medwireNews: Genetic liability to type 2 diabetes manifests in altered lipid profiles from as early as 8 years of age, say researchers.
Joshua Bell (University of Bristol, UK) told journalists at the 55th EASD Annual Meeting in Barcelona, Spain, that his team looked at metabolic changes in relation to genetic liability in order to identify those that are part of the early preclinical diabetes disease process.
They studied blood samples taken at ages 8, 16, 18, and 25 years from 6218 offspring in the Avon Longitudinal Study of Parents and Children cohort who had genetic data plus a blood sample for at least one timepoint. Only 0.4% of these people had developed type 2 diabetes by the age of 25 years.
Genetic liability was quantified using a genetic risk score based on 162 variants associated with type 2 diabetes risk in previous genome-wide association studies.
At the age of 8 years, there was just one significant association between genetic liability and metabolic profiles, with a higher genetic risk score being associated with a reduction in the cholesterol, triglyceride, and other lipid content of very large and large high-density lipoprotein (HDL).
These associations persisted at age 16 years, but other relationships also became evident, with higher genetic risk now associated with higher lipid content in very low-density lipoprotein (VLDL) and lower lipid content in LDL. It was also associated negatively with citrate levels and positively with levels of glucose and glycoprotein acetyls.
Associations with branched chain and aromatic amino acids came into play at age 18 years and with several fatty acid traits at age 25 years. By this oldest age, the associations between genetic liability and lipid content of LDL were as strong as those for lipid content of HDL particles.
Despite this progression with age, Bell emphasized that many people with high genetic liability never actually develop the condition. “We’re talking about subtle differences in metabolism in young people who are more genetically prone, or liable, to develop the disease later on in their life,” he noted.
Bell said the implications of the findings are for the preclinical phase of type 2 diabetes, including identifying “which features may be targetable much earlier than we already do to prevent progression to full-blown diabetes and all the complications that come with that.”
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EASD 2019; Barcelona, Spain: 16–20 September