Clinical trial NCT06351176: Impact of Glycemic Control on Skeletal Outcomes in Adults With Type 1 Diabetes
Official title: Impact of Glycemic Control on Skeletal Outcomes in Adults With Type 1 Diabetes : DenSiFy (Diabetes Spine Fractures) Cohort
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Diabetes Mellitus, Type 1
Bone Health
Bone Loss
Bone Diseases, Metabolic
Hyperglycaemia Due to Type 1 Diabetes Mellitus
Lead sponsor: CHU de Quebec-Universite Laval
Sponsor class: OTHER
Collaborators: name: Diabetes Canada
First posted: 2024-04-08
Enrollment: 163
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 127 individuals with type 1 diabetes and 65 healthy subjects from the DenSiFy (Diabetes Spine Fractures) study (NCT04064437)

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.


Eligibility 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.

Exclusion Criteria :

* As above (as individuals with diabetes), and :
* Diagnosis of diabetes or prediabetes;
* Celiac disease;
* Chronic kidney disease (CrCl \< 60 mL/min).

Primary outcomes:
measure: Change in areal bone mineral density (aBMD) at the femoral neck in g/cm2
timeFrame: Between the baseline and the 4-year visit
Secondary outcomes:
measure: Change in areal bone mineral density (aBMD) at the spine in g/cm2
timeFrame: Between the baseline and the 4-year visit
measure: Change in areal bone mineral density (aBMD) at the total hip in g/cm2
timeFrame: Between the baseline and the 4-year visit
measure: Change in areal bone mineral density (aBMD) at the distal third of radius in g/cm2
timeFrame: Between the baseline and the 4-year visit
measure: Change in Trabecular bone score (TBS) (unitless)
timeFrame: Between the baseline and the 4-year visit
measure: Glycemic control, assessed with mean glycated hemoglobin (HbA1c) of the past 7 years
timeFrame: 4-year visit
measure: Glycemic control, assessed with skin advanced glycation end products (AGEs)
timeFrame: 4-year visit
measure: Presence of a microvascular complication (neuropathy, nephropathy, retinopathy)
timeFrame: 4-year visit
Other outcomes:
measure: Areal bone mineral density at the femoral neck, g/cm2
timeFrame: 4-year visit
measure: Areal bone mineral density at the femoral neck, T-Score
timeFrame: 4-year visit
measure: Areal bone mineral density at the femoral neck, Z-Score
timeFrame: 4-year visit
measure: Areal bone mineral density at the total hip, g/cm2
timeFrame: 4-year visit
measure: Areal bone mineral density at the total hip, T-score
timeFrame: 4-year visit
measure: Areal bone mineral density at the total hip, Z-score
timeFrame: 4 year visit
measure: Areal bone mineral density at the spine, g/cm2
timeFrame: 4-year visit
measure: Areal bone mineral density at the spine, T-Score
timeFrame: 4-year visit
measure: Areal bone mineral density at the spine, Z-score
timeFrame: 4-year visit
measure: Areal bone mineral density at the distal third of radius, g/cm2
timeFrame: 4-year visit
measure: Areal bone mineral density at the distal third of radius, T-score
timeFrame: 4-year visit
measure: Areal bone mineral density at the distal third of radius, Z-score
timeFrame: 4-year visit
measure: Trabecular bone score (TBS) at the lumbar spine (L1-L4) (unitless)
timeFrame: 4-year visit
measure: Vertebral Fracture Assessment (VFA) from the T4 to L5 vertebrae to detect the presence of vertebral fracture
timeFrame: 4-year visit
measure: Lean mass (arm, leg, trunk, android, gynoid and total) (g)
timeFrame: 4-year visit
measure: Fat mass (arm, leg, trunk, android, gynoid and total) (g)
timeFrame: 4-year visit
measure: C-terminal cross-linking telopeptide of type I collagen (C-telopeptide, CTX) (ng/mL)
timeFrame: 4-year visit
measure: Procollagen type 1 N-terminal propeptide (P1NP) (ng/mL)
timeFrame: 4-year visit
measure: Osteocalcin (ng/mL)
timeFrame: 4-year visit
measure: Sclerostin (pmol/mL)
timeFrame: 4-year visit
measure: Change in C-terminal cross-linking telopeptide of type I collagen (C-telopeptide, CTX) (ng/mL)
timeFrame: Between the baseline and the 4-year visit
measure: Change in osteocalcin (ng/mL)
timeFrame: Between the baseline and the 4-year visit
measure: Change in procollagen type 1 N-terminal propeptide (P1NP) (ng/mL)
timeFrame: Between the baseline and the 4-year visit
measure: Change in sclerostin (pmol/mL)
timeFrame: Between the baseline and the 4-year visit
measure: Skin advanced glycation end-products (AGEs) (arbitrary units)
timeFrame: 4-year visit
measure: Glycated hemoglobin (HbA1c, %)
timeFrame: 4-year visit
measure: Fasting glucose (mmol/L)
timeFrame: 4-year visit
measure: Complete blood count
timeFrame: 4-year visit
measure: Thyroid-stimulating hormone (TSH) (mU/L)
timeFrame: 4-year visit
measure: Lipid panel (total cholesterol, LDL-cholesterol, HDL-cholesterol, non-HDL-cholesterol, total cholesterol/HDL-cholesterol ratio, triglycerides, in mmol/L)
timeFrame: 4-year visit
measure: Creatinine (umol/L)
timeFrame: 4-year visit
measure: Microalbuminuria (mg/mmol)
timeFrame: 4-year visit
measure: Liver enzymes (AST, ALT) (U/L)
timeFrame: 4-year visit
measure: Calcium (mmol/L)
timeFrame: 4-year visit
measure: Albumine (g/L)
timeFrame: 4-year visit
measure: Phosphate (mmol/L)
timeFrame: 4-year visit
measure: 25-hydroxyvitamin D3 (nmol/L)
timeFrame: 4-year visit
measure: Parathormone (PTH) (ng/L)
timeFrame: 4-year visit
measure: Antitransglutaminase antibodies (U/mL)
timeFrame: 4-year visit
measure: Immunoglobulin A (IgA) (g/L)
timeFrame: 4-year visit
measure: Insulin like growth factor-1 (IGF-1) (ng/mL)
timeFrame: 4-year visit
measure: Follicle stimulating hormone (FSH, women) (U/L)
timeFrame: 4-year visit
measure: Total testosterone (men) (nmol/L)
timeFrame: 4-year visit
measure: Sex hormone-binding globulin (SHBG, men) (nmol/L)
timeFrame: 4-year visit
Locations:
city: Montréal
country: Canada
facility: Institut de recherches cliniques de Montréal (IRCM)
state: Quebec
city: Quebec City
country: Canada
facility: Centre de recherche du CHU de Québec-Université Laval
state: Quebec
Study officials:
affiliation: CHU de Québec- Université Laval
name: Claudia Gagnon, MD
role: PRINCIPAL_INVESTIGATOR
References: