Genetic profiling of lipids can predict diabetes
MedWire News: Lipidomic profiling may become a more reliable predictor of future diabetes than traditional factors such as glucose and insulin levels, report researchers from the European Human Genetics Conference in Amsterdam, The Netherlands.
"Currently one in 10 US adults suffers from diabetes and recently the Centers for Disease Control has predicted that this will increase to one in three by 2050," said Joanne Curran (Texas Biomedical Research Institute, San Antonio, USA), who presented the results.
"We are optimistic that our discovery will lead to new treatments, but in the short-term the importance of finding out at an early stage whether any individual is likely to develop it cannot be overstated."
Curran and colleagues profiled the lipidome of 1202 Mexican Americans from the San Antonio Heart Study. In total, they identified and quantified 356 different lipid species, the majority of which they found to be heritable.
At baseline, 861 out of the 1202 participants did not have diabetes, but 110 developed the condition during 10 years of follow-up. Of the 356 lipid species profiled, 128 were found to predict 10-year progression to diabetes in nondiabetic individuals.
The lipid species that most strongly predicted progression to diabetes over 10 years was the biosynthetic precursor to ceramide 18:0, dihydroceramide (dhCer) 18:0.
This lipid was found to be extremely heritable and present in significantly higher quantities in diabetics compared with nondiabetics. It was also found in higher quantities in patients without diabetes who went on to develop the condition, compared with those who did not.
The association between dhCer and diabetes was independent of fasting glucose and insulin levels, suggesting that dhCer may be an independent predictor of diabetes risk.
"A test based on dhCer levels will help to avoid the serious health effects that diabetes has in its own right, such as kidney failure, amputations, and blindness," suggested Curran. "It is, of course, also a risk for cardiovascular disease, so the health burden of this condition is enormous."
Following identification of dhCer as a diabetes risk factor, Curran and team carried out a genome-wide association analysis, which isolated two single nucleotide polymorphisms (SNPs) on chromosome 3 (3p22), located between the genes SNORA62 and MOBP. These SNPs showed a significant association with concentrations of dhCer 18:0.
"Through whole genome sequencing, we are now attempting to identify this causal gene in the hope that it will be informative in the understanding of the pathogenesis of diabetes, and also suggest new avenues for treatment," explained Curran.
MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011
By Helen Albert