- Email: [email protected]
A Tough Nut to Crack
A Tough Nut to Crack
he traditional Mediterranean diet is taking on an almost cultlike aura, having been linked to possible beneficial effects related to risks for cardiovascular disease, cancer, aging, diabetes, and lung disease in human beings. This diet, made up predominately of fruits, vegetables, breads, whole grain cereals, legumes, and nuts with moderate intake of milk and dairy products and limited amounts of meat and poultry, developed in the olive growing areas of the Mediterranean region. Thus olive oil is the primary source of fat, although consumption of fish also provides fat in the form of omega-3 polyunsaturated fatty acids in some areas. Such a diet results in a higher ratio of monounsaturated to saturated fats and greater antioxidant intake than the typical northern European and North American diet. Not surprisingly, there are local variations as to the proportional make-up of these foods in the diet. “Fast food” has also made inroads into the region, especially among the young. Compared with the other disease states listed, relatively little has been published regarding the impact of a Mediterranean diet on lung disease, particularly in children. Although not addressing diet directly, the International Study of Asthma and Allergies in Childhood has found a lower prevalence of asthma in the Mediterranean region.1 A study of 20,106 school children 6 to 7 years of age in 8 Spanish cities found a small beneficial effect of Mediterranean diet on asthma symptom frequency in girls, but not in boys.2 Individual foods found to be protective for frequent asthma symptoms in both boys and girls were seafood and cereals; consumption of fast food was a risk factor for more frequent symptoms. 2 A study of 690 children living in 4 rural areas of Crete found a nonstatistically significant trend for a protective effect of Mediterranean diet on wheezing, although daily consumption of grapes, oranges, apples, and fresh tomatoes were individually associated with significantly less wheezing.3 Although not evaluating the Mediterranean diet as a whole, a study of children on the island of Menorca found similar protective effects from a diet high in fruity vegetables often considered part of such a diet (tomatoes, eggplant, cucumber, green beans, zucchini).4 In this issue of The Journal, Castro-Rodriguez et al5 examine the impact of the Mediterranean diet on wheezing in preschool children. Their study of 1757 Spanish children age 3 to 4 years attempted to control for some of the confounding variables plaguing previous studies. In their population, children in the highest quartile of adherence to a Mediterranean diet had significantly less wheezing than did children in the lowest quartile. Interestingly, there was no difference in type of cooking oil used between currently wheezing and nonwheezing children. Multivariate analysis found that adherence to a traditional Mediterranean diet was associated with a protective effect against wheezing that was independent of
T
obesity, sex, level of physical activity, and exposure to livestock (including exposure of the mother during pregnancy). Older age was also independently associated with less wheezing, suggesting that duration of adherence to this diet is less important than adherence alone. A number of unanswered questions remain regarding the role of diet in childhood wheezing and asthma. It is not clear whether it is the intake of more healthful foods or avoidance of foods that may be proinflammatory among Mediterranean diet adherents that is responsible for the effects noted. As noted above, consumption of fast food was a risk factor for more frequent wheezing among Spanish schoolchildren,2 as was margarine intake among the children of rural Crete.3 A diet high in fatty foods was shown to be a risk factor for wheezing among children in Taiwan.6 However, another fat source typically considered unhealthful, milk fat, has been associated with beneficial effects in other settings.7,8 Although this study was able to delineate an effect of diet independent of obesity, others have not. The interplay between diet, obesity, and physical activity is a complex one that will need further exploration. It is not clear whether there are key foods within the