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Dietary metabolite profiling brings new insight into the relationship between nutrition and metabolic risk : An IMI DIRECT study

Eriksen, Rebeca ; Perez, Isabel Garcia ; Posma, Joram M. ; Haid, Mark ; Sharma, Sapna ; Prehn, Cornelia ; Thomas, Louise E. ; Koivula, Robert W. LU ; Bizzotto, Roberto and Mari, Andrea , et al. (2020) In EBioMedicine 58.
Abstract

Background: Dietary advice remains the cornerstone of prevention and management of type 2 diabetes (T2D). However, understanding the efficacy of dietary interventions is confounded by the challenges inherent in assessing free living diet. Here we profiled dietary metabolites to investigate glycaemic deterioration and cardiometabolic risk in people at risk of or living with T2D. Methods: We analysed data from plasma collected at baseline and 18-month follow-up in individuals from the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohort 1 n = 403 individuals with normal or impaired glucose regulation (prediabetic) and cohort 2 n = 458 individuals with new onset of T2D. A dietary metabolite... (More)

Background: Dietary advice remains the cornerstone of prevention and management of type 2 diabetes (T2D). However, understanding the efficacy of dietary interventions is confounded by the challenges inherent in assessing free living diet. Here we profiled dietary metabolites to investigate glycaemic deterioration and cardiometabolic risk in people at risk of or living with T2D. Methods: We analysed data from plasma collected at baseline and 18-month follow-up in individuals from the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohort 1 n = 403 individuals with normal or impaired glucose regulation (prediabetic) and cohort 2 n = 458 individuals with new onset of T2D. A dietary metabolite profile model (Tpred) was constructed using multivariable regression of 113 plasma metabolites obtained from targeted metabolomics assays. The continuous Tpred score was used to explore the relationships between diet, glycaemic deterioration and cardio-metabolic risk via multiple linear regression models. Findings: A higher Tpred score was associated with healthier diets high in wholegrain (β=3.36 g, 95% CI 0.31, 6.40 and β=2.82 g, 95% CI 0.06, 5.57) and lower energy intake (β=-75.53 kcal, 95% CI -144.71, -2.35 and β=-122.51 kcal, 95% CI -186.56, -38.46), and saturated fat (β=-0.92 g, 95% CI -1.56, -0.28 and β=–0.98 g, 95% CI -1.53, -0.42 g), respectively for cohort 1 and 2. In both cohorts a higher Tpred score was also associated with lower total body adiposity and favourable lipid profiles HDL-cholesterol (β=0.07 mmol/L, 95% CI 0.03, 0.1), (β=0.08 mmol/L, 95% CI 0.04, 0.1), and triglycerides (β=-0.1 mmol/L, 95% CI -0.2, -0.03), (β=-0.2 mmol/L, 95% CI -0.3, -0.09), respectively for cohort 1 and 2. In cohort 2, the Tpred score was negatively associated with liver fat (β=-0.74%, 95% CI -0.67, -0.81), and lower fasting concentrations of HbA1c (β=-0.9 mmol/mol, 95% CI -1.5, -0.1), glucose (β=-0.2 mmol/L, 95% CI -0.4, -0.05) and insulin (β=-11.0 pmol/mol, 95% CI -19.5, -2.6). Longitudinal analysis showed at 18-month follow up a higher Tpred score was also associated lower total body adiposity in both cohorts and lower fasting glucose (β=-0.2 mmol/L, 95% CI -0.3, -0.01) and insulin (β=-9.2 pmol/mol, 95% CI -17.9, -0.4) concentrations in cohort 2. Interpretation: Plasma dietary metabolite profiling provides objective measures of diet intake, showing a relationship to glycaemic deterioration and cardiometabolic health. Funding: This work was supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115,317 (DIRECT), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007–2013) and EFPIA companies.

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Contribution to journal
publication status
published
subject
keywords
Cardiometabolic health, Dietary patterns, Metabolic profiling, Type 2 diabetes
in
EBioMedicine
volume
58
article number
102932
publisher
Elsevier
external identifiers
  • scopus:85088933440
  • pmid:32763829
ISSN
2352-3964
DOI
10.1016/j.ebiom.2020.102932
language
English
LU publication?
yes
id
5cd63ee5-9d37-4e8d-8b75-9665aa3efb5a
date added to LUP
2020-08-13 08:40:24
date last changed
2024-05-01 16:14:37
@article{5cd63ee5-9d37-4e8d-8b75-9665aa3efb5a,
  abstract     = {{<p>Background: Dietary advice remains the cornerstone of prevention and management of type 2 diabetes (T2D). However, understanding the efficacy of dietary interventions is confounded by the challenges inherent in assessing free living diet. Here we profiled dietary metabolites to investigate glycaemic deterioration and cardiometabolic risk in people at risk of or living with T2D. Methods: We analysed data from plasma collected at baseline and 18-month follow-up in individuals from the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohort 1 n = 403 individuals with normal or impaired glucose regulation (prediabetic) and cohort 2 n = 458 individuals with new onset of T2D. A dietary metabolite profile model (T<sub>pred</sub>) was constructed using multivariable regression of 113 plasma metabolites obtained from targeted metabolomics assays. The continuous T<sub>pred</sub> score was used to explore the relationships between diet, glycaemic deterioration and cardio-metabolic risk via multiple linear regression models. Findings: A higher T<sub>pred</sub> score was associated with healthier diets high in wholegrain (β=3.36 g, 95% CI 0.31, 6.40 and β=2.82 g, 95% CI 0.06, 5.57) and lower energy intake (β=-75.53 kcal, 95% CI -144.71, -2.35 and β=-122.51 kcal, 95% CI -186.56, -38.46), and saturated fat (β=-0.92 g, 95% CI -1.56, -0.28 and β=–0.98 g, 95% CI -1.53, -0.42 g), respectively for cohort 1 and 2. In both cohorts a higher T<sub>pred</sub> score was also associated with lower total body adiposity and favourable lipid profiles HDL-cholesterol (β=0.07 mmol/L, 95% CI 0.03, 0.1), (β=0.08 mmol/L, 95% CI 0.04, 0.1), and triglycerides (β=-0.1 mmol/L, 95% CI -0.2, -0.03), (β=-0.2 mmol/L, 95% CI -0.3, -0.09), respectively for cohort 1 and 2. In cohort 2, the T<sub>pred</sub> score was negatively associated with liver fat (β=-0.74%, 95% CI -0.67, -0.81), and lower fasting concentrations of HbA1c (β=-0.9 mmol/mol, 95% CI -1.5, -0.1), glucose (β=-0.2 mmol/L, 95% CI -0.4, -0.05) and insulin (β=-11.0 pmol/mol, 95% CI -19.5, -2.6). Longitudinal analysis showed at 18-month follow up a higher T<sub>pred</sub> score was also associated lower total body adiposity in both cohorts and lower fasting glucose (β=-0.2 mmol/L, 95% CI -0.3, -0.01) and insulin (β=-9.2 pmol/mol, 95% CI -17.9, -0.4) concentrations in cohort 2. Interpretation: Plasma dietary metabolite profiling provides objective measures of diet intake, showing a relationship to glycaemic deterioration and cardiometabolic health. Funding: This work was supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115,317 (DIRECT), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007–2013) and EFPIA companies.</p>}},
  author       = {{Eriksen, Rebeca and Perez, Isabel Garcia and Posma, Joram M. and Haid, Mark and Sharma, Sapna and Prehn, Cornelia and Thomas, Louise E. and Koivula, Robert W. and Bizzotto, Roberto and Mari, Andrea and Giordano, Giuseppe N. and Pavo, Imre and Schwenk, Jochen M. and De Masi, Federico and Tsirigos, Konstantinos D. and Brunak, Søren and Viñuela, Ana and Mahajan, Anubha and McDonald, Timothy J. and Kokkola, Tarja and Rutter, Femke and Teare, Harriet and Hansen, Tue H. and Fernandez, Juan and Jones, Angus and Jennison, Chris and Walker, Mark and McCarthy, Mark I. and Pedersen, Oluf and Ruetten, Hartmut and Forgie, Ian and Bell, Jimmy D. and Pearson, Ewan R. and Franks, Paul W. and Adamski, Jerzy and Holmes, Elaine and Frost, Gary}},
  issn         = {{2352-3964}},
  keywords     = {{Cardiometabolic health; Dietary patterns; Metabolic profiling; Type 2 diabetes}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{EBioMedicine}},
  title        = {{Dietary metabolite profiling brings new insight into the relationship between nutrition and metabolic risk : An IMI DIRECT study}},
  url          = {{http://dx.doi.org/10.1016/j.ebiom.2020.102932}},
  doi          = {{10.1016/j.ebiom.2020.102932}},
  volume       = {{58}},
  year         = {{2020}},
}