title: Neonatal macrosomia is an independent risk factor for adult metabolic syndrome.
abstract: BACKGROUND
  Weight in infancy correlates with risk of type 2 diabetes, hypertension, and obesity in adulthood. Clinical observations have been confounded by obesity-prone genotypes and obesity-linked lifestyles.
  
  
  OBJECTIVE
  To define the effects of isolated neonatal macrosomia in isogenic animals, we compared macrosomic and control C57Bl6 mice co-fostered by healthy dams receiving standard laboratory feed.
  
  
  METHODS
  Naturally occurring neonatal macrosomia was identified by a gender-specific weanling weight above the 90th percentile for the colony. Macrosomic and control mice were phenotyped in adulthood by exercise wheel, tail cuff and intraperitoneal insulin or glucose challenge.
  
  
  RESULTS
  Compared to control males, adult males with a history of neonatal macrosomia had significantly increased body weight, reduced voluntary activity, insulin resistance, fasting hyperinsulinemia, and impaired glucose tolerance. In contrast, adult females with neonatal macrosomia had no significant alteration in body weight or endocrine phenotypes, but did have higher blood pressures and lower heart rates than control females. After these baseline studies, all mice were switched to a hypercaloric, high fat diet (5 kcal/g, 45% of energy as fat). Twenty weeks later, male mice had impaired glucose tolerance and insulin resistance, independent of their weanling weight classification. While on high fat feeds, macrosomic males maintained a significantly higher body weight than control males.
  
  
  CONCLUSIONS
  We conclude that (1) in our murine model, neonatal macrosomia is an independent risk factor of adult metabolic syndrome, and (2) neonatal macrosomia accentuates the sexually dimorphic predisposition of C57Bl6 male mice towards glucose intolerance and C57Bl6 female mice towards hypertension.
authors.affiliation: Department of Pediatrics, University of Iowa, Carver College of Medicine, Iowa City, Iowa 52242, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Hermann
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Dallas
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Haskell
authors.forename: Robert D
authors.initials: RD
authors.lastname: Roghair
mesh_terms: D000821:Animal Feed; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000831:Animals, Newborn; D004036:Diet, Atherogenic; D004041:Dietary Fats / Q000494:pharmacology; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000209:etiology; D005260:Female; D005320:Fetal Macrosomia / Q000150:complications*; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D011247:Pregnancy; D012307:Risk Factors
chemical_list: D004041:Dietary Fats
references.citation: Neonatology. 2009;95(1):23-32
references.pmid: 18787334
references.citation: J Physiol. 2005 May 15;565(Pt 1):3-8
references.pmid: 15695245
references.citation: Eur J Endocrinol. 2006 Oct;155(4):601-7
references.pmid: 16990660
references.citation: Neonatology. 2008;94(4):245-54
references.pmid: 18836284
references.citation: Endocrinology. 2009 May;150(5):2109-17
references.pmid: 19164473
references.citation: Physiol Behav. 2004 Apr;81(2):243-8
references.pmid: 15159170
references.citation: Pediatr Res. 2007 Oct;62(4):399-404
references.pmid: 17667847
references.citation: Physiol Behav. 2008 Apr 22;94(1):17-28
references.pmid: 18155097
references.citation: Pediatrics. 2005 Mar;115(3):e290-6
references.pmid: 15741354
references.citation: Am J Physiol Regul Integr Comp Physiol. 2008 Feb;294(2):R290-301
references.pmid: 17989137
references.citation: Obesity (Silver Spring). 2007 Aug;15(8):1996-2005
references.pmid: 17712117
references.citation: Circulation. 2004 Aug 31;110(9):1097-102
references.pmid: 15326063
references.citation: Cell Mol Neurobiol. 2002 Dec;22(5-6):479-500
references.pmid: 12585676
references.citation: Gend Med. 2008;5 Suppl A:S121-32
references.pmid: 18395678
references.citation: Am J Physiol Endocrinol Metab. 2006 Oct;291(4):E792-9
references.pmid: 16720630
references.citation: Cell Biochem Biophys. 2007;48(2-3):79-88
references.pmid: 17709877
references.citation: Int J Obes Relat Metab Disord. 1999 Nov;23 Suppl 8:S1-107
references.pmid: 10641588
references.citation: Br J Nutr. 2009 Aug;102(4):514-9
references.pmid: 19203419
references.citation: Diabetes Care. 2003 Feb;26(2):343-8
references.pmid: 12547860
references.citation: J Appl Physiol (1985). 2004 Jul;97(1):369-76
references.pmid: 15047670
references.citation: Pediatr Res. 2009 Jul;66(1):53-8
references.pmid: 19342983
references.citation: Nutr J. 2009 Feb 17;8:11
references.pmid: 19220919
references.citation: Hypertension. 2007 Oct;50(4):679-85
references.pmid: 17724277
references.citation: J Clin Endocrinol Metab. 2009 Oct;94(10):3708-13
references.pmid: 19723754
references.citation: BMJ. 1994 Apr 9;308(6934):942-5
references.pmid: 8173400
references.citation: Diabetologia. 2005 Apr;48(4):675-86
references.pmid: 15729571