Pilot Study DiaDEP

Summary

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.

Conditions

• Diabetes Mellitus, Type 1
• Type1diabetes

Interventions

DRUG

Iohexol renal clearance measurement

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

DEVICE

microcirculation assessment through Laser Doppler associated to iontophoresis.

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

DEVICE

Cardiovascular assessment though Intima-media Thickness and Extra-media Thickness measurement

carotid ultrasound (during Day 1)

BIOLOGICAL

Blood sampling

37 mL of blood sample will be performed at Day 1

BIOLOGICAL

Urine sampling

The urinary collection will be done during the Day 1, on the first morning urination

DEVICE

High-resolution peripheral quantitative computed tomography (HR-pQCT)

assessment of the Body Mass Index by HR-pQCT (during the Day 1)

RADIATION

Dual-energy X-ray (DXA)

assessment of bone parameters by DXA (during the Day 1)

Sponsors & Collaborators

• Hospices Civils de Lyon

  lead OTHER

Study Design

Allocation

NA

Purpose

OTHER

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

10 Years

Max Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-07-09

Primary Completion

2020-11-20

Completion

2020-11-20

Countries

• France

Study Locations