Study of High Density Lipoprotein Function in Type 1 Diabetic Patients With Nephropathy (DID&NEPHRO)

A number of arguments suggest that the deterioration in high density lipoproteins (HDL) functioning may worsen with the development of nephropathy during type 1 diabetes (T1D).

The objective of this study will be to investigate to what extent nephropathy in T1D patients in the microalbuminuria and macroalbuminuria stages, compared to T1D patients without nephropathy, is associated with an alteration in HDL functionality and changes in HDL size and composition (lipids with detailed study of phosphates and sphingolipids, main lipoproteins, inflammatory markers).

Study Overview

• Status: Recruiting
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Biological: Blood samples; Biological: Urine sample

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

Study Locations

• France
  • Dijon, France, 21000
    • Recruiting
    • Chu Dijon Bourogne
    • Contact: Laurence DUVILLARD; Phone Number: 03.80.29.34.53; Email: laurence.duvillard@chu-dijon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

patients treated in the Endocrinology, Diabetology or Nephrology departments of the CHU Dijon Bourgogne or in local nephrology or diabetology practices

Description

Inclusion Criteria:

INCLUSION CRITERIA GROUP C (CONTROLS) :

• age > 18 years
• a person who has given oral consent
• Non-diabetics
• Fasting plasma glucose < 6.10 mmol/L (1.1 g/L)
• Triglyceridemia < 1.7 mmol/L (1.5 g/l)
• HDL-C concentration > 1.30 mmol/L (for women and 1.03 mmol/L for men)
• Glomerular filtration flow rate > 90 mL/min/1.73m2 (These thresholds correspond to the standard thresholds for these parameters)

INCLUSION CRITERIA GROUP T1D-N (WITH NORMAL ALBUMINURIA) :

• age > 18 years
• a person who has given oral consent
• Diabetic type 1 (based on the patient's clinical history and/or the presence of anti-glutamate decarboxylase autoantibodies and/or plasma C-peptide less than 0.5 ng/l)
• HbA1c between 6 and 9%.
• normal albuminuria (albumin/creatinine ratio < 2.5 mg/mmol in men and < 3.5 in women)
• glomerular filtration rate > 90 mL/min/1.73m2

INCLUSION CRITERIA GROUP T1D-MICRO (WITH MICROALBUMINURIA)

• age > 18 years
• a person who has given oral consent
• Diabetic type 1 (based on the patient's clinical history and/or the presence of anti-glutamate decarboxylase autoantibodies and/or plasma C-peptide less than 0.5 ng/l)
• HbA1c between 6 and 9%.
• Microalbuminuria (albumin/creatinine ratio > 2.5 mg/mmol in men and > 3.5 in women, and < 30 mg/mmol)
• glomerular filtration rate > 90 mL/min/1.73m2

INCLUSION CRITERIA GROUP T1D-MACRO (WITH MACROALBUMINURIA)

• age > 18 years
• a person who has given oral consent
• Diabetic type 1 (based on the patient's clinical history and/or the presence of anti-glutamate decarboxylase autoantibodies and/or plasma C-peptide less than 0.5 ng/l)
• HbA1c between 6 and 9%.
• Macroalbuminuria (albumin/creatinine ratio > 30 mg/mmol)
• glomerular filtration rate > 45 mL/min/1.73m2

Exclusion Criteria:

• Protected adult
• Patient not affiliated to a social security scheme
• Pregnant or breastfeeding woman
• Drugs interfering with lipid metabolism outside insulin for DT1 : hypolipidemic (only for patients included in the DT1-micro group), corticosteroid, estroprogestogens, retinoic acid, antiproteases.
• BMI > 30 kg/m2

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
control	Biological: Blood samples; 5 EDTA tubes of 7ml and 1 dry tube of 7 ml taken on an empty stomach; Biological: Urine sample; Urine sample on an empty stomach
T1D with normal albumin levels	Biological: Blood samples; 5 EDTA tubes of 7ml and 1 dry tube of 7 ml taken on an empty stomach; Biological: Urine sample; Urine sample on an empty stomach
T1D with macroalbuminuria	Biological: Blood samples; 5 EDTA tubes of 7ml and 1 dry tube of 7 ml taken on an empty stomach; Biological: Urine sample; Urine sample on an empty stomach
T1D with microalbuminuria	Biological: Blood samples; 5 EDTA tubes of 7ml and 1 dry tube of 7 ml taken on an empty stomach; Biological: Urine sample; Urine sample on an empty stomach
T1D with microalbuminuria and statins	Biological: Blood samples; 5 EDTA tubes of 7ml and 1 dry tube of 7 ml taken on an empty stomach; Biological: Urine sample; Urine sample on an empty stomach

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ability to induce cholesterol efflux	amount of cholesterol captured from cells expressed as %.	inclusion
Nitric oxide synthesis	variation in the presence of HDL compared to the basal state, i.e. in the absence of HDL	inclusion
Anti-inflammatory effect	variation in the expression of adhesion molecules (VCAM-1 [vascular cell adhesion molecule 1], ICAM-1 [InterCellular Adhesion Molecule 1] and E selectin) under the influence of TNF-alpha [Tumor Necrosis Factor alpha] in the presence of HDL compared to the absence of HDL.	inclusion

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Dijon

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2018
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: April 11, 2018
• First Submitted That Met QC Criteria: April 18, 2018
• First Posted (Actual): April 30, 2018

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Endocrine System Diseases; Diabetes Mellitus; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Diabetes Mellitus, Type 1
• Other Study ID Numbers: DUVILLARD 2017

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No