Burden of non-communicable disease: Global overview

Non-communicable diseases continue to be important public health problems in the world, being responsible for sizeable mortality and morbidity. Non-communicable diseases (NCDs) are the leading causes of death and disability worldwide. In 2005 NCDs caused an estimated 35 million deaths, 60% of all deaths globally, with 80% in low income and middle-income countries and approximately 16 million deaths in people less than 70 years of age. Total deaths from NCDs are projected to increases by a further 17% over the next 10 years. Knowing the risk factors for chronic disease means that approximately 80% premature heart disease and stroke, 80% of Type 2 diabetes and 40% of cancers are preventable. Within next 20 years, NCDs will be responsible for virtually half of the global burden of disease in the developing countries. Risk factors, such as tobacco and alcohol use, improper nutrition and sedentary behavior contribute substantially to the development of NCDs, which are sweeping the entire globe, with an increasing trend mostly in developing countries where, the transition imposes more constraints to deal with an increasing burden of over population with existing communicable diseases overwhelmed with increasing NCDs in poorly maintained sanitation and environment.By 2020, it is predicted that these diseases will be causing seven out of every 10 deaths in developing countries. A major feature of the developmental transition is the rapid urbanization and the large shifts in population from rural to urban areas. Even the rural people are increasingly adapting urbanized lifestyle. The changing pattern of lifestyle leads to the development of obesity, stroke, stress, atherosclerosis, cancer and other NCDs.Considering the future burden of NCDs and our existing health care system we should emphasize the need to prioritize the prevention and control of NCDs. Our strategies should be directed to monitor the incidence of NCDs along with their risk factors. Some NCDs have their common risk factors which should be addressed with minimum cost but maximum output. The three key components of the strategy are surveillance, health promotion and primary prevention, and management and health care.According to the WHO criteria there are three steps for screening of NCDs. Step 1: Estimation population need through assessing the current risk profile and advocate for action. Step 2: Formulate and adopt NCD policy. Step 3: Identify policy implementation steps. Management of NCDs should be to increased awareness among the public regarding the signs and symptoms of the disease and its complications.Health promotion strategies, with a strong focus on disease prevention, are needed to empower people to act both individually and collectively to prevent risky behavior, and to create economic, political and environmental conditions that prevent NCDs and their risks. Risk trends need to be monitored and intervention strategies need to be evaluated with respect to their expected outcomes. Issues such as rapid population ageing, gender and income inequality, persistent poverty and the needs of developing countries require close consideration as they influence the prevalence of NCDs – and the success of interventions.     

Narrative review of reviews of preconception interventions to prevent an increased risk of obesity and non‐communicable diseases in children

Evidence for the effect of preconception and periconceptional risk factors on childhood outcomes such as obesity and other non‐communicable diseases (NCDs) in later life is growing. Issues such as maternal malnutrition need to be addressed before pregnancy, to prevent a transgenerational passage of risk of NCDs. The aim of this review was to evidence for preconception interventions to prevent obesity and other risk factors for NCDs in children. A search for systematic reviews of interventions in the preconception period published between 2006 and 2018 was conducted on academic databases. Fifteen reviews were included, two of the reviews also included pregnant women. None of the reviews directly reported on obesity or NCD outcomes in children. Results suggest that exercise‐ and diet‐based interventions significantly reduced maternal weight postpartum, weight gain during pregnancy, and improved prevention and control of gestational diabetes. Balanced protein energy supplementation during and before pregnancy was associated with an increase in mean birth weight and reduction of low birth weight babies. There is a dearth of evidence for preconception programmes that follow up on childhood outcomes related to a risk of NCDs. Nevertheless, results suggest that women who received preconception interventions were more likely to have improved pregnancy‐related and behavioural outcomes.     

