Delta insulin-like growth factor binding protein-1 (Delta IGFBP-1): a marker of hepatic insulin resistance?

Background Insulin-like growth factor binding protein-1 (IGFBP-1) is a hepatically synthesised protein which can be used as a marker of insulin resistance. We hypothesised that the fall in serum IGFBP-1 at 2h following a glucose load (IGFBP-1(0-2h)) would be a more robust measure of hepatic insulin resistance than a fasting level alone. Methods All subjects had a standard 75g oral GTT including IGFBP-1 and insulin measurement to enable calculation of IGFBP-1(0-2h), Insulin(0-2h), and insulin sensitivity indices. At a second visit, subjects had a frequently sampled intravenous glucose tolerance test (FSIVGTT) in order to determine the insulin sensitivity index, Si. Results Twenty-two individuals had normal glucose tolerance (NGT) and 9 impaired fasting glucose (IFG). IGFBP-1(0-2h) correlated with Si in total subjects (r=0.49, p=0.005) and NGT subjects (r=0.50, p=0.02) but not in IFG subjects (r=0.43, p=0.24). Insulin(0-2h)/IGFBP-1(0-2h) correlated significantly with Si in total subjects (r=-0.68, p<0.001) and in NGT subjects (r=-0.57, p=0.005). Multivariate analysis was fitted using different models while keeping other explanatory variables constant. The fasting IGFBP-1 model was a better predictor of Si (=0.431, p<0.0001) than the Insulin(0-2h)/IGFBP1(0-2h) model (=-0.185, p=0.004). Conclusions The dynamic indices IGFBP-1(0-2h) and Insulin(0-2h)/IGFBP-1(0-2h) appear suitable markers of (hepatic) insulin resistance with potential clinical utility.