Normal Values of Circulating Insulin-Like Growth Factor-I Bioactivity in the Healthy Population: Comparison with Five Widely Used IGF-I Immunoassays

Brugts, Michael P.; Ranke, Michael B.; Hofland, Leo J.; Wansem, Katy van der; Weber, Karin; Frystyk, Jan; Lamberts, Steven W. J.; Janssen, Joseph A M J L

doi:10.1210/jc.2007-2454

Cited by 58 publications

(50 citation statements)

References 24 publications

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“…Our data support this finding because we found that IGFBP1 significantly and negatively predicted bioactive IGF1 in multiple linear regression analysis. Although this regression analysis did not identify total IGF1 as a significant predictor of bioactive IGF1, we found that total and bioactive IGF1 were closely related in a correlation analysis and other studies have also demonstrated the positive associations between immunoreactive IGF1 and bioactive IGF1 (23,33).…”

Section: Discussioncontrasting

confidence: 94%

“…In contrast to our observations, Brugts et al observed higher levels of bioactive IGF1 in females compared with males until the age of 55 years, whereafter bioactive IGF1 decreased markedly in females resulting in higher levels in males. A decline in bioactive IGF1 related to the menopause was suggested (23). This age-related decrease in bioactive IGF1 in females was not accompanied by a decrease in total serum IGF1 levels.…”

Section: Discussionmentioning

confidence: 91%

“…bioactive IGF1) (21). Subsequent studies have demonstrated that bioactive IGF1 is inversely correlated with age (22), significantly higher in females compared with males (23), and positively correlated with IGF1 as measured by immunoassay (i.e. total IGF1).…”

Section: Introductionmentioning

confidence: 98%

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Serum levels of bioactive IGF1 and physiological markers of ageing in healthy adults

Vestergaard

Hansen

Frystyk

et al. 2014

European Journal of Endocrinology

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Objective: Senescent changes in body composition and muscle strength are accompanied by reduced production of GH and IGF1, but the causal relationship remains elusive. We speculate that serum bioactive IGF1, measured by the IGF1 kinase receptor activation assay, is closer related to human physiological ageing than total IGF1 measured by immunoassay. Design: We conducted a cross-sectional study in 150 adult males and females, between 20 and 70 years. After an overnight fasting, serum levels of bioactive IGF1, total IGF1 and IGF-binding protein 1 (IGFBP1) and IGFBP3 were assessed. Furthermore, body composition and muscle strength was measured. Results: Total IGF1 levels were higher in females (PZ0.048). Bioactive IGF1 were identical in males and females (PZ0.31), decreasing with age. Total IGF1 tended to decrease more with age compared with bioactive IGF1 (K1.48 vs K0.89 percent/year, PZ0.052). Total body fat (TBF) was lower and BMI was higher in males (P!0.001 and PZ0.005), and both increased with age. Knee extension and elbow flexion force were higher in males (PZ0.001 and PZ0.001), but decreased with age in both genders.Total but not bioactive IGF1 was positively correlated to TBF, knee extension and muscle function in males. In multiple linear regression, only age predicted total IGF1, whereas age and IGFBP1 predicted bioactive IGF1. Conclusions: Bioactive IGF1 tends to decrease to a lesser extent than total IGF1 with age and was not correlated with measures of body composition or muscle strength. Therefore, levels of circulating bioactive IGF1 does not appear to be a better biomarker of physiological ageing than total IGF1.

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Section: Discussioncontrasting

confidence: 94%

Section: Discussionmentioning

confidence: 91%

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Serum levels of bioactive IGF1 and physiological markers of ageing in healthy adults

Vestergaard

Hansen

Frystyk

et al. 2014

European Journal of Endocrinology

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“…In our laboratory, we have developed three bioassays, specific for the human IR-A, the human IR-B and the human IGF1R, which quantify ligand-stimulated phosphorylation of tyrosine residues within the specific receptors (Brugts et al 2008, Varewijck et al 2010. These assays use human embryonal kidney (HEK) cells which are stably transfected with cDNA of either the human IR-A, the human IR-B or the human IGF1R.…”

Section: In Vitro/ex Vivo Cell Culture Systemsmentioning

confidence: 99%

Insulin and its analogues and their affinities for the IGF1 receptor

Varewijck¹,

Janssen²

2012

Endocrine-Related Cancer

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Insulin analogues have been developed in an attempt to achieve a more physiological replacement of insulin and thereby a better glycaemic control. However, structural modification of the insulin molecule may result in altered binding affinities and activities to the IGF1 receptor (IGF1R). As a consequence, insulin analogues may theoretically have an increased mitogenic action compared to human insulin. In view of the lifelong exposure and large patient populations involved, insulin analogues with an increased mitogenic effect in comparison to human insulin may potentially constitute a major health problem, since these analogues may possibly induce the growth of pre-existing neoplasms. This hypothesis has been evaluated extensively in vitro and also in vivo by using animal models. In vitro, all at present commercially available insulin analogues have lower affinities for the insulin receptor (IR). Although it has been suggested that especially insulin analogues with an increased affinity for the IGF1R (such as insulin glargine) are more mitogenic when tested in vitro in cells expressing a high proportion of IGF1R, the question remains whether this has any clinical consequences. At present, there are several uncertainties which make it very difficult to answer this question decisively. In addition, recent data suggest that insulin (or insulin analogues)-mediated stimulation of IRs may play a key role in the progression of human cancer. More detailed information is required to elucidate the exact mechanisms as to how insulin analogues may activate the IR and IGF1R and how this activation may be linked to mitogenesis.

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“…Circulating IGF1 bioactivity was measured using an in-house IGF1 kinase receptor activation assay (IGF1 KIRA) as was previously described (10,11). The methodology of this latter assay is based on another principle than that of IGF1 immunoassays.…”

Section: Igf1 Kinase Receptor Activation Assaymentioning

confidence: 99%

Heterophilic antibodies may be a cause of falsely low total IGF1 levels

Brugts

Luermans

Lentjes

et al. 2009

European Journal of Endocrinology

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Background: A low serum total IGF1 is considered as a diagnostic indicator of GH deficiency (GHD) in the presence of hypopituitarism. Introduction of IRMA and chemiluminescent immunometric assay (CLIA) IGF1 immunoassays has introduced endogenous antibodies as a new source of interference. In general, this goes unnoticed and might lead to unnecessary diagnostic and therapeutic interventions. Case: A 56-year-old man was referred with a decline in physical performance, unexplained osteopenia, and weight loss of 3 kg over the past 8 months. Although clinical signs and symptoms were unremarkable, laboratory results pointed to secondary hypothyroidism and secondary hypogonadism. In addition, the serum total IGF1 level (CLIA; Siemens Medical Solutions Diagnostics) was in the low normal range. Two GH stimulation tests were performed, but these tests did not support the diagnosis GHD. Moreover, IGF1 bioactivity measured by the kinase receptor activation assay was normal. Interference of heterophilic antibodies was considered. After pretreatment with specific heterophilic blocking tubes that contain blocking reagents to eliminate heterophilic antibodies, serum-free thyroxine, testosterone, and IGF1 levels turned out to be normal. Conclusion: To the best of our knowledge, we here describe the first case in the literature of a patient with low serum total IGF1 levels due to interference from heterophilic antibodies in the used IGF1 immunoassay. When confronted with low-IGF1 levels that do not fit the clinical picture, interference of heterophilic antibodies should be considered in the differential diagnosis.

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Normal Values of Circulating Insulin-Like Growth Factor-I Bioactivity in the Healthy Population: Comparison with Five Widely Used IGF-I Immunoassays

Cited by 58 publications

References 24 publications

Serum levels of bioactive IGF1 and physiological markers of ageing in healthy adults

Serum levels of bioactive IGF1 and physiological markers of ageing in healthy adults

Insulin and its analogues and their affinities for the IGF1 receptor

Heterophilic antibodies may be a cause of falsely low total IGF1 levels

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