Aims/hypothesis. Insulin resistance/hyperinsulinaemia is implicated in the development of cardiovascular disease and diabetes but its role
and causal pathways are not clear. We tested the hypothesis that the insulin-like growth factor system is independently associated
with cardiovascular risk within susceptible populations based on previous reports of the links between low circulating insulin-like
growth factor binding protein-1 concentrations and increased macrovascular disease in Type II (non-insulin-dependent) diabetes
mellitus.
Methods. In a population-based study 272 subjects (142 subjects of European and 130 Pakistani of origin) underwent a 75 g oral glucose
tolerance test and standardised anthropometry. Fasting concentrations of insulin-like growth factor binding protein-1 (IGFBP-1),
insulin-like growth factor-I (IGF-I), insulin-like growth factor-II (IGF-II), intact insulin and lipids were measured and
were related to 2-h glucose tolerance test status. Insulin sensitivity was calculated using the homeostasis model assessment
(HOMA).
Results. Insulin-like growth factor binding protein-1 was significantly lower in subjects with impaired glucose tolerance when compared
with normal glucose tolerance in both ethnic groups (Europeans F = 6.7,
p = 0.002 and Pakistanis F = 4.4,
p = 0.01). Multiple linear regression modelling showed that insulin-like growth factor binding protein-1 was independently
associated with 2-h glucose (
β = 0.16,
p = 0.009) and logistic regression indicated a 40 % reduction in risk of impaired glucose tolerance for every 2.7 ng/ml increase
in the insulin-like growth factor binding protein-1 concentration [odds ratio 0.6 (CI = 0.49–0.71),
p = 0.001)]. In addition, insulin-like growth factor binding protein-1 was significantly correlated negatively with several
established cardiovascular factors, and positively with insulin sensitivity.
Conclusion/interpretation. Insulin-like growth factor binding protein-1 is closely related to risk factors for diabetes and cardiovascular disease in
people of European and Pakistani origin. It has potential use as a marker of (hepatic) insulin resistance in clinical intervention
studies and further implicates the insulin-like growth factor system in the development of macrovascular disease. [Diabetologia
(2001) 44: 333–339]
Keywords IGFBP-1 - glucose tolerance - cardiovascular risk - ethnicity.
Received: 18 May 2000 and in revised form: 22 September 2000