Can biomarkers be used to improve diagnosis and prediction of metabolic syndrome in childhood cancer survivors? A systematic review

Abstract

Childhood cancer survivors (CCS) are at increased risk to develop metabolic syndrome (MetS), diabetes, and cardiovascular disease. Common criteria underestimate adiposity and possibly underdiagnose MetS, particularly after abdominal radiotherapy. A systematic literature review and meta-analysis on the diagnostic and predictive value of nine newer MetS related biomarkers (adiponectin, leptin, uric acid, hsCRP, TNF-alpha, IL-1, IL-6, apolipoprotein B (apoB), and lipoprotein(a) [lp(a)]) in survivors and adult non-cancer survivors was performed by searching PubMed and Embase. Evidence was summarized with GRADE after risk of bias evaluation (QUADAS-2/QUIPS). Eligible studies on promising biomarkers were pooled. We identified 175 general population and five CCS studies. In the general population, valuable predictive biomarkers are uric acid, adiponectin, hsCRP and apoB (high level of evidence), and leptin (moderate level of evidence). Valuable diagnostic biomarkers are hsCRP, adiponectin, uric acid, and leptin (low, low, moderate, and high level of evidence, respectively). Meta-analysis showed OR for hyperuricemia of 2.94 (age-/ sex-adjusted), OR per unit uric acid increase of 1.086 (unadjusted), and AUC for hsCRP of 0.71 (unadjusted). Uric acid, adiponectin, hsCRP, leptin, and apoB can be alternative biomarkers in the screening setting for MetS in survivors, to enhance early identification of those at high risk of subsequent complications.

Biomarkers of Glucose Metabolism Alterations and the Onset of Metabolic Syndrome in Survivors of Childhood Acute Lymphoblastic Leukemia

“…In this regard, special attention is paid to early detection of the components of metabolic syndrome that promote the development of lifestyle diseases. To successfully prevent possible complications, it is, however, necessary to understand the underlying mechanisms and their etiopathogenesis [ 8 , 17 ].…”

“…The metabolic pathways are regulated by the number of factors whose changed secretion may be associated with the onset of insulin resistance and obesity [ 8 ]. The major markers include C-peptide, ghrelin, gastric inhibitory peptide (GIP), glucagon, insulin, plasminogen activator inhibitor-1 (PAI-1), resistin, leptin, and visfatin.…”

Biomarkers Predictive of Metabolic Syndrome and Cardiovascular Disease in Childhood Cancer Survivors

“…The lack of leptin action on the hypothalamus causes an increase in adipose tissue, confirmed by the finding that high circulating levels of leptin are strongly associated with BMI percentiles for age, sex, and visceral adiposity. The high level of leptin leads to glucose intolerance and insulin resistance [ 19 ]. As a consequence of leptin resistance, CCS exposed to cranial irradiation have a higher BMI, fat mass, and central adiposity.…”

“…Based on the pathogenetic mechanisms that lead to the onset of MetS and consequent increase in cardiovascular risk, in recent years, biomarkers capable of predicting the onset of Mets were identified in CCS [ 19 ]. Among these are the adipokines adiponectin and leptin, uric acid, the inflammatory markers high sensitivity C-reactive protein (hsCRP), Tumor Necrosis Factor-alpha (TNF-α), interleukin 1 (IL-1) and interleukin 6 (IL-6), and the lipid markers apolipoprotein B (apoB) and lipoprotein(a) (Lp(a)) [ 19 ].…”

“…This chronic low-grade inflammation facilitates the onset of MetS in CCS and the general population [ 92 , 93 ]. The close relationship between inflammation and MetS in CCS is evidenced by numerous studies that show correlations between the values of hs-CRP with each of the components of MetS [ 19 , 94 , 95 ]. The measurement hs-CRP can be performed using immunological tests and laser nephelometry with results reported in mg/dL or mg/L.…”