Type 1 Diabetes Mellitus
Conditions
Brief summary
This single center case control study will assess differences in bone structure between women and men with longstanding type 1 diabetes (diabetes duration\>/= 25 years) and healthy controls.
Detailed description
Based on a cross-sectional approach the investigators aim to assess microstructural, biomechanical and densitometric bone characteristics in patients with longstanding type 1 diabetes and age- and sex-matches controls. The investigators examine whether the presence of microvascular disease and/or poor diabetic control is associated with an altered bone microarchitecture and whether any such effect is independent of bone mineral density. Furthermore, the investigators aim to look into the relationship between an altered bone microarchitecture and advanced glycation end product (AGE) formation as well as biochemical markers of bone formation and bone turnover. The study aims to identify type 1 diabetic patients with high fracture risk by assessing the discriminatory power of parameters of cortical and trabecular microstructure measured via high resolution peripheral quantitative computed tomography (HR-pQCT) of the distal radius and tibia and high resolution quantitative computed tomography (HR-QCT) of the proximal femur and tibia with and without adjustment for bone density.
Interventions
DIAGNOSTIC_TESTBiochemical Tests
The investigators will perform blood tests in every participant.
DIAGNOSTIC_TESTOsteodensitometry
The investigators will perform an osteodensitometry in every participant.
DIAGNOSTIC_TESTClinical Tests
The investigators perform the following clinical tests: vibration threshold test, monofilament test, chair rise test and timed up and go test in every participant.
DIAGNOSTIC_TESTHR-QCT
The investigators will perform HR-QCT measurements of the proximal femur and tibia in every participant.
DIAGNOSTIC_TESTHR-pQCT
The investigators will perform HR-pQCT measurements of the distal radius and distal tibia in every participant.
Sponsors
Insel Gruppe AG, University Hospital Bern
University Hospital Schleswig-Holstein
University Hospital, Basel, Switzerland
Christian Meier
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
Identical diagnostic procedures will be performed in participants with type 1 diabetes and age- and sex-matched controls.
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
Yes
Inclusion criteria
* women and men with longstanding type 1 diabetes (age 40-80 years, BMI 18-37 kg/m2 and age- and sex matched non-diabetic controls * presence of type 1 diabetes for at least 25 years (defined by history of Insulin treatment)
Exclusion criteria
* Patients unable to give written informed consent, e.g. with severe dementia or patients not understanding German (or other local language) * Any medical or psychiatric condition which would preclude the participant from adhering to the protocol * Idiopathic or premenopausal osteoporosis or coexisting metabolic bone disease (e.g. Paget´s disease, primary hyperparathyroidism) * Previous treatment with osteoporosis medication (bisphosphonates, denosumab) or intake of medications that are known to affect bone metabolism (e.g. steroids, anticonvulsants) within 6 months prior to enrollment * Patients with medical conditions known to affect bone health ( e.g. metastatic bone disease, celiac disease, inflammatory bone disease, hypogonadism, thyrotoxicosis, hypercortisolism, chronic kidney disease stage IV and V (KDIGO), liver dysfunction (serum aspartate amino transferase (ASAT) \>3 times the upper limit of normal) * Inability to keep the extremities still for a few minutes of an HR-pQCT examination (e.g. Parkinson disease, spastic syndrome) * Pregnant or breastfeeding women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| volumetric bone mineral density in mg hydroxyapatite (HA)/ccm | through study completion, an average of 6 months | measured by HR-pQCT at the distal radius and tibia |
| cortical porosity in % | through study completion, an average of 6 months | measured by HR-pQCT at the distal radius and tibia |
| bone stiffness in kilonewton (kN)/mm | through study completion, an average of 6 months | a measure of bone strength, measured by HR-pQCT at the distal radius and tibia |
| failure load in kN | through study completion, an average of 6 months | a measure of bone strength, measured by HR-pQCT at the distal radius and tibia |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| cortical thickness at the mid tibia in cm | through study completion, an average of 6 months | the cortical thickness will be measured by pulse-echo ultrasound and high resolution quantitative computed tomography (HR-QCT) |
| density weighed cortical thickness at the mid tibia in cm | through study completion, an average of 6 months | the density weighed cortical thickness will be measured by pulse-echo ultrasound and HR- QCT |
| bone marrow adiposity in mg/cm3 | through study completion, an average of 6 months | measured by HR-pQCT |
| measurement of serum carboxy-terminal collagen crosslinks (CTX) in pg/ml | through study completion, an average of 6 months | biochemical marker of bone resorption |
| measurement of serum n-terminal procollagen type 1 (P1NP) in mcg/l | through study completion, an average of 6 months | biochemical marker of bone formation |
| measurement of serum pentosidine in pmol/m | through study completion, an average of 6 months | biochemical marker associated with bone fragility |
| measurement of serum carboxymethyl-lysine (CML) in pmol/ml | through study completion, an average of 6 months | biochemical marker associated with bone fragility |
| areal bone mineral density of the spine in g/cm2 | through study completion, an average of 6 months | measured by osteodensitometry (DXA) |
| measurement of serum sclerostin in pg/ml | through study completion, an average of 6 months | biochemical marker associated with bone fragility |
| measurement of serum adiponectin in ng/ml | through study completion, an average of 6 months | biochemical marker associated with bone fragility |
| measurement of serum insulin like growth factor -1 (IGF1) in nM | through study completion, an average of 6 months | biochemical marker associated with bone fragility |
| measurement of serum ultrasensitive c-reactive protein (usCRP) in mg/l | through study completion, an average of 6 months | biochemical marker associated with bone fragility |
| measurement of serum interleukin 6 (IL6) in pg/ml | through study completion, an average of 6 months | biochemical marker associated with bone fragility |
| measurement of serum periostin in ng/ml | through study completion, an average of 6 months | biochemical marker associated with bone fragility |
| measurement of serum insulin in mU/ml | through study completion, an average of 6 months | biochemical marker associated with bone fragility |
| areal bone mineral density of the proximal femur in g/cm2 | through study completion, an average of 6 months | measured by osteodensitometry |
| areal bone mineral density of the distal radius in g/cm2 | through study completion, an average of 6 months | measured by osteodensitometry |
| trabecular bone score of the spine | through study completion, an average of 6 months | a measure of bone texture, measured by osteodensitometry |
Countries
Switzerland
Outcome results
None listed