Impact of Glycemic Control on Skeletal Outcomes in Adults With Type 1 Diabetes

Diabetes Mellitus, Type 1 Clinical Trial

— DenSiFy cohort  

Official title:

Impact of Glycemic Control on Skeletal Outcomes in Adults With Type 1 Diabetes : DenSiFy (Diabetes Spine Fractures) Cohort

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06351176
• Other study ID #: 2024-6819
• Status: Enrolling by invitation
• Start date: July 4, 2023
• Est. completion date: August 29, 2025

Study information

• Verified date: April 2024
• Source: CHU de Quebec-Universite Laval
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 163
• Est. completion date: August 29, 2025
• Est. primary completion date: December 22, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Bone Diseases
• Bone Diseases, Metabolic
• Bone Health
• Bone Loss
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Hyperglycemia
• Metabolic Diseases

Intervention

Diagnostic Test:
• Clinical tests
The investigators perform the following clinical tests: vibration threshold test, monofilament test, and height, weight and waist circumference measurement in every participant.
• Biochemical tests
The investigators perform blood and urine tests in every participant.
• DXA 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.
• AGEReader
The investigators perform a skin advanced glycation end products (AGEs) measurement with the AGE Reader machine in every participant.

Locations

Country	Name	City	State
Canada	Institut de recherches cliniques de Montréal (IRCM)	Montréal	Quebec
Canada	Centre de recherche du CHU de Québec-Université Laval	Quebec City	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
CHU de Quebec-Universite Laval	Diabetes Canada

