Abstract
Background: Weight loss through lifestyle interventions, notably low-energy diets, offers glycemic benefits in populations with overweight-associated prediabetes. However, >50% of these individuals fail to achieve normoglycemia after weight loss. Circulating lipids hold potential for evaluating dietary impacts and predicting diabetes risk. Objectives: This study sought to identify serum lipids that could serve as evaluative or predictive biomarkers for individual glycemic changes following diet-induced weight loss. Methods: We studied 104 participants with overweight-associated prediabetes, who lost ≥8% weight via a low-energy diet over 8 wk. High-coverage lipidomics was conducted in serum samples before and after the dietary intervention. The lipidomic recalibration was assessed using differential lipid abundance comparisons and partial least squares discriminant analyses. Associations between lipid changes and clinical characteristics were determined by Spearman correlation and Bootstrap Forest of ensemble machine learning model. Baseline lipids, predictive of glycemic parameters changes postweight loss, were assessed using Bootstrap Forest analyses. Results: We quantified 439 serum lipid species and 9 related organic acids. Dietary intervention significantly reduced diacylglycerols, ceramides, lysophospholipids, and ether-linked phosphatidylethanolamine. In contrast, acylcarnitines, short-chain fatty acids, organic acids, and ether-linked phosphatidylcholine increased significantly. Changes in certain lipid species (e.g., saturated and monounsaturated fatty acid-containing glycerolipids, sphingadienine-based very long-chain sphingolipids, and organic acids) were closely associated with clinical glycemic parameters. Six baseline bioactive sphingolipids primarily predicted changes in fasting plasma glucose. In addition, a number of baseline lipid species, mainly diacylglycerols and triglycerides, were predictive of clinical changes in hemoglobin A1c, insulin and homeostasis model assessment of insulin resistance. Conclusions: Newly discovered serum lipidomic alterations and the associated changes in lipid-clinical variables suggest broad metabolic reprogramming related to diet-mediated glycemic control. Novel lipid predictors of glycemic outcomes could facilitate early stratification of individuals with prediabetes who are metabolically less responsive to weight loss, enabling more tailored intervention strategies beyond 1-size-fits-all lifestyle modification advice. The PREVIEW lifestyle intervention study was registered at clinicaltrials.gov as NCT01777893 (https://clinicaltrials.gov/study/NCT01777893).
Originalsprog | Engelsk |
---|---|
Bogserie | American Journal of Clinical Nutrition |
Vol/bind | 120 |
Udgave nummer | 4 |
Sider (fra-til) | 864-878 |
ISSN | 0002-9165 |
DOI | |
Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:The PREVIEW study was supported by funding received from the EU framework program 7 (FP7/2007\u20132013) grant agreement (#312057), the National Health and Medical Research Council (NHMRC)-EU Collaborative Grant (Australia 8, ID 1067711), the Glycemic Index Foundation Australia through royalties to The University of Sydney, the New Zealand Health Research Council (#14/191), and the University of Auckland Faculty Research Development Fund. The Cambridge Weight Plan donated all products for the 8-wk LED period. Funding was also received from the Danish Agriculture & Food Council, the Danish Meat and Research Institute, National Institute for Health Research Biomedical Research Centre (United Kingdom), the Biotechnology and Biological Sciences Research Council (United Kingdom), and Engineering and Physical Sciences Research Council (United Kingdom). Nutritics (Dublin) donated all dietary analysis software used by University of Nottingham. Support was received from Juho Vainio Foundation (Finland), Academy of Finland (#272376, 314383, 266286, 314135), Finnish Medical Foundation, Gyllenberg Foundation, Novo Nordisk Foundation, Finnish Diabetes Research Foundation, University of Helsinki, Government Research Funds for Helsinki University Hospital (Finland), Jenny and Antti Wihuri Foundation (Finland), and Emil Aaltonen Foundation (Finland). In addition, this substudy was supported by NHMRC Ideas Grant GNT2002660 (to ASD and YQ; Australia), New South Wales Health Cardiovascular Early-Mid Researcher Grant G205977 (to YQ; Australia), and Centenary Institute Future Leader Fellowship (to YQ; Australia). The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report.
Funding Information:
The PREVIEW study was supported by funding received from the EU framework programme 7 (FP7/2007\u20132013) grant agreement (#312057), the National Health and Medical Research Council (NHMRC)-EU Collaborative Grant (Australia 8, ID 1067711), the Glycemic Index Foundation Australia through royalties to the University of Sydney, the New Zealand Health Research Council (#14/191) and the University of Auckland Faculty Research Development Fund. The Cambridge Weight Plan donated all products for the 8-week LED period. Funding was also received from the Danish Agriculture & Food Council, the Danish Meat and Research Institute, National Institute for Health Research Biomedical Research Centre (U.K.), the Biotechnology and Biological Sciences Research Council (U.K.) and Engineering and Physical Sciences Research Council (U.K.). Nutritics (Dublin) donated all dietary analysis software used by University of Nottingham. Support was received from Juho Vainio Foundation (Finland), Academy of Finland (#272376, 314383, 266286, 314135), Finnish Medical Foundation, Gyllenberg Foundation, Novo Nordisk Foundation, Finnish Diabetes Research Foundation, University of Helsinki, Government Research Funds for Helsinki University Hospital (Finland), Jenny and Antti Wihuri Foundation (Finland), Emil Aaltonen Foundation (Finland). In addition, the present sub-study was supported by NHMRC Ideas Grant GNT2002660 (A.S.D and Y.Q, Australia), New South Wales Health Cardiovascular Early-Mid Researcher Grant G205977 (Y.Q, Australia) and Centenary Institute Future Leader Fellowship (Y.Q, Australia). The funders had no role in study design, data collection, data analysis, data interpretation or writing of the report.
Publisher Copyright:
© 2024 American Society for Nutrition