Deep Phenotyping of Bone Disease in Type 2 Diabetes and Relations to Diabetic Neuropathy
Aalborg University Hospital
300 participants
Feb 24, 2023
OBSERVATIONAL
Conditions
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
Eligibility
Inclusion Criteria9
- Men and women with minimum 40 years of age.
- Diagnosis of T2D. At least one of the following criteria must be met at diagnosis:
- HbA1c ≥ 48 mmol/mol (6,5 %)
- Plasma glucose ≥ 11,1 mmol/l
- Fasting plasma glucose ≥7,0 mmol/l Clinical effect of oral antidiabetic medication strengthens the diagnosis.
- Diagnosis of diabetes at least one year prior to inclusion of the study to avoid honeymoon diabetes.
- A history of fracture(s) (confirmed by radiographs analyzed by radiologist) following the diabetes diagnosis (T2D F+ group)
- 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)
- Signed the informed consent.
Exclusion Criteria16
- Severe decreased liver function (Alanin amino-transaminase (ALAT) \>250 U/l, Gamma-Glutamyltransferase (GGT) \>150 U/l).
- Moderate to severe kidney dysfunction, estimated Glomerular Filtration Rate (eGFR) \<15 mmol/L/1,73m2.
- Pregnancy or breast feeding.
- Active malignancy or terminal ill.
- Previous chemotherapy or immunomodulating treatment
- Known severe vitamin deficiency
- Current or previous alcohol- or drug abuse.
- Not being able to understand Danish written and/or verbally.
- Terms according to investigators judgement that makes subjects unsuitable to participate including lack of ability to understand and comply with instructions and/or reduced physical ability, limiting the ability to participate in the examinations.
- Participating in other clinical studies utilizing experimental treatment or medication.
- Subjects with pathologic fractures (defined as fractures due to local tumors, tumor-like lesions, or focal demineralization as visualized on radiographs).
- Primary hyperparathyroidism, Paget's disease and other metabolic bone diseases, uncontrolled thyrotoxicosis, celiac disease not controlled by diet, known hypogonadism, severe COPD, hypopituitarism, Cushing's disease.
- Fracture \< 6 month ago
- Initiation of antiresorptive or bone anabolic drugs \<12 months ago to ensure stable bone turnover markers.
- History of fractures following the diagnosis of diabetes (T2D F-/N- and T2D N+ groups).
- History of peripheral or autonomic neuropathy defined by cardiac autonomic reflex tests or severe abnormalities in orthostatic blood pressure (T2D F-/N- group).
Interventions
Evaluation of body composition and bone mass density
High-resolution peripheral quantitative computed tomography (HR-pQCT) assesses both volumetric bone mineral density (vBMD) and trabecular and cortical microarchitecture.
Measures Bone Material Strength Index (BMSi) of cortical bone.
Heat and cold perception thresholds
Nerve conduction and amplitude of sural nerve
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
Transcutaneous stimulation of large and small nerve fibres using weak electrical currents
Electrocardiographic recordings at rest and during cardiovascular autonomic reflex tests.
Evaluation of muscle strength
Evaluation of balance while standing still
Biochemistry including bone turnover markers, glycemic status, inflammation markers i.e
Evaluation of muscle strength
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.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT05642143