Diabetes Mellitus, Type 1, Bone Health, Bone Loss, Bone Diseases, Metabolic, Hyperglycaemia Due to Type 1 Diabetes Mellitus
Conditions
Brief summary
Background : Type 1 diabetes (T1D) is associated with an increased risk of fractures. The mechanisms accounting for this bone fragility are not yet fully understood. As T1D is often diagnosed in childhood or early adulthood, the lower bone mineral density (BMD) and deteriorated bone microarchitecture observed in T1D may reflect changes in the bone that occurred before or at the time of peak bone mass achievement. There is a lack of high-quality prospective studies to determine whether adults with T1D continue to lose BMD or deteriorate bone quality compared with controls. Moreover, while chronic hyperglycemia is a risk factor for fracture in T1D, it is unknown if better glycemic control affects bone outcomes. This prospective multicenter cohort study aims: (1) To compare the changes in the following outcomes over 4 years in adults with T1D and controls without diabetes of similar age, sex and body-mass index distribution: BMD by dual-energy X-ray absorptiometry (DXA) at the femoral neck, hip, spine, and radius, trabecular bone score (TBS) by DXA, and serum biochemical markers of bone turnover (BTMs); (2) To evaluate whether long-term glycemic control or the presence of a microvascular complication are independent predictors of the changes in BMD and TBS in people with T1D.
Interventions
DIAGNOSTIC_TESTClinical tests
The investigators perform the following clinical tests: vibration threshold test, monofilament test, and height, weight and waist circumference measurement in every participant.
DIAGNOSTIC_TESTBiochemical tests
The investigators perform blood and urine tests in every participant.
DIAGNOSTIC_TESTDXA scan with TBS and VFA
The investigators perform a dual energy x-ray absorptiometry (DXA scan or osteodensitometry) including trabecular bone score (TBS) and Vertebral Fracture Assessment (VFA) in every participant.
DIAGNOSTIC_TESTAGEReader
The investigators perform a skin advanced glycation end products (AGEs) measurement with the AGE Reader machine in every participant.
Sponsors
Diabetes Canada
CHU de Quebec-Universite Laval
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Individuals with type 1 diabetes who have participated in the DenSiFy (Diabetes Spine Fractures) study (NCT04064437) Inclusion Criteria: * Diagnosis of type 1 diabetes for at least 5 years; * Age 20 years and older.
Exclusion criteria
* Pregnancy, delivery or breastfeeding in the past 6 months; * Conditions associated with bone disease (significant liver disease, intestinal malabsorption other than celiac disease, organ transplant, active cancer, rheumatoid arthritis, hyperthyroidism, hypothyroidism with abnormal TSH, hyperparathyroidism, hypoparathyroidism, hypogonadism, acromegaly, Cushing syndrome, adrenal insufficiency); * Any of these medications since the first DenSiFy study visit : biphosphonates, teriparatide, denosumab, calcitonin, glucocorticoids ≥ 7,5 mg prednisone/day or equivalency ≥ 3 months, aromatase inhibitors, antiandrogens, antiepileptic drugs, anticoagulants, thiazolidinediones; * Inability to consent. Healthy controls who have participated in the DenSiFy (Diabetes Spine Fractures) study (NCT04064437) Inclusion Criteria: * Age 20 years and older.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in areal bone mineral density (aBMD) at the femoral neck in g/cm2 | Between the baseline and the 4-year visit | aBMD measured by DXA scan |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in areal bone mineral density (aBMD) at the total hip in g/cm2 | Between the baseline and the 4-year visit | aBMD measured by DXA scan |
| Change in areal bone mineral density (aBMD) at the distal third of radius in g/cm2 | Between the baseline and the 4-year visit | aBMD measured by DXA scan |
| Change in Trabecular bone score (TBS) (unitless) | Between the baseline and the 4-year visit | TBS with the software TBSinSight |
| Change in areal bone mineral density (aBMD) at the spine in g/cm2 | Between the baseline and the 4-year visit | aBMD measured by DXA scan |
| Glycemic control, assessed with skin advanced glycation end products (AGEs) | 4-year visit | Skin AGEs measured with AGEReader (autofluorescence) |
| Presence of a microvascular complication (neuropathy, nephropathy, retinopathy) | 4-year visit | From the information available in the medical record and from monofilament and vibration testing (for neuropathy) and from microalbuminuria (nephropathy) |
