Brief Summary

Sex might interact with cardioautonomic neuropathy (CAN) in the development of macrovascular disease in patients with type 1 diabetes (T1D). The regulation of the autonomic system shows sexual dimorphism, and may contribute to the cardiovascular risk overload in women with T1D. The aims of this project are: A.1) Determining the prevalence of CAN and subclinical atherosclerosis in a large cohort of consecutive patients with T1D as a function of sex (cross-sectional study). A.2.) Addressing the progression of CAN and subclinical atherosclerosis in patients with T1D as a function of sex (longitudinal prospective study). A.3.) Investigating the influence of sex steroids and circulating biomarkers in the development and progression of CAN and subclinical atherosclerosis. Research designs: A cross-sectional design/prevalence screening study determining the prevalence of CAN as a function of sex in 320 consecutive individuals with DM1. A longitudinal prospective study: the cohort of prevalence screening study will be prospectively followed, and the assessment of cardiovascular autonomic function and subclinical atherosclerosis will be repeated over time.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

320

participants targeted

Target at P75+ for all trials

Timeline

Completed

Started Sep 2018

Longer than P75 for all trials

Geographic Reach

1 country

1 active site

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

6.9 years study duration

Study Start

First participant enrolled

September 1, 2018

Completed

2.7 years until next milestone

First Submitted

Initial submission to the registry

May 30, 2021

Completed

1 month until next milestone

First Posted

Study publicly available on registry

July 6, 2021

Completed

4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2025

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2025

Completed

Last Updated

August 7, 2025

Status Verified

August 1, 2025

Enrollment Period

6.9 years

First QC Date

May 30, 2021

Last Update Submit

August 5, 2025

Conditions

type1diabetes

Keywords

cardioautonomic neuropathysexual dimorphismsubclinical atherosclerosis

Outcome Measures

Primary Outcomes (6)

To address sexual dimorphism in the prevalence of CAN in patients with T1D.
Blood pressure (mmHg) to active standing and Ewing and Clarke tests.
Two years
To address sexual dimorphism in the prevalence of CAN in patients with T1D.
Heart rate responses (bpm) to active standing and Ewing and Clarke tests.
Two years
To address sexual dimorphism in subclinical atherosclerosis in patients with T1D.
Mean carotid intima-media thickness (mm)
Two years
To assess the role of sex on the progression of cardiovascular dysautonomy in patients with T1D.
Blood pressure (mmHg) to active standing and Ewing and Clarke tests.
Four years
To assess the role of sex on the progression of cardiovascular dysautonomy in patients with T1D.
Heart rate responses (bpm) to active standing and Ewing and Clarke tests.
Four years
To assess the role of sex on the progression of subclinical atherosclerosis in patients with T1D.
Mean carotid intima-media thickness (mm)
Four years

Secondary Outcomes (6)

To identify the influence of sex steroids on the evolution of cardiac autonomic dysfunction.
Four years
To identify the influence of sex steroids on the evolution of cardiac autonomic dysfunction.
Four years
To identify the influence of sex steroids on the evolution of subclinical atherosclerosis
Four years
To identify novel circulating markers of CAN
Four years
To identify novel circulating markers of CAN
Four years
+1 more secondary outcomes

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

Sampling MethodProbability Sample

Study Population

Participants are selected from a consecutive cohort of individuals with T1D, who are regularly attending the outpatient clinic of the Diabetes Unit from Hospital Universitario Ramón y Cajal of Madrid.

You may qualify if:

\- Diagnosis of type 1 diabetes mellitus, as defined by ADA criteria

You may not qualify if:

Renal transplantation or renal replacement therapy;
prior diagnosis of macrovascular disease (CHD, cerebrovascular disease, carotid disease, PAD, or atherosclerotic aortic aneurism);
ongoing pregnancy;
diagnosis of types of diabetes mellitus other than type 1;
diagnosis of types of neuropathy other than diabetic neuropathy.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajallead

Study Sites (1)

Lía Nattero Chávez

Madrid, Madrid, 28034, Spain

Location

Related Publications (4)

Nattero-Chavez L, Insenser M, Amigo N, Samino S, Martinez-Micaelo N, Dorado Avendano B, Quintero Tobar A, Escobar-Morreale HF, Luque-Ramirez M. Quantification of lipoproteins by proton nuclear magnetic resonance spectroscopy (1H-NMRS) improves the prediction of cardiac autonomic dysfunction in patients with type 1 diabetes. J Endocrinol Invest. 2024 Aug;47(8):2075-2085. doi: 10.1007/s40618-023-02289-9. Epub 2024 Jan 6.
PMID: 38182920BACKGROUND
Insenser MR, Nattero-Chavez L, Luque-Ramirez M, Quinones SL, Quintero-Tobar A, Samino S, Amigo N, Dorado Avendano B, Fiers T, Escobar-Morreale HF. Investigating the Link between Intermediate Metabolism, Sexual Dimorphism, and Cardiac Autonomic Dysfunction in Patients with Type 1 Diabetes. Metabolites. 2024 Aug 6;14(8):436. doi: 10.3390/metabo14080436.
PMID: 39195532BACKGROUND
Nattero-Chavez L, Insenser M, Quintero Tobar A, Fernandez-Duran E, Dorado Avendano B, Fiers T, Kaufman JM, Luque-Ramirez M, Escobar-Morreale HF. Sex differences and sex steroids influence on the presentation and severity of cardiovascular autonomic neuropathy of patients with type 1 diabetes. Cardiovasc Diabetol. 2023 Feb 15;22(1):32. doi: 10.1186/s12933-023-01766-y.
PMID: 36793089BACKGROUND
Nattero-Chavez L, Alonso Diaz S, Jimenez-Mendiguchia L, Garcia-Cano A, Fernandez-Duran E, Dorado Avendano B, Escobar-Morreale HF, Luque-Ramirez M. Sexual Dimorphism and Sex Steroids Influence Cardiovascular Autonomic Neuropathy in Patients With Type 1 Diabetes. Diabetes Care. 2019 Nov;42(11):e175-e178. doi: 10.2337/dc19-1375. Epub 2019 Sep 17. No abstract available.
PMID: 31530659BACKGROUND

Study Design

Study Type: observational
Observational Model: COHORT
Time Perspective: PROSPECTIVE
Sponsor Type: OTHER
Responsible Party: SPONSOR

Study Record Dates

First Submitted

May 30, 2021

First Posted

July 6, 2021

Study Start

September 1, 2018

Primary Completion

August 1, 2025

Study Completion

August 1, 2025

Last Updated

August 7, 2025

Record last verified: 2025-08

Locations

ES(1)

Sexual Dimorphism in Cardiovascular Autonomic Neuropathy in Patients With Type 1 Diabetes

Brief Summary

Trial Health

Trial Health Score

Trial Relationships

Study Timeline

Study Start

First Submitted

First Posted

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (6)

Secondary Outcomes (6)

Eligibility Criteria

You may qualify if:

You may not qualify if:

Sponsors & Collaborators

Study Sites (1)

Related Publications (4)

Related Links

Study Design

Study Record Dates

Locations

Brief Summary

Trial Health

Trial Health Score

Trial Relationships

Related Scientific Literature

Study Timeline

Study Start

First Submitted

First Posted

Primary Completion

Study Completion

Conditions

Keywords

Outcome Measures

Primary Outcomes (6)

Secondary Outcomes (6)

Eligibility Criteria

You may qualify if:

You may not qualify if:

Sponsors & Collaborators

Study Sites (1)

Related Publications (4)

Related Links

Study Design

Study Record Dates

Locations