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Hyperinsulinemia-Insulin Resistance is now-a-days a "clinical" Diagnosis.
- Sergio Stagnaro (16 August 2002)
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Low DHEA May Explain These Findings
- James M. Howard (17 August 2002)
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The "U shaped Relationship" is due to loss of DHEA
- James M. Howard (17 August 2002)
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Hypertension in Mother with low birth weight
- Debasish Banerjee (19 August 2002)
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Transfer of Disease from unborn child to mother
- Anita Banerjee (20 August 2002)
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Re: Transfer of Disease from unborn child to mother
- James M. Howard (21 August 2002)
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Transgenerational link with maternal insulin resistance may not be 'genetic'
- Henry S Kahn (22 August 2002)
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Re: Re: Transfer of Disease from unborn child to mother
- Anita Banerjee (23 August 2002)
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Re: Transgenerational link with maternal insulin resistance may not be 'genetic'
- James M. Howard (26 August 2002)
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Re: Re: Transgenerational link with maternal insulin resistance may not be 'genetic'
- James M. Howard (27 August 2002)
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Offspring's birth weight and maternal insulin resistance
- Chittaranjan Yajnik, Caroline Fall, Caroline Fall, Jacqueline Hill, Samantha Leary, Charudatta Joglekar (3 September 2002)
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Authors' reply: Trans-generational associations are present for fathers and mothers
- Debbie A Lawlor, George Davey Smith, Shah Ebrahim (3 September 2002)
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Authors' reply to Yajnik et al.
- Debbie A Lawlor, George Davey Smith, Shah Ebrahim (6 September 2002)
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Sergio Stagnaro, Specialist in Blood, Gastrointestinal, and Metabolic Diseases. Researcher in Biophysical Semeiotics. Via Erasmo Piaggio N° 23/8. 16037 Riva Trigoso (Genoa) Italy
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Sirs, In order to evaluate individual’s insulin-resistance, there are, now-a- days, fortunately “clinical” biophysical semeiotic methods, of different difficulty to perform, that can be applied on very large scale, and are surely more efficacious and reliable than those suggested, among other authors, by Debbie A Lawlor et al.(1). At first, I found and described previously the so-called “Diabetic Constitution”, doctor can recognize and quantify, rapidly and easily, at the bed-side by means of Biophysical Semeiotics (See my site, HONCode ID. N. 233736 http://digilander.libero.it/semeioticabiofisica: Diabetes; Diabetic Constitution, and Bibliography) (2-5). I am sorry to find out that doctors, all around the world, continue to ignore or overlook clearly the new physical semeiotics, i.e. Biophysical Semeiotics, about which a lot of papers are posted “uselessly” in my site, in the Page, I hold weekly in the italian site www.katamed.it , in www.piazzetta.sfera.it, in BMJ.com Rapid Responses, in “all” Discussion Forum on Medscape, a.s.o. Ferrero- Marigo’s biophysical-semeiotic Manoeuvre(2) as well as a large number of other signs and manoeuvres, fully described in above-cited sites and papers, allow doctor to recognize by “quantitative” way the hyperinsulinaemia-insulinresistance. Interestingly, all these biophysical semeiotic signs and manoeuvres, including obviously the “Diabetic Constitution”, can result clearly positive, i.e. pathological, from a really long time before diabetes onset, since genetic factors are associated with the metabolism of insulin and its impairement. Patho- physiological mechanisms, underlying hyperinsulinaemia-insulinresistance, are really complex. In addition, speaking about peripheral insulin- resistance, we have to remember also the “central” receptors resistance of beta-cells of Langherans islets. A skilled physician can rapidly recognize (in a few minutes) at the bed- side the Diabetic Constitution and Reaven’ syndrome, both classic and “variant”, the later I described in previous papers (2,3) by means of the “new” (but really 50-year-old!) physical semeiotics. References. 1) Lawlor DA., Smith GD., Ebrahim S. Birth weight of offspring and insulin resistance in late adulthood: cross sectional survey. (BMJ 2002;325:359, 17 August ). 2) Stagnaro-Neri M., Stagnaro S., Semeiotica Biofisica: la manovra di Ferrero-Marigo nella diagnosi clinica della iperinsulinemia- insulinoresistenza. Acta Med. Medit. 13, 125, 1997. 3) Stagnaro-Neri M., Stagnaro S., La “Costituzione Colelitiasica”: ICAEM- a, Sindrome di Reaven variante e Ipotonia-Ipocinesia delle Vie biliari. Epatol. 20, 239, 1993. 4) Stagnaro S.-Neri M., Stagnaro S., Sindrome di Reaven, classica e variante, in evoluzione diabetica. Il ruolo della Carnitina nella prevenzione del diabete mellito. Il Cuore. 6, 617, 1993. 5) Stagnaro S., Stagnaro-Neri M. Valutazione percusso-ascoltatoria del Diabete Mellito. Aspetti teorici e pratici. Epat. 32, 131, 1986 |
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James M. Howard 1037 North Woolsey Avenue, Fayetteville, Arkansas 72701, U.S.A.
