According to the 2014 National Diabetes Statistics Report published by the US Center for Disease Control and Prevention1, an estimated 29.1 million Americans, or 9.3% of the US population have diabetes. This number will continue increasing in the next few decades. Once simplistically viewed as a disease of impaired glucose metabolism, diabetes is now recognized as a complex interaction of genetics, hormonal defects, metabolism and the environment. This complexity is reflected in multiple diabetic comorbidities such as hyperglycemia, high blood pressure, high blood LDL cholesterol, heart disease, stroke, blindness, and kidney disease.

The exact biochemical pathways involved in diabetes have yet to be fully defined. As a result, diabetes is usually diagnosed after profound metabolic changes are underway and tissue and organ damage have already occurred. As a result, researchers are looking for biomarkers signaling the earliest signs of disease progression, which may also offer insight into pathophysiology and potential interventions.

Abu Baker and his co-authors2 explore how researchers are using metabolomics to characterize diabetes biomarkers by reviewing journals and books from Web of science, Pubmed, and related databases. They summarized examples of where metabolomics approaches have been used to identify potential biomarkers and associated mechanisms behind obesity and type 2 diabetes. Their review focuses on publications featuring mass spectroscopy and nuclear magnetic resonance. These are the technologies most often used in these types of studies.

Overall, a total of 336 references were cited in this extensive review. Abu Baker et al2 describe several potential obesity and diabetes biomarker classes that were identified using metabolomics approaches. These include fatty acids, TCA cycle intermediates, carbohydrates, amino acids, choline and bile acids. The article provides the reader with an appreciation of the complex molecular interactions and the interrelated network of pathways involved in obesity and type 2 diabetes and how these pathways are altered during disease progression. Intriguingly, some of these metabolic pathways are shared between diabetes and other diseases such as cancer, liver diseases, atherosclerosis and neurological disorders. This article also touches on intriguing (and unproven) theories in diabetes pathophysiology including mitochondrial dysfunction, intestinal microflora metabolism and altered bile acid pool size and composition.

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Abu Baker et al2 recommend combining metabolomics with other approaches such as genomics, transcriptomics and proteomics to delineate disease processes. The authors conclude that scientists might use metabolomics successfully to discover novel biomarkers and to help comprehend disease progression in obesity and type 2 diabetes. They suggest that diagnosing a disease this complex will require an entire panel of biomarkers.

This review gives us a view of the heterogeneity and complexity of obesity and type 2 diabetes — not dissimilar from the diversity found in cancer subtyping. It is possible that in future we will view diabetes type 2 not as a monolithic disorder but one with many causal pathways. Based on a more precise diagnosis, treatment could then be tailored to meet each patient’s needs.

 

1Centers for Disease Control and Prevention. (2014) “National Diabetes Statistics Report: Estimates of Diabetes and Its Burden in the United States, 2014.” Atlanta, GA: U.S. Department of Health and Human Services. Available at: http://www.cdc.gov/diabetes/pubs/statsreport14/national-diabetes-report-web.pdf

2Abu Bakar MH, (2015) “Metabolomics – the complementary field in systems biology: a review on obesity and type 2 diabetes” Molecular BioSystems, 11 (17) (pp. 1742-1774).