IGFBP2 is a biomarker for predicting longitudinal deterioration in renal function in type 2 diabetes

Narayanan, Ram Prakash; Fu, Bo; Heald, Adrian; Siddals, Kirk; Oliver, R.; Hudson, Julie E; Payton, Antony; Anderson, Simon; White, Anne; Ollier, William; Gibson, J. M.

doi:10.1530/ec-12-0053

Cited by 29 publications

(29 citation statements)

References 34 publications

(15 reference statements)

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“…Interestingly, glomerular IGFBP‐2 expression has been reported to be increased in animal models of anti–glomerular basement membrane glomerulonephritis and MRL/lpr lupus . IGFBP‐2 has also been documented to be raised in patients with diabetic nephropathy . Our study is the first to show that IGFBP‐2 is elevated in patients with active SLE.…”

Section: Discussionsupporting

confidence: 52%

Axl, Ferritin, Insulin‐Like Growth Factor Binding Protein 2, and Tumor Necrosis Factor Receptor Type II as Biomarkers in Systemic Lupus Erythematosus

Mok

Ding

Kharboutli

et al. 2016

Arthritis Care & Research

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Objective-To evaluate the performance of 4 serum protein markers for detecting concurrent clinical activity in patients with systemic lupus erythematosus (SLE).Methods-Consecutive patients who fulfilled ≥4 ACR criteria for SLE and healthy controls were recruited for serological testing of 4 protein markers identified by antibody-coated microarray screen, namely Axl, ferritin, IGFBP2 and TNFR2. SLE disease activity was assessed by the SELENA-SLEDAI and physician's global assessment (PGA). Levels of these markers were correlated with SLEDAI and their sensitivity and specificity for clinical SLE activity was determined.Results-A total of 94 SLE patients (98% women; age 28.7±9.4 years, disease duration 5.4±5.0 years) and 49 healthy controls were studied. Fifty-two patients had clinically active SLE (SLEDAI score ≥6 or having a flare). The serum concentrations of Axl, ferritin, IGFBP2 and TNFR2 were significantly higher in patients with active SLE than inactive SLE or controls. The levels of these markers correlated strongly and significantly with anti-dsDNA, C3, clinical SLEDAI and PGA scores. These markers were more specific, but less sensitive, in detecting concurrent SLE activity than elevated anti-dsDNA or depressed C3. Levels of Axl, TNFR2 and IGFBP2, but not ferritin, could differentiate active renal from active non-renal or inactive SLE. The specificity of Axl and IGFBP2 for concurrent active lupus nephritis was higher than anti-dsDNA or C3. Contributions to this work:Chi Chiu 1b, 1c,2, 1b,2,1b,2, 1b,2,3 HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptConclusions-Serum proteomic markers are potentially useful for diagnosing SLE and monitoring disease activity. The performance of Axl and IGFBP2 in lupus nephritis should be further explored in a longitudinal cohort of SLE patients.

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Section: Discussionsupporting

confidence: 52%

Axl, Ferritin, Insulin‐Like Growth Factor Binding Protein 2, and Tumor Necrosis Factor Receptor Type II as Biomarkers in Systemic Lupus Erythematosus

Mok

Ding

Kharboutli

et al. 2016

Arthritis Care & Research

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“…In human immunoglobulin (Ig)A nephropathy, glomerular expression levels of IGFBP‐2 mRNA were increased significantly compared to normal glomeruli . Of relevance to our study, IGFBP‐2 has also been reported to be increased in nephrotic syndrome in paediatric patients and as a predictor of longitudinal deterioration of renal function in type 2 diabetes . Although the above reports suggest that IGFBP‐2 is a reliable biomarker of renal deterioration, our results still indicate that it had high sensitivity and specificity in discriminating kidney disease caused by SLE from other origins.…”

Section: Discussionmentioning

confidence: 53%

“…It is the second most abundant IGFBP found in serum, and has been found to be a robust diagnostic and prognostic biomarker for several malignant tumours . IGFBP‐2 has also been reported to be increased in nephrotic syndrome and to be a predictor of longitudinal deterioration of renal function in type 2 diabetes .…”

Section: Introductionmentioning

confidence: 99%

Insulin-like growth factor binding protein-2 as a novel biomarker for disease activity and renal pathology changes in lupus nephritis

Ding

Kharboutli

Saxena

et al. 2016

Clinical and Experimental Immunology

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SummaryLupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus. Invasive renal biopsy remains the gold standard for the diagnosis and management of LN. The objective of this study is to validate serum insulin-like growth factor binding protein-2 (IGFBP-2) as a novel biomarker for clinical disease and renal pathology in LN. Eighty-five biopsyproven lupus nephritis patients, 18 chronic kidney disease (CKD) patients and 20 healthy controls were recruited for enzyme-linked immunosorbent assay (ELISA) testing of serum IGFBP-2 levels. Compared to CKD patients of origins other than lupus or healthy controls, serum IGFBP-2 levels were elevated significantly in LN patients. Serum IGFBP-2 was able to discriminate LN patients from the other two groups of patients [area under the curve (AUC) 5 0Á65, 95% confidence interval (CI) 5 0Á52-0Á78; P 5 0Á043 for LN versus CKD; 0Á97, 95% CI 5 0Á93-1Á00; P < 0Á0001 for LN versus healthy controls]. Serum IGFBP-2 was a potential indicator of both global disease activity and renal disease activity in LN patients, correlated with serum creatinine levels (r 5 0Á658, P < 0Á001, n 5 85) and urine protein-to-creatinine levels (r 5 0Á397, P < 0Á001, n 5 85). More importantly, in 19 concurrent patient samples, serum IGFBP-2 correlated with the chronicity index of renal pathology (r 5 0Á576, P 5 0Á01, n 5 19) but not renal pathological classification. In conclusion, serum IGFBP-2 is a promising biomarker for lupus nephritis, reflective of disease activity and chronicity changes in renal pathology.

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“…For example, transgenic mice that overexpressed IGFBP-2 showed significantly higher blood glucose levels than controls at 30, 60 and 90 minutes during an oral glucose tolerance test, as well as lower levels of GLUT4–the insulin-dependent glucose transporter–at cell surfaces compared to controls [5]. Abnormally high IGFBP-2 levels are often an indicator of severe catabolic events, such as gastric cancer, anorexia nervosa and renal failure [6-8]. In a study of 625 men and women aged 70 and older, plasma IGFBP-2 significantly predicted mortality from all causes after adjusting for markers of body composition, as well as fasting glucose and insulin [9].…”

Section: Introductionmentioning

confidence: 99%

Peripheral versus Central Index of Metabolic Dysfunction and Associations with Clinical and Pathological Outcomes in Alzheimer’s Disease

McLimans

Webb

Anantharam

et al. 2017

JAD

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Background/Objective Insulin-like growth factor binding protein 2 (IGFBP-2) regulates blood glucose levels, facilitates hippocampal synaptic plasticity and may have a predictive value for Alzheimer’s disease (AD) diagnosis. Methods IGFBP-2 levels were studied in plasma in 566 subjects and in cerebrospinal fluid (CSF) in 245 subjects across the AD spectrum from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Variants in the IGFBP-2 gene were examined. Linear mixed modeling in SPSS tested main effects of IGFBP-2 and interactions with APOE4 on neurocognitive indices and biomarkers. Voxel-wise regression was used to gauge IGFBP-2 and regional gray matter and glucose metabolism associations. Results Each point increase in IGFBP-2 corresponded to a 3 times greater likelihood of having mild cognitive impairment (MCI) or AD. IGFBP-2 showed beneficial associations with respect to cognitive scores in individuals with two APOE4 alleles. Higher IGFBP-2 predicted higher insulin resistance, but not CSF amyloid or tau. Voxel-wise analyses showed that plasma IGFBP-2 predicted lower grey matter volume and FDG metabolism in a large area spanning the frontal, temporal, and occipital lobes. CSF IGFBP-2 levels showed similar voxel-wise analysis results, but were uniquely associated with CSF amyloid and tau. Analysis of single nucleotide polymorphisms (SNPs) in IGFBP-2 showed that subjects carrying risk alleles versus common alleles had increased risk of AD and lower memory scores. Voxel-wise analyses of these SNPs also implicated the hippocampus and prefrontal cortex. Conclusions IGFBP-2 is associated with AD risk and outcomes; plasma IGFBP-2 provides stronger predictive power for brain outcomes, while CSF IGFBP-2 provides improved predictive accuracy for AD CSF biomarkers.

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IGFBP2 is a biomarker for predicting longitudinal deterioration in renal function in type 2 diabetes

Cited by 29 publications

References 34 publications

Axl, Ferritin, Insulin‐Like Growth Factor Binding Protein 2, and Tumor Necrosis Factor Receptor Type II as Biomarkers in Systemic Lupus Erythematosus

Axl, Ferritin, Insulin‐Like Growth Factor Binding Protein 2, and Tumor Necrosis Factor Receptor Type II as Biomarkers in Systemic Lupus Erythematosus

Insulin-like growth factor binding protein-2 as a novel biomarker for disease activity and renal pathology changes in lupus nephritis

Peripheral versus Central Index of Metabolic Dysfunction and Associations with Clinical and Pathological Outcomes in Alzheimer’s Disease

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