Type 2 Diabetes, Bone Disease, Osteoporosis, Diabetic Neuropathy Peripheral, Autonomic Neuropathy, Diabetic
Conditions
Brief summary
Objectives: The goal of this cross sectional clinical trial is to examine the phenotype of bone disease in type 2 diabetes.The main aims are to: 1. Compare bone microarchitecture, bone biomechanical competence, and bone turnover markers as well as postural control in T2D patients with and without fractures. 2. Examine how autonomic and peripheral neuropathy affects bone microarchitecture, bone material strength and bone turnover markers as well as postural control in T2D. Methods: The trial is of cross-sectional design and consists of examinations including * Blood samples to analyze bone markers, glycemic state i.e. * Bone scans including dual energy x-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HRpQCT) to evaluate Bone Mineral Density, t-score and bone structure. * Microindentation to evaluate bone material strength * Skin autofluorescence to measure levels of advanced glycation endproducts (AGEs) in the skin * Assesment of nerve function (peripheral and autonomic) * Assesment of postural control, muscle strength and gait Participants: A total of 300 type 2 diabetes patients divided to three groups: * 160 with no history of fractures or diabetic neuropathy * 100 with a history of fracture(s) * 40 with autonomic neuropathy or severe peripheral neuropathy
Interventions
DIAGNOSTIC_TESTDual Energy X-ray Absorbtiometry scan
Evaluation of body composition and bone mass density
DIAGNOSTIC_TESTHigh-resolution peripheral quantitative computed tomography
High-resolution peripheral quantitative computed tomography (HR-pQCT) assesses both volumetric bone mineral density (vBMD) and trabecular and cortical microarchitecture.
DIAGNOSTIC_TESTMicroindentation
Measures Bone Material Strength Index (BMSi) of cortical bone.
DIAGNOSTIC_TESTThermal perception thresholds
Heat and cold perception thresholds
DIAGNOSTIC_TESTNerve conduction studies
Nerve conduction and amplitude of sural nerve
DIAGNOSTIC_TESTComposite Autonomic Symptom Score 31
A validated self-assessment questionnaire quantifying the severity and distribution of autonomic symptoms across six domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder and pupillomotor functions) by scoring 31 clinically selected questions
Skin biopsy
DIAGNOSTIC_TESTPerception Threshold Tracking
Transcutaneous stimulation of large and small nerve fibres using weak electrical currents
DIAGNOSTIC_TESTAssessment of cardiovascular autonomic neuropathy
Electrocardiographic recordings at rest and during cardiovascular autonomic reflex tests.
DIAGNOSTIC_TESTHandgrip strength
Evaluation of muscle strength
DIAGNOSTIC_TESTForce plate platform
Evaluation of balance while standing still
DIAGNOSTIC_TESTBiospecimen collection
Biochemistry including bone turnover markers, glycemic status, inflammation markers i.e
DIAGNOSTIC_TESTIsometric leg extension strength
Evaluation of muscle strength
DIAGNOSTIC_TESTMichigan Neuropathy Screening Instrument
MNSI is used to assess status of peripheral neuropathy. It includes two separate assessments: a 15-item self-administered questionnaire and a lower extremity examination that includes inspection and assessment of vibratory sensation and ankle reflexes.
Sponsors
Aalborg University Hospital
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Men and women with minimum 40 years of age. 2. Diagnosis of T2D. At least one of the following criteria must be met at diagnosis: 1. HbA1c ≥ 48 mmol/mol (6,5 %) 2. Plasma glucose ≥ 11,1 mmol/l 3. Fasting plasma glucose ≥7,0 mmol/l Clinical effect of oral antidiabetic medication strengthens the diagnosis. 3. Diagnosis of diabetes at least one year prior to inclusion of the study to avoid honeymoon diabetes. 4. A history of fracture(s) (confirmed by radiographs analyzed by radiologist) following the diabetes diagnosis (T2D F+ group) 5. Diagnosed with severe peripheral (VPT ≥ 50) or autonomic neuropathy defined by cardiac autonomic reflex tests or severe abnormalities in orthostatic blood pressure (T2D N+ group) 6. Signed the informed consent. 7. Not defined by the
Exclusion criteria
.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of differences in bone microarchitecture between T2D patients with and without previous fractures assessed by HRpQCT. | Through study completion, estimated 3.5 years | Bone microarchitecture is a composite outcome assessed by HRpQCT at radius and tibia: Total volumetric mineral density, Trabecular volumetric mineral density, Cortical volumetric mineral density, Trabecular number, Trabecular thickness, Cortical thickness, Trabecular separation, Cortical porosity, bone stiffness and failure load. |
| Evaluation of differences in bone turnover markers between T2D patients with and without previous fractures by biochemical analysis of different bone markers (CTX, P1NP, osteocalcin (OC), ucOC, sclerostin, osteoglycin and osteopontin). | Through study completion, estimated 3.5 years | — |