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The mother produces DHEA for herself and her fetus. A small neonate may indicate reduced growth due to reduced availability of DHEA. The mother's DHEA is also reduced following birth. Since DHEA may ameliorate the onset of diabetes (Diabetes Technol Ther 2001 Summer;3(2):211-9), I suggest that the increased probability of diabetes in the mother. |
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James M. Howard 1037 Woolsey Avenue, Fayetteville, Arkansas 72701, U.S.A.
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It is my hypothesis that the hormone, dehydroepiandrosterone (DHEA), optimizes transcription and replication of DNA. In fact, I think this phenomenon is so important that DHEA was involved in the evolution of mammals (Howard, J., Hormones in mammalian evolution, Rivista di Biologia / Biology Forum 2001; 94: 177-184). Subordinate to this hypothesis, I suggest all tissues compete for available DHEA. The pregnant mother produces all DHEA for herself and her fetus. Therefore, a competition exists between the mother and the fetus for DHEA. A mother who is, herself, low DHEA will have difficulty becoming pregnant. If she does, her low DHEA will produce reduced growth in her fetus. (In fact, the additional use of DHEA by her fetus may produce pathologies in the mother.) Anyway, back to the point, a low DHEA mother should produce a small neonate. There is simply not sufficient DHEA for proper growth of the fetus. It is known that DHEA declines in mothers postpartum and that DHEA provides protection from diabetes. Therefore, I suggest the increased incidence of diabetes in these women results from the excessive use of, and reduction in, DHEA during and following birth. The DHEA is not there to protect from the formation of diabetes. Lawlor, et al., state: “A U shaped relation between birth weight of offspring and diabetes in older age was found; women with the lightest and heaviest offspring had the highest prevalence of diabetes.” DHEA naturally begins to decline around ages 20-25, reaching very low levels in old age. Older pregnant women produce less DHEA. Therefore, the phenomena Lawlor, et al., report should appear more often in those older women producing the lightest offspring. Now, in the competition between mother and fetus, some fetuses will compete more effectively for DHEA. These fetuses should grow large from the extra DHEA. Therefore, older women who produce larger neonates represent women whose DHEA is lower due to this effect. It is loss of DHEA in older women who produce the lightest and the heaviest offspring who are at most risk of low DHEA and development of diabetes. |
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Debasish Banerjee, Fellow, Nephrology Miami, USA, 33140
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Since hypertension is related to insulin resistance, one possibility (yet to be investigated) will be that low birth weight is also related to development of hypertension in the mothers. Moreover it is possible that the etiology of diabetes/insulin resistance/hypertension in the mother is due the transfer of stem cells from the foetus to the mother. This would explain why the low birth weight baby and the mother acquire the risk for similar chronic diseases. |
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Anita Banerjee, post doctorate associate University of Miami, Miami, 33140 USA
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I would be interested to know the reason for the cause of low birth weight babies, if placental-uterine dysfuction may have been a factor. If so, perhaps the transfer of fetal cells or fetal DNA (as has been shown in preeclampsia) may be a causal effect of hypertension. |
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James M. Howard 1037 North Woolsey, Avenue, Fayetteville, Arkansas 72701, U.S.A.
