervention
Body composition assessed with bioelectric impedance analysis (BIA)	Measured during fasting	12-week change. Comparison between pre-intervention and end-intervention
Circulating adiponectin	Fasting	12-week change. Comparison between pre-intervention and end-intervention
Leptin (n/mL)	Fasting	12-week change. Comparison between pre-intervention and end-intervention
Alpha-hydroxybutyrate (μg/mL)	Fasting	12-week change. Comparison between pre-intervention and end-intervention
Monocyte chemoattractant protein-1 (pg/ml)	Fasting	12-week change. Comparison between pre-intervention and end-intervention
Interleukin 1 beta (pg/ml)	Fasting	12-week change. Comparison between pre-intervention and end-intervention
Interleukin 6 (pg/ml)	Fasting	12-week change. Comparison between pre-intervention and end-intervention
Estimated glomerular filtration rate (ml/min/1,73m2)	Fasting	12-week change. Comparison between pre-intervention and end-intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Thyroid-stimulating hormone (international unit (IU)/l)	Fasting	12-week change. Comparison between pre-intervention and end-intervention
High sensitivity C reactive protein (mg/l)	Fasting	12-week change. Comparison between pre-intervention and end-intervention
Thyroid stimulating hormone (pmol/l)	Fasting	12-week change. Comparison between pre-intervention and end-intervention
Creatinine (μmol/l)	Fasting	12-week change. Comparison between pre-intervention and end-intervention
Activity tracking	Measured with accelerometer on thigh of non-dominant leg	12-week change. Comparison between pre-intervention and end-intervention
Activity level - questionnaire		12-week change. Comparison between pre-intervention and end-intervention
Diet diary (3 days)		12-week change. Comparison between pre-intervention and end-intervention
Urine albumin-to-creatinine ratio (mg/g)	Fasting	12-week change. Comparison between pre-intervention and end-intervention

Collaborators and Investigators

• Sponsor: Aarhus University Hospital
• Collaborators: The Novo Nordic Foundation; Aalborg University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2022
• Primary Completion (Actual): June 26, 2025
• Study Completion (Actual): June 28, 2025

Study Registration Dates

• First Submitted: October 30, 2024
• First Submitted That Met QC Criteria: October 30, 2024
• First Posted (Actual): October 31, 2024

Study Record Updates

• Last Update Posted (Actual): August 14, 2025
• Last Update Submitted That Met QC Criteria: August 11, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Bone; Diabetes Mellitus, Type 2; Bone turnover; Bioelectric impedance; Diabetic bone disease; Insulin supression test (IST)
• Additional Relevant MeSH Terms: Endocrine System Diseases; Hyperinsulinism; Diabetes Mellitus, Type 2; Osteoporosis; Diabetes Mellitus; Insulin Resistance; Musculoskeletal Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Bone Diseases; Bone Diseases, Metabolic
• Other Study ID Numbers: 1-10-72-221-19

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No