OBJECTIVE To assess 1) the association between metabolic dysfunction-associated steatotic liver disease (MASLD) in pediatric obesity and youth-onset type 2 diabetes, 2) the joint effect of MASLD and intermediate hyperglycemia on type 2 diabetes risk, and 3) the effect of obesity treatment on type 2 diabetes risk. RESEARCH DESIGN AND METHODS A cohort study using the Swedish Childhood Obesity Treatment Register (Barnobesitas Registret i Sverige [BORIS]) (1999–2020) linked with national registers was conducted. We included 10,346 children with overweight or obesity and 59,336 matched control individuals. MASLD was defined by transaminases and diagnosis code, separately. Type 2 diabetes was ascertained from national registers. RESULTS In the obesity cohort, median age at type 2 diabetes diagnosis was 16.9 (quartile 1 [Q1], quartile 3 [Q3]: 14.7, 21.4) years, median follow-up was 8.1 (Q1, Q3: 5.1, 11.7) years. Cumulative incidence of type 2 diabetes at age 30 was 22.7% (obesity and MASLD), 9.9% (obesity alone), and 0.7% (control individuals). MASLD was associated with risk for type 2 diabetes (hazard ratio [HR] 2.71 [95% CI 2.14–3.43]), independently of age, sex, degree of obesity, intermediate hyperglycemia, and parental type 2 diabetes. Joint effect of MASLD and intermediate hyperglycemia increased type 2 diabetes risk (HR 9.04 [6.38–12.79]). Optimal response in obesity treatment reduced the risk (HR 0.23 [0.09–0.57]). CONCLUSIONS MASLD, defined by transaminases or diagnosis code, in pediatric obesity is associated with increased risk for youth-onset type 2 diabetes. MASLD interacts synergistically with intermediate hyperglycemia to dramatically increase the risk. Optimal response in obesity treatment reduces type 2 diabetes risk, despite MASLD.

中文翻译：

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儿童肥胖中的脂肪性肝病和青年发病 2 型糖尿病的风险增加


目的 评估 1） 儿童肥胖代谢功能障碍相关脂肪性肝病 （MASLD） 与青年发病 2 型糖尿病之间的关联，2） MASLD 和中度高血糖对 2 型糖尿病风险的联合影响，以及 3） 肥胖治疗对 2 型糖尿病风险的影响。研究、设计和方法 使用瑞典儿童肥胖治疗登记册 （Barnobesitas Registret i Sverige [BORIS]） （1999-2020） 进行了一项与国家登记册相关联的队列研究。我们纳入了 10,346 名超重或肥胖儿童和 59,336 名匹配的对照组个体。MASLD 分别由转氨酶和诊断代码定义。2 型糖尿病是从国家登记册中确定的。结果 在肥胖队列中，2 型糖尿病诊断的中位年龄为 16.9 （四分位数 1 [Q1]，四分位数 3 [Q3]： 14.7， 21.4） 年，中位随访时间为 8.1 （Q1， Q3： 5.1， 11.7） 年。2 岁时 30 型糖尿病的累积发病率为 22.7%（肥胖和 MASLD）、9.9%（仅肥胖）和 0.7%（对照个体）。MASLD 与 2 型糖尿病风险相关 （风险比 [HR] 2.71 [95% CI 2.14–3.43]），与年龄、性别、肥胖程度、中等高血糖和父母 2 型糖尿病无关。MASLD 和中度高血糖的联合作用增加了 2 型糖尿病的风险 （HR 9.04 [6.38–12.79]）。肥胖治疗的最佳反应降低了风险 （HR 0.23 [0.09–0.57]）。结论 儿童肥胖中由转氨酶或诊断代码定义的 MASLD 与青年发病 2 型糖尿病的风险增加相关。MASLD 与中等高血糖协同作用，大大增加了风险。尽管存在 MASLD 但肥胖治疗的最佳反应可降低 2 型糖尿病风险。