TY - JOUR
T1 - Analysis of the SYSDIET Healthy Nordic Diet randomized trial based on metabolic profiling reveal beneficial effects on glucose metabolism and blood lipids
AU - Gürdeniz, Gözde
AU - Uusitupa, Matti
AU - Hermansen, Kjeld
AU - Savolainen, Markku J.
AU - Schwab, Ursula
AU - Kolehmainen, Marjukka
AU - Brader, Lea
AU - Cloetens, Lieselotte
AU - Herzig, Karl Heinz
AU - Hukkanen, Janne
AU - Rosqvist, Fredrik
AU - Ulven, Stine Marie
AU - Gunnarsdóttir, Ingibjörg
AU - Thorsdottir, Inga
AU - Orešič, Matej
AU - Poutanen, Kaisa S.
AU - Risérus, Ulf
AU - Åkesson, Björn
AU - Dragsted, Lars Ove
N1 - Funding Information:
Systems biology in controlled dietary interventions and cohort studies (SYSDIET) is one of the three projects in the Nordic Centre of Excellence Programme on Food, Nutrition and Health nominated and funded by NordForsk for years 2007–2012 (SYSDIET; 070014). The SYSDIET intervention was also funded by the Academy of Finland, Finnish Diabetes Research Foundation, Finnish Foundation for Cardiovascular Research, The Sigfrid Juselius Foundation, and EVO funding from Kuopio University Hospital (Finland); the Druvan Foundation, ESPEN, Skåne County Council Research and Development Foundation, The Heart-Lung Foundation, Diabetesfonden, and Foundation Cerealia (Sweden), The Danish Obesity Research Centre (DanORC, www.danorc.dk), The Danish Council for Strategic Research (DairyHealth, BioFunCarb, FoodBAll) (Denmark), The Agricultural Productivity Fund, The Research Fund of the University of Iceland (Iceland). The metabolomics analysis was supported by a Semper Ardens grant on biomarkers from the Carlsberg Foundation to LOD.
Publisher Copyright:
© 2022 The Authors
PY - 2022/2
Y1 - 2022/2
N2 - Background & aims: Intake assessment in multicenter trials is challenging, yet important for accurate outcome evaluation. The present study aimed to characterize a multicenter randomized controlled trial with a healthy Nordic diet (HND) compared to a Control diet (CD) by plasma and urine metabolic profiles and to associate them with cardiometabolic markers. Methods: During 18–24 weeks of intervention, 200 participants with metabolic syndrome were advised at six centres to eat either HND (e.g. whole-grain products, berries, rapeseed oil, fish and low-fat dairy) or CD while being weight stable. Of these 166/159 completers delivered blood/urine samples. Metabolic profiles of fasting plasma and 24 h pooled urine were analysed to identify characteristic diet-related patterns. Principal components analysis (PCA) scores (i.e. PC1 and PC2 scores) were used to test their combined effect on blood glucose response (primary endpoint), serum lipoproteins, triglycerides, and inflammatory markers. Results: The profiles distinguished HND and CD with AUC of 0.96 ± 0.03 and 0.93 ± 0.02 for plasma and urine, respectively, with limited heterogeneity between centers, reflecting markers of key foods. Markers of fish, whole grain and polyunsaturated lipids characterized HND, while CD was reflected by lipids containing palmitoleic acid. The PC1 scores of plasma metabolites characterizing the intervention is associated with HDL (β = 0.05; 95% CI: 0.02, 0.08; P = 0.001) and triglycerides (β = −0.06; 95% CI: −0.09, −0.03; P < 0.001). PC2 scores were related with glucose metabolism (2 h Glucose, β = 0.1; 95% CI: 0.05, 0.15; P < 0.001), LDL (β = 0.06; 95% CI: 0.01, 0.1; P = 0.02) and triglycerides (β = 0.11; 95% CI: 0.06, 0.15; P < 0.001). For urine, the scores were related with LDL cholesterol. Conclusions: Plasma and urine metabolite profiles from SYSDIET reflected good compliance with dietary recommendations across the region. The scores of metabolites characterizing the diets associated with outcomes related with cardio-metabolic risk. Our analysis therefore offers a novel way to approach a per protocol analysis with a balanced compliance assessment in larger multicentre dietary trials. The study was registered at clinicaltrials.gov with NCT00992641.
AB - Background & aims: Intake assessment in multicenter trials is challenging, yet important for accurate outcome evaluation. The present study aimed to characterize a multicenter randomized controlled trial with a healthy Nordic diet (HND) compared to a Control diet (CD) by plasma and urine metabolic profiles and to associate them with cardiometabolic markers. Methods: During 18–24 weeks of intervention, 200 participants with metabolic syndrome were advised at six centres to eat either HND (e.g. whole-grain products, berries, rapeseed oil, fish and low-fat dairy) or CD while being weight stable. Of these 166/159 completers delivered blood/urine samples. Metabolic profiles of fasting plasma and 24 h pooled urine were analysed to identify characteristic diet-related patterns. Principal components analysis (PCA) scores (i.e. PC1 and PC2 scores) were used to test their combined effect on blood glucose response (primary endpoint), serum lipoproteins, triglycerides, and inflammatory markers. Results: The profiles distinguished HND and CD with AUC of 0.96 ± 0.03 and 0.93 ± 0.02 for plasma and urine, respectively, with limited heterogeneity between centers, reflecting markers of key foods. Markers of fish, whole grain and polyunsaturated lipids characterized HND, while CD was reflected by lipids containing palmitoleic acid. The PC1 scores of plasma metabolites characterizing the intervention is associated with HDL (β = 0.05; 95% CI: 0.02, 0.08; P = 0.001) and triglycerides (β = −0.06; 95% CI: −0.09, −0.03; P < 0.001). PC2 scores were related with glucose metabolism (2 h Glucose, β = 0.1; 95% CI: 0.05, 0.15; P < 0.001), LDL (β = 0.06; 95% CI: 0.01, 0.1; P = 0.02) and triglycerides (β = 0.11; 95% CI: 0.06, 0.15; P < 0.001). For urine, the scores were related with LDL cholesterol. Conclusions: Plasma and urine metabolite profiles from SYSDIET reflected good compliance with dietary recommendations across the region. The scores of metabolites characterizing the diets associated with outcomes related with cardio-metabolic risk. Our analysis therefore offers a novel way to approach a per protocol analysis with a balanced compliance assessment in larger multicentre dietary trials. The study was registered at clinicaltrials.gov with NCT00992641.
KW - Glucose and lipid metabolism
KW - Healthy Nordic diet
KW - LC–MS metabolomics
KW - Plasma metabolite scores
KW - Randomized controlled trial
UR - http://www.scopus.com/inward/record.url?scp=85122434050&partnerID=8YFLogxK
U2 - 10.1016/j.clnu.2021.12.031
DO - 10.1016/j.clnu.2021.12.031
M3 - Article
AN - SCOPUS:85122434050
SN - 0261-5614
VL - 41
SP - 441
EP - 451
JO - Clinical Nutrition
JF - Clinical Nutrition
IS - 2
ER -