Insulin-like growth factor-binding protein-1 in the prediction and development of type 2 diabetes in middle-aged Swedish men

Abstract

Aims/hypothesis Insulin-like growth factor-binding protein-1 (IGFBP-1) production in the liver is inhibited by insulin, and low circulating levels are associated with the metabolic syndrome. The aim of this study was to evaluate the predictive role and change in IGFBP-1 concentrations during development of abnormal glucose regulation. Methods IGFBP-1 levels were determined at baseline and at 10 years in an incident case-control prospective study of Swedish white men aged 35-56 years. Individuals with normal glucose tolerance at baseline who developed abnormal glucose tolerance during a 10 year period (n=355) according to WHO criteria were pair-matched to controls for age and family history of diabetes. Results Fasting IGFBP-1 concentrations were lower in individuals who later developed abnormal glucose regulation and correlated inversely with fasting proinsulin values (r =−0.48; p<0.0001), and both were significant predictors. Individuals in the highest quartile at baseline for an algorithm incorporating fasting IGFBP-1, blood glucose, proinsulin and waist and height had a 40-fold increased risk of developing type 2 diabetes compared with the lowest quartile (95% CI 7.7-214). IGFBP-1 increased 32% (95% CI 17-49%) during the 10 years in those developing diabetes and was increased in relation to insulin levels, suggesting the emergence of hepatic insulin resistance. Moreover, elevated IGFBP-1 levels at follow-up were associated with higher 2 h glucose values during an OGTT. Conclusions/interpretation Low IGFBP-1 predicts the development of abnormal glucose regulation and, as an inhibitor of the insulin-like actions of insulin-like growth factors, elevated levels of IGFBP-1 after the development of diabetes may also play a pathophysiological role.

Low serum 25-hydroxyvitamin D level predicts progression to type 2 diabetes in individuals with prediabetes but not with normal glucose tolerance

“…In line with our previous reports, high IGFBP-1 concentrations predicted a reduced risk of diabetes in both men and women [17,18], and these effects were evident regardless of 25(OH)D serum concentrations. Interestingly, in the presence of low serum IGFBP-1 concentrations, high 25(OH)D concentrations did not predict a reduced risk of progression to , separately and in combination, associated with prediabetes at baseline in women (grey lines) and men (black lines).…”

“…An alternative link between vitamin D and glucose homeostasis might be the IGF system [9]. We have shown that low serum levels of IGF-binding protein-1(IGFBP-1) in men and women with normal glucose tolerance (NGT) strongly predict risk of type 2 diabetes and prediabetes (impaired fasting glucose [IFG], impaired glucose tolerance [IGT] or the two combined) at a follow-up 8-10 years later [17,18]. In addition, a combination of high concentrations of 25(OH)D and IGF-1 has been associated with a low risk of the metabolic syndrome [19].…”

Parent-of-origin specific linkage and association of the IGF2 gene region with birth weight and adult metabolic risk factors

“…[42][43][44] Low IGFBP1 levels predict the development of abnormal glucose regulation and have been associated with an unfavorable cardiovascular risk profile. 45,46 Conversely, in patients with acute myocardial infarction and type 2 diabetes, high IGFBP1 levels have been associated with an increased risk of cardiovascular mortality and morbidity, which is probably the result of hepatic insulin resistance in these patients. 47 As circulating IGFBP1 is generally considered to be of hepatic origin, the effect observed in this study is possibly the result of a modified IGFBP1 expression mediated by IGF2 in the liver.…”

Atorvastatin administration is associated with dose-related changes in IGF bioavailability

“…IGFBP1 is a marker of insulin sensitivity (20). In clinical and population studies, low circulating IGFBP1 concentration has been associated with insulin resistance (11,21) and an increased risk for incident gestational diabetes, glucose intolerance and type 2 diabetes (4, 10, 11, 22).…”

“…IGF binding protein 1 (IGFBP1) is an acute modulator of IGF1 and IGF2 bioavailability, and altered IGFBP1 levels have also been linked to diabetes rates (10,11,12). IGFBP3 is the principal carrier protein of IGF1 and IGF2.…”