Insulin-like growth factor binding protein 1 (IGFBP-1): A potential marker of insulin resistance and cardiovascular risk.

Insulin resistance is a central feature of the metabolic syndrome and strongly associated with diabetes and cardiovascular disease. The frequently sampled intravenous glucose tolerance test (FSIVGTT) is an alternative method to the euglycaemic hyperinsulinaemic clamp technique for quantitation of insulin resistance. Other simple indices can also be derived from single time point fasting sample (e.g. homeostasis model assessment). The serum protein insulin-like growth factor binding protein 1 (IGFBP-1) is an emerging marker and may be useful in the assessment of insulin resistance. Few ethnic studies have been undertaken and to date, neither insulin resistance nor IGFBP-1 have been compared between Caucasian and Saudi population. The main aims of the project were therefore to directly compare insulin resistance between these two populations and to investigate IGFBP-1 as a marker of insulin resistance and cardiovascular risk. In addition the project aimed to investigate variations of different methods of insulin resistance over different time-intervals. After establishing the analytical criteria of an ELISA technique, serum IGFBP-1 was observed to be highly associated with the insulin sensitivity (Si) parameter derived from FSIVGTT (r = 0.79, p < 0.0001) in normal subjects (n = 22) and could therefore be used as a reliable marker of insulin resistance in these subjects. Total variation (reproducibility) was determined for serum IGFBP-1 in subjects with normal glucose tolerance (NGT = 15), impaired fasting glucose (IFG = 9), impaired glucose tolerance (IGT = 9) and type 2 diabetics (DM = 9). Reproducibility was 20.9%, 29.5%, 33.1% and 48.0% for subjects with NGT, IFG, IGT and DM respectively. IGFBP-1 measurement was least variable in NGT individuals and variability increased with deteriorating glucose tolerance. Insulin resistance was compared in subjects from two populations (33 Saudis and 28 Caucasians matched for adiposity) using FSIVGTT and several simple surrogate indices of insulin resistance. These subjects were from different categories of glucose tolerance. Saudis in the NGT category had a significantly lower mean Si (p < 0.01) and fasting IGFBP-1 (p < 0.05) compared to Caucasians. The data suggest that Saudis with NGT are more insulin resistant than matched Caucasians. In addition to this the phosphorylation status of serum IGFBP-1 was investigated in individuals with (n = 36) and without (n = 39) cardiovascular disease. Significant differences were found between the two groups in less-phosphorylated IGFBP-1 (p < 0.001), phosphorylated IGFBP-1 (p < 0.01) and their ratio (p < 0.01). IGF-I was negatively associated with the ratio (r = - 0.45, p < 0.0001). It therefore appears that low serum levels of different forms of IGFBP-1 could be used as a potential marker of coronary risk, and the ratio may be an index of biologically active IGF-I