Biochemical Bone Turnover Markers and Bone Mechanical Properties Following Exercise Induced Changes in Insulin Sensitivity in People With Type 2 Diabetes
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Diabetes Mellitus, Type 2
- Sponsor
- Aarhus University Hospital
- Enrollment
- 42
- Locations
- 1
- Primary Endpoint
- Steady state plasma glucose during stage 1 of insulin suppression test (mmol/L)
- Status
- Completed
- Last Updated
- 8 months ago
Overview
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.
Investigators
Søren Gregersen
Clinical Associate Professor
Aarhus University Hospital
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)
Outcomes
Primary Outcomes
Steady state plasma glucose during stage 1 of insulin suppression test (mmol/L)
Time Frame: 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)
Time Frame: 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 Outcomes
- Circulating P1NP (µg/l)(12-week change. Comparison between pre-intervention and end-intervention)
- Circulating Sclerostin (µg/l)(12-week change. Comparison between pre-intervention and end-intervention)
- Ionized calcium (mmol/l)(12-week change. Comparison between pre-intervention and end-intervention)
- Hemoglobin A1c (mmol/mol)(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)(12-week change. Comparison between pre-intervention and end-intervention)
- Circulating insulin (pmol/l)(12-week change. Comparison between pre-intervention and end-intervention)
- Alkaline phosphatase (total and bone type) (U/l)(12-week change. Comparison between pre-intervention and end-intervention)
- Circulating CTX (µg/l)(12-week change. Comparison between pre-intervention and end-intervention)
- Circulating Osteocalcin (µg/l)(12-week change. Comparison between pre-intervention and end-intervention)
- Circulating Osteoglycin (µg/l)(12-week change. Comparison between pre-intervention and end-intervention)
- Vitamin D (nmol/l)(12-week change. Comparison between pre-intervention and end-intervention)
- Bone Mineral Density (t-score) in hip and spine(12-week change. Comparison between pre-intervention and end-intervention)
- Advanced glycation end-products (AGEs) in skin(12-week change. Comparison between pre-intervention and end-intervention)
- Results from the HRpQCT scan including trabecular and cortical state(12-week change. Comparison between pre-intervention and end-intervention)
- Body composition assessed with whole-body Dual-energy X-ray absorptiometry (DXA)(12-week change. Comparison between pre-intervention and end-intervention)
- FIB-4 score(12-week change. Comparison between pre-intervention and end-intervention)
- Alanine aminotransferase (unit(U)/l)(12-week change. Comparison between pre-intervention and end-intervention)
- Triglycerides (mmol/l)(12-week change. Comparison between pre-intervention and end-intervention)
- Blood pressure (mmHg)(12-week change. Comparison between pre-intervention and end-intervention)
- Body composition assessed with bioelectric impedance analysis (BIA)(12-week change. Comparison between pre-intervention and end-intervention)
- Circulating adiponectin(12-week change. Comparison between pre-intervention and end-intervention)
- Leptin (n/mL)(12-week change. Comparison between pre-intervention and end-intervention)
- Alpha-hydroxybutyrate (μg/mL)(12-week change. Comparison between pre-intervention and end-intervention)
- Monocyte chemoattractant protein-1 (pg/ml)(12-week change. Comparison between pre-intervention and end-intervention)
- Interleukin 1 beta (pg/ml)(12-week change. Comparison between pre-intervention and end-intervention)
- Interleukin 6 (pg/ml)(12-week change. Comparison between pre-intervention and end-intervention)
- Estimated glomerular filtration rate (ml/min/1,73m2)(12-week change. Comparison between pre-intervention and end-intervention)
- Circulating Parathyroid hormone (pmol/l)(12-week change. Comparison between pre-intervention and end-intervention)
- Aspartate aminotransferase (U)/l)(12-week change. Comparison between pre-intervention and end-intervention)
- Thrombocytes (10^9/l)(12-week change. Comparison between pre-intervention and end-intervention)
- Bioelectric impedance analysis (BIA)(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)(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),(12-week change. Comparison between pre-intervention and end-intervention)
- Low density lipoprotein (LDL) (mmol/l)(12-week change. Comparison between pre-intervention and end-intervention)
- High density lipoprotein (HDL) (mmol/l)(12-week change. Comparison between pre-intervention and end-intervention)