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

• Conditions: Bone Health; Bone Loss; Hyperglycaemia Due to Type 1 Diabetes Mellitus; Diabetes Mellitus, Type 1; Bone Diseases, Metabolic
• Interventions: Diagnostic Test: Clinical tests; Diagnostic Test: Biochemical tests; Diagnostic Test: DXA scan with TBS and VFA; Diagnostic Test: AGEReader

• Registration Number: NCT06351176
• Lead Sponsor: CHU de Quebec-Universite Laval

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2023-07-04
• Status Verified: 2024-04
• Study First Submitted: 2024-04-02
• Study First Submitted QC: 2024-04-02
• Last Update Submitted: 2024-04-02
• Study First Posted: 2024-04-08
• Last Update Posted: 2024-04-08
• Primary Completion: 2024-12-22
• Study Completion: 2025-08-29

Recruitment & Eligibility

• Status: ENROLLING_BY_INVITATION
• Sex: All
• Target Recruitment: 163

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).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Individuals with type 1 diabetes	Clinical tests	-
Healthy controls	Biochemical tests	-
Healthy controls	DXA scan with TBS and VFA	-
Healthy controls	AGEReader	-
Individuals with type 1 diabetes	Biochemical tests	-
Individuals with type 1 diabetes	AGEReader	-
Healthy controls	Clinical tests	-
Individuals with type 1 diabetes	DXA scan with TBS and VFA	-

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
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
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)

Trial Locations

Locations (2)

Centre de recherche du CHU de Québec-Université Laval; 🇨🇦 Quebec City, Quebec, Canada

Institut de recherches cliniques de Montréal (IRCM); 🇨🇦 Montréal, Quebec, Canada