Prevalence and characteristics of metabolic syndrome in adults from the French childhood leukemia survivors' cohort: a comparison with controls from the French population

Claire Oudin, Julie Berbis, Yves Bertrand, Camille Vercasson, Frédérique Thomas, Pascal Chastagner, Stéphane Ducassou, Justyna Kanold, Marie-Dominique Tabone, Catherine Paillard, Marilyne Poirée, Dominique Plantaz, Jean-Hugues Dalle, Virginie Gandemer, Sandrine Thouvenin, Nicolas Sirvent, Paul Saultier, Sophie Béliard, Guy Leverger, André Baruchel, Pascal Auquier, Bruno Pannier, Gérard Michel, Claire Oudin, Julie Berbis, Yves Bertrand, Camille Vercasson, Frédérique Thomas, Pascal Chastagner, Stéphane Ducassou, Justyna Kanold, Marie-Dominique Tabone, Catherine Paillard, Marilyne Poirée, Dominique Plantaz, Jean-Hugues Dalle, Virginie Gandemer, Sandrine Thouvenin, Nicolas Sirvent, Paul Saultier, Sophie Béliard, Guy Leverger, André Baruchel, Pascal Auquier, Bruno Pannier, Gérard Michel

Abstract

The prevalence of the metabolic syndrome among adults from the French LEA childhood acute leukemia survivors' cohort was prospectively evaluated considering the type of anti-leukemic treatment received, and compared with that of controls. The metabolic profile of these patients was compared with that of controls. A total of 3203 patients from a French volunteer cohort were age- and sex-matched 3:1 to 1025 leukemia survivors (in both cohorts, mean age: 24.4 years; females: 51%). Metabolic syndrome was defined according to the National Cholesterol Education Program's Adult Treatment Panel III criteria. Metabolic syndrome was found in 10.3% of patients (mean follow-up duration: 16.3±0.2 years) and 4.5% of controls, (OR=2.49; P<0.001). Patients transplanted with total body irradiation presented the highest risk (OR=6.26; P<0.001); the other treatment groups also showed a higher risk than controls, including patients treated with chemotherapy only. Odd Ratios were 1.68 (P=0.005) after chemotherapy only, 2.32 (P=0.002) after chemotherapy and cranial irradiation, and 2.18 (P=0.057) in patients transplanted without irradiation. Total body irradiation recipients with metabolic syndrome displayed a unique profile compared with controls: smaller waist circumference (91 vs 99.6 cm; P=0.01), and increased triglyceride levels (3.99 vs 1.5 mmol/L; P<0.001), fasting glucose levels (6.2 vs 5.6 mmol/L; P=0.049), and systolic blood pressure (137.9 vs 132.8 mmHg; P=0.005). By contrast, cranial irradiation recipients with metabolic syndrome had a larger waist circumference (109 vs 99.6 cm; P=0.007) than controls. Regardless of the anti-leukemic treatment, metabolic syndrome risk was higher among childhood leukemia survivors. Its presentation differed depending on the treatment type, thus suggesting a divergent pathophysiology. This study is registered at clinicaltrials.gov identifier: 01756599.

Trial registration: ClinicalTrials.gov NCT01756599.

Copyright© 2018 Ferrata Storti Foundation.

Figures

Figure 1.
Figure 1.
Biological markers. Biological markers of metabolic syndrome (triglycerides, HDL-cholesterol and fasting glucose levels) among Leukemia in Childhood and Adolescents (LEA) cohort patients displaying a metabolic syndrome (n=106) according to treatment modality: hematopoietic stem cell transplantation (HSCT) with total body irradiation (TBI): n=39; HSCT without TBI: n=7; no HSCT with central nervous system (CNS) irradiation: n=18; no HSCT/no CNS irradiation: n=42. LEA patients were compared with Investigation and Clinical Prevention (IPC) group patients (controls) with metabolic syndrome (n=145), adjusted according to sex and age. Results are expressed as mean±Standard Error of Mean (SEM). (A) Triglyceride levels. (B) HDL cholesterol levels. (C) Fasting glucose levels.
Figure 2.
Figure 2.
Clinical markers. Clinical markers (blood pressure and waist circumference) of metabolic syndrome among Leukemia in Childhood and Adolescents (LEA) cohort patients who show a metabolic syndrome (n=106) according to treatment modality: hematopoietic stem cell transplantation (HSCT) with total body irradiation (TBI): n=39; HSCT without TBI: n=7; no HSCT with central nervous system (CNS) irradiation: n=18; no HSCT/no CNS irradiation: n=42. LEA patients with metabolic syndrome were compared with Investigation and Clinical Prevention (IPC) group patients (controls) with metabolic syndrome (n=145). Results are expressed as mean±Standard Error of Mean (SEM). (A) Waist circumference. (B) Systolic blood pressure. (C) Diastolic blood pressure. *Significant difference,

References

    1. Silverman LB, Stevenson KE, O’Brien JE, et al. Long-term results of Dana-Farber Cancer Institute ALL Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1985–2000). Leukemia. 2010;24(2):320–334.
    1. Hunger SP, Lu X, Devidas M, et al. Improved survival for children and adolescents with acute lymphoblastic leukemia between 1990 and 2005: a report from the children’s oncology group. J Clin Oncol. 2012;30(14):1663–1669.
    1. Hunger SP, Mullighan CG. Acute Lymphoblastic Leukemia in Children. N Engl J Med. 2015;373(16):1541–1552.
    1. Zwaan CM, Kolb EA, Reinhardt D, et al. Collaborative Efforts Driving Progress in Pediatric Acute Myeloid Leukemia. J Clin Oncol. 2015;33(27):2949–2962.
    1. Creutzig U, Zimmermann M, Bourquin JP, et al. Randomized trial comparing liposomal daunorubicin with idarubicin as induction for pediatric acute myeloid leukemia: results from Study AML-BFM 2004. Blood. 2013;122(1):37–43.
    1. Gamis AS, Alonzo TA, Meshinchi S, et al. Gemtuzumab ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children’s Oncology Group trial AAML0531. J Clin Oncol. 2014;32(27):3021–3032.
    1. Bhatia S, Armenian SH, Armstrong GT, et al. Collaborative Research in Childhood Cancer Survivorship: The Current Landscape. J Clin Oncol. 2015;33(27):3055–3064.
    1. Mottillo S, Filion KB, Genest J, et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol. 2010;56(14):1113–1132.
    1. Ford ES. Risks for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care. 2005;28(7):1769–1778.
    1. Gami AS, Witt BJ, Howard DE, et al. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol. 2007;49(4):403–414.
    1. Nottage KA, Ness KK, Li C, Srivastava D, Robison LL, Hudson MM. Metabolic syndrome and cardiovascular risk among long-term survivors of acute lymphoblastic leukaemia - From the St. Jude Lifetime Cohort. Br J Haematol. 2014;165(3):364–374.
    1. Eschwege E. The dysmetabolic syndrome, insulin resistance and increased cardiovascular (CV) morbidity and mortality in type 2 diabetes: aetiological factors in the development of CV complications. Diabetes Metab. 2003;29(4 Pt 2):6S19–27.
    1. Oudin C, Simeoni MC, Sirvent N, et al. Prevalence and risk factors of the metabolic syndrome in adult survivors of childhood leukemia. Blood. 2011;117(17):4442–4448.
    1. Oudin C, Auquier P, Bertrand Y, et al. Metabolic syndrome in adults who received hematopoietic stem cell transplantation for acute childhood leukemia: an LEA study. Bone Marrow Transplant. 2015;50(11):1438–1444.
    1. Saultier P, Auquier P, Bertrand Y, et al. Metabolic syndrome in long-term survivors of childhood acute leukemia treated without hematopoietic stem cell transplantation: an L.E.A. study. Haematologica. 2016;101(12):1603–1610.
    1. Majhail NS, Flowers ME, Ness KK, et al. High prevalence of metabolic syndrome after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2009;43(1):49–54.
    1. Oeffinger KC, Adams-Huet B, Victor RG, et al. Insulin resistance and risk factors for cardiovascular disease in young adult survivors of childhood acute lymphoblastic leukemia. J Clin Oncol. 2009;27(22):3698–3704.
    1. Friedman DN, Hilden P, Moskowitz CS, et al. Cardiovascular Risk Factors in Survivors of Childhood Hematopoietic Cell Transplantation Treated with Total Body Irradiation: A Longitudinal Analysis. Biol Blood Marrow Transplant. 2017;23(3):475–482.
    1. Ervin RB. Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003–2006. Natl Health Stat Report. 2009;(13):1–7.
    1. Procopiou M, Philippe J. The metabolic syndrome and type 2 diabetes: epidemiological figures and country specificities. Cerebrovasc Dis. 2005;20(Suppl 1):2–8.
    1. Cameron AJ, Shaw JE, Zimmet PZ. The metabolic syndrome: prevalence in worldwide populations. Endocrinol Metab Clin North Am. 2004;33(2):351–375.
    1. Oeffinger KC. Are survivors of acute lymphoblastic leukemia (ALL) at increased risk of cardiovascular disease? Pediatr Blood Cancer. 2008;50(2 Suppl):462–467.
    1. Pannier B, Thomas F, Eschwege E, et al. Cardiovascular risk markers associated with the metabolic syndrome in a large French population: the “SYMFONIE” study. Diabetes Metab. 2006;32(5 Pt 1):467–474.
    1. Vernay M, Salanave B, de Peretti C, et al. Metabolic syndrome and socioeconomic status in France: The French Nutrition and Health Survey (ENNS, 2006–2007). Int J Public Health. 2013;58(6):855–864.
    1. Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009;120(16):1640–1645.
    1. Scuteri A, Vuga M, Najjar SS, et al. Education eclipses ethnicity in predicting the development of the metabolic syndrome in different ethnic groups in midlife: the Study of Women’s Health Across the Nation (SWAN). Diabet Med. 2008;25(12):1390–1399.
    1. Berbis J, Michel G, Baruchel A, et al. Cohort Profile: the French childhood cancer survivor study for leukaemia (LEA Cohort). Int J Epidemiol. 2015;44(1):49–57.
