LITMIR.BIZ

Скачать книгу

to human health and human development. They are chronic conditions that do not result from an acute infectious process. They are noncommunicable diseases (NCDs), they have a prolonged course, they are not cured spontaneously, and a complete cure is rarely achieved. Finally, lifestyle diseases may result from a combination of genetic, physiological, environmental, and behavioral factors. NCDs include cardiovascular diseases (CVDs; e.g., coronary heart disease [CHD] and stroke), cancer, chronic respiratory disease (CRD), type 2 diabetes mellitus, chronic neurologic disorders (e.g., Alzheimer's, dementia), arthritis/musculoskeletal diseases, and unintentional injuries (e.g., from traffic accidents). According to the World Health Organization (WHO), NCDs cause more deaths than all other causes combined, and NCD deaths are projected to increase from 38 million in 2012 to 52 million by 2030. Figure 2.1 shows the proportion of deaths by cause among people who were 70 years and older.

       Key Point

      NCDs cause more deaths than all other causes combined.

Globally, approximately 45% of all NCD deaths occur before the age of 70 years. Figure 2.2 shows the country‐dependent probability of dying from the four main NCDs between the ages of 30 and 70 years.

      In general, NCDs have a multifactorial etiology. Risk factors include certain aspects of lifestyle as well as environmental and genetic determinants. It is well known that genetic predisposition alone cannot explain all the disease risk; lifestyle and environmental factors are also key contributors.

       Key Point

      NCDs have a multifactorial etiology. Risk factors include certain aspects of lifestyle as well as environmental and genetic determinants.

Genetic Background and NCD Development

      Genetic predisposition has been acknowledged to have a significant contribution to the incidence of NCDs. A number of mutations in the coding regions of the human genome have been considered as causative factors for various NCDs. Nonsynonymous nucleotide substitutions result in missense, nonsense, or frameshift changes in protein coding sequence; this may lead to loss‐of‐function or gain‐of‐function in certain proteins that have linked with specific disease phenotypes. However, the vast majority of single‐nucleotide polymorphisms (SNPs) are distributed throughout the human genome, in the noncoding regions. Therefore, it is difficult to establish a causal relationship between the allelic variants originating from SNPs and the disease phenotype.

      The relationship between heritable genetic traits and metabolic morbidity has been accrued through genome‐wide association studies (GWASs), which examine similarities in the entire DNA sequence of different people, as regards specific SNPs, and the presence of certain diseases across this population. Data from GWASs have shown that SNPs are preferentially concentrated in functional genomic regions, namely enhancer elements, DNase hypersensitivity regions, and epigenetically important chromatin markers, playing a crucial role in the development of a variety of diseases, including cancer, stroke, and cerebrovascular diseases. Moreover, the epigenetic modifications in the form of DNA methylation lay among the most critical processes that could change gene expression, while at the same time leaving intact the nucleotide sequence (please refer to Chapter 3 for more information about the epigenetic mechanism).

FIGURE 2.1 Results of the Global Burden of Disease Collaborative Network, Global Burden of Disease Study 2017. Institute for Health Metrics and Evaluation (IHME) (2018).

FIGURE 2.2 Probability of dying from the four main noncommunicable diseases between the ages of 30 and 70 years, comparable estimates, 2012.

      Source: Reprinted with permission from WHO Library Cataloguing‐in‐Publication Data Global Status Report on Noncommunicable Diseases, 2014 ed.

Diet, physical activity, sleep patterns, and stress have been shown to significantly affect the development of many NCDs. These factors can influence pathogenetic pathways and even gene expression, and therefore may positively or negatively affect the development of a disease. In the following paragraphs, we are presenting the epidemiology of the most important NCDs and the effect of the modern lifestyle. The protective role of several other lifestyle aspects in NCDs will be presented in Unit III.

Obesity: Epidemiology and Impact of Modern Lifestyle

The prevalence of obesity has nearly doubled since 1980. More than 39 million children under the age of 5 were overweight or obese in 2020; 13% of adults in the world were obese in 2020, whereas 39% were overweight. The prevalence of obesity varies significantly between countries (Figure 2.3.).

This “globesity” phenomenon may have contributed to the rise in the global incidence of major NCDs. Obesity often leads to adverse effects on blood pressure (BP), cholesterol, triacylglycerols (TAGs), and insulin resistance (IR). The risk of CHD, ischemic stroke, and type 2 diabetes mellitus (T2DM) increases steadily with increasing body mass index (BMI). Overweight and obesity have also been associated with several types of cancer – namely, breast, colon, prostate, endometrium, kidney, and gall bladder cancer. Furthermore, overall mortality rates seem to be higher among severely obese individuals compared to the general population.

FIGURE 2.3 Age‐standardized prevalence of underweight, obesity, and severe obesity by sex and country in 2014. Underweight (BMI < 18.5 kg/m²); obesity (BMI ≥ 30 kg/m²); and severe obesity (BMI ≥ 35 kg/m²).

      Source: NCD Risk Factor Collaboration (2016).

       Key Point

      The “globesity” phenomenon may have contributed to the rise in the global incidence of major NCDs.

      The genetic background plays a crucial role in the development of obesity and obesity‐associated comorbidities. However, genes cannot be changed. Among several modifiable risk factors, physical inactivity, unhealthy diet, sleep deprivation, and chronic stress overload are the main contributors of overweight and obesity. These lifestyle behaviors not only acutely affect weight status but may also cause epigenetic modifications; i.e., these habits hold the potential to affect the expression of certain genes in the long term, which, in turn, can influence the predisposition to some chronic diseases.

      Obesity is the consequence of a long‐term energy imbalance, whereby energy intake is higher than energy expenditure. A dramatic change in the way people consume food, ingest drinks, and move has been recorded during the past decades. A significant increase in the consumption of energy‐dense foods and simple sugars has been recorded worldwide. At the same time physical activity has decreased, due to the sedentary character of the working environment, changes in transportation,

Скачать книгу