Effect of Serum LDL Cholesterol Concentration on Pancreatic Insulin Secretion
Status:
Recruiting
Trial end date:
2022-06-15
Target enrollment:
Participant gender:
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.