With a revolutionary new approach that analyzed just a few drops of blood, scientists from Northwestern Medicine, the University of Chicago and Wuhan University in China detected earlier and more accurately if diabetic patients had developed life-threatening vascular complications such as heart disease, atherosclerosis and kidney failure.
It is the latest discovery in a new blood-testing technology that Northwestern scientists used most recently to detect liver cancer in patients and is now being tested in other major cancers.
“We’re very excited to apply our earlier findings in cancer patients to diabetic patients,” said co-corresponding author Wei Zhang, associate professor of cancer epidemiology and prevention at Northwestern University Feinberg School of Medicine. “This discovery is going to revolutionize how quickly and non-invasively we can identify potentially fatal complications in the hundreds of millions of diabetic patients worldwide.”
2/3About two-thirds of the 424 million diabetic patients worldwide die from vascular complications.
The prototype of this novel technology was developed by Dr. Chuan He, the John T. Wilson Distinguished Service Professor at the University of Chicago. Zhang and He worked together to create the blood test.
About two-thirds of the 424 million diabetic patients worldwide die from vascular (i.e. blood vessel) complications. Detecting these complications early could spur treatments to control the development of severe disease or death.
Current methods of diagnosing vascular complications in diabetic patients – analyzing a patient’s body mass index (BMI), the length of time they’ve had diabetes or a blood test analyzing how much waste product is present – are prone to error and don’t identify complications early enough to intervene with treatment.
This blood test is different.
How it works
With just three to five milliliters of blood, the non-invasive, clinically convenient test analyzes a patient’s DNA by using highly sensitive blood biomarkers.
If the diabetic patient has developed a vascular complication, the damaged blood vessels release new DNA into the bloodstream, which appears in the blood test and signals the problem to doctors.
The findings were published Oct. 1 in Clinical Chemistry, the leading international journal of clinical laboratory science.
5-Hydroxymethylcytosines in Circulating Cell-Free DNA Reveal Vascular Complications of Type 2 Diabetes
The study examined 62 diabetic patients (12 patients without vascular complications, 34 patients with a singular vascular complication and 16 with multiple vascular complications). This highly sensitive blood test was able to identify if a patient had vascular complications much more accurately than current diagnostic methods.
Abstract
Background: Long-term complications of type 2 diabetes (T2D), such as macrovascular and microvascular events, are the major causes for T2D-related disability and mortality. A clinically convenient, noninvasive approach for monitoring the development of these complications would improve the overall life quality of patients with T2D and help reduce healthcare burden through preventive interventions.
Methods: A selective chemical labeling strategy for 5-hydroxymethylcytosines (5hmC-Seal) was used to profile genome-wide 5hmCs, an emerging class of epigenetic markers implicated in complex diseases including diabetes, in circulating cell-free DNA (cfDNA) from a collection of Chinese patients (n = 62). Differentially modified 5hmC markers between patients with T2D with and without macrovascular/microvascular complications were analyzed under a case–control design.
Results: Statistically significant changes in 5hmC markers were associated with T2D-related macrovascular/microvascular complications, involving genes and pathways relevant to vascular biology and diabetes, including insulin resistance and inflammation. A 16-gene 5hmC marker panel accurately distinguished patients with vascular complications from those without [testing set: area under the curve (AUC) = 0.85; 95% CI, 0.73–0.96], outperforming conventional clinical variables such as urinary albumin. In addition, a separate 13-gene 5hmC marker panel could distinguish patients with single complications from those with multiple complications (testing set: AUC = 0.84; 95% CI, 0.68–0.99), showing superiority over conventional clinical variables.
Conclusions: The 5hmC markers in cfDNA reflected the epigenetic changes in patients with T2D who developed macrovascular/microvascular complications. The 5hmC-Seal assay has the potential to be a clinically convenient, noninvasive approach that can be applied in the clinic to monitor the presence and severity of diabetic vascular complications.
- Received for publication April 8, 2019.
- Accepted for publication August 6, 2019.
- © 2019 American Association for Clinical Chemistry
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