| Glycemic control, assessed with mean glycated hemoglobin (HbA1c) of the past 7 years | 4-year visit | Mean HbA1c of the past 7 years from all the available HbA1c in the medical record |
Other
| Measure | Time frame | Description |
|---|---|---|
| Areal bone mineral density at the total hip, T-score | 4-year visit | Measured by DXA scan |
| Areal bone mineral density at the total hip, Z-score | 4 year visit | Measured by DXA scan |
| Areal bone mineral density at the spine, g/cm2 | 4-year visit | Measured by DXA scan |
| Areal bone mineral density at the spine, T-Score | 4-year visit | Measured by DXA scan |
| Areal bone mineral density at the spine, Z-score | 4-year visit | Measured by DXA scan |
| Areal bone mineral density at the distal third of radius, g/cm2 | 4-year visit | Measured by DXA scan |
| Areal bone mineral density at the distal third of radius, T-score | 4-year visit | Measured by DXA scan |
| Areal bone mineral density at the distal third of radius, Z-score | 4-year visit | Measured by DXA scan |
| Trabecular bone score (TBS) at the lumbar spine (L1-L4) (unitless) | 4-year visit | TBS calculated with the software TBSinSight |
| Vertebral Fracture Assessment (VFA) from the T4 to L5 vertebrae to detect the presence of vertebral fracture | 4-year visit | Image acquired by DXA |
| Lean mass (arm, leg, trunk, android, gynoid and total) (g) | 4-year visit | Body composition measured by DXA scan |
| Fat mass (arm, leg, trunk, android, gynoid and total) (g) | 4-year visit | Body composition measured by DXA scan |
| C-terminal cross-linking telopeptide of type I collagen (C-telopeptide, CTX) (ng/mL) | 4-year visit | Bone turnover marker, bone resorption (serum) |
| Procollagen type 1 N-terminal propeptide (P1NP) (ng/mL) | 4-year visit | Bone turnover marker, bone formation (serum) |
| Osteocalcin (ng/mL) | 4-year visit | Bone turnover marker, bone formation (serum) |
| Sclerostin (pmol/mL) | 4-year visit | Inhibitor of bone formation (serum) |
| Change in C-terminal cross-linking telopeptide of type I collagen (C-telopeptide, CTX) (ng/mL) | Between the baseline and the 4-year visit | Bone turnover marker, bone resorption (serum) |
| Change in osteocalcin (ng/mL) | Between the baseline and the 4-year visit | Bone turnover marker, bone formation (serum) |
| Change in procollagen type 1 N-terminal propeptide (P1NP) (ng/mL) | Between the baseline and the 4-year visit | Bone turnover marker, bone formation (serum) |
| Change in sclerostin (pmol/mL) | Between the baseline and the 4-year visit | Inhibitor of bone formation (serum) |
| Skin advanced glycation end-products (AGEs) (arbitrary units) | 4-year visit | Measured with AGEReader (autofluorescence) |
| Glycated hemoglobin (HbA1c, %) | 4-year visit | Diabetes control marker |
| Fasting glucose (mmol/L) | 4-year visit | Blood level measurement |
| Complete blood count | 4-year visit | Blood level measurement |
| Immunoglobulin A (IgA) (g/L) | 4-year visit | Blood level measurement |
| Lipid panel (total cholesterol, LDL-cholesterol, HDL-cholesterol, non-HDL-cholesterol, total cholesterol/HDL-cholesterol ratio, triglycerides, in mmol/L) | 4-year visit | Blood level measurement |
| Creatinine (umol/L) | 4-year visit | Blood level measurement |
| Microalbuminuria (mg/mmol) | 4-year visit | Urine microalbuminuria/ urine creatinine ratio measurement |
| Liver enzymes (AST, ALT) (U/L) | 4-year visit | Blood level measurement |
| Calcium (mmol/L) | 4-year visit | Blood level measurement |
| Albumine (g/L) | 4-year visit | Blood level measurement |
| Phosphate (mmol/L) | 4-year visit | Blood level measurement |
| 25-hydroxyvitamin D3 (nmol/L) | 4-year visit | Blood level measurement |
| Parathormone (PTH) (ng/L) | 4-year visit | Blood level measurement |
| Antitransglutaminase antibodies (U/mL) | 4-year visit | Blood level measurement |
| Sex hormone-binding globulin (SHBG, men) (nmol/L) | 4-year visit | Blood level measurement |
| Thyroid-stimulating hormone (TSH) (mU/L) | 4-year visit | Blood level measurement |
| Insulin like growth factor-1 (IGF-1) (ng/mL) | 4-year visit | Blood level measurement |
| Follicle stimulating hormone (FSH, women) (U/L) | 4-year visit | Blood level measurement |
| Total testosterone (men) (nmol/L) | 4-year visit | Blood level measurement |
| Areal bone mineral density at the femoral neck, g/cm2 | 4-year visit | Measured by DXA scan |
| Areal bone mineral density at the femoral neck, T-Score | 4-year visit | Measured by DXA scan |
| Areal bone mineral density at the femoral neck, Z-Score | 4-year visit | Measured by DXA scan |
| Areal bone mineral density at the total hip, g/cm2 | 4-year visit | Measured by DXA scan |
Countries
Canada
Outcome results
None listed