Endocrine Abstracts

Background: Elevated low-density lipoprotein cholesterol (LDL-C), which arises due to genetic and environmental factors, has a causal role in the pathogenesis of cardiovascular disease (CVD). Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are approved for patients with familial hypercholesterolaemia (FH) and patients at high risk of CVD due to non-familial hypercholesterolaemia (non-FH). In clinical trials, PCSK9 inhibitors are well-tolerated and lead to redu...

Background: In the UK, NICE guidelines for familial hypercholesterolaemia (FH) recommend a greater than 50% reduction in low-density lipoprotein-cholesterol (LDL-C) as the therapeutic target. However, despite the availability of a range of lipid lowering medication, this target is often difficult to achieve and, more importantly, maintain life-long. Understanding factors that affect LDL-C target achievement is key to reducing cardiovascular disease (CVD) risk. Currently, there...

Background: Cardiovascular disease (CVD) risk in familial hypercholesterolaemia (FH) is driven by cumulative exposure to high low-density lipoprotein cholesterol (LDL-C) levels. Previously, LDL-C burden has been loosely approximated using the cholesterol year score (CYS) based on two LDL-C readings only. We aimed to determine whether a more sophisticated LDL-C burden score based on serial LDL-C measurements, could more accurately predict major atherosclerotic cardiovascular ev...

We have previously described how signaling responses for the glucagon-like peptide-1 receptor (GLP-1R), a class B GPCR that plays key roles in metabolic regulation and is a prime type 2 diabetes (T2D) target, are modulated by intracellular membrane trafficking. We have also recently shown that binding to the therapeutic GLP-1R agonist exendin-4 (Exenatide) triggers increased clustering and segregation of biologically active GLP-1Rs into cholesterol-rich plasma membrane nanodom...

We present the case of a 53-year-old lady who was recently diagnosed with Type 2 Diabetes, Hypertension and Dyslipidaemia. She was referred by the lipid clinic with a 3-month history of progressive facial swelling, hyperpigmentation and proximal myopathy. Clinical history and examination were highly suspicious of endogenous hypercortisolaemia. An initial overnight dexamethasone suppression test yielded an elevated morning cortisol (752 nmol/l, normal <50nmol/l). Two 24-hou...

Glucagon-like peptide-1 receptor (GLP-1R) agonists are effective treatments for type 2 diabetes and obesity. We recently described ‘biased’ peptide GLP-1R agonists modelled on exendin-4 which uncouple the pronounced endocytosis that usually accompanies GLP-1R activation, leading to prolongation of intracellular signalling responses. Here, we show that the metabolic consequences of biased GLP-1R activation in vivo are dominated by improvements in blood glucos...

Obesity is a growing global epidemic and current medical therapies have proven inadequate. Endogenous satiety hormones provide an attractive target for the development of drugs which aim to cause effective weight loss with minimal side effects. Two related peptide hormones, glucagon and glucagon-like peptide 1 (GLP-1), are the subject of this investigation. Both have been found to reduce appetite and cause weight loss. Additionally, glucagon increases energy expenditure. It is...