Insulin-like growth factor binding protein-2 (IGFBP-2) is a marker for the metabolic syndrome.
OBJECTIVE
IGFs and their binding proteins are increasingly recognised as important in understanding the pathogenesis of cardiovascular disease. Low IGFBP-1, particularly coupled with low IGF-I, is associated with increased cardiovascular risk. In relation to structural and regulatory parallels between IGFBP-1 and - 2 we have now examined the hypothesis that IGFBP-2 may be a marker for cardiovascular risk.


METHODS
Fasting IGFBP-2, IGFBP-1, IGFBP-3, IGF-I, IGF-II, insulin, C-peptide, glucose, lipids, NEFAs, and HbA1c were measured in a cohort of 163 patients with type 2 diabetes. Individuals were categorised according to the presence or absence of the metabolic syndrome.


RESULTS
Patients with the metabolic syndrome had a lower IGFBP-2 concentration. Low circulating IGFBP-2 was associated with elevated fasting glucose (rho = - 0.23, p = 0.003). IGFBP-2 correlated negatively with triglycerides (rho = - 0.19, p = 0.01) and LDL-cholesterol (rho = - 0.20, p = 0.01), and positively with insulin sensitivity (HOMA-S) (rho = 0.26, p = 0.02). Multivariate logistic regression demonstrated that low IGFBP-2 was independently associated with an increased risk of the metabolic syndrome (OR 0.31 [95 % CI 0.11 - 0.90]; p = 0.03). IGFBP-3 did not differ according to the presence or absence of metabolic syndrome.


CONCLUSIONS
Low IGFBP-2 is associated with multiple cardiovascular risk factors similarly to IGFBP-1. Such associations were not apparent for IGFBP-3. Lack of marked prandial regulation of IGFBP-2, in contradistinction to IGFBP-1, may make IGFBP-2 a more robust biomarker for identification of insulin-resistant individuals at high cardiovascular risk in epidemiological studies.
Heald
A H
AH
Diabetes & Endocrinology, University of Manchester, Hope Hospital, Salford, United Kingdom. aheald@fs1.ho.man.ac.uk
Kaushal
K
K
Siddals
K W
KW
Rudenski
A S
AS
Anderson
S G
SG
Gibson
J M
JM
D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure; D002096:C-Peptide / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D003927:Diet, Diabetic; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D008055:Lipids / Q000097:blood; D024821:Metabolic Syndrome / Q000097:blood*; D008875:Middle Aged
D015415:Biomarkers; D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D008055:Lipids; D002097:C-Reactive Protein