ORCID Profile
0000-0002-5832-0221
Current Organisations
University of Oulu
,
University of Helsinki
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Publisher: American Association for Cancer Research (AACR)
Date: 2019
DOI: 10.1158/1055-9965.EPI-18-0079
Abstract: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer–metabolite associations using two-s le Mendelian randomization (MR). The case–control portion of the study was conducted in nine UK centers with men ages 50–69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Thirty-five metabolites were strongly associated with prostate cancer (P & 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios) (ii) fatty acids and ratios (iii) amino acids (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal. We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk. The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.
Publisher: Cold Spring Harbor Laboratory
Date: 25-10-2020
DOI: 10.1101/2020.10.21.20215921
Abstract: This study examines associations between 51 urinary metabolites and risk of progression of diabetic nephropathy in in iduals with type 1 diabetes by employing an automated nuclear magnetic resonance (NMR) metabolomics technique suitable for large-scale urine s le collections. For 2,670 in iduals with type 1 diabetes from the FinnDiane Study, we collected 24-hour urine s les and measured metabolite concentrations by NMR. In iduals were followed for 9.0 ± 5.0 years until their first sign of progression of diabetic nephropathy, end-stage kidney disease or study end. Cox regression analyses were performed on the entire study population (overall progression), on 1,999 in iduals with normoalbuminuria and 347 in iduals with macroalbuminuria at baseline. Seven urinary metabolites were associated with overall progression after adjustment for baseline albuminuria and chronic kidney disease stage (p 8 × 10 -4 ): Leucine (hazard ratio 1.47, 95% confidence interval [1.30, 1.66] per 1-SD creatinine-scaled metabolite concentration), valine (1.38 [1.22, 1.56]), isoleucine (1.33 [1.18, 1.50]), pseudouridine (1.25 [1.11, 1.42]), threonine (1.27 [1.11, 1.46]) and citrate (0.84 [0.75, 0.93]). 2-hydroxyisobutyrate was associated with overall (1.30 [1.16, 1.45]) and also progression from normoalbuminuria (1.56 [1.25, 1.95]). Six amino acids and pyroglutamate were associated with progression from macroalbuminuria. Branched-amino acids and other urinary metabolites were associated with the progression of diabetic nephropathy on top of baseline albuminuria and chronic kidney disease. We found differences in associations for overall progression and progression from normo- and macroalbuminuria. These novel biomarker discoveries illustrate the utility of analysing urinary metabolites in entire population cohorts. In iduals with type 1 diabetes are vulnerable to diabetic nephropathy and would benefit from earlier detection of disease progression. Urinary metabolites as a direct read-out of kidney function are potential progression markers. However, analytical tools to quantify a broad panel of urinary metabolites at large scale and low cost are lacking. Recent developments in nuclear magnetic resonance address this need. This study in 2,670 in iduals with type 1 diabetes identified ten urinary metabolites associated with progression of diabetic nephropathy. Importantly, different albuminuria categories had different urinary profiles: 2-hydroxyisobutyrate was associated with progression from normoalbuminuria and branched-chain amino acids with progression from macroalbuminuria. These results provide new potential biomarkers and highlight the potential of analysing urinary metabolites on a larger scale.
Publisher: Springer Science and Business Media LLC
Date: 22-10-2021
DOI: 10.1007/S00125-021-05584-3
Abstract: This prospective, observational study examines associations between 51 urinary metabolites and risk of progression of diabetic nephropathy in in iduals with type 1 diabetes by employing an automated NMR metabolomics technique suitable for large-scale urine s le collections. We collected 24-h urine s les for 2670 in iduals with type 1 diabetes from the Finnish Diabetic Nephropathy study and measured metabolite concentrations by NMR. In iduals were followed up for 9.0 ± 5.0 years until their first sign of progression of diabetic nephropathy, end-stage kidney disease or study end. Cox regressions were performed on the entire study population (overall progression), on 1999 in iduals with normoalbuminuria and 347 in iduals with macroalbuminuria at baseline. Seven urinary metabolites were associated with overall progression after adjustment for baseline albuminuria and chronic kidney disease stage ( p 8 × 10 −4 ): leucine (HR 1.47 [95% CI 1.30, 1.66] per 1-SD creatinine-scaled metabolite concentration), valine (1.38 [1.22, 1.56]), isoleucine (1.33 [1.18, 1.50]), pseudouridine (1.25 [1.11, 1.42]), threonine (1.27 [1.11, 1.46]) and citrate (0.84 [0.75, 0.93]). 2-Hydroxyisobutyrate was associated with overall progression (1.30 [1.16, 1.45]) and also progression from normoalbuminuria (1.56 [1.25, 1.95]). Six amino acids and pyroglutamate were associated with progression from macroalbuminuria. Branched-chain amino acids and other urinary metabolites were associated with the progression of diabetic nephropathy on top of baseline albuminuria and chronic kidney disease. We found differences in associations for overall progression and progression from normo- and macroalbuminuria. These novel discoveries illustrate the utility of analysing urinary metabolites in entire population cohorts.
Publisher: Springer Science and Business Media LLC
Date: 04-05-2018
Publisher: Oxford University Press (OUP)
Date: 26-03-2012
Abstract: High-throughput metabolite quantification holds promise for cardiovascular risk assessment. Here, we evaluated whether metabolite quantification by nuclear magnetic resonance (NMR) improves prediction of subclinical atherosclerosis in comparison to conventional lipid testing. Circulating lipids, lipoprotein subclasses, and small molecules were assayed by NMR for 1595 in iduals aged 24-39 years from the population-based Cardiovascular Risk in Young Finns Study. Carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis, was measured in 2001 and 2007. Baseline conventional risk factors and systemic metabolites were used to predict 6-year incidence of high IMT (≥ 90 th percentile) or plaque. The best prediction of high intima-media thickness was achieved when total and HDL cholesterol were replaced by NMR-determined LDL cholesterol and medium HDL, docosahexaenoic acid, and tyrosine in prediction models with risk factors from the Framingham risk score. The extended prediction model improved risk stratification beyond established risk factors alone area under the receiver operating characteristic curve 0.764 vs. 0.737, P =0.02, and net reclassification index 17.6%, P =0.0008. Higher docosahexaenoic acid levels were associated with decreased risk for incident high IMT (odds ratio: 0.74 95% confidence interval: 0.67-0.98 P = 0.007). Tyrosine (1.33 1.10-1.60 P = 0.003) and glutamine (1.38 1.13-1.68 P = 0.001) levels were associated with 6-year incident high IMT independent of lipid measures. Furthermore, these amino acids were cross-sectionally associated with carotid IMT and the presence of angiographically ascertained coronary artery disease in independent populations. High-throughput metabolite quantification, with new systemic biomarkers, improved risk stratification for subclinical atherosclerosis in comparison to conventional lipids and could potentially be useful for early cardiovascular risk assessment.
Publisher: Public Library of Science (PLoS)
Date: 31-07-2014
Publisher: Public Library of Science (PLoS)
Date: 18-03-2015
Publisher: Wiley
Date: 07-12-2018
DOI: 10.1002/IJC.31929
Publisher: Springer Science and Business Media LLC
Date: 29-01-2012
DOI: 10.1038/NG.1073
Publisher: Public Library of Science (PLoS)
Date: 23-10-2019
Publisher: Oxford University Press (OUP)
Date: 29-09-2011
Abstract: To test whether serum apolipoprotein B (apoB) and low-density lipoprotein (LDL) particle characteristics (oxidation and mean particle size) predict the incidence of metabolic syndrome (MetS). The 6-year follow-up study included 1429 adults (baseline mean age 31.5). Lipids, apoB, and apoA1 were measured at baseline in 2001. LDL oxidation was measured with monoclonal antibody-based enzyme-linked immunosorbent assay (oxLDL-prot) and with a method measuring oxidized lipids in LDL (oxLDL-lipids). Mean LDL particle size was calculated from proton nuclear magnetic resonance spectroscopy data. Increased concentrations of both oxLDL-measures were associated with increased apoB levels but not with LDL particle size. The odds ratios (95% confidence intervals) for MetS incidence during a 6-year follow up by quartiles of apoB were 2.0 (1.0-3.8) for the second quartile, 3.1 (1.7-5.7) for the third quartile, and 4.2 (2.3-7.6) for the fourth quartile. This association remained after adjusting for age, sex, body mass index, homeostasis model assessment for insulin resistance, C-reactive protein, smoking, LDL cholesterol, oxidized LDL measures (p ≤ 0.01) in addition to risk factors comprising the MetS (p = 0.03). OxLDL-prot and oxLDL-lipids levels were not independently associated with incident MetS after adjusting for apoB. Mean LDL particle size was not associated with the incidence of MetS. ApoB is associated with increased risk of MetS incidence. We found no clear evidence to suggest that increased LDL oxidation or small mean LDL particle size would facilitate the development of MetS.
Publisher: BMJ
Date: 07-2019
DOI: 10.1136/BMJOPEN-2017-020900
Abstract: Nuclear magnetic resonance (NMR) metabolomics is high throughput and cost-effective, with the potential to improve the understanding of disease and risk. We examine the circulating metabolic profile by quantitative NMR metabolomics of a s le of Australian 11–12 year olds children and their parents, describe differences by age and sex, and explore the correlation of metabolites in parent–child dyads. The population-based cross-sectional Child Health CheckPoint study nested within the Longitudinal Study of Australian Children. Blood s les collected from CheckPoint participants at assessment centres in seven Australian cities and eight regional towns February 2015–March 2016. 1180 children and 1325 parents provided a blood s le and had metabolomics data available. This included 1133 parent–child dyads (518 mother–daughter, 469 mother–son, 68 father–daughter and 78 father–son). 228 metabolic measures were obtained for each participant. We focused on 74 biomarkers including amino acid species, lipoprotein subclass measures, lipids, fatty acids, measures related to fatty acid saturation, and composite markers of inflammation and energy homeostasis. We identified differences in the concentration of specific metabolites between childhood and adulthood and in metabolic profiles in children and adults by sex. In general, metabolite concentrations were higher in adults than children and sex differences were larger in adults than in children. Positive correlations were observed for the majority of metabolites including isoleucine (CC 0.33, 95% CI 0.27 to 0.38), total cholesterol (CC 0.30, 95% CI 0.24 to 0.35) and omega 6 fatty acids (CC 0.28, 95% CI 0.23 to 0.34) in parent–child comparisons. We describe the serum metabolite profiles from mid-childhood and adulthood in a population-based s le, together with a parent–child concordance. Differences in profiles by age and sex were observed. These data will be informative for investigation of the childhood origins of adult non-communicable diseases and for comparative studies in other populations.
Publisher: American Diabetes Association
Date: 06-2020
DOI: 10.2337/DB20-516-P
Abstract: People living with type 1 diabetes have increased risk to develop diabetic nephropathy. No targeted cure exists, but the progression can be slowed down if detected early. We tested whether metabolic biomarkers measured in urine could predict progression of diabetic nephropathy (DN) in the Finnish nationwide FinnDiane Study. At baseline, 18 urine metabolites were measured with nuclear magnetic resonance metabolomics and scaled relative to urine creatinine. In iduals were followed for DN status for 9.0 years (± 5.1 years) until they progressed to their most severe DN status (334 events) or the latest known DN status for non-progressors. A Bonferroni-corrected P& .003 was considered significant. Five out of 18 urine metabolites were robustly associated with risk for DN progression in Cox regression models adjusted for sex, year of diabetes diagnosis as well as baseline age, DN status, BMI and eGFR. In iduals with elevated urinary levels of alanine (Hazard Ratio (HR) = 1.49 [1.26, 1.77] per 1-SD creatinine-scaled metabolite concentration, , P=3×10-6), valine (HR = 1.34 [1.22, 1.48], P=4×10-9), 2–hydroxyisobutyrate (HR = 1.48 [1.30, 1.67], P=1×10-9), cis-Aconitate (HR = 1.17 [1.06, 1.28], P=9×10-4) and pseudouridine (HR = 1.45 [1.24, 1.69], P=4×10-6) showed higher DN progression rate. We conclude that urinary biomarkers are indicative of kidney disease progression in type 1 diabetes, independently of baseline microalbuminuria and eGFR. The urinary biomarkers span multiple metabolic pathways, including microbial metabolism, citric acid cycle, and amino acids reflecting adiposity and dietary quality. S. Mutter: None. E.A. Valo: None. V. Aittomäki: Employee Self Nightingale Health Ltd. Other Relationship Self Nightingale Health Ltd. C. Forsblom: None. P. Groop: Advisory Panel Self Boehringer Ingelheim International GmbH, Sanofi, Sanofi. Speaker’s Bureau Self Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medscape, Merck Sharp & Dohme Corp., Mundipharma International. P. Wurtz: Employee Self Nightingale Health Ltd. Stock/Shareholder Self Nightingale Health Ltd. Folkhälsan Finland Novo Nordisk Foundation Academy of Finland
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2018
DOI: 10.1161/CIRCGEN.118.002234
Abstract: Integration of systems-level biomolecular information with electronic health records has led to recent interest in the glycoprotein acetyls (GlycA) biomarker—a serum- or plasma-derived nuclear magnetic resonance spectroscopy signal that represents the abundance of circulating glycated proteins. GlycA predicts risk of erse outcomes, including cardiovascular disease, type 2 diabetes mellitus, and all-cause mortality however, the underlying detailed associations of GlycA’s morbidity and mortality risk are currently unknown. We used 2 population-based cohorts totaling 11 861 adults from the Finnish general population to test for an association with 468 common incident hospitalization and mortality outcomes during an 8-year follow-up. Further, we utilized 900 angiography patients to test for GlycA association with mortality risk and potential utility for mortality risk discrimination during 12-year follow-up. New associations with GlycA and incident alcoholic liver disease, chronic renal failure, glomerular diseases, chronic obstructive pulmonary disease, inflammatory polyarthropathies, and hypertension were uncovered, and known incident disease associations were replicated. GlycA associations for incident disease outcomes were in general not attenuated when adjusting for hsCRP (high-sensitivity C-reactive protein). Among 900 patients referred to angiography, GlycA had hazard ratios of 4.87 (95% CI, 2.45–9.65) and 5.00 (95% CI, 2.38–10.48) for 12-year risk of mortality in the fourth and fifth quintiles by GlycA levels, demonstrating its prognostic potential for identification of high-risk in iduals. When modeled together, both hsCRP and GlycA were attenuated but remained significant. GlycA was predictive of myriad incident diseases across many major internal organs and stratified mortality risk in angiography patients. Both GlycA and hsCRP had shared and independent contributions to mortality risk, suggesting chronic inflammation as an etiological factor. GlycA may be useful in improving risk prediction in specific disease settings.
