HU research maps warnings for Type 2 diabetes

Hebrew University researchers have found the first proof of molecular risk factors for Type 2 diabetes that indicate susceptibility to the disease.

This could provide an “early warning” sign and eventually lead to new treatment approaches, the researchers said, as well as mapping susceptibility at an early stage to other diseases as well.

Type 2 diabetes, which has been diagnosed in 500,000 Israelis, and not yet diagnosed in an equal number at a preliminary stage called pre-diabetes – generally results from being overweight and a lack of exercise.

A research team led by Dr. Asaf Hellman of HU’s Israel Canada Institute of Medical Research has developed a novel technique for analyzing the disease – contributing epigenetic variations in patients. Epigenetic variations – which are small molecular marks superimposed on the DNA structure – have been frequently thought to modify predisposition, but direct evidence was lacking.

The research team decided to map variation in DNA methylation – a naturally occurring mechanism for regulating genes and protect DNA – instead conventionally mapping variation in DNA sequence. The team conducted a proof-of-concept study among 1,169 type 2 diabetes patients and a healthy control group. The results showed the unique abilities of this approach by revealing a clear-cut, disease-predisposing DNA methylation “signature.” This is a first report in the scientific literature of epigenetic risk factor for this kind of diabetes.

DNA methylation is one of the regulatory processes spoken of as epigenetic, in which an alteration in gene expression occurs without a change in the sequence of nucleotides (molecules that make up DNA). Defects in this process cause several types of diseases that afflict humans.

The research was presented in a scientific conference at the Cambridge University Genomic Center and recently published in the scientific journal Human Molecular Genetics. Hellman’s technique was developed during his postdoctoral training at Harvard University Medical School. Later, his research students in Jerusalem, Gidon Tperoff and Dvir Aran, further developed it into an efficient, genome-wide mapping method.

This analysis revealed, for the first time not only a clear-cut epigenetic signature in diabetes, but telltale methylation signature marks on the DNA of young people who later developed impaired glucose metabolism, even before signs of clinical diabetes showed up.

The HU findings seem likely to lead to the understanding of similar mechanisms in a long list of common human diseases, including many metabolic, autoimmune and psychiatric disorders.

As epigenetic marks are sensitive to a wide range of environmental influences including diets, chemical exposures and intrauterine environments, as well as to therapeutic drugs, these findings may open the way for the development of new prevention and/or intervention epigenetic therapies, the researchers said.