Effect of Serum LDL Cholesterol Concentration on Pancreatic Insulin Secretion

University Hospital Tuebingen

Status: Terminated

Conditions: Hypercholesterolemia; Insulin Secretion; Insulin Resistance

Treatments: Drug: Lowering cholesterol concentrations by PCSK-9 inhibitor

Study type: Interventional

Funder types: Other

Identifiers

NCT04314167

045/2020BO2

Details and patient eligibility

About

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.

Enrollment: 9 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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9 participants in 1 patient group

LDL lowering therapy

Experimental group

Description:

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

Treatment:

Drug: Lowering cholesterol concentrations by PCSK-9 inhibitor