Glycemic Control and Osteohealth in Adults Living with Type 1 Diabetes (GLYCO-OSTEO)

GLYcemic COntrol and OSTEOhealth: Impact of Short-Term Glycemic Control on Skeletal Outcomes in Adults with Type 1 Diabetes

Bone damage is frequently observed in type 1 diabetes, and hyperglycemia is associated with an increased risk of fracture. This pilot study in 25 people living with type 1 diabetes aims to determine whether the introduction of an automated insulin delivery (AID) system improves bone markers through rapide optimization of glycemic control. Measurements will be taken before the start of AID, 2 months and 4 months afterwards.

Study Overview

• Status: Recruiting
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Device: AID

Detailed Description

Background: Bone damage is a frequently overlooked complication of type 1 diabetes (T1D), but significantly increases the risk of fractures as early as childhood. Fractures in individuals with T1D increase the risk of delayed healing, postoperative complications, loss of autonomy, reduced quality of life and even mortality. The pathophysiology of bone alterations in T1D probably differs from that of primary osteoporosis. Studies show lower bone mineral density in T1D, but this is not sufficient to fully explain the risk of fractures. T1D is also characterized by low bone remodeling and altered bone microarchitecture. Although chronic hyperglycemia is a risk factor for fracture in T1DM, the effect of improved glycemic control on bone markers remains unclear. The main hypothesis is that rapid optimization of the glycemic profile (hyperglycemia and variability) may improve bone remodeling in people living with T1DM who have suboptimal glycemic control.

Aim: The primary objective of this pilot study is to quantify the proportion of participants significantly increasing at least one of the serum markers of bone remodeling post-installation of an automated insulin delivery system.

Secondary objectives are to quantify: 1) the magnitude of change in each of the serum markers of bone remodeling pre-intervention and at 2 and 4 months post-intervention; 2) the efficacy of the automated insulin delivery system in terms of glycemic control and variability (mean change in HbA1c and glycemic parameters derived from the continuous glucose monitoring system).

Methods: method: This is a prospective pilot study involving 25 adults aged 18 and over living with T1DM or latent autoimmune diabetes of adults (LADA) who are interested in starting an automated insulin delivery system (artificial pancreas).

This study will involve 3 visits:

1. Visit 1: before installation of the automated insulin delivery system,
2. Visit 2: follow-up at 2 months after installation of the automated insulin delivery system,
3. Visit 3: follow-up at 4 months after installation of the automated insulin delivery system.

During visits 1 and 3, participants will take a blood sample, perform a brief physical examination and complete questionnaires.

During visit 1, participants will also undertake a urine sample, and the research team will conduct a brief interview to obtain information on their diabetes diagnosis, associated complications, and medication use.

During Visit 2: blood sample only.

The project will not interfere with the participant's diabetes management. They will be asked to share a copy of their 14-day continuous glucose monitoring profile during the visit periods.

• Study Type: Observational
• Enrollment (Estimated): 25
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Elisabeth Nguyen; Phone Number: 514-987-5617; Email: elisabeth.nguyen@ircm.qc.ca
• Study Contact Backup: Name: Valérie Boudreau; Phone Number: 514-987-5643; Email: valerie.boudreau@ircm.qc.ca

Study Locations

• Canada
  • Montreal, Canada
    • Recruiting
    • Centre Hospitalier de l'Université de Montréal
    • Contact: Remi Rabasa-Lhoret; Phone Number: 3227 514-987-5500; Email: remi.rabasa-lhoret@ircm.qc.ca
    • Contact: Remi Rabasa-Lhoret
  • Quebec
    • Montréal, Quebec, Canada, H2X 3E4
      • Recruiting
      • CHUM
      • Contact: Rémi Rabasa-Lhoret; Phone Number: 1-514-987-5762; Email: remi.rabasa-lhoret@ircm.qc.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

People living with type 1 diabetes who do not use an automated insulin delivery system but wish to do so. The study takes place around the initiation of AID.

Description

Inclusion Criteria:

• Age ≥ 18 years;
• Diagnosis of T1D or latent autoimmune diabetes of adults (LADA) for at least one year;
• Current HbA1c >8.0% and high glycemic variability (CV >36.0% using CGM);
• Participant planning to start using one of the commercially available AID;
• Anticipated use of the closed-loop mode;
• Willing to share CGM data during the study period.

Exclusion Criteria:

• Woman who was pregnant, gave birth or breastfed less than 6 months before the beginning of the study or who plans to become pregnant during the study;
• Conditions affecting bone turnover markers, such as chronic kidney disease (estimated GFR <30 ml/min), liver disease, intestinal malabsorption including celiac disease, organ transplant, active cancer, rheumatoid arthritis, and endocrinopathies (active hyperthyroidism, uncontrolled hypothyroidism with abnormal TSH, parathyroid disease, hypogonadism, Cushing syndrome, adrenal insufficiency and acromegaly);
• Anticipated therapeutic change and/or type of CGM sensor, insulin pump, or AID during the study period;
• Anticipated need to use acetaminophen during the study period at a dose above 1g every 6 hours;
• Current or anticipated use of hydroxyurea;
• Intake in the past 12 months of drugs influencing bone turnover markers, such as oral or intra-articular glucocorticoids (≥ 7.5 mg daily Prednisone or equivalent during ≥ 3 months or ≥ four intra-articular glucocorticoid infiltrations in the past year), aromatase inhibitor therapy for breast cancer and anti-androgen therapy for prostate cancer, anticoagulants, SGLT-2 inhibitors, thiazolidinediones, and anti-osteoporosis drugs;
• Unable to consent.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
AID initiation; The participants will be selected on the basis that they are planning to start using one of the commercially available AID. They will start treatment after the initial measurements (baseline), then repeat the measurements at 2 and 4 months post-AID.	Device: AID; Initiation of an automated insulin delivery system

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone remodeling improvement	The proportion of participants increasing at least one of the serum bone turnover markers above the least significant change (>43% for CTX, >25.49% for procollagen type 1 N-terminal propeptide (P1NP) and >25.65% for osteocalin).	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Carboxy-terminal collagen crosslinks change	Magnitude of the change and the variance for CTX	2 months
Carboxy-terminal collagen crosslinks change	Magnitude of the change and the variance for CTX	4 months
N-terminal propeptide (P1NP) change	Magnitude of the change and the variance for P1NP	2 months
N-terminal propeptide (P1NP) change	Magnitude of the change and the variance for P1NP	4 months
Osteocalin change	Magnitude of the change and the variance for Osteocalin	2 months
Osteocalin change	Magnitude of the change and the variance for Osteocalin	4 months
HbA1c change	Mean change of glycated hemoglobin (HbA1c)	2 months
HbA1c change	Mean change of glycated hemoglobin (HbA1c)	4 months

Collaborators and Investigators

• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Collaborators: Institut de Recherches Cliniques de Montreal; Laval University
• Investigators: Principal Investigator: Rémi Rabasa-Lhoret, MD, PhD, IRCM

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: November 28, 2023
• First Submitted That Met QC Criteria: November 28, 2023
• First Posted (Actual): December 6, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 24, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Type 1 Diabetes; Bone Health; Automated Insulin Delivery
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: MP-02-2024-11708

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No