Temporal changes and genetic susceptibility to type 2 diabetes (1984-2019; HUNT): a longitudinal, population-based study

Abstract

Background: The global prevalence of type 2 diabetes has nearly doubled between 1990 and 2020. Genetic susceptibility confers increased risk of type 2 diabetes, but environmental exposures could modify this risk. We aimed to investigate how societal changes have affected the prevalence of type 2 diabetes in people with high and low genetic susceptibility, using chronological time as an indicator for these changes.

Methods: This longitudinal, population-based study included observations from four surveys from the HUNT study between 1984 and 2019, for participants aged 20-79 years. Diabetes was indicated by self-report and by non-fasting glucose or HbA_1c in secondary analyses. We used a polygenic score for type 2 diabetes including more than 1 100 000 genetic variants to approximate genetic susceptibility. We used generalised estimating equations to estimate diabetes prevalence for the top and bottom deciles of the polygenic score at each timepoint, allowing for three-way interaction between time, polygenic score category, and 20-year age group. To explore underlying mechanisms, we did similar analyses for incidence by polygenic score category and 10-year mortality by diabetes status.

Findings: The study included 198 312 observations from 86 194 individuals. 45 654 (53·0%) of 86 194 participants were female and 40 540 (47·0%) were male. From the mid-1980s to the late 2010s, diabetes prevalence increased by 0·4 percentage points (pp; 95% CI 0·1-0·7) among the bottom decile of the polygenic score, 3·0 pp (2·7-3·2) among the mid-80%, and 9·1 pp (8·0-10·1) among the top decile. The difference in diabetes prevalence between the top and bottom deciles of genetic susceptibility increased over time for all age groups. Findings were similar when laboratory measurements were added to define hyperglycaemia. Additional analyses suggested an increasing diabetes incidence in participants aged 20-39 years in the top decile of genetic susceptibility, and improved diabetes survival from 1996-2006 to 2007-17.

Interpretation: Our findings suggest an increasing gap in diabetes prevalence between the most and least genetically susceptible. This suggests that people with a high genetic susceptibility to type 2 diabetes could be especially affected by a diabetogenic environment and highlights the need for public health measures.

Funding: The study was funded by The Liaison Committee for education, research and innovation in Central Norway.