PMID- 36289459
OWN - NLM
STAT- MEDLINE
DCOM- 20221101
LR  - 20230918
IS  - 1741-7015 (Electronic)
IS  - 1741-7015 (Linking)
VI  - 20
IP  - 1
DP  - 2022 Oct 27
TI  - Metabolomics analysis of type 2 diabetes remission identifies 12 metabolites with 
      predictive capacity: a CORDIOPREV clinical trial study.
PG  - 373
LID - 10.1186/s12916-022-02566-z [doi]
LID - 373
AB  - BACKGROUND: Type 2 diabetes mellitus (T2DM) is one of the most widely spread 
      diseases, affecting around 90% of the patients with diabetes. Metabolomics has 
      proven useful in diabetes research discovering new biomarkers to assist in 
      therapeutical studies and elucidating pathways of interest. However, this 
      technique has not yet been applied to a cohort of patients that have remitted 
      from T2DM. METHODS: All patients with a newly diagnosed T2DM at baseline 
      (n = 190) were included. An untargeted metabolomics approach was employed to 
      identify metabolic differences between individuals who remitted (RE), and those 
      who did not (non-RE) from T2DM, during a 5-year study of dietary intervention. 
      The biostatistical pipeline consisted of an orthogonal projection on the latent 
      structure discriminant analysis (O-PLS DA), a generalized linear model (GLM), a 
      receiver operating characteristic (ROC), a DeLong test, a Cox regression, and 
      pathway analyses. RESULTS: The model identified a significant increase in 12 
      metabolites in the non-RE group compared to the RE group. Cox proportional hazard 
      models, calculated using these 12 metabolites, showed that patients in the 
      high-score tercile had significantly (p-value < 0.001) higher remission 
      probabilities (Hazard Ratio, HR, (high versus low) = 2.70) than those in the 
      lowest tercile. The predictive power of these metabolites was further studied 
      using GLMs and ROCs. The area under the curve (AUC) of the clinical variables 
      alone is 0.61, but this increases up to 0.72 if the 12 metabolites are 
      considered. A DeLong test shows that this difference is statistically significant 
      (p-value = 0.01). CONCLUSIONS: Our study identified 12 endogenous metabolites 
      with the potential to predict T2DM remission following a dietary intervention. 
      These metabolites, combined with clinical variables, can be used to provide, in 
      clinical practice, a more precise therapy. TRIAL REGISTRATION: 
      ClinicalTrials.gov, NCT00924937.
CI  - (c) 2022. The Author(s).
FAU - Mora-Ortiz, Marina
AU  - Mora-Ortiz M
AD  - Lipids and Atherosclerosis Unit, Internal Medicine Unit, Reina Sofia University 
      Hospital, 14004, Cordoba, Spain.
AD  - Department of Medical and Surgical Science, University of Cordoba, 14004, 
      Cordoba, Spain.
AD  - Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Av. Menendez Pidal, 
      s/n, 14004, Cordoba, Spain.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud 
      Carlos III, 28029, Madrid, Spain.
FAU - Alcala-Diaz, Juan F
AU  - Alcala-Diaz JF
AD  - Lipids and Atherosclerosis Unit, Internal Medicine Unit, Reina Sofia University 
      Hospital, 14004, Cordoba, Spain.
AD  - Department of Medical and Surgical Science, University of Cordoba, 14004, 
      Cordoba, Spain.
AD  - Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Av. Menendez Pidal, 
      s/n, 14004, Cordoba, Spain.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud 
      Carlos III, 28029, Madrid, Spain.
FAU - Rangel-Zuniga, Oriol Alberto
AU  - Rangel-Zuniga OA
AD  - Lipids and Atherosclerosis Unit, Internal Medicine Unit, Reina Sofia University 
      Hospital, 14004, Cordoba, Spain.
AD  - Department of Medical and Surgical Science, University of Cordoba, 14004, 
      Cordoba, Spain.
AD  - Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Av. Menendez Pidal, 
      s/n, 14004, Cordoba, Spain.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud 
      Carlos III, 28029, Madrid, Spain.
FAU - Arenas-de Larriva, Antonio Pablo
AU  - Arenas-de Larriva AP
AD  - Lipids and Atherosclerosis Unit, Internal Medicine Unit, Reina Sofia University 
      Hospital, 14004, Cordoba, Spain.
AD  - Department of Medical and Surgical Science, University of Cordoba, 14004, 
      Cordoba, Spain.
AD  - Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Av. Menendez Pidal, 
      s/n, 14004, Cordoba, Spain.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud 
      Carlos III, 28029, Madrid, Spain.
FAU - Abollo-Jimenez, Fernando
AU  - Abollo-Jimenez F
AD  - Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Av. Menendez Pidal, 
      s/n, 14004, Cordoba, Spain.
FAU - Luque-Cordoba, Diego
AU  - Luque-Cordoba D
AD  - Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Av. Menendez Pidal, 
      s/n, 14004, Cordoba, Spain.
AD  - Department of Analytical Chemistry and Nanochemistry University Institute, 
      Universidad de Cordoba, Cordoba, Spain.
