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

Abstract

Owing to advances in treatment modalities and supportive care, overall survival rates have reached up to 90% among children with acute lymphoblastic leukemia (ALL). However, due to the underlying illness and therapy, they are at a greater risk of developing lifestyle diseases. Hence, special attention is paid to early detection of the components of metabolic syndrome (MetS). This study aimed at investigating the association of plasma levels of nine diabetes markers with being overweight and components of MetS in ALL survivors. The study included 56 subjects with mean age of 12.36 ± 5.15 years. The commercially available Bio-Plex Pro Human Diabetes 10-Plex Panel kit was used to evaluate levels of diabetes biomarkers. ALL survivors presented statistically higher concentrations of GIP (p = 0.026), glucagon (p = 0.001), leptin (p = 0.022), and PAI-1 (p = 0.047), whereas the concentration of ghrelin was lower (p < 0.001) compared to the control group. Moreover, subjects within normal BMI range showed higher GIP (p = 0.005) and lower ghrelin concentration (p < 0.001) compared to healthy peers. At least one risk factor of MetS was present in 58.9% of participants, who showed significantly higher levels of C-peptide (p = 0.028), leptin (p = 0.003), and PAI-1 (p = 0.034) than survivors who did not meet any MetS criteria. In conclusion, ALL survivors are at greater risk of disturbances in carbohydrate metabolism. Understanding the pathogenesis and applicability of diabetes markers is crucial for developing strategies to prevent metabolic syndrome in ALL survivors.

Circulating leptin is associated with adverse vascular changes in young adult survivors of childhood cancer

“…This finding is in concordance with previous metabolic studies of other childhood cancer survivor cohorts. 18,19 In childhood cancer survivors, leptin has been linked to obesity and central fat mass as well as to other components of the metabolic syndrome. 20,21 In the current study, leptin was positively correlated with lowdensity lipoprotein suggesting that leptin might reflect increased adiposity.…”

Aldehyde-mediated inhibition of asparagine biosynthesis has implications for diabetes and alcoholism

“…Recent studies on pancreatic cancer have identified an unexpected role for asparagine and ASNS in enabling proliferation when respiration is limited. 59 Interestingly, ALL survivors are reported to have a greater incidence of diabetes, 60 a finding which raises the possibility that, in some circumstances, perturbed carbohydrate metabolism may confer a selective advantage.…”

Vitamin D Deficiency and Carotid Media-Intima Thickness in Childhood Cancer Survivors

“…The study included 111 childhood cancer survivors (62 males, 49 females) visiting the follow-up outpatients' clinic at the Department of Pediatric Oncology and Hematology, Medical University of Bialystok (Poland). Patients were treated for acute lymphoblastic leukemia (54), acute myeloid leukemia (5), non-Hodgkin lymphoma (9), Hodgkin lymphoma (3), neuroblastoma (6), Wilms tumor (11), rhabdomyosarcoma (4), histiocytosis (5), and other cancers (14).…”

“…Recently, it has been increasingly emphasized that in addition to the influence of genetic and environmental factors, the earlier development of many diseases as compared to the general population results from previous anticancer treatment [ 1 , 2 ]. An emerging population of childhood cancer survivors (CCS) is also predisposed to dyslipidemia, metabolic syndrome and subsequent cardiovascular disorders [ 3 , 4 , 5 ]. Moreover, growing evidence supports a molecular basis for premature aging in association with the use of cytostatics and radiation therapy, including processes such as pro-inflammatory cytokines production, telomere attrition, and oxidative stress, which ultimately leading to damage to various cells in the body [ 6 , 7 , 8 ].…”