Proteomic and integrative omic profiles of sugar- and artificially sweetened beverage consumption and changes in type 2 diabetes risk factors
NIH
BRIGHAM AND WOMEN'S HOSPITAL
PROJECT SUMMARY: Type 2 diabetes (T2D) is caused both by genetic and environmental factors, such as diet, as well as the complex interactions between them. While diet is the cornerstone for T2D prevention, dietary interventions are often difficult to implement and monitor due to limitations in dietary assessment techniques and strategies to produce dietary changes. Despite efforts to reduce SSB consumption, SSBs remain the largest single source of added sugar in the US. SSB consumption has been linked to a higher risk of T2D and related risk factors, but the underlying biological mechanisms are not completely understood. Proteomic profiling and multi-omic integration allow for more detailed phenotyping that may provide a broader view of diet-associated metabolic changes and their functional interpretation. Examination of plasma proteomic and integrative omic profiles that reflect SSB intake and a common alternative beverage, artificially sweetened beverages (ASB), may enhance current dietary assessment methods and unveil novel biological pathways linking diet to T2D and related risk factors through identification of novel dietary biomarkers.  Discovery of plasma proteomic and multi-omic profiles of SSB and ASB consumption has immense potential to provide an objective assessment of individual beverage intake and enable informed beverage choices, which is in line with the precision nutrition approaches emphasized in the National Institute of Health’s (NIH) 10-year strategic plan. This proposal cost-effectively leverages existing proteomics profiling among the Nurses’ Health Study II and Health Professionals Follow-up Study cohorts (n=648). It also examines repeated assays in the ongoing NIH-funded SUBstituting with Preferred OPtions trial, a randomized parallel-arm 6- month beverage trial testing the effects of substituting SSBs with ASB or water among daily SSB consumers. We will utilize proteomic and multi-omic network and machine learning analyses to identify discriminatory profiles between SSB and ASB consumption levels and evaluate the associations of these profiles with T2D risk factors. The central hypothesis is that distinct proteomic and omic profiles reflect habitual SSB or ASB intake and that changes in their omic biomarkers are associated with changes in T2D risk factors, revealing novel biomarkers of beverage consumption and biological pathways modified by beverage consumption. This K01 career development award expands on the applicant’s experience in nutritional epidemiology, omics, and biostatistics to gain proficiency in the design and management of intervention studies, implementation of cutting-edge multi-omic statistical analysis techniques, and scientific leadership for precision nutrition applications for T2D prevention. With mentorship from a renowned multidisciplinary research team, the applicant will gain the crucial skills necessary to advance T2D prevention and refine a framework for the utilization of innovative multi-omics techniques in complementary interventional and epidemiological study designs to inform precision nutrition initiatives and transition to an independent investigator. PROJECT NARRATIVE: The majority of type 2 diabetes (T2D) cases could be prevented or reversed through successful implementation of diet and lifestyle treatment and prevention strategies, yet diet and lifestyle interventions are difficult to adhere to due to an abundance of calories in the environment, which includes calories from sugar sweetened beverages. This proposal presents a unique sub-study within an ongoing randomized controlled trial and existing population-based cohort studies aiming to explore the underlying mechanisms of how sugar- and artificially sweetened beverage consumption influence T2D risk factors; we aim to identify novel biomarkers of dietary consumption that could lead to an individualized, objective assessment of beverage intake to increase efficacy of dietary interventions for T2D prevention. The unique career development plan provides training in the design and management of RCTs, the implementation of cutting-edge multi-omic statistical analysis techniques, and scientific leadership in T2D prevention that complements the applicants current training in nutritional epidemiology, omics, and biostatistics.
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