Other secular trends may explain the associations with diabetes risk
The report by Bingley and colleagues of an association between age of
the mother and birth order, and risk of type 1 diabetes mellitus in
children is of interest but the findings do not seem to be consistent (1).
If the age of the mother is associated with a real increase in risk, then
it is surprising that subsequent children could possibly have reduced risk
given that maternal age must have increased. The hypothesis given to
explain the apparent relationship, of more mature immune responses in
older women priming the fetal system in some way, is biologically
improbable given the functional immaturity of the fetal immune system.
Since the cohort spans a significant interval, it is not clear that
the authors have adjusted for secular trends that might have been
associated with greater risk. The most important of these factors is the
trend towards childbirth in older women over the study period. The
greatest risk of type 1 diabetes mellitus was reported in the offspring of
a very small group of mothers giving birth after 45 years of age (1).
There may have been a number of other factors in older woman that could
have influenced the reported observation, including assisted reproduction,
ethnicity, maternal illness and obesity that were not presented.
Other potentially confounding factors not examined include the
changing incidences of type 1 diabetes mellitus and the increasing rate of
obesity in childhood, which tends to lower the age of onset of children at
risk of type one diabetes, because of insulin resistance (2,3).
Finally, it appears that type 1 pre-diabetes antibodies were not
measured to validate the diagnosis of type 1 diabetes mellitus. Clinical
diagnosis based on apparent requirement for insulin therapy or
presentation with ketoacidosis is not specific at a time of increasing
type 2 diabetes mellitus in children.
1. Bingley PJ, Douek IF, Rogers CA, Gale EA. Influence of maternal
age at delivery and birth order on risk of type 1 diabetes in childhood:
prospective population based family study. BMJ 2000 Aug 12;321(7258):420-
4.
2. Rangasami JJ, Greenwood DC, McSporran B, Smaill PJ, Patterson CC, Waugh
NR. Rising incidence of type 1 diabetes mellitus in Scottish children 1984
-93. Arch Dis Child 1997;77:210-13.
3. Kitigawa T, Owada M, Urakami T, Tajima N. Epidemiology of type 1
(insulin dependent) and type 2 (non-insulin-dependent) diabetes mellitus
in Japanese children. Diabetes Res Clin Pract 1994;24(suppl):S7-13.
Competing interests:
No competing interests
04 September 2000
Alistair J Gunn
Paediatrician, Paediatrician, Paediatrician, and Clinical Fellow
Wayne S Cutfield, Paul L Hofman, Craig Jeferries
Dept of Paediatrics, University of Auckland, Auckland, New Zealand
Rapid Response:
Other secular trends may explain the associations with diabetes risk
The report by Bingley and colleagues of an association between age of
the mother and birth order, and risk of type 1 diabetes mellitus in
children is of interest but the findings do not seem to be consistent (1).
If the age of the mother is associated with a real increase in risk, then
it is surprising that subsequent children could possibly have reduced risk
given that maternal age must have increased. The hypothesis given to
explain the apparent relationship, of more mature immune responses in
older women priming the fetal system in some way, is biologically
improbable given the functional immaturity of the fetal immune system.
Since the cohort spans a significant interval, it is not clear that
the authors have adjusted for secular trends that might have been
associated with greater risk. The most important of these factors is the
trend towards childbirth in older women over the study period. The
greatest risk of type 1 diabetes mellitus was reported in the offspring of
a very small group of mothers giving birth after 45 years of age (1).
There may have been a number of other factors in older woman that could
have influenced the reported observation, including assisted reproduction,
ethnicity, maternal illness and obesity that were not presented.
Other potentially confounding factors not examined include the
changing incidences of type 1 diabetes mellitus and the increasing rate of
obesity in childhood, which tends to lower the age of onset of children at
risk of type one diabetes, because of insulin resistance (2,3).
Finally, it appears that type 1 pre-diabetes antibodies were not
measured to validate the diagnosis of type 1 diabetes mellitus. Clinical
diagnosis based on apparent requirement for insulin therapy or
presentation with ketoacidosis is not specific at a time of increasing
type 2 diabetes mellitus in children.
1. Bingley PJ, Douek IF, Rogers CA, Gale EA. Influence of maternal
age at delivery and birth order on risk of type 1 diabetes in childhood:
prospective population based family study. BMJ 2000 Aug 12;321(7258):420-
4.
2. Rangasami JJ, Greenwood DC, McSporran B, Smaill PJ, Patterson CC, Waugh
NR. Rising incidence of type 1 diabetes mellitus in Scottish children 1984
-93. Arch Dis Child 1997;77:210-13.
3. Kitigawa T, Owada M, Urakami T, Tajima N. Epidemiology of type 1
(insulin dependent) and type 2 (non-insulin-dependent) diabetes mellitus
in Japanese children. Diabetes Res Clin Pract 1994;24(suppl):S7-13.
Competing interests: No competing interests