Correspondence
Childhood Obesity, Other Cardiovascular Risk Factors, and Premature Death
N Engl J Med 2010; 362:1840-1842May 13, 2010
- Article
To the Editor:
Franks et al. (Feb. 11 issue)1 report that childhood obesity and glucose intolerance greatly increased the risk of premature death among Pima Indians. Seeking to understand the likely effect of epidemic global increases in these risk factors in childhood on future life spans, findings were discussed in terms of cardiovascular disease and prevention of type 2 diabetes.2 Yet, the greatest cause of premature death observed was alcoholic liver disease, which accounted for 35.5% of deaths from endogenous causes. These findings highlight the importance of investigating the extent to which childhood obesity and glucose intolerance interact with patterns of alcohol drinking and chronic hepatitis C infection to produce high rates of chronic liver disease in the population studied.3 Obese people are more susceptible to liver damage when they drink alcohol; elevated aminotransferase levels have been reported in obese persons who consume more than one drink per day or who binge drink and consume one or two drinks per day.4 Liver damage that occurs at relatively low levels of alcohol intake in vulnerable persons is a potential concern, given current thinking that moderate drinking is cardioprotective.
Marcia Russell, Ph.D., M.P.H.
Pacific Institute for Research and Evaluation, Berkeley, CA
russell@prev.org Maurizio Trevisan, M.D.
Nevada System of Higher Education, Las Vegas, NVSaverio Stranges, M.D., Ph.D.
University of Warwick Medical School, Coventry, United KingdomNo potential conflict of interest relevant to this letter was reported.
4 References1
Franks PW ,Hanson RL ,Knowler WC ,Sievers ML ,Bennett PH ,Looker HC . Childhood obesity, other cardiovascular risk factors, and premature death. N Engl J Med 2010;362:485-493
Full Text | Web of Science | Medline2
Gregg EW . Are children the future of type 2 diabetes prevention? N Engl J Med 2010;362:548-550
Full Text | Web of Science | Medline3
Bialek SF ,Redd JT ,Lynch A , et al. Chronic liver disease among two American Indian populations in the southwestern United States, 2000-2003. J Clin Gastroenterol 2008;42:949-954
CrossRef | Medline4
Ruhl CE ,Everhart JE . Joint effects of body weight and alcohol on elevated serum alanine aminotransferase in the United States population. Clin Gastroenterol Hepatol 2005;3:1260-1268
CrossRef | Web of Science | Medline
To the Editor:
Franks et al. highlight the importance of childhood obesity in premature death in adulthood, and their findings provide support for the need for primary prevention of obesity as early as possible. Numerous studies have shown that childhood obesity is often preceded by a high birth weight.1 Maternal hyperglycemia during pregnancy is probably the most important cause of macrosomia and excess body fat at birth.2 Remarkably, a study involving the same population as that studied by Franks et al. showed that exposure to maternal diabetes in utero increased the risk of childhood obesity.3 Therefore, it would be of particular interest to know whether premature death in this population was preceded by high birth weight and whether there was any relation between prenatal exposure to maternal diabetes or obesity and mortality among adults. Ultimately, such findings would indicate that in the future, the prevention of type 2 diabetes4 may begin even earlier than reported (i.e., in the prenatal period).
Andreas Plagemann, M.D.
Thomas Harder, M.D.
Joachim W. Dudenhausen, M.D.
Charité, Berlin, Germany
andreas.plagemann@charite. de No potential conflict of interest relevant to this letter was reported.
4 References1
Harder T ,Schellong K ,Stupin J ,Dudenhausen JW ,Plagemann A . Where is the evidence that low birthweight leads to obesity? Lancet 2007;369:1859-1859
CrossRef | Web of Science | Medline2
The HAPO Study Cooperative Research Group
Full Text | Web of Science | Medline3
Pettitt DJ ,Baird HR ,Aleck KA ,Bennett PH ,Knowler WC . Excessive obesity in offspring of Pima Indian women with diabetes during pregnancy. N Engl J Med 1983;308:242-245
Full Text | Web of Science | Medline4
Gregg EW . Are children the future of type 2 diabetes prevention? N Engl J Med 2010;362:548-550
Full Text | Web of Science | Medline
To the Editor:
Franks et al. show that the presence of obesity, hypertension, and impaired glucose tolerance in childhood significantly increased the risk of premature death in a selected population of North American Indians.
