Metabolomics Brings New Insights to Type 2 Diabetes Research

Diabetes, a serious metabolic condition that results from higher than normal blood sugar levels, is a nationwide epidemic. According to the Diabetes Research Institute Foundation, more than 30 million Americans and 422 million people worldwide have been diagnosed with diabetes.

Type 2 diabetes (T2D) is the most common form of diabetes representing about 90% of diabetic cases, according to the Diabetes Research Institute Foundation. While adults are especially at risk for T2D, the disease can also affect children and young adults. T2D causes an impaired response to insulin; blood sugar levels are not adequately controlled, resulting in too much glucose in circulation and not enough glucose in tissues. Measuring changes in metabolites – small molecules present in the blood – using metabolomics could provide clues into how the disease develops and, subsequently, new treatments. Metabolomics enables simultaneous assessment of hundreds of compounds present in living systems, making it a critical tool that advances our understanding of disease mechanism and opens doors to identify novel targets and treatments.

Metabolon scientists are hard at work searching for new insights to aid in understanding mechanisms contributing to the development of T2D. Most recently, our technology contributed to the identification of a key gut microbiome-derived compound linked to insulin resistance. The study by Koh et al., identified an important connection between microbially produced compound and insulin resistance that helps us better understand how the gut microbiome affects their host’s physiology.

The human body is home to trillions of microorganisms known as the microbiome that live on our skin, in our mouth, nose and gastrointestinal tract. These microorganisms are vital to human health as they produce vitamins, contribute to food digestion and prevent pathogen colonization. Numerous studies have reported that diseases such as obesity and diabetes are associated with altered gut microbiota community structure. To identify factors that may be linked to abnormal activity of gut bacteria and trigger changes contributing to these metabolic diseases, in the Koh et al., study metabolomics was performed on plasma from subjects with T2D. Metabolomic profiling of these samples revealed that the microbiome-derived metabolite, imidazole propionate (ImP), was elevated in patients with T2D. Additionally, ImP-exposed mice showed impaired glucose tolerance. Researchers were able to mechanistically identify that ImP inhibited insulin signaling at the levels of insulin receptor substrate, which occurred through activation of mTORC1pathway. The damaged insulin signaling contributed to insulin resistance.

This work identifies an important connection between microbial activity in the gut, metabolite signaling and effects on host physiology. Metabolomics has provided another puzzle piece that will help researchers better understand how diabetes develops and how it can be treated. Improved understanding of gut microbiota metabolism linked to generation of ImP may also reveal new targets and lead to new treatments aimed to improve insulin signaling.

This study is just one example of how metabolomic profiling supports evolving perspectives by providing biological insights that drive scientific advancement. Metabolomics reveals biological insights otherwise unseen. By providing a better understanding of biology, we can unravel the mystery of human health and disease, and with a global capacity to conduct research and compare data, Metabolon can make connections where others can’t.

Disease processes are complex and we need new understandings to drive discoveries. These groundbreaking innovations can only occur through a deep understanding of the manifestation of living system – something only Metabolon can provide.

To learn more about how partnering with Metabolon can help you uncover actionable insights contact us at hello@metabolon.com.