Clinical trial NCT04314167: Effect of Serum LDL Cholesterol Concentration on Pancreatic Insulin Secretion
Official title: Effect of Serum LDL Cholesterol Concentration on Pancreatic Insulin Secretion
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Hypercholesterolemia
Insulin Resistance
Insulin Secretion
Lead sponsor: University Hospital Tuebingen
Sponsor class: OTHER
First posted: 2020-03-19
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


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

Primary outcomes:
measure: Change in insulin secretion.
timeFrame: before and after 12 weeks of treatment with a PCSK9-inhibitor.
Secondary outcomes:
measure: Change in insulin sensitivity.
timeFrame: before and after 12 weeks of treatment with a PCSK9-inhibitor.
measure: Change in insulin clearance.
timeFrame: before and after 12 weeks of treatment with a PCSK9-inhibitor.
measure: Change in glucose tolerance.
timeFrame: before and after 12 weeks of treatment with a PCSK9-inhibitor.
Other outcomes:
Locations:
city: Tuebingen
country: Germany
facility: University of Tuebingen, Department of Internal Medicine IV
Study officials:
References: