The serum levels of proinsulin and their relationship with IGFBP-1 in obese children.
OBJECTIVE
Serum proinsulin (PI) levels were investigated in obese children to determine whether PI is a sensitive indicator of insulin resistance, as previously shown in adults with type 2 diabetes mellitus (DM), and to evaluate their relationship with insulin-like growth factor-binding protein-1 (IGFBP-1) known as a predictor of the development of cardiovascular disease in diabetic adults.


METHODS
Forty-two obese children without DM (age, 12.1 +/- 1.5 year) and 42 age-matched control children were included in the study. The serum levels of PI, immunoreactive insulin (IRI), IGFBP-1 and free insulin-like growth factor-1 (IGF-1) were measured in the fasting state.


RESULTS
The fasting levels of serum PI and IRI were significantly higher in obese children than in controls (PI, 10.5 +/- 6.8 vs. 5.6 +/- 2.0 pmol/l, p < 0.001; IRI, 72.0 +/- 41.8 vs. 32.7 +/- 19.5 pmol/l, p < 0.001). Serum IGFBP-1 levels were significantly lower in obese children than in controls (37.7 +/- 24.6 vs. 76.3 +/- 26.5 microg/l, p < 0.001). The ratio of PI to IRI (calculated as molar ratios) did not differ significantly between obese and control subjects (0.16 +/- 0.08 vs. 0.19 +/- 0.11, p = 0.08). For the whole group, serum PI levels correlated positively with IRI and inversely with IGFBP-1 (IRI, r = 0.67, p < 0.001; IGFBP-1, r = -0.49, p < 0.001). Serum IGFBP-1 levels correlated inversely with both BMI and IRI (BMI, r = -0.73, p < 0.001; IRI, r = -0.60, p < 0.001). Multiple regression analysis revealed that the best predictive parameters for IGFBP-1 were BMI and PI (R2 = 0.57, p < 0.001 and p < 0.05, respectively).


CONCLUSIONS
These findings suggest that fasting serum PI levels may be a better predictor than fasting insulin levels for the future development of type 2 DM and cardiovascular disease in obese children, and PI, in addition to insulin, contributes to the suppression of hepatic IGFBP-1 production.
Kamoda
T
T
Department of Pediatrics, University of Tsukuba, Ibaraki, Japan. tkamoda@md.tsukuba.ac.jp
Saitoh
H
H
Inudoh
M
M
Miyazaki
K
K
Matsui
A
A
D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis; D003925:Diabetic Angiopathies / Q000175:diagnosis; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000097:blood*; D011384:Proinsulin / Q000378:metabolism*
D018970:Insulin-Like Growth Factor Binding Protein 1; D011384:Proinsulin