Mediterranean diet or a threshold of consumption that must be met to realize a benefit. For example, one study found that a modest amount of fish consumption was protective against wheezing, with larger amounts offering no additional protection.9 The same study found that intake of cod oil actually had a u-shaped association with asthma, with greater risk in those consuming it either never or daily.9 Furthermore, a distinction must be made between the impact of Mediterranean diet on wheezing/asthma and on other atopic diseases because the associations between diet and disease differ in that regard.2 Thus what may protect against wheezing/asthma may increase risk of allergic rhinitis or eczema. Finally, the timing of dietary exposure and its impact must be clarified. Although no such studies have been carried out with regard to the Mediterranean diet, other studies, particularly with fish and fish oils, See related article, p 823 suggest that maternal diet during pregnancy Reprint requests: Mark A. Brown, MD, Decan influence risk partment of Pediatrics and Arizona Respiratory Center, Section of Pediatric Pulmonolfor wheezing, asthma, ogy and Allergy, Box 245073, University of 10-12 and atopic disease. Arizona, Tucson, AZ 85724-5073. E-mail: [email protected]. Even though this J Pediatr 2008;152:749-50 study demonstrates an 0022-3476/$ - see front matter association between deCopyright © 2008 Mosby Inc. All rights creased wheezing and reserved. adherence to a Mediter10.1016/j.jpeds.2008.02.027
Editorials
749
ranean diet, we have barely scratched the surface in understanding the influence that diet has on risk for wheezing and asthma in childhood, with much work left to be done. A tough nut to crack, indeed. Mark A. Brown, MD Department of Pediatrics and Arizona Respiratory Center Section of Pediatric Pulmonology and Allergy University of Arizona Tucson, Arizona
REFERENCES 1. Worldwide variations in the prevalence of asthma symptoms: the International Study of Asthma and Allergies in Childhood (ISAAC). Eur Respir J 1998;12:315-35. 2. Garcia-Marcos L, Canflanca IM, Garrido JB, Varela AL-S, Garcia-Hernandez G, Grima FG, et al. Relationship of asthma and rhinoconjunctivitis with obesity, exercise and Mediterranean diet in Spanish schoolchildren. Thorax 2007;62:503-8. 3. Chatzi L, Apostolaki G, Bibakis I, Skypala I, Bibaki-Liakou V, Tzanakis N, et al. Protective effect of fruits, vegetables and the Mediterranean diet on asthma and allergies among children in Crete. Thorax 2007;62:677-83. 4. Chatzi L, Torrent M, Romieu I, Garcia-Esteban R, Ferrer C, Vioque J, et al. Diet wheeze and atopy in school children in Menorca, Spain. Pediatr Allergy Immunol 2007;18:480-5.
5. Castro-Rodriguez JA, Garcia-Marcos L, Alfonseda Rojas JD, Valverde-Molina J, Sanchez-Solis M. Mediterranean diet as a protective factor for wheezing in preschool children. J Pediatr 2008;152:823-8. 6. Huang SL, Lin KC, Pan WH. Dietary factors associated with physician-diagnosed asthma and allergic rhinitis in teenagers: analyses of the first Nutrition and Health Survey in Taiwan. Clin Exp Allergy 2001;31:259-64. 7. Wijga AH, Smit HA, de Jongste JC, Gerritsen J, Neijens HJ, Boshuizen HC, et al. Association of consumption of products containing milk fat with reduced asthma risk in preschool children: the PIAMA birth cohort study. Thorax 2003;58:567-72. 8. Kim JL, Elfman L, Mi Y, Johansson M, Smedje G, Norbäck D. Current asthma and respiratory symptoms among pupils in relation to dietary factors and allergens in the school environment. Indoor Air 2005;15:170-82. 9. Laerum BN, Wentzel-Larsen T, Gulsvik A, Omenaas E, Gíslason T, Janson C, et al. Relationship of fish and cod oil intake with adult asthma. Clin Exp Allergy 2007;37:1616-23. 10. Denburg JA, Hatfield HM, Cyr MM, Hayes L, Holt PG, Sehmi R, et al. Fish oil supplementation in pregnancy modifies neonatal progenitors at birth in infants at risk of atopy. Pediatr Res 2005;57:276-81. 11. Dunstan JA, Mori TA, Barden A, Beilin LJ, Taylor AL, Holt PG, Prescott SL. Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: a randomized, controlled trial. J Allergy Clin Immunol 2003;112:1178-84. 12. Salam MT, Li Y-F, Langholz B, Gilliland FD. Maternal fish consumption during pregnancy and risk of early childhood asthma. J Asthma 2005;42:513-8.
