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

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:

1. Compare bone microarchitecture, bone biomechanical competence, and bone turnover markers as well as postural control in T2D patients with and without fractures.
2. 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

Conditions

• Type 2 Diabetes
• Bone Disease
• Osteoporosis
• Diabetic Neuropathy Peripheral
• Autonomic Neuropathy, Diabetic

Interventions

DIAGNOSTIC_TEST

Dual Energy X-ray Absorbtiometry scan

Evaluation of body composition and bone mass density

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High-resolution peripheral quantitative computed tomography

High-resolution peripheral quantitative computed tomography (HR-pQCT) assesses both volumetric bone mineral density (vBMD) and trabecular and cortical microarchitecture.

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Microindentation

Measures Bone Material Strength Index (BMSi) of cortical bone.

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Thermal perception thresholds

Heat and cold perception thresholds

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Nerve conduction studies

Nerve conduction and amplitude of sural nerve

DIAGNOSTIC_TEST

Composite Autonomic Symptom Score 31

A validated self-assessment questionnaire quantifying the severity and distribution of autonomic symptoms across six domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder and pupillomotor functions) by scoring 31 clinically selected questions

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Skin biopsies with quantification of intra-epidermal nerve fibre density

Skin biopsy

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Perception Threshold Tracking

Transcutaneous stimulation of large and small nerve fibres using weak electrical currents

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Assessment of cardiovascular autonomic neuropathy

Electrocardiographic recordings at rest and during cardiovascular autonomic reflex tests.

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Handgrip strength

Evaluation of muscle strength

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Force plate platform

Evaluation of balance while standing still

DIAGNOSTIC_TEST

Biospecimen collection

Biochemistry including bone turnover markers, glycemic status, inflammation markers i.e

DIAGNOSTIC_TEST

Isometric leg extension strength

Evaluation of muscle strength

DIAGNOSTIC_TEST

Michigan Neuropathy Screening Instrument

MNSI is used to assess status of peripheral neuropathy. It includes two separate assessments: a 15-item self-administered questionnaire and a lower extremity examination that includes inspection and assessment of vibratory sensation and ankle reflexes.

Sponsors & Collaborators

• Aalborg University Hospital

  lead OTHER

Eligibility

Min Age

40 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-02-24

Primary Completion

2026-04-30

Completion

2026-04-30

Countries

• Denmark

Study Locations