Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Diabetologia. 2023 Jun;66(6):1052-1056. doi: 10.1007/s00125-023-05883-x. Epub 2023 Feb 27.
AIMS/HYPOTHESIS: We investigated whether the impacts of childhood adiposity on adult-onset diabetes differ across proposed diabetes subtypes using a Mendelian randomisation (MR) design.
We performed MR analysis using data from European genome-wide association studies of childhood adiposity, latent autoimmune diabetes in adults (LADA, proxy for severe autoimmune diabetes), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD) and mild age-related diabetes (MARD).
Higher levels of childhood adiposity had positive genetically predicted effects on LADA (OR 1.62, 95% CI 1.05, 2.52), SIDD (OR 2.11, 95% CI 1.18, 3.80), SIRD (OR 2.76, 95% CI 1.60, 4.75) and MOD (OR 7.30, 95% CI 4.17, 12.78), but not MARD (OR 1.06, 95% CI 0.70, 1.60).
CONCLUSIONS/INTERPRETATION: Childhood adiposity is a risk factor not only for adult-onset diabetes primarily characterised by obesity or insulin resistance, but also for subtypes primarily characterised by insulin deficiency or autoimmunity. These findings emphasise the importance of preventing childhood obesity.
目的/假设：我们使用孟德尔随机化（MR）设计，研究了儿童肥胖对成年发病糖尿病的影响是否因所提出的糖尿病亚型而不同。
我们使用来自欧洲儿童肥胖症全基因组关联研究、成人隐匿性自身免疫性糖尿病（LADA，严重自身免疫性糖尿病的代表）、严重胰岛素缺乏性糖尿病（SIDD）、严重胰岛素抵抗性糖尿病（SIRD）、轻度肥胖相关糖尿病（MOD）和轻度年龄相关性糖尿病（MARD）的遗传数据进行了 MR 分析。
较高水平的儿童肥胖症与 LADA（OR 1.62，95%CI 1.05，2.52）、SIDD（OR 2.11，95%CI 1.18，3.80）、SIRD（OR 2.76，95%CI 1.60，4.75）和 MOD（OR 7.30，95%CI 4.17，12.78）呈正相关，但与 MARD（OR 1.06，95%CI 0.70，1.60）无关。
结论/解释：儿童肥胖不仅是成年发病糖尿病的危险因素，主要特征为肥胖或胰岛素抵抗，也是以胰岛素缺乏或自身免疫为主要特征的亚型的危险因素。这些发现强调了预防儿童肥胖的重要性。
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