DDI

IMMUNOLOGY & MICROBIOLOGY DEPARTMENT

In this issue of the newsletter, we will be highlighting the research being carried out by
Immunology & Microbiology Department at DDI, led by Dr. Rasheed Ahmad.

RESEARCH UPDATE

Find out what is new within the Research Sector at DDI

Novel Non-invasive Method To Detect Vascular Complications In Patients With Type 2 Diabetes

Complications of diabetes can be an emotional topic for those with diabetes. The high sugar level in the blood can damage tissues throughout the body, such as nerves, eyes, or kidneys. These side effects are also known as “vascular complications”. If left untreated, vascular complications may lead to death in patients with T2D. Typically, these patients must go through a series of clinical tests, including blood screens, ultrasounds and eye tests, which would indicate the risk of developing vascular complications.

Obtaining a non-invasive simple mean of detecting vascular complications during the disease progression has been a long-sought goal for scientists in the field. To resolve this issue, a research group from Zhongnan Hospital of Wuhan University in China, developed a novel blood test that can predict the likelihood for a diabetic patient to develop these complications. Their idea utilized the science of “Epigenetics”. The group argued that in diseases, such as cancer, injured cells spill free DNA into the blood stream. They studied this effect in the blood of diabetic patient with vascular complications. Using the distinct epigenetic modifications known as hydroxymethylation of freely circulating DNA, the group developed a tool in which they can measure the presence of 5-hydroxymethylcytosines (5hmC) free circulating DNA. 5hmC is an epigenetic marker that is expressed on the most active parts of the DNA.

To test their hypothesis, they recruited 62 patients with T2D at Wuhan University in China. Twelve of them did not have any vascular complications (control group), while the remainder experienced a range of symptoms—including atherosclerotic plaques, heart disease, stroke, or damage to nerves, eyes, or kidneys. The team collected blood from each participant and extracted circulating cell-free DNA. The 5hmC bound to cell-free DNA was isolated via magnetic bead, then sequenced with Next Generation Sequencing.

The group then compared the degree of hydroxymethylation between the control group and those with vascular complications. There results came back revealing 135 genes with significantly different patterns of hydroxymethylation between the two groups. Those genes were often implicated in insulin resistance or inflammation. The group further investigated those changes and identified 16 genes with the most distinct differences between the two groups. They concluded that they could use the hydroxymethylation patterns of these 16 genes to distinguish patients with vascular complications from those without at an accuracy of 85% or higher. The group published their findings in journal of Clinical Chemistry3, with the hope of further developing this technique (Figure 3).

Figure 3: DNA sequencing identified 5hmC labeled free circulating DNA in patients with T2D. (A) Heatmaps and (B), the weighted scores of the training and testing groups showed the performance of the 16 marker genes for distinguishing Control group from those with vascular complications.

However, as exciting as their finding sound, the technology needs further development. It lacks the ability to identify the various forms of vascular complications. This means those patients found to be positive must continue with additional medical test to distinguish the specifics of their disease. Nevertheless, their work advances the idea of measuring epigenetic changes such as hydroxymethylation in cell-free DNA in different conditions.

REFERENCES

Lee, Y. S., Wollam, J. and Olefsky, J. M., An Integrated View of Immunometabolism. Cell 2018. 172: 22-40.

Epigenetic landscape priming by high fat dietary nutrients and adipokines plays a major role in metabolic inflammation and diabetes

Yang, Y., Zeng, C., Lu, X., Song, Y., Nie, J., Ran, R., Zhang, Z., He, C., Zhang, W. and Liu, S. M., 5-Hydroxymethylcytosines in Circulating Cell-Free DNA Reveal Vascular Complications of Type 2 Diabetes. Clin Chem 2019. 65: 1414-1425.