doi: 10.1161/CIRCULATIONAHA.107.691303
(Circulation. 2007;115:e463-e464.)
© 2007 American Heart Association, Inc.
Correspondence |
Response to Letter Regarding Article, "Low Birth Weight, a Risk Factor for Cardiovascular Diseases in Later Life, Is Already Associated With Elevated Fetal Glycosylated Hemoglobin at Birth"
Center for Cardiovascular Research/Institute of Pharmacology, Charité, Berlin, Germany
Department of Nephrology, Charité, Berlin, Germany
Department of Obstetrics and Gynecology, Charité, Berlin, Germany
Institute of Laboratory Medicine, Charité, Berlin, Germany
We thank Harder et al for their interest in our work.1 We would like to reply to the issues raised on a point-to-point basis:
1. Glycosylated hemoglobins (eg, total glycosylated hemoglobin [TGH]) are established, validated measures of average glucose levels during the preceding 6 to 8 weeks, and they are significantly correlated with fasting plasma glucose and 2-hour postchallenge plasma glucose.2,3 Insulin secretion and sensitivity determine glycosylated hemoglobin in diabetic patients.4 An association between glycosylated hemoglobin and insulin resistance also has been observed in a nondiabetic cohort.5 We suggest that these findings in adults can be extrapolated to newborns. However, for technical and ethical reasons, this link was not directly proven in newborns—as we state explicitly in our paper.1
2. The statement that no infant with a low birth weight has a level of TGH in the upper tertile of the distribution is incorrect. In Figure 2A of our original article, the distribution of TGH is not displayed in tertiles.1 In the lowest tertile of the distribution of TGH, 1.47% of the newborns have a birth weight below 2500 g, as compared with 3.07% in the highest tertile.
3. Harder et al suggest that parameters of weight relative to length should have been used instead of birth weight. To our knowledge, it has not been clearly shown that measures such as the ponderal index are more closely associated with estimates of insulin resistance in newborns than is birth weight. Several epidemiological studies have confirmed that low birth weight is independently associated with insulin resistance in children and adults.6–12
4. We are well aware that correlations between variables within a regression model can be problematic. All possible correlations are, therefore, analyzed and displayed in a correlation matrix in Table 4 of our original article. To prevent incorrect results attributable to the expected correlation between maternal and fetal TGH, we performed separate regression models that each included only 1 variable at a time. Tables 3B and 3C confirm that maternal and fetal TGH are significantly associated with birth weight when added separately to the regression model.1 Unfortunately, there is a typing error in the first line of Table 3B: it says TGH instead of Child TGH.
5. Harder et al suggest that a positive correlation between maternal and fetal TGH and a negative correlation of the latter with birth weight implies a negative relation between maternal TGH and birth weight in a considerable number of cases. This conclusion would only be correct in cases of large correlation coefficients. Because the determination of birth weight is multifactorial, the correlation with maternal and fetal TGH only accounts for a small proportion of its variance. Moreover, the conclusion would imply the existence of subgroups; this is not supported by the scatter plot in Figure 2B.1 We cannot exclude an underestimation of gestational diabetes. However, its incidence is not crucial for the statistical models used, because our work focuses on the continuous variable of TGH instead of the binary definition of gestational diabetes.
6. Because the sixth statement of Harder et al is not supported by any reference, we are not able to directly comment on it. To the best of our knowledge, our study is the first to analyze the association between a newborn’s TGH and birth weight in a considerable number of cases.
We acknowledge that Harder et al have raised some interesting and important issues. As we state in the article, the results of our large study support, but do not prove, the hypothesis that the well-known association between birth weight and alterations of the glucose metabolism develops in utero.1 Its mechanisms remain to be investigated.
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Acknowledgments |
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Disclosures
None.
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References |
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