BARCELONA – Disturbed HDL cholesterol metabolism is one of the earliest features that may predispose individuals to the development of type 2 diabetes, according to data from a genetics and metabolomics study conducted in the United Kingdom.
Changes in HDL cholesterol metabolism were seen in children as young as 8 years, decades before the clinical onset of disease,, a research fellow at the University of Bristol (England), reported at the annual meeting of the European Association for the Study of Diabetes.
“We know that type 2 diabetes certainly doesn’t develop overnight,” Dr. Bell said. Indeed, data exist showing that there are changes in glucose metabolism several years before a formal diagnosis may be made in adults. “What we don’t know is what the very earliest features of diabetes look like,” he added.
“The main assumption is that type 2 diabetes is a metabolic disease, and so disease features are visible in systemic metabolism,” explained Dr. Bell. What was not clear, however, was that if any metabolic features – seen mainly in observational studies and in adults – were caused by the disease itself or perhaps were independent causes of type 2 diabetes.To investigate, Dr. Bell and associates performed a study linking genetic liability with metabolomic data collected at four time points from 4,761 offspring from participants in the Avon Longitudinal Study of Parents and Children cohort, which is also known as the Children of the 90s cohort. More than 200 metabolic traits were considered, and a genetic risk score comprising more than 162 single nucleotide polymorphisms previously linked to adult type 2 diabetes was used.
The metabolomic traits considered included lipoprotein subclass-specific cholesterol and triglyceride content, amino and fatty acids, and inflammatory glycoprotein acetyls, which had been measured in childhood at the age of 8 years, in adolescence at 16 years, in young adulthood at 18 years, and in adulthood at 25 years.
Early metabolic features of type 2 diabetes liability were grouped together and one feature that stood out was the sizes of lipid particles. In particular, it was the size of HDL cholesterol particle subtypes in children at the age of 8 years. Before other types of changes in lipid particles were being seen, there were reductions in the lipid content of HDL cholesterol particle subtypes, notably those that were very large.
By age 16 years, strong associations remained with lower lipids in HDL cholesterol particle subtypes and type 2 diabetes liability, which became stronger with preglycemic traits, such as citrate, and with glycoprotein acetyls. By age 18 years, elevations were seen in branched amino acids, and by age 25, association had strengthened for the lipid content of very low–density lipoprotein cholesterol.
“Linking genetic liability to adult disease with traits measured much earlier in life can tell you something about how the disease activity unfolds over a lifetime,” Dr. Bell said, adding that the feature that was “most consistently tracked” could be evaluated and could help reveal whether or not an individual might go on to develop type 2 diabetes.
In a press release issued by the EASD, Dr. Bell observed: “It’s remarkable that we can see signs of adult diabetes in the blood from such a young age. Knowing what early features of type 2 diabetes look like, could help us to intervene much earlier to halt progression to full-blown diabetes and its complications.”
The study was funded by Diabetes U.K., Cancer Research U.K., the Elizabeth Blackwell Institute for Health Research, the Wellcome Trust, the Medical Research Council, and the University of Bristol. Dr. Bell said he had no conflicts of interest to declare.
SOURCE: Bell J et al. bioRxiv. 2019 Sep 17. .