Blood Test Could Revolutionize Detection of Diabetic Vascular Complications

Diabetic vascular complications could soon be detected earlier and more accurately thanks to a novel test developed by a team of international researchers at Northwestern Medicine, University of Chicago, and Wuhan University in China. Using highly sensitive biomarkers and just a few drops of blood, the test can analyze a diabetic patient’s DNA and make doctors aware of problems such as heart disease and atherosclerosis. The discovery could revolutionize how diabetic patients are monitored and help reduce the incidence of diabetes-associated deaths. The findings are published in the journal Clinical Chemistry.

With an estimated global prevalence of over 422 million, diabetes is a chronic disease that results in the inefficient regulation of blood sugar. Uncontrolled, the condition can cause hyperglycaemia, which over time can cause vascular damage across many parts of the body, including the heart, blood vessels, eyes, kidneys and nerves. Diabetic adults have a two- to three-fold increased risk of heart attacks and strokes, and the disease contributes to a large proportion of kidney failure cases.

Earlier, more accurate detection

“To date, there lacks an effective approach to detect these complications early in these patients. We reasoned [that] using this non-invasive blood based technology … that can be integrated into the routine care of diabetic patients, physicians would be equipped with a promising tool for early detection of patients who are developing potentially life-threatening vascular complications, thus allowing more time for intervention approaches to improve clinical outcomes,” Dr Wei Zhang, Associate Professor of Cancer Epidemiology and Prevention at Northwestern University Feinberg School of Medicine told us.

The test builds on a technology invented by Dr Chuan He at the University of Chicago in 2011, the “5hmC-Seal”, which can measure 5hmC (5-hydroxymethylcytosine, a novel type of DNA epigenetic mark) in the human genome. Using just five milliters of blood, the new non-invasive test overcomes some of the limitations of traditional methods of diagnosing vascular complications, detecting the complications earlier and much more accurately.

“This test starts from collecting [a] patient's blood,” Zhang explained. “We just need a few mL of whole blood (i.e., <5 mL of plasma) to extract the so-called circulating cell-free DNA (cfDNA). Then the nano-5hmC-Seal will be used to profile genome-wide 5hmC levels in cfDNA through two steps. Step 1: a chemical labeling step to label 5hmC in cfDNA, followed by a pull-down procedure to obtain the 5hmC-containing cfDNA fragments, Step 2: PCR amplification to prepare sequencing libraries and the next-generation sequencing. After sequencing, we use our established bioinformatic pipeline to summarize the 5hmC levels in cfDNA in terms of genes or other genomic features (e.g., promoters, cis-regulatory elements etc).”

The level and magnitude of changes seen in 5hmC profiles between diabetic patients who developed vascular complications and those who did not, was not clear before the study. “Therefore, it is both surprising and exciting to see that this novel technology can sensitively detect the subtle 5hmC changes associated with diabetic complications,” Zhang told us.

He goes on to say: “We expect that this test can be part of a routine monitoring plan for the care of diabetic patients. Patients who are detected with high probability of developing vascular complications could be put into more close clinical surveillance, and intervention (e.g., preventive treatment, lifestyle change). Our team is working on a larger scale validation study and moving towards a clinical trial in the near future.”

Testing for a suite of cancers

The potential of the blood-testing technology to be used in the diagnosis of diseases other than diabetes has already been demonstrated. He and Zhang, collaborating with leading liver cancer experts in China, Dr. Jia Fan and Dr. Hongyang Wang, have been working together to bring the nano-5hmC-Seal technology into blood tests for several human cancers, including liver cancer, the results of which were published in Gut in July this year. Here, the researchers used it to detect liver cancer in over 3,000 people’s blood samples, and importantly, the test was able to detect about 88% of tumors. Liver cancer often has a poor prognosis and is usually detected at a late stage, so a test enabling earlier detection could lead to great improvements in survival rates.