Dr.Donal O'Gorman

Metabolic Research Unit
St. James's Hospital
Dublin

'Obesity, type II diabetes and cardiovascular disease risk in children and adolescence'

Donal O Gorman, MSc, PE graduate of the University of Limerick, completed a Master degree in Penn State University with Dr John Kirwan.
Donal is currently completing his Ph.D degree at Trinity college Dublin. He is completing his research at St James hospital, Dublin investigating the impact of exercise on Diabetic patients.

Those of us interested in metabolism are very aware of an increase in prevalence and a decrease in the onset age of some of out most common diseases. Though we do not have substantive data in Ireland, we know from other countries that the incidence of obesity has increased dramatically in the past decade. Obesity is a co-morbidity of Type 2 diabetes, cardiovascular disease and hypertension, leading it to be a major target for our future health management. The focus of today's presentation is on the incidence, risk and prevention of obesity, Type 2 diabetes and cardiovascular disease in children and adolescents.

Obesity

Adult obesity

Obesity is defined in terms of body composition, the amount of body fat relative to lean body mass, and clinically by the body mass index (BMI), which is the relationship between body mass and body height (kg/m2). The clinical classification of health and disease weight is outlined in Table 1.

Table 1. Body Mass Index (BMI) classification of health and disease

BMI (kg/m2)
Underweight < 18.5
Normal 18.5-24.9
Overweight 25.0-29.9
Obese ›30

Over the past 16 years detailed obesity data has been collected in the United States. In 1990, 4 states had an obesity prevalence of 15-19%, 33 states between 10-14%, 8 states were less than 10%, with no data on the remaining (10). Throughout the 1990's there was an increase in obesity prevalence from 12.0% to 19.8%. By the year 2000, 22 states had obesity rates greater than 20%, 27 between 15-19% with only Colorado in the 10-14% category (9). This dramatic change in obesity prevalence has serious implications for the health of the population and the incidence of related diseases.

Data on European countries is not as comprehensive but the International Obesity Task Force (IOTF) shows that four out of twenty countries surveyed had obesity rates greater than 20%. Interestingly, the higher obesity rates were present in countries with poor economies such as Yugoslavia, Hungary and the Czech Republic while countries like France and Germany had relatively low rates of obesity. This indicates an inverse relationship between obesity and economic status in Europe. The only available data in Ireland was recently complied by the North/South Food Consumption Survey (7). A total of 1379 adults between 18-64 years were examined. A total of 42% had normal BMI, 39% were overweight and 18% were obese. In 1990 the prevalence of obesity was 11%, a 67% increase in the intervening years. These data, if verified on a larger sample of the population, would make Ireland one of the most obese countries in Europe. The trend and prevalence is more reflective of changes in the United States, rather than Europe, because of the parallel increase in economic prosperity. This study also found that while television viewing accounted for 19.1 hr/week and 18.3 hr/week for males and females, respectively, vigorous exercise only accounted for 1.7 hr/week and 1.0 hr/week for males and females.

Childhood Obesity

Devising a classification or definition of obesity in children and adolescents is more difficult because of different rates of maturational and physiological development. In the United States children above the 95th percentile are deemed overweight while those greater than the 97th percentile are classified obese. These data are specific to the United States and cannot reliably be used in Ireland. A recent paper published in the British Medical Journal has compiled childhood obesity data from a number of countries around the world and devised an age dependent classification for obesity (3,free on-line www.bmj.com). While a BMI of 25 kg/m2 is considered normal for an adult, a 7-year old male should have a BMI of 17.92 kg/m2 while a 12-year old female should be 21.68 kg/m2. Similarly, an obese adult has a BMI of 30 kg/m2 while an obese 11-year old boy is 25.1 kg/m2 and a 15-year old girl is 29.11 kg/m2. These are the best available data we have at the moment though the classification of childhood obesity is constantly being revised.

In the United States, 10.1% of 6-11 year old non-Hispanic white boys are obese while the incidence was 11.1% for boys aged 12-17 years. Similar data are available for girls with 9.2% of 6-11 year olds and 8.6% of 12-17 year olds obese. Once again data on European countries is not as comprehensive but the IOTF have shown that greater than 30% of 10 year old boys in Malta, Germany, Italy, and Hungary are overweight or obese.

Factors contributing to Obesity

Though the total number of calories consumed per person is not thought to have increased over the past 50 years, and may even have declined slightly, dietary habits have changed. In the United States 38% of meals are prepared outside the home, 13% of schools have contracts with fast food establishments and 31% of 15 year olds eat chips every day. Total energy intake may not have changed but the composition of our diet has changed with a greater proportion coming from fat, especially saturated fat sources.

The second major contributing factor is physical activity. A recent study conducted in St. Patrick's College Drumcondra (1) on 1700 children in 5th class revealed that 45% travel to school by car, though one-third live within 1-km of the school. Activity patterns of parents were poor with 44% of mother and 29% of fathers hardly ever or never exercise. However, physical education was the favourite of 81% of boys and 63% of girls, though classes were taught by their own class teacher who received little or no in-service training. Parents and teachers were perceived to be the most important providers of information on health though 61% get dietary information from television. At the time of the study 15% of girls and 10% of boys were on a diet.

Therefore, changes in dietary patterns and primarily decreased physical activity has resulted in an energy balance shift with increasing numbers of children and adults storing an excessive amount of energy in the form of body fat.

Physiological factors associated with obesity

The regulation of body weight, appetite and energy balance is extremely complex and not fully understood. It is thought than the brain, as a central regulator, plays a vital role in stabilising body weight and controlling appetite while energy storage and utilisation are regulated in metabolic tissue such as the liver, skeletal muscle and adipose by endocrine hormones and other metabolic pathways. Chronic overeating can alter the signalling mechanisms controlling appetite and weight control leading to a gradual increase in body weight. Skeletal muscle can also act as a safety valve for excess energy intake by uncoupling energy to produce heat. However, it has been shown that obese individuals have a reduced capacity to 'uncouple' energy and this may also be a key factor contributing to weight gain.

Excess fat is stored in our existing fat cells. Each of us has approximately 75 billion cells that become larger with increased fat storage. The fat cells of a 75 kg male may be 0.2µg/cell, whereas at 103 kg they may be 0.6µg/cell and at 149 kg they would be 0.9 µg/cell. Though fat is distributed throughout the body, abdominal adiposity in particular is associated with an increased health risk and an increased prevalence of Type 2 diabetes. Therefore, increases in fat cell size and specific localisation of fat stores have serious implications for health and associated diseases.

Where does it begin?

The risk of developing obesity can be traced back to the in utero development of the foetus. The maternal diet is obviously important as the developing baby is supplied with the same nutrients. In addition, low birth weight babies are more prone to storing fat and are also at greater risk of developing Type 2 diabetes later in life (4). The early conditioning of the baby is also important. Breast fed babies are less likely to become overweight and are less prone to developing Type 2 diabetes than bottle fed babies (6). Dietary habits and patterns can also be established in early childhood with a greater likelihood this conditioning will be continued into adult life.

There are environmental and genetic reasons why a child may become obese. Though genetic traits cannot be altered, environmental and behavioural factors can. Table 2 outlines the influence of parental obesity on the development of obesity in offspring (13). If a child is not obese, the risk of becoming obese as an adult decreases from 10% at 1-2 years to 5% at 15-17 years. However, if one or more parent is obese the risk decreases from 28% to 14%. Therefore, a lean child with a history of obesity is 2.8 times more likely to become obese themselves as adults. If a child is obese the risk of becoming an obese adult increases from 8% at 1-2 years to 54% at 15-17 years. However, if one or more parent is obese this risk increases from 40% to 73%.

