Abnormal Structure and Bone Density in Diabetes
Condition: Type 1 Diabetes; Type 2 Diabetes
MeSH terms: Diabetes Mellitus
Study type: Interventional

Summary: 
      Assumptions and Objectives: The working hypotheses are: 1 - subjects with type 1 diabetes and
      / or type 2, compared to subjects without diabetes are at risk for osteopenia and / or
      abnormal bone structure the foot (calcaneus and ankle) can lead to bone deformities,
      fractures and final stage of Charcot foot. These anomalies are favored by the presence of
      peripheral neuropathy and plasma levels of advanced glycation end products higher than in
      diabetic subjects without bone abnormalities.

      The objectives of this research are to evaluate these anomalies quantitative and qualitative
      bone in the foot (calcaneus and ankle) through the use of MicroScanner. In parallel a whole
      body bone mineral density (BMD) and calcaneal ultrasound will be performed to measure bone
      mineral density as realized in clinical practice in a defined population of patients with
      type 1 or type 2. These bone abnormalities will be correlated with the presence of peripheral
      neuropathy and the rate of advanced glycation end products of proteins and reference to
      parameters of chronic inflammation and oxidative stress to better understand the
      pathophysiology and target a population at risk.

      The importance of this study is paramount in the management of diabetic foot. Indeed for the
      moment we are dealing primarily the consequences of diabetes impact bone when bone
      deformities have appeared with their attendant disability and the risk of recurrent
      infections in areas of friction in this fragile environment. The ultimate goal is to target
      people with diabetes have abnormal bone subclinical and take care to avoid changes to bone
      deformities and find ways to treat them.
    

Detailed description: 
      The population studies on subjects with type 1 and 2 diabetes have revealed a fracture risk
      multiplied by 4 to 12, especially at the shoulder, hip, ankle and foot, compared to a
      population of non-diabetic subjects matched for age and sex.

      If osteopenia (decreased bone mineral density) is consistently associated with fracture risk
      in diabetic patients with type 1 diabetes type 2 often have a bone mineral density comparable
      or superior to non diabetes subjects.

      The various causes mentioned in this alteration of the quantity and bone quality in the
      context of chronic hyperglycemia is a disturbance of the interaction between osteoblasts
      (cells forming bone) and osteoclasts (cells that resorb bone), partly mediated by the system
      RANK / RANK-L / osteoprotegerin with decreased bone formation and increased osteolyses. The
      peripherical neuropathy, the glycation proteins (modifications of proteins by addition of
      glucose) and the receptor of glycation proteins are directly involved.

      At the foot, these changes in the bones (osteopenia and decreased bone quality) are
      responsible for deformations observed in some diabetic subjects, resulting in the formation
      of "Charcot foot" and the risk of sores and amputation as a major disability cause. Few
      studies have examined the abnormalities that we could find at the foot of the diabetic
      patients before the development of deformities observed in the Charcot foot. One study looked
      at bone mineral density measured by ultrasound at the Charcot foot and the contralateral foot
      in subjects with type 1 or type 2 compared to subjects with no diabetic Charcot foot. The
      authors found a decrease in bone density measured by ultrasound at the Charcot foot compared
      with the contralateral foot in subjects with type 1 and type 2. Bone density at the
      contralateral foot was reduced compared with control subjects with diabetes only in subjects
      with type 1 diabetes but not in patients with type 2 diabetes. The link with the peripheral
      neuropathy is not clear. A second study in women with type 1 diabetes in premenopausal also
      found a decrease in bone density at the calcaneus measured by ultrasound compared with women
      without diabetes. None of these studies focused on the local structure of the bone. Yet we
      may suspect that hyperglycemia, including glycation of proteins may cause structural changes
      in the bone of diabetic subjects. Previously, it was difficult to understand the structure of
      bone by non-invasive, the MicroScanner developed by the Scanco company can measure bone
      density and trabecular architecture of the wrist and ankle with a discrimination of 42
      microns . He does a minimal radiation (3 microsV) and allows a resolution of 80 microns. It
      has already been used in osteopenic women and showed significant differences in terms of bone
      architecture between women with fracture and those who do not.

      Assumptions and Objectives: The working hypotheses are: 1 - subjects with type 1 diabetes and
      / or type 2, compared to subjects without diabetes are at risk for osteopenia and / or
      abnormal bone structure the foot (calcaneus and ankle) can lead to bone deformities,
      fractures and final stage of Charcot foot. These anomalies are favored by the presence of
      peripheral neuropathy and plasma levels of advanced glycation end products higher than in
      diabetic subjects without bone abnormalities.

      The objectives of this research are to evaluate these anomalies quantitative and qualitative
      bone in the foot (calcaneus and ankle) through the use of MicroScanner. In parallel a whole
      body BMD and calcaneal ultrasound will be performed to measure bone mineral density as
      realized in clinical practice in a defined population of patients with type 1 or type 2.
      These bone abnormalities will be correlated with the presence of peripheral neuropathy and
      the rate of advanced glycation end products of proteins and reference to parameters of
      chronic inflammation and oxidative stress to better understand the pathophysiology and target
      a population at risk.

      The importance of this study is paramount in the management of diabetic foot. Indeed for the
      moment we are dealing primarily the consequences of diabetes impact bone when bone
      deformities have appeared with their attendant disability and the risk of recurrent
      infections in areas of friction in this fragile environment. The ultimate goal is to target
      people with diabetes have abnormal bone subclinical and take care to avoid changes to bone
      deformities and find ways to treat them.
    

Intervention name(s): Radiography; Urine and Blood sampling; Echography
Intervention type(s): Radiation; Other; Other
Intervention description(s): Radiography, microscanner, osteodensitometry; mainly dosage of bones metabolism; body bones echography
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: diabetes; osteopenia; neuropathy; foot; AGE