Epigenetics and prenatal influences on asthma and allergic airways disease

Uterine life is arguably the most critical time in developmental programming, when environmental exposures may have the greatest potential to influence evolving fetal structure and function. There has been substantial progress in understanding the epigenetic mechanisms through which environmental exposures can permanently alter the expression of fetal genes and contribute to the increasing propensity for many complex diseases. These concepts of "developmental origins" of disease are being applied across virtually all fields of medicine, and emerging epigenetic paradigms are the likely mechanism behind the environment-driven epidemic of asthma and allergic disease. Here, we examine the epigenetic regulation of immune development and the early immune profiles that contribute to allergic risk. In particular we review new evidence that key environmental exposures, such as microbial exposure, dietary changes, tobacco smoke, and pollutants, can induce epigenetic changes in gene expression and alter disease risk. Although most of these factors have already been clearly implicated in epidemiologic studies of asthma and allergic disease, new studies investigating the mechanisms of these effects may provide new avenues for using these pathways for disease prevention.     

Morbidity compression or expansion? A temporal analysis of the age at onset of non-communicable diseases in India

While there is evidence of morbidity compression in many countries, temporal patterns of non-communicable diseases (NCDs) in developing countries, such as India, are less clear. Age at onset of disease offers insights to understanding epidemiologic trends and is a key input for public health programs. Changes in age at onset and duration of major NCDs were estimated for 2004 (n = 38,044) and 2018 (n = 43,239) using health surveys from the India National Sample Survey (NSS). Survival regression models were used to compare trends by sociodemographic characteristics. Comparing 2004 to 2018, there were reductions in age at onset and increases in duration for overall and cause-specific NCDs. Median age at onset decreased for NCDs overall (57 to 53 years) and for diabetes, hypertension, heart disease, asthma, mental diseases, eye disease, and bone disease in the range of 2–7 years and increased for cancer, neurological disorders, some genitourinary disorders, and injuries/accidents in the range of 2–14 years. Hazards of NCDs were higher among females for cancers (HR 1.51, 95% CI 1.19–1.90) and neurological disorders (HR 1.18, 95% CI 1.06–1.32) but lower for heart diseases (HR 0.88, 95% CI 0.79–0.97) and injuries/accidents (HR 0.87, 95% CI 0.77–0.99). Hazards were greater among those with lower educational attainment at younger ages and higher educational attainment later in life. Unlike many countries, chronic disease morbidity may be expanding in India for many chronic diseases, indicating excess strain on the health system. Public health programs should focus on early diagnosis and prevention of NCDs.

     

Physical activity interventions in early life aimed at reducing later risk of obesity and related non‐communicable diseases: A rapid review of systematic reviews

To identify useful components of interventions aimed at prevention of childhood obesity and related non‐communicable diseases (NCDs), which included physical activity and which targeted any or all of four life‐course stages: peri‐conception; pregnancy; infancy and toddlerhood (0 to 23 months); and early childhood (24 to 59 months). In May 2016, WHO Geneva searched the Cochrane Library and PubMed for systematic reviews of interventions including physical activity to prevent childhood obesity or risk factors for obesity‐related NCDs. Using a narrative synthesis, the efficacy of randomized controlled trials (RCTs) to alter energy balance outcomes (measures of weight status or body fatness) was characterized by life‐course stage, study characteristics, intervention functions (as defined in the behaviour change wheel), and level of the socio‐ecological model (SEM) targeted. The quality of included systematic reviews was assessed. We retrieved 82 reviews from the World Health Organization (WHO) search, of which 23 were eligible for the present synthesis. The number of eligible studies by life‐course stage was: 0 (peri‐conception); 0 (pregnancy); 8 (infancy and toddlerhood, age 0 to 23 months; seven RCTs; age); and 37 (early childhood, age 24 to 59 months; 30 RCTs;). Thus, there was a lack of evidence for physical activity interventions during peri‐conception and pregnancy. Almost all relevant studies in the 0‐ to 23‐ and 24‐ to 59‐month life‐course stages were multicomponent interventions (ie, targeted physical activity, dietary, and/or sedentary behaviours). Interventions with evidence of efficacy tended to target multiple levels of the SEM, with emphasis on parents, and extend over long periods. Effective intervention elements for early life obesity prevention included classes on parenting skills, alteration of the kindergarten playground, and financial incentives. Evidence from low‐ and middle‐income countries was scarce, and evidence for intervention effect on obesity‐related NCDs was missing. Future physical activity interventions in toddlerhood and early childhood aimed at prevention of obesity should adopt the characteristics typical of effective interventions identified by the present synthesis. There is an urgent need for more evidence on physical activity interventions set in low‐ and middle‐income countries and which target the peri‐conception and pregnancy periods.     

