Premature Birth and Insulin Resistance
http://www.100md.com
《新英格兰医药杂志》
To the Editor: Low birth weight resulting from intrauterine growth retardation is a known risk factor for the later appearance of insulin resistance. Hofman et al. (Nov. 18 issue)1 conclude that children who are small at birth because of prematurity, regardless of their growth in utero, are also at risk for metabolic disease.
However, the authors comment very little on the effect of interactions between size at birth and early postnatal growth on subsequent insulin sensitivity; a number of recent articles have shown these interactions to be quite relevant.2,3,4 In this regard, it is noteworthy that children in this study who were small for gestational age were rather short and appear to have been recruited at a pediatric endocrinology clinic.5 Many population-based studies report that most children (up to 90 percent) who were small for gestational age at birth, either term or premature, have complete catch-up growth before four years of age.6 Therefore, we would suggest caution when extending the observations of Hofman et al. to other populations.
Rodrigo A. Bazaes, M.D., Ph.D.
Verónica Mericq, M.D.
University of Chile
Santiago 226-3, Chile
vmericq@med.uchile.cl
References
Hofman PL, Regan F, Jackson WE, et al. Premature birth and later insulin resistance. N Engl J Med 2004;351:2179-2186.
Bavdekar A, Yajnik CS, Fall CH, et al. Insulin resistance syndrome in 8-year-old Indian children: small at birth, big at 8 years, or both? Diabetes 1999;48:2422-2429.
Ong KK, Petry CJ, Emmett PM, et al. Insulin sensitivity and secretion in normal children related to size at birth, postnatal growth, and plasma insulin-like growth factor-I levels. Diabetologia 2004;47:1064-1070.
Soto N, Bazaes RA, Pe?a V, et al. Insulin sensitivity and secretion are related to catch-up growth in small-for-gestational-age infants at age 1 year: results from a prospective cohort. J Clin Endocrinol Metab 2003;88:3645-3650.
Hofman PL, Cutfield WS, Robinson EM, et al. Insulin resistance in short children with intrauterine growth retardation. J Clin Endocrinol Metab 1997;82:402-406.
Hokken-Koelega AC, De Ridder MA, Lemmen RJ, Den Hartog H, De Muinck Keizer-Schrama SM, Drop SL. Children born small for gestational age: do they catch up? Pediatr Res 1995;38:267-271.
To the Editor: Hofman et al. state that almost all studies of low birth weight and the programming of later diseases have focused on subjects who had been born at term but had been small for gestational age. To the contrary, a systematic review of the literature on birth weight and later type 2 diabetes, characterized by insulin resistance, reveals 13 studies (Medline/Embase, 1966 to 2004), of which only 2 considered gestational age.1,2 In these two studies, low birth weight and high birth weight were associated with an increased risk (low birth weight: unadjusted relative risk, 1.83; 95 percent confidence interval, 1.55 to 2.161; high birth weight: unadjusted odds ratio, 2.53; 95 percent confidence interval, 1.66 to 3.872), irrespective of gestational age. In full-term subjects only, the relative risk was 1.75 (95 percent confidence interval, 1.51 to 2.03),1 and the odds ratio was 2.42 (95 percent confidence interval, 1.42 to 4.13).2 In fact, the influence of maturity at birth seems to have been largely ignored in the literature to date. The finding that the risk among appropriate-for-gestational-age children who were born prematurely is similar to the risk among small-for-gestational-age children who were born at term argues strongly against diminished prenatal food supply as a causal factor for the later outcome. This may have wide-ranging consequences throughout the field of programming by low birth weight.3
Andreas Plagemann, M.D.
Thomas Harder, M.D.
Charité Clinic of Obstetrics
13353 Berlin, Germany
andreas.plagemann@charite.de
References
Rich-Edwards JW, Colditz GA, Stampfer MJ, et al. Birthweight and the risk for type 2 diabetes in adult women. Ann Intern Med 1999;130:278-284.
Dyck RF, Klomp H, Tan L. From "thrifty phenotype" to "hefty fetal phenotype": the relationship between high birthweight and diabetes in the Saskatchewan Registered Indians. Can J Public Health 2001;92:340-344.
