Association between Insulin-Like Growth Factor-I

Abstract

Several prospective observational studies have suggested that elevated circulating IGF-I levels are associated with an increased risk of cancer. These observations may provide a potential mechanism through which previously identified metabolic and anthropometric factors, such as obesity and elevated insulin and glucose levels, may operate. We therefore examined metabolic and anthropometric influences on circulating levels of insulinlike growth factor-I (IGF-I), insulin-like growth factorbinding protein-1 (IGFBP-1), and the IGF-I:IGFBP-1 ratio in a middle-aged population of 349 men and 492 women. IGF-I showed only modest inverse associations with indices of adiposity. However, we found that low IGFBP-I levels and an increased IGF-I:IGFBP-1 ratio were strongly associated with increased levels of insulin and glucose in men and women. Body mass index was also positively related to the IGF-I:IGFBP-1 ratio in men (P < 0.001) and women (P < 0.001), independent of metabolic correlates of IGFBP-1 and IGF-I. Similarly, waist:hip ratio and waist circumference were also associated with an increased IGF-I:IGFBP-1 ratio and low circulating IGFBP-1 levels. These findings suggest that individuals with greater fat mass and upper body obesity may have elevated levels of bioavailable or free IGF-I, which could, in part, mediate the reported associations among metabolic and anthropometric factors and cancer risk.

Body Mass Index, Physical Activity, and Risk of Multiple Myeloma

“…Thus, IL-6 dysregulation is one plausible biological mechanism underlying the relation of BMI with multiple myeloma. Obesity is also associated with insulin resistance and other metabolic disorders that can result indirectly in the modulation of bioavailable insulin-like growth factor-I (27)(28)(29), another important growth and survival factor in multiple myeloma (30)(31)(32). Furthermore, synergy in the IL-6 and insulin-like growth factor-I pathways has been suggested by in vitro experiments on multiple myeloma cell lines (33).…”

25-Hydroxyvitamin D, IGF-1, and Metabolic Syndrome at 45 Years of Age

“…Both vitamin D status and IGF-1 concentrations are reduced in obesity (1,2); however, for both factors, lower concentrations have been associated with disturbed glucose metabolism (3)(4)(5)(6)(7)(8), high blood pressure (9 -11), adverse lipid profiles (2,12,13), and cardiovascular disease (8,14,15) independently of body mass. The evidence for associations between vitamin D and IGF-1 axes with metabolic risk includes prospective studies, clinical trials, and dose-related effects, suggesting that associations may prove to be causal.…”

Relationship Between IGF-1 and Cortisol/ DHEA-S Ratio in Adult Men With Diabetic Metabolic Syndrome Versus Non-Diabetic Metabolic Syndrome

“…In addition, patients with type 2 diabetes often exhibit reduced circulating total IGF-1 levels [14]. Lower concentrations have been also associated with obesity [22], disturbed glucose metabolism [14,23], fasting insulin and HOMA-IR [24], high blood pressure [25], and adverse lipid profi les [22] independently of body mass.…”

“…This is probably a compensatory mechanism to maintain normal glucose tolerance, since raised IGF-1 bioactivity improves insulin sensitivity [28]. High IGF-1 bioactivity may suppresses GH secretion as part of a negative feedback system, thereby inducing lower total IGF-1 levels [22]. This may explain why low total IGF-1 levels have been previously reported to be associated with the metabolic syndrome [21].…”