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Plasma proteomic si...
Plasma proteomic signatures of a direct measure of insulin sensitivity in two population cohorts
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- Zanetti, Daniela (författare)
- Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA.;VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA,Stanford University School of Medicine, Stanford, CA, USA; VA Palo Alto Health Care System, Palo Alto, CA, USA
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- Stell, Laurel (författare)
- VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA.;Stanford Univ, Dept Biomed Data Sci, Sch Med, Stanford, CA USA,VA Palo Alto Health Care System, Palo Alto, CA, USA; Stanford University School of Medicine, Stanford, CA, USA
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- Gustafsson, Stefan (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Uppsala University, Uppsala
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- Abbasi, Fahim (författare)
- Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA.;Stanford Univ, Stanford Diabet Res Ctr, Sch Med, Stanford, CA 94305 USA,Stanford University School of Medicine, Stanford, CA, USA
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- Tsao, Philip S. (författare)
- Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA.;VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA.;Stanford Univ, Stanford Cardiovasc Inst, Sch Med, Stanford, CA 94305 USA,Stanford University School of Medicine, Stanford, CA, USA; VA Palo Alto Health Care System, Palo Alto, CA, USA
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- Knowles, Joshua W. (författare)
- Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA.;Stanford Univ, Stanford Diabet Res Ctr, Sch Med, Stanford, CA 94305 USA.;Stanford Univ, Stanford Cardiovasc Inst, Sch Med, Stanford, CA 94305 USA.;Stanford Univ, Stanford Prevent Res Ctr, Sch Med, Stanford, CA USA,Stanford University School of Medicine, Stanford, CA, USA
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- Zethelius, Björn (författare)
- Uppsala universitet,Geriatrik,Uppsala University, Uppsala
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- Ärnlöv, Johan, 1970- (författare)
- Högskolan Dalarna,Karolinska Institutet,Karolinska Inst, Care Sci & Soc, Div Family Med & Primary Care, Dept Neurobiol, Stockholm, Sweden.;Dalarna Univ, Dept Hlth & Social Studies, Falun, Sweden. Ctr Res Epidemiol & Populat Hlth, Clin Epidemiol, Inserm U1018, Villejuif, France,Medicinsk vetenskap,Karolinska Institutet, Stockholm
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- Balkau, Beverley (författare)
- Centre for Research in Epidemiology and Population Health, Villejuif, France
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- Walker, Mark (författare)
- Newcastle Univ, Translat & Clin Res Inst, Newcastle Upon Tyne, England
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- Lazzeroni, Laura C. (författare)
- Stanford Univ, Dept Biomed Data Sci, Sch Med, Stanford, CA USA.;Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA USA
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- Lind, Lars (författare)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA.;VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA.;Stanford Univ, Stanford Diabet Res Ctr, Sch Med, Stanford, CA 94305 USA.;Stanford Univ, Stanford Cardiovasc Inst, Sch Med, Stanford, CA 94305 USA.;Stanford Univ, Dept Epidemiol & Populat Hlth, Sch Med, Stanford, CA 94305 USA,Stanford University School of Medicine, Stanford, CA, USA; VA Palo Alto Health Care System, Palo Alto, CA, USA
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- Petrie, John R. (författare)
- Univ Glasgow, Coll Med Vet & Life Sci, Sch Hlth & Wellbeing, Glasgow, Scotland
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- Assimes, Themistocles L. (författare)
- Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA.;VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA.;Stanford Univ, Stanford Diabet Res Ctr, Sch Med, Stanford, CA 94305 USA.;Stanford Univ, Stanford Cardiovasc Inst, Sch Med, Stanford, CA 94305 USA.;Stanford Univ, Dept Epidemiol & Populat Hlth, Sch Med, Stanford, CA 94305 USA
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Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA;VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA Stanford University School of Medicine, Stanford, CA, USA; VA Palo Alto Health Care System, Palo Alto, CA, USA (creator_code:org_t)
- Springer, 2023
- 2023
- Engelska.
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 66:9, s. 1643-1654
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Abstract
Ämnesord
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- Aims/hypothesis The euglycaemic-hyperinsulinaemic clamp (EIC) is the reference standard for the measurement of whole-body insulin sensitivity but is laborious and expensive to perform. We aimed to assess the incremental value of high-through-put plasma proteomic profiling in developing signatures correlating with the M value derived from the EIC.Methods We measured 828 proteins in the fasting plasma of 966 participants from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study and 745 participants from the Uppsala Longitudinal Study of Adult Men (ULSAM) using a high-throughput proximity extension assay. We used the least absolute shrinkage and selection operator (LASSO) approach using clinical variables and protein measures as features. Models were tested within and across cohorts. Our primary model performance metric was the proportion of the M value variance explained (R-2).Results A standard LASSO model incorporating 53 proteins in addition to routinely available clinical variables increased the M value R-2 from 0.237 (95% CI 0.178, 0.303) to 0.456 (0.372, 0.536) in RISC. A similar pattern was observed in ULSAM, in which the M value R-2 increased from 0.443 (0.360, 0.530) to 0.632 (0.569, 0.698) with the addition of 61 proteins. Models trained in one cohort and tested in the other also demonstrated significant improvements in R-2 despite differences in baseline cohort characteristics and clamp methodology (RISC to ULSAM: 0.491 [0.433, 0.539] for 51 proteins; ULSAM to RISC: 0.369 [0.331, 0.416] for 67 proteins). A randomised LASSO and stability selection algorithm selected only two proteins per cohort (three unique proteins), which improved R-2 but to a lesser degree than in standard LASSO models: 0.352 (0.266, 0.439) in RISC and 0.495 (0.404, 0.585) in ULSAM. Reductions in improvements of R-2 with randomised LASSO and stability selection were less marked in cross-cohort analyses (RISC to ULSAM R-2 0.444 [0.391, 0.497]; ULSAM to RISC R-2 0.348 [0.300, 0.396]). Models of proteins alone were as effective as models that included both clinical variables and proteins using either standard or randomised LASSO. The single most consistently selected protein across all analyses and models was IGF-binding protein 2.Conclusions/interpretation A plasma proteomic signature identified using a standard LASSO approach improves the cross-sectional estimation of the M value over routine clinical variables. However, a small subset of these proteins identified using a stability selection algorithm affords much of this improvement, especially when considering cross-cohort analyses. Our approach provides opportunities to improve the identification of insulin-resistant individuals at risk of insulin resistance-related adverse health consequences.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Euglycaemic-hyperinsulinaemic clamp
- Insulin resistance
- Insulin sensitivity
- LASSO
- Plasma proteomics
- Population study
- Stability selection
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Zanetti, Daniela
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Stell, Laurel
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Gustafsson, Stef ...
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Abbasi, Fahim
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Tsao, Philip S.
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Knowles, Joshua ...
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visa fler...
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Zethelius, Björn
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Ärnlöv, Johan, 1 ...
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Balkau, Beverley
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Walker, Mark
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Lazzeroni, Laura ...
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Lind, Lars
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Petrie, John R.
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Assimes, Themist ...
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Endokrinologi oc ...
- Artiklar i publikationen
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Diabetologia
- Av lärosätet
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Uppsala universitet
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Karolinska Institutet
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Högskolan Dalarna