Table 2. Prevalence (%) of progression to adult obesity based on childhood and parent obesity status

Age (years)	Not obese in childhood 0 parent obese =1 parent obese 0 parent obese =1 parent obese	Obese in childhood
1-2 3-5 6-9 10-14 15-17	10------------- 28 8-------------- 23 7 --------------17 8-------------- 15 5 --------------14	8-------------- 40 24 -------------62 37 -------------71 64 -------------79 54------------- 73 Adapted from reference 13

Pharmacological treatment

Though a number of products have been developed to treat obesity, two are currently licensed for use in Ireland. One acts to inhibit the absorption of fat from the gut, reducing fat ingestion, while the other acts to suppress appetite, reducing calorie intake. Though these products produce clinically significant reductions in body weight, there are no products available for the treatment of childhood obesity.

Obesity, Type 2 diabetes and adolescents

Global trends indicate that the prevalence of Type 2 diabetes has increased dramatically in recent years. In 1994, 100 million people worldwide had diabetes, increasing to 160 million in 2000 and projected to rise to 215 million by 2010. Type 2 diabetes is a metabolic disorder associated with high blood glucose because of resistance to the action of insulin, the hormone responsible for glucose uptake into tissues, and secondly because of a decreased insulin response to glucose. However, diabetes is also associated with cardiovascular disease, hypertension, abnormal blood lipids, central obesity and impaired glucose tolerance.

When the insulin sensitivity of a group of people with Type 2 diabetes is compared with a normal control population we can see that for the same insulin level, the Type 2 diabetes patients have a significantly lower rate of glucose clearance from the blood. Interestingly, the first-degree relatives of people with Type 2 diabetes also have a significantly impaired rate of glucose clearance, indicating a genetic predisposition to the development of diabetes (11). When we compare insulin sensitivity to aerobic fitness levels, measured by oxygen consumption, the people with the higher fitness levels have the highest insulin sensitivity, indicating the more exercise a person does the greater the level of insulin sensitivity they will have. Conversely, insulin sensitivity is inversely related to intra-abdominal fat. The greater the amount of abdominal fat the lower the insulin sensitivity. Therefore, the two factors associated with obesity and Type 2 diabetes, dietary patterns and physical activity, are directly associated with insulin resistance.

At St. James's Hospital we have recently begun to see a number of young people with Type 2 diabetes. The onset of this disease is usually associated with people greater than 40 years but there is an increasing prevalence of those diagnosed under the age of 25 years. In particular these patients tend to be very heavy, with a high body fat, blood pressure and blood lipid profile. They typically have a two-to-three generation family history of diabetes and our results indicate that they are extremely insulin resistant. In a comparison with young Mexican-Americans, a group genetically predisposed to develop diabetes, we found the Irish group to be equally as insulin resistant. Similarly, when we compared them to an older group who had a longer duration of diabetes, we found the same results. These younger people are severely insulin resistant and have potentially 40-50 years trying to prevent complications associated with diabetes. Therefore, the cost to the medical service is not just related to diabetes treatment but the increased risk of heart disease, kidney disease, eye disease and foot problems. It is extremely important we work to try and prevent to onset of young Type 2 diabetes, a job that physical education teachers have a very important role to play as primary health care providers.

Cardiovascular disease and children

In 1998 cardiovascular disease and lung cancer accounted for 261,611 deaths or 47% of all cause mortality in the United Kingdom. Cardiovascular disease is also the biggest single cause of death in Ireland and the United States. In addition, 57% of people with Type 2 diabetes die of cardiovascular disease supporting the strong link that exists between these two diseases. As the prevalence of obesity and diabetes is increasing and the onset age is decreasing, our medical service is going to be put under tremendous pressure in the coming years.

Both weight gain during childhood and higher childhood BMI are associated with cardiovascular mortality. In the United States, 10% of 12-19 year olds have elevated cholesterol. Therefore, many of the risk factors for cardiovascular disease are already present in childhood. Another study conducted on 15 year old boys who were accidentally killed revealed many of them already had evidence of macrophage rich lesions, the plaque formation associated with cardiovascular disease (8). We have also seen in our studies that young people with Type 2 diabetes are also hypertensive and have elevated cholesterol, therefore, putting them at much higher risk.

The Bogalusa Heart Study examined 9167 5-17 year old children (5). They found that 11% of the group were overweight or obese. Those overweight children were at much higher risk of having risk factors associated with cardiovascular disease and Type 2 diabetes as can be seen in Table 3. Of the overweight group, 58% had at least one risk factor for cardiovascular disease. If children were classified solely on being overweight, 50% of children with two or more risk factors for cardiovascular disease would have been identified. The Taipei Children Heart Study (2) also provides supporting evidence. They found that while 14% of nonobese boys had high blood pressure, 37.6% of obese boys did, while females were 12.2% and 42.6%, respectively. Similar results are available for fasting blood lipids. Not only does cardiovascular disease manifest itself in childhood but most likely has its origin during this period of life.

Lifestyle intervention and prevention of Type 2 diabetes.

The role of the physical education teacher in the prevention of obesity, Type 2 diabetes and cardiovascular disease cannot be emphasised strongly enough. We have seen that children look to their teachers for information on health and they enjoy physical education classes. The physical education teacher is the professional most qualified and capable of influencing children's health and activity patterns. In the primary prevention of future disease support should be provided to physical education teachers to implement combative strategies.

At St. James's Hospital we have undertaken a research project to study the effects of exercise on people who have Type 2 diabetes. This study is designed to analyse the effect of one bout of exercise, for 1-hour, and 7 consecutive days of exercise on insulin sensitivity. Though the study is on-going I will present two case reports of patients who have completed the study.

Subject A is a 54 year old gentleman with newly diagnosed Type 2 diabetes. He is obese with a BMI of 33 kg/m2 and an elevated waist-to-hip ratio of 0.95. Baseline studies revealed he was quite insulin resistant but after one bout of exercise there was a 63% improvement in insulin sensitivity. This increased a further 39% following 7 days of exercise with an overall increase of 126%. Though this is an exceptionally good response it is clear that exercise, even one bout, has significant benefits on insulin sensitivity in patients with Type 2 diabetes. There is no pharmacological treatment that can achieve these sort of results. Subject B is a 44 year old male with a 3-year history of Type 2 diabetes. He was morbidly obese with a BMI of 42 kg/m2, had a fasting glucose of 15 mmol/l (normal is 5 mmol/l), was on treatment for hypertension and had an elevated blood lipid profile. After the completion of the study this individual continued to exercise 3-4 times a week for 1-hour. In the following 4 months his weight dropped from 115.8 kg to 106.4 kg, his fasting glucose is now in the 5-6 mmol/l range, his fasting lipids are normal and he has recently been taken off his blood pressure medication. Though this person is still obese, he has reduced the risk of disease progression immensely and no longer receives treatment. Therefore, exercise is not only useful in the prevention of disease but is extremely valuable as a treatment modality.

On a broader scale, the US Diabetes Prevention Programme followed 3234 subjects with impaired glucose tolerance, but not diabetes (in press). They were divided into a control group and a lifestyle intervention group. The intervention group were to reduce body weight by 7% through a low fat diet and 150-minutes of exercise per week. Though the control group received information on diet and exercise they did not have the intense lifestyle management of the intervention group. The programme was stopped one year early because of the positive results. While 29% of the control group developed Type 2 diabetes, only 14% of the intervention group did, a 57% risk reduction for the development of diabetes.

Therefore, diet and exercise have extremely positive roles to play in the prevention of metabolic diseases such as obesity and Type 2 diabetes, as well as cardiovascular disease. It is evident that early intervention is crucial and that the physical education teacher is ideally suited and qualified to deal with this positive action policy.

