Calorically restricted diets decrease PCSK9 in overweight adolescents

Abstract

Background and aims: Nutritional therapy is the first line approach to treatment of hyperlipidemia in childhood. Proprotein convertase subtilisin kexin type 9 (PCSK9) is a key regulator of plasma cholesterol levels and a target of novel lipid-lowering pharmacotherapies. We examined the effects of an intensive nutritional intervention on PCSK9 levels in overweight adolescents with cardiovascular disease (CVD) risk factors.

Methods and results: Twenty seven obese and overweight adolescents with CVD risk factors were assigned to either a low fat or low glycemic load diet. During an 8-week "Intensive Phase," assigned meals were delivered to the home, and all participants received weekly in-person home nutrition counseling and phone calls. The subjects then underwent a 4-month "Maintenance Phase" without food provision and with no in-person contact. Anthropometric measurements, laboratory data, and serum PCSK9 protein levels were measured at baseline, 8 weeks, and 6 months. PCSK9 decreased by 16.5% at 8 weeks (201.2 ± 56.3 vs 165.6 ± 58.4 ng/mL; p < 0.001); PCSK9 levels returned to baseline levels at 6 months, after the Maintenance Phase. Change in PCSK9 was associated with change in fasting insulin, HOMA-IR, and AUC insulin, independent of weight loss.

Conclusions: PCSK9 decreased in youth participating in an intensive dietary intervention. Change in HOMA-IR was associated with change in PCSK9, independent of weight loss, suggesting an important relationship with insulin sensitivity. ClinicalTrials.gov Identifier: NCT01080339.

Keywords: Adolescents; Dyslipidemia; Nutritional Therapy; Obesity; PCSK9.

Conflict of interest statement

CONFLICT OF INTEREST

Dr. Ludwig reported receiving royalties for books about nutrition and obesity. Dr. de Ferranti has received royalties for UpToDate topics on treatment of pediatric lipid disorders.

Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Figures

Appendix Figure 1

Change in PCSK9 by dietary group at baseline (A), 8 weeks (B), and 6 months (C).

Figure 1

Change in PCSK9 (A) and LDL-cholesterol (B) levels across three study visits. Boxes display mean (+), median (center line), interquartile range (top and bottom boundaries), and minimum and maximum (vertical lines). Gray lines depict time course for each of 27 individual subjects. *Paired comparison showed a significant mean decline between baseline and 8 wk (p

Figure 2

Change in PCSK9 from baseline to 8 weeks (“Intensive Phase”, X axis) vs change in PCSK9 from 8 weeks to 6 months (“Maintenance Phase”, Y axis). Black circles represent each individual study subject. Linear crosshairs indicate where zero change occurred.

Figure 3

Correlation between change in (ln)PCSK9 and change in HOMA-IR and fasting insulin at 8 weeks (A, B) and 6 months (C, D).