Interstitial Fluid in the Development of Cardiovascular Disease

Studies of the Importance of Interstitial Fluid in the Development of Cardiovascular Disease, an Expanded Study.

At a given level of serum cholesterol, patients with T2D have an increased risk of developing atherosclerosis compared with nondiabetic subjects.

In a previous study we showed that the interstitial fluid-to-serum gradient of LDL and VLDL cholesterol is reduced in T2D patients compared with healthy controls. This was not found for HDL cholesterol. However, the cholesterol transporting function of HDL particles from interstitial fluid from patients with T2D were lower than in healthy controls. We hypothesize that that the apo B-containing particles in T2D patients are more susceptible to be retained or consumed in the extravascular space.

We are to study if skin biopsies from T2D patients contain more cholesterol than biopsies from healthy controls. We hypothesize that samples from T2D patients are richer in cholesterol, which could explain why VLDL and LDL cholesterol are lower in relation to their plasma levels in T2D.

Study Overview

• Status: Completed
• Conditions: Atherosclerosis; Type2 Diabetes
• Intervention / Treatment: Other: Collection of interstitial fluid, skin biopsies and blood

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden, 11219
    • Stiftelsen Stockholms Sjukhems Husläkarmottagning
  • Stockholm, Sweden, 11433
    • GIH (gymnastik och idrottshögskolan)
  • Ekerö Kommun
    • Ekerö, Ekerö Kommun, Sweden, 17831
      • Ekerö Vårdcentral
  • Stockholm
    • Huddinge, Stockholm, Sweden, 14186
      • Patient research centre, Clinic of endocrinology, Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Healthy controls and type 2 diabetes patients over 18 years old, matched for age and gender.

Description

Inclusion criteria:

• Over 18 years.
• For the T2D study group: Diagnosed with type 2 diabetes.

Exclusion criteria:

For subjects with type 2 diabetes:

• Systemic inflammatory disease that requires active treatment
• Thyroid disease that requires active treatment
• Skin disease that requires active treatment and causes significant changes in the area of the skin that is to be investigated
• Treatment with oral glucocorticoids
• Levels of SR, TSH, T4 or Hemoglobin in the blood pronouncedly outside the reference range
• Pregnancy

For healthy controls:

• Registered disease in the health declaration that requires continuous systemic treatment. Exception to the above: well controlled hypertension in which case the subject should not have treatment with more than one antihypertensive drug, the drug must not be an alpha-blocker or beta-blocker or thiazide diuretic
• Skin disease that requires active treatment and causes significant changes in the area of the skin that is to be investigated
• Blood pressure pronouncedly above 140/90
• Blood test results pronouncedly outside the reference range
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Other

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy controls	Other: Collection of interstitial fluid, skin biopsies and blood; Collection of interstitial fluid, skin biopsies and blood
Type 2 diabetes patients	Other: Collection of interstitial fluid, skin biopsies and blood; Collection of interstitial fluid, skin biopsies and blood

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Interstitial fluid-to-serum ratio for LDL cholesterol	2 hours
Cholesterol level in skin biopsies	30 minutes

Collaborators and Investigators

• Sponsor: Karolinska University Hospital
• Collaborators: Karolinska Institutet
• Investigators: Principal Investigator: Mats Rudling, Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Actual): January 10, 2018
• Primary Completion (Actual): September 3, 2021
• Study Completion (Actual): September 3, 2021

Study Registration Dates

• First Submitted: December 21, 2017
• First Submitted That Met QC Criteria: December 21, 2017
• First Posted (Actual): December 29, 2017

Study Record Updates

• Last Update Posted (Actual): September 9, 2021
• Last Update Submitted That Met QC Criteria: September 7, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Cholesterol; Interstitial fluid
• Additional Relevant MeSH Terms: Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Cardiovascular Diseases; Atherosclerosis
• Other Study ID Numbers: DiabetesIC2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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