The ACTIVE Study

Finally, from the data presented here today it is obvious that we have very little data available of Irish people. Therefore, it is impossible to accurately gauge the extent of the metabolic problems in this country. However, the little data we have suggests that Ireland may well have a worse metabolic profile than many of our European colleagues.

Therefore, a collaborative, multi-disciplinary team has been established to evaluate the physical fitness and health status of Irish teenage children for the first time. No quantitative or normative data exist by which we can judge our children, their projected health status or risk of disease as they grow and develop. A working group comprising of hospital consultants and academic scientists have designed a protocol to collect data on a large number of Irish children. Because of the positive role of the physical education teacher we would like to also work in conjunction with Physical Education Association of Ireland (PEAI) to answer some of the key questions related to the fitness and health of our adolescent children.

References

1. Broderick, D., Shiel, G. Diet and activity patterns of children in primary schools in Ireland. St. Patricks College Dublin, 2000.

2. Chu, N-F., Rimm, E.B., Wang, D-J., Liou, H-S., and Shieh, S-M. Clustering of cardiovascular disease risk factors among schoolchildren: the Taipei Children heart study. American Journal of Clinical Nutrition 67: 1141-1146, 1998.

3. Cole, T.J., Bellizzi, M.C., Flegal, K.M., and Dietz, W.H. Establishing a standard definition for child overweight and obesity worldwide: international survey. British Journal of Medicine 320: 1-6, 2000.

4. Forsen T, Eriksson J, Tuomilehto J, Reunanen A, Osmond C, Barker D. The fetal and childhood growth of persons who develop type 2 diabetes. Annals of Internal Medicine 133(3):176-82, 2000.

5. Freedman, D.S., Dietz, W.H., Srinivasan, S.R., and Berenson, G.S. The relation of overweight to cardiovascular risk factors among children and adolescents: the Bogalusa heart study. Pediatrics 103(6): 1175-1182, 1999.

6. Gillman MW, Rifas-Shiman SL, Camargo CA Jr, Berkey CS, Frazier AL, Rockett HR, Field AE, Colditz GA. Risk of overweight among adolescents who were breastfed as infants. Journal of the American Medical Association 285(19): 2506-7, 2001.

7. Irish Universities Nutrition Alliance. North/South Ireland Food Consumption Survey. Food Safety Promotion Board, Abbey Court, Dublin 1, 2001.

8. Kortelainen, M-L., and Sarkioja, T. Visceral fat and coronary pathology in male adolescents. International Journal of Obesity 25: 228-232, 2001.

9. Mokdad, A.H., Bowman, B.A., Ford, E.S., Vinicor, F., Marks, J.S., and Koplan, J.P. The continuing epidemics of obesity and diabetes in the United States. Journal of the American Medical Association 286(10): 1195-1200, 2001.

10. Mokdad, A.H., Serdula, M.K., Dietz, W.H., Bowman, B.A., Marks, J.S., and Koplan, J.P. The spread of the obesity epidemic in the United States, 1991-1998. Journal of the American Medical Association 282(16): 1519-1522, 1999.

11. Schalin-Jantti, C., Harkonen, M., and Groop, L. Impaired activation of glycogen synthase in people at increased risk for developing NIDDM. Diabetes 41(5): 598-604, 1992.

12. Troiano, R.P., Flegal, K.M., Kuczmarski, R.J., Campbell, S.M., and Johnson, C.L. Overweight prevalence and trends for children and adolescents: the National Health and Nutrition Examination Surveys. Archives in Paediatric and Adolescent Medicine 149: 1085-1091, 1995.

13. Whitaker, R.C., Wright, J.A., Pepe, M.S., Seidel, K.D., and Dietz, W.H. Predicting obesity in young adulthood from childhood and parental obesity. New England Journal of Medicine 337(13): 869-873, 1997.