title: Advanced glycation end products in infant formulas do not contribute to insulin resistance associated with their consumption.
abstract: BACKGROUND
  Infant formula-feeding is associated with reduced insulin sensitivity. In rodents and healthy humans, advanced glycation end product (AGE)-rich diets exert diabetogenic effects. In comparison with human breast-milk, infant formulas contain high amounts of AGEs. We assessed the role of AGEs in infant-formula-consumption-associated insulin resistance.
  
  
  METHODS
  Total plasma levels of N(ε)-(carboxymethyl)lysine (CML), AGEs-associated fluorescence (λ(ex) = 370 nm/λ(em) = 445 nm), soluble adhesion molecules, markers of micro- binflammation (hsCRP), oxidative stress (malondialdehyde, 8-isoprostanes) and leptinemia were determined, and correlated with insulin sensitivity in a cross-sectional study in 166 healthy term infants aged 3-to-14 months, subdivided according to feeding regimen (breast-milk- vs. infant formula-fed) and age (3-to-6-month-olds, 7-to-10-month-olds, and 11-to-14-month-old infants). Effects of the consumption of low- vs. high-CML-containing formulas were assessed. 36 infants aged 5.8 ± 0.3 months were followed-up 7.5 ± 0.3 months later.
  
  
  RESULTS
  Cross-sectional study: 3-to-6-month-olds and 7-to-10-month-old formula-fed infants presented higher total plasma CML levels and AGEs-associated fluorescence (p<0.01, both), while only the 3-to-6-month-olds displayed lower insulin sensitivity (p<0.01) than their breast-milk-fed counterparts. 3-to-6-month-olds fed low-CML-containing formulas presented lower total plasma CML levels (p<0.01), but similar insulin sensitivity compared to those on high-CML-containing formulas. Markers of oxidative stress and inflammation, levels of leptin and adhesion molecules did not differ significantly between the groups. Follow-up study: at initial investigation, the breast-milk-consuming infants displayed lower total plasma CML levels (p<0.01) and AGEs-associated fluorescence (p<0.05), but higher insulin sensitivity (p<0.05) than the formulas-consuming infants. At follow-up, the groups did not differ significantly in either determined parameter.
  
  
  CONCLUSIONS
  In healthy term infants, high dietary load with CML does not play a pathophysiological role in the induction of infant formula-associated insulin resistance. Whether a high load of AGEs in early childhood affects postnatal programming remains to be elucidated.
authors.affiliation: Department of Clinical and Experimental Pharmacotherapy, Medical Faculty, Slovak Medical University, Bratislava, Slovakia. brandlova@its.czu.cz
authors.forename: Kristína Simon
authors.initials: KS
authors.lastname: Klenovics
authors.forename: Peter
authors.initials: P
authors.lastname: Boor
authors.forename: Veronika
authors.initials: V
authors.lastname: Somoza
authors.forename: Peter
authors.initials: P
authors.lastname: Celec
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Fogliano
authors.forename: Katarína
authors.initials: K
authors.lastname: Sebeková
mesh_terms: D001942:Breast Feeding; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004032:Diet; D005260:Female; D017127:Glycation End Products, Advanced / Q000737:chemistry*; D006801:Humans; D007223:Infant; D041943:Infant Formula / Q000737:chemistry*; D007249:Inflammation; D007333:Insulin Resistance; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood; D008297:Male; D008895:Milk, Human; D018384:Oxidative Stress
chemical_list: D017127:Glycation End Products, Advanced; C048496:N(6)-carboxymethyllysine; D008239:Lysine