Plagemann A. `Fetal programming' and `functional teratogenesis': on epigenetic mechanisms and prevention of perinatally acquired lasting health risks. J Perinat Med 2004;32:297-305.
The authors reply: Drs. Bazaes and Mericq question the effect of postnatal growth. We did not report data on postnatal growth, although it was examined in those children with complete neonatal records. Weight and length both at term and at one year were recorded in this subgroup, and no association with later insulin sensitivity was found. Concern was expressed about the effect of short stature masking the difference between the preterm small-for-gestational-age and appropriate-for-gestational-age cohorts. There is no evidence that height has any effect on insulin sensitivity in normal children.1 Although it is possible that it has an effect, we consider this unlikely, especially since height was included in our statistical modeling. We agree that caution should be used in generalizing these observations, since ours was a relatively small cohort and a reduction in insulin sensitivity in preterm small-for-gestational-age children cannot be excluded. However, a 40 percent reduction in insulin sensitivity in all preterm children is dramatic and of similar magnitude to that observed in low-birth-weight term children. Further studies are required to determine whether the changes in insulin sensitivity observed persist and whether they are similar in survivors from different neonatal units.
Drs. Plagemann and Harder correctly state that most studies reported in the literature do not specifically comment on gestational age, and the two studies cited in their letter do so at a rudimentary level only. However, the seminal work in the field of low birth weight and programming was performed by David Barker and his team, and their subjects were almost all born at term. Gestational age has not been specifically examined in most studies, especially birth at 32 weeks or less of gestation, as in our study. We disagree that our data argue against diminished prenatal nutrition as causing a later adverse outcome in term growth-retarded children, as we discussed in our article. Although other factors may be more relevant, nutrition both before and after birth must still be considered of potential importance in the etiology of these metabolic changes.
Paul L. Hofman, M.B., Ch.B.
Wayne S. Cutfield, M.D.
Liggins Institute
Auckland, New Zealand
p.hofman@auckland.ac.nz
References
Hofman PL, Cutfield WS, Robinson EM, et al. Insulin resistance in short children with intrauterine growth retardation. J Clin Endocrinol Metab 1997;82:402-406.
However, the authors comment very little on the effect of interactions between size at birth and early postnatal growth on subsequent insulin sensitivity; a number of recent articles have shown these interactions to be quite relevant.2,3,4 In this regard, it is noteworthy that children in this study who were small for gestational age were rather short and appear to have been recruited at a pediatric endocrinology clinic.5 Many population-based studies report that most children (up to 90 percent) who were small for gestational age at birth, either term or premature, have complete catch-up growth before four years of age.6 Therefore, we would suggest caution when extending the observations of Hofman et al. to other populations.
Rodrigo A. Bazaes, M.D., Ph.D.
Verónica Mericq, M.D.
University of Chile
Santiago 226-3, Chile
vmericq@med.uchile.cl
References
Hofman PL, Regan F, Jackson WE, et al. Premature birth and later insulin resistance. N Engl J Med 2004;351:2179-2186.
Bavdekar A, Yajnik CS, Fall CH, et al. Insulin resistance syndrome in 8-year-old Indian children: small at birth, big at 8 years, or both? Diabetes 1999;48:2422-2429.
Ong KK, Petry CJ, Emmett PM, et al. Insulin sensitivity and secretion in normal children related to size at birth, postnatal growth, and plasma insulin-like growth factor-I levels. Diabetologia 2004;47:1064-1070.
Soto N, Bazaes RA, Pe?a V, et al. Insulin sensitivity and secretion are related to catch-up growth in small-for-gestational-age infants at age 1 year: results from a prospective cohort. J Clin Endocrinol Metab 2003;88:3645-3650.
Hofman PL, Cutfield WS, Robinson EM, et al. Insulin resistance in short children with intrauterine growth retardation. J Clin Endocrinol Metab 1997;82:402-406.
Hokken-Koelega AC, De Ridder MA, Lemmen RJ, Den Hartog H, De Muinck Keizer-Schrama SM, Drop SL. Children born small for gestational age: do they catch up? Pediatr Res 1995;38:267-271.
