Highlights
- •Healthy lifestyle is associated with cardiovascular disease (CVD) risk among diabetic subjects.
- •Adherence to multiple healthy lifestyle factors was associated with improved nuclear magnetic resonance (NMR) metabolites from different pathways.
- •Fatty acids showed mediating effects in the association of multiple lifestyle factors with CVD risk.
- •Targeting shared mediators may facilitate effective CVD prevention strategies among people with diabetes.
Abstract
Background and aims
Lifestyle management is a fundamental aspect of diabetes care to prevent cardiovascular
disease (CVD); however, the underlying metabolic mechanism is not well established.
We aimed to identify metabolites associated with different lifestyle factors, and
estimate their mediating roles between lifestyle and CVD risk among people with diabetes.
Methods
Lifestyle and metabolomic data were available for 5072 participants with diabetes
who were free of CVD at baseline in the UK Biobank. The healthy level of 5 lifestyle
factors was defined as non-central obesity, non-current smoking, moderate alcohol
intake, physically active, and healthy diet. A total of 44 biomarkers across 7 metabolic
pathways including lipoprotein particles, fatty acids, amino acids, fluid balance,
inflammation, ketone bodies, and glycolysis were quantified by nuclear magnetic resonance
(NMR) spectroscopy.
Results
All 44 assayed metabolites were significantly associated with at least one lifestyle
factor. Approximately half of metabolites, which were mostly lipoprotein particles
and fatty acids, showed a mediating effect between at least one lifestyle factor and
CVD risk. NMR metabolites jointly mediated 43.4%, 30.0%, 16.8%, 43.4%, and 65.5% of
the association of non-central obesity, non-current smoking, moderate alcohol intake,
physically active, and healthy diet with lower CVD risk, respectively. In general,
though metabolites that significantly associated with lifestyle were mostly different
across the 5 lifestyle factors, the pattern of association was consistent between
fatty acids and all 5 lifestyle factors. Further, fatty acids showed significant mediating
effects in the association between all 5 lifestyle factors and CVD risk with mediation
proportion ranging from 12.2% to 26.8%.
Conclusions
There were large-scale differences in circulating NMR metabolites between individuals
with diabetes who adhered to a healthy lifestyle and those did not. Differences in
metabolites, especial fatty acids, could partially explain the association between
adherence to multiple healthy lifestyle and lower CVD risk among people with diabetes.
Graphical abstract
Graphical Abstract
Keywords
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References
- Trends in predominant causes of death in individuals with and without diabetes in England from 2001 to 2018: an epidemiological analysis of linked primary care records.Lancet Diabetes Endocrinol. 2021; 9: 165-173https://doi.org/10.1016/S2213-8587(20)30431-9
- Trends in cause-specific mortality among adults with and without diagnosed diabetes in the USA: an epidemiological analysis of linked national survey and vital statistics data.Lancet. 2018; 391: 2430-2440https://doi.org/10.1016/S0140-6736(18)30314-3
- A, 5. Lifestyle management: standards of medical care in diabetes-2019.Diabetes Care. 2019; 42: S46-S60https://doi.org/10.2337/dc19-S005
- Comprehensive management of cardiovascular risk factors for adults with type 2 diabetes: a scientific statement from the American heart association.Circulation. 2022; (CIR0000000000001040)https://doi.org/10.1161/CIR.0000000000001040
- Combined lifestyle factors and risk of incident type 2 diabetes and prognosis among individuals with type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies.Diabetologia. 2020; 63: 21-33https://doi.org/10.1007/s00125-019-04985-9
- Metabolomics for investigating physiological and pathophysiological processes.Physiol. Rev. 2019; 99: 1819-1875https://doi.org/10.1152/physrev.00035.2018
- Quantitative serum nuclear magnetic resonance metabolomics in large-scale Epidemiology: a primer on -omic technologies.Am. J. Epidemiol. 2017; 186: 1084-1096https://doi.org/10.1093/aje/kwx016
- Metabolic profiling of alcohol consumption in 9778 young adults.Int. J. Epidemiol. 2016; 45: 1493-1506https://doi.org/10.1093/ije/dyw175
- Metabolic signatures of adiposity in young adults: Mendelian randomization analysis and effects of weight change.PLoS Med. 2014; 11e1001765https://doi.org/10.1371/journal.pmed.1001765
- Long-term leisure-time physical activity and serum metabolome.Circulation. 2013; 127: 340-348https://doi.org/10.1161/CIRCULATIONAHA.112.105551
- Lipids, lipoproteins, and metabolites and risk of myocardial infarction and stroke.J. Am. Coll. Cardiol. 2018; 71: 620-632https://doi.org/10.1016/j.jacc.2017.12.006
- Metabolite profiling and cardiovascular event risk: a prospective study of 3 population-based cohorts.Circulation. 2015; 131: 774-785https://doi.org/10.1161/CIRCULATIONAHA.114.013116
- Profound perturbation of the metabolome in obesity is associated with health risk.Cell Metabol. 2019; 29: 488-500 e482https://doi.org/10.1016/j.cmet.2018.09.022
- Physical activity, sedentary leisure time, circulating metabolic markers, and risk of major vascular diseases.Circ Genom Precis Med. 2019; 12: 386-396https://doi.org/10.1161/CIRCGEN.118.002527
- The Mediterranean diet, plasma metabolome, and cardiovascular disease risk.Eur. Heart J. 2020; 41: 2645-2656https://doi.org/10.1093/eurheartj/ehaa209
- Improved lipidomic profile mediates the effects of adherence to healthy lifestyles on coronary heart disease.Elife. 2021; 10https://doi.org/10.7554/eLife.60999
- Metabolomics in prediabetes and diabetes: a systematic review and meta-analysis.Diabetes Care. 2016; 39: 833-846https://doi.org/10.2337/dc15-2251
- Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1.9 million people.Lancet Diabetes Endocrinol. 2015; 3: 105-113https://doi.org/10.1016/S2213-8587(14)70219-0
- Associations of combined genetic and lifestyle risks with incident cardiovascular disease and diabetes in the UK Biobank study.JAMA cardiology. 2018; 3: 693-702https://doi.org/10.1001/jamacardio.2018.1717
Nightingale Health Metabolic Biomarkers: Phase 1 release, available at: https://biobank.ndph.ox.ac.uk/showcase/ukb/docs/nmrm_companion_doc.pdf.
- Estimation and inference for the mediation proportion.Int. J. Biostat. 2017; 13https://doi.org/10.1515/ijb-2017-0006
- Adiposity, metabolites, and colorectal cancer risk: Mendelian randomization study.BMC Med. 2020; 18: 396https://doi.org/10.1186/s12916-020-01855-9
- Associations among smoking status, lifestyle and lipoprotein subclasses.J Clin Lipidol. 2010; 4: 522-530https://doi.org/10.1016/j.jacl.2010.09.003
- Tobacco smoking, estrogen receptor alpha gene variation and small low density lipoprotein level.Hum. Mol. Genet. 2005; 14: 2405-2413https://doi.org/10.1093/hmg/ddi242
- Consensus and controversy in the debate over the biphasic impact of alcohol consumption on the cardiovascular system.Nutrients. 2021; 13https://doi.org/10.3390/nu13041076
- Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: systematic review and meta-analysis of interventional studies.BMJ. 2011; 342: d636https://doi.org/10.1136/bmj.d636
- High-density lipoprotein subclasses are a potential intermediary between alcohol intake and reduced risk of cardiovascular disease: the Rancho Bernardo Study.Br. J. Nutr. 2010; 104: 1034-1042https://doi.org/10.1017/S0007114510001595
- Metabolomics, physical activity, exercise and health: a review of the current evidence.Biochim. Biophys. Acta, Mol. Basis Dis. 2020; 1866165936https://doi.org/10.1016/j.bbadis.2020.165936
- Associations of device-measured physical activity across adolescence with metabolic traits: prospective cohort study.PLoS Med. 2018; 15e1002649https://doi.org/10.1371/journal.pmed.1002649
- Use of metabolomics in improving assessment of dietary intake.Clin. Chem. 2018; 64: 82-98https://doi.org/10.1373/clinchem.2017.272344
- Metabolomic profiles as reliable biomarkers of dietary composition.Am. J. Clin. Nutr. 2017; 105: 547-554https://doi.org/10.3945/ajcn.116.144428
- Identifying biomarkers of dietary patterns by using metabolomics.Am. J. Clin. Nutr. 2017; 105: 450-465https://doi.org/10.3945/ajcn.116.144501
- Metabolomic biomarkers of healthy dietary patterns and cardiovascular outcomes.Curr. Atherosclerosis Rep. 2021; 23: 26https://doi.org/10.1007/s11883-021-00921-8
- Primary prevention of cardiovascular disease with a mediterranean diet supplemented with Extra-virgin olive oil or nuts.N. Engl. J. Med. 2018; 378: e34https://doi.org/10.1056/NEJMoa1800389
- Lifestyle factors and high-risk atherosclerosis: pathways and mechanisms beyond traditional risk factors.Eur J Prev Cardiol. 2020; 27: 394-406https://doi.org/10.1177/2047487319869400
- Dietary fats and mortality among patients with type 2 diabetes: analysis in two population based cohort studies.BMJ. 2019; 366: l4009https://doi.org/10.1136/bmj.l4009
- Effects of long-term vitamin D and n-3 fatty acid supplementation on inflammatory and cardiac biomarkers in patients with type 2 diabetes: secondary analyses from a randomised controlled trial.Diabetologia. 2021; 64: 437-447https://doi.org/10.1007/s00125-020-05300-7
- Effects of n-3 fatty acid supplements in diabetes mellitus.N. Engl. J. Med. 2018; 379: 1540-1550https://doi.org/10.1056/NEJMoa1804989
- Lipoproteins and lipids in cardiovascular disease: from mechanistic insights to therapeutic targeting.Adv. Drug Deliv. Rev. 2020; 159: 4-33https://doi.org/10.1016/j.addr.2020.07.019
- Association of nonfasting vs fasting lipid levels with risk of major coronary events in the anglo-scandinavian cardiac outcomes trial-lipid lowering arm.JAMA Intern. Med. 2019; 179: 898-905https://doi.org/10.1001/jamainternmed.2019.0392
- Fasting is not routinely required for determination of a lipid profile: clinical and laboratory implications including flagging at desirable concentration cut-points-a joint consensus statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine.Eur. Heart J. 2016; 37: 1944-1958https://doi.org/10.1093/eurheartj/ehw152
Article info
Publication history
Published online: December 26, 2022
Accepted:
December 21,
2022
Received in revised form:
December 6,
2022
Received:
September 15,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Elsevier B.V. All rights reserved.
