Close relation of fasting insulin-like growth factor binding protein-1 (IGFBP-1) with glucose tolerance and cardiovascular risk in two populations

Abstract

Cardiovascular disease is the leading cause of morbidity and mortality in patients with Type II (non-insulin-dependent) diabetes mellitus accounting for up to 75 % of deaths [1]. Although insulin and insulin resistance have been considered major factors in the pathogenesis of cardiovascular disease [2,3], given the close links between the insulin-like growth factor-system and insulin action we examined the potential role of the insulin-like growth factor-system in the pathogenesis of macrovascular disease. Diabetologia (2001) Abstract 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 (IG-FBP-1), insulin-like growth factor-I (IGF-I), insulinlike 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 (b = 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]

Marked differences in the IGF system that are associated with migration in comparable populations of Gujaratis living in Sandwell, UK, and Gujarat, India

“…HOMA-S is low in the Sandwell Gujaratis. However, in our previous paper [15], which described HOMA-S in South Asians of Pakistani origin living in the UK, HOMA-S in individuals of normal glucose tolerance status was similar to the values reported here.…”

“…It is well established that increased total energy intake results in higher levels of IGF-I [29]. The lower IGFBP-1 in Sandwell Gujaratis is in keeping with lower insulin sensitivity (HOMA-S; Table 2), as we have described previously in other ethnic groups [15]. HOMA-S is low in the Sandwell Gujaratis.…”

“…Of the six IGFBPs fully characterised, IGFBP-1 is considered to be the principal hour-to-hour regulator of circulating IGF activity [14], forming the link between dietary ingestion, glucose metabolism and the IGF axis. We and others have established close links between the IGF system and the development of impaired glucose tolerance, obesity and macrovascular disease [15][16][17][18]. In a white European population, we demonstrated that such changes predict the development of worsening glucose tolerance at the 5-year follow-up [6].…”

“…Given the association between IGFBP-1 and glucose level found previously, both cross-sectionally [15] and prospectively [6], the relation between IGFBP-1 glucose and other metabolic variables was examined using a regression model. Forward stepwise linear regression analyses in a model that also included sex, height and log total energy intake showed that, for Navsaris, IGFBP-1 was positively associated with fasting glucose (β = 0.32, p=0.003).…”

Diabetes and the risk of prostate cancer: the role of diabetes treatment and complications

“…5 However, it is consistent with some reports that low IGF binding protein-1 (and thus high bioavailability of IGF-1, which could increase prostate cancer risk) is associated with increased cardiovascular risk in individuals with type 2 diabetes and other populations. [20][21][22] Diabetic men with microvascular complications had a decreased risk of prostate cancer (HR 0.62, CI 0.39-0.98), compared to non-diabetic men. This finding is consistent with the one other study of microvascular complications 2 and with studies suggesting that decreased IGF-1 is associated with neuropathy.…”