Childhood obesity, a ticking time bomb for cardiometabolic diseases

Childhood obesity, a ticking time bomb for cardiometabolic diseases

OVERVIEW

  • Obesity rates among Canadian children and teens have more than tripled over the past 40 years.
  • Childhood obesity is associated with a marked increase in the risk of type 2 diabetes and cardiovascular disease in adulthood, which can significantly reduce healthy life expectancy.
  • Policies to improve the diet of young people are key to reversing this trend and preventing an epidemic ofcardiometabolic diseases affecting young adults in the coming years.

One of the most dramatic changes to have occurred in recent years is undoubtedly the marked increase in the number of overweight children. For example, obesity rates among Canadian children and adolescents have more than tripled over the past 40 years. Whereas in 1975, obesity was a fairly rare problem affecting less than 3% of children aged 5–19, the prevalence of obesity has made a gigantic leap since that time, affecting nearly 14% of boys and 10% of girls in 2016 (Figure 1). If data on overweight is added to these figures, then approximately 25% of young Canadians are overweight (a similar trend is observed in Quebec). This prevalence of obesity appears to have plateaued in recent years, but recent US surveys suggest that the COVID-19 pandemic may have caused an upsurge in the number of overweight young people, particularly among 5-11-year-olds.

Figure 1. Increase in the prevalence of obesity among Canadian children over the past 40 years. From NCD Risk Factor Collaboration (2017).

Measuring childhood obesity
Although not perfect, the most common measure used to determine the presence of overweight in young people under the age of 19 is the body mass index (BMI), calculated by dividing the weight by the square of height (kg/m²). However, the values obtained must be adjusted according to age and sex to take into account changes in body composition during growth, as shown in Figure 2.

Figure 2. WHO growth standards for boys aged 5–19 living in Canada. Data comes from WHO (2007).

Note that a wide range of BMI on either side of the median (50th percentile) is considered normal. Overweight children have a BMI higher than that of 85–95% of the population of the same age (85th-95th percentile), while the BMI of obese children is higher than that of 97% of the population of the same age (97th percentile and above). Using z-scores is another way to visualize childhood overweight and obesity. This measurement expresses the deviation of the BMI from the mean value, in standard deviation. For example, a z-score of 1 means that the BMI is one standard deviation above normal (corresponding to overweight), while z-scores of 2 and 3 indicate, respectively, the presence of obesity and severe obesity.

This marked increase in the proportion of overweight children, and particularly obese children, is a worrying trend that bodes very badly for the health of future generations of adults. On the one hand, it is well established that obesity during childhood (and especially during adolescence) represents a very high risk factor for obesity in adulthood, with more than 80% of obese adults who were already obese during their childhood. This obesity in adulthood is associated with an increased risk of a host of health problems, both from a cardiovascular point of view (hypertension, dyslipidemia, ischemic diseases) and the development of metabolic abnormalities (hyperglycemia, resistance to insulin, type 2 diabetes) and certain types of cancer. Obesity can also cause discrimination and social stigma and therefore have devastating consequences on the quality of life, both physically and mentally.

Another very damaging aspect of childhood obesity, which is rarely mentioned, is the dramatic acceleration of the development of all the diseases associated with overweight. In other words, obese children are not only at higher risk of suffering from the various pathologies caused by obesity in adulthood, but these diseases can also affect them at an early age, sometimes even before reaching adulthood, and thus considerably reduce their healthy life expectancy. These early impacts of childhood obesity on the development of diseases associated with overweight are well illustrated by the results of several recent studies on type 2 diabetes and cardiovascular disease.

Early diabetes
Traditionally, type 2 diabetes was an extremely rare disease among young people (it was even called “adult diabetes” at one time), but its incidence has increased dramatically with the rise in the proportion of obese young people. For example, recent US statistics show that the prevalence of type 2 diabetes in children aged 10–19 has increased from 0.34 per 1000 children in 2001 to 0.67 in 2017, an increase of almost 100% since the beginning of the millennium.

The main risk factors for early diabetes are obesity, especially severe obesity (BMI greater than 35) or when the excess fat is mainly located in the abdomen, a family history of the disease, and belonging to certain ethnic groups. However, obesity remains the main risk factor for type 2 diabetes: in obese children (4–10 years) and adolescents (11–18 years), glucose intolerance is frequently observed during induced hyperglycemia tests, a phenomenon caused by the early development of insulin resistance. A characteristic of type 2 diabetes in young people is its rapid development. Whereas in adults, the transition from a prediabetic state to clearly defined diabetes is generally a gradual process, occurring over a period of 5–10 years, this transition can occur very quickly in young people, in less than 2 years. This means that the disease is much more aggressive in young people than in older people and can cause the early onset of various complications, particularly at the cardiovascular level.

A recent study, published in the prestigious New England Journal of Medicine, clearly illustrates the dangers that arise from early-onset type 2 diabetes, appearing during childhood or adolescence. In this study, the researchers recruited extremely obese children (BMI ≥ 35) who had been diagnosed with type 2 diabetes in adolescence and subsequently examined for ten years the evolution of different risk factors and pathologies associated with this disease.

The results are very worrying, because the vast majority of patients in the study developed one or more complications during follow-up that significantly increased their risk of developing serious health problems (Figure 3). Of particular note is the high incidence of hypertension, dyslipidemia (LDL-cholesterol and triglyceride levels too high), and kidney (nephropathies) and nerve damage (neuropathies) in this population, which, it should be remembered, is only 26 years on average. Worse still, almost a third of these young adults had 2 or more complications, which obviously increases the risk of deterioration of their health even more. Moreover, it should be noted that 17 serious cardiovascular accidents (infarction, heart failure, stroke) occurred during the follow-up period, which is abnormally high given the young age of the patients and the relatively small number of people who participated in the study (500 patients).

Figure 3. Incidence of different complications associated with type 2 diabetes in adolescents. From TODAY Study Group (2021).

It should also be noted that these complications occurred despite the fact that the majority of these patients were treated with antidiabetic drugs such as metformin or insulin. This is consistent with several studies showing that type 2 diabetes is much harder to control in young people than in middle-aged people. The mechanisms responsible for this difference are still poorly understood, but it seems that the development of insulin resistance and the deterioration of the pancreatic cells that produce this hormone progress much faster in young people than in older people, which complicates blood sugar control and increases the risk of complications.

This difficulty in effectively treating early type 2 diabetes means that young diabetics are much more at risk of dying prematurely than non-diabetics (Figure 4). For example, young people who develop early diabetes, before the age of 30, have a mortality rate 3 times higher than the population of the same age who is not diabetic. This increase remains significant, although less pronounced, until about age 50, while cases of diabetes that appear at older ages (60 years and over) do not have a major impact on mortality compared to the general population. It should be noted that this increase in mortality affecting the youngest diabetics is particularly pronounced at a young age, around 40 years of age.

These results therefore show how early type 2 diabetes can lead to a rapid deterioration in health and take decades off life, including years that are often considered the most productive of life (forties and fifties). For all these reasons, type 2 diabetes must be considered one of the main collateral damages of childhood obesity.

Figure 4. Age-standardized mortality rates for diagnosis of type 2 diabetes. Standardized mortality rates represent the ratio of mortality observed in individuals with diabetes to anticipated mortality for each age group. From Al-Saeed et al. (2016).

Cardiovascular disease
In recent years, there has been an upsurge in the incidence of cardiovascular disease in young adults. This new trend is surprising given that mortality from cardiovascular diseases has been in constant decline for several years in the general population (thanks in particular to a reduction in the number of smokers and improved treatments), and one might have expected that young people would also benefit from these positive developments.

The data collected so far strongly suggests that the increase in the prevalence of obesity among young people contributes to this upsurge of premature cardiovascular diseases, before the age of 55. On the one hand, it has been shown that a genetic predisposition to develop overweight during childhood is associated with an increased risk of coronary heart disease (and type 2 diabetes) in adulthood. On the other hand, this increased risk has also been observed in long-term studies examining the association between the weight of individuals during childhood and the incidence of cardiovascular events once they have reached adulthood. For example, a large Danish study of over 275,000 school-aged children (7–13 years old) showed that each one-unit increase in BMI z-score at these ages (see legend to Figure 2 for the definition of the z-score) was associated with an increased risk of cardiovascular disease in adulthood, after 25 years (Figure 5).

