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Birth characteristics of offspring and parental diabetes: evidence for the fetal insulin hypothesis
  1. G Davey Smith1,
  2. J A C Sterne1,
  3. P Tynelius2,
  4. F Rasmussen2
  1. 1Department of Social Medicine, University of Bristol, Bristol, UK
  2. 2Department of Epidemiology, Karolinska Institute, Division of Epidemiology, Karolinska University Hospital, Stockholm, Sweden
  1. Correspondence to:
 Professor G Davey Smith
 Department of Social Medicine, University of Bristol, Canynge Hall, Whiteladies Road, Clifton, Bristol BS8 2PR, UK; zetkinbristol.ac.uk

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Birth weight of people is related to their risk of non-insulin dependent diabetes mellitus (NIDDM), which may reflect intra-uterine programming of disease risk, or common genetic factors related both to birth weight and to NIDDM risk. The latter has been called the “fetal insulin hypothesis”.1 Currently there is little direct evidence for this hypothesis, although two studies have shown an inverse association between fathers’ risk of diabetes and the birth weight of their offspring.23 Findings with respect to paternal diabetes are of particular interest because they cannot directly reflect an influence of the intra-uterine environment. Conversely, impaired glucose tolerance in pregnant women is associated with greater offspring birth weight,4 and as women with impaired glucose tolerance during pregnancy are at an increased risk of developing diabetes5 the expectation is of a positive association between offspring birth weight and maternal diabetes risk. This evidence suggests that as time increases after the birth of offspring an inverse association emerges between offspring birth weight and maternal insulin resistance6 and diabetes.3

METHODS AND RESULTS

We investigated the association between parental diabetes and offspring birth characteristics using data from the Swedish Medical Birth Register linked to the Swedish Cause of Death Register. Date of birth, sex, birth weight, birth length, and gestational age, together with the mother’s and father’s unique identity numbers were extracted from the birth register for all 783 814 children born in Sweden between 1973 and 1980. The identity numbers of 783 340 mothers and 768 583 fathers were recorded in the birth register and mortality data up to 31 December 1997 were obtained. Children with implausible birth weight, birth length, or gestational age (extreme values or …

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