Association of Carbamylated HDL and CAD in T2DM Patients

Type 2 Diabetes Mellitus With Circulatory Complciation Clinical Trial

Official title:

An Observational Cross-sectional Study to Compare Carbamylated High-density Lipoprotein Levels Among Normal Subjects, Type 2 Diabetes Mellitus Patients With and Without Coronary Heart Disease.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04390711
• Other study ID #: c-HDL study
• Status: Completed
• Start date: September 1, 2018
• Est. completion date: March 30, 2019

Study information

• Verified date: May 2020
• Source: RenJi Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is an observational cross-sectional study aimed at investigating the alterations of the carbamylated-HDL levels in T2DM patients, and comparing the concentration of carbamylated-HDL between the T2DM patients with CAD and without CAD to explore the association between carbamylated-HDL and risk of CAD in T2DM patients.

Description:

High-density lipoprotein (HDL) is involved in various atheroprotective processes, including reverse cholesterol transport, inhibition of lipid oxidation and inflammatory cytokine secretion, endothelial repair, and antiapoptotic function, which all contribute to the regression of plague burden. Recent studies have shown that oxidative stress and chronic inflammation — both implicated in the process of diabetes — can contribute to an irreversible post-translational modification called carbamylation. Carbamylation levels reflect the burden of enhanced inflammation, oxidative stress, and renal impairment, and can serve as a biomarker of certain pathological conditions. Several clinical studies have demonstrated positive associations between cardiovascular risk, mortality, and serum carbamylation-derived product levels in the general population and particularly in patients with kidney failure. Increasing evidence also shows that carbamylated lipoprotein plays a pivotal role in atherosclerosis.18 However, most studies concerning carbamylation have been performed under a kidney disease background. Whether HDL particles in patients with type 2 diabetes mellitus (T2DM) show enhanced carbamylation and whether this enhancement is associated with vascular complications remains unknown. Thus, in the present study, the investigators aim to test whether HDL experiences carbamylation in T2DM patients and investigated the pro-atherogenic effects of carbamylated HDL on endothelial-monocyte adhesion.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 282
• Est. completion date: March 30, 2019
• Est. primary completion date: March 30, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 90 Years

Eligibility

Inclusion Criteria:

1:Clinical diagnosis of T2DM (according to the criteria of the American Diabetes Association.)

Exclusion Criteria:

1. end-stage renal disease (ESRD)

2. acute coronary syndrome,

3. heart failure,

4. chronic viral or bacterial infection,

5. cancer,

6. immune system disorders

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus With Circulatory Complciation

Intervention

Other:
• High density lipoprotein isolation, detection and in-vitro study.
All blood samples were taken on the day of cardiac catheterization after overnight fasting.High density lipoprotein from each participants was isolated and further collected for carbamylation level detection and in-vitro study.

Locations

Country	Name	City	State
China	Rui Jin Hospital	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
RenJi Hospital	Ruijin Hospital

Country where clinical trial is conducted

China, 

References & Publications (7)

Delanghe S, Delanghe JR, Speeckaert R, Van Biesen W, Speeckaert MM. Mechanisms and consequences of carbamoylation. Nat Rev Nephrol. 2017 Sep;13(9):580-593. doi: 10.1038/nrneph.2017.103. Epub 2017 Jul 31. Review. — View Citation

Femlak M, Gluba-Brzózka A, Cialkowska-Rysz A, Rysz J. The role and function of HDL in patients with diabetes mellitus and the related cardiovascular risk. Lipids Health Dis. 2017 Oct 30;16(1):207. doi: 10.1186/s12944-017-0594-3. Review. — View Citation

Long J, Vela Parada X, Kalim S. Protein Carbamylation in Chronic Kidney Disease and Dialysis. Adv Clin Chem. 2018;87:37-67. doi: 10.1016/bs.acc.2018.07.002. Epub 2018 Aug 23. Review. — View Citation

Rosenson RS, Brewer HB Jr, Ansell BJ, Barter P, Chapman MJ, Heinecke JW, Kontush A, Tall AR, Webb NR. Dysfunctional HDL and atherosclerotic cardiovascular disease. Nat Rev Cardiol. 2016 Jan;13(1):48-60. doi: 10.1038/nrcardio.2015.124. Epub 2015 Sep 1. Review. — View Citation

Sun JT, Liu Y, Lu L, Liu HJ, Shen WF, Yang K, Zhang RY. Diabetes-Invoked High-Density Lipoprotein and Its Association With Coronary Artery Disease in Patients With Type 2 Diabetes Mellitus. Am J Cardiol. 2016 Dec 1;118(11):1674-1679. doi: 10.1016/j.amjcard.2016.08.044. Epub 2016 Aug 30. — View Citation

Sun JT, Yang K, Mao JY, Shen WF, Lu L, Wu QH, Wang YP, Wu LP, Zhang RY. Cyanate-Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion. J Am Heart Assoc. 2016 Dec 16;5(12). pii: e004700. — View Citation

Verbrugge FH, Tang WH, Hazen SL. Protein carbamylation and cardiovascular disease. Kidney Int. 2015 Sep;88(3):474-8. doi: 10.1038/ki.2015.166. Epub 2015 Jun 10. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Carbamylated-HDL levels alteration between the control and the T2DM patients with and without concomitant CAD.	HDL was isolated from subjects' plasma and its carbamylation levels were further detected by the enzyme-linked immunosorbent assay	within 1week after enrollment