Bolier Melissa, de Winter Demi T C, Fiocco Marta, van den Berg Sjoerd A A, Bresters Dorine, van Dulmen-den Broeder Eline, van der Heiden-van der Loo Margriet, Hoefer Imo, Janssens Geert O, Kremer Leontien C M, Loonen Jacqueline J, Louwerens Marloes, van der Pal Heleen J, Pluijm Saskia M F, Tissing Wim J E, van Santen Hanneke M, de Vries Andrica C H, van der Lely Aart-Jan, van den Heuvel-Eibrink Marry M, Neggers Sebastian J C M M
Dept. of Internal Medicine, section Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands.
Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
J Clin Endocrinol Metab. 2025 Feb 7. doi: 10.1210/clinem/dgaf078.
CONTEXT/OBJECTIVE: Diabetes mellitus (DM), a possible adverse effect of childhood cancer treatment, is strongly associated with cardiovascular disease and early mortality in adult childhood cancer survivors (CCS). Here, we assess the prevalence and determinants of DM in our nationwide CCS cohort.
DESIGN/METHODS: In this cross-sectional study, the prevalence of DM was assessed in 2,338 CCS, using the Lifelines cohort (n=132,226 adults with no history of cancer) as a reference. DM was defined through serum glucose measurement (fasting glucose ≥7.0mmol/L or non-fasting ≥11.1mmol/L) and/or self-report (previous diagnosis and/or medication use). Multivariable logistic regression models, adjusted for age, sex, and BMI, were used to assess the cohort effect on the presence of DM. Multivariable logistic regression analysis was used to identify determinants of DM in CCS.
Survivors (median age 34.7 years, median follow-up time 27.1 years) showed increased odds for hyperglycemia (aOR=2.72, 95%CI=2.06-3.59), previous DM diagnosis (aOR=3.03, 95%CI=2.33-3.95), and anti-diabetic medication use (aOR=2.94, 95%CI=2.17-3.99), compared to the reference cohort. Age (OR=4.32, 95%CI=1.84-10.15, >35 versus 18-35 years), BMI (OR=1.12, 95%CI=1.08-1.16, per point), family history of DM (OR=2.38, 95%CI=1.51-3.76), prior abdominal/pelvic radiotherapy (OR=4.19, 95%CI=2.32-7.55), total body irradiation (OR=14.31, 95%CI=6.98-29.34), hypogonadism (OR=2.40, 95%CI=1.15-4.99), hypertension (OR=1.71, 95%CI=1.06-2.76), and dyslipidemia (OR=3.81, 95%CI=2.15-6.75) were associated with DM in CCS. A significant interaction between age and sex on the development of DM in survivors was identified.
The identified three-fold increased risk of DM in CCS, along with the clinically relevant -and some modifiable- determinants, underscores the importance of early risk-based screening and the exploration of lifestyle interventions in this population.
背景/目的：糖尿病（DM）是儿童癌症治疗可能产生的不良后果，与成年期儿童癌症幸存者（CCS）的心血管疾病和早期死亡率密切相关。在此，我们评估了我国全国范围内CCS队列中DM的患病率及其决定因素。
设计/方法：在这项横断面研究中，我们以生命线队列（n = 132,226名无癌症病史的成年人）作为对照，评估了2338名CCS中DM的患病率。DM通过血清葡萄糖测量（空腹血糖≥7.0mmol/L或非空腹血糖≥11.1mmol/L）和/或自我报告（既往诊断和/或用药情况）来定义。使用调整了年龄、性别和BMI的多变量逻辑回归模型来评估队列对DM存在情况的影响。采用多变量逻辑回归分析来确定CCS中DM的决定因素。
与对照队列相比，幸存者（中位年龄34.7岁，中位随访时间27.1年）出现高血糖（调整后比值比[aOR]=2.72，95%置信区间[CI]=2.06 - 3.59）、既往DM诊断（aOR = 3.03，95%CI = 2.33 - 3.95）以及使用抗糖尿病药物（aOR = 2.94，95%CI = 2.17 - 3.99）的几率增加。年龄（OR = 4.32，95%CI = 1.84 - 10.15，>35岁与18 - 35岁相比）、BMI（OR = 1.12，95%CI = 1.08 - 1.16，每单位）、DM家族史（OR = 2.38，95%CI = 1.51 - 3.76）、既往腹部/盆腔放疗（OR = 4.19，95%CI = 2.32 - 7.55）、全身照射（OR = 14.31，95%CI = 6.98 - 29.34）、性腺功能减退（OR = 2.40，95%CI = 1.15 - 4.99）、高血压（OR = 1.71，95%CI = 1.06 - 2.76）和血脂异常（OR = 3.81，95%CI = 2.15 - 6.75）与CCS中的DM相关。在幸存者中，年龄和性别对DM发生存在显著交互作用。
在CCS中确定的DM风险增加三倍，以及临床相关的且部分可改变的决定因素，凸显了基于风险的早期筛查以及探索该人群生活方式干预措施的重要性。
