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Metabolome-Defined Obesity and the Risk of Future Type 2 Diabetes and Mortality

Ottosson, Filip LU ; Smith, Einar LU ; Ericson, Ulrika LU ; Brunkwall, Louise LU ; Orho-Melander, Marju LU ; Di Somma, Salvatore LU ; Antonini, Paola ; Nilsson, Peter M LU ; Fernandez, Céline LU and Melander, Olle LU orcid (2022) In Diabetes Care 45(5). p.1260-1267
Abstract

OBJECTIVE: Obesity is a key risk factor for type 2 diabetes; however, up to 20% of patients are normal weight. Our aim was to identify metabolite patterns reproducibly predictive of BMI and subsequently to test whether lean individuals who carry an obese metabolome are at hidden high risk of obesity-related diseases, such as type 2 diabetes.

RESEARCH DESIGN AND METHODS: Levels of 108 metabolites were measured in plasma samples of 7,663 individuals from two Swedish and one Italian population-based cohort. Ridge regression was used to predict BMI using the metabolites. Individuals with a predicted BMI either >5 kg/m2 higher (overestimated) or lower (underestimated) than their actual BMI were characterized as outliers and further... (More)

OBJECTIVE: Obesity is a key risk factor for type 2 diabetes; however, up to 20% of patients are normal weight. Our aim was to identify metabolite patterns reproducibly predictive of BMI and subsequently to test whether lean individuals who carry an obese metabolome are at hidden high risk of obesity-related diseases, such as type 2 diabetes.

RESEARCH DESIGN AND METHODS: Levels of 108 metabolites were measured in plasma samples of 7,663 individuals from two Swedish and one Italian population-based cohort. Ridge regression was used to predict BMI using the metabolites. Individuals with a predicted BMI either >5 kg/m2 higher (overestimated) or lower (underestimated) than their actual BMI were characterized as outliers and further investigated for obesity-related risk factors and future risk of type 2 diabetes and mortality.

RESULTS: The metabolome could predict BMI in all cohorts (r2 = 0.48, 0.26, and 0.19). The overestimated group had a BMI similar to individuals correctly predicted as normal weight, had a similar waist circumference, were not more likely to change weight over time, but had a two times higher risk of future type 2 diabetes and an 80% increased risk of all-cause mortality. These associations remained after adjustments for obesity-related risk factors and lifestyle parameters.

CONCLUSIONS: We found that lean individuals with an obesity-related metabolome have an increased risk for type 2 diabetes and all-cause mortality compared with lean individuals with a healthy metabolome. Metabolomics may be used to identify hidden high-risk individuals to initiate lifestyle and pharmacological interventions.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes Care
volume
45
issue
5
article number
dc212402
pages
1260 - 1267
publisher
American Diabetes Association
external identifiers
  • pmid:35287165
  • scopus:85130631490
ISSN
1935-5548
DOI
10.2337/dc21-2402
language
English
LU publication?
yes
additional info
© 2022 by the American Diabetes Association.
id
9f966b7f-9fb5-4f39-b921-7add57c2494d
date added to LUP
2022-05-05 13:40:31
date last changed
2024-06-25 06:25:40
@article{9f966b7f-9fb5-4f39-b921-7add57c2494d,
  abstract     = {{<p>OBJECTIVE: Obesity is a key risk factor for type 2 diabetes; however, up to 20% of patients are normal weight. Our aim was to identify metabolite patterns reproducibly predictive of BMI and subsequently to test whether lean individuals who carry an obese metabolome are at hidden high risk of obesity-related diseases, such as type 2 diabetes.</p><p>RESEARCH DESIGN AND METHODS: Levels of 108 metabolites were measured in plasma samples of 7,663 individuals from two Swedish and one Italian population-based cohort. Ridge regression was used to predict BMI using the metabolites. Individuals with a predicted BMI either &gt;5 kg/m2 higher (overestimated) or lower (underestimated) than their actual BMI were characterized as outliers and further investigated for obesity-related risk factors and future risk of type 2 diabetes and mortality.</p><p>RESULTS: The metabolome could predict BMI in all cohorts (r2 = 0.48, 0.26, and 0.19). The overestimated group had a BMI similar to individuals correctly predicted as normal weight, had a similar waist circumference, were not more likely to change weight over time, but had a two times higher risk of future type 2 diabetes and an 80% increased risk of all-cause mortality. These associations remained after adjustments for obesity-related risk factors and lifestyle parameters.</p><p>CONCLUSIONS: We found that lean individuals with an obesity-related metabolome have an increased risk for type 2 diabetes and all-cause mortality compared with lean individuals with a healthy metabolome. Metabolomics may be used to identify hidden high-risk individuals to initiate lifestyle and pharmacological interventions.</p>}},
  author       = {{Ottosson, Filip and Smith, Einar and Ericson, Ulrika and Brunkwall, Louise and Orho-Melander, Marju and Di Somma, Salvatore and Antonini, Paola and Nilsson, Peter M and Fernandez, Céline and Melander, Olle}},
  issn         = {{1935-5548}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{5}},
  pages        = {{1260--1267}},
  publisher    = {{American Diabetes Association}},
  series       = {{Diabetes Care}},
  title        = {{Metabolome-Defined Obesity and the Risk of Future Type 2 Diabetes and Mortality}},
  url          = {{http://dx.doi.org/10.2337/dc21-2402}},
  doi          = {{10.2337/dc21-2402}},
  volume       = {{45}},
  year         = {{2022}},
}