Effect of Serum LDL Cholesterol Concentration on Pancreatic Insulin Secretion

NCT ID: NCT04314167

Last Updated: 2024-05-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-28
• Study Completion Date: 2024-03-01

Brief Summary

Dyslipidemia is characterized by low levels of HDLs, hypertriglyceridemia as well as an increases proportion of small dense LDLs. Changes in lipoprotein particles and its concentrations, especially increased levels of pro-atherogenic LDL particles play an important role in the development of cardiovascular diseases. It is well established that statin/PCSK9-inhibitor treatment is very effective in lowering LDL cholesterol levels and therefore in preventing cardiovascular events. Besides the beneficial effects on cardiovascular system, these therapies are unfortunately linked to increased risk for type 2 diabetes.

However underlying mechanisms for the association between LDL cholesterol levels and the risk for type 2 diabetes remains largely unknown.Type 2 diabetes is especially characterized by insulin resistance and impaired insulin secretion from pancreatic beta-cells. Insulin resistance alone is insufficient to cause type 2 diabetes, as long as the ß-cell is able to compensate for the increased demand for insulin. Once this compensatory mechanism reaches its physiological limits, individuals progress to type 2 diabetes. Accordingly we aimed to investigate the associations between LDL cholesterol concentrations and the key issue in the pathogenesis of type 2 diabetes, insulin secretion before and after lowering cholesterol concentration by treatment with Evolocumab for 12 weeks in patients with medical indication for a treatment with a PCSK9-inhibitor. Therefore, patients will either undergo a hyperglycemic clamp or a oral glucose tolerance test in randomized manner.

Conditions

Hypercholesterolemia; Insulin Resistance; Insulin Secretion

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

LDL lowering therapy

Patients will receive the PCSK9-inhibitor Evolocumab as part of routine clinical management within the indication of this drug.

Group Type: EXPERIMENTAL

Lowering cholesterol concentrations by PCSK-9 inhibitor

Intervention Type: DRUG

Patients will receive the PCSK9-inhibitor Evolocumab as part of routine clinical management within the indication of this drug.

Interventions

Lowering cholesterol concentrations by PCSK-9 inhibitor

Patients will receive the PCSK9-inhibitor Evolocumab as part of routine clinical management within the indication of this drug.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures
• Medical indication for the treatment with a PCSK9-inhibitor
• HbA1c < 6,5%

Exclusion Criteria

• Diabetes mellitus
• Pregnant women or breastfeeding
• Hb < 11.5 g/dl (males) or Hb < 10.5 g/dl (females)
• treatment with any medication that effects on blood glucose concentrations, e.g. antidiabetic drugs or steroids
• Any pancreatic disease

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Tuebingen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Tuebingen, Department of Internal Medicine IV

Tübingen, , Germany

Countries

Germany

Other Identifiers

045/2020BO2

Identifier Type: -

Identifier Source: org_study_id