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Debasish Banerjee suggested (above) that hypertension and insulin resistance are connected and may be due to “transfer of stem cells from the foetus to the mother.” Now you suggest, again, that “transfer of fetal cells or fetal DNA … may be a causal effect of hypertension.” One need not resort to a transfer of fetal cells or fetal DNA to explain hypertension and insulin resistance in these patients. In my two rapid responses to Lawlor, et al., (above), I suggested low DHEA may be causal and how this could develop. Suzuki, et al., have reported a connection of low DHEAS (DHEA sulfate, the precursor to DHEA) with both hypertension and insulin resistance: “In nonobese and nondiabetic essential hypertension, serum DHEAS was lower and insulin resistance was the most significant independent determinant of reduced serum DHEAS, followed by systolic blood pressure and fasting plasma insulin.” (Endocr J 1999 Aug;46(4):521-8) I suggest low DHEA is causal in these cases. I have examined preeclampsia and its rise in the U.S.A. I invite you to read it at: http://www.naples.net/~nfn03605/dheapree.htm . My work suggests increased testosterone reduces overall availability of DHEA. Therefore, increased testosterone should increase pathologies I attribute to reduced DHEA; preeclampsia is one of these. If you take the time to read my explanation of the increase in preeclampsia, please keep this connection of testosterone and DHEA in mind as I only deal with the connection of testosterone on the incidence of preeclampsia at the web address I included in this paragraph. |
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Henry S Kahn, Medical Epidemiologist Centers for Disease Control and Prevention, Atlanta, Georgia 30341 USA
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Lawlor et al. described a transgenerational association between low birth weight (in the offspring) and increased late-adult insulin resistance (in the mother).1 Their finding is especially interesting because mothers who bear heavier newborns often have glucose intolerance and insulin resistance during their pregnancies. Thus, they have reported an instructive paradox. I question, however, the authors’ unsupported conclusion that “common genetic factors” contribute to the association they observed. Their transgenerational finding could equally well be explained by non-genetic stressors (e.g., physiological, social, psychological, toxic) acting on the mother before delivery and throughout her life. In support of this non-genetic explanation, the authors’ table shows that mothers who bore infants in the lowest birth weight quartile were also more likely to have ever smoked, to belong to low socioeconomic groups, and to have the lowest mean age at metabolic assessment (suggesting reduced survival in later adulthood). It is also possible that the low birth weight infants were more often born prematurely, another correlate of maternal stressors. Mothers’ adverse environment and behaviors might lead both to her bearing a smaller infant and to her developing her own later insulin resistance.2,3 Statistical adjustments may not be sufficient to disprove the existence of environmental and behavioral explanations, since there could always be some residual confounding due to poorly measured factors. Henry S. Kahn, MD
1. Lawlor DA, Davey Smith G, Ebrahim S. Birth weight of offspring and insulin resistance in late adulthood: cross sectional survey. BMJ 2002;325(7360):359-62. 2. Bjorntorp P, Holm G, Rosmond R. Hypothalamic arousal, insulin resistance and Type 2 diabetes mellitus. Diabet Med 1999;16(5):373-83. 3. Smith U. Smoking elicits the insulin resistance syndrome: new aspects of the harmful effect of smoking. J Intern Med 1995;237(5):435-7. {{I declare no competing interest. HSK}} |
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Anita Banerjee, post-doctorate associate University of Miami, 33140, USA
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The mother’s risk of insulin resistance with associated cardiovascular morbidity and the baby’s low birth weight have three components in common: genetic factors, the in utero microenviroment and the “crosstalk’ of maternal-fetal circulation that occurred in utero. Dr Lawlor et al have found in this study that’ birth weight of offspring is inversely related to maternal insulin resistance in later life’.(1) Since all diseases may have multifactorial etiologies, it is possible for Dr. Howard’s hypothesis and Dr Lawlor’s to be true. I would like you to refer to Dr Bianchi’ s work and others which was very well summarized in the June 2002 issue of Science titled ‘Cells Exchanged During Pregnancy Live On”. (2) Fetal microchimerism has been implicated in modulating and causing diseases in pregnancy and postpartum. (3) Perhaps this factor should be considered when following up multiparous women and their offspring, particularly those mothers who had a degree utero-placental dysfunction enhancing leakage of fetal cells and fetal DNA into the maternal circulation. Whether these cells are stem cells or produce a toxin that has an effect has yet to be clarified. 1 Lawlor DA, Davey Smith G, Ebrahim S. Birth weight of offspring and insulin resistance in late adulthood: sectional survey. BMJ 2002;325(7360):359-62. 2 Cells exchanged during pregnancy live on. Science. 2002 Jun 21;296(5576):2169-72. 3 Microchimerism of presumed fetal origin in thyroid specimens from women: a case-control study. Lancet. 2001 Dec 15;358(9298):2034-8. |
