Circulating IGFBP-3 concentration is independently associated with insulin resistance and BMI
AH Heald1, S Anderson2, JK Cruickshank2 & JM Gibson1
Recent studies have confirmed that IGF-I is an important determinant of future glucose homeostasis and cardiovascular risk. Insulin-like growth factor binding protein-3 (IGFBP-3) is the principal carrier protein for IGF-I in the circulation. Therefore we tested the relationship of IGF-I and IGFBP-3 to insulin resistance in an ethnic group with a high incidence of type 2 diabetes and cardiovascular disease.
Methods. In a population-based study 100 subjects of Pakistani-origin living in Manchester UK underwent a 75g oral glucose tolerance test and standardised anthropometry. Fasting concentrations of IGFBP-3, IGF-I, IGF-II, intact insulin and non-esterified fatty acids (NEFA) were measured. Insulin sensitivity was calculated using homeostasis model assessment (HOMA.
Results. Higher levels of circulating IGFBP-3 were associated with BMI (Spearman's rho = 0.29, p=0.01), fasting insulin (0.27, p=0.02) and NEFA (0.24, p=0.03), and negatively with age (-0.22, p=0.05) and insulin sensitivity (-0.24, p=0.03). The relationship with insulin sensitivity was independent of age, sex and IGF-II based on partial correlation analyses (-0.25, p=0.04). IGFBP-3 correlated with IGF-I (rho= 0.23, p=0.04) and more strongly with IGF-II (0.48, p<0.001). There was no difference between fasting and 2hr post glucose load IGFBP-3. Forward stepwise regression analyses demonstrated that IGFBP-3 was independently associated with increasing circulating concentrations of NEFA (beta = 0.53), BMI (beta = 0.24), fasting IGF-II (beta = 0.28) and IGF-I (beta = 0.14), in a model containing age, sex, BMI, as well as IGFBP-1, IGF-I, HOMA-S and NEFA.
In this cross-sectional study a higher circulating IGFBP-3 correlated inversely with insulin sensitivity and showed independent associations with increasing free fatty acid levels and with BMI. This may be an adaptive phenomenon to increase IGF delivery to peripheral tissues in individuals with increasing peripheral insulin resistance and deteriorating glucose homeostasis. This study adds further insight into the complex relationship between the IGF-system and insulin resistance / the metabolic syndrome.