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

Aarhus University Hospital42 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Diabetes Mellitus, Type 2 Insulin Resistance Bone Diseases, Metabolic Osteoporosis, Osteopenia

Eligibility

Sex: ALLMin age: 45 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 220, 230 and 240 minutes after test-start. 12-week change. Comparison between pre-intervention and end-intervention steady state plasma glucose