Protein Biomarkers Identified for Dysglycemia Cardiovascular Risk

Impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes independently increase the risk of cardiovascular (CV) outcomes, and diabetes reduces life expectancy by up to 15 years.

Despite recent reductions in the incidence of CV outcomes in people with diabetes, both diabetes and lesser degrees of dysglycemia remain independent CV risk factor. The pathophysiologic reasons for this excess and for variations in incidence among people who already have established dysglycemia remain unclear.


A team of scientists working with a group at the Hamilton General Hospital (Hamilton, ON, Canada) recruited from a trial 12,537 people with either diabetes, impaired glucose tolerance or impaired fasting glucose and additional CV risk factors and followed for a median of 6.2 years. A subset of 8,494 (68%) also provided written consent for the collection and storage of a blood sample for future measurement of CV risk factors. Baseline fasting samples were collected, spun, separated ̧ and divided into 1.5-2.0 mL aliquots.

The team used a customized Human Discovery Multi-Analyte Profile 250+ panel on the LUMINEX 100/200platforms (Luminex; Austin, TX, USA). The DiscoveryMAP platform (Myriad RBM Inc.; Austin, TX, USA) measured a panel of 284 biomarkers in a serum sample from each participant. The panel included a combination of assays that had already been developed plus additional biomarker assays that were newly developed for the study.

The DiscoveryMAP platform successfully identified combinations of 15 protein biomarkers associated with cardiovascular (CV) events or death in people with pre-diabetes or early type 2 diabetes. After forcing in the clinical risk factors, 8 out of a possible 237 biomarkers each independently improved the ability to predict the CV composite outcome. Three of these eight biomarkers plus an additional four, a total of seven, were identified when the process was repeated for the expanded CV composite outcome. Three biomarkers, N-terminal of the prohormone brain natriuretic peptide (NT-proBNP), angiopoietin 2 and gluthathione S transferase alpha, were persistently identified in all models and for all outcomes.

Hertzel Gerstein, MD, the lead study investigator, said, “Our study is one of the largest scientific investigations in history to identify specific cardiovascular biomarkers associated with serious cardiovascular outcomes, including heart attacks, strokes and death. Our results highlight the potential value of cardiovascular biomarkers for identifying people with dysglycemia at the highest risk of future events.” The study was published on October 30, 2015, in the journal Circulation.

Related Links:
Hamilton General Hospital 
Luminex
Myriad RBM Inc.