Neonatal exposure to estradiol/bisphenol A alters promoter methylation and expression of Nsbp1 and Hpcal1 genes and transcriptional programs of Dnmt3a/b and Mbd2/4 in the rat prostate gland throughout life

Evidence supporting an early origin of prostate cancer is growing. We demonstrated previously that brief exposure of neonatal rats to estradiol or bisphenol A elevated their risk of developing precancerous lesions in the prostate upon androgen-supported treatment with estradiol as adults. Epigenetic reprogramming may be a mechanism underlying this inductive event in early life, because we observed overexpression of phosphodiesterase 4D variant 4 (Pde4d4) through induction of hypomethylation of its promoter. This epigenetic mark was invisible in early life (postnatal d 10), becoming apparent only after sexual maturation. Here, we asked whether other estrogen-reprogrammable epigenetic marks have similar or different patterns in gene methylation changes throughout life. We found that hypomethylation of the promoter of nucleosome binding protein-1 (Nsbp1), unlike Pde4d4, is an early and permanent epigenetic mark of neonatal exposure to estradiol/bisphenol A that persists throughout life, unaffected by events during adulthood. In contrast, hippocalcin-like 1 (Hpcal1) is a highly plastic epigenetic mark whose hypermethylation depends on both type of early-life exposure and adult-life events. Four of the eight genes involved in DNA methylation/demethylation showed early and persistent overexpression that was not a function of DNA methylation at their promoters, including genes encoding de novo DNA methyltransferases (Dnmt3a/b) and methyl-CpG binding domain proteins (Mbd2/4) that have demethylating activities. Their lifelong aberrant expression implicates them in early-life reprogramming and prostate carcinogenesis during adulthood. We speculate that the distinctly different fate of early-life epigenetic marks during adulthood reflects the complex nature of lifelong editing of early-life epigenetic reprogramming.     

Maternal and In Utero Determinants of Type 2 Diabetes Risk in the Young

The global prevalence of diabetes mellitus has reached epidemic proportions. In 2010, it was estimated that 6.4 % of the adult population (285 million) have diabetes. In recent years, the incidence of type 2 diabetes (T2D), a condition traditionally associated with aging, has been steadily increasing among younger individuals. It is now a well-established notion that the early-life period is a critical window of development and that influences during this period can “developmentally prime” the metabolic status of the adult. This review discusses the role of maternal and in utero influences on the developmental priming of T2D risk. Both human epidemiological studies and experimental animal models are beginning to demonstrate that early dietary challenges can accelerate the onset of age-associated metabolic disturbances, including insulin resistance, T2D, obesity, hypertension, and cardiovascular disease. These findings show that poor maternal nutrition can prime a prediabetes phenotype, often manifest as insulin resistance, by very early stages of life. Thus, the maternal diet is a critical determinant of premature T2D risk. While the mechanisms that link early nutrition to age-associated metabolic decline are currently unclear, preliminary findings suggest perturbations in a number of processes involved in cellular aging, such as changes in longevity-associated Sirtuin activity, epigenetic regulation of key metabolic genes, and mitochondrial dysfunction. Preliminary studies show that pharmacological interventions in utero and dietary supplementation in early postnatal life may alleviate insulin resistance and reduce T2D risk. However, further studies are warranted to fully understand the relationship between the early environment and long-term effects on metabolism. Such mechanistic insights will facilitate strategic interventions that prevent accelerated metabolic decline and the premature onset of T2D in the current and future generations.     

Early-Life Exposures and Risk of Diabetes Mellitus and Obesity

Purpose of Review

Type 2 diabetes is a growing concern worldwide with increasing incidence in youth. Development of preventive strategies in earlier stages of life is crucial. We aimed to examine epidemiological evidence of early-life exposures and their associations with childhood and later risk of obesity and diabetes, and to discuss potential mechanisms.