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James M. Howard 1037 Woolsey Avenue, Fayetteville, Arkansas 72701-2046, U.S.A.
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In my third response to Lawlor, et al., above, I point out my hypothesis that testosterone reduces overall availability of DHEA, regarding preeclampsia. Now, my work also suggests that levels of testosterone affect abilities usually attributed to “the environment.” More specifically, I think early puberty and increased testosterone adversely affect final development of the brain. This suggests that the ability to learn is adversely affected by high levels of testosterone. This is supported: “The presence of learning disabilities was significantly associated with higher salivary testosterone.” (Physiol Behav 1993 Mar;53(3):583-6). Therefore, individuals who exhibit these qualities, i.e., higher testosterone, may lack the abilities necessary to compete in a job market increasingly dependent upon advanced learning; they will be increased in percentage in low socioeconomic levels. In 1985, I developed my hypothesis that the “stress hormone,” cortisol, evolved to counteract the effects of DHEA. This has just recently been supported: “We have demonstrated that each steroid has its distinct gene expression profile, although DHEA and testosterone co- regulated most genes in a similar direction while glucocorticoids frequently regulated the same genes in an opposite direction.” (Horm Metab Res 2001; 33: 691-5) Therefore, stress may affect birth outcome; it would simply be worse in a woman of higher testosterone. (I apologize for my delayed response; I have been on vacation.) |
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James M. Howard 1037 Woolsey Avenue, Fayetteville, Arkansas 72701-2046, U.S.A.
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In my response to Dr. Kahn, above, I forgot to also include the connection of smoking with testosterone. The increased testosterone in these women who give birth to low birth weight babies may also be part of the increased smoking in women who give birth to LBW babies. That is, it may be increased testosterone that is involved in both the smoking and LBW babies in these women. Am J Public Health 1999 Sep;89(9):1377-83 Prenatal effects of maternal smoking on daughters' smoking: nicotine or testosterone exposure? Kandel DB, Udry JR. Department of Psychiatry, Columbia University, New York, NY 10032, USA. OBJECTIVES: The purpose of this study was to specify the effect of prenatal fetal exposure to maternal cotinine and testosterone on daughters' smoking in adolescence and adulthood. METHODS: Longitudinal causal models were estimated among 240 White mother-daughter pairs from the Child Health and Development Study. Mothers and daughters were reinterviewed when daughters were aged 15 to 17 years, and daughters were interviewed at 27 to 30 years of age. Blood samples were obtained from both parents during pregnancy and from adult daughters. RESULTS: Testosterone and smoking were positively correlated among mothers during their pregnancy and among adult daughters. Maternal prenatal cotinine had no direct effect on daughters' smoking; self-reported smoking in pregnancy did have a direct effect. Smoking among daughters during adolescence was determined by maternal prenatal testosterone and self-reported maternal smoking during pregnancy and postnatally. Smoking among adult daughters reflected chronic smoking since adolescence and the continuing effect of postnatal maternal smoking. Prenatal maternal testosterone affected adult daughters' testosterone. CONCLUSIONS: Estimates of the impact of prenatal maternal smoking depend on the measure of smoking. Prenatal testosterone exposure is a previously unrecognized risk factor for smoking among female offspring. |
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Chittaranjan Yajnik, Director,Diabetes Unit, King Edward Memorial Hospital & Research Centre Sardar Moodliar Road, Rasta peth, Pune 411011, India, Caroline Fall, Caroline Fall, Jacqueline Hill, Samantha Leary, Charudatta Joglekar
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Lawlor et al report that mothers who had lower birth weight babies have higher insulin resistance (HOMA) in old age1. There was a U shaped relationship between offspring birth weight and maternal diabetes. Previously they have reported increased cardiovascular deaths in parents of low birth weight children2,3. They propose that their findings support a genetic basis for the relationship between birth weight and cardiovascular risk (fetal insulin hypothesis4).
