the Type ONe dIabetic Bone Collaboration Study

In this cross-sectional clinical study, we will examine the bones of 111 Type 1 Diabetes (T1D) patients and 37 age-matched healthy controls with the aim of describing a T1D Bone Phenotype. The main Objectives of the study is a) to determine if the material properties of the bones are affected in diabetic bone disease and b) to determine if the mitochondrial function in osteoclasts and osteoblasts is impaired in T1D. Secondary end points are c) to establishment of the T1D bone phenotype and d) to investigate if mitochondrial dysfunction in T1D bone cells correlates to changes in gene expression, gene activity, bone remodelling, bone density, microarchitecture, geometry and material properties. Furthermore, in terms of contributing to knowledge on etiology and pathology of type one diabetic bone disease, we will study the predictory value of muscle mass in T1D patients and controls, as well as other characteristics such as heart rate variability (HRV) and AGE content. Furthermore, we will study the epidemiology of osteoporosis and fractures in Danish T1D patients.To assess the material properties of the bones, we will measure the bone mass density (BMD), use High Resolution peripheral Quantitative Computed Tomography (HRpQCT) for assessment of the microarchitecture and finite element analysis of bone strength, and by microindentation, we will obtain direct measures of the strength of the cortical bone of the tibia. Further we will measure bone turnover markers and circulating microRNA and in a subgroup of participants (24 T1D, 12 controls) bone samples will be retrieved for examination of bone histomorphometry (structural and static parameters) and cell samples from blood and bone marrow will be used for in vitro experiments focused on cell differentiation mitochondrial function, as hyperglycemia may affect mitochondrial function. Finally measures of some possible predictors of bone fragility in subjects with T1D are examined (sarcopenia, skin advanced glycation end products (AGE) content, autonomic neuropathy)

Inclusion Criteria:T1D subjects: Clinical diagnosis of T1D <18 years of age, C-peptide <200 pmol L-1 at any time point.Controls: HbA1c <44 mmol mol-1Exclusion Criteria:BMI < 18.5 kg/m2Primary hyperparathyroidism and other calcium metabolic conditionsPaget's disease and other metabolic bone diseasesVitamin D <25 nM (re-test after vitamin D replacement acceptable)Known disorders affecting bone metabolism, e.g. uncontrolled thyrotoxicosis, chronic kidney disease (eGFR <30 ml min-1), liver dysfunction (alkaline phosphatase higher than twice the upper limit), celiac disease not controlled by diet, known hypogonadism, severe chronic obstructive pulmonary disease, hypopituitarism and Cushing's diseaseAntiresorptive or bone metabolic drugs for the last 12 monthsUse of anabolic steroids in the last 12 monthsHistory of pancreatitisAllergy to the medicines usedInability to give informed consentPregnancy