| Differences in Bone material strength index (BMSi) between T2D patients with and without previous fractures measured by microindentation. | Through study completion, estimated 3.5 years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The impact of peripheral neuropathy on bone material strength in T2D assessed by microindentation. | Through study completion, estimated 3.5 years | Compare bone material strength (assessed by microindentation) in T2D patients with and without peripheral neuropathy (assessed by MNSI, PTT, QST, sural nerve conduction study and intraepidermal nerve fiber density) |
| The impact of peripheral neuropathy on bone turnover markers in T2D. | Through study completion, estimated 3.5 years | Compare bone turnover markers in T2D patients with and without peripheral neuropathy (assessed by MNSI, PTT, QST, sural nerve conduction study and intraepidermal nerve fiber density). |
| Compare postural control between T2D patients with and without fractures assessed by force platform. | Through study completion, estimated 3.5 years | — |
| Compare postural control between T2D patients with and without peripheral/autonomic neuropathy. | Through study completion, estimated 3.5 years | Neuropathy assessed by PTT, QST, sural nerve conduction study, skin biopsies, COMPASS-31, MNSI and Vagus device. Postural control assessed by force platform. |
| Compare muscle mass and strength in T2D patients with and without fractures | Through study completion, estimated 3.5 years | Compare muscle mass (assessed by DXA scan) and muscle strength (assessed by hand grip, leg extension strength and functional tests) in T2D patients with and without fractures. |
| Compare muscle mass and strength in T2D patients with and without neuropathy | Through study completion, estimated 3.5 years | Compare muscle mass (assessed by DXA scan) and muscle strength (assessed by hand grip, leg extension strength and functional tests) in T2D patients with and without neuropathy (assessed by PTT, QST, sural nerve conduction study, skin biopsies, COMPASS-31, MNSI and Vagus device). |
| The impact of autonomic neuropathy on bone microarchitecture in T2D assessed by HR-pQCT. | Through study completion, estimated 3.5 years | Compare bone microarchitectural parameters (assessed by HR-pQCT) in T2D patients with and without autonomic neuropathy (assessed by CAN-score from Vagus™ device, COMPASS31-score, intraepidermal nerve fiber density, orthostatic BP and ECG). |
| The impact of autonomic neuropathy on bone material strength in T2D assessed by microindentation. | Through study completion, estimated 3.5 years | Compare bone material strength (assessed by microindentation) in T2D patients with and without autonomic neuropathy (assessed by CAN-score from Vagus™ device, COMPASS31-score, intraepidermal nerve fiber density, orthostatic BP and ECG). |
| The impact of autonomic neuropathy on bone turnover markers in T2D. | Through study completion, estimated 3.5 years | Compare bone turnover markers in T2D patients with and without autonomic neuropathy (assessed by CAN-score from Vagus™ device, COMPASS31-score, intraepidermal nerve fiber density, orthostatic BP and ECG) |
| The impact of peripheral neuropathy on bone microarchitecture in T2D assessed by HR-pQCT. | Through study completion, estimated 3.5 years | Compare bone microarchitectural parameters (assessed by HR-pQCT) in T2D patients with and without peripheral neuropathy (assessed by MNSI, PTT, QST, sural nerve conduction study and intraepidermal nerve fiber density) |
Other
| Measure | Time frame | Description |
|---|---|---|
| The correlation between levels of Advanced Glycation End Products (AGEs) (assessed by skin autofluorescence) and bone material strength (assessed by microindentation). | Through study completion, estimated 3.5 years | — |
| Co-existence of peripheral and autonomic neuropathy | Through study completion, estimated 3.5 years | Presence of autonomic neuropathy (assessed by CAN-score from Vagus™ device, COMPASS31-score, intraepidermal nerve fiber density, orthostatic BP and ECG) will be compared with presence of peripheral neuropathy (assessed by PTT, QST, sural nerve conduction test and intraepidermal nerve fiber density) in T2D. |
| The impact of insulin resistance (assessed by HOMA-IR and -%B) on bone material strength (assessed by microindentation) in T2D. | Through study completion, estimated 3.5 years | — |
| The impact of insulin resistance (assessed by HOMA-IR and -%B) on bone microarchitecture (assessed by HR-pQCT) in T2D. | Through study completion, estimated 3.5 years | — |
| The impact of insulin resistance (assessed by HOMA-IR and -%B) on bone turnover markers in T2D. | Through study completion, estimated 3.5 years | — |
Countries
Denmark
Contacts
Primary ContactJulie Lindgård Graversen, MD
Backup ContactPeter Vestergaard, MD, PhD, Professor
Outcome results
None listed