The authors state that no previous studies have directly assessed the fetal insulin hypothesis by looking at the association between offspring birth weight and parental insulin resistance. They are mistaken. We have reported our findings in the Pune Maternal Nutrition Study (PMNS) 5,6 and Pune Children's Study (PCS)7. We also have relevant data from the Mysore Parthenon Study (MPS)8. Our findings are opposite to those of Lawlor et al and pose a challenge to the fetal insulin hypothesis.
In all three studies (see table), there was a direct relationship between offspring birth weight at term and maternal insulin resistance, measured using the HOMA equation either in mid-pregnancy (PMNS and MPS, rural and urban Indian mothers respectively) or 8 years after the birth of the child (PCS, urban Indian mothers). Adjustment for maternal body mass index (BMI) reduced the significance of the association, suggesting a role for maternal body size. There was only 1 diabetic woman in the PMNS, 38 in the MPS and 21 in the PCS. In the MPS there was a linear increase in the prevalence of maternal gestational diabetes with increasing offspring birth weight (p<0.001). In the PCS, like Lawlor et al, we found a borderline U shaped relationship (p=0.06 for the quadratic term). Eight years after the birth of the child, mothers of the heaviest (upper third) babies had 3.64 times (CI 1.04-12.80) higher risk of diabetes than the average birth weight (middle third) group. For mothers of the lowest birth weight babies (lowest third) the risk was 2.35 times (CI 0.62-8.92). Contrary to the postulate of the fetal insulin hypothesis, in the PMNS there was a direct relationship between offspring birth weight and paternal insulin resistance5.
We have proposed9 that maternal insulin resistance during gestation may be a 'necessary evil' for fetal growth by ensuring supply of adequate nutrients (glucose, amino acids, triglycerides). There is considerable evidence for this concept in the literature10. Chronic (pre-gestational) maternal insulin resistance (genetic or non-genetic) is associated with greater hyperglycemia and increased fetal growth11. Even in the normoglycemic range there is a linear relationship between maternal glycemia and fetal growth8,12. Insulin resistance in pregnancy is a predictor of the future development of diabetes11,13
Thus, as discussed by Lawlor et al, the inverse relationship between offspring birth weight and maternal insulin resistance many years later is counterintuitive. Possible explanations may include: 1) These findings may have arisen by chance; despite a large sample size the relationship is weak. 2) The women were 68 years old when studied and were not followed as a birth cohort. There may have been bias caused by survival effects. Selective loss of mothers of large birth weight children due to pathology related to insulin resistance will give an inverse relationship with birth weight in the survivors. 3) Birth weight was obtained only by recall and there is no information on gestational age. The authors are therefore not able to adjust for one of the strongest determinants of birth weight. 4) There may be different time relationships in the pathogenesis of insulin resistance in relation to low and high birth weight of the offspring. 5) Maternal and offspring birth weight are strongly related. Mothers of low birth weight babies would have been of lower birth weight themselves.