All risk factors considered are constitutive elements of the metabolic syndrome, a cluster of at least three of the following conditions: obesity, high blood pressure, disorders of glucose, and disorders of lipid metabolism.1
In adulthood, the metabolic syndrome predicts the morbidity and mortality resulting from coronary heart disease and cardiovascular disease, and it increases the overall cardiovascular risk more strongly than its individual constitutive elements. In particular, the presence of the metabolic syndrome increases morbidity and increases the risk of death in an exponential rather than in a linear manner.2,3
Over the past several years, the metabolic syndrome has been described in pediatric patients and thus may be present at any age, though in variable degrees.4,5 A supplemental analysis of data obtained by Franks et al., including a classification of the subjects with and without the metabolic syndrome, might furnish very intriguing information regarding the prognostic value of the metabolic syndrome in childhood.
Gianpaolo De Filippo, M.D.
Domenico Rendina, M.D.
Pasquale Strazzullo, M.D.
Federico II University Medical School, Naples, Italy
domenico.rendina@unina. it No potential conflict of interest relevant to this letter was reported.
5 References1
Cornier MA ,Dabelea D ,Hernandez TL , et al. The metabolic syndrome. Endocr Rev 2008;29:777-822
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Lakka HM ,Laaksonen DE ,Lakka TA , et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002;288:2709-2716
CrossRef | Web of Science | Medline3
Malik S ,Wong ND ,Franklin SS , et al. Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation 2004;110:1245-1250
CrossRef | Web of Science | Medline4
Weiss R ,Dziura J ,Burgert TS , et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004;350:2362-2374
Full Text | Web of Science | Medline5
Viggiano D ,De Filippo G ,Rendina D , et al. Screening of metabolic syndrome in obese children: a primary care concern. J Pediatr Gastroenterol Nutr 2009;49:329-334
CrossRef | Web of Science | Medline
Author/Editor Response
In response to Russell et al.: we used the CAGE questionnaire1 to test whether the relationship between childhood body-mass index (BMI) and death from endogenous causes was modified by alcohol dependency in 2672 adults. A positive association of alcohol dependency with premature death was evident in participants who had not been obese in childhood (0.65 deaths per 1000 person-years of follow-up in participants who were not dependent on alcohol vs. 1.43 deaths per 1000 person-years of follow-up in participants who were dependent on alcohol); these findings contrasted with the effect in participants who were obese in childhood (4.19 vs. 2.34 deaths per 1000 person-years of follow-up). Therefore, childhood obesity appears to be far more important than alcohol dependence in adulthood in contributing to death from endogenous causes, although this interpretation is limited by differences in the precision of measurement between these two variables and the different ages at which they were assessed in our participants. Insufficient data were available to examine causes of death that were specific to the liver. However, in models in which such deaths were excluded, the incidence-rate ratio for the fourth versus the first quartile of childhood BMI was 2.54 (95% confidence interval [CI], 1.48 to 4.35; P=0.005 for trend).
In response to Plagemann et al.: we compared mortality rates among 137 children with and 4239 without intrauterine exposure to diabetes. The incidence-rate ratios for death from all causes and death from endogenous causes were 1.67 (95% CI, 0.99 to 2.80) and 2.73 (95% CI, 0.99 to 7.52). Adjusting the childhood BMI models for intrauterine exposure to diabetes had little effect. Insufficient data were available to address the effects of birth weight on mortality.
In response to De Filippo et al.: we examined whether the metabolic syndrome accounted for the effects of BMI on mortality. Because of a lack of a consensus definition of metabolic syndrome in children, we tested whether a summary score (the sum of age-standardized and sex-standardized BMI, blood-pressure levels, 2-hour glucose levels, and cholesterol concentrations) predicted death from endogenous causes or death from all causes. The score was less predictive than BMI of death from endogenous causes or death from all causes. For example, for deaths from endogenous causes, the incidence-rate ratio for the fourth versus the first quartile of the score was 1.66 (95% CI, 1.01 to 2.74), whereas the incidence-rate ratio for the fourth versus the first quartile of standardized BMI was 2.30 (95% CI, 1.46 to 3.62). In other words, inclusion of the additional variables, equally weighted, weakened the predictive ability of BMI, suggesting that obesity underlies the association of the score with mortality. These findings do not provide support for the notion that an underlying syndrome exists in which the combined effect of these traits on the risk of death is greater than the sum of the parts.
Paul W. Franks, Ph.D.
Umeå University Hospital, Umeå, Sweden
paul.franks@medicin. umu. se William C. Knowler, M.D., Dr.P.H.
National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZHelen C. Looker, M.B., B.S.
Mount Sinai School of Medicine, New York, NYSince publication of their article, the authors report no further potential conflict of interest.
1 References1
Ewing JA . Detecting alcoholism: the CAGE questionnaire. JAMA 1984;252:1905-1907
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