Consumo de bebidas ricas em açúcares de adição: investigando as redes de interações das doenças crônicas não transmissíveis bucais e sistêmicas nos ciclos da vida

Abstract

The complex network approach emerges as a promising tool to explore the intricate web of interactions among the risk factors for both oral and systemic non-communicable diseases (NCDs). This perspective allows for an understanding of how these connections are organized and evolve throughout the life course, from early years to adulthood, while also identifying strategic targets for the development of public policies and interventions aimed at reducing the burden of these diseases. This thesis is composed of seven chapters. The first two chapters provide an initial exploration of the relationship between periodontitis and behavioral and metabolic risk factors, with an emphasis on the consumption of sugar-sweetened beverages, the main source of discretionary calories in the Western diet. The next three chapters delve deeper into the investigation through the application of complex network analysis, aiming to explore the interrelationships between oral and systemic diseases, as well as their shared risk factors, across different stages of the life cycle. The sixth chapter broadens the scope of the thesis by examining the global spread of the consumption of sugar-sweetened beverages and projecting its impact through the year 2050. Finally, the last chapter is dedicated to translating the knowledge generated in this doctoral work to society through the development of a digital book for dentists, offering an unprecedented approach to the Developmental Origins of Health and Disease (DOHaD) theory as applied to Dentistry. CHAPTER 1 presents the hypothesis that the prevalence of periodontitis in Brazil has increased over the past three decades, accompanied by a rise in the consumption of beverages high in added sugars. This chapter resulted in the original article “Behavioral and metabolic risk factors associated with periodontitis in Brazil, 1990–2019: a multidimensional analysis for the Global Burden of Disease Study 2019”, published in the journal Clinical Oral Investigations (Impact Factor 3.1, DOI: 10.1007/s00784 023-05384-6). The aim of this study was to analyze the relationship between periodontitis and behavioral and metabolic risk factors common to NCDs among Brazilian adults over a 30-year period. To achieve this, data from the Global Burden of Disease Study 2019 were used. The analysis was conducted using Prais-Winsten regression to identify trends in time series, and fixed effects regression to investigate associations between variables. The results indicated that, since 2005, the prevalence of periodontitis has been increasing in Brazil, even in the context of declining tobacco use. Moreover, periodontal disease was found to be associated with the consumption of sugar-sweetened beverages, overweight/obesity, dyslipidemia, and hyperglycemia. These findings offer a new perspective on the interconnection between periodontitis and NCDs, highlighting the importance of preventive strategies focused on behavioral and metabolic factors. This study also marked the beginning of my involvement with the Graduate Programs in Dentistry (PPGO-UFMA), Health Sciences (PPGCS-UFMA), and Computer Science (PPGCC-UFMA) within the scope of the Graduate Program Development Initiative in the Legal Amazon (PDPG Amazônia Legal–CAPES), through which I receive my doctoral scholarship. In addition, this study was a key milestone in establishing a partnership with a researcher from Duke-NUS Medical School in Singapore, who later became my co supervisor. Following the publication of this first article, I had the opportunity to complete a doctoral exchange program at that institution, supported by the National Academic Cooperation Program in the Amazon (PROCAD Amazônia–CAPES). During this period, I deepened my analytical skills and advanced my understanding of the interrelations between behavioral and metabolic factors in periodontitis. The product of this internship is presented in CHAPTER 2 of this thesis, which corresponds to the original article entitled “Sugar-sweetened beverage consumption and periodontitis among adults: A population-based cross-sectional study”, published in the Journal of Clinical Periodontology (Impact Factor 6.8, DOI: 10.1111/jcpe.13961). This study investigated the relationship between the consumption of sugar-sweetened beverages and periodontitis using data from the Third National Health and Nutrition Examination Survey (NHANES III), involving American adults aged 30 to 50 years. Beverage consumption was associated with periodontitis when individuals reported intake of ≥5, ≥7, and ≥14 times per week. The results contribute to a better understanding of the factors that influence oral health and highlight the importance of interventions aimed at preventing the excessive consumption of these beverages. These findings motivated us to deepen our understanding of the interconnections between oral and systemic NCDs, since sugar consumption appears to be a common link among them. This perspective led us to formulate the third hypothesis of this study: NCDs may be interconnected from the earliest years of life, with their complexity increasing as additional organs and systems are affected with age. To better understand the dynamics of these diseases and their interrelations, we sought a close collaboration with the Institute of Mathematics and Computer Sciences (ICMC/USP), which enabled the application of advanced analytical approaches in complex network analysis. CHAPTER 3 of this thesis is based on the original article entitled “Caries Is the Hub of a Complex Network of Chronic Diseases across the Life Decades”, published in the Journal of Dental Research (Impact Factor 5.9, DOI: 10.1177/00220345251317487). This study explored the interconnections among NCDs across all life stages using complex network analysis to uncover pathways that may support enhanced intervention strategies and improve NCD management from childhood through old age. The research used data from the 2011 2012 and 2013–2014 cycles of the National Health and Nutrition Examination Survey (NHANES), which included indicators of metabolic risk, diabetes, cancer, cardiovascular, autoimmune, respiratory, mental, and oral diseases. From early life, dental caries was closely linked to overweight/obesity and asthma. As age progressed, new diseases became interconnected, increasing the network’s complexity. Depression played a central role in adulthood, while in old age, episodes of forgetfulness and mental confusion became more relevant. The centrality of diabetes, cardiovascular diseases, and cancer increased with age, peaking in individuals aged 60 and over, with diabetes emerging as the most prominent condition. The results showed that all age groups exhibited high clustering coefficients among NCDs, demonstrating the interdependence between diseases. Dental caries remained the central hub across the decades, with other health conditions orbiting around it. This study represented a significant advancement in the application of complex networks as an analytical tool, offering a clearer and more dynamic view of disease relationships. This, in turn, enabled more precisely targeted interventions to reduce the NCD burden in the population. The findings obtained in the previous chapter, which mapped the interconnections among NCDs throughout life, encouraged a deeper investigation—not only into the diseases themselves but also into their social determinants, in addition to behavioral and metabolic risk factors in Brazilian adolescents. Adolescence is a sensitive developmental period in which patterns shaping the development of NCDs can be identified, allowing for more impactful preventive interventions. Thus, CHAPTER 4 resulted in the original article entitled “High free sugars, insulin resistance, and low socioeconomic indicators: the hubs in the Complex Network of Non-Communicable Diseases in Adolescents”, published in Diabetology & Metabolic Syndrome (Impact Factor 3.9, DOI: 10.1186/s13098-024-01469-8). This study used data from the RPS Cohort Consortium in the city of São Luís, focusing on adolescents aged 18 to 19 years (n = 2,515). Through complex network analysis, we investigated how socioeconomic, behavioral, and metabolic variables, including income, diet, sleep quality, the TyG index (a marker of insulin resistance), and chronic conditions such as depression, asthma, caries, and periodontitis— interact and shape the dynamics of NCDs in this age group. To characterize the network, we applied metrics such as degree, betweenness, eigenvector centrality, local transitivity, Shannon entropy, and clustering coefficients. The results highlighted three main hubs in the overall network: high free sugar intake, insulin resistance, and low socioeconomic status. Among boys, low fiber intake and a high triglyceride/HDL ratio stood out as cardiometabolic risk markers. Among girls, sedentary behavior and inadequate sleep were strongly associated with metabolic and psychological outcomes. In both sexes, dental caries reaffirmed the central role of oral health in its interaction with systemic conditions. These findings reinforce adolescence as a strategic period for integrated interventions that address the identified central elements. Understanding adolescence as a window of opportunity for the prevention of NCDs broadened our perspective on the importance of investigating earlier stages of life course. In this context, CHAPTER 5 deepens the investigation of the transgenerational roots of NCDs, exploring exposures during pregnancy and the early years of life, through the article “Decoding the Complexity of Health-Related Factors Connections around the First Thousand Days of Life: Network Analysis”. The manuscript will be submitted to the scientific journal Pediatrics (Impact Factor 6.4). This study used data from the BRISA Prenatal Cohort in São Luís (N = 1,383), with data collected at three time points: between the 22nd and 25th weeks of gestation, at birth, and during the child’s second year of life. Network analysis was based on the Jaccard index to identify patterns of co-occurrence, complemented by centrality metrics and clustering measures. The constructed network revealed high connectivity among the factors analyzed. The main hubs identified during pregnancy were the consumption of ultra-processed foods, sugar sweetened beverages, low socioeconomic status, and dental caries. Sugar-sweetened beverage consumption and low socioeconomic status during pregnancy showed strong links with all adverse birth outcomes. Subsequently, in the child’s second year of life, new hubs emerged: sugar exposure, allergies, and non-exclusive breastfeeding. Regarding the onset of NCDs in childhood, factors such as maternal intake of ultra-processed foods and sugar-sweetened beverages, low socioeconomic status, anemia, and dental caries during pregnancy—together with early-life exposure to sugars—were strongly associated with the development of allergies, overweight/obesity, asthma, and dental caries in children. These findings reinforce that socioeconomic factors, behavioral risks, and systemic and oral health conditions during pregnancy exert a decisive influence on adverse birth outcomes and the early emergence of NCDs, highlighting the importance of early interventions to break the transgenerational cycle of these diseases. CHAPTER 6 presents the article “Global, regional, and national burden of high sugar-sweetened beverages consumption, 1990–2021, with projections up to 2050: a systematic analysis for the Global Burden of Disease Study 2021”, which was published in The American Journal of Clinical Nutrition (Impact Factor 6.9, DOI: 10.1016/j.ajcnut.2025.07.033). The study investigated the global burden of excessive consumption of sugar-sweetened beverages (SSBs) over the past three decades and projected trends through 2050, as well as its impact on the burden of NCDs. We used data from the Global Burden of Disease Study 2021 to estimate population exposure to high SSB consumption and the burden of NCDs attributable to this behavior, including cardiovascular diseases, diabetes, and kidney diseases. To assess the impacts, we analyzed mortality rates, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life years (DALYs). Projections of SSB exposure rates were conducted using ensemble models based on the Socio demographic Index (SDI). Findings revealed that, in 2021, the global population exposure to high SSB consumption was 30.56%, with the highest levels observed in high-income super regions and Latin America and the Caribbean. A correlation was found between increased SSB consumption and SDI, with higher rates in more developed countries. The global burden of NCDs attributable to SSB consumption included an age-standardized rate of 0.89 deaths per 100,000 population and 41.39 DALYs. Projections indicate a +9.54% increase in global SSB consumption by 2050. This study highlights the growing impact of sugar-sweetened beverages on the global burden of NCDs over the past three decades, pointing to an even more concerning scenario in the future if effective public health measures are not implemented. The findings reinforce the urgency of targeted policies to reduce the consumption of these beverages, especially in more vulnerable regions. CHAPTER 7 of this thesis presents the development of a digital book focused on the prevention of NCDs starting from the first thousand days of life, based on evidence from the Developmental Origins of Health and Disease (DOHaD) theory, with an emphasis on Dentistry. The book is entitled “The first thousand days of life: a DOHaD perspective to dentistry”. The material was produced in both Portuguese (https://ares.unasus.gov.br/acervo/handle/ARES/27271) and English (https://ares.unasus.gov.br/acervo/handle/ARES/29558). The publications were grounded in four core premises derived from the DOHaD framework: (1) dental caries are associated with childhood asthma, obesity, and are predictive of future diseases such as diabetes and cardiovascular conditions; (2) the consumption of ultra-processed foods and sugar is a major risk factor for both oral and systemic NCDs; (3) microbiome imbalance affects both oral and systemic health; and (4) breastfeeding has a protective effect. The Portuguese edition has reached over 7,000 accesses in Brazil and other countries, including the United States, United Kingdom, Germany, Ireland, Sweden, and Japan, which prompted the release of the English version to expand its reach and impact. This work represents the first book to address the DOHaD framework within the field of Dentistry, making a significant contribution to the theoretical advancement of the area. As an innovative educational resource, the publication promotes professional training and strengthens comprehensive health care practices, highlighting the value of interdisciplinary initiatives in the global dissemination of DOHaD informed knowledge. Throughout this thesis, added sugars—especially those found in sugar sweetened beverages—emerge as a common axis in complex health networks, associated with oral diseases and other NCDs, underscoring the urgent need for coordinated public policies aimed at reducing consumption.