Gout is a common and excruciatingly painful inflammatory arthritis associated with hyperuricemia. Gout represents a metabolically-driven arthropathy that could be substantially controlled through dietary and lifestyle modifications. With the continued "western" lifestyle in the US, the prevalence and incidence of gout have increased over the last few decades and it is estimated that 3.9% of US adults (8.3 million individuals) have had gout according to the latest US NHANES data. This remarkable burden of gout is further complicated by its high level of cardiovascular (CV)-metabolic comorbidities (e.g., hypertension in 74% and obesity in 53% of cases) and their consequences (e.g., increased future risk of myocardial infarction and premature death). The current low-purine dietary approach to gout offers limited efficacy, palatability, and sustainability, and promotes increased consumption of refined carbohydrates and saturated fat that can actually worsen gout's CV-metabolic comorbidities by leading to insulin-resistance and increased levels of plasma glucose, triglycerides, and LDL-cholesterol. Therefore, there is an urgent need for a unifying, sustainable, and effective prevention strategy that holistically addresses both gout and its associated comorbidities. In fact, there are proven, effective dietary approaches to reduce CV-metabolic conditions (including obesity) that could also lower serum uric acid (SUA) levels and the risk of gout by lowering adiposity and insulin resistance. These existing approaches could potentially provide an ideal dietary strategy to reduce both the risk of gout and its associated CV-metabolic conditions. In this study, we will build upon our extensive experience with gout prevention research to examine the impact of these dietary approaches on the outcomes of both SUA and gout. We will investigate their effects on SUA levels using stored blood samples from 6 landmark randomized controlled trials of various dietary approaches to reduce CV-metabolic conditions (including the Mediterranean, Atkins, and DASH diets) (Aims 1-3). Through participation of the PIs of all 6 trials in this project, we will take full advantage of the originl RCT designs and collected data. Further, we will evaluate their impact on the risk of gout based on 3 large prospective cohorts: the Nurses'Health Study (NHS) I (n=121,700 women), NHS II (n=116,430 younger women), and the Health Professionals Follow-up Study (HPFS;n=51,529 men) (Aim 4). We will take advantage of systematically collected high- quality data that have undergone rigorous validation including >3,200 confirmed cases of incident gout.
These aims hold the potential to revolutionize our non-pharmacological urate-lowering approaches to hyperuricemia and gout by simultaneously investigating multiple candidate diets using a highly cost-effective study design. These measures will also comprehensibly address the major comorbidities associated with the rising disease burden of gout. With our extensive gout research experience combined with resourceful data access, we are in a unique and unparalleled position to address these key issues facing the field in the US and beyond.

Public Health Relevance

There is a remarkable, increasing disease burden of gout and its associated cardiovascular-metabolic comorbidities in the US, underscoring an urgent need for holistic strategies to effectively address these conditions. The current project will address this need by simultaneously investigating multiple candidate diets using a highly cost-effective study design. This proposal holds the potential to revolutionize non- pharmacological urate-lowering approaches to gout and will substantially contribute to the goal of reducing the disease burden of both gout and associated comorbidities in the US and beyond.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01AR065944-02
Application #
8739149
Study Section
Neurological, Aging and Musculoskeletal Epidemiology Study Section (NAME)
Program Officer
Witter, James
Project Start
Project End
Budget Start
Budget End
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Boston University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02118
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Lu, Na; Dubreuil, Maureen; Zhang, Yuqing et al. (2016) Gout and the risk of Alzheimer's disease: a population-based, BMI-matched cohort study. Ann Rheum Dis 75:547-51
Jutkowitz, Eric; Dubreuil, Maureen; Lu, Na et al. (2016) The cost-effectiveness of HLA-b*5801 screening to guide initial urate-lowering therapy for gout in the United States. Semin Arthritis Rheum :
Dubreuil, Maureen; Zhu, Yanyan; Zhang, Yuqing et al. (2015) Allopurinol initiation and all-cause mortality in the general population. Ann Rheum Dis 74:1368-72
Zhang, Yuqing; Peloquin, Christine E; Dubreuil, Maureen et al. (2015) Sleep Apnea and the Risk of Incident Gout: A Population-Based, Body Mass Index-Matched Cohort Study. Arthritis Rheumatol 67:3298-302
Bao, Ying; Curhan, Gary; Merriman, Tony et al. (2015) Lack of gene-diuretic interactions on the risk of incident gout: the Nurses' Health Study and Health Professionals Follow-up Study. Ann Rheum Dis 74:1394-8
Lu, Na; Misra, Devyani; Neogi, Tuhina et al. (2015) Total joint arthroplasty and the risk of myocardial infarction: a general population, propensity score-matched cohort study. Arthritis Rheumatol 67:2771-9

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