Metformin as a Weight-Loss Tool in “At-Risk” Obese Adolescents: A Magic Bullet?
he list of predictors of childhood overweight has gotten longer and more varied and includes maternal history of gestational diabetes mellitus,1 birth weight, weight velocity during infancy,2 parental perceptions,3 precocious adrenarche,4,5 urban planning,6,7 voluntary exercise,8 and involuntary exercise.9 Although new perspectives on obesity have broadened the range of possible targets for prevention, lifestyle changes remain the cornerstone of all weight-loss strategies, regardless of age. In contrast to type 1 diabetes mellitus, which is not related to body weight,10 obesity predisposes patients to type 2 diabetes mellitus. Indeed, the childhood obesity epidemic has redefined the natural history of type 2 diabetes mellitus, which now affects younger individuals and can masquerade as type 1 diabetes mellitus.10 Obesity is an insulin-resistant state, especially when it is associated with a sedentary lifestyle,11 central adiposity,12 or both. In adults, fasting hyperinsulinemia characteristic of insulin resistance can predate the onset of type 2 diabetes mellitus for several years, as suggested by the presence of complications at the time of diagnosis.13 The insidious loss of beta cell function that accompanies the onset of so-called “pre-diabetic” states and the resulting post-pran-
T
IGT
750
Impaired glucose tolerance
Editorials
dial hyperglycemia, can span several years, if not decades, before detection. In youth however, the transition from prediabetes to frank type 2 diabetes mellitus may occur in a matter of months rather than years.14 The potentially more aggressive nature of type 2 diabetes mellitus in youth underscores the need for prevention. Adding to the alarm are recent reports of enhanced cardiovascular risk in obese children with microalbuminuria.15 There is agreement that children who are at risk may benefit from screening if it results in the delay or prevention of type 2 diabetes mellitus at a young age. In screening for long-term metabolic risk, the same challenges documented See related article, p 817 in the adult population apply to youth.16 The Reprint requests: Josephine Z. Kasa-Vubu, MD, MS, Department of Pediatrics, Endolack of consensus on crine Division, University of Michigan Medsuitable metabolic preical Center, Ann Arbor, MI 48019-0718. dictors for this age E-mail: [email protected]. J Pediatr 2008;152:750-2 group add a level of un0022-3476/$ - see front matter certainty.17-19 For exCopyright © 2008 Mosby Inc. All rights ample, fasting glucose reserved. level is of limited value 10.1016/j.jpeds.2008.03.006 The Journal of Pediatrics • June 2008
he traditional Mediterranean diet is taking on an almost cultlike aura, having been linked to possible beneficial effects related to risks for cardiovascular disease, cancer, aging, diabetes, and lung disease in human beings. This diet, made up predominately of fruits, vegetables, breads, whole grain cereals, legumes, and nuts with moderate intake of milk and dairy products and limited amounts of meat and poultry, developed in the olive growing areas of the Mediterranean region. Thus olive oil is the primary source of fat, although consumption of fish also provides fat in the form of omega-3 polyunsaturated fatty acids in some areas. Such a diet results in a higher ratio of monounsaturated to saturated fats and greater antioxidant intake than the typical northern European and North American diet. Not surprisingly, there are local variations as to the proportional make-up of these foods in the diet. “Fast food” has also made inroads into the region, especially among the young. Compared with the other disease states listed, relatively little has been published regarding the impact of a Mediterranean diet on lung disease, particularly in children. Although not addressing diet directly, the International Study of Asthma and Allergies in Childhood has found a lower prevalence of asthma in the Mediterranean region.1 A study of 20,106 school children 6 to 7 years of age in 8 Spanish cities found a small beneficial effect of Mediterranean diet on asthma symptom frequency in girls, but not in boys.2 Individual foods found to be protective for frequent asthma symptoms in both boys and girls were seafood and cereals; consumption of fast food was a risk factor for more frequent symptoms. 2 A study of 690 children living in 4 rural areas of Crete found a nonstatistically significant trend for a protective effect of Mediterranean diet on wheezing, although daily consumption of grapes, oranges, apples, and fresh tomatoes were individually associated with significantly less wheezing.3 Although not evaluating the Mediterranean diet as a whole, a study of children on the island of Menorca found similar protective effects from a diet high in fruity vegetables often considered part of such a diet (tomatoes, eggplant, cucumber, green beans, zucchini).4 In this issue of The Journal, Castro-Rodriguez et al5 examine the impact of the Mediterranean diet on wheezing in preschool children. Their study of 1757 Spanish children age 3 to 4 years attempted to control for some of the confounding variables plaguing previous studies. In their population, children in the highest quartile of adherence to a Mediterranean diet had significantly less wheezing than did children in the lowest quartile. Interestingly, there was no difference in type of cooking oil used between currently wheezing and nonwheezing children. Multivariate analysis found that adherence to a traditional Mediterranean diet was associated with a protective effect against wheezing that was independent of
T
obesity, sex, level of physical activity, and exposure to livestock (including exposure of the mother during pregnancy). Older age was also independently associated with less wheezing, suggesting that duration of adherence to this diet is less important than adherence alone. A number of unanswered questions remain regarding the role of diet in childhood wheezing and asthma. It is not clear whether it is the intake of more healthful foods or avoidance of foods that may be proinflammatory among Mediterranean diet adherents that is responsible for the effects noted. As noted above, consumption of fast food was a risk factor for more frequent wheezing among Spanish schoolchildren,2 as was margarine intake among the children of rural Crete.3 A diet high in fatty foods was shown to be a risk factor for wheezing among children in Taiwan.6 However, another fat source typically considered unhealthful, milk fat, has been associated with beneficial effects in other settings.7,8 Although this study was able to delineate an effect of diet independent of obesity, others have not. The interplay between diet, obesity, and physical activity is a complex one that will need further exploration. It is not clear whether there are key foods within the Mediterranean diet or a threshold of consumption that must be met to realize a benefit. For example, one study found that a modest amount of fish consumption was protective against wheezing, with larger amounts offering no additional protection.9 The same study found that intake of cod oil actually had a u-shaped association with asthma, with greater risk in those consuming it either never or daily.9 Furthermore, a distinction must be made between the impact of Mediterranean diet on wheezing/asthma and on other atopic diseases because the associations between diet and disease differ in that regard.2 Thus what may protect against wheezing/asthma may increase risk of allergic rhinitis or eczema. Finally, the timing of dietary exposure and its impact must be clarified. Although no such studies have been carried out with regard to the Mediterranean diet, other studies, particularly with fish and fish oils, See related article, p 823 suggest that maternal diet during pregnancy Reprint requests: Mark A. Brown, MD, Decan influence risk partment of Pediatrics and Arizona Respiratory Center, Section of Pediatric Pulmonolfor wheezing, asthma, ogy and Allergy, Box 245073, University of 10-12 and atopic disease. Arizona, Tucson, AZ 85724-5073. E-mail: [email protected]. Even though this J Pediatr 2008;152:749-50 study demonstrates an 0022-3476/$ - see front matter association between deCopyright © 2008 Mosby Inc. All rights creased wheezing and reserved. adherence to a Mediter10.1016/j.jpeds.2008.02.027
Editorials
749
ranean diet, we have barely scratched the surface in understanding the influence that diet has on risk for wheezing and asthma in childhood, with much work left to be done. A tough nut to crack, indeed. Mark A. Brown, MD Department of Pediatrics and Arizona Respiratory Center Section of Pediatric Pulmonology and Allergy University of Arizona Tucson, Arizona
REFERENCES 1. Worldwide variations in the prevalence of asthma symptoms: the International Study of Asthma and Allergies in Childhood (ISAAC). Eur Respir J 1998;12:315-35. 2. Garcia-Marcos L, Canflanca IM, Garrido JB, Varela AL-S, Garcia-Hernandez G, Grima FG, et al. Relationship of asthma and rhinoconjunctivitis with obesity, exercise and Mediterranean diet in Spanish schoolchildren. Thorax 2007;62:503-8. 3. Chatzi L, Apostolaki G, Bibakis I, Skypala I, Bibaki-Liakou V, Tzanakis N, et al. Protective effect of fruits, vegetables and the Mediterranean diet on asthma and allergies among children in Crete. Thorax 2007;62:677-83. 4. Chatzi L, Torrent M, Romieu I, Garcia-Esteban R, Ferrer C, Vioque J, et al. Diet wheeze and atopy in school children in Menorca, Spain. Pediatr Allergy Immunol 2007;18:480-5.
