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Is reduced metabolic rate associated with obesity?
THE J O U R N A L OF
PEDIATRICS NOVEMBER
Volume 129
1996
Number 5
EDITORIALS Is reduced metabolic rate associated with obesity? The hypothesis that reduced energy expenditure constitutes a risk factor for obesity provides an attractive explanation for increased susceptibility to weight gain. Furthermore, early studies that demonstrated no significant differences in energy intakes among obese and nonobese children and adolescents 1-s supported the hypothesis that energy requirements were reduced among the obese and, by extension, among the preobese. However, new approaches to the measurement of energy expenditure have indicated that the use of self-reported food intake may underestimate energy requirements, especially among obese subjects. The use of water labeled with the stable isotopes of hydrogen and oxygen (2H2180) represents the most powerful of the new technologies. 4 After administration of aH2180, the 2H equilibrates with the hydrogen in body water. The 2H enrichment of body water then declines as body water enriched with 2H is lost as urine, perspiration, and water vapor and is diluted by the ingestion of relatively unenriched water. Because 1SO is in equilibrium with both body water and bicarbonate, the difference in enrichment of body water with 180 and 2H reflects carbon dioxide production. If the respiratory quotient (carbon dioxide production/ oxygen consumption) is known or approximated from dietary intake, energy expenditure can be calculated. Comparison of reported energy intake with energy expenditure measured by doubly labeled water under conditions of weight maintenance demonstrated that energy intake was underreported by adolescents 5 and that dietary intakes Partially supported by National Institutes of Health grants DK/HD 50537, DK 46200, and RR 00088. J Pediatr 1996;129:621-3 Copyright © 1996 by Mosby-Year Book, Inc. 0022-3476/96/$5.00 + 0 9/18/76849
reported by obese subjects were less accurate than those reported by nonobese subjects. Therefore the bias inherent in the use of self-reported food intakes to compare energy requirements among obese and nonobese subjects makes such comparisons less reliable than direct comparisons of energy expenditure. Energy expenditure consists of restiflg energy expenditure, the thermic effects of food, and the energy spent on activity. REE accounts for more than 60% of total daily energy expenditure in adolescence. Fat free mass represents the most significant determinant of resting metabolic rate. Metabolic rate expressed as a function of fat free mass is
See related articles, pp. 637 and 643.
[
REE
Restingenergy expenditure
[
highest in infancy, when the mass of liver, brain, heart, lungs, and kidneys accounts for the greatest proportion of fat free mass. 6 As human beings mature, muscle mass increases as a proportion of fat free mass. Because muscle at rest is not as metabolically active as other organs, REE expressed as a function of fat free mass decreases. Furthermore, because fat free mass exerts such a significant effect on REE, valid comparisons of REE between groups depend on accurate and reliable measures of body composition. Comparisons of obese and nonobese adolescents have shown that total daily energy expenditure and REE of obese adolescents are greater than in their nonobese counterparts. 7 However, because these studies used a cross-sectional design, they did not exclude the possibility that reduced energy expenditure constituted a risk factor for
621
622
Editorials
obesity or that the development of obesity obliterated preexisting differences in either REE or total daily energy expenditure. Lack of differences among obese subjects has led to studies such as those of Morrison et al. and Kaplan et al., published in this issue of The Journal of Pediatrics. Both groups measured resting metabolic rate in black children and white children. Both groups demonstrated that resting metabolic rates in black children were significantly lower than resting metabolic rates among white children. The observed differences of approximately 200 kcal/day observed in preadolescents from the two ethnic groups in both studies increase confidence in the results. Persistence of the ethnic differences in REE after control for fat free mass, bone density, and maturational stage suggests that the differences are not attributable to differences in body composition. Both groups speculate that the lower resting metabolic rates found in black children could account for the increased susceptibility of black adolescent girls to the development of obesity. Several explanations other than an ethnic difference in REE may account for the differences observed in one or both of these studies. These include lack of control for cigarette smoking, prior food intake, or stage of the menstrual cycle. Among adolescents, 28% of white girls, but only 9% of black girls, regularly smoke cigarettes.8 Furthermore, the recent increase in the frequency of smoking among white female adolescents9 may reflect the use of smoking as a mechanism to control body weight or appetite. 