    1. Michel G, Bordigoni P, Simeoni MC, et al. Health status and quality of life in long-term survivors of childhood leukaemia: the impact of haematopoietic stem cell transplantation. Bone Marrow Transplant. 2007;40(9):897–904.
    1. Karakurt H, Sarper N, Kilic SC, Gelen SA, Zengin E. Screening survivors of childhood acute lymphoblastic leukemia for obesity, metabolic syndrome, and insulin resistance. Pediatr Hematol Oncol. 2012;29(6):551–561.
    1. Follin C, Thilen U, Ahren B, Erfurth EM. Improvement in cardiac systolic function and reduced prevalence of metabolic syndrome after two years of growth hormone (GH) treatment in GH-deficient adult survivors of childhood-onset acute lymphoblastic leukemia. J Clin Endocrinol Metab. 2006;91(5):1872–1875.
    1. Blijdorp K, van Waas M, van der Lely AJ, Pieters R, van den Heuvel-Eibrink M, Neggers S. Endocrine sequelae and metabolic syndrome in adult long-term survivors of childhood acute myeloid leukemia. Leuk Res. 2013;37(4):367–371.
    1. Chow EJ, Simmons JH, Roth CL, et al. Increased cardiometabolic traits in pediatric survivors of acute lymphoblastic leukemia treated with total body irradiation. Biol Blood Marrow Transplant. 2010;16(12):1674–1681.
    1. Gurney JG, Ness KK, Sibley SD, et al. Metabolic syndrome and growth hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia. Cancer. 2006;107(6):1303–1312.
    1. Rosen GP, Nguyen HT, Shaibi GQ. Metabolic syndrome in pediatric cancer survivors: a mechanistic review. Pediatr Blood Cancer. 2013;60(12):1922–1928.
    1. Vernay M, Malon A, Oleko A, et al. Association of socioeconomic status with overall overweight and central obesity in men and women: the French Nutrition and Health Survey 2006. BMC Public Health. 2009;9:215.
    1. Smith WA, Li C, Nottage KA, et al. Lifestyle and metabolic syndrome in adult survivors of childhood cancer: a report from the St. Jude Lifetime Cohort Study. Cancer. 2014;120(17):2742–2750.
    1. Gavrila D, Salmeron D, Egea-Caparros JM, et al. Prevalence of metabolic syndrome in Murcia Region, a southern European Mediterranean area with low cardiovascular risk and high obesity. BMC Public Health. 2011;11:562.
    1. Faienza MF, Delvecchio M, Giordano P, et al. Metabolic syndrome in childhood leukemia survivors: a meta-analysis. Endocrine. 2015;49(2):353–360.
    1. Annaloro C, Usardi P, Airaghi L, et al. Prevalence of metabolic syndrome in long-term survivors of hematopoietic stem cell transplantation. Bone Marrow Transplant. 2008;41(9):797–804.
    1. Paris C, Yates L, Lama P, Zepeda AJ, Gutierrez D, Palma J. Evaluation of metabolic syndrome after hematopoietic stem cell transplantation in children and adolescents. Pediatr Blood Cancer. 2012;59(2):306–310.
    1. Garmey EG, Liu Q, Sklar CA, et al. Longitudinal changes in obesity and body mass index among adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Clin Oncol. 2008;26(28):4639–4645.
    1. Oeffinger KC, Mertens AC, Sklar CA, et al. Obesity in adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Clin Oncol. 2003;21(7):1359–1365.
    1. Chow EJ, Pihoker C, Hunt K, Wilkinson K, Friedman DL. Obesity and hypertension among children after treatment for acute lymphoblastic leukemia. Cancer. 2007;110(10):2313–2320.
    1. Razzouk BI, Rose SR, Hongeng S, et al. Obesity in survivors of childhood acute lymphoblastic leukemia and lymphoma. J Clin Oncol. 2007;25(10):1183–1189.
    1. Link K, Moell C, Garwicz S, et al. Growth hormone deficiency predicts cardiovascular risk in young adults treated for acute lymphoblastic leukemia in childhood. J Clin Endocrinol Metab. 2004;89(10):5003–5012.
    1. DeBoer MD, Gurka MJ, Woo JG, Morrison JA. Severity of the metabolic syndrome as a predictor of type 2 diabetes between childhood and adulthood: the Princeton Lipid Research Cohort Study. Diabetologia. 2015;58(12):2745–2752.
    1. de Vathaire F, El-Fayech C, Ben Ayed FF, et al. Radiation dose to the pancreas and risk of diabetes mellitus in childhood cancer survivors: a retrospective cohort study. Lancet Oncol. 2012;13(10):1002–1010.
    1. Frisk P, Rossner SM, Norgren S, Arvidson J, Gustafsson J. Glucose metabolism and body composition in young adults treated with TBI during childhood. Bone Marrow Transplant. 2011;46(10):1303–1308.
    1. Wei C, Thyagiarajan MS, Hunt LP, Shield JP, Stevens MC, Crowne EC. Reduced insulin sensitivity in childhood survivors of haematopoietic stem cell transplantation is associated with lipodystropic and sarcopenic phenotypes. Pediatr Blood Cancer. 2015;62(11):1992–1999.
    1. Virtue S, Vidal-Puig A. Adipose tissue expandability, lipotoxicity and the Metabolic Syndrome–an allostatic perspective. Biochim Biophys Acta. 2010;1801(3):338–349.
    1. Poglio S, Galvani S, Bour S, et al. Adipose tissue sensitivity to radiation exposure. Am J Pathol. 2009;174(1):44–53.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever