Genetic evidence that high BMI in childhood has a protective effect on intermediate diabetes traits, including measures of insulin sensitivity and secretion, after accounting for BMI in adulthood.

ABSTRACT:

Aims/hypothesis

Determining how high BMI at different time points influences the risk of developing type 2 diabetes and affects insulin secretion and insulin sensitivity is critical.

Methods

By estimating childhood BMI in 441,761 individuals in the UK Biobank, we identified which genetic variants had larger effects on adulthood BMI than on childhood BMI, and vice versa. All genome-wide significant genetic variants were then used to separate the independent genetic effects of high childhood BMI from those of high adulthood BMI on the risk of type 2 diabetes and insulin-related phenotypes using Mendelian randomisation. We performed two-sample MR using external studies of type 2 diabetes, and oral and intravenous measures of insulin secretion and sensitivity.

Results

We

SUBMITTER: Hawkes G 

PROVIDER: S-EPMC10317883 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature