Circulating IGF-I, IGFBP-3 and the IGF-I/IGFBP-3 Molar Ratio Concentration and Height Outcome in Prepubertal Short Children on rhGH Treatment over Two Years of Therapy

Ballerini, Marı́a Gabriela; Braslavsky, Débora; Scaglia, Paula; Keselman, Ana; Rodrı́guez, Marı́a Eugenia; Martínez, A; Freire, Analía; Domené, Horacio M.; Jásper, H; Bergadá, Ignacio; Ropelato, María Gabriela

doi:10.1159/000479691

Cited by 14 publications

(16 citation statements)

References 32 publications

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“…We also found that the intervention resulted in increased IGF-I:IGFBP3 molar ratio. The molar ratio between total IGF-I and IGFBP-3 (IGF-I/IGFBP-3) has been suggested to indirectly reflect free as well as with bioactive IGF-I [35,36]. Changes in concentrations of IGFBP-3 and the IGF-I:IGFBP-3 ratio deserve attention as they present potential clinical implications suggested by epidemiological data showing significant associations between IGFBP-3 or the IGF-I:IGFBP-3 ratio and various diseases such as cancer, coronary events, hepatic steatosis, and lung function to mortality [37].…”

Section: Discussionmentioning

confidence: 99%

Data Independent Acquisition Mass Spectrometry Can Identify Circulating Proteins That Predict Future Weight Loss with a Diet and Exercise Programme

Malipatil

Fachim

Siddals

et al. 2019

JCM

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We investigated biological determinants that would associate with the response to a diet and weight loss programme in impaired glucose regulation (IGR) people using sequential window acquisition of all theoretical fragment ion spectra (SWATH) mass spectrometry (MS), a data acquisition method which complement traditional mass spectrometry-based proteomics techniques. Ten women and 10 men with IGR underwent anthropometric measurements and fasting blood tests. SWATH MS was carried out with subsequent immunoassay of specific peptide levels. After a six-month intervention, 40% of participants lost 3% or more in weight, 45% of patients remained within 3% of their starting weight and 15% increased their weight by 3% or more. Hemoglobin A1c (HbA1C) level was reduced with weight loss with improvements in insulin sensitivity. SWATH MS on pre-intervention samples and subsequent principal component analysis identified a cluster of proteins associated with future weight loss, including insulin-like growth factor-II (IGF-II) and Vitamin D binding protein. Individuals who lost 3% in weight had significantly higher baseline IGF-II levels than those who did not lose weight. SWATH MS successfully discriminated between individuals who were more likely to lose weight and potentially improve their sensitivity to insulin. A higher IGF-II baseline was predictive of success with weight reduction, suggesting that biological determinants are important in response to weight loss and exercise regimes. This may permit better targeting of interventions to prevent diabetes in the future.

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Section: Discussionmentioning

confidence: 99%

Data Independent Acquisition Mass Spectrometry Can Identify Circulating Proteins That Predict Future Weight Loss with a Diet and Exercise Programme

Malipatil

Fachim

Siddals

et al. 2019

JCM

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“…As an easier available surrogate marker, the IGF-I/IGFBP-3 molar ratio has been suggested. It might not provide all the information which could be extracted from direct assessment of free IGF-I, but has been shown to correlate with clinical endpoints such as efficacy of recombinant human GH treatment (70,71).…”

Section: Free Igf-imentioning

confidence: 99%

Laboratory investigations in the diagnosis and follow-up of GH-related disorders

Schilbach¹,

Bidlingmaier²

2019

Archives of Endocrinology and Metabolism

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In addition to auxiological, clinical and metabolic features measurements of growth hormone (GH) and insulin-like growth factor I (IGF-I) complement our tools in diagnosis and follow-up of GH-related disorders. While comparably robust during the pre-analytical phase, measurement and interpretation of concentrations of both hormones can be challenging due to analytical issues and biological confounders. Assay methods differ in terms of antibody specificity, interference from binding proteins, reference preparations and sensitivity. GH assays have different specificity towards different GHisoforms (e.g. 20 kDa GH, placental GH) and interference from the GH antagonist Pegvisomant. The efficacy to prevent binding protein interference is most important in IGF-I assays. Methodological differences between assays require that reference intervals and diagnostic cutoffs are assay-specific. Among biological variables, pubertal development and age are most relevant for IGF-I, making detailed reference intervals mandatory for interpretation. GH has pulsatile secretion and short half-life. Its concentration is modified by acute factors such as stress, exercise and sleep, but also by intake of oral estrogens and anthropometric factors (e.g. BMI). Other GH dependent biomarkers such as free IGF-I, IGF binding protein 3 (IGFBP 3) and acid labile subunit (ALS) have been proposed. Their concentrations largely mirror the information obtained through measurement of IGF-I, but their measurement can be helpful in particular situations. In this review, we describe the evolution of analytical methods to measure biomarkers of GH action, the impact of the methodological changes on laboratory results and the need to include biological variables in their interpretation.

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“…In another study involving 63 children treated with GH, the molar ratio of IGF-I to IGFBP-3, a proxy for free IGF-I levels, was significantly increased in children with an adequate response to GH therapy compared with nonresponders. These studies, albeit limited, support the hypothesis that increasing free IGF-I levels should lead to increased growth [ 11 ].…”

mentioning

confidence: 58%

PAPPA2 as a Therapeutic Modulator of IGF-I Bioavailability: in Vivo and in Vitro Evidence

Andrew

Liao

Fujimoto

et al. 2018

Journal of the Endocrine Society

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ContextPregnancy-associated plasma protein A2 (PAPPA2) is a protease that cleaves IGF-binding protein (IGFBP)-3 and IGFBP-5, liberating free IGF-I. Five patients from two families with genetic mutations in PAPPA2 presented with growth retardation, elevated total IGF-I, and IGFBP-3 but decreased free IGF-I.ObjectiveTo determine whether plasma transfusion or recombinant human (rh)PAPPA2 could increase free IGF-I in patients with PAPPA2 deficiency or idiopathic short stature (ISS).DesignSingle patient interventional study combined with in vitro experimentation.SettingAcademic medical center.PatientsThree siblings with PAPPA2 deficiency and four patients with ISS.InterventionsAn adult female with PAPPA2 deficiency received a 20 mL/kg plasma transfusion. PAPPA2, intact IGFBP-3, and free and total IGF-I levels were monitored during 2 weeks. rhPAPPA2 was added to serum from patients with PAPPA2 deficiency and ISS in vitro for 4 hours. Intact IGFBP-3 and free IGF-I levels were assayed via ELISA.Main Outcome MeasuresFree IGF-I concentrations.ResultsPlasma transfusion resulted in a 2.5-fold increase of free IGF-I levels on day 1 posttransfusion with a return to baseline during a 2-week period. In vitro studies demonstrated a dose-dependent increase in free IGF-I and decrease in intact IGFBP-3 after the addition of rhPAPPA2. The increase in free IGF-I was more pronounced in patients with PAPPA2 deficiency compared with those with ISS.ConclusionsPAPPA2 plays a key role in regulation of IGF-I bioavailability. rhPAPPA2 is a promising therapy to increase free IGF-I levels both in patients with PAPPA2 deficiency as well as in patients with ISS.

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Circulating IGF-I, IGFBP-3 and the IGF-I/IGFBP-3 Molar Ratio Concentration and Height Outcome in Prepubertal Short Children on rhGH Treatment over Two Years of Therapy

Cited by 14 publications

References 32 publications

Data Independent Acquisition Mass Spectrometry Can Identify Circulating Proteins That Predict Future Weight Loss with a Diet and Exercise Programme

Data Independent Acquisition Mass Spectrometry Can Identify Circulating Proteins That Predict Future Weight Loss with a Diet and Exercise Programme

Laboratory investigations in the diagnosis and follow-up of GH-related disorders

PAPPA2 as a Therapeutic Modulator of IGF-I Bioavailability: in Vivo and in Vitro Evidence

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