Background: Low birth weight (LBW) individuals are at increased risk of developing Type 2 diabetes (T2D) , especially when exposed to an affluent dietary pattern. Impaired subcutaneous adipose tissue expandability and ectopic fat storage may represent key features explaining the link between LBW and risk of T2D. We hypothesized that a 4-week simple carbohydrate overfeeding challenge (+25% energy) (COF) would adversely influence dysmetabolic traits including hepatic fat content in LBW compared to normal birth weight (NBW) men.
Methods: Twenty-two non-obese LBW and 21 age- and BMI-matched NBW men with a mean age of 37.6 years were included. Body composition, hepatic fat (MR spectroscopy) , glucose and insulin metabolism, hepatic glucose production (HGP; deuterium glucose) , energy metabolism (indirect calorimetry) and selected plasma biomarkers (multiplex ELISA) were measured before and after 4 weeks COF.
Results: Fasting plasma glucose and C-peptide levels, as well as energy expenditure (EE) and fat oxidation (FOX) rates increased significantly more in response to COF among the LBW compared to NBW subjects (all P<0.05) . However, despite significantly increased baseline hepatic fat content, COF resulted in similar body weight and hepatic fat content increments in LBW compared to NBW subjects. HGP and hepatic insulin resistance were unaffected by COF in both groups. Fasting plasma adiponectin levels were significantly reduced in LBW versus NBW subjects before and after COF, whereas plasma leptin and FGF21 levels were increased (both P<0.005) after COF in LBW men only.
Conclusion: LBW compared to NBW subjects respond to COF with differential increments in plasma glucose, C-peptide, leptin and FGF21 levels, as well as increased EE and FOX rates. The results underscore the importance of LBW individuals avoiding simple carbohydrate overfeeding. Further studies are needed to understand the role of increased hepatic fat and insulin resistance as key mechanisms linking LBW with increased risk of T2D.
C.Brøns: Stock/Shareholder; Novo Nordisk. A.B.Thuesen: None. L.Justesen: None. L.Elingaard-larsen: None. J.Størling: None. E.R.Danielsen: None. T.Hansen: None. A.A.Vaag: Stock/Shareholder; AstraZeneca.
Novo Nordisk Foundation (NNF15OC0016692) , Aase and Ejnar Danielsens Fond, Augustinus Foundation, Simon Spies Fonden, TrygFonden.