The relationship between birth weight and insulin resistance (in the same individual or its parents) may be different in different populations. The biological basis for this may be variation between populations in the distribution of mechanisms responsible for the regulation of fetal growth. These include maternal nutrition, metabolism and lifestyle e.g. smoking, placental factors and innate metabolic characteristics of the fetus all of which may be influenced by genetic as well as non-genetic factors. It is premature to make assertions about genetic vs non-genetic aetiology of birth weight and disease relationship.
Table Study (n) Maternal age Insulin resistance measured at Difference in log maternal insulin resistance (HOMA) per kg increase in offspring's birth weight (CI) Adjusted for maternal age, sex of baby Adjusted for maternal age and BMI, sex of baby PMNS (633) 21 y 28 wks gestation 0.25, (0.06 , 0.44), p<0.01 0.18, (-0.01 , 0.38), p=0.06 MPS (597) 24 y 29 wks gestation 0.20, (0.08 , 0.32), p<0.001 0.002, (-0.09 , 0.15), p=0.65 PCS (477) 32 y 8 y after delivery 0.21, (0.06 , 0.35), p<0.005 0.11, (0.06 , 0.35), p=0.12 Lawlor et al 69 y 69 y after delivery -0.04, (-0.08, -0,01), p<0,05 -0.08, (-0.13, -0.04) <\pre> |
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Debbie A Lawlor, MRC / Department of Health Research Training Fellow, Department of Social Medicine, University of Br BS8 2PR, George Davey Smith, Shah Ebrahim
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JM Howard, D Banerjee and H Khan all suggest alternative (to the foetal insulin hypothesis) explanations for the associations between offspring birthweight and maternal insulin resistance in later life. We agree that these are all possible explanations - our conclusion was that common genetic factors contribute to the relationship between birth weight and cardiovascular disease and diabetes mellitus in adults.[1] The possible explanations presented by these authors are unlikely to explain the associations between low offspring birth weight and a father's cardiovascular disease and diabetes risk. This association has been found in several studies that were cited in our paper [2][3][4] and one additional study not cited.[5] The most plausible explanation for these associations is genetic. Interestingly the associations between offspring birthweight and paternal disease risk tend to be weaker than those between offspring birthweight and maternal disease risk. We feel that genetic factors and maternal environmental factors play a part in the trans- generational associations between birth weight and cardiovascular disease[6] and agree with A Banerjee that these associations are likely to be complex and multi-factorial. D Banerjee states that the possibility that low offspring birth weight is also related to hypertension in the mothers is yet to be tested - but we present data on the inverse association between offspring birthweight and systolic blood pressure in our paper.[1] A Banerjee asks about the causes of low birth weight - for women in this cohort we do not have these data. However, the association of offspring birthweight with insulin resistance was linear across the birthweight distribution and therefore unlikely to be explained by specific causes of low birthweight at just one end of the distribution. S Stadnaro suggests an interesting clinical 'bed-side' method for assessing insulin resistance status - we are not convinced that this is valid or reliable for epidemiological studies or clinical practice. Debbie A Lawlor, George Davey Smith, Shah Ebrahim Department of Social Medicine, University of Bristol References 1. Lawlor DA, Davey Smith G, Ebrahim S. Birth weight of offspring and insulin resistance in late adulthood: cross sectional survey. BMJ 2002;325:359-562. 2. Davey Smith G, Hart C, Ferrell C, et al. Birth weight of offspring and mortality in the Renfrew and Paisley study: prospective observational study. BMJ 1997;315:1189-1193. 3. Rasmussen F, Sterne J, Davey Smith G, Tynelius P, Leon DA. Fetal growth is associated with parents' cardiovascular mortality. Am J Epidemiol 1992 135:266-273 2001;153 (Suppl):S98. 4. Rasmussen F, Davey Smith G, Sterne J, Tynelius P, Leon DA. Birth characteristics of offspring and parental diabetes. Am J Epidemiol 2001;153 (Suppl): S47 5. Lawlor DA, Davey Smith G, Whincup P, Wannamethee G, Papacosta O, Dhanjil S, Griffin M, Nicolaides AN, Ebrahim S. The association between offspring birth weight and atherosclerosis in middle aged men and women: British Regional Heart Study. J Epidemiol & Community Health 2002 (in press) 6. Lawlor DA, Davey Smith G, Ebrahim S. Association between leg length and offspring birthweight: partial explanation for the transgenerational associations between birthweight and cardiovascular disease. Paediatric & Perinatal Epidemiology 2002 (in press) |
