Effects of Evolocumab on the Postprandial Kinetics of Apo (Apolipoprotein) B100- and B48-Containing Lipoproteins in Subjects With Type 2 Diabetes.

Objective: Increased risk of atherosclerotic cardiovascular disease in subjects with type 2 diabetes is linked to elevated levels of triglyceride-rich lipoproteins and their remnants. The metabolic effects of PCSK9 (proprotein convertase subtilisin/kexin 9) inhibitors on this dyslipidemia were investigated using stable-isotope-labeled tracers. Approach and Results: Triglyceride transport and the metabolism of apos (apolipoproteins) B48, B100, C-III, and E after a fat-rich meal were investigated before and on evolocumab treatment in 13 subjects with type 2 diabetes.

Impact of proprotein convertase subtilisin/kexin type 9 inhibition with evolocumab on the postprandial responses of triglyceride-rich lipoproteins in type II diabetic subjects.

Background: Monoclonal antibodies to proprotein convertase subtilisin/kexin type 9 (PCSK9) significantly lower the levels of low-density lipoprotein and very-low-density lipoproteins (VLDL), but their effect on postprandial lipoprotein metabolism in dyslipidemic subjects is unclear.

Objective: This study aimed to investigate the effects of evolocumab on postprandial lipid responses, ectopic fat depots, whole-body cholesterol synthesis, hepatic lipogenesis, and fat oxidation in patients with type II diabetes.

Methods: The trial was a single-phase, nonrandomized study of 12-week treatment with evolocumab 140 mg subcutaneously every 2 weeks in 15 patients with type II diabetes on background statin therapy.

Role of apolipoprotein C-III overproduction in diabetic dyslipidaemia.

Aims: To investigate how apolipoprotein C-III (apoC-III) metabolism is altered in subjects with type 2 diabetes, whether the perturbed plasma triglyceride concentrations in this condition are determined primarily by the secretion rate or the removal rate of apoC-III, and whether improvement of glycaemic control using the glucagon-like peptide-1 analogue liraglutide for 16 weeks modifies apoC-III dynamics.

Materials And Methods: Postprandial apoC-III kinetics were assessed after a bolus injection of [5,5,5- H ]leucine using ultrasensitive mass spectrometry techniques. We compared apoC-III kinetics in two situations: in subjects with type 2 diabetes before and after liraglutide therapy, and in type 2 diabetic subjects with matched body mass index (BMI) non-diabetic subjects.

ApoA-II HDL Catabolism and Its Relationships With the Kinetics of ApoA-I HDL and of VLDL1, in Abdominal Obesity.

We study the associations between apoA-II fractional catabolic rate (FCR) and the kinetics of VLDL subspecies and apoA-I and show that, in abdominally obese individuals, apoA-II FCR is positively and independently associated with both apoA-I FCR and VLDL1-TG indirect FCR.

Kinetic and Related Determinants of Plasma Triglyceride Concentration in Abdominal Obesity: Multicenter Tracer Kinetic Study.

Objectives: Patients with obesity and diabetes mellitus have increased risk of cardiovascular disease. A major cause is an atherogenic dyslipidemia related primarily to elevated plasma concentrations of triglyceride-rich lipoproteins. The aim of this study was to clarify determinants of plasma triglyceride concentration.

Interrelationships between the kinetics of VLDL subspecies and HDL catabolism in abdominal obesity: a multicenter tracer kinetic study.

Context: Low plasma high-density lipoprotein (HDL) cholesterol is a major abnormality in abdominal obesity. This relates due to accelerated HDL catabolism, but the underlying mechanism requires further elucidation. The relationships between HDL catabolism and other variables that may be modified in abdominal obesity, such as very low-density lipoprotein (VLDL) subspecies (VLDL1, VLDL2) kinetics, liver fat, or visceral adiposity, remain to be investigated.

[Statin therapy--for whom?].

For patients with cardiovascular disease, statins belong to routine medical treatment irrespective of blood lipid levels. In primary prevention also, statins have been found to prevent cardiovascular diseases, associated deaths and decrease overall mortality. In previously healthy persons the use of statins should be based on the assessment of total risk--mere cholesterol level does not usually constitute an indication for treatment.

Dual metabolic defects are required to produce hypertriglyceridemia in obese subjects.

Objective: Obesity increases the risk of cardiovascular disease and premature death. However, not all obese subjects develop the metabolic abnormalities associated with obesity. The aim of this study was to clarify the mechanisms that induce dyslipidemia in obese subjects.

Reviewing statin therapy in diabetes--towards the best practise.

Statin therapy is considered critical both in primary and secondary prevention of cardiovascular disease in diabetes. Cholesterol Treatment Trialists' Collaborators meta-analysis of 14 randomised trials of statins in 18686 people with diabetes provides the latest and largest evidence showing a significant 21% reduction in major vascular events per mmol/l reduction in LDL cholesterol. Importantly, the risk reduction was similar in both types of diabetes.

Apolipoprotein E polymorphism is associated with both carotid and coronary atherosclerosis in patients with coronary artery disease.

Background And Aims: Apolipoprotein E (apoE) polymorphism plays a significant role in the development of atherosclerosis and cardiovascular disease. Therefore, the aim of the present study was to examine the association between apoE polymorphism and carotid intima-media thickness (IMT), and severity and extent of coronary artery disease (CAD).

Methods And Results: B-mode ultrasound and quantitative coronary angiography (QCA) were used to assess carotid, and coronary artery atherosclerosis in 91 patients with clinically suspected CAD referred for cardiac catheterization.

Insulin resistance as predictor of the angiographic severity and extent of coronary artery disease.

Background: Insulin resistance (IR) is frequently observed in patients with coronary artery disease (CAD). Aim. To examine the association between IR and severity and extent of CAD.

ApoE polymorphism is associated with C-reactive protein in low-HDL family members and in normolipidemic subjects.

The study was aimed to compare inflammatory parameters between carriers of apoE4 isoforms (apoE4/3, apoE4/2, and apoE4/4 phenotypes) and those of carrying apoE3 isoform without apoE4 isoform (apoE3/3 phenotypes and apoE2/3 phenotypes). The concentrations of serum hsCRP, sVCAM-1, sICAM-1, and sE-selectin were measured in 211 subjects from Finnish low-HDL families and in 157 normolipidemic subjects. The subjects with apoE4 isoform had lower concentrations of serum hsCRP both in low-HDL family members (p < 0.

Association of paraoxonase-1 activity and concentration with angiographic severity and extent of coronary artery disease.

Objectives: The goal of this study was to examine the association between paraoxonase-1 (PON1) activity and concentration and the severity and extent of coronary artery disease (CAD).

Background: Paraoxonase-1, a high-density lipoprotein-associated enzyme, is proposed to have an antiatherogenic effect by protecting low-density lipoproteins against oxidation.

Methods: We studied PON1 activity and concentration in 107 patients with known or suspected CAD referred for cardiac catheterization.

Association of carotid intima-media thickness with angiographic severity and extent of coronary artery disease.

The present study examined the association between carotid intima-media thickness (IMT) and severity and extent of coronary artery disease (CAD). B-mode ultrasound and quantitative coronary angiography were used to assess carotid and coronary artery atherosclerosis in 108 patients with known or suspected CAD who had been referred for cardiac catheterization. Maximum and mean IMT values of carotid arteries were measured and expressed as mean aggregate values.