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Areal bone mineral density at the femoral neck, g/cm2	Measured by DXA scan	4-year visit
Other	Areal bone mineral density at the femoral neck, T-Score	Measured by DXA scan	4-year visit
Other	Areal bone mineral density at the femoral neck, Z-Score	Measured by DXA scan	4-year visit
Other	Areal bone mineral density at the total hip, g/cm2	Measured by DXA scan	4-year visit
Other	Areal bone mineral density at the total hip, T-score	Measured by DXA scan	4-year visit
Other	Areal bone mineral density at the total hip, Z-score	Measured by DXA scan	4 year visit
Other	Areal bone mineral density at the spine, g/cm2	Measured by DXA scan	4-year visit
Other	Areal bone mineral density at the spine, T-Score	Measured by DXA scan	4-year visit
Other	Areal bone mineral density at the spine, Z-score	Measured by DXA scan	4-year visit
Other	Areal bone mineral density at the distal third of radius, g/cm2	Measured by DXA scan	4-year visit
Other	Areal bone mineral density at the distal third of radius, T-score	Measured by DXA scan	4-year visit
Other	Areal bone mineral density at the distal third of radius, Z-score	Measured by DXA scan	4-year visit
Other	Trabecular bone score (TBS) at the lumbar spine (L1-L4) (unitless)	TBS calculated with the software TBSinSight	4-year visit
Other	Vertebral Fracture Assessment (VFA) from the T4 to L5 vertebrae to detect the presence of vertebral fracture	Image acquired by DXA	4-year visit
Other	Lean mass (arm, leg, trunk, android, gynoid and total) (g)	Body composition measured by DXA scan	4-year visit
Other	Fat mass (arm, leg, trunk, android, gynoid and total) (g)	Body composition measured by DXA scan	4-year visit
Other	C-terminal cross-linking telopeptide of type I collagen (C-telopeptide, CTX) (ng/mL)	Bone turnover marker, bone resorption (serum)	4-year visit
Other	Procollagen type 1 N-terminal propeptide (P1NP) (ng/mL)	Bone turnover marker, bone formation (serum)	4-year visit
Other	Osteocalcin (ng/mL)	Bone turnover marker, bone formation (serum)	4-year visit
Other	Sclerostin (pmol/mL)	Inhibitor of bone formation (serum)	4-year visit
Other	Change in C-terminal cross-linking telopeptide of type I collagen (C-telopeptide, CTX) (ng/mL)	Bone turnover marker, bone resorption (serum)	Between the baseline and the 4-year visit
Other	Change in osteocalcin (ng/mL)	Bone turnover marker, bone formation (serum)	Between the baseline and the 4-year visit
Other	Change in procollagen type 1 N-terminal propeptide (P1NP) (ng/mL)	Bone turnover marker, bone formation (serum)	Between the baseline and the 4-year visit
Other	Change in sclerostin (pmol/mL)	Inhibitor of bone formation (serum)	Between the baseline and the 4-year visit
Other	Skin advanced glycation end-products (AGEs) (arbitrary units)	Measured with AGEReader (autofluorescence)	4-year visit
Other	Glycated hemoglobin (HbA1c, %)	Diabetes control marker	4-year visit
Other	Fasting glucose (mmol/L)	Blood level measurement	4-year visit
Other	Complete blood count	Blood level measurement	4-year visit
Other	Thyroid-stimulating hormone (TSH) (mU/L)	Blood level measurement	4-year visit
Other	Lipid panel (total cholesterol, LDL-cholesterol, HDL-cholesterol, non-HDL-cholesterol, total cholesterol/HDL-cholesterol ratio, triglycerides, in mmol/L)	Blood level measurement	4-year visit
Other	Creatinine (umol/L)	Blood level measurement	4-year visit
Other	Microalbuminuria (mg/mmol)	Urine microalbuminuria/ urine creatinine ratio measurement	4-year visit
Other	Liver enzymes (AST, ALT) (U/L)	Blood level measurement	4-year visit
Other	Calcium (mmol/L)	Blood level measurement	4-year visit
Other	Albumine (g/L)	Blood level measurement	4-year visit
Other	Phosphate (mmol/L)	Blood level measurement	4-year visit
Other	25-hydroxyvitamin D3 (nmol/L)	Blood level measurement	4-year visit
Other	Parathormone (PTH) (ng/L)	Blood level measurement	4-year visit
Other	Antitransglutaminase antibodies (U/mL)	Blood level measurement	4-year visit
Other	Immunoglobulin A (IgA) (g/L)	Blood level measurement	4-year visit
Other	Insulin like growth factor-1 (IGF-1) (ng/mL)	Blood level measurement	4-year visit
Other	Follicle stimulating hormone (FSH, women) (U/L)	Blood level measurement	4-year visit
Other	Total testosterone (men) (nmol/L)	Blood level measurement	4-year visit
Other	Sex hormone-binding globulin (SHBG, men) (nmol/L)	Blood level measurement	4-year visit
Primary	Change in areal bone mineral density (aBMD) at the femoral neck in g/cm2	aBMD measured by DXA scan	Between the baseline and the 4-year visit
Secondary	Change in areal bone mineral density (aBMD) at the spine in g/cm2	aBMD measured by DXA scan	Between the baseline and the 4-year visit
Secondary	Change in areal bone mineral density (aBMD) at the total hip in g/cm2	aBMD measured by DXA scan	Between the baseline and the 4-year visit
Secondary	Change in areal bone mineral density (aBMD) at the distal third of radius in g/cm2	aBMD measured by DXA scan	Between the baseline and the 4-year visit
Secondary	Change in Trabecular bone score (TBS) (unitless)	TBS with the software TBSinSight	Between the baseline and the 4-year visit
Secondary	Glycemic control, assessed with mean glycated hemoglobin (HbA1c) of the past 7 years	Mean HbA1c of the past 7 years from all the available HbA1c in the medical record	4-year visit
Secondary	Glycemic control, assessed with skin advanced glycation end products (AGEs)	Skin AGEs measured with AGEReader (autofluorescence)	4-year visit
Secondary	Presence of a microvascular complication (neuropathy, nephropathy, retinopathy)	From the information available in the medical record and from monofilament and vibration testing (for neuropathy) and from microalbuminuria (nephropathy)	4-year visit