This increased risk is directly proportional to the age at which children are overweight, i.e., the more a high BMI is present at older ages, the greater the risk of suffering a cardiovascular event later in adulthood. For example, an increase of 1 in the z -score of 13-year-old children is associated with twice as much of an increase in risk in adulthood as a similar increase in a 7-year-old child (Figure 5). Similar results are observed for girls, but the increased risk of cardiovascular disease is lower than for boys.


Figure 5. Relationship between body mass index in childhood and the risk of cardiovascular disease in adulthood. The values represent the risks associated with a 1-unit increase in BMI z-score at each age. From Baker et al. (2007).

Early atherosclerosis
Several studies suggest that the increased risk of cardiovascular disease in adulthood observed in overweight children is a consequence of the early development of several risk factors that accelerate the process of atherosclerosis. Autopsy studies of obese adolescents who died of non-cardiovascular causes (e.g., accidents) revealed that fibrous atherosclerotic plaques were already present in the aorta and coronary arteries, indicating an abnormally rapid progression of atherosclerosis.

As mentioned earlier, type 2 diabetes is certainly the worst risk factor that can generate this premature progression, because the vast majority of diabetic children and adolescents very quickly develop several abnormalities that considerably increase the risk of serious damage to blood vessels (Figure 3). But even without the presence of early diabetes, studies show that several risk factors for cardiovascular disease are already present in overweight children, such as hypertension, dyslipidemia, chronic inflammation, glucose intolerance or even vascular abnormalities (thickening of the internal wall of the carotid artery, for example). Exposure to these factors that begins in childhood therefore creates favourable conditions for the premature development of atherosclerosis, thereby increasing the risk of cardiovascular events in adulthood.

It should be noted, however, that the negative impact of childhood obesity on health in adulthood is not irreversible. Indeed, studies show that people who were overweight or obese during childhood, but who had a normal weight in adulthood, have a risk of cardiovascular disease similar to that of people who have been thin all their lives. However, obesity is extremely difficult to treat, both in childhood and in adulthood, and the best way to avoid prolonged chronic exposure to excess fat and damage to cardiovascular health (and health in general) which results from it is obviously to prevent the problem at the source by modifying lifestyle factors, which are closely associated with an increased risk of developing overweight, in particular the nature of the diet and physical activity (psychosocial stress may also play a role). Given the catastrophic effects of childhood obesity on health, cardiovascular health in particular, the potential for this early preventive approach (called “primordial prevention”) is immense and could help halt the current rise in diabetes and premature mortality affecting young adults.

Ideal cardiovascular health
A recent study shows how this primordial prevention approach can have an extraordinary impact on cardiovascular health. In this study, researchers determined the ideal cardiovascular health score, as defined by the American Heart Association (Table 1), of more than 3 million South Koreans with an average age of 20–39 years. Excess weight is a very important element of this score because of its influence on other risk factors also used in the score such as hypertension, fasting hyperglycemia and cholesterol.

Participants were followed for a period of approximately 16 years, and the incidence of premature cardiovascular disease (before age 55) was assessed using as the primary endpoint a combination of hospitalization for infarction, stroke, cardiac insufficiency, or sudden cardiac death.

Table 1. Parameters used to define the ideal cardiovascular health score. Since there is 1 point for each target reached, a score of 6 reflects optimal cardiovascular health. Adapted from Lloyd-Jones et al. (2010), excluding dietary factors that were not assessed in the Korean study.

As shown in Figure 6, cardiovascular health in early adulthood has a decisive influence on the risk of cardiovascular events that occur prematurely, before the age of 55. Compared to participants in very poor cardiovascular health at the start (score of 0), each additional target reached reduces the risk of cardiovascular events, with maximum protection of approximately 85% in people whose lifestyle allows achieving 5 or more ideal heart health targets (scores of 5 and 6). Similar results were obtained in the United States and show how early health, from childhood through young adulthood, plays a key role in preventing the development of cardiovascular disease during aging.

Figure 6. Influence of cardiovascular health in young adults on the risk of premature cardiovascular events. From Lee et al. (2021).

Yet our society remains strangely passive in the face of the rise in childhood obesity, as if the increase in body weight of children and adolescents has become the norm and that nothing can be done to reverse this trend. This lack of interest is really difficult to understand, because the current situation is a ticking time bomb that risks causing a tsunami of premature chronic diseases in the near future, affecting young adults. This is an extremely worrying scenario if we consider that our healthcare system, in addition to having to contend with diseases that affect an aging population (1 out of 4 Quebecers will be over 65 in 2030), will also have to deal with younger patients suffering from cardiometabolic diseases caused by overweight. Needless to say, this will be a significant burden on healthcare systems.

This situation is not inevitable, however, as governments have concrete legislative means that can be used to try to reverse this trend. Several policies aimed at improving diet quality to prevent disease can be quickly implemented:

  • Taxing sugary drinks. A simple and straightforward approach that has been adopted by several countries is to introduce a tax on industrial food products, especially soft drinks. The principle is the same as for all taxes affecting other products harmful to health such as alcohol and tobacco, i.e., an increase in prices is generally associated with a reduction in consumption. Studies that have examined the impact of this approach for soft drinks indicate that this is indeed the case, with reductions in consumption observed (among others) in Mexico, Berkeley (California) and Barbados. This approach therefore represents a promising tool, especially if the amounts collected are reinvested in order to improve the diet of the population (subsidies for the purchase of fruit and vegetables, for example).
  • Requiring clear nutrition labels on packaging. We can help consumers make informed choices by clearly indicating on the front of the product whether it is high in sugar, fat or salt, as is the case in Chile (see our article on this subject).
  • Eliminating the marketing of unhealthy foods for children. The example of Chile also shows that severe restrictions can be imposed on the marketing of junk food products by prohibiting the advertising of these products in programs or websites aimed at young people as well as by prohibiting their sale in schools. The United Kingdom plans to take such an approach very soon by eliminating all advertising online and on television of products high in sugar, salt and fat before 9 p.m., while Mexico has gone even further by banning all sales of junk food products to children.

There is no reason Canada should not adopt such approaches to protect the health of young people.

Effectiveness of exercise to prevent and mitigate diabetes: An important role of the gut microbiota

Effectiveness of exercise to prevent and mitigate diabetes: An important role of the gut microbiota

OVERVIEW

  • In overweight, prediabetic and sedentary men, exercise induced changes in the gut microbiota that are correlated with improvements in blood sugar control and insulin sensitivity.
  • The microbiota of the participants who are “responders” to exercise had a greater ability to produce short chain fatty acids (SCFAs) and to eliminate branched-chain amino acids (BCAAs). Conversely, the microbiota of non-responders was characterized by an increased production of metabolically harmful compounds.
  • Transplantation of the fecal microbiota of responders into obese mice produced roughly the same beneficial effects of exercise on insulin resistance. Such effects were not observed after transplanting the microbiota of non-responders.
Regular exercise has beneficial effects on blood glucose control and insulin sensitivity, and is therefore an interesting strategy to prevent and mitigate type 2 diabetes. Unfortunately, in some people, exercise does not cause a favourable metabolic response, a phenomenon called “exercise resistance”. The causes of this phenomenon have not been clearly established, although some researchers have suggested that genetic predispositions and epigenetic changes may contribute to this.

A growing body of data indicates that an imbalance in the gut microbiota (dysbiosis) plays an important role in the development of insulin resistance and type 2 diabetes. Several different mechanisms are involved, including an increase in intestinal permeability and increased endotoxemia, changes in the production of certain short chain fatty acids and branched-chain amino acids, and disturbances in bile acid metabolism. Changes in the composition and function of the gut microbiota have been observed in people with type 2 diabetes and prediabetics. One study also showed that transplanting a healthy person’s microbiota into the intestines of people with metabolic syndrome results in increased microbial diversity and improved blood sugar control as well as sensitivity to insulin.

The intestinal microbiota (formerly intestinal flora) is a complex ecosystem of bacteria, archaea (small microorganisms without nuclei), eukaryotic microorganisms (fungi, protists) and viruses, which has evolved with human beings for several thousands of years. A human gut microbiota, which can weigh up to 2 kg, is absolutely necessary for digestion, metabolic function, and resistance to infection. The human gut microbiota has an enormous metabolic capacity, with more than 1,000 different species of bacteria and 3 million unique genes (the microbiome).

Recent data indicate that exercise modulates the gut microbiota in humans as well as in other species of animals. For example, it has been found that the gut microbiota of professional athletes is more diverse and has a healthier metabolic capacity than the microbiota of sedentary people. However, it is still unclear how these exercise-induced changes in the microbiota are involved in the metabolic benefits (see figure below).

Figure. Changes in the gut microbiota and intestinal epithelium through exercise and health benefits. BDNF: Brain-derived neurotrophic factor (growth factor). From: Mailing et al., 2019.

A study published in Cell Metabolism tried to answer this question by performing an intervention in overweight, prediabetic and sedentary men. Study participants were randomly assigned to a control group (sedentary) or to a 12-week supervised training program. Blood and fecal samples were collected before and after the procedure. After the 12 weeks, modest but significant weight loss and fat loss were observed in people who exercised, with improvements in several metabolic parameters, such as insulin sensitivity, favourable lipid profiles, improved cardiorespiratory capacity and levels of adipokines (signalling molecules secreted by adipose tissues) which are functionally associated with insulin sensitivity. The researchers observed that there was a high interpersonal variability in the results. After classifying the participants as “non-responders” and “responders”, according to their insulin sensitivity score, the researchers analyzed the composition of each participant’s microbiota.

Among responders, exercise altered the concentration of more than 6 species of bacteria belonging to the genera Firmicutes, Bacteroidetes, and Probacteria. Among these bacteria, those belonging to the genus Bacteroidetes are involved in the metabolism of short chain fatty acids (SCFAs). Among the most striking differences between the microbiota of responders and non-responders, the researchers noted a 3.5-fold increase in the number of Lanchospiraceae bacterium, a butyrate producer (a SCFA), which is an indicator of intestinal health. The bacterium Alistipes shahii, which has already been associated with inflammation and is present in higher amounts in obese people, decreased by 43% in responders, while it increased 3.88 times in non-responders. The Prevotella copri bacteria proliferated at a reduced rate in the responders; it is one of the main bacteria responsible for the production of branched-chain amino acids (BCAAs) in the gut and contributes to insulin resistance.

The researchers then transplanted the fecal microbiota of responders and non-responders into obese mice. The fecal microbiota transplantation (FMT) of the responders had the effect in mice of reducing blood sugar and insulin as well as improving insulin sensitivity, while such favourable effects were not observed in mice that received a FMT from non-responders.

Mice saw their blood levels of SCFAs increase significantly, while the levels of BCAAs (leucine, isoleucine, valine) and aromatic amino acids (phenylalanine, tryptophan) decreased after receiving the microbiota from responders. In contrast, mice that received the microbiota from non-responders saw opposite changes in the levels of these same metabolites. BCAA supplementation attenuated the beneficial effects of FMT from responders on blood sugar regulation and insulin sensitivity, while SCFA supplementation in mice that received the microbiota of non-responders partially corrected the defect in blood glucose regulation and insulin sensitivity.

Taken together, these results suggest that the gut microbiota and its metabolites are involved in the beneficial metabolic effects caused by exercise. In addition, this study indicates that poor adaptation of the gut microbiota is partly responsible for the lack of a favourable metabolic response in people who do not respond to exercise.

Health risks of a sedentary lifestyle

Health risks of a sedentary lifestyle

Physical inactivity and unhealthy eating have become major public health issues since, combined, these two poor lifestyle habits are the second leading cause of death after smoking in the United States. Physical inactivity is also associated with an increased risk of developing or worsening chronic diseases such as heart failure, cardiovascular disease, stroke, type 2 diabetes, hypertension, some cancers, and osteoporosis. In Canada, 76% of adult men and 79% of adult women do not perform the minimum physical activity recommended by the World Health Organization, i.e., 150 minutes/week, and Canadian adults spend an average of 9 hours 48 minutes of their waking hours doing sedentary activities. Recent research on physical activity suggests that it is no longer sufficient to follow the minimal recommendations of public health agencies to minimize the risk of cardiovascular disease. Physical inactivity and sedentary behaviour each have their own health effects that need to be addressed separately to better understand their distinct mechanisms.

