title: Predictors of Circulating Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor-Binding Protein-3 in Critical Illness.
abstract: OBJECTIVE
  To characterize predictors of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 in acute critical illness with the hypothesis that acute factors associated with critical illness will more strongly predict circulating insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 than chronic clinical or genetic factors.
  
  
  METHODS
  Observational study nested within a large prospective study using multivariable linear regression to model circulating insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 with acute and chronic clinical variables, and genotype from five polymorphisms in insulin-like growth factor pathway genes.
  
  
  METHODS
  ICUs from two large academic medical centers.
  
  
  METHODS
  Five hundred forty-three Caucasian patients with risk factors for acute respiratory distress syndrome and available plasma from early in critical illness.
  
  
  METHODS
  None.
  
  
  RESULTS
  Total insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 were measured in plasma using IMMULITE assays (Siemens, Malvern, PA). We examined age, gender, body mass index, cirrhosis, and diabetes, as well as Acute Physiology, Age, and Chronic Health Evaluation III score, acute hepatic dysfunction, pneumonia and aspiration, sepsis/septic shock, acute respiratory distress syndrome, and receipt of corticosteroids. Body mass index, cirrhosis, and acute respiratory distress syndrome were strongly associated with insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 levels; Acute Physiology, Age, and Chronic Health Evaluation III was strongly associated with insulin-like growth factor-1 levels; and age was strongly associated with insulin-like growth factor-binding protein-3. Five polymorphisms (IGF1: rs1520220, rs35767, rs2946834; IGFBP1: rs4619; IGFBP3: rs2854746) were analyzed for associations with plasma levels. When genotypes were added to models, rs2854746 was significantly associated with plasma insulin-like growth factor-binding protein-3. Genotype explained an additional 2% of variability with an overall adjusted R-square of 0.18.
  
  
  CONCLUSIONS
  Despite the acute derangements of critical illness, both acute and chronic health factors significantly influence circulating levels of insulin-like growth factor-1 and insulin-like growth factor-binding protein-3 early in critical illness. rs2854746 is also significantly associated with insulin-like growth factor-binding protein-3 levels in this ICU cohort. Overall, phenotypic and genotypic factors explained only a modest amount of variability in insulin-like growth factor-1 and insulin-like growth factor-binding protein-3. Further research is needed to understand how to apply these findings to patient care.
authors.affiliation: 1Section of Pulmonary, Critical Care, and Sleep Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, CT. 2Environmental and Occupational Medicine and Epidemiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA. 3Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA. 4Pulmonary and Critical Care Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Ahasic
authors.forename: Paula
authors.initials: P
authors.lastname: Tejera
authors.forename: Yongyue
authors.initials: Y
authors.lastname: Wei
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
authors.forename: Ednan K
authors.initials: EK
authors.lastname: Bajwa
authors.forename: B Taylor
authors.initials: BT
authors.lastname: Thompson
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
mesh_terms: D018806:APACHE; D000046:Academic Medical Centers; D000208:Acute Disease; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D002908:Chronic Disease; D016638:Critical Illness; D005260:Female; D005838:Genotype; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood* / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000032:analysis* / Q000235:genetics*; D007362:Intensive Care Units / Q000706:statistics & numerical data; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I