Childhood adiposity and novel subtypes of adult-onset diabetes: a Mendelian randomisation and genome-wide genetic correlation study

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Abstract
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. Methods: 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). Results: 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. Graphical
Funding Information
  • Novo Nordisk Foundation (NNF19OC0057274)
  • Research Council for Health, Working Life and Welfare (2018-00337)
  • from the China Scholarship Council (student number 202006010041)
  • the Swedish Research Council (2018-03035)

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