Clinical Biomarkers Derived from Metabolomics: The Making of an Insulin Resistance Test
Insulin resistance (IR) is a risk factor for type 2 diabetes (T2DM) and can be present for years prior to any changes in glycemic measures (e.g., fasting glucose, HbA1C). Determining individuals who are IR and at risk for developing type 2 diabetes will aid in the targeting of interventions to prevent T2DM. Further, a convenient and quantitative measure of IR may have utility in monitoring these interventions. Although many genome-wide association studies have derived associations to T2DM risk, they have generally fallen short in improving risk prediction.
Metabolomics is a new tool for determining associations and potential diagnostics. Metabolites function as a surrogate to the phenotype and are a product of gene activity. As such, metabolomics is proving to be a useful tool in epidemiological studies and biomarker discovery. Metabolomics was applied to a subset of the EGIR RISC cohort to reveal novel biomarkers of IR. These biomarkers were then validated and now reside within a novel IR test called Quantose IR™, which requires a single fasting blood draw.
In studying the comparison to other standards for predicting IR, the Quantose test outperformed all standard measures including HOMA IR, and the biomarkers were independent risk factors for the development of T2DM and IGT in the EGIR RISC and Botnia cohorts. The effectiveness of the Quantose IR test for gauging insulin resistance in an intervention study was further evaluated in the ACT NOW study.
The novel Quantose IR test can be used to monitor intervention in a prediabetic state and offers the ability to easily measure insulin sensitivity/resistance in baseline subjects or during intervention studies. Further, the development of this test via a systematic, discovery metabolomics approach demonstrates the power and utility of metabolomics. This approach allows for deriving novel and significant associations in large populations and for understanding the basis of risk and developing innovative diagnostics from these novel associations.
Who Should Attend:
- Discovery Biology
- Discovery Chemistry
- Preclinical Development
- Clinical Development
- Biomarker/Target Discovery
- Translational medicine
- Molecular biology/medicine
|Jeff Cobb, Ph.D. - Sr. Director of Diabetes Research, Metabolon, Inc.
Dr. Cobb has focused his career on the early stages of drug discovery including target identification and validation, lead generation and optimization. Dr. Cobb is a trained synthetic organic chemist who received his Ph.D. degree from the University of South Carolina and followed with completion of a postdoctoral assignment at Oxford University. His medicinal chemistry experience is extensive, having worked for 13 years in drug discovery at Sandoz, Glaxo, and GlaxoWellcome. For the next 8 years, Dr. Cobb worked as Director, New Drugs for Metabolic Diseases at GlaxoSmithKline where he was responsible for the early nurture of discovery projects ultimately producing clinical candidates. Dr. Cobb is the co-inventor of Farglitizar® (diabetes). Following four years serving as a drug discovery consultant, Dr. Cobb assumed his current role of Sr. Director of Diabetes Research at Metabolon, Inc. working on the discovery and validation of new diagnostic tests for metabolic disease.
Duration: 32 minutes