Endocrinology Advisor: What are the current and future treatment implications for clinicians?
Dr Mullur: The authors discuss at length the use of “-omics” technologies applied to the field of diabetes, as the field has been rapidly advancing since the turn of the century.2 Genomics studies in T2D have identified many new genetic loci that can characterize an individual’s risk for diabetes.
Many of these genome-wide associated studies (GWAS) have not yet led to large clinical advances in the prevention and management of T2D, and the authors rightly point out that the current evidence does not support the use of genomics to make personalized dietary recommendations. This is likely because of the heterogeneity of T2D. In addition, we cannot ignore the potential mitigating changes in the DNA methylation and epigenetics that occur with healthy lifestyle interventions.
The authors then discuss a more promising aspect of precision nutrition2: the use of metabolomics to identify nutrient metabolites before, during, and after dietary interventions. This not only gives us a more precise understanding of dietary intake but also can provide a reliable marker of dietary change.
Measurement of these metabolites in urine and plasma can identify the presence of fruits, vegetables, fish, and meats in an individual’s diet. When this is then coupled with a traditional dietary assessment, it provides much more useful information about dietary adherence and areas for potential intervention.
Even in long-term studies of diabetes prevention, such as the PREDIMED trial, the authors discuss the application of metabolomics to the Mediterranean diet, showing that diets rich in extra-virgin olive oil resulted in a decrease in branched chain amino acid concentrations, which also predicted a lower incidence of T2D.6
Although many of the studies of dietary intervention and metabolomics occur over many months to years, changes in the gut flora can occur within days to weeks of a change in intake. The authors discuss the significant effect that even modest dietary changes can have on the microbiome. They cite a small trial that consisted of only a 3-day intervention, in which participants in the intervention group ate a barley kernel-based bread.7
This simple dietary change not only modified the ratio of different bacteria species but also showed improvements in glucose metabolism. Although it is unclear what significance this type of intervention would have long-term, integrating metabolomics and evaluation of the gut microbiome may provide the much-needed link to explain the role of these microbes in modifying individual responses to dietary changes and disease risk. An important caveat of the microbiome studies in patients with prediabetes or diabetes is the use of metformin, which can confound the classic microbial signatures that are measured in these studies.
Finally, the authors review a study by Zeevi and colleagues, who developed a machine learning algorithm that predicted postprandial glycemic responses based on integrated data from several sources.8 Using information from dietary intake assessments, biomarkers, physical activity, sleep, anthropometric variables, continuous glucose monitoring, gut microbiota, and 16S rRNA metagenomics profiling, the investigators were able to successfully design a personalized dietary intervention protocol that was more effective in reducing postprandial blood glucose than traditional dietary advice.
This successful pilot study is essentially the goal of precision nutrition applied to the care and management of T2D. However, this incredibly promising proof-of-concept trial is limited because of the huge amounts of data that need to be collected before the application of this predictive modeling, and the large amount of glycemic variability observed in the participants, which may have affected the results. Ultimately, this type of integrated approach is the goal of truly personalized dietary counseling, and this successful pilot study underscores the role of precision nutrition in T2D.
Ms Sartor: As consumers continue to be influenced by direct-to-consumer marketing and digital technology, it challenges healthcare professionals and federal agencies to protect consumers from false advertising, faulty testing practices, and unsubstantiated claims. Many consumers curate accurate and evidence-based nutritional advice from an MD, DO, NP, PA, RD, or RN, but many will fall prey to false claims and erroneous or even dangerous advice from unqualified individuals.
Clinicians, likewise, are challenged to embrace the paradigm shift from traditional allopathic treatment to that of disease prevention and complementary lifestyle modalities. By use of these cutting-edge technologies, clinicians help foster patient trust and compliance. Clinicians trained in precision medicine and nutrition will provide safe and effective testing and treatment options to those seeking their clinical use and efficacy. A greater challenge remains making this technology accessible to all persons at high risk for T2D, regardless of income, education, and socioeconomic status.
Endocrinology Advisor: What should be next steps in this area, in terms of research or otherwise?
Dr Mullur: Despite the promising preliminary data, precision nutrition is still novel, and at this point it is unlikely to be widely used in clinical and public health settings. Nonetheless, commercial interests have already begun marketing personalized nutrition assessments directly to patients, so as endocrinologists, our understanding and facility with these technologies must keep pace with the demands of our patients.
Studies using precision techniques in nutrition remain small because of the high cost of -omics technologies. I suspect that as these technologies are become more cost-effective, they not only will be more widely used but also will provide more clinically useful biomarkers for predicting, preventing, and targeting T2D. A predictive dietary intervention algorithm, such as the one that was piloted by Zeevi and colleagues, will need to be scaled to reach a larger population and will need to be studied for long-term efficacy, safety, and cost-effectiveness.
Finally, our traditional dietary intervention approaches should be tailored and improved to provide more personalized advice to our patients. We cannot ignore the complex role of food and diet in the essence of our lives: Food is integrally related to social behaviors, neural networks of comfort, reward and pleasure, economics, lifestyle, and education. Knowing this, as physicians, we must be mindful of the effect our dietary counseling may have on an individual with T2D, and offer more than platitudes and general guidelines if we expect to truly affect health outcomes.
Ms Sartor: As academic medical centers across the United States and world embrace this important and cutting-edge technology, strides in health promotion as well as disease prevention can be realized. Advanced research will drive clinically significant patient treatment strategies and, eventually, health policy development and promotion. Precision medicine and precision nutrition will drive the wellness of future generations.
- Statistics about diabetes. American Diabetes Association. http://www.diabetes.org/diabetes-basics/statistics/. Updated March 22, 2018. Accessed on April 16, 2018.
- Wang DD, Hu FB. Precision nutrition for prevention and management of type 2 diabetes. Lancet Diabetes Endocrinol. 2018;6(5):416-426.
- Florez JC, Udler MS, Hanson RL. Genetics of type 2 diabetes. In: Cowie CC, Casagrande SS, Menke A, eds. Diabetes in America, 3rd ed. Bethesda, MD: National Institutes of Health; 2016.
- Manolio TA, Collins FS, Cox NJ, et al. Finding the missing heritability of complex diseases. Nature. 2009;461(7265):747-753.
- Guasch-Ferre M, Hruby A, Toledo E, et al. Metabolomics in prediabetes and diabetes: a systematic review and meta-analysis. Diabetes Care. 2016;39(5):833-846.
- Vazquez-Fresno R, Llorach R, Urpi-Sarda M, et al. Metabolomic pattern analysis after mediterranean diet intervention in a nondiabetic population: a 1- and 3-year follow-up in the PREDIMED study. J Proteome Res. 2015;14(1):531-540.
- Kovatcheva-Datchary P, Nilsson A, Akrami R, et al. Dietary fiber-induced improvement in glucose metabolism is associated with increased abundance of Prevotella.Cell Metab. 2015;22(6):971-982.
- Zeevi D, Korem T, Zmora N, et al. Personalized nutrition by prediction of glycemic responses. Cell. 2015;163(5):1079-1094.