1° Because cigarette smoking increases REE, 11 increased smoking by the white girls included in the study by Morrison et al. could have accounted for the differences observed. Morrison et al. also studied their subjects 3 hours after a meal rather than after an overnight fast. Because the thermic effect of a meal is proportional to caloric intake, and because the effects of a meal on metabolic rate may persist for more than 3 hours after the meal, 12' 13 differences in meal size between the two ethnic groups may also have contributed to the differences observed. Finally, because REE may be higher during the luteal phase of the menstrual cycle, 14' 15 failure to control for the stage of the menstrual cycle may have introduced an additional source of error. The latter error would obviously not affect the ethnic differences in resting metabolic rate that the authors observed in the prepubertal girls. Despite these limitations, the possibility remains that reduced resting metabolic rate may increase susceptibility to obesity. Data from adult studies are contradictory. Among already obese Pima Indian adults, a post hoc analysis indicated that metabolic rate was lower at baseline among already obese individuals who gained more than 10 kg dur-
The Journal of Pediatrics November 1996 ing a 2-year period. 16 However, although heredity also affects metabolic ~rate, 17 obesity was no more prevalent among families with low metabolic rates than among families with higher metabolic rates. The effect of reduced metabolic rate has been studied less intensively in children and adolescents. Twenty years ago, Griffiths and Payne 18 compared the metabolic rates and total energy expenditure estimated from heart rate monitors in 8 children of obese and 12 children of nonobese parents. Resting energy and total daily energy expenditures were both significantly lower among children whose parents were obese. Morrison et al. incorrectly asserted that this group was subsequently restudied. 19 However, the study cited by Morrison et al. (Griffiths et al. 19) represents a follow-up study of children of obese parents who had reduced food intakes at baseline2° but who had no significant differences in body composition 12 years later. No follow-up studies of the Griffiths-Payne cohort in which metabolic rate was measured have been published. Whether reduced metabolic rate or alterations in the thermic effects of food or activity constitute risk factors for the subsequent development of obesity must await prospective studies of the effect of these components of energy expenditure on the incidence of obesity. The observation that leptin may increase metabolic rate 21 suggests that careful phenotypic descriptions of obese patients or those at risk of obesity may yet link reductions in one or more components of energy metabolism to genotypes associated with obesity.
William H. Dietz, MD, PhD Professor of Pediatrics Department of Pediatric Gastroenterology and Nutrition New England Medical Center Boston, MA 02111 REFERENCES
1. Bradfield RB, Paulos J, Grossman L. Energy expenditure and heart rate of obese high school girls. Am J Clin Nutr 1971; 24:1482-8. 2. Stefanik PA, Heald FP, Mayer J. Caloric intake in relation to energy output of obese and nonobese adolescent boys. Am J Chn Nutr 1959;7:55-62. 3. Johnson ML, Burke BS, Mayer J. Relative importance of inactivity and overeating in the energy balance of high school girls. Am J Clin Nutr 1956;4:37-44. 4. Schoeller DA, Ravussin E, Schutz Y, Acheson KJ, Boertschi P, Jeqnier E. Energy expenditure by doubly labeled water: validation in humans and proposed calculation. Am J Physiol 1986;250:R823-30. 5. Bandini LB, Schoeller DA, Dietz WH. Validity of reported energy intake in obese and nonobese adolescents. Am J Clin Nutr 1990;52:421-5. 6. Holliday MA. Metabolic rate and organ size during growth
The Journal of Pediatrics Volume 129, Number 5
7.
8.
9.
10.
11.
12.
13.
from infancy to maturity and during late gestation and early infancy. Pediatrics 1971;47:169-78. Bandini LG, Schoeller DA, Dietz WH. Energy expenditure in obese and nonobese adolescents. Pediatr Res 1990;27:198203. Kann L, Warren CW, Harris WA, et al. Youth Risk Behavior Surveillance--United States, 1993. MMWR Morb Mortal Wldy Rep 1995;44(ss-1):1-56. Centers for Disease Control. Trends in smoking initiation among adolescentsand young adults--United States, 1980-89. MMWR Morb Mortal Wkly Rep 1995;44:521-5. Camp DE, Klesges RC, Relyea G. The relationship between body weight concerns and adolescentsmoking.Health Psychol 1993;12:24-32. HofstetterA, Schutz Y, Jequier E, Wahren J. Increased 24-hour energy expenditure in cigarette smokers. N Engl J Med 1986; 314:79-82. Bandini LG, Schoeller DA, Edwards J, Young VR, Oh SH, Dietz WH. Energy expenditure during carbohydrate overfeeding in obese and nonobese adolescents. Am J Physiol 1989; 256:E357-67. SegalKR, Gutin B, Nyman AM, Pi-SunyerFX. Thermic effect of food at rest, during exercise, and after exercise in lean and obese men of similar body weight. J Clin Invest 1985i76:110712.
Editorials
623
14. Ferraro R, Lillioja S, Fontvieille A-M, Rising R, Bogardus C, Ravussin E. Lower sedentary metabolic rate in women compared with men. J Clin Invest 1992;90:780-4. 15. Bisdee JT, James WPT, Shaw MA. Changes in energy expenditure during the menstrual cycle. Br J Nutr 1989;61: 187-99. 16. Ravussin E, Lillioja S, Knowler WC, et al. Reduced rate of energy expenditure as a risk factor for body weight gain. N Engl J Med 1988;318:467-721 17. Bogardus C, Lillioja S, Ravussin E, et al. Familial dependence of the resting metabolic rate. N Engl J Med 1986;315:96100. 18. Griffiths M, Payne PR. Energy expenditure in small children of obese and nonobese parents. Nature 1976;260:698-700. 19. Griffiths M, Payne PR, Stunkard AJ, Rivers JPW, Cox M. Metabolic rate and physical developmentin children at risk of obesity. Lancet 1990;336:76-8. 20. Griffiths M, Rivers JPW, Payne PR. Energy intake in children at high and low risk of obesity. Hum Nutr:Clin Nutr 1987; 41C:425-30. 21. PelleymounterMA, Cullen MJ, Baker MB, et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995;269:540-3.
Assessing prognosis in infants infected with human immunodeficiency virus It is now 15 years since the first cases of acquired irnmunodeficiency syndrome were described in the United States. The World Health Organization estimates that, worldwide, more than 25 million people have been infected with human immunodeficiencyvirus thus far, including about 1.5 million childrenl; the majority of cases have Occurred in developing countries. It is probable that the HIV pandemic has caused the deaths of more than 1 million children worldwide. 2 In the United States since 1982, more than 6900 children with AIDS, aged less than 13 years, have been reported to the Centers for Disease Control and Prevention, constituting some 1% to 2% of the total number of cases (ML Lindegren: personal communication, CDC, 1996). In 1993, HIV infection (AIDS) was the sixth leading cause of death in children aged 1 to 4 years and the seventh leading cause in children aged 5 to 14 years. 3 It is estimated that approximately 6000 to 7000 infants are born to HIV-infected mothers each year in the United States4; assuming a 25% transmission rate, 5 this translates into about 1600 infected J Pediatr 1996;129:623-5 Copyright © 1996 by Mosby-Year Book, Inc. 0022-3476/96/$5.00 + 0 9/18/77053
infants' being born each year. There is some evidence that after publication of the U.S. Public Health Service recommendations in August 1994 on the use of maternal and neonatal zidovudine to reduce perinatal transmission,6 the number of HIV-infected infants being born may be on the decrease in some parts of the United States. 7 In Europe, more than 6000 pediatric AIDS cases were reported until early
See related article, p. 648.
AIDS CDC HIV PCP
Acquiredimmunodeficiencysyndrome Centersfor Disease Controland Prevention Humanimmunodeficiencyvirus Pneumocystiscarinii pneumonia
1996. 8 The largest numbers are from Romania, where most of the children have acquired disease by nosocomial transmission by means of infected needles and blood products.9 In the United Kingdom since 1982, a total of 669 children have been reported as infected with HIV, with about 247 having been reported as having AIDS) ° As in the United States, perinatal transmission accounts for
PEDIATRICS NOVEMBER
Volume 129
1996
Number 5
EDITORIALS Is reduced metabolic rate associated with obesity? The hypothesis that reduced energy expenditure constitutes a risk factor for obesity provides an attractive explanation for increased susceptibility to weight gain. Furthermore, early studies that demonstrated no significant differences in energy intakes among obese and nonobese children and adolescents 1-s supported the hypothesis that energy requirements were reduced among the obese and, by extension, among the preobese. However, new approaches to the measurement of energy expenditure have indicated that the use of self-reported food intake may underestimate energy requirements, especially among obese subjects. The use of water labeled with the stable isotopes of hydrogen and oxygen (2H2180) represents the most powerful of the new technologies. 4 After administration of aH2180, the 2H equilibrates with the hydrogen in body water. The 2H enrichment of body water then declines as body water enriched with 2H is lost as urine, perspiration, and water vapor and is diluted by the ingestion of relatively unenriched water. Because 1SO is in equilibrium with both body water and bicarbonate, the difference in enrichment of body water with 180 and 2H reflects carbon dioxide production. If the respiratory quotient (carbon dioxide production/ oxygen consumption) is known or approximated from dietary intake, energy expenditure can be calculated. Comparison of reported energy intake with energy expenditure measured by doubly labeled water under conditions of weight maintenance demonstrated that energy intake was underreported by adolescents 5 and that dietary intakes Partially supported by National Institutes of Health grants DK/HD 50537, DK 46200, and RR 00088. J Pediatr 1996;129:621-3 Copyright © 1996 by Mosby-Year Book, Inc. 0022-3476/96/$5.00 + 0 9/18/76849
reported by obese subjects were less accurate than those reported by nonobese subjects. Therefore the bias inherent in the use of self-reported food intakes to compare energy requirements among obese and nonobese subjects makes such comparisons less reliable than direct comparisons of energy expenditure. Energy expenditure consists of restiflg energy expenditure, the thermic effects of food, and the energy spent on activity. REE accounts for more than 60% of total daily energy expenditure in adolescence. Fat free mass represents the most significant determinant of resting metabolic rate. Metabolic rate expressed as a function of fat free mass is
See related articles, pp. 637 and 643.
[
REE
Restingenergy expenditure
[
highest in infancy, when the mass of liver, brain, heart, lungs, and kidneys accounts for the greatest proportion of fat free mass. 6 As human beings mature, muscle mass increases as a proportion of fat free mass. Because muscle at rest is not as metabolically active as other organs, REE expressed as a function of fat free mass decreases. Furthermore, because fat free mass exerts such a significant effect on REE, valid comparisons of REE between groups depend on accurate and reliable measures of body composition. Comparisons of obese and nonobese adolescents have shown that total daily energy expenditure and REE of obese adolescents are greater than in their nonobese counterparts. 7 However, because these studies used a cross-sectional design, they did not exclude the possibility that reduced energy expenditure constituted a risk factor for
621
622
Editorials
obesity or that the development of obesity obliterated preexisting differences in either REE or total daily energy expenditure. Lack of differences among obese subjects has led to studies such as those of Morrison et al. and Kaplan et al., published in this issue of The Journal of Pediatrics. Both groups measured resting metabolic rate in black children and white children. Both groups demonstrated that resting metabolic rates in black children were significantly lower than resting metabolic rates among white children. The observed differences of approximately 200 kcal/day observed in preadolescents from the two ethnic groups in both studies increase confidence in the results. Persistence of the ethnic differences in REE after control for fat free mass, bone density, and maturational stage suggests that the differences are not attributable to differences in body composition. Both groups speculate that the lower resting metabolic rates found in black children could account for the increased susceptibility of black adolescent girls to the development of obesity. Several explanations other than an ethnic difference in REE may account for the differences observed in one or both of these studies. These include lack of control for cigarette smoking, prior food intake, or stage of the menstrual cycle. Among adolescents, 28% of white girls, but only 9% of black girls, regularly smoke cigarettes.8 Furthermore, the recent increase in the frequency of smoking among white female adolescents9 may reflect the use of smoking as a mechanism to control body weight or appetite. 1° Because cigarette smoking increases REE, 11 increased smoking by the white girls included in the study by Morrison et al. could have accounted for the differences observed. Morrison et al. also studied their subjects 3 hours after a meal rather than after an overnight fast. Because the thermic effect of a meal is proportional to caloric intake, and because the effects of a meal on metabolic rate may persist for more than 3 hours after the meal, 12' 13 differences in meal size between the two ethnic groups may also have contributed to the differences observed. Finally, because REE may be higher during the luteal phase of the menstrual cycle, 14' 15 failure to control for the stage of the menstrual cycle may have introduced an additional source of error. The latter error would obviously not affect the ethnic differences in resting metabolic rate that the authors observed in the prepubertal girls. Despite these limitations, the possibility remains that reduced resting metabolic rate may increase susceptibility to obesity. Data from adult studies are contradictory. Among already obese Pima Indian adults, a post hoc analysis indicated that metabolic rate was lower at baseline among already obese individuals who gained more than 10 kg dur-
The Journal of Pediatrics November 1996 ing a 2-year period. 16 However, although heredity also affects metabolic ~rate, 17 obesity was no more prevalent among families with low metabolic rates than among families with higher metabolic rates. The effect of reduced metabolic rate has been studied less intensively in children and adolescents. Twenty years ago, Griffiths and Payne 18 compared the metabolic rates and total energy expenditure estimated from heart rate monitors in 8 children of obese and 12 children of nonobese parents. Resting energy and total daily energy expenditures were both significantly lower among children whose parents were obese. Morrison et al. incorrectly asserted that this group was subsequently restudied. 19 However, the study cited by Morrison et al. (Griffiths et al. 19) represents a follow-up study of children of obese parents who had reduced food intakes at baseline2° but who had no significant differences in body composition 12 years later. No follow-up studies of the Griffiths-Payne cohort in which metabolic rate was measured have been published. Whether reduced metabolic rate or alterations in the thermic effects of food or activity constitute risk factors for the subsequent development of obesity must await prospective studies of the effect of these components of energy expenditure on the incidence of obesity. The observation that leptin may increase metabolic rate 21 suggests that careful phenotypic descriptions of obese patients or those at risk of obesity may yet link reductions in one or more components of energy metabolism to genotypes associated with obesity.
William H. Dietz, MD, PhD Professor of Pediatrics Department of Pediatric Gastroenterology and Nutrition New England Medical Center Boston, MA 02111 REFERENCES
1. Bradfield RB, Paulos J, Grossman L. Energy expenditure and heart rate of obese high school girls. Am J Clin Nutr 1971; 24:1482-8. 2. Stefanik PA, Heald FP, Mayer J. Caloric intake in relation to energy output of obese and nonobese adolescent boys. Am J Chn Nutr 1959;7:55-62. 3. Johnson ML, Burke BS, Mayer J. Relative importance of inactivity and overeating in the energy balance of high school girls. Am J Clin Nutr 1956;4:37-44. 4. Schoeller DA, Ravussin E, Schutz Y, Acheson KJ, Boertschi P, Jeqnier E. Energy expenditure by doubly labeled water: validation in humans and proposed calculation. Am J Physiol 1986;250:R823-30. 5. Bandini LB, Schoeller DA, Dietz WH. Validity of reported energy intake in obese and nonobese adolescents. Am J Clin Nutr 1990;52:421-5. 6. Holliday MA. Metabolic rate and organ size during growth
The Journal of Pediatrics Volume 129, Number 5
7.
8.
9.
10.
11.
12.
13.
from infancy to maturity and during late gestation and early infancy. Pediatrics 1971;47:169-78. Bandini LG, Schoeller DA, Dietz WH. Energy expenditure in obese and nonobese adolescents. Pediatr Res 1990;27:198203. Kann L, Warren CW, Harris WA, et al. Youth Risk Behavior Surveillance--United States, 1993. MMWR Morb Mortal Wldy Rep 1995;44(ss-1):1-56. Centers for Disease Control. Trends in smoking initiation among adolescentsand young adults--United States, 1980-89. MMWR Morb Mortal Wkly Rep 1995;44:521-5. Camp DE, Klesges RC, Relyea G. The relationship between body weight concerns and adolescentsmoking.Health Psychol 1993;12:24-32. HofstetterA, Schutz Y, Jequier E, Wahren J. Increased 24-hour energy expenditure in cigarette smokers. N Engl J Med 1986; 314:79-82. Bandini LG, Schoeller DA, Edwards J, Young VR, Oh SH, Dietz WH. Energy expenditure during carbohydrate overfeeding in obese and nonobese adolescents. Am J Physiol 1989; 256:E357-67. SegalKR, Gutin B, Nyman AM, Pi-SunyerFX. Thermic effect of food at rest, during exercise, and after exercise in lean and obese men of similar body weight. J Clin Invest 1985i76:110712.
Editorials
623
14. Ferraro R, Lillioja S, Fontvieille A-M, Rising R, Bogardus C, Ravussin E. Lower sedentary metabolic rate in women compared with men. J Clin Invest 1992;90:780-4. 15. Bisdee JT, James WPT, Shaw MA. Changes in energy expenditure during the menstrual cycle. Br J Nutr 1989;61: 187-99. 16. Ravussin E, Lillioja S, Knowler WC, et al. Reduced rate of energy expenditure as a risk factor for body weight gain. N Engl J Med 1988;318:467-721 17. Bogardus C, Lillioja S, Ravussin E, et al. Familial dependence of the resting metabolic rate. N Engl J Med 1986;315:96100. 18. Griffiths M, Payne PR. Energy expenditure in small children of obese and nonobese parents. Nature 1976;260:698-700. 19. Griffiths M, Payne PR, Stunkard AJ, Rivers JPW, Cox M. Metabolic rate and physical developmentin children at risk of obesity. Lancet 1990;336:76-8. 20. Griffiths M, Rivers JPW, Payne PR. Energy intake in children at high and low risk of obesity. Hum Nutr:Clin Nutr 1987; 41C:425-30. 21. PelleymounterMA, Cullen MJ, Baker MB, et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995;269:540-3.
Assessing prognosis in infants infected with human immunodeficiency virus It is now 15 years since the first cases of acquired irnmunodeficiency syndrome were described in the United States. The World Health Organization estimates that, worldwide, more than 25 million people have been infected with human immunodeficiencyvirus thus far, including about 1.5 million childrenl; the majority of cases have Occurred in developing countries. It is probable that the HIV pandemic has caused the deaths of more than 1 million children worldwide. 2 In the United States since 1982, more than 6900 children with AIDS, aged less than 13 years, have been reported to the Centers for Disease Control and Prevention, constituting some 1% to 2% of the total number of cases (ML Lindegren: personal communication, CDC, 1996). In 1993, HIV infection (AIDS) was the sixth leading cause of death in children aged 1 to 4 years and the seventh leading cause in children aged 5 to 14 years. 3 It is estimated that approximately 6000 to 7000 infants are born to HIV-infected mothers each year in the United States4; assuming a 25% transmission rate, 5 this translates into about 1600 infected J Pediatr 1996;129:623-5 Copyright © 1996 by Mosby-Year Book, Inc. 0022-3476/96/$5.00 + 0 9/18/77053
infants' being born each year. There is some evidence that after publication of the U.S. Public Health Service recommendations in August 1994 on the use of maternal and neonatal zidovudine to reduce perinatal transmission,6 the number of HIV-infected infants being born may be on the decrease in some parts of the United States. 7 In Europe, more than 6000 pediatric AIDS cases were reported until early
See related article, p. 648.
AIDS CDC HIV PCP
Acquiredimmunodeficiencysyndrome Centersfor Disease Controland Prevention Humanimmunodeficiencyvirus Pneumocystiscarinii pneumonia
1996. 8 The largest numbers are from Romania, where most of the children have acquired disease by nosocomial transmission by means of infected needles and blood products.9 In the United Kingdom since 1982, a total of 669 children have been reported as infected with HIV, with about 247 having been reported as having AIDS) ° As in the United States, perinatal transmission accounts for