A placebo-controlled proof-of-concept study of alirocumab on postprandial lipids and vascular elasticity in insulin-treated patients with type 2 diabetes mellitus

Autor: Jeannine Huisbrink, Manuel Castro Cabezas, Monique T. Mulder, Nadine Pouw, Gert-Jan M. van de Geijn, Benjamin Burggraaf, Leonie C. van Vark-van der Zee, Patrick C.N. Rensen, Ellen van der Zwan, Wouter W. de Herder, Salvador Fernandez Arroyo, Erwin Birnie
Přispěvatelé: Health Psychology Research (HPR), Internal Medicine
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
medicine.medical_specialty
Very low-density lipoprotein
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
LEUKOCYTE ACTIVATION
ENDOTHELIAL FUNCTION
apolipoprotein
LOW-DENSITY-LIPOPROTEIN
030209 endocrinology & metabolism
postprandial
030204 cardiovascular system & hematology
Pulse Wave Analysis
METABOLISM
Antibodies
Monoclonal
Humanized
PCSK9
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Endocrinology
SDG 3 - Good Health and Well-being
Internal medicine
Internal Medicine
medicine
Humans
Insulin
triglycerides
Alirocumab
RISK
business.industry
Cholesterol
CHOLESTEROL
Area under the curve
lipids and lipoproteins
Lipids
Elasticity
Postprandial
NONFASTING TRIGLYCERIDES
chemistry
Diabetes Mellitus
Type 2
CARDIOVASCULAR-DISEASE
lipids (amino acids
peptides
and proteins)
Proprotein Convertase 9
business
ARTERIAL STIFFNESS
Lipoprotein
Zdroj: Diabetes obesity & metabolism, 22(5), 807-816. Wiley
Diabetes, Obesity and Metabolism, 22(5), 807-816. Wiley-Blackwell Publishing Ltd
Diabetes, Obesity and Metabolism, 22(5), 807-816. WILEY
ISSN: 1462-8902
Popis: AIM: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular disease (CVD) linked to atherogenic dyslipidaemia and postprandial hyperlipidaemia. Alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, improves CVD risk by reducing the concentration of low-density lipoprotein-cholesterol (LDL-C). However, effects of PCK9 inhibitors on other aspects of diabetic dyslipidaemia, particularly in the postprandial situation, are less clear.MATERIAL AND METHODS: Twelve male patients with T2DM on an intensive insulin regimen completed a 6-week randomized, double-blind, placebo-controlled, proof-of-concept study. Participants received three biweekly dosages of subcutaneous alirocumab (150 mg) or placebo. Before and after the intervention, fasting and postprandial triglyceride (TG) plasma levels, apolipoprotein (apo) B48, lipoprotein composition isolated by ultracentrifugation, vascular function and markers of inflammation were evaluated.RESULTS: Alirocumab treatment reduced fasting plasma TG levels (between group median change -24.7%; P = 0.018) and fasting apoB48 serum levels (-35.9%; P = 0.039) compared with placebo. Alirocumab reduced the plasma TG area under the curve (AUC) (-26.4%; P = 0.006) and apoB48 AUC (-55.7%; P = 0.046), as well as plasma TG incremental AUC (-21.4%; P = 0.04) and apoB48 incremental AUC (-26.8%; P = 0.02). In addition, alirocumab reduced fasting and postprandial TG levels in very low-density lipoprotein (VLDL) and LDL. Alirocumab improved fasting pulse wave velocity, but no changes in postprandial markers of inflammation were observed.CONCLUSIONS: In addition to the well-known LDL-C-reducing effects, 6 weeks of alirocumab treatment lowered both fasting and postprandial plasma TG levels by reducing the TG levels in VLDL and LDL and the concentration of intestinal remnants.
Databáze: OpenAIRE
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