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Insulin-like growth factor binding protein-1 to screen for insulin resistance in children
Roja Motaghedi1, Sahil Gujral, Sunil Sinha
1Weill Cornell Medical College, New York, New York, USA.
Insights
Insulin resistance (IR) in children can be detected using Insulin-like Growth Factor Binding Protein-1 (IGFBP-1) levels. This marker is particularly sensitive in children under 10, aiding early preventative strategies for diabetes and atherosclerosis.
Area of Science:
- Pediatric Endocrinology
- Metabolic Disorders
- Biomarker Discovery
Background:
- Obesity-associated insulin resistance (IR) contributes to diabetes and atherosclerosis.
- Early detection of IR in children is crucial for preventative interventions.
- Peripheral insulin levels are insensitive indicators of hepatic insulin fluxes.
Purpose of the Study:
- To evaluate insulin-regulated hepatic insulin-like growth factor binding proteins (IGFBPs)-1 and -3 as potential screening markers for childhood IR.
- To investigate the relationship between serum IGFBP-1 and IGFBP-3 levels and insulin sensitivity in obese children and adolescents.
Main Methods:
- Utilized the tolbutamide-modified frequently sampled intravenous glucose tolerance test (FSIVGTT) and oral glucose tolerance test (OGTT) in 118 subjects under 21 with obesity.
- Assessed insulin sensitivity index (SiIVGTT) via minimal modeling.
- Correlated SiIVGTT with fasting/OGTT insulin and glucose values and serum IGFBP-1 and IGFBP-3 levels.
Main Results:
- IGFBP-1 significantly correlated with SiIVGTT, mirroring correlations of other insulin sensitivity indices.
- The correlation between IGFBP-1 and SiIVGTT was strongest in children aged 10 years and younger.
- All subjects (100%) with IR (SiIVGTT < 4.5 +/- 0.5 x 10(-4) min(-1)/(microIU/mL)) exhibited inappropriately low IGFBP-1 levels.
- IGFBP-3 did not show a significant correlation with SiIVGTT.
Conclusions:
- IGFBP-1 levels decrease with increasing obesity and IR.
- IGFBP-1 serves as a convenient and sensitive marker for detecting IR in young individuals, especially those under 10 years old.
- Elevated fasting insulin is less sensitive but more specific for identifying IR in this population.
Background:
Diabetes and atherosclerosis are burgeoning health problems complicating obesity-associated insulin resistance (IR). Early detection of IR in children is a key to preventative strategies. Since peripheral insulin levels insensitively reflect hepatic insulin fluxes, we studied the insulin-regulated hepatic insulin-like growth factor binding proteins (IGFBPs)-1 and -3 as possible screening markers of childhood IR.
Methods:
The tolbutamide-modified frequently sampled intravenous glucose tolerance test (FSIVGTT) and the oral glucose tolerance test (OGTT) were performed in 118 subjects < 21 years old with obesity. The relationships between insulin sensitivity index by minimal modeling (SiIVGTT), other Sis derived from fasting and OGTT insulin and glucose values, and the candidate serum markers were sought.
Results:
Significant correlation was found between IGFBP-1 and SiIVGTT, similar to the correlations of insulin sensitivity indices with SiIVGTT. In children < or = 10 years old, correlation of IGFBP-1 with SiIVGTT was the strongest. All (100%) subjects with IR defined by SiIVGTT < 4.5 +/- 0.5 x 10(-4) min(-1) /(microIU/mL) had inappropriately low IGFBP-1 levels. IGFBP-3 was not correlated with SiIVGTT.
Conclusions:
IGFBP-1 levels decrease with obesity and IR. We propose that in young subjects, especially children under the age of 10 years, IGFBP-1 is a convenient and sensitive marker of IR, whereas elevated fasting insulin is less sensitive but more specific.
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