5. Castro-Rodriguez JA, Garcia-Marcos L, Alfonseda Rojas JD, Valverde-Molina J, Sanchez-Solis M. Mediterranean diet as a protective factor for wheezing in preschool children. J Pediatr 2008;152:823-8. 6. Huang SL, Lin KC, Pan WH. Dietary factors associated with physician-diagnosed asthma and allergic rhinitis in teenagers: analyses of the first Nutrition and Health Survey in Taiwan. Clin Exp Allergy 2001;31:259-64. 7. Wijga AH, Smit HA, de Jongste JC, Gerritsen J, Neijens HJ, Boshuizen HC, et al. Association of consumption of products containing milk fat with reduced asthma risk in preschool children: the PIAMA birth cohort study. Thorax 2003;58:567-72. 8. Kim JL, Elfman L, Mi Y, Johansson M, Smedje G, Norbäck D. Current asthma and respiratory symptoms among pupils in relation to dietary factors and allergens in the school environment. Indoor Air 2005;15:170-82. 9. Laerum BN, Wentzel-Larsen T, Gulsvik A, Omenaas E, Gíslason T, Janson C, et al. Relationship of fish and cod oil intake with adult asthma. Clin Exp Allergy 2007;37:1616-23. 10. Denburg JA, Hatfield HM, Cyr MM, Hayes L, Holt PG, Sehmi R, et al. Fish oil supplementation in pregnancy modifies neonatal progenitors at birth in infants at risk of atopy. Pediatr Res 2005;57:276-81. 11. Dunstan JA, Mori TA, Barden A, Beilin LJ, Taylor AL, Holt PG, Prescott SL. Fish oil supplementation in pregnancy modifies neonatal allergen-specific immune responses and clinical outcomes in infants at high risk of atopy: a randomized, controlled trial. J Allergy Clin Immunol 2003;112:1178-84. 12. Salam MT, Li Y-F, Langholz B, Gilliland FD. Maternal fish consumption during pregnancy and risk of early childhood asthma. J Asthma 2005;42:513-8.
Metformin as a Weight-Loss Tool in “At-Risk” Obese Adolescents: A Magic Bullet?
he list of predictors of childhood overweight has gotten longer and more varied and includes maternal history of gestational diabetes mellitus,1 birth weight, weight velocity during infancy,2 parental perceptions,3 precocious adrenarche,4,5 urban planning,6,7 voluntary exercise,8 and involuntary exercise.9 Although new perspectives on obesity have broadened the range of possible targets for prevention, lifestyle changes remain the cornerstone of all weight-loss strategies, regardless of age. In contrast to type 1 diabetes mellitus, which is not related to body weight,10 obesity predisposes patients to type 2 diabetes mellitus. Indeed, the childhood obesity epidemic has redefined the natural history of type 2 diabetes mellitus, which now affects younger individuals and can masquerade as type 1 diabetes mellitus.10 Obesity is an insulin-resistant state, especially when it is associated with a sedentary lifestyle,11 central adiposity,12 or both. In adults, fasting hyperinsulinemia characteristic of insulin resistance can predate the onset of type 2 diabetes mellitus for several years, as suggested by the presence of complications at the time of diagnosis.13 The insidious loss of beta cell function that accompanies the onset of so-called “pre-diabetic” states and the resulting post-pran-
T
IGT
750
Impaired glucose tolerance
Editorials
dial hyperglycemia, can span several years, if not decades, before detection. In youth however, the transition from prediabetes to frank type 2 diabetes mellitus may occur in a matter of months rather than years.14 The potentially more aggressive nature of type 2 diabetes mellitus in youth underscores the need for prevention. Adding to the alarm are recent reports of enhanced cardiovascular risk in obese children with microalbuminuria.15 There is agreement that children who are at risk may benefit from screening if it results in the delay or prevention of type 2 diabetes mellitus at a young age. In screening for long-term metabolic risk, the same challenges documented See related article, p 817 in the adult population apply to youth.16 The Reprint requests: Josephine Z. Kasa-Vubu, MD, MS, Department of Pediatrics, Endolack of consensus on crine Division, University of Michigan Medsuitable metabolic preical Center, Ann Arbor, MI 48019-0718. dictors for this age E-mail: [email protected]. J Pediatr 2008;152:750-2 group add a level of un0022-3476/$ - see front matter certainty.17-19 For exCopyright © 2008 Mosby Inc. All rights ample, fasting glucose reserved. level is of limited value 10.1016/j.jpeds.2008.03.006 The Journal of Pediatrics • June 2008