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

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 2 h following a glucose load (ΔIGFBP-10-2h) would be a more robust measure of hepatic insulin resistance than a fasting level alone.

All subjects had a standard 75 g oral GTT including IGFBP-1 and insulin measurement to enable calculation of ΔIGFBP-10-2h, ΔInsulin0-2h, 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.

Twenty-two individuals had normal glucose tolerance (NGT) and 9 impaired fasting glucose (IFG). ΔIGFBP-10-2h 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). ΔInsulin0-2h/ΔIGFBP-10-2h 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 (β = 0.431, p < 0.0001) than the ΔInsulin0-2h/ΔIGFBP10-2h model (β = -0.185, p = 0.004).

The dynamic indices ΔIGFBP-10-2h and ΔInsulin0-2h/ΔIGFBP-10-2h appear suitable markers of (hepatic) insulin resistance with potential clinical utility.