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Metabolic perturbations and ectopic fat deposition in men with low birth weight : Effects of a 4-week carbohydrate overfeeding challenge

Brøns, Charlotte ; Elingaard-Larsen, Line Ohrt ; Justesen, Louise ; Villumsen, Sofie Olund ; Thuesen, Anne Cathrine Baun ; Engelhard, Leonie Mieke LU ; Gertsen, Sidsel Seide ; Ried-Larsen, Mathias ; Prasad, Rashmi B. LU orcid and Hansen, Torben , et al. (2025) In Diabetes 74(11). p.2044-2059
Abstract

Low birth weight (LBW) is a risk factor for type 2 diabetes (T2D). We hypothesized that 4 weeks of carbohydrate overfeeding (COF) with +25% energy would unmask key T2D perturbations among 22 nonobese LBW men, including five with screen-detected metabolic dysfunction-associated steatotic liver disease (MASLD), compared with 21 healthy control participants with normal birth weight (NBW). Body weight, lean and fat mass, and hepatic fat content increased to the same extent in both groups during COF, whereas fasting glucose and insulin resistance increased significantly more in LBW compared with NBW participants. The differential COF responses were most pronounced in LBW participants without MASLD, including increased resting energy... (More)

Low birth weight (LBW) is a risk factor for type 2 diabetes (T2D). We hypothesized that 4 weeks of carbohydrate overfeeding (COF) with +25% energy would unmask key T2D perturbations among 22 nonobese LBW men, including five with screen-detected metabolic dysfunction-associated steatotic liver disease (MASLD), compared with 21 healthy control participants with normal birth weight (NBW). Body weight, lean and fat mass, and hepatic fat content increased to the same extent in both groups during COF, whereas fasting glucose and insulin resistance increased significantly more in LBW compared with NBW participants. The differential COF responses were most pronounced in LBW participants without MASLD, including increased resting energy expenditure. Plasma adiponectin was lower, whereas fibroblast growth factor 21 levels increased more during COF in LBW participants. Subcutaneous adipose tissue (SAT) density was lower in LBW participants and decreased during COF in both groups. Serum alanine, phosphatidylcholines, and triglycerides increased significantly more in LBW participants during COF. Multiomics analysis of SAT RNA sequencing, serum lipidomics, and metabolomics uncovered impaired peroxisome proliferator-activated receptor signaling as well as aberrant collagen and extracellular matrix regulation in LBW participants. The results document differential and MASLD-independent metabolic perturbations in LBW participants during COF.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
74
issue
11
pages
16 pages
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:41115414
  • scopus:105019629329
ISSN
0012-1797
DOI
10.2337/db25-0307
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2025 by the American Diabetes Association.
id
8bf216f0-f217-4ce9-adcb-ef92d40d374c
date added to LUP
2025-12-16 15:40:36
date last changed
2025-12-16 15:41:52
@article{8bf216f0-f217-4ce9-adcb-ef92d40d374c,
  abstract     = {{<p>Low birth weight (LBW) is a risk factor for type 2 diabetes (T2D). We hypothesized that 4 weeks of carbohydrate overfeeding (COF) with +25% energy would unmask key T2D perturbations among 22 nonobese LBW men, including five with screen-detected metabolic dysfunction-associated steatotic liver disease (MASLD), compared with 21 healthy control participants with normal birth weight (NBW). Body weight, lean and fat mass, and hepatic fat content increased to the same extent in both groups during COF, whereas fasting glucose and insulin resistance increased significantly more in LBW compared with NBW participants. The differential COF responses were most pronounced in LBW participants without MASLD, including increased resting energy expenditure. Plasma adiponectin was lower, whereas fibroblast growth factor 21 levels increased more during COF in LBW participants. Subcutaneous adipose tissue (SAT) density was lower in LBW participants and decreased during COF in both groups. Serum alanine, phosphatidylcholines, and triglycerides increased significantly more in LBW participants during COF. Multiomics analysis of SAT RNA sequencing, serum lipidomics, and metabolomics uncovered impaired peroxisome proliferator-activated receptor signaling as well as aberrant collagen and extracellular matrix regulation in LBW participants. The results document differential and MASLD-independent metabolic perturbations in LBW participants during COF.</p>}},
  author       = {{Brøns, Charlotte and Elingaard-Larsen, Line Ohrt and Justesen, Louise and Villumsen, Sofie Olund and Thuesen, Anne Cathrine Baun and Engelhard, Leonie Mieke and Gertsen, Sidsel Seide and Ried-Larsen, Mathias and Prasad, Rashmi B. and Hansen, Torben and Danielsen, Else Rubæk and Van Hall, Gerrit and Sparks, Lauren M. and López-Andrés, Natalia and Vaag, Allan}},
  issn         = {{0012-1797}},
  language     = {{eng}},
  number       = {{11}},
  pages        = {{2044--2059}},
  publisher    = {{American Diabetes Association Inc.}},
  series       = {{Diabetes}},
  title        = {{Metabolic perturbations and ectopic fat deposition in men with low birth weight : Effects of a 4-week carbohydrate overfeeding challenge}},
  url          = {{http://dx.doi.org/10.2337/db25-0307}},
  doi          = {{10.2337/db25-0307}},
  volume       = {{74}},
  year         = {{2025}},
}