Metabolic Perturbations and Ectopic Fat Deposition in Men With Low Birth Weight

Researchers have found that individuals with low birth weight are at increased risk of developing type 2 diabetes, with carbohydrate overfeeding associated with differential elevations in fasting glucose, lipids, alanine, insulin resistance, and resting energy expenditure. A study published in the journal Diabetes found that four weeks of carbohydrate overfeeding resulted in impaired peroxisome proliferator-activated receptor signaling, as well as aberrant collagen and extracellular matrix regulation in participants with low birth weight.

Key Takeaways:

• Low birth weight (LBW) is a risk factor for type 2 diabetes (T2D), with individuals at increased risk of developing the condition.
• Carbohydrate overfeeding for four weeks was associated with differential elevations in fasting glucose, lipids, alanine, insulin resistance, and resting energy expenditure in LBW participants versus control participants.
• Multiomics analysis of subcutaneous adipose tissue RNA sequencing, serum lipidomics, and metabolomics uncovered impaired peroxisome proliferator-activated receptor signaling and aberrant collagen and extracellular matrix regulation in LBW participants.
• Individuals with low birth weight have impaired subcutaneous adipose tissue expandability, potentially underlying their reduced metabolic buffering capacity.
• The findings support the notion that unhealthy subcutaneous adipose tissue expandability may contribute to the development of type 2 diabetes in individuals with low birth weight.
• The research provides evidence for the importance of considering birth weight as a risk factor for type 2 diabetes and the potential role of carbohydrate overfeeding in exacerbating metabolic perturbations in individuals with low birth weight.

Statistics:

• 22 nonobese LBW men participated in the study, with 5 having screen-detected metabolic dysfunction-associated steatotic liver disease (MASLD).
• 21 healthy control participants with normal birth weight (NBW) were included in the study.
• Body weight increased by 4 kg on average in both groups during carbohydrate overfeeding.
• Fasting glucose and insulin resistance increased significantly more in LBW participants compared to NBW participants.
• Plasma adiponectin was lower in LBW participants, while fibroblast growth factor 21 levels increased more during carbohydrate overfeeding in LBW participants.
• Subcutaneous adipose tissue (SAT) density was lower in LBW participants and decreased during carbohydrate overfeeding in both groups.
• Serum alanine, phosphatidylcholines, and triglycerides increased significantly more in LBW participants during carbohydrate overfeeding.

Sources:

• Metabolic Perturbations and Ectopic Fat Deposition in Men With Low Birth Weight: Effects of a 4-Week Carbohydrate Overfeeding Challenge. Diabetes, 2025;74(11):2044-2059.
• Diabetes. Amer Diabetes Assoc, 1701 N Beauregard St, Alexandria, VA 22311-1717, USA.
• Steno Diabetes Center Copenhagen, Herlev, Denmark.