Deep Phenotyping of Bone Disease in Type 2 Diabetes and Relations to Diabetic Neuropathy

Aalborg University Hospital1 site in 1 country300 target enrollmentFebruary 24, 2023

ConditionsType 2 Diabetes Bone Disease Osteoporosis Diabetic Neuropathy Peripheral Autonomic Neuropathy, Diabetic

Overview

Phase: Not Applicable
Intervention: Not specified
Conditions: Type 2 Diabetes
Sponsor: Aalborg University Hospital
Enrollment: 300
Locations: 1
Primary Endpoint: Evaluation of differences in bone turnover markers between T2D patients with and without previous fractures by biochemical analysis of different bone markers (CTX, P1NP, osteocalcin (OC), ucOC, sclerostin, osteoglycin and osteopontin).
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

Objectives:

The goal of this cross sectional clinical trial is to examine the phenotype of bone disease in type 2 diabetes.The main aims are to:

Compare bone microarchitecture, bone biomechanical competence, and bone turnover markers as well as postural control in T2D patients with and without fractures.
Examine how autonomic and peripheral neuropathy affects bone microarchitecture, bone material strength and bone turnover markers as well as postural control in T2D.

Methods:

The trial is of cross-sectional design and consists of examinations including

Blood samples to analyze bone markers, glycemic state i.e.
Bone scans including dual energy x-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HRpQCT) to evaluate Bone Mineral Density, t-score and bone structure.
Microindentation to evaluate bone material strength
Skin autofluorescence to measure levels of advanced glycation endproducts (AGEs) in the skin
Assesment of nerve function (peripheral and autonomic)
Assesment of postural control, muscle strength and gait

Participants:

A total of 300 type 2 diabetes patients divided to three groups:

160 with no history of fractures or diabetic neuropathy
100 with a history of fracture(s)
40 with autonomic neuropathy or severe peripheral neuropathy

Registry

clinicaltrials.gov

Start Date

February 24, 2023

End Date

April 2026

Last Updated

2 years ago

Study Type

Observational

Sex

All

Investigators

Sponsor

Aalborg University Hospital

Responsible Party

Principal Investigator

Julie Lindgård Nielsen

Principal Investigator

Aalborg University Hospital

Eligibility Criteria

Inclusion Criteria

•Men and women with minimum 40 years of age.
•Diagnosis of T2D. At least one of the following criteria must be met at diagnosis:
•HbA1c ≥ 48 mmol/mol (6,5 %)
•Plasma glucose ≥ 11,1 mmol/l
•Fasting plasma glucose ≥7,0 mmol/l Clinical effect of oral antidiabetic medication strengthens the diagnosis.
•Diagnosis of diabetes at least one year prior to inclusion of the study to avoid honeymoon diabetes.
•A history of fracture(s) (confirmed by radiographs analyzed by radiologist) following the diabetes diagnosis (T2D F+ group)
•Diagnosed with severe peripheral (VPT ≥ 50) or autonomic neuropathy defined by cardiac autonomic reflex tests or severe abnormalities in orthostatic blood pressure (T2D N+ group)
•Signed the informed consent.
•Not defined by the exclusion criteria.

Exclusion Criteria

•Severe decreased liver function (Alanin amino-transaminase (ALAT) \>250 U/l, Gamma-Glutamyltransferase (GGT) \>150 U/l).
•Moderate to severe kidney dysfunction, estimated Glomerular Filtration Rate (eGFR) \<15 mmol/L/1,73m
•Pregnancy or breast feeding.
•Active malignancy or terminal ill.
•Previous chemotherapy or immunomodulating treatment
•Known severe vitamin deficiency
•Current or previous alcohol- or drug abuse.
•Not being able to understand Danish written and/or verbally.
•Terms according to investigators judgement that makes subjects unsuitable to participate including lack of ability to understand and comply with instructions and/or reduced physical ability, limiting the ability to participate in the examinations.
•Participating in other clinical studies utilizing experimental treatment or medication.

Outcomes

Primary Outcomes

Evaluation of differences in bone turnover markers between T2D patients with and without previous fractures by biochemical analysis of different bone markers (CTX, P1NP, osteocalcin (OC), ucOC, sclerostin, osteoglycin and osteopontin).

Time Frame: Through study completion, estimated 3.5 years

Evaluation of differences in bone microarchitecture between T2D patients with and without previous fractures assessed by HRpQCT.

Time Frame: Through study completion, estimated 3.5 years

Bone microarchitecture is a composite outcome assessed by HRpQCT at radius and tibia: Total volumetric mineral density, Trabecular volumetric mineral density, Cortical volumetric mineral density, Trabecular number, Trabecular thickness, Cortical thickness, Trabecular separation, Cortical porosity, bone stiffness and failure load.

Differences in Bone material strength index (BMSi) between T2D patients with and without previous fractures measured by microindentation.

Time Frame: Through study completion, estimated 3.5 years

Secondary Outcomes

The impact of autonomic neuropathy on bone material strength in T2D assessed by microindentation.(Through study completion, estimated 3.5 years)
The impact of autonomic neuropathy on bone turnover markers in T2D.(Through study completion, estimated 3.5 years)
The impact of peripheral neuropathy on bone turnover markers in T2D.(Through study completion, estimated 3.5 years)
Compare muscle mass and strength in T2D patients with and without neuropathy(Through study completion, estimated 3.5 years)
Compare postural control between T2D patients with and without fractures assessed by force platform.(Through study completion, estimated 3.5 years)
Compare muscle mass and strength in T2D patients with and without fractures(Through study completion, estimated 3.5 years)
The impact of autonomic neuropathy on bone microarchitecture in T2D assessed by HR-pQCT.(Through study completion, estimated 3.5 years)
The impact of peripheral neuropathy on bone microarchitecture in T2D assessed by HR-pQCT.(Through study completion, estimated 3.5 years)
The impact of peripheral neuropathy on bone material strength in T2D assessed by microindentation.(Through study completion, estimated 3.5 years)
Compare postural control between T2D patients with and without peripheral/autonomic neuropathy.(Through study completion, estimated 3.5 years)