Diabetes and Familial Hypercholesterolemia: Interplay between Lipid and Glucose Metabolism

Abstract

Familial hypercholesterolemia (FH) is a genetic disease characterized by high low-density lipoprotein (LDL) cholesterol (LDL-c) concentrations that increase cardiovascular risk and cause premature death. The most frequent cause of the disease is a mutation in the LDL receptor (LDLR) gene. Diabetes is also associated with an increased risk of cardiovascular disease and mortality. People with FH seem to be protected from developing diabetes, whereas cholesterol-lowering treatments such as statins are associated with an increased risk of the disease. One of the hypotheses to explain this is based on the toxicity of LDL particles on insulin-secreting pancreatic β-cells, and their uptake by the latter, mediated by the LDLR. A healthy lifestyle and a relatively low body mass index in people with FH have also been proposed as explanations. Its association with superimposed diabetes modifies the phenotype of FH, both regarding the lipid profile and cardiovascular risk. However, findings regarding the association and interplay between these two diseases are conflicting. The present review summarizes the existing evidence and discusses knowledge gaps on the matter.

PCSK9 plasma concentration is associated with epicardial adipose tissue volume and metabolic control in patients with type 1 diabetes

“…In this context, we could hypothesize that the association between PCSK9 levels and glycemic control is mediated by increased cholesterol concentration. However, in subjects with familial hypercholesterolemia, including those with a gain of function mutation in PCSK9, epidemiological studies have shown a lower DM prevalence 34 .Thus, the underlying mechanism explaining the relationship between PCSK9 concentration and poor glycemic control remains to be clarified.…”

Familial Hypercholesterolemia and Its Current Diagnostics and Treatment Possibilities: A Literature Analysis

“…Patients with heterozygous FH mostly have subclinical form or aortic valve stenosis [43]. Patients with FH predominantly does not have arterial hypertension, type 2 diabetes mellitus (DM), metabolic syndrome, or hyperuricemia (the incidence of these diseases is statistically lower than in the population) [44].…”

“…While screening for FH within primary care has been demonstrated to be cost-effective [45], which screening approach is cost-effective has not been established [46]. The model found that the addition of primary care case identification by database search for patients with recorded total cholesterol > 9.3 mmol/L was more cost effective than cascade testing alone [44]. A cost-effectiveness study in Poland showed that screening patients with acute coronary syndrome (ACS) younger than 55-65 years is the most cost-effective strategy.…”

Familial Hypercholesterolaemia as a Predisposing Factor for Atherosclerosis

“…The cholesterol concentrations and the subjects’ clinical pattern depends on the patient’s genetics. The level of abnormality in LDLR genes also affects the natural course considerably for heterozygous FH patients, as well as various risk factors such as smoking, hypertension, and diabetes mellitus [ 14 ]. The risk of myocardial infarction before the age of sixty in unidentified FH patients is 60% higher in men and 30% higher in women [ 15 ].…”