Pilot Study DiaDEP (DiaDEP)

Endothelial Dysfunction Could be an Early Biomarker of Renal Impairment in Children and Adolescent With Type 1 Diabetes. Pilot Study DiaDEP

With an increased incidence of pediatric type 1 diabetes (T1D) and a decrease in age at diagnosis, children are exposed to complications such as renal impairment at a very young age. The current biomarker used to diagnose renal impairment is microalbuminuria, but it's a late marker. Early screening is a major issue to reduce T1D consequences. Early glomerular hyperfiltration (GHF) could participate in the development and progression of nephropathy. Hyperfiltration has also been associated with a systemic endothelial dysfunction and with changes in arterial stiffness, suggesting, at least to a certain extent, a state of generalized vascular dysfunction. Diabetes is responsible for very early neurovascular dysfunctions, detectable with techniques to evaluate cutaneous neurovascular interaction. Those should help bringing to light very early microcirculation impairment, particularly precocious endothelial dysfunction (ED). No study about correlation between GHF and ED is currently available. The hypothesis assessed is those of a strong correlation between ED and GHF in children and adolescent with a story of T1D for at least 10 years. This pilot study should allow assessing ED's and GHF's proportions in our population, in order to conduct a larger study to prove, in a prospective way, the prognostic value of ED in the apparition of nephropathy, taking into count other factors such as diabetes duration or stability. This measure could be included in the global evaluation of microangiopathy risk in children and then take action to prevent negative outcomes. The second aspect of this study is the assessment of other functions and metabolisms possibly impaired in T1D: osseous microarchitecture, vitamin D status and precocious evaluation of macro angiopathy through intima media thickness measurement. Long term diabetes in children is associated with shorter and leaner bones, despite a correct mineralization, a reduced bone density and a fracture risk increased six fold. Bone status in the population will be evaluated through the study of bones microarchitecture via HR-pQCT (High Resolution peripheral Quantitative Computed Tomography) on both tibia and radius, dual-energy X-ray absorptiometry (DXA), and bone turn over biochemical markers. Results on bone microarchitecture in a preexisting cohort of healthy children and adolescents will be used to compare results.

Diabetes mellitus type 1, Type 1 diabetes, diabetes, pediatrics, Glomerular hyperfiltration, endothelial dysfunction, children, adolescent

Children and adolescent from 10 to 18 years old, with a history of type 1 diabetes for at least 10 years. Glomerular hyper filtration and endothelial dysfunction will be evaluate.

intravenous injection of Iohexol (Omnipaque 300mg) with blood sampling at 0, 120, 180 and 240 minutes (during Day 1.

endothelial function evaluated following a protocol of iontophoresis of acetylcholine (during Day 1).

Endothelial function will be evaluated by the microcirculation assessment through Laser Doppler associated to iontophoresis of acetylcholine.

bone density will be performed by Dual-energy X-ray absorptiometry (DXA) on both spine and whole body.

quantization of bone mineral content will be performed by Dual-energy X-ray absorptiometry (DXA) on both spine and whole body.

Volumetric compartmental density will be performed by High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) on radius and tibia (Right tibia and non-dominant arm radius). (Unless there is a history of fracture for one of those bones, in which case the opposite side will be studied instead.)

trabecular microarchitecture will be performed by High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) on radius and tibia (Right tibia and non-dominant arm radius). (Unless there is a history of fracture for one of those bones, in which case the opposite side will be studied instead.)

Inclusion Criteria: Aged ≥ 10 et < 18 years old Type 1 diabetes diagnosed more than 10 years previously. Written informed consent signed by both parents or legal representatives, child or adolescent's agreement. Health cover Exclusion Criteria: Associated pathology with a potential impact on cutaneous microcirculation or renal function. Aspirin or other non-steroid anti-inflammatory treatment with potential impact on endothelial function in the 3 weeks preceding the visit. Examination with injection of contrast agent during the last 48 hours Smoking Ongoing pregnancy or breast feeding Hypersensitivity to acetylcholine Contraindication to Iohexol Ongoing treatment with growth hormone, non-inhaled corticosteroids or anti-calcineurins; History of treatment with oral corticosteroids (not inhaled) more than 3 successive months regardless of seniority; Paracetamol treatment less than a week old;