INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEIN-1 RESPONSE TO ACUTE INSULIN-INDUCED HYPOGLYCEMIA IN TYPE-1 DIABETES

OBJECTIVES Insulin is believed to be the prime regulator of insulin-li ke growth factor binding protein 1 (IGFBP-1) secretion, and in normal subjects acute insulin induced hypoglycaemia exerts a rapid effect on concentrations of IGFBP-1, and may also influence insulin-like growth factor I (IGF-I) concentrations. The rise in IGFBP-1 concentrations in normal subjects following hypoglycaemia has been suggested to be due to suppression of endogenous Insulin secretion. We have examined this further by studying diabetics with no endogenous insulin secretion. DE SIGN We have compared the IGFBP-1 response to acute insulin induced hy poglycaemia in normal subjects and patients with Type 1 (insulin depen dent) diabetes mellitus. METHODS Insulin tolerance tests were performe d using a bolus of insulin (0.15 U/kg), in six control subjects and si x patients with Type 1 diabetes. MEASUREMENTS Serum levels of IGFBP-1, insulin, glucose, and IGF-I were measured at regular intervals during the insulin tolerance test. RESULTS Blood glucose fell to a nadir whi ch coincided with the onset of the acute autonomic reaction 'R' in bot h groups. The basal concentration of IGF-I was significantly lower in the diabetic group at 0.4 +/- 0.1 kU/l, compared to 0.9 +/- 0.1 kU/l i n the control group, but there was no significant change in IGF-I conc entrations in response to hypoglycaemia in either group. Hypoglycaemia provoked a fall in IGFBP-1 in patients with Type 1 diabetes, from 38 +/- 9 mu g/l basally to 17 +/- 3 mu g/l at R + 120 minutes, with a ret urn to basal values of 45 +/- 11 mu g/l at R + 180 minutes. In the con trol subjects there was no fall in IGFBP-1, but a significant increase to 71 +/- 14 mu g/l at R + 180 minutes. CONCLUSION This difference in the IGFBP-1 response in the presence of a similar glucose response su ggests that in Type 1 diabetes there may be different sensitivities to the actions of exogenous insulin on IGFBP-1 regulation.