AD  - CIBER de Fragilidad Y Envejecimiento Saludable (CIBERFES), Instituto de Salud 
      Carlos III, Madrid, Spain.
FAU - Priego-Capote, Feliciano
AU  - Priego-Capote F
AD  - Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Av. Menendez Pidal, 
      s/n, 14004, Cordoba, Spain.
AD  - Department of Analytical Chemistry and Nanochemistry University Institute, 
      Universidad de Cordoba, Cordoba, Spain.
AD  - CIBER de Fragilidad Y Envejecimiento Saludable (CIBERFES), Instituto de Salud 
      Carlos III, Madrid, Spain.
FAU - Malagon, Maria M
AU  - Malagon MM
AD  - Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Av. Menendez Pidal, 
      s/n, 14004, Cordoba, Spain.
AD  - Department of Cell Biology, Physiology and Immunology, University of Cordoba, 
      14004, Cordoba, Spain.
FAU - Delgado-Lista, Javier
AU  - Delgado-Lista J
AD  - Lipids and Atherosclerosis Unit, Internal Medicine Unit, Reina Sofia University 
      Hospital, 14004, Cordoba, Spain.
AD  - Department of Medical and Surgical Science, University of Cordoba, 14004, 
      Cordoba, Spain.
AD  - Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Av. Menendez Pidal, 
      s/n, 14004, Cordoba, Spain.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud 
      Carlos III, 28029, Madrid, Spain.
FAU - Ordovas, Jose M
AU  - Ordovas JM
AD  - Nutrition and Genomics Laboratory, J.M.-US Department of Agriculture Human 
      Nutrition Research Center On Aging at, Tufts University, Boston, MA, 02111, USA.
AD  - IMDEA Alimentacion, Madrid, Spain.
AD  - CNIC, 28049, Madrid, Spain.
FAU - Perez-Martinez, Pablo
AU  - Perez-Martinez P
AD  - Lipids and Atherosclerosis Unit, Internal Medicine Unit, Reina Sofia University 
      Hospital, 14004, Cordoba, Spain.
AD  - Department of Medical and Surgical Science, University of Cordoba, 14004, 
      Cordoba, Spain.
AD  - Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Av. Menendez Pidal, 
      s/n, 14004, Cordoba, Spain.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud 
      Carlos III, 28029, Madrid, Spain.
FAU - Camargo, Antonio
AU  - Camargo A
AD  - Lipids and Atherosclerosis Unit, Internal Medicine Unit, Reina Sofia University 
      Hospital, 14004, Cordoba, Spain. antonio.camargo@imibic.org.
AD  - Department of Medical and Surgical Science, University of Cordoba, 14004, 
      Cordoba, Spain. antonio.camargo@imibic.org.
AD  - Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Av. Menendez Pidal, 
      s/n, 14004, Cordoba, Spain. antonio.camargo@imibic.org.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud 
      Carlos III, 28029, Madrid, Spain. antonio.camargo@imibic.org.
FAU - Lopez-Miranda, Jose
AU  - Lopez-Miranda J
AUID- ORCID: 0000-0002-8844-0718
AD  - Lipids and Atherosclerosis Unit, Internal Medicine Unit, Reina Sofia University 
      Hospital, 14004, Cordoba, Spain. jlopezmir@uco.es.
AD  - Department of Medical and Surgical Science, University of Cordoba, 14004, 
      Cordoba, Spain. jlopezmir@uco.es.
AD  - Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Av. Menendez Pidal, 
      s/n, 14004, Cordoba, Spain. jlopezmir@uco.es.
AD  - CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud 
      Carlos III, 28029, Madrid, Spain. jlopezmir@uco.es.
LA  - eng
SI  - ClinicalTrials.gov/NCT00924937
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221027
PL  - England
TA  - BMC Med
JT  - BMC medicine
JID - 101190723
RN  - 0 (Biomarkers)
SB  - IM
MH  - Humans
MH  - Biomarkers
MH  - *Diabetes Mellitus, Type 2/diagnosis
MH  - Discriminant Analysis
MH  - Metabolomics/methods
MH  - ROC Curve
PMC - PMC9609192
OTO - NOTNLM
OT  - Diabetes
OT  - Insulin resistance
OT  - Metabolomics
OT  - Prospective human study
COIS- The authors declare that they have no competing interests.
EDAT- 2022/10/28 06:00
MHDA- 2022/10/29 06:00
PMCR- 2022/10/27
CRDT- 2022/10/27 00:14
PHST- 2022/05/16 00:00 [received]
PHST- 2022/09/12 00:00 [accepted]
PHST- 2022/10/27 00:14 [entrez]
PHST- 2022/10/28 06:00 [pubmed]
PHST- 2022/10/29 06:00 [medline]
PHST- 2022/10/27 00:00 [pmc-release]
AID - 10.1186/s12916-022-02566-z [pii]
AID - 2566 [pii]
AID - 10.1186/s12916-022-02566-z [doi]
PST - epublish
SO  - BMC Med. 2022 Oct 27;20(1):373. doi: 10.1186/s12916-022-02566-z.