Impact of the Rapid Normalization of Chronic Hyperglycemia and the Practice of Moderate Physical Activity on the "Receptor Activator of Nuclear Factor-kappa B Ligand / Osteoprotégérine (RANKL / OPG) System in Patients Living With Type II Diabetes

The rapid normalization of hyperglycemia can cause a neuropathy called Diabetes Treatment-Induced Neuropathy (NITD). This phenomenon induces the presence of hyper vascularization and inflammation in contact with the nerve ends.

In another register in patients living with diabetes, it has been observed the development of a rare and devastating complication for the joints called the so-called neuroarthropathy of Charcot (CN). The pathophysiology of CN is not completely known but there is an activation of markers of inflammation and bone remodeling, disruption of the osteoblast and osteoclast system, activation of the RANKL system (Receptor activator of nuclear factor-kappa B ligand) and its antagonist osteoprogesterin (OPG). Inflammation and peripheral hypervascularization therefore seem to be a common link between the two pathologies mentioned (NITD and CN). We have confirmation that the rapid correction of chronic hyperglycemia can trigger (not systematically) NITD, but what about the influence of this rapid correction on the appearance of CN. Furthermore, physical activity (PA) and exercise have long been recognized as the cornerstones of the prevention and management of chronic diseases, due to their beneficial effects on the clinical parameters of various diseases. The practice of PA has a preventive and therapeutic effect against osteoporosis (a disease in which the level of RANKL is particularly high), so there is in theory a preventive effect of the practice of physical activity on the development of CN.

Inclusion criteria

Group G1:

• Male or female patient aged 18 to 70, not practicing regular physical activity (Baecke score <10)
• Patient with type 2 diabetes for at least 1 year
• Patient treated with metformin +/- SU +/- DPP4 inhibitor +/- GLP1 analogue +/- insulin therapy
• Patient insufficiently balanced under his current treatment with an HbA1c level> 8.5% for 6 months.
• Patient able to practice physical activity on a regular basis
• Patient having performed a coronary artery disease screening test in the year prior to inclusion
• Woman of childbearing age with effective contraception put in place and monitored throughout the trial
• Patient having given his consent to participate in the study and having signed an informed consent
• Within the G1 group, a controlled 1: 1 randomization, stratified on age (≤65 years or> 65 years) and BMI (≤ 30 or> 30) will determine the inclusion of patients in the G1A group (correction of HbA1c) or G1B (correction of HbA1c + physical activity).

Group G2:

• Male or female patient aged 18 to 70, not practicing regular physical activity
• Patient with type 2 diabetes for at least 1 year
• Patient treated with metformin +/- SU +/- DPP4 inhibitor +/- GLP1 analogue +/- insulin therapy
• Patient balanced under his current treatment with an HbA1c level <7% for 6 months.
• Women of childbearing potential with effective contraception put in place and monitored throughout the trial
• Patient having given his consent to participate in the study and having signed an informed consent
• Matching with the last patient included in group G1 on age (± 5 years), sex, duration of diabetes (± 2 years) and BMI (± 2kg / m2).

Exclusion criteria

• Fetal and maternal pathologies requiring maturation Patient with type 1 diabetes
• Patient with regular physical activity
• History of severe cardiovascular pathologies (myocardial infarction, or acute coronary syndrome, or stroke in the past year)
• Patient with a history of severe hypoglycemia in the 6 months preceding entry into the study and / or not experiencing hypoglycemia at all
• Patient pregnant or likely to be
• Severe obesity (BMI> 35kg / m2)
• Other pathologies likely to interfere with the glycemic variation: in particular the use of corticosteroids during the study
• Patient already having Charcot's neuroarthropathy or symptomatic autonomic neuropathy: orthostatic hypotension and / or gastro-paresis
• Patient with preproliferative diabetic retinopathy
• Patient having anti RANKL treatment
• Subject under tutorship or curatorship
• Subject not affiliated to social security.