Postprandial paradoxical IGFBP-1 response in obese patients with Type 2 diabetes

Abstract

IGFs (insulin-like growth factors), which in an unbound form induce glucose and amino acid uptake, circulate bound to IGFBPs (IGF-binding proteins), which modulate their bioavailability and activity. The aim of the present study was to examine the effect of a standard meal [2301 kJ (550 kcal)] on the serum levels of IGFBP-1 in obese patients with T2DM (Type 2 diabetes mellitus), non-obese patients with T1DM (Type 1 diabetes mellitus) and healthy controls, using the artificial pancreas (Biostator®) to obtain a normal glycaemic response to the meal. IGFBP-1 levels decreased by 50% over 2 h following the meal at a similar clearance in both the healthy controls and patients with T1DM, but no significant decline was seen in the patients with T2DM, despite a several-fold increase in insulin levels. The patients with T2DM were also studied during Sandostatin® (somatostatin) infusion to decrease the inappropriate secretion of glucagon during the meal. During the 210 min of somatostatin infusion, the glucagon response was suppressed and IGFBP-1 levels were increased concomitantly with the peak in insulin levels, without any significant decrease after the meal. In conclusion, the impaired IGFBP-1 response to meal-related hyperinsulinaemia in obese patients with T2DM suggests a decreased availability of active IGF-1, leading to a decrease in glucose uptake during and after a meal in these patients. The stimulated meal response to glucagon, which contributes to postprandial hyperglycaemia, could not explain the increase in serum IGFBP-1 in these obese patients with T2DM.