Examining bone disease in people with type 2 diabetes and its relation to nerve damage

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

This study looks at how bone disease affects people with type 2 diabetes and whether nerve damage plays a role in their bone health and balance.

Quick facts

• Study type: Observational
• Enrollment: 300 (estimated)
• Ages: 40 Years and up
• Sex: All
• Sponsor: Aalborg University Hospital (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Aalborg)
• Trial ID: NCT05642143 on ClinicalTrials.gov

What this trial studies

This observational study aims to investigate the characteristics of bone disease in individuals with type 2 diabetes (T2D). It will compare bone microarchitecture, biomechanical competence, and turnover markers between T2D patients with and without fractures. Additionally, the study will explore how autonomic and peripheral neuropathy impacts these bone characteristics and postural control. Various examinations, including blood tests, bone scans, and nerve assessments, will be conducted to gather comprehensive data.

Who should consider this trial

Good fit: Ideal candidates include men and women aged 40 and older with a diagnosis of type 2 diabetes and a history of fractures or severe neuropathy.

Not a fit: Patients with severe liver or kidney dysfunction may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and management of bone health in patients with type 2 diabetes.

How similar studies have performed: While there have been studies on diabetes and bone health, this specific approach focusing on deep phenotyping in relation to neuropathy is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Men and women with minimum 40 years of age.
2. Diagnosis of T2D. At least one of the following criteria must be met at diagnosis:

   1. HbA1c ≥ 48 mmol/mol (6,5 %)
   2. Plasma glucose ≥ 11,1 mmol/l
   3. Fasting plasma glucose ≥7,0 mmol/l Clinical effect of oral antidiabetic medication strengthens the diagnosis.
3. Diagnosis of diabetes at least one year prior to inclusion of the study to avoid honeymoon diabetes.
4. A history of fracture(s) (confirmed by radiographs analyzed by radiologist) following the diabetes diagnosis (T2D F+ group)
5. 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)
6. Signed the informed consent.
7. Not defined by the exclusion criteria.

Exclusion Criteria:

1. Severe decreased liver function (Alanin amino-transaminase (ALAT) \>250 U/l, Gamma-Glutamyltransferase (GGT) \>150 U/l).
2. Moderate to severe kidney dysfunction, estimated Glomerular Filtration Rate (eGFR) \<15 mmol/L/1,73m2.
3. Pregnancy or breast feeding.
4. Active malignancy or terminal ill.
5. Previous chemotherapy or immunomodulating treatment
6. Known severe vitamin deficiency
7. Current or previous alcohol- or drug abuse.
8. Not being able to understand Danish written and/or verbally.
9. 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.
10. Participating in other clinical studies utilizing experimental treatment or medication.
11. Subjects with pathologic fractures (defined as fractures due to local tumors, tumor-like lesions, or focal demineralization as visualized on radiographs).
12. Primary hyperparathyroidism, Paget's disease and other metabolic bone diseases, uncontrolled thyrotoxicosis, celiac disease not controlled by diet, known hypogonadism, severe COPD, hypopituitarism, Cushing's disease.
13. Fracture \< 6 month ago
14. Initiation of antiresorptive or bone anabolic drugs \<12 months ago to ensure stable bone turnover markers.
15. History of fractures following the diagnosis of diabetes (T2D F-/N- and T2D N+ groups).
16. History of peripheral or autonomic neuropathy defined by cardiac autonomic reflex tests or severe abnormalities in orthostatic blood pressure (T2D F-/N- group).

Where this trial is running

Aalborg

• Steno Diabetes Center Nordjylland — Aalborg, Denmark (Recruiting)

Study contacts

• Study coordinator: Julie Lindgård Graversen, MD

Conditions Type 2 Diabetes; Bone Disease; Osteoporosis; Diabetic Neuropathy Peripheral; Autonomic Neuropathy, Diabetic