Recent Findings

Parental obesity and diabetes in the preconception period may influence offspring’s obesity risk via epigenetic mechanisms influencing gametogenesis and early development that could have significant transgenerational effects. A more comprehensive understanding of these effects is needed to identify possible avenues for interventions in both fathers and mothers to be. In addition, current evidence suggests that growth and body weight trajectories in infancy and childhood are useful indicators of later obesity and type 2 diabetes. Moreover, the composition and variations in the microbiome in early life are associated with long-term health and could mediate associations between several early-life exposures and later risk of diseases.

Summary

Altogether, the epidemiological evidence supports the need for preconception and early-life interventions to reduce the obesity and diabetes burden in later life.

     

Identifying obese women most at risk from cardiovascular disease

In Western countries, more women than men die every year of cardiovascular disease (CVD) and women spend more life years with cardiovascular disease than men. Fortunately, premature cardiovascular disease in women is preventable. Evidence-based guidelines for the prevention of cardiovascular disease in women recommend an initial risk assessment. However, recommended risk-assessment tools such as the Systematic Coronary Risk Evaluation (SCORE) system may not be sufficient to detect risk in women with obesity. A further barrier to prevention in women is the fact that physicians may underestimate the effects of risk factors that are particularly dangerous or prevalent in women. These include type 2 diabetes, hypertension, smoking, abdominal obesity, poor exercise capacity and the metabolic syndrome. Several of these factors, as well as some novel biomarkers, may increase the risk of cardiovascular disease relatively more in women than in men. To assess risk in obese women, a multifactorial assessment that encompasses assessment of body-fat distribution should be undertaken. Weight loss and lifestyle changes that have been shown to improve risk-factor profiles are crucial interventions and should be considered, even if standard risk calculators do not indicate an elevated cardiovascular risk.     

Addressing the Global Burden of Cardiovascular Diseases; Need for Scalable and Sustainable Frameworks

Only 14 countries are on track to attain the Sustainable Development Goal (SDG) target of reducing premature mortality from Noncommunicable Diseases (NCDs) by one-third by 2030. This target cannot be reached without reducing the burden of cardiovascular diseases (CVDs) which is the major contributor to premature mortality from NCDs. Sustainable and scalable national responses to address both CVDs and their risk factors are urgently needed. Although smoking rates have decreased globally, consumption of alcohol and physical inactivity are on the rise. No country is on course to achieve the target to halt the rise in obesity or to reduce salt intake: targets critical for reducing the diabetes related cardiovascular burden and for hypertension control. Although very cost-effective scalable interventions are available, they are underutilized. Unless pathways selected to tackle CVDs prioritize prevention, primary health care and universal health coverage, countries will fall further behind in the attainment of the SDG target.     

Amount and quality of dietary proteins during the first two years of life in relation to NCD risk in adulthood

During late infancy many infants have a protein intake, which is more than three times as high as the physiological need. Several observational studies have shown an association between a high-protein intake (>15 energy %) early in life and an increased risk of developing obesity and thereby non-communicable diseases (NCDs) later in life. This effect was supported by a recent intervention study with infant formulas with two levels of protein, showing that a higher protein intake during the first year of life resulted in a higher body mass index (BMI) at age 2 years. It is also plausible that an important reason for the slower growth in breast-fed infants is the lower content of protein in breastmilk, but other qualities of breastmilk could also play a role. A high intake of protein, especially dairy protein, stimulates the growth factors insulin-like growth factor (IGF-I) and insulin, and it has been suggested that the lower risk of NCDs in breast-fed infants is mediated through a regulation of IGF-I. A low quality of protein, as in cereal-based diets with no animal foods as often seen in low-income countries, may contribute to undernutrition, which can also result in an increased risk of NCDs later in life. In conclusion, there is some evidence that a high protein intake during the complementary feeding period is associated with increased risk of NCDs and that avoidance of a high protein intake could reduce the risk of obesity. In low-income countries, emphasis should be on providing sufficient amounts of high-quality protein to improve survival, growth and development.     

Early-life origin of adult disease: Evidence from natural experiments

Until the present time, disease susceptibility was believed to be determined solely by the genetic information carried in the DNA sequence. In recent years, however, it has become clear that epigenetic rearrangements play an equally essential role in the disease development and that this process, particularly at key developmental stages, is very susceptible to environmental modulations. The extensive studies, both human and animal, have shown that early-life environment is probably the most important causal component in the etiology of some diseases including cancer as well as metabolic and cardiovascular disorders. This review considers the natural experiment-based evidence regarding the developmental origin of human adult disease.     

Secular changes in blood pressure in childhood,adolescence and young adulthood: systematic review of trends from 1948 to 1998

One plausible reason for the decline in cardiovascular disease (CVD), and in particular stroke, in the last century is population reductions in blood pressure. Blood pressure tracks from childhood into adulthood, and early-life blood pressure is associated with increased cardiovascular risk but few studies have reported on blood pressure trends among young individuals who are free of CVD and not taking antihypertensive medication. Knowledge of such trends may improve understanding of the causes of hypertension and enhance prevention. We report that declines in blood pressure have been taking place in high-income countries in 5 to 34-year-olds of both sexes and from a range of ethnic groups for at least the last 50 years, indicating that exposures acting in early life are important determinants of blood pressure. Possible explanations for these favourable trends include improvements in early-life diet and there is also intriguing evidence suggesting that blood pressure may be programmed by sodium intake in infancy. Occurring throughout the blood pressure distribution, these trends may have made important contributions to declining CVD rates. There may therefore be scope for intervening in early life to prevent high blood pressure in adulthood, and the downward trends reported in several recent studies suggest that the prevalence of adult hypertension and cardiovascular risk will continue to decline. However, persisting high rates of CVD in the developed world, the impending CVD epidemic in developing countries, along with increasing childhood obesity, and the possibility that favourable blood pressure trends may be plateauing point to the need for enhanced measures to control blood pressure, and for further research to improve understanding of its determinants.     

Biological Versus Chronological Aging: JACC Focus Seminar

Aging is the main risk factor for vascular disease and ensuing cardiovascular and cerebrovascular events, the leading causes of death worldwide. In a progressively aging population, it is essential to develop early-life biomarkers that efficiently identify individuals who are at high risk of developing accelerated vascular damage, with the ultimate goal of improving primary prevention and reducing the health care and socioeconomic impact of age-related cardiovascular disease. Studies in experimental models and humans have identified 9 highly interconnected hallmark processes driving mammalian aging. However, strategies to extend health span and life span require understanding of interindividual differences in age-dependent functional decline, known as biological aging. This review summarizes the current knowledge on biological age biomarkers, factors influencing biological aging, and antiaging interventions, with a focus on vascular aspects of the aging process and its cardiovascular disease related manifestations.     

Epigenetics and Development of Food Allergy (FA) in Early Childhood

This review aims to highlight the latest advance on epigenetics in the development of food allergy (FA) and to offer future perspectives. FA, a condition caused by an immunoglobulin (Ig) E-mediated hypersensitivity reaction to food, has emerged as a major clinical and public health problem worldwide in light of its increasing prevalence, potential fatality, and significant medical and economic impact. Current evidence supports that epigenetic mechanisms are involved in immune regulation and that the epigenome may represent a key “missing piece” of the etiological puzzle for FA. There are a growing number of population-based epigenetic studies on allergy-related phenotypes, mostly focused on DNA methylation. Previous studies mostly applied candidate-gene approaches and have demonstrated that epigenetic marks are associated with multiple allergic diseases and/or with early-life exposures relevant to allergy development (such as early-life smoking exposure, air pollution, farming environment, and dietary fat). Rapid technological advancements have made unbiased genome-wide DNA methylation studies highly feasible, although there are substantial challenge in study design, data analyses, and interpretation of findings. In conclusion, epigenetics represents both an important knowledge gap and a promising research area for FA. Due to the early onset of FA, epigenetic studies of FA in prospective birth cohorts have the potential to better understand gene-environment interactions and underlying biological mechanisms in FA during critical developmental windows (preconception, in utero, and early childhood) and may lead to new paradigms in the diagnosis, prevention, and management of FA and provide novel targets for future drug discovery and therapies for FA.     

UN High-Level Meeting on Non-Communicable Diseases: addressing four questions

Non-communicable diseases (NCDs), principally heart disease, stroke, cancer, diabetes, and chronic respiratory diseases, are a global crisis and require a global response. Despite the threat to human development, and the availability of affordable, cost-effective, and feasible interventions, most countries, development agencies, and foundations neglect the crisis. The UN High-Level Meeting (UN HLM) on NCDs in September, 2011, is an opportunity to stimulate a coordinated global response to NCDs that is commensurate with their health and economic burdens. To achieve the promise of the UN HLM, several questions must be addressed. In this report, we present the realities of the situation by answering four questions: is there really a global crisis of NCDs; how is NCD a development issue; are affordable and cost-effective interventions available; and do we really need high-level leadership and accountability? Action against NCDs will support other global health and development priorities. A successful outcome of the UN HLM depends on the heads of states and governments attending the meeting, and endorsing and implementing the commitments to action. Long-term success requires inspired and committed national and international leadership.     

Progress in National and Regional Guidelines Development and Deployment for the Clinical Prevention and Control of CVD and Diabetes in Africa

Successful efforts to reduce cardiovascular disease in many countries have come as a result of both population based interventions and individually guided interventions. Guidelines serve two purposes directed at the promotion of the individually guided interventions. First, they serve as a method to summarize approved and successful life-style and medical interventions to reduce the burden of cardiovascular disease. Second, they guide health providers on how to identify those at high risk for cardiovascular disease and who might benefit from the available interventions. However, guidelines have been increasingly complex and at times contradictory from one body to another or they may not exist at all in certain countries. This paper will review the current status of guidelines for the region as well as for individual countries. Guidelines for the prevention of CVD as a whole will be evaluated as well as guidelines for individual risk factors such as hypertension, cholesterol, and diabetes. Finally, this paper will address the pitfalls of individual risk factor based guidelines as opposed to the absolute risk approach integrating multiple risk factors into one comprehensive set of guidelines.     

Persistent epigenetic differences associated with prenatal exposure to famine in humans

Extensive epidemiologic studies have suggested that adult disease risk is associated with adverse environmental conditions early in development. Although the mechanisms behind these relationships are unclear, an involvement of epigenetic dysregulation has been hypothesized. Here we show that individuals who were prenatally exposed to famine during the Dutch Hunger Winter in 1944–45 had, 6 decades later, less DNA methylation of the imprinted IGF2 gene compared with their unexposed, same-sex siblings. The association was specific for periconceptional exposure, reinforcing that very early mammalian development is a crucial period for establishing and maintaining epigenetic marks. These data are the first to contribute empirical support for the hypothesis that early-life environmental conditions can cause epigenetic changes in humans that persist throughout life.     

The influence of early-life conditions on cardiovascular disease later in life among ethnic minority populations: a systematic review

Ethnic minority groups are disproportionately affected by cardiovascular diseases (CVDs). The reasons for the high prevalence of CVD in ethnic minority groups are not fully understood. Recently, the importance of early-life developmental factors and their impact on CVDs in adulthood is increasingly being recognised, but little is known about this among ethnic minority groups. Therefore, the current paper aimed to fill this knowledge gap by reviewing the available literature to assess the influence of early-life conditions on CVDs and its risk factors in ethnic minority populations residing in Western countries. A systematic search was performed in PubMed and EMBASE between 1989 and 2014. In total, 1418 studies were identified of which 19 met the inclusion criteria. Six studies investigated the relationship between early-life anthropometrics and CVD risk factors of which all except one found significant associations between the assessed anthropometric measures and CVD risk factors. Seven studies evaluated the influence of childhood socio-economic status (SES) on CVD and risk factors of which five found significant associations between childhood SES measures and CVD risk factors. Five studies investigated the relationship between other early-life conditions including early-life nutrition, physical development, and childhood psychosocial conditions, and CVD risk factors. Four of these studies found significant associations between the assessed childhood conditions and CVD risk factors. This review reinforces the importance of early-life conditions on adult CVD in ethnic minority groups. Improvement of early-life conditions among ethnic minority groups may contribute to reducing CVD risk in these populations.