Lack of physiological suppression of circulating IGFBP-1 in puberty in patients with insulin-dependent diabetes mellitus

Abstract

Objective: To evaluate the interaction between serum free insulin, insulin-like binding protein (IGFBP)-1 and leptin concentrations during puberty in insulin-dependent diabetes mellitus (IDDM). Design: Adolescent patients with IDDM (n = 101, age > 9 years, duration > 2 years) from the Outpatient Clinic of the Department of Pediatrics at Oulu University Hospital, and non-diabetic controls, were recruited to the study. Free insulin, IGFBP-1, leptin and insulin antibody concentrations were measured from a fasting serum sample. Results: Free insulin concentrations were lower in the patients than in the controls (4.3±2.3 mU/I compared with 6.5 ± 3.1 mU/1, P < 0.001), and there was an inverse correlation between free insulin and fasting blood glucose in the boys with diabetes (r = -0.53, P < 0.001), whereas a positive correlation was observed between free insulin and leptin concentrations in the girls with diabetes (r = 0.30, P = 0.020). The IGFBP-1 concentrations were greater in the patients than in the controls (16.5±10.6 μg/I compared with 4.0±4-3.3, P < 0.001), and they correlated significantly with blood glucose (r = 0.63, P < 0.001) and free insulin (r = -0.35, P <0.001). No significant difference was observed in the leptin concentrations between the patients and controls overall, despite greater total body fat in the girls with diabetes compared with the control girls. Conclusions: Adolescents with IDDM are characterised by morning hypoinsulinaemia and high circulating IGFBP-1 concentrations, which may contribute to insulin resistance and impaired metabolic control during puberty. The mechanism behind the increased total body fat in the postpubertal female patients remains to be determined.