To the Editor: Hofman et al. state that almost all studies of low birth weight and the programming of later diseases have focused on subjects who had been born at term but had been small for gestational age. To the contrary, a systematic review of the literature on birth weight and later type 2 diabetes, characterized by insulin resistance, reveals 13 studies (Medline/Embase, 1966 to 2004), of which only 2 considered gestational age.1,2 In these two studies, low birth weight and high birth weight were associated with an increased risk (low birth weight: unadjusted relative risk, 1.83; 95 percent confidence interval, 1.55 to 2.161; high birth weight: unadjusted odds ratio, 2.53; 95 percent confidence interval, 1.66 to 3.872), irrespective of gestational age. In full-term subjects only, the relative risk was 1.75 (95 percent confidence interval, 1.51 to 2.03),1 and the odds ratio was 2.42 (95 percent confidence interval, 1.42 to 4.13).2 In fact, the influence of maturity at birth seems to have been largely ignored in the literature to date. The finding that the risk among appropriate-for-gestational-age children who were born prematurely is similar to the risk among small-for-gestational-age children who were born at term argues strongly against diminished prenatal food supply as a causal factor for the later outcome. This may have wide-ranging consequences throughout the field of programming by low birth weight.3
Andreas Plagemann, M.D.
Thomas Harder, M.D.
Charité Clinic of Obstetrics
13353 Berlin, Germany
andreas.plagemann@charite.de
References
Rich-Edwards JW, Colditz GA, Stampfer MJ, et al. Birthweight and the risk for type 2 diabetes in adult women. Ann Intern Med 1999;130:278-284.
Dyck RF, Klomp H, Tan L. From "thrifty phenotype" to "hefty fetal phenotype": the relationship between high birthweight and diabetes in the Saskatchewan Registered Indians. Can J Public Health 2001;92:340-344.
Plagemann A. `Fetal programming' and `functional teratogenesis': on epigenetic mechanisms and prevention of perinatally acquired lasting health risks. J Perinat Med 2004;32:297-305.
The authors reply: Drs. Bazaes and Mericq question the effect of postnatal growth. We did not report data on postnatal growth, although it was examined in those children with complete neonatal records. Weight and length both at term and at one year were recorded in this subgroup, and no association with later insulin sensitivity was found. Concern was expressed about the effect of short stature masking the difference between the preterm small-for-gestational-age and appropriate-for-gestational-age cohorts. There is no evidence that height has any effect on insulin sensitivity in normal children.1 Although it is possible that it has an effect, we consider this unlikely, especially since height was included in our statistical modeling. We agree that caution should be used in generalizing these observations, since ours was a relatively small cohort and a reduction in insulin sensitivity in preterm small-for-gestational-age children cannot be excluded. However, a 40 percent reduction in insulin sensitivity in all preterm children is dramatic and of similar magnitude to that observed in low-birth-weight term children. Further studies are required to determine whether the changes in insulin sensitivity observed persist and whether they are similar in survivors from different neonatal units.
Drs. Plagemann and Harder correctly state that most studies reported in the literature do not specifically comment on gestational age, and the two studies cited in their letter do so at a rudimentary level only. However, the seminal work in the field of low birth weight and programming was performed by David Barker and his team, and their subjects were almost all born at term. Gestational age has not been specifically examined in most studies, especially birth at 32 weeks or less of gestation, as in our study. We disagree that our data argue against diminished prenatal nutrition as causing a later adverse outcome in term growth-retarded children, as we discussed in our article. Although other factors may be more relevant, nutrition both before and after birth must still be considered of potential importance in the etiology of these metabolic changes.
Paul L. Hofman, M.B., Ch.B.
Wayne S. Cutfield, M.D.
Liggins Institute
Auckland, New Zealand
p.hofman@auckland.ac.nz
References
Hofman PL, Cutfield WS, Robinson EM, et al. Insulin resistance in short children with intrauterine growth retardation. J Clin Endocrinol Metab 1997;82:402-406.