Effect of Serum LDL Cholesterol Concentration on Pancreatic Insulin Secretion

  • STATUS
    Recruiting
  • participants needed
    40
  • sponsor
    University Hospital Tuebingen
Updated on 4 July 2022
diabetes
cardiovascular disease
type 2 diabetes mellitus
insulin resistance
low density lipoprotein
LDL Cholesterol
serum cholesterol
dyslipidemia
cholesterol measurement
hmg-coa reductase inhibitors
evolocumab
serum low density lipoprotein
pcsk9

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 -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.

Details
Condition Hypercholesterolemia, elevated cholesterol, Insulin Secretion, High Cholesterol, Hyperlipidemia, Insulin Resistance, hypercholesteremia, High Cholesterol (Hyperlipidemia)
Treatment Lowering cholesterol concentrations by PCSK-9 inhibitor
Clinical Study IdentifierNCT04314167
SponsorUniversity Hospital Tuebingen
Last Modified on4 July 2022

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