According to a systematic review and meta-analysis of 16 prospective studies and 2 cross-sectional studies of 794,577 participants, highly sedentary people are 112% more likely to have diabetes than those who are not sedentary, and they have a 147% higher risk of cardiovascular events, a 90% higher risk of mortality from cardiovascular disease, and a 49% higher risk of all-cause mortality. Another study on sedentary behaviours (driving and watching television) was conducted in the United States from 1989 to 2003 among 7,744 men aged 20 to 89 who had no history of cardiovascular disease. Participants who reported driving more than 10 hours/week or engaging in two sedentary behaviours (driving and watching television) more than 23 hours/week had an 82% and 64% higher risk of dying from cardiovascular disease than those who reported driving less than 4 h/week or driving and watching TV less than 11 h/week, respectively. Participants who were physically active at work and in their leisure time, but were otherwise sedentary, were less at risk of dying from cardiovascular disease than those who were both sedentary and physically inactive. Moreover, having a normal blood pressure, a healthy weight, and being older were associated with a lower risk of cardiovascular death.

“Physical activity” has been defined as any body movement produced by skeletal muscles that requires energy expenditure, and “exercise” as a subcategory of physical activity. Exercise involves structured and repeated behaviour in order to maintain or improve physical fitness. One method to more accurately estimate the intensity of physical activity is to use the Metabolic Equivalent of Task (MET) method. A MET unit is the energy spent at rest. Physical activity can be considered low intensity (<3 METs), moderate intensity (3-6 METs), and high intensity (>6 METs). Defining what is “sedentary behaviour” or “physical inactivity” is more difficult, and not everyone agrees on a definition. The objective measurement of physical activity, using an accelerometer-type physical activity monitor, for example, makes it possible to better assess sedentary behaviours than with the data obtained by questionnaires. Accelerometry allows researchers to record daily the time participants devote to activities at all levels of intensity: sedentary, light, moderate and high. To illustrate the usefulness of this technique, Pate et al. present the cases of two people who have very different activity profiles. Subject A could be considered a sedentary person in several studies since they do not engage in moderate or intense physical activity for at least 30 minutes a day. However, if the analysis of the accelerometer data shows that the subject was sedentary for 25% of the day, they were doing low intensity activities for about 75% of that day. Subject B could be considered as an active person in most studies, as they engage in medium-high intensity physical activity during the day for 1 hour. The accelerometer data, however, show that subject B spends most of the day (70%) in sedentary life (sitting on a chair, for example) or engaging in low-intensity physical activity (23%). In total, subject A, considered “inactive” according to conventional criteria, expended more energy (26.3 METs) than subject B, considered “active” (23.6 METs).

A study of the sedentary behaviours of Americans aged 45 and over showed that a large proportion of total sedentary time is accumulated over long, uninterrupted periods. Participants in this study spent an average of more than 11 hours of their day being sedentary and almost half of this sedentary time was accumulated over periods of 30 minutes or more. Sedentary periods of more than 20, 30, 60 and 90 minutes accounted for 60%, 48%, 26% and 14% of total sedentary time, respectively. Several factors, including older age, male gender, obesity, winter, and low levels of physical activity, were associated with prolonged sedentary behaviours. Laboratory studies have shown that long periods of uninterrupted sedentary behaviours have cardiometabolic effects, suggesting that it is not only the total sedentary time that is important for the risk of cardiovascular disease but also how this time is accumulated.

Data from an epidemiological study seem to confirm this hypothesis since adults whose sedentary behaviour extended over long uninterrupted periods had a less favourable cardiometabolic profile (larger waist circumference, lower HDL cholesterol level, and other markers) compared to that of people who interrupt their periods of inactivity, regardless of the total duration of sedentary time. A recent study of 7,985 people aged 45 or older indicates that the risk of mortality increases not only with the number of hours of sedentary life but also with the duration of each of the uninterrupted sedentary periods. People who were both very sedentary (≥12.5 hours per day) and for long uninterrupted periods (≥10 min/period) had the highest risk of death.

Spending long periods of time sitting is very common in modern societies, and this will only increase with future technological and social innovations. In addition to promoting regular physical exercise, public health organizations will likely also need to include a reduction in sedentary time in their guidelines and emphasize the importance of taking “active” breaks. It is important to note that taking breaks does not necessarily mean exercising, but may include walking for a minute, getting a glass of water, or doing light housework for those working at home. It’s as simple as that!