Predictors of Circulating Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein-3 in Critical Illness
Published Date:Dec 2015
Source:Crit Care Med. 43(12):2651-2659.
Keywords:Academic Medical Centers
Acute Respiratory Distress Syndrome
Aged, 80 And Over
Body Mass Index
Insulin-like Growth Factor-1
Insulin-like Growth Factor Binding Protein-3
Insulin-Like Growth Factor Binding Protein 3
Insulin-Like Growth Factor I
Intensive Care Units
Single Nucleotide Polymorphisms
Pubmed Central ID:PMC4651824
Funding:R01 ES009860/ES/NIEHS NIH HHS/United States
R01 OH002421/OH/NIOSH CDC HHS/United States
R01 CA092824/CA/NCI NIH HHS/United States
T42 OH008416/OH/NIOSH CDC HHS/United States
R01 HL060710/HL/NHLBI NIH HHS/United States
U01 HL123009/HL/NHLBI NIH HHS/United States
T32 ES007069/ES/NIEHS NIH HHS/United States
T32 HL116275/HL/NHLBI NIH HHS/United States
P30 CA006516/CA/NCI NIH HHS/United States
R01HL60710/HL/NHLBI NIH HHS/United States
To characterize predictors of insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 in acute critical illness with the hypothesis that acute factors associated with critical illness will more strongly predict circulating IGF-1 and IGFBP-3 than chronic clinical or genetic factors.
Observational study nested within a large prospective study using multivariable linear regression to model circulating IGF-1 and IGFBP-3 with acute and chronic clinical variables, and genotype from five polymorphisms in IGF pathway genes.
Setting and Patients
Five-hundred forty-three Caucasian patients with risk factors for acute respiratory distress syndrome (ARDS) and available plasma from early in critical illness, recruited from intensive care units (ICUs) of two large academic medical centers.
Measurements and Main Results
Total IGF-1 and IGFBP-3 were measured in plasma using IMMULITE assays. We examined age, gender, body mass index (BMI), cirrhosis, and diabetes, as well as APACHE III score, acute hepatic dysfunction, pneumonia and aspiration, sepsis/septic shock, ARDS, and receipt of corticosteroids. BMI, cirrhosis, and ARDS were strongly associated with IGF-1 and IGFBP-3 levels; APACHE III was strongly associated with IGF-1 levels; and age was strongly associated with IGFBP-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 IGFBP-3. Genotype explained an additional 2% of variability with an overall adjusted R-square of 0.18.
Despite the acute derangements of critical illness, both acute and chronic health factors significantly influence circulating levels of IGF-1 and IGFBP-3 early in critical illness. Rs2854746 is also significantly associated with IGFBP-3 levels in this ICU cohort. Overall, phenotypic and genotypic factors explained only a modest amount of variability in IGF-1 and IGFBP-3. Further research is needed to understand how to apply these findings to patient care.
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