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

Diabetologia. 2023 Jun;66(6):1052-1056. doi: 10.1007/s00125-023-05883-x. Epub 2023 Feb 27.

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.

Keywords: Epidemiology; Obesity; Prediction, Prevention, Type 2 diabetes; Weight regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / genetics
  • Adult
  • Child
  • Correlation of Data
  • Diabetes Mellitus, Type 2* / genetics
  • Genome-Wide Association Study
  • Humans
  • Insulin / genetics
  • Insulin Resistance* / genetics
  • Pediatric Obesity*

Substances

  • Insulin