Clinical trial NCT01870557: Markers of Bone Status in Diabetes Mellitus (Type 1 and Type 2)
Official title: Markers of Bone Status in Diabetes Mellitus (Type 1 and Type 2)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetes Mellitus
Osteoporosis
Osteopenia
Keywords: Diabetes Mellitus
Bone
Bone Status
Glycemic Markers
Osteoporosis
Osteopenia
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2013-06-06
Enrollment: 197
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: 200 Diabetes Mellitus patients. 100 with type 1 diabetes and 100 with type 2 diabetes. Of the 100 type 2 diabetes patients half should be treated with insulin (n=50) and the other half treated with other oral antidiabetics and not insulin.

Brief summary: Objective To collate the bone status in type 1 and type 2 diabetics using biochemical markers and bone scans.

Methods:

This is a multicenter trial involving the University Hospitals of three major danish cities: Aalborg, Aarhus and Odense. The trial is of cross-sectional design and consists of examinations including:

* Blood samples to analyze bone markers, glycemic state, kidney function and sex-hormones.
* 24 hour urine sample to analyze bone markers and kidney function.
* 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.

Participants:

100 type 1 diabetics and 100 type 2 diabetics recruited from outpatient clinics at Aalborg, Aarhus and Odense, general practitioners and flyers.

Detailed description: Diabetes Mellitus and Osteoporosis are common conditions. Patients with Diabetes Mellitus are known to have more fractures than their non-diabetic counterparts. However bone mineral density (BMD) which is the most commonly used measure of fracture risk seems to be insensitive in diabetes, thus BMD is lowered in type 1 diabetes but not enough to explain an almost seven fold in fracture risk. BMD is increased in type 2 diabetes although they still have an increased fracture risk.

The investigators investigate this paradox in diabetes by assessing type 1 and type 2 diabetes patients bone status by blood- and urine samples (assessing markers of bone- and glycemic state) and two types of bone scans comprising of DXA and HRpQCT scan.

The diabetes mellitus patients are recruited from outpatients clinics in the three study sites (Aalborg, Aarhus and Odense) as well as general practitioners and by flyers and adds.

Eligibility criteria: Inclusion Criteria:

* Type 1 or type 2 diabetes.
* Age ≥ 50 years.
* Unaltered treatment of diabetes during the previous six months (no changes in drugs, but an increase or decrease in dose is accepted) and HbA1c is stable with a level of ± 1 in the same period.
* HbA1c level≥ 7 % through the previous six months.
* BMI between 19 og 35.

Specific inclusion criteria for type 2 diabetes:

* Either treatment with metformin, sulfonylureas, dipeptidyl peptidase IV (DPP IV) inhibitors or glucagon-like peptide 1 (GLP-1) analogs.
* Treatment with insulin and insulin in the combination with metformin, sulfonylureas, DPP IV inhibitors or GLP-1 analogs.

Exclusion Criteria:

* HbA1C \> 10%
* Pregnancy.
* Metal implanted at both ankles and wrists.
* Patients treated with: Antiresorptive (incl. hormone replacement therapy) or bone anabolic treatment, glucocorticoids, lithium and anticonvulsives.
* Patients with a bone disease other than osteoporosis.
* Vertebral fracture visible by vertebral fracture assessment (VFA).
* Patients with renal disease defined by estimated glomerular filtration rate(eGFR) \< 50.
* Other medical disease in unstable phase (fx. cancer, hyperthyroidism).
* Heart failure; New York Heart Association (NYHA) class IV.
* Patients which the investigator does not believe is fit to participate in the study

Primary outcomes:
measure: HbA1c
timeFrame: Baseline
measure: Bone Mineral Density (t-score)
timeFrame: Baseline
Secondary outcomes:
measure: Biochemical Bone Markers
timeFrame: Baseline
measure: Sex-hormones
timeFrame: Baseline
measure: Electrolytes
timeFrame: Baseline
measure: Vitamin D (25ODH /1,25OHD)
timeFrame: Baseline
measure: Results from the HRpQCT scan including Trabecular and Cortical state
timeFrame: Baseline
measure: Markers of fat tissue and glycemic status
timeFrame: Baseline
measure: Verterbral fracture assessment
timeFrame: Baseline
measure: Lifestyle and Medical history
timeFrame: Baseline
Other outcomes:
measure: urine creatinine albumin ratio
timeFrame: Baseline
Locations:
city: Aalborg
country: Denmark
facility: Department of Endocrinology, Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Department of Endocrinology and Internal Medicine, Aarhus University Hospital
Study officials:
affiliation: Aalborg University Hospital
name: Peter Vestergaard, Professor MD PhD DrMedSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Odense University Hospital
name: Kim Brixen, Professor MD PhD DrMedSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Aarhus University Hospital
name: Søren Gregersen, MD PhD
role: STUDY_CHAIR
affiliation: Aarhus University Hospital
name: Bente Lomholt Langdahl, Professor MD PhD DrMedSc
role: STUDY_CHAIR
affiliation: Aarhus University Hospital
name: Ellen-Magrethe Hauge, MD PhD
role: STUDY_CHAIR
References:
citation: Starup-Linde JK, Viggers R, Langdahl B, Gregersen S, Lykkeboe S, Handberg A, Vestergaard P. Associations of Circulating Osteoglycin With Bone Parameters and Metabolic Markers in Patients With Diabetes. Front Endocrinol (Lausanne). 2021 Mar 15;12:649718. doi: 10.3389/fendo.2021.649718. eCollection 2021.
citation: Starup-Linde J, Lykkeboe S, Gregersen S, Hauge EM, Langdahl BL, Handberg A, Vestergaard P. Bone Structure and Predictors of Fracture in Type 1 and Type 2 Diabetes. J Clin Endocrinol Metab. 2016 Mar;101(3):928-36. doi: 10.1210/jc.2015-3882. Epub 2016 Jan 12.
citation: Starup-Linde J, Lykkeboe S, Gregersen S, Hauge EM, Langdahl BL, Handberg A, Vestergaard P. Differences in biochemical bone markers by diabetes type and the impact of glucose. Bone. 2016 Feb;83:149-155. doi: 10.1016/j.bone.2015.11.004. Epub 2015 Nov 10.