Insulin-like growth factors and binding proteins in patients with recent-onset type 1 (insulin-dependent) diabetes mellitus: influence of diabetes control and intraportal insulin infusion

Abstract

Type 1 diabetes mellitus is associated with decreased insulin-like growth factor-1 (IGF-1) levels, enhanced values of growth hormone (GH) and IGF-binding protein 1 (IGFBP-1). Since the liver is the major source of IGF and IGFBP production, we have therefore examined whether levels of IGFs (IGF-1 and IGF-11) and IGFBPs (IGFBP-1 and IGFBP-3) differ when insulin is infused into the portal or peripheral vascular system. IGF, IGFBP, and GH levels were determined within 1-3 weeks of diagnosis in 36 patients (ranging in age from 18 to 22 years) with Type 1 diabetes mellitus. IGF-1 levels were low before insulin therapy administration (0.49 +/- 0.05 vs. 1.11 +/- 0.04 U/ml in controls, P < 0.01). With insulin treatment, IGF-1 levels rose to the normal range and IGF-1 normalisation depended on diabetes control and the route of insulin infusion. Diabetic patients with conventional insulin therapy (CIT; n = 12) had low IGF-1 (0.57 +/- 0.07 U/ml) compared with patients with continuous subcutaneous insulin infusion (CSII; n = 12; 0.75 +/- 0.08 U/ml; P < 0.05) and intraportal insulin infusion (IPII; n = 12; 1.07 +/- 10.05 U/ml; P < 0.05). Significant correlations were found between IGF-1 and parameters of glycemic control: HbA1c (r = -0.64; P < 0.01) and glycemia (r = -0.56; P < 0.05). The pattern of changes in IGF-11 levels was not significantly different from that of controls and was not altered by insulin therapy (0.98 +/- 0.08 and 1.01 +/- 0.04 U/ml in controls). Measured fasting 08:00 h IGFBP-1 levels were elevated 3-fold and IGFGP-3 levels were 2-fold lower in diabetic patients than in controls. Elevated IGFBP-1 levels were significantly correlated with metabolic control (glycemia, r = 0.64, P < 0.01; HbA1c, r = 0.71, P < 0.01). The mean elevated GH level before insulin administration (13.4 +/- 0.9 mg/l) was decreased by intensified insulin therapy (CSII, 8.8 +/- 0.6, P < 0.05; IPII, 5.6 +/- 0.9 mg/l, P < 0.001). There was a negative correlation between GH and IGF-1 (r = -0.72, P < 0.01). These results show the role of glycemic control and the route of insulin administration in the normalisation of IGF-1, IGFBP-1 and GH up to non-diabetic controls in patients with recent-onset Type 1 diabetes mellitus.