Bone Diseases, Metabolic, Diabetes Mellitus, Type 2, Glucose Metabolism Disorders, Insulin Resistance, Metabolic Disease, Musculoskeletal Diseases, Osteoporosis, Osteopenia
Conditions
Keywords
Diabetes Mellitus, Type 2, Bone, Bioelectric impedance, Diabetic bone disease, Insulin supression test (IST), Bone turnover
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.
Interventions
BEHAVIORALModerate intensity bike exercise
Participants will do moderate intensity bike exercise for up to one hour thrice weekly for 12 weeks.
Sponsors
The Novo Nordic Foundation
Aalborg University Hospital
Aarhus University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Monocyte chemoattractant protein-1 (pg/ml) | 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Triglycerides (mmol/l) | 12-week change. Comparison between pre-intervention and end-intervention | Fasting |
Other
| Measure | Time frame | Description |
|---|---|---|
| Creatinine (μmol/l) | 12-week change. Comparison between pre-intervention and end-intervention | Fasting |
| Activity tracking | 12-week change. Comparison between pre-intervention and end-intervention | Measured with accelerometer on thigh of non-dominant leg |
| 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) | 12-week change. Comparison between pre-intervention and end-intervention | Fasting |
| High sensitivity C reactive protein (mg/l) | 12-week change. Comparison between pre-intervention and end-intervention | Fasting |
| Thyroid stimulating hormone (pmol/l) | 12-week change. Comparison between pre-intervention and end-intervention | Fasting |
| Thyroid-stimulating hormone (international unit (IU)/l) | 12-week change. Comparison between pre-intervention and end-intervention | Fasting |
Countries
Denmark
Outcome results
None listed