Publisher: Elsevier BV
Date: 2013
Abstract: Impaired fetal growth is independently associated with an increased risk of cardiovascular events in adulthood. Prevention strategies that can be implemented during adulthood have not been identified. The objective was to determine whether habitual omega-3 (n-3) fatty acid intake is associated with the rate of increase of carotid intima-media thickness during adulthood in in iduals with impaired fetal growth. This was a population-based, prospective cohort study of 1573 adults in Finland. Carotid intima-media thickness was assessed in 2001 (at ages 24-39 y) and in 2007. Participants were categorized as having had impaired fetal growth (term birth with birth weight <10th percentile for sex or preterm birth with birth weight <25th percentile for gestational age and sex n = 193) or normal fetal growth (all other participants n = 1380). Omega-3 fatty acid intake was assessed by using a food-frequency questionnaire and on the basis of serum fatty acid concentrations. In multivariable models, the 6-y progression of carotid intima-media thickness was inversely associated with dietary omega-3 fatty acids in those with impaired fetal growth (P = 0.04). Similarly, serum omega-3 fatty acid concentrations were inversely associated with the 6-y progression of carotid intima-media thickness in those with impaired fetal growth (P = 0.04) but were not noted in those with normal fetal growth (P = 0.94 and P = 0.26, respectively). Dietary intake of omega-3 fatty acids is associated with a slower rate of increase in carotid intima-media thickness in those with impaired fetal growth.
Publisher: Elsevier BV
Date: 12-2019
Publisher: Springer Science and Business Media LLC
Date: 08-2017
Publisher: The Endocrine Society
Date: 09-2011
DOI: 10.1210/JC.2011-1243
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2014
DOI: 10.1161/ATVBAHA.113.302934
Abstract: There is some evidence that people born with high birth weight may be at increased risk of cardiovascular disease in adulthood. Details of the underlying mechanisms remain unknown. We sought to determine whether people born large for gestational age have poor arterial health, increased adiposity, and a poor cardiovascular risk factor profile. Carotid intima-media thickness, brachial flow–mediated dilatation, and cardiovascular risk factors were compared between young adults (24–45 years) born at term who were large for gestational age (birth weight th percentile n=171), and a control group with normal birth weight (50–75th percentile n=525), in the Cardiovascular Risk in Young Finns Study. Those born large for gestational age had higher body mass index throughout childhood, adolescence, and as young adults (26.4 kg/m 2 [SD 4.9], versus normal birth weight 25.1 kg/m 2 [SD 4.6] P =0.002), and 2-fold greater risk of obesity. Other cardiovascular risk factors and arterial function did not differ however, carotid intima-media thickness was increased in people born large for gestational age (0.60 mm [SD 0.09], versus normal birth weight 0.57 mm [SD 0.09] P =0.003), independent of cardiovascular risk factors ( P =0.001 after adjustment). Both obesity and high birth weight were independently associated with carotid intima-media thickness in a graded and additive fashion. Young adults born large for gestational age are more likely to be obese, yet have an otherwise healthy cardiovascular risk profile. Nonetheless, they have increased carotid intima-media thickness, a marker of subclinical atherosclerosis, consistent with an increased risk of cardiovascular disease.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Peter Würtz.