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Debbie A Lawlor, MRC/Department of Health Research Fellow Department of Social Medicine, University of Bristol, BS8 2PR, George Davey Smith, Shah Ebrahim
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Our first author's reply appeared at the same time as Yajnik et als response and therefore was unable to respond to it; we respond to their comments here. We feel that our study is unique and not comparable to the studies mentioned by Yajnik et al conducted either during pregnancy or during a woman's reproductive years. The metabolic disruptions of pregnancy are well established - as one author in the BMJ recently pointed out pregnancy should be considered a stress test of maternal carbohydrate and lipid metabolism.[1] We state in our paper that "the association in older age, rather than during a mothers' reproductive years is more supportive of a genetic mechanism than a temporary hormonal effect of pregnancy".[2] The metabolic changes of pregnancy are likely to mask any genetic effects - which then become apparent as the woman is out of her reproductive years. Although chance may be an explanation for the findings in our study (p = 0.04 for the age adjusted association) this is unlikely given the consistent inverse associations between offspring birth weight and maternal and paternal cardiovascular disease, diabetes and insulin resistance identified in several studies of older individuals from different populations. [2-6] Similarly survivor bias though possibly important in our study would not be so in prospective studies. [3-6] Maternal report of offspring birth weight is likely to be accurate [7] but any misclassification bias would tend to lead to an underestimate of the effect - thus if this were important our results would be conservative. Maternal and offspring birth weight are only moderately correlated and we have found in this study that the associations of the womens' offspring birth weight with their insulin resistance and the womens' own birth weight with their insulin resistance are independent of each other.[8] As stated earlier we feel that the trans-generational associations between birth weight and cardiovascular disease and risk factors are complex involving a number of factors - including genetic and non-genetic. Debbie A Lawlor, George Davey Smith, Shah Ebrahim
References 1. Satter N, Greer IA. Pregnancy complications and maternal cardiovascular risk: opportunities for intervention and screening? BMJ 2002;325:157-160. 2. Lawlor DA, Davey Smith G, Ebrahim S. Birth weight of offspring and insulin resistance in late adulthood: cross sectional survey. BMJ 2002;325:359-562. 3. Davey Smith G, Hart C, Ferrell C, et al. Birth weight of offspring and mortality in the Renfrew and Paisley study: prospective observational study. BMJ 1997;315:1189-1193. 4. Rasmussen F, Sterne J, Davey Smith G, Tynelius P, Leon DA. Fetal growth is associated with parents' cardiovascular mortality. Am J Epidemiol 1992 135:266-273 2001;153 (Suppl):S98. 5. Rasmussen F, Davey Smith G, Sterne J, Tynelius P, Leon DA. Birth characteristics of offspring and parental diabetes. Am J Epidemiol 2001;153 (Suppl): S47 6. Lawlor DA, Davey Smith G, Whincup P, Wannamethee G, Papacosta O, Dhanjil S, Griffin M, Nicolaides AN, Ebrahim S. The association between offspring birth weight and atherosclerosis in middle aged men and women: British Regional Heart Study. J Epidemiol & Community Health 2002 (in press) 7. O'Sullivan JJ, Pearce MS, Parker L. Parental recall of birth weight: how accurate is it? Arch.Dis.Child 2000;82:202-203. 8. Lawlor DA, Davey Smith G, Ebrahim S. Life course influences on insulin resistance: findings from the British Women's Heart and Health Study. (submitted - details available from authors) |
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