Diabetes mellitus and
glucose dysregulation have significant effects on the circulating level of
insulin-like growth factor-I (
IGF-I) and
IGF binding proteins (IGFBPs). In the present study, serum and urine
IGFBP (IGFBP-1, -2, and -3) and serum
IGF-I and -II levels were measured by radioimmunoassay (RIA) in 27 patients with
type 1 diabetes aged 9 to 48 years compared with 9 healthy subjects aged 10 to 28 years. The patients were divided into 3 groups according to the amount of
albumin excreted in 24 hours. The macroalbuminuria group (>500 mg/24 h) had elevated serum
IGFBP-1 and -2 and decreased
IGF-I levels (P < .01 v normal controls). Serum
IGFBP-3 and
IGF-II were not different among the patient groups and controls (P > .05). The mean urinary
IGFBP-1 was decreased in all 3 patient groups compared with the controls (P < .05). Urinary
IGFBP-2 and
IGFBP-3 were increased in patients with macroalbuminuria. Immunoblot analysis showed increased low-molecular-weight fragments of urinary
IGFBP-2 in the poorly controlled diabetics, and direct evidence for increased urinary
IGFBP-2 proteolytic activity could be demonstrated in both the microalbuminuric and macroalbuminuric groups. Low-molecular-weight fragments of urinary
IGFBP-3 were also increased in both the microalbuminuric and macroalbuminuric groups. In conclusion, alterations of IGFBPs in urine and serum are related to metabolic control in diabetic patients, and there is an increase of urinary
IGFBP-2 protease activity in poorly controlled diabetics. The changes in serum
IGFBP concentrations (eg, increases in
IGFBP-1 and
IGFBP-2) may lead to alterations in the availability of
IGF-I to peripheral tissues.