title: Disassociation of liver and muscle insulin resistance from ectopic lipid accumulation in low-birth-weight individuals.
abstract: BACKGROUND
  Low birth weight (LBW) is a marker of fetal stress and is associated with an increased prevalence of type 2 diabetes (T2D). Insulin resistance plays a prominent role in the development of T2D; however, the pathogenesis of T2D in LBW is controversial.
  
  
  OBJECTIVE
  The objective of the study was to assess whole-body and tissue-specific insulin sensitivity and intramyocellular lipid (IMCL) and hepatic lipid content in LBW and matched control subjects.
  
  
  METHODS
  These were prospective and pair-matched studies.
  
  
  METHODS
  The study was conducted at Yale University Center for Clinical Investigation.
  
  
  METHODS
  Young, lean, nonsmoking, sedentary LBW (n = 45) and matched control subjects participated in the study.
  
  
  METHODS
  Interventions included an oral glucose tolerance test and hyperinsulinemic-euglycemic clamps and (1)H magnetic resonance spectroscopy.
  
  
  METHODS
  The main outcomes measures included insulin sensitivity index; whole-body and tissue-specific insulin sensitivity; liver lipid and IMCL contents; and fasting concentrations of cortisol, GH, and IGF-I as markers of the hypothalamic-pituitary-adrenal and IGFI/GH axes.
  
  
  RESULTS
  The LBW subjects were insulin resistant as reflected by a 20% reduction in insulin sensitivity index as compared with the controls (P = 0.0017), which could be attributed to both liver and muscle insulin resistance. There were no differences in IMCL or hepatic triglyceride content between LBW and control groups. In the LBW group, fasting plasma concentrations of cortisol (P = 0.01) and GH (P = 0.01) were increased, and IGF-I concentrations reduced (P < 0.05) a pattern, which may suggest potential dysregulation of the hypothalamic-pituitary-adrenal and IGF-I/GH axes.
  
  
  CONCLUSIONS
  These results support the hypothesis that fetal stress and LBW lead to liver and muscle insulin resistance and show that this is independent of lipid deposition in these organs.
authors: Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8020, USA.
authors: Sylvie
authors: S
authors: Dufour
authors: Kitt Falk
authors: KF
authors: Petersen
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D005951:Glucose Tolerance Test; D006801:Humans; D007230:Infant, Low Birth Weight / Q000378:metabolism*; D007231:Infant, Newborn; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D050356:Lipid Metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D011446:Prospective Studies
chemical